Dr. Nathan Pennell and Dr. Cheryl Czerlanis discuss challenges in lung cancer screening and potential solutions to increase screening rates, including the use of AI to enhance risk prediction and screening processes.

Dr. Nate Pennell: Hello, and welcome to By the Book, a monthly podcast series for ASCO Education that features engaging discussions between editors and authors from the ASCO Educational Book. I'm Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research for the Taussig Cancer Center. I'm also the editor-in-chief for the ASCO Educational Book. 

Lung cancer is one of the leading causes of cancer-related mortality worldwide, and most cases are diagnosed at advanced stages where curative treatment options are limited. On the opposite end, early-stage lung cancers are very curable. If only we could find more patients at that early stage, an approach that has revolutionized survival for other cancer types such as colorectal and breast cancer. 

On today's episode, I'm delighted to be joined by Dr. Cheryl Czerlanis, a professor of medicine and thoracic medical oncologist at the University of Wisconsin Carbone Cancer Center, to discuss her article titled, "Broadening the Net: Overcoming Challenges and Embracing Novel Technologies in Lung Cancer Screening." The article was recently published in the ASCO Educational Book and featured in an Education Session at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode. 

Cheryl, it's great to have you on the podcast today. Thanks for being here.

Dr. Cheryl Czerlanis: Thanks, Nate. It’s great to be here with you.

Dr. Nate Pennell: So, I'd like to just start by asking you a little bit about the importance of lung cancer screening and what evidence is there that lung cancer screening is beneficial.

Dr. Cheryl Czerlanis: Thank you. Lung cancer screening is extremely important because we know that lung cancer survival is closely tied to stage at diagnosis. We have made significant progress in the treatment of lung cancer, especially over the past decade, with the introduction of immunotherapies and targeted therapies based on personalized evaluation of genomic alterations. But the reality is that outside of a lung screening program, most patients with lung cancer present with symptoms related to advanced cancer, where our ability to cure the disease is more limited. 

While lung cancer screening has been studied for years, the National Lung Screening Trial, or the NLST, first reported in 2011 a significant reduction in lung cancer deaths through screening. Annual low-dose CT scans were performed in a high-risk population for lung cancer in comparison to chest X-ray. The study population was comprised of asymptomatic persons aged 55 to 74 with a 30-pack-year history of smoking who were either active smokers or had quit within 15 years. The low-dose CT screening was associated with a 20% relative risk reduction in lung cancer-related mortality. A similar magnitude of benefit was also reported in the NELSON trial, which was a large European randomized trial comparing low-dose CT with a control group receiving no screening.

Dr. Nate Pennell: So, this led, of course, to approval from CMS (Centers for Medicare and Medicaid Services) for lung cancer screening in the Medicare population, probably about 10 years ago now, I think. And there are now two major trials showing an unequivocal reduction in lung cancer-related mortality and even evidence that it reduces overall mortality with lung cancer screening. But despite this, lung cancer screening rates are very low in the United States. So, first of all, what's going on? Why are we not seeing the kinds of screening rates that we see with mammography and colonoscopy? And what are the barriers to that here?

Dr. Cheryl Czerlanis: That's a great question. Thank you, Nate. In the United States, recruitment for lung cancer screening programs has faced numerous challenges, including those related to socioeconomic, cultural, logistical, and even racial disparities. Our current lung cancer screening guidelines are somewhat imprecise and often fail to address differences that we know exist in sex, smoking history, socioeconomic status, and ethnicity. We also see underrepresentation in certain groups, including African Americans and other minorities, and special populations, including individuals with HIV. And even where lung cancer screening is readily available and we have evidence of its efficacy, uptake can be low due to both provider and patient factors. On the provider side, barriers include having insufficient time in a clinic visit for shared decision-making, fear of missed test results, lack of awareness about current guidelines, concerns about cost, potential harms, and evaluating both true and false-positive test results. 

And then on the patient side, barriers include concerns about cost, fear of getting a cancer diagnosis, stigma associated with tobacco smoking, and misconceptions about the treatability of lung cancer.

Dr. Nate Pennell: I think those last two are really what make lung cancer unique compared to, say, for example, breast cancer, where there really is a public acceptance of the value of mammography and that breast cancer is no one's fault and that it really is embraced as an active way you can take care of yourself by getting your breast cancer screening. Whereas in lung cancer, between the stigma of smoking and the concern that, you know, it's a death sentence, I think we really have some work to be made up, which we'll talk about in a minute about what we can do to help improve this. 

Now, that's in the U.S. I think things are probably, I would imagine, even worse when we leave the U.S. and look outside, especially at low- and middle-income countries.

Dr. Cheryl Czerlanis: Yes, globally, this issue is even more complex than it is in the United States. Widespread implementation of low-dose CT imaging for lung cancer screening is limited by manpower, infrastructure, and economic constraints. Many low- and middle-income countries even lack sufficient CT machines, trained personnel, and specialized facilities for accurate and timely screenings. Even in urban centers with advanced diagnostic facilities, the high screening and follow-up care costs can limit access. Rural populations face additional barriers, such as geographic inaccessibility of urban centers, transportation costs, language barriers, and mistrust of healthcare systems. In addition, healthcare systems in these regions often prioritize infectious diseases and maternal health, leaving limited room for investments in noncommunicable disease prevention like lung cancer screening. Policymakers often struggle to justify allocating resources to lung cancer screening when immediate healthcare needs remain unmet. Urban-rural disparities exacerbate these challenges, with rural regions frequently lacking the infrastructure and resources to sustain screening programs.

Dr. Nate Pennell: Well, it's certainly an intimidating problem to try to reduce these disparities, especially between the U.S. and low- and middle-income countries. So, what are some of the potential solutions, both here in the U.S. and internationally, that we can do to try to increase the rates of lung cancer screening?

Dr. Cheryl Czerlanis: The good news is that we can take steps to address these challenges, but a multifaceted approach is needed. Public awareness campaigns focused on the benefits of early detection and dispelling myths about lung cancer screening are essential to improving participation rates. Using risk-prediction models to identify high-risk individuals can increase the efficiency of lung cancer screening programs. Automated follow-up reminders and screening navigators can also ensure timely referrals and reduce delays in diagnosis and treatment. Reducing or subsidizing the cost of low-dose CT scans, especially in low- or middle-income countries, can improve accessibility. Deploying mobile CT scanners can expand access to rural and underserved areas. 

On a global scale, integrating lung cancer screening with existing healthcare programs, such as TB or noncommunicable disease initiatives, can enhance resource utilization and program scalability. Implementing lung cancer screening in resource-limited settings requires strategic investment, capacity building, and policy interventions that prioritize equity. Addressing financial constraints, infrastructure gaps, and sociocultural barriers can help overcome existing challenges. By focusing on cost-effective strategies, public awareness, and risk-based eligibility criteria, global efforts can promote equitable access to lung cancer screening and improve outcomes. 

Lastly, as part of the medical community, we play an important role in a patient's decision to pursue lung cancer screening. Being up to date with current lung cancer screening recommendations, identifying eligible patients, and encouraging a patient to undergo screening often is the difference-maker. Electronic medical record (EMR) systems and reminders are helpful in this regard, but relationship building and a recommendation from a trusted provider are really essential here.

Dr. Nate Pennell: I think that makes a lot of sense. I mean, there are technology improvements. For example, our lung cancer screening program at The Cleveland Clinic, a few years back, we finally started an automated best practice alert in our EMR for patients who met the age and smoking requirements, and it led to a six-fold increase in people referred for screening. But at the same time, there's a difference between just getting this alert and putting in an order for lung cancer screening and actually getting those patients to go and actually do the screening and then follow up on it. And that, of course, requires having that relationship and discussion with the patient so that they trust that you have their best interests.

Dr. Cheryl Czerlanis: Exactly. I think that's important. You know, certainly, while technology can aid in bringing patients in, there really is no substitute for trust-building and a personal relationship with a provider.

Dr. Nate Pennell: I know that there are probably multiple examples within the U.S. where health systems or programs have put together, I would say, quality improvement projects to try to increase lung cancer screening and working with their community. There's one in particular that you discuss in your paper called the "End Lung Cancer Now" initiative. I wonder if you could take us through that.

Dr. Cheryl Czerlanis: Absolutely. "End Lung Cancer Now" is an initiative at the Indiana University Simon Comprehensive Cancer Center that has the vision to end suffering and death from lung cancer in Indiana through education and community empowerment. We discuss this as a paradigm for how community engagement is important in building and scaling a lung cancer screening program. 

In 2023, the "End Lung Cancer Now" team decided to focus its efforts on scaling and transforming lung cancer screening rates in Indiana. They developed a task force with 26 experts in various fields, including radiology, pulmonary medicine, thoracic surgery, public health, and advocacy groups. The result of this work is an 85-page blueprint with key recommendations that any system and community can use to scale lung cancer screening efforts. After building strong infrastructure for lung cancer screening at Indiana University, they sought to understand what the priorities, resources, and challenges in their communities were. To do this, they forged strong partnerships with both local and national organizations, including the American Lung Association, American Cancer Society, and others. In the first year, they actually tripled the number of screening low-dose CTs performed in their academic center and saw a 40% increase system-wide. One thing that I think is the most striking is that through their community outreach, they learned that most people prefer to get medical care close to home within their own communities. Establishing a way to support the local infrastructure to provide care became far more important than recruiting patients to their larger system. 

In exciting news, "End Lung Cancer Now" has partnered with the IU Simon Comprehensive Cancer Center and IU Health to launch Indiana's first and only mobile lung screening program in March of 2025. This mobile program travels around the state to counties where the highest incidence of lung cancer exists and there is limited access to screening. The mobile unit parks at trusted sites within communities and works in partnership, not competition, with local health clinics and facilities to screen high-risk populations.

Dr. Nate Pennell: I think that sounds like a great idea. Screening is such an important thing that it doesn't necessarily have to be owned by any one particular health system for their patients. I think. And I love the idea of bringing the screening to patients where they are. I can speak to working in a regional healthcare system with a main campus in the downtown that patients absolutely hate having to come here from even 30 or 40 minutes away, and they'd much rather get their care locally. So that makes perfect sense. 

So, under the current guidelines, there are certainly things that we can do to try to improve capturing the people that meet those. But are those guidelines actually capturing enough patients with lung cancer to make a difference? There certainly are proposals within patient advocacy communities and even other countries where there's a large percentage of non-smokers who perhaps get lung cancer. Can we expand beyond just older, current and heavy smokers to identify at-risk populations who could benefit from screening?

Dr. Cheryl Czerlanis: Yes, I think we can, and it's certainly an active area of research interest. We know that tobacco is the leading cause of lung cancer worldwide. However, other risk factors include secondhand smoke, family history, exposure to environmental carcinogens, and pulmonary diseases like COPD and interstitial lung disease. Despite these known associations, the benefit of lung cancer screening is less well elucidated in never-smokers and those at risk of developing lung cancer because of family history or other risk factors. We know that the eligibility criteria associated with our current screening guidelines focus on age and smoking history and may miss more than 50% of lung cancers. Globally, 10% to 25% of lung cancer cases occur in never-smokers. And in certain parts of the world, like you mentioned, Nate, such as East Asia, many lung cancers are diagnosed in never-smokers, especially in women. Risk-prediction models use specific risk factors for lung cancer to enhance individual selection for screening, although they have historically focused on current or former smokers. 

We know that individuals with family members affected by lung cancer have an increased risk of developing the disease. To this end, several large-scale, single-arm prospective studies in Asia have evaluated broadening screening criteria to never-smokers, with or without additional risk factors. One such study, the Taiwan Lung Cancer Screening in Never-Smoker Trial, was a multicenter prospective cohort study at 17 medical centers in Taiwan. The primary outcome of the TALENT trial was lung cancer detection rate. Eligible patients aged 55 to 75 had either never smoked or had a light and remote smoking history. In addition, inclusion required one or more of the following risk factors: family history of lung cancer, passive smoke exposure, history of TB or COPD, a high cooking index, which is a metric that quantifies exposure to cooking fumes, or a history of cooking without ventilation. Participants underwent low-dose CT screening at baseline, then annually for 2 years, and then every 2 years for up to 6 years. The lung cancer detection rate was 2.6%, which was higher than that reported in the NLST and NELSON trials, and most were stage 0 or I cancers. Subsequently, this led to the Taiwan Early Detection Program for Lung Cancer, a national screening program that was launched in 2022, targeting 2 screening populations: individuals with a heavy history of smoking and individuals with a family history of lung cancer. 

We really need randomized controlled trials to determine the true rates of overdiagnosis or finding cancers that would not lead to morbidity or mortality in persons who are diagnosed, and to establish whether the high lung detection rates are associated with a decrease in lung cancer-related mortality in these populations. However, the implementation of randomized controlled low-dose CT screening trials in never-smokers has been limited by the need for large sample sizes, lengthy follow-up, and cost. 

In another group potentially at higher risk for developing lung cancer, the role of lung cancer screening in individuals who harbor germline pathogenic variants associated with lung cancer also needs to be explored further.

Dr. Nate Pennell: We had this discussion when the first criteria came out because there have always been risk-based calculators for lung cancer that certainly incorporate smoking but other factors as well and have discussion about whether we should be screening people based on their risk and not just based on discrete criteria such as smoking. But of course, the insurance coverage for screening, you have to fit the actual criteria, which is very constrained by age and smoking history. Do you think in the U.S. there's hope for broadening our screening beyond NLST and NELSON criteria?

Dr. Cheryl Czerlanis: I do think at some point there is hope for broadening the criteria beyond smoking history and age, beyond the criteria that we have typically used and that is covered by insurance. I do think it will take some work to perhaps make the prediction models more precise or to really understand who can benefit. We certainly know that there are many patients who develop lung cancer without a history of smoking or without family history, and it would be great if we could diagnose more patients with lung cancer at an earlier stage. I think this will really count on there being some work towards trying to figure out what would be the best population for screening, what risk factors to look for, perhaps using some new technologies that may help us to predict who is at risk for developing lung cancer, and trying to increase the group that we study to try and find these early-stage lung cancers that can be cured.

Dr. Nate Pennell: Part of the reason we, of course, try to enrich our population is screening works better when you have a higher pretest probability of actually having cancer. And part of that also is that our technology is not that great. You know, even in high-risk patients who have CT scans that are positive for a screen, we know that the vast majority of those patients with lung nodules actually don't have lung cancer. And so you have to follow them, you have to use various models to see, you know, what the risk, even in the setting of a positive screen, is of having lung cancer. 

So, why don't we talk about some newer tools that we might use to help improve lung cancer screening? And one of the things that everyone is super excited about, of course, is artificial intelligence. Are there AI technologies that are helping out in early detection in lung cancer screening?

Dr. Cheryl Czerlanis: Yes, that's a great question. We know that predicting who's at risk for lung cancer is challenging for the reasons that we talked about, knowing that there are many risk factors beyond smoking and age that are hard to quantify. Artificial intelligence is a tool that can help refine screening criteria and really expand screening access. Machine learning is a form of AI technology that is adept at recognizing patterns in large datasets and then applying the learning to new datasets. Several machine learning models have been developed for risk stratification and early detection of lung cancer on imaging, both with and without blood-based biomarkers. This type of technology is very promising and can serve as a tool that helps to select individuals for screening by predicting who is likely to develop lung cancer in the future. 

A group at Massachusetts General Hospital, represented in our group for this paper by my co-authors, Drs. Fintelmann and Chang, developed Sybil, which is an open-access 3D convolutional neural network that predicts an individual's future risk of lung cancer based on the analysis of a single low-dose CT without the need for human annotation or other clinical inputs. Sybil and other machine learning models have tremendous potential for precision lung cancer screening, even, and perhaps especially, in settings where expert image interpretation is unavailable. They could support risk-adapted screening schedules, such as varying the frequency and interval of low-dose CT scans according to individual risk and potentially expand lung cancer screening eligibility beyond age and smoking history. Their group predicts that AI tools like Sybil will play a major role in decoding the complex landscape of lung cancer risk factors, enabling us to extend life-saving lung cancer screening to all who are at risk.

Dr. Nate Pennell: I think that that would certainly be welcome. And as AI is working its way into pretty much every aspect of life, including medical care, I think it's certainly promising that it can improve on our existing technology. 

We don't have to spend a lot of time on this because I know it's a little out of scope for what you covered in your paper, but I'm sure our listeners are curious about your thoughts on the use of other types of testing beyond CT screening for detecting lung cancer. I know that there are a number of investigational and even commercially available blood tests, for example, for detection of lung cancer, or even the so-called multi-cancer detection blood tests that are now being offered, although not necessarily being covered by insurance, for multiple types of cancer, but lung cancer being a common cancer is included in that. So, what do you think?

Dr. Cheryl Czerlanis: Yes, like you mentioned, there are novel bioassays such as blood-based biomarker testing that evaluate for DNA, RNA, and circulating tumor cells that are both promising and under active investigation for lung cancer and multi-cancer detection. We know that such biomarker assays may be useful in both identifying lung cancers but also in identifying patients with a high-risk result who should undergo lung cancer screening by conventional methods.

Dr. Nate Pennell: Anything that will improve on our rate of screening, I think, will be welcome. I think probably in the future, it will be some combination of better risk prediction and better interpretation of screening results, whether those be imaging or some combination of imaging and biomarkers, breath-based, blood-based. There's so much going on that it is pretty exciting, but we're still going to have to overcome the stigma and lack of public support for lung cancer screening if we're going to move the needle.

Dr. Cheryl Czerlanis: Yes, I think moving the needle is so important because we know lung cancer is still a very morbid disease, and our ability to cure patients is not where we would like it to be. But I do believe there's hope. There are a lot of motivated individuals and groups who are passionate about lung cancer screening, like myself and my co-authors, and we're just happy to be able to share some ways that we can overcome the challenges and really try and make an impact in the lives of our patients.

Dr. Nate Pennell: Well, thank you, Dr. Czerlanis, for joining me on the By the Book Podcast today and for all of your work to advance care for patients with lung cancer.

Dr. Cheryl Czerlanis: Thank you, Dr. Pennell. It's such a pleasure to be with you today. Thank you.

Dr. Nate Pennell: And thank you to our listeners for joining us today. You'll find a link to Dr. Czerlanis' article in the transcript of this episode. 

Please join us again next month for By the Book's next episode and more insightful views on topics you'll be hearing at the education sessions from ASCO meetings throughout the year, and our deep dives on approaches that are shaping modern oncology.

Disclaimer:

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Follow today’s speakers:    

Dr. Nathan Pennell   

@n8pennell  

@n8pennell.bsky.social

Dr. Cheryl Czerlanis

Follow ASCO on social media:    

@ASCO on X (formerly Twitter)    

ASCO on Bluesky   

ASCO on Facebook    

ASCO on LinkedIn    

Disclosures:   

Dr. Nate Pennell:       

Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron      

Research Funding (Institution): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi   

Dr. Cheryl Czerlanis:

Research Funding (Institution): LungLife AI, AstraZeneca, Summit Therapeutics

Host Dr. Nate Pennell and his guest, Dr. Chloe Atreya, discuss the ASCO Educational Book article, “Integrative Oncology: Incorporating Evidence-Based Approaches to Patients With GI Cancers,” highlighting the use of mind-body approaches, exercise, nutrition, acupuncture/acupressure, and natural products.

Dr. Nate Pennell: Welcome to ASCO Education: By the Book, our new monthly podcast series that will feature engaging discussions between editors and authors from the ASCO Educational Book. We'll be bringing you compelling insights on key topics featured in Education Sessions at ASCO meetings and some deep dives on the approaches shaping modern oncology. 

I'm Dr. Nate Pennell, director of the Cleveland Clinic Lung Cancer Medical Oncology Program as well as vice chair of clinical research for the Taussig Cancer Institute. Today, I'm delighted to welcome Dr. Chloe Atreya, a professor of Medicine in the GI Oncology Group at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, and the UCSF Osher Center for Integrative Health, to discuss her article titled, “Integrative Oncology Incorporating Evidence-Based Approaches to Patients With GI Cancers”, which was recently published in the ASCO Educational Book.

Our full disclosures are available in the transcript of this episode. 

Dr. Atreya, it's great to have you on the podcast today. Thanks for joining me.

Dr. Chloe Atreya: Thanks Dr. Pennell. It's a pleasure to be here.

Dr. Nate Pennell: Dr. Atreya, you co-direct the UCSF Integrative Oncology Program with a goal to really help patients with cancer live as well as possible. And before we dive into the review article and guidelines, I'd love to just know a little bit about what inspired you to go into this field?

Dr. Chloe Atreya: Yeah, thank you for asking. I've had a long-standing interest in different approaches to medicine from global traditions and I have a degree in pharmacology, and I continue to work on new drug therapies for patients with colorectal cancer. And one thing that I found is that developing new drugs is a long-term process and often we're not able to get the drugs to the patients in front of us. And so early on as a new faculty member at UCSF, I was trying to figure out what I could do for the patient in front of me if those new drug therapies may not be available in their lifetime. And one thing I recognized was that in some conversations the patient and their family members, even if the patient had metastatic disease, they were able to stay very present and to live well without being sidelined by what might happen in the future. And then in other encounters, people were so afraid of what might be happening in the future, or they may have regrets maybe about not getting that colonoscopy and that was eroding their ability to live well in the present. 

So, I started asking the patients and family members who were able to stay present, “What's your secret? How do you do this?” And people would tell me, “It's my meditation practice,” or “It's my yoga practice.” And so, I became interested in this. And an entry point for me, and an entry point to the Osher Center at UCSF was that I took the Mindfulness-Based Stress Reduction Program to try to understand experientially the evidence for this and became very interested in it. I never thought I would be facilitating meditation for patients, but it became a growing interest. And as people are living longer with cancer and are being diagnosed at younger ages, often with young families, how one lives with cancer is becoming increasingly important.

Dr. Nate Pennell: I've always been very aware that it seemed like the patients that I treated who had the best quality of life during their life with cancer, however that ended up going, were those who were able to sort of compartmentalize it, where, when it was time to focus on discussing treatment or their scans, they were, you know, of course, had anxiety and other things that went along with that. But when they weren't in that, they were able to go back to their lives and kind of not think about cancer all the time. Whereas other people sort of adopt that as their identity almost is that they are living with cancer and that kind of consumes all of their time in between visits and really impacts how they're able to enjoy the rest of their lives. And so, I was really interested when I was reading your paper about how mindfulness seemed to be sort of like a formal way to help patients achieve that split. I'm really happy that we're able to talk about that.

Dr. Chloe Atreya: Yeah, I think that's absolutely right. So, each of our patients is more than their cancer diagnosis. And the other thing I would say is that sometimes patients can use the cancer diagnosis to get to, “What is it that I really care about in life?” And that can actually heighten an experience of appreciation for the small things in life, appreciation for the people that they love, and that can have an impact beyond their lifetime.

Dr. Nate Pennell: Just in general, I feel like integrative medicine has come a long way, especially over the last decade or so. So, there's now mature data supporting the incorporation of elements of integrative oncology into comprehensive cancer care. We've got collaborations with ASCO. They've published clinical practice guidelines around diet, around exercise, and around the use of cannabinoids. ASCO has worked with the Society for Integrative Oncology to address management of pain, anxiety, depression, fatigue – lots of different evidence bases now to try to help guide people, because this is certainly something our patients are incredibly interested in learning about. Can you get our listeners up to speed a little bit on the updated guidelines and resources supporting integrative oncology?

Dr. Chloe Atreya: Sure. I can give a summary of some of the key findings. And these are rigorous guidelines that came together by consensus from expert panels. I had the honor of serving on the anxiety and depression panel. So, these panels will rate the quality of the evidence available to come up with a strength of recommendation. I think that people are at least superficially aware of the importance of diet and physical activity and that cannabis and cannabinoids have evidence of benefit for nausea and vomiting. They may not be aware of some of the evidence supporting these other modalities. So, for anxiety and depression, mindfulness-based interventions, which include meditation and meditative movement, have the strongest level of evidence. And the clinical practice guidelines indicate that they should be offered to any adult patient during or after treatment who is experiencing symptoms of anxiety or depression. Other modalities that can help with anxiety and depression include yoga and Tai Chi or Qigong. And with the fatigue guidelines, mindfulness-based interventions are also strongly recommended, along with exercise and cognitive behavioral therapy, Tai Chi and Qigong during treatment, yoga after treatment. 

And some of these recommendations also will depend on where the evidence is. So, yoga is an example of an intervention that I think can be helpful during treatment, but most of our evidence is on patients who are post-treatment. So, most of our guidelines separate out during treatment and the post-treatment phase because the quality of evidence may be different for these different phases of treatment. 

With the pain guidelines, the strongest recommendation is for acupuncture, specifically for people with breast cancer who may be experiencing joint pain related to aromatase inhibitors. However, acupuncture and other therapies, including massage, can be helpful with pain as well. So those are a few of the highlights.

Dr. Nate Pennell: Yeah, I was surprised at the really good level of evidence for the mindfulness-based practices because I don't think that's the first thing that jumps to mind when I think about integrative oncology. I tend to think more about physical interventions like acupuncture or supplements or whatnot. So, I think this is really fantastic that we're highlighting this. 

And a lot of these interventions like the Qigong, Tai Chi, yoga, is it the physical practice of those that benefits them or is it that it gives them something to focus on, to be mindful of? Is that the most important intervention? It doesn't really matter what you're doing as long as you have something that kind of takes you out of your experience and allows you to focus on the moment.

Dr. Chloe Atreya: I do think it is a mind, body and spirit integration, so that all aspects are important. We also say that the best practice is the one that you actually practice. So, part of the reason that it's important to have these different modalities is that not everybody is going to take up meditation. And there may be people for whom stationary meditation, sitting and meditating, works well, and other people for whom meditative movement practices may be what they gravitate to. And so, I think that it's important to have a variety of options. And one thing that's distinct from some of our pharmacologic therapies is that the safety of these is, you know, quite good. So, it becomes less important to say, “Overall, is Tai Chi better or is yoga better?” for instance. It really depends on what it is that someone is going to take up.

Dr. Nate Pennell: And of course, something that's been really nice evidence-based for a long time, even back when I was in my training in the 2000s with Jennifer Temel at Massachusetts General Hospital, was the impact of physical activity and exercise on patients with cancer. It seems like that is pretty much a universally good recommendation for patients.

Dr. Chloe Atreya: Yes, that's absolutely right. Physical activity has been associated with improved survival after a cancer diagnosis. And that's both cancer specific survival and overall survival. 

The other thing I'll say about physical activity, especially the mindful movement practices like Tai Chi and Qigong and yoga, is that they induce physiologic shifts in the body that can promote relaxation, so they can dampen that stress response in a physiologic way. And these movement practices are also the best way to reduce cancer-associated fatigue.

Dr. Nate Pennell: One of the things that patients are always very curious about when they talk to me, and I never really feel like I'm as well qualified as I'd like to be to advise them around dietary changes in nutrition. And can you take me a little bit through some of the evidence base for what works and what doesn't work?

Dr. Chloe Atreya: Sure. I do think that it needs to be tailored to the patient's needs. Overall, a diet that is plant-based and includes whole grains is really important. And I often tell patients to eat the rainbow because all of those different phytochemicals that cause the different colors in our fruits and vegetables are supporting different gut microbiota. So that is a basis for a healthy gut microbiome. That said, you know, if someone is experiencing symptoms related to cancer or cancer therapy, it is important to tailor dietary approaches. This is where some of the mindful eating practices can help. So, sometimes actually not just focusing on what we eat, but how we eat can help with symptoms that are associated with eating. So, some of our patients have loss of appetite, and shifting one's relationship to food can help with nutrition. Sometimes ‘slow it down’ practices can help both with appetite and with digestion.

Dr. Nate Pennell: One of the things that you said both in the paper and just now on our podcast, talking about how individualized and personalized this is. And I really liked the emphasis that you had on flexibility and self-compassion over rigid discipline and prescriptive recommendations here. And this is perhaps one of the real benefits of having an integrative oncology team that can work with patients as opposed to them just trying to find things online.

Dr. Chloe Atreya: Yes, particularly during treatment, I think that's really important. And that was borne out by our early studies we called “Being Present.” So, after I was observing the benefits anecdotally among my patients of the ability to be present, we designed these pilot studies to teach meditation and meditative practices to patients. And in these pilot studies, the original ones were pretty prescriptive in a way that mindfulness-based stress reduction is fairly prescriptive in terms of like, “This is what we're asking you to do. Just stick with the program.” And there can be benefits if you can stick with the program. It's really hard though if someone is going through treatment and with GI cancers, it may be that they're getting chemotherapy every two weeks and they have one week where they're feeling really crummy and another week where they're trying to get things done. And we realized that sometimes people were getting overwhelmed and feeling like the mindfulness practice was another thing on their to-do list and that they were failing if they didn't do this thing that was important for them. And so, we've really kind of changed our emphasis. And part of our emphasis now is on incorporating mindfulness practices into daily life. Any activity that doesn't require a lot of executive function can be done mindfully, meaning with full attention. And so, especially for some of our very busy patients, that can be a way of, again, shifting how I'm doing things rather than adding a new thing to do.

Dr. Nate Pennell: And then another part I know that patients are always very curious about that I'm really happy to see that we're starting to build an evidence base for is the use of supplements and natural products. So, can you take us a little bit through where we stand in terms of evidence behind, say, cannabis and some of the other available products out there?

Dr. Chloe Atreya: Yeah, I would say that is an area that requires a lot more study. It's pretty complicated because unlike mindfulness practices where there are few interactions with other treatments, there is the potential for interactions, particularly with the supplements. And the quality of the supplements matters. And then there tends to be a lot of heterogeneity among the studies both in the patients and what other treatments they may be receiving, as well as the doses of the supplements that they're receiving. 

One of my earliest mentors at Yale is someone named Dr. Tommy Chang, who has applied the same rigor that that we apply to testing of biomedical compounds to traditional Chinese medicine formulas. And so, ensuring that the formulation is stable and then formally testing these formulations along with chemotherapy. And we need more funding for that type of research in order to really elevate our knowledge of these natural products. We often will direct patients to the Memorial Sloan Kettering ‘About Herbs, Botanicals, and Other Products’ database as one accessible source to learn more about the supplements. We also work with our pharmacists who can provide the data that exists, but we do need to take it with a grain of salt because of the heterogeneity in the data. And then it's really important if people are going to take supplements, for them to take supplements that are of high quality. And that's something in the article that we list all of the things that one should look for on the label of a supplement to ensure that it is what it's billed to be.

Dr. Nate Pennell: So, most of what we've been talking about so far has really been applying to all patients with cancer, but you of course are a GI medical oncologist, and this is a publication in the Educational Book from the ASCO GI Symposium. GI cancers obviously have an incredibly high and rising incidence rate among people under 50, representing a quarter of all cancer incidence worldwide, a third of cancer related deaths worldwide. Is there something specific that GI oncologists and patients with GI cancers can take home from your paper or is this applicable to pretty much everyone?

Dr. Chloe Atreya: Yeah, so the evidence that we review is specifically for GI cancers. So, it shows both its strengths and also some of the limitations. So many of the studies have focused on other cancers, especially breast cancer. In the integrative oncology field, there are definitely gaps in studying GI cancers. At the same time, I would say that GI cancers are very much linked to lifestyle in ways that are complicated, and we don't fully understand. However, the best ways that we can protect against development of GI cancers, acknowledging that no one is to blame for developing a GI cancer and no one is fully protected, but the best things that we can do for overall health and to prevent GI cancers are a diet that is plant-based, has whole grains. There's some data about fish that especially the deep-water fish, may be protective and then engaging in physical activity. 

One thing I would like for people to take away is that these things that we know that are preventative against developing cancer are also important after development of a GI cancer. Most of the data comes from studies of patients with colorectal cancer and that again, both cancer specific and overall mortality is improved with better diet and with physical activity. So, this is even after a cancer diagnosis. And I also think that, and this is hard to really prove, but we're in a pretty inflammatory environment right now. So, the things that we can do to decrease stress, improve sleep, decrease inflammation in the body, and we do know that inflammation is a risk factor for developing GI cancers. So, I think that all of the integrative modalities are important both for prevention and after diagnosis.

Dr. Nate Pennell: And one of the things you just mentioned is that most of the studies looking at integrative oncology and GI cancers have focused on colorectal cancer, which of course, is the most common GI cancer. But you also have pointed out that there are gaps in research and what's going on and what needs to be done in order to broaden some of this experience to other GI cancers.

Dr. Chloe Atreya: Yeah, and I will say that there are gaps even for colorectal cancer. So right now, some of the authors on the article are collaborating on a textbook chapter for the Society for Integrative Oncology. And so, we're again examining the evidence specifically for colorectal cancer and are in agreement that the level of evidence specific to colorectal cancer is not as high as it is for all patients with adult cancers. And so even colorectal cancer we need to study more. 

Just as there are different phases of cancer where treatments may need to be tailored, we also may need to tailor our treatments for different cancer types. And that includes what symptoms the patients are commonly experiencing and how intense the treatment is, and also the duration of treatment. Those are factors that can influence which modalities may be most important or most applicable to a given individual.

Dr. Nate Pennell: So, a lot of this sounds fantastic. It sounds like things that a lot of patients would really appreciate working into their care. Your article focused a little bit on some of the logistics of providing this type of care, including group medical visits, multidisciplinary clinics staffed by multiple types of clinicians, including APPs and psychologists, and talked about the sustainability of this in terms of increasing the uptake of guideline-based integrative oncology. Talk a little bit more about both at your institution, I guess, and the overall health system and how this might be both sustainable and perhaps how we broaden this out to patients outside of places like UCSF.

Dr. Chloe Atreya: Yes, that's a major focus of our research effort. A lot of comprehensive cancer centers and other places where patients are receiving care, people may have access to dietitians, which is really important and nutritionists. In the article we also provide resources for working with exercise therapists and those are people who may be working remotely and can help people, for instance, who may be in, in rural areas. And then our focus with the mind-body practices in particular has been on group medical visits. And this grew out of, again, my ‘being present’ pilot studies where we were showing some benefit. But then when the grant ends, there isn't a way to continue to deliver this care. And so, we were asking ourselves, you know, is there a way to make this sustainable? And group medical visits have been used in other settings, and they've been working really well at our institution and other institutions are now taking them up as well. And this is a way that in this case it's me and many of my colleagues who are delivering these, where I can see eight or ten patients at once. In my case, it's a series of four two-hour sessions delivered by telehealth. So, we're able to focus on the integrative practices in a way that's experiential. So, in the clinic I may be able to mention, you know, after we go over the CT scans, after we go over the labs and the molecular profiling, you know, may be able to say, “Hey, you know, meditation may be helpful for your anxiety,” but in the group medical visits we can actually practice meditation, we can practice chair yoga. And that's where people have that experience in their bodies of these different modalities. And the feedback that we're receiving is that that sticks much more to experience it then you have resources to continue it. And then the group is helpful both in terms of delivery, so timely and efficient care for patients. It's also building community and reducing the social isolation that many of our patients undergoing treatment for cancer experience.

Dr. Nate Pennell: I think that makes perfect sense, and I'm glad you brought up telehealth as an option. I don't know how many trained integrative oncologists there are out there, but I'm going to guess this is not a huge number out there. And much like other specialties that really can improve patients’ quality of life, like palliative medicine, for example, not everyone has access to a trained expert in their cancer center, and things like telemedicine and telehealth can really potentially broaden that. How do you think telehealth could help broaden the exposure of cancer patients and even practitioners of oncology to integrative medicine?

Dr. Chloe Atreya: Yes, I think that telehealth is crucial for all patients with cancer to be able to receive comprehensive cancer care, no matter where they're receiving their chemotherapy or other cancer-directed treatments. So, we will routinely be including patients who live outside of San Francisco. Most of our patients live outside of San Francisco. There's no way that they could participate if they had to drive into the city again to access this. And in the group setting, it's not even safe for people who are receiving chemotherapy to meet in a group most times. And with symptoms, often people aren't feeling so well and they're able to join us on Zoom in a way that they wouldn't be able to make the visit if it was in person. And so, this has really allowed us to expand our catchment area and to include patients, in our case, in all of California. You also mentioned training, and that's also important. So, as someone who's involved in the [UCSF] Osher Collaborative, there are faculty scholars who are at universities all over the US, so I've been able to start training some of those physicians to deliver group medical visits at their sites as well via telehealth.

Dr. Nate Pennell: I'm glad we were able to make a plug for that. We need our political leadership to continue to support reimbursement for telehealth because it really does bring access to so many important elements of health care to patients who really struggle to travel to tertiary care centers. And their local cancer center can be quite a distance away. 

So, sticking to the theme of training, clinician education and resources are really crucial to continue to support the uptake of integrative oncology in comprehensive cancer care. Where do you think things stand today in terms of clinician education and professional development in integrative oncology.

Dr. Chloe Atreya: It's growing. Our medical students now are receiving training in integrative medicine, and making a plug for the Educational Book, I was really happy that ASCO let us have a table that's full of hyperlinks. So that's not typical for an article. Usually, you have to go to the reference list, but I really wanted to make it practical and accessible to people, both the resources that can be shared with patients that are curated and selected that we thought were of high-quality examples for patients. At the bottom of that table also are training resources for clinicians, and some of those include: The Center for Mind-Body Medicine, where people can receive training in how to teach these mind-body practices; The Integrated Center for Group Medical Visits, where people can learn how to develop their own group medical visits; of course, there's the Society for Integrative Oncology; and then I had just mentioned the Osher Collaborative Faculty Fellowship.

Dr. Nate Pennell: Oh, that is fantastic. And just looking through, I mean, this article is really a fantastic resource both of the evidence base behind all of the elements that we've discussed today. Actually, the table that you mentioned with all of the direct hyperlinks to the resources is fantastic. Even recommendations for specific dietary changes after GI cancer diagnosis. So, I highly recommend everyone read the full paper after they have listened to the podcast today. 

Before we wrap up, is there anything that we didn't get a chance to discuss that you wanted to make sure our listeners are aware of?

Dr. Chloe Atreya: One thing that I did want to bring up is the disparities that exist in access to high quality symptom management care. So, patients who are racial and ethnic minorities, particularly our black and Latinx patients, the evidence shows that they aren't receiving the same degree of symptom management care as non-Hispanic White patients. And that is part of what may be leading to some of the disparities in cancer outcomes. So, if symptoms are poorly managed, it's harder for patients to stay with the treatment, and integrative oncology is one way to try to, especially with telehealth, this is a way to try to improve symptom management for all of our patients to help improve both their quality of life and their cancer outcomes.

Dr. Nate Pennell: Well, Dr. Atreya, it's been great speaking with you today and thank you for joining me on the ASCO Education: By the Book Podcast and thank you for all of your work in advancing integrative oncology for GI cancers and beyond.

Dr. Chloe Atreya: Thank you, Dr. Pennell. It's been a pleasure speaking with you.

Dr. Nate Pennell: And thank you to all of our listeners who joined us today. You'll find a link to the article discussed today in the transcript of the episode. We hope you'll join us again for more insightful views on topics you'll be hearing at the Education Sessions from ASCO meetings throughout the year and our deep dives on approaches that are shaping modern oncology.

Disclaimer:

The purpose of this podcast is to educate, educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Follow today’s speakers:   

Dr. Nathan Pennell  

@n8pennell 

@n8pennell.bsky.social 

Dr. Chloe Atreya

 Follow ASCO on social media:   

@ASCO on X (formerly Twitter)   

ASCO on Bluesky  

ASCO on Facebook   

ASCO on LinkedIn   

Disclosures:  

Dr. Nate Pennell:      

Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron     

Research Funding (Institution): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi  

Dr. Chloe Atreya:

Consulting or Advisory Role: Roche Genentech, Agenus

Research Funding (Institution): Novartis, Merck, Bristol-Myers Squibb, Guardant Health, Gossamer Bio, Erasca, Inc.

People who live in major cities in the US and abroad tend to benefit from better cancer care due to having access to more doctors, facilities and equipment. In contrast, those who live in rural areas face many challenges accessing consistent and quality care. 

In Part One of this ASCO Education Podcast Dr. Jack Hensold, a hematologist/oncologist in Bozeman, Montana and Chair of the ASCO Rural Cancer Care Task Force, Dr. Chris Prakash, Medical Oncologist in Paris, Texas and Medical Director of Texas Oncology and President of the Texas Society of Clinical Oncology, and Professor Sabe Sabesan, a Medical Oncologist in Townsville, Australia and the President-Elect of the Clinical Oncology Society of Australia will examine the realties practicing oncology in rural areas. 
They discuss the difficulties of having to travel long distances for treatment (5:30), the effectiveness of telehealth (8:07) and solutions to recruiting a supportive care workforce in rural areas  and facilitating access to imaging facilities and specialized treatment (18:12).

Speaker Disclosures
Sabe Sabesan: Speakers Bureau - Merck
Sucharu Prakash: Speakers Bureau - Myriad Genetics  
Jack Hensold:  Consulting or Advisory Role Company - Vibliome Therapeutics

Resources 
Policy Recommendations for Improving Rural Cancer Services in the United States 

If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org.

TRANSCRIPT

Disclosures for this podcast are listed on the podcast page.

 Dr. Jack Hensold: Hello and welcome to this two-part episode of the ASCO Education Podcast. Today we will explore some real-time and real-world issues that oncologists face while practicing in rural areas in the US and abroad. Cities tend to benefit from having more doctors, facilities, and equipment to address the health needs of the population. In contrast, people who live in rural areas – estimated to be about 25% of the US population – face various challenges to obtaining consistent health care, including scarce medical personnel and infrastructure. Transportation of that care may involve considerable time and financial expense.

 I'm Dr. Jack Hensold, the Hematologist/Oncologist in Bozeman, Montana, and Chair of the ASCO Rural Cancer Care Task Force. I also serve as Medical Director of Regional Outreach at Bozeman Health. Joining me is Chris Prakash, Oncologist and Medical Director of Texas Oncology and President of the Texas Society of Clinical Oncology. Chris is also the Director of Quality Services for the statewide group and leads Texas Oncologist's Precision Medicine Initiative.

 Also joining me is Professor Sabe Sabesan, a Medical Oncologist in regional Australia. He is the President-Elect of the Clinical Oncology Society of Australia and Clinical Director of the Australian Teledyne Health Program, led by the Queensland State Department of Health. Professor Sabesan is an internationally recognized expert in the area of tele-oncology. He has developed and evaluated various oncology models to deliver cancer care closer to home. 

Providing healthcare is a very involved career, more so in rural areas. Dr. Prakash, you finished your oncology training in Detroit, yet you practice primarily in rural Texas. Can you detail the factors that led to your decision in practicing oncology in a rural setting?

 Dr. Chris Prakash: Thank you, Jack, for having me as part of this podcast. I finished my fellowship at Wayne State in Detroit, Michigan, and we were looking for a place to raise our kids and family and to find a good practice for myself. My daughter was two years old at that time. We were looking for a quiet, safe place with a laidback lifestyle, but at the same time a dynamic oncology practice. That's how I found East Texas, which is primarily a rural area. The small community here, good schools, and nice, accepting people really appealed to us. So we decided to give it a chance. We are still here almost 23 years later. My daughter has grown up and is in medical school. My son, who was born in Paris, Texas, is planning to go to med school next year.

 Over the last couple of decades, I've found that practicing oncology in a rural setting is indeed very rewarding. You can make a difference in people's lives here. People are simple. They have faith and respect and follow doctors' advice. Practicing here, I've had a real chance to make a difference in not only people's lives but also in the overall healthcare system and in health policy. As you know, Jack, about 18% to 20% of the population lives in rural areas in the US. But only 3% of oncologists are available to provide care for them. So I'm not only fulfilling a need but also satisfying a desire to contribute.

 Dr. Jack Hensold: Chris, could you clarify the nature of your practice? Are you a solo oncologist within a much larger group spread out over the state, or is there more than one oncologist on your site?

Dr. Chris Prakash: Yeah, so I'm part of Texas Oncology, which is a statewide large group with multiple sites of service. In my location, there are three medical oncologists and one radiation oncologist. So we serve the catchment area of Northeast Texas and Southeast Oklahoma. But within Texas Oncology, we have locations spread out all over the state.

Dr. Jack Hensold: Thank you for that clarity. Professor Sabesan, you started in Sri Lanka and are now in a rural area of Australia. How did that happen?

 Professor Sabe Sabesan: I grew up in northern Sri Lanka in a village but moved to Australia because of the war in Sri Lanka in ‘90. So I did my med school in Adelaide, Australia. During my med school, we had to do a lot of rural clinical placements. And also as a result of that, I did my internship in a central Australian town called Alice Springs. Throughout that journey, I saw firsthand the difficulties these communities face in accessing healthcare, basic healthcare. So when I finished my training in medical oncology, I was looking for a place where I could contribute to minimizing these difficulties, but also taking an academic angle to this. So I chose a regional center called Townsville in North Queensland as our home that actually serves a large rural and indigenous population, but also it is an academic hub for rural medicine. So it kind of served my clinical and academic needs, and we've been there last 20 years now.

Dr. Jack Hensold: A significant hurdle for patients in rural areas is transportation. Patients sometimes travel an entire day or stay overnight near the clinic, where they will be examined or treated. What resources have been developed to assist with transportation to help patients come back for test results, appointments, and treatments? Chris? 

Dr. Chris Prakash: Transportation, that's a big hurdle for many patients across the country, but mainly for the rural population. So, as I just said, my practice is in Paris, Texas, but the draw is about a quarter of a million. So patients come to see us here to receive their medical care from all over Northeast Texas as well as Southeast Oklahoma, and there is no public transportation in many of these areas. The average time to commute for many of my patients is in excess of an hour and a half each way. Patients do travel sometimes an entire day. They sometimes have to stay overnight to receive their treatments the next day. 

I recall a patient with tonsillar cancer last year who was receiving concurrent chemotherapy and radiation. So he lived almost three hours away. This was too cost prohibitive for him to travel back and forth on a daily basis for radiation therapy. So what he did was set up his camper right behind the cancer center, which certainly made it a lot easier for him to get his treatments that way. I would not recommend that as a routine practice for everybody, but it did work out for him  

Close by there is a community of Choctaw Indians here in Southeast Oklahoma also, and they do have some options for transportation for just their citizens. And locally, some local church groups and volunteer organizations provide assistance with transportation for some patients as well. But that is a problem. Transportation is a big access issue for my population.

Dr. Jack Hensold: Thank you. And just to make a comment, there's actually a fair amount of literature regarding what we refer to as financial toxicity associated with the need to travel. Sabe, do you have some transportation problems in your area? I would assume…

Professor Sabe Sabesan: This is similar to what Chris and you are describing, Jack. Our area is 2000 by 1000 kilometers with about 650,000 population. There are scattered rural hospitals, but really there's no consistent public transport. But the government does pay for transport and accommodation. I heard that it doesn't fully cover it. But one of the disappointing things is that if you're traveling for clinical trials, that subsidy is not there for them. So that's probably one of the reasons why the governments have gone for the telehealth investment.

Dr. Jack Hensold: Thank you. Telehealth is a critical tool for providing healthcare in many areas, including rural areas. How do you manage the health literacy problems of ethnically, educationally, and socioeconomically diverse populations using telehealth? Chris?

Dr. Chris Prakash: Telehealth has been around for a long time, but during the pandemic, that’s when we needed to keep our patients safe and away in their homes and still continue to give healthcare to them. So we conducted many visits through telemedicine at that time. Telehealth is especially used for many patients in rural areas because they have problems with access. But there are many challenges. As you know there is a broadband divide in the US. About 1 in 4 Americans do not have a good broadband connection so it is very difficult for them to perform a video telehealth visit. Audio works out okay a lot of times, but to do a good video telehealth visit, that’s a difficulty.  

Also, as you know, many of the flexibilities that we were afforded during the pandemic regarding telemedicine, they are slowly going away. So that’s making telemedicine even more difficult to do. But telemedicine is a boon for many of the patients who live in rural areas. I remember just the other day I saw an elderly couple, the man had just been diagnosed with advanced lung cancer. In the room, he requested that his children join the conversation via FaceTime on his phone so that they can listen in to what I had to say and what I had to tell them. This was indeed very helpful for them. I was able to explain to the patient, his wife, as well as his children who joined via FaceTime about the diagnosis, which was new, the treatment plan, expectations moving forward, and all of that.  

So even though this was not a true televisit, it really demonstrates how technology can help us deliver good communication and good oncology care in many situations. But still, I would say that for many patients, telemedicine is not ideal. It’s especially true given the devastating diagnosis of cancer. Patients want to see their doctors face-to-face. As a doctor, I want to examine them. And also, body language is very important. It is important for my patients to trust me as a physician, and that’s hard to do sometimes via video chat. 

So right now my nurse practitioners do a lot of chemo teaching through telemedicine. Now that is really helpful for them because this can be done over multiple teaching sessions, it makes it a lot easier for the patient. Because rather than coming into the clinic for all these visits, they can learn from the comfort of their homes before they really start the toxic chemotherapy. 

Dr. Jack Hensold: Chris, thank you for that. I think that you make a very valid point and one that I've made, which is that telehealth is a great tool for overcoming geographic barriers in rural areas. But I think we just simply have to accept the fact that it's not as good as a face-to-face visit. So how we blend the use of telehealth with face-to-face visits I think is going to be a challenge moving forward.

Dr. Chris Prakash: Yeah, I totally agree. I think toxicity management is great. I mean, it's a great tool to call and see how patients are doing after treatment. But that initial visit, there's something to be said about establishing a rapport and faith and trust in your doctor when you're treating cancer.

Dr. Jack Hensold: I completely agree. Sabe, you sound like you're one of the experts in Australia regarding telehealth. I wonder if you have some comments about your experience.

Professor Sabe Sabesan: Yeah, I would say it's an evolving experience which has evolved over 15 years. So in terms of the health literacy needs, my observation is actually the same whether it's in person or in telehealth. What we observed is that we just need to tailor to the patient's needs. When we first developed the telemedicine, we had the same issues, developing rapport and seeing first consultations in person. But what we did, we started doing a lot of shared care models and tele supervision models with rural facilities rather than directly into homes. So what that meant, we had patients' families can attend, especially the primary care physicians, and the rural nurses were able to sit in with the patients. So that means if there were any communication issues or any translation aspects, language-wise or explaining medical lingo, there was a system in place in the rural sector that is close to home that was provided by the primary care physicians and the families. 

And also then from that experience, we did some research and the patients actually said they were happy to continue initial consultations on the telehealth consultation, provided there were families involved, the primary care physicians were in there, and also the aboriginal health workers. So for some regions now we do the initial consultation purely on telehealth because what also what telehealth does for the first consultation, if we need to then bring them to our center, then we would be able to coordinate the whole trip rather than coming back and forth. So that's actually probably the difference in a couple of the larger centers. But the other main benefit I actually found for indigenous patients is that we can involve the whole family in the patient care and normally that means they are able to ensure compliance and compliance with clinic visits. So it's been evolving but really it is what our models, some of them are tele-oncology replacing face-to-face, some of them are hybrid, some of them are treatment-related. So it's really based on the needs of that little communities. That's what we've been doing.

Dr. Chris Prakash: If I can ask you a question Sabe, on that, do you experience barriers to practice across state boundaries in Australia? Because I know in the US that's a big issue, that's a hurdle. Licensing is an issue across state boundaries and also broadband issue because a lot of my patients, they simply don't have the broadband width to get on a video chat. Do you experience that in Australia as well?

Professor Sabe Sabesan: So we definitely have the broadband divide in Australia, but luckily the state governments have actually invested heavily on fiber. So all the health facilities, whether they are small or large, they are all connected on fiber. So if you do video calls or telehealth within that system, it is pretty good. But as soon as you go outside to a primary care facility that is not part of a state facility or home, you run into trouble with broadband. But in terms of the state boundaries, I think it is a bit loose. I don't know whether there's actually a strict monitoring of the systems, but because the whole Australian system is funded by Medicare, it really doesn't matter where the patient lives as long as you bill the patient based on the consultation.

Dr. Jack Hensold: And I'd like to just respond to something you said, Sabe, too, which is the involvement of primary care doctors and local healthcare workers in the care of patients, is something I will return to later in this conversation. But I think it's important that we consider when we're keeping patients out of our larger centers and treating them in their own home areas, that we are relying on supportive care by those primary care providers. Any other comments regarding the telehealth issue?  

Professor Sabe Sabesan: In terms of the primary care shared care models and collaborations, that is actually one of the important aspects of telehealth because we have in the rural sector, the turnover of the staff is pretty high. So then what happens if we want to provide consistent medical service on telehealth? Something needs to be consistent so we become the consistent aspect of the partnership. So then that gives us bit more safety that there's a shared care model, but also what we found now that in terms of educating on oncology topics, the shared care models actually give you an opportunity for case-based discussion. I think there is a benefit for workforce development as well, as well as connecting the rural workforce with a network of workforce.

Dr. Chris Prakash: Involving primary care physicians in the total care of the patient is vital, especially in rural areas because they really depend upon their PCPs and often these are APPs providing their primary care. You’ve got to manage their diabetes and hypertension and go through all their medications, antiemetics pain medications, work with the local pharmacy. There are so many issues that go into treating a patient with cancer and as an oncologist sitting 100 miles away, I'm not going to be able to take care of every detailed aspect of their care. So what I do is involve their primary physician from the very beginning. So when the patient first comes to me, it could be via telemedicine or not, I'm calling them back and saying, “Hey, I saw so and so. This is my diagnosis, this is my plan. I'm going to do all the treatments here at my center. But whatever's possible you can do locally, I would appreciate that.” If there's labs that can be drawn, imaging that can be done locally, any testing that can be done locally, patients really value that because they don't want to travel 2 hours just for a CT scan if they can avoid it. That's my practice.  

Dr. Jack Hensold: Thank you. You mentioned something that we're going to touch on next, which is that in rural areas it is often difficult to access labs, imaging facilities, and other specialized treatments, certainly CAR T therapy and other highly technical therapies. There are other services that may be limited in a rural area such as mental health, fertility preservation, palliative care, access to social workers. Do you have solutions to address that really supportive care and those needs?

Dr. Chris Prakash: Yeah, I think, Jack, you touched on a very, very critical challenge right now. It's a workforce issue. It's very hard to hire and keep good support staff not only in rural areas but all over the country right now. So you mentioned social workers, nurses, nutrition specialists, mental health providers, even fertility services. They're very hard to find in rural areas. There's a big workforce problem, right, all over the country. But the pandemic really exacerbated that. I mean, it's hard to find good staff anywhere and there's no easy solution to fix this problem. So what we need to look for is maybe provide incentives such as loan forgiveness programs or tuition payment programs, or repayment. Really anything that keeps professionals in rural settings. And we need to find people who like working in these areas because that's a very difficult problem as well. 

And as you know, many specialized treatments, stem cell transplants, CAR T cell therapy, specialized neurosurgeries or cardiothoracic surgeries, or many oncologic surgeries, they can only be done at big tertiary centers in big cities often. So patients have got to travel a few hours to go there. So what we can do to make it easier on them is provide the first consultations with those specialists via telemedicine. And if they're thought to be good candidates for the procedures, then they can make a trip that's necessary to the city, let's say. But also you mentioned consistency, that is the key. It's very important to be consistent if you want to provide quality cancer care. It could be imaging, it could be diagnostics, molecular testing, or any kind of therapy that you deliver. They should all be consistent no matter where a patient is being treated. So that brings into question provider education. Many oncologists in rural areas, they're generalists, they treat all cancers. They do not specialize in one area. It's really hard to keep up with all the latest information that's coming out. So it's important that we provide all educational tools possible to keep them up to date. 

I just moderated a meeting called Oncology Congress. So this is geared towards cancer care providers in rural areas. It's a free CME webcast, various topics on cancer, excellent faculty, and the main thing is that the discussion is geared towards improving multidisciplinary care in those rural settings. So I think another thing that we could think of as a solution to this problem is virtual tumor boards. I mean, they're very helpful where somebody can get on and get an opinion regarding a difficult case. But I think most helpful is if you have a network of doctors or specialists that you can rely on, you can call somebody, a quick consult or say, “Hey, I have a problem, a challenging case, what would you recommend?” Because sometimes we just don't have time to wait for that tumor board or wait for an official consultation. So, yeah, it's a difficult challenge.

Dr. Jack Hensold: Yes. And again, a point that you made that I'd like to respond to is the virtual tumor boards and basically shared education with maybe a larger group. As we've kind of in Montana looked at a development of hub and spoke models, we've realized it may make sense to consider a hub and spoke communicating with a spoke and hub. In other words, a larger center with what becomes the hub for a smaller community, and then that reaches out. So there's a series of educational connections that need to be made.

Dr. Chris Prakash: Yeah, I think you almost need multiple hubs. One central big hub in this day and age is probably not going to help solve that problem. So you got to have a big hub and then maybe a series of regional hubs where patients can easily access and doctors can access information.

Dr. Jack Hensold: Yes, I think that's absolutely correct. The education piece, too, is, I think, something that keeps oncology practitioners out of smaller communities where they may be practicing by themselves. Because it's difficult, as you know, as an oncologist, to feel like you're staying current with everything you need to stay up to date with, and therefore practicing in a larger group where you can turn to someone else for some immediate education. 

Dr. Chris Prakash: That's very true. And if you really look at what these CME programs or educational programs are geared to, none of them are geared towards rural practice. They talk about big clinical trials. And those populations are really not my patient population, for sure. So you really need a program where people who know rural medicine, who have experienced it firsthand, like you, me, and Sabe, and say, “Okay, this is what really happens. You cannot give CAR T therapy to every Lymphoma that walks in.” I think those are the kind of educations we are talking about. There's so many educational programs that are available, but not many for rural practitioners.

Dr. Jack Hensold: Right. And it does speak to whether or not we need to be thinking about developing some type of education that's easily accessible to those very busy practitioners who may be a solo practitioner with no one around for hundreds of miles, I guess. 

Dr. Chris Prakash: And not to throw in a plug for my conference, but the Oncology Congress that I do twice a year, that's the sole purpose. We will have faculty from big centers. But I make sure that the conversation moves towards rural settings where we do not have all the latest technologies and the therapies available. And we had a really good turnout this past weekend, so I'm happy to share information if anybody's interested. 

Dr. Jack Hensold: Yes, that would be great. Again, I think this conversation has been terrific because I've really become focused on the issue of the inadequate education we have not only for our oncologists who are out in practice in smaller areas but also for the primary care providers who need a better understanding of what's required for supportive care of oncology patients. And there's very limited material that focuses on that as well. 

Dr. Chris Prakash: Totally agree. Just one last point I want to make is with the checkpoint inhibitors. That's a perfect example. Many of these toxicities are multi-organ, and the patients in the community, the docs in the community sometimes are not aware of the skin rash or lung symptoms, or pneumonia is really related to the therapy. So very important to involve the whole team in their care.

Dr. Jack Hensold: Completely agree. Sabe, what about your experience in this regard?

Professor Sabe Sabesan: Exactly the similar experience Chris has been describing. Another group of rural people, there are actually smaller rural communities. Sometimes they are like 500 or 1000 population maximum. So those kinds of places, they completely miss out because they are too small even for standard general medicine specialties. What we've been observing over time or focusing on is really how do we build those capabilities at rural sites because if they keep doing the same stuff, then they are not going to grow or build. So what we've been doing is let's build some rural capabilities and let's also focus on expanding the scope of practice. So to do that, we actually have to start shifting specialist services like chemotherapy administration or rheumatology infusions back to those smaller towns. And then we have to utilize tele-supervision and share care models with allied health and the rural health workforce. So when that happens, we need more staff because there are more activities happening. 

And what we found in the western Queensland town of Mount Isa before 2007, maybe a few chemotherapy patients had to travel for everything. Over time we shifted all the chemotherapy and biotherapy to that 20,000 population town. That meant that over that ten years they had more resources from the government, more staff like registrars and residents, and also needed infrastructure. So that gave us some confidence that maybe we have to leverage the telemedicine technologies to build rural systems, not just seeing patients. 

Dr. Jack Hensold: Thank you Dr. Prakash, for your insight into this topic and also to Professor Sabesan for his perspective from his practice in Australia. In part two of this podcast, we will explore how the difference between American and Australian healthcare systems impact care for rural patients, the need for advocacy from doctors in a pilot project in Montana I'm working on with ASCO. 

I'm Dr. Hensold and I would like to thank all of our listeners of the Cancer Topics ASCO Education Podcast. This is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologist well-being and professional development. If you have an idea for a topic or guest you'd like to hear on the show, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, visit education.asco.org.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  

Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Nancy Baxter from St. Michael's Hospital in Toronto, senior author on "Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Baxter.

Thanks very much, Shannon, for speaking with me. I'm happy to share our work developing this guideline.

So first, can you give us a general overview of what this guideline covers and the studies which provide the evidence?

Absolutely. So use of adjuvant therapy for patients with stage III colon cancer is common, and it's effective. We know that these patients are at substantial risk of recurrence of their disease and that adjuvant therapy can reduce that risk.
But we also know that comes with a cost. The most effective adjuvant therapy is FOLFOX or oxaliplatin-containing chemotherapy regimens. And we know that a really substantial number of people will end up with neurotoxicity, with peripheral sensory neurotoxicity, that can be long lasting and certainly affects their quality of life.
So the whole question was whether the duration of oxaliplatin-containing chemotherapeutic regimens could be shortened when they're used for adjuvant therapy, so if we could give three months instead of six months. Because we know that if we give three months of therapy, the risk of neurotoxicity is much lower. So if we had the same effectiveness with the shorter duration, then we could spare patients the negative consequences of the agent given for a longer period of time.
So in developing these guidelines, we looked at the results of international group of trials, the six trials from the IDEA collaboration. So these were six randomized trials in various jurisdictions that tried to look at this question, so three months of an oxaliplatin-based chemotherapeutic regimen for adjuvant therapy for stage III cancer versus six months duration of therapy. And so there was a planned analysis to bring all of these data together to develop the evidence base to make this recommendation.
So our guideline and our systematic review basically identified this is the key piece of literature to base our recommendations and guidelines on. That's essentially the main study, so the meta-analysis of these six randomized controlled trials that formed the basis of the IDEA collaboration.
So the IDEA collaboration studies-- there were six individual randomized trials that formed part of the IDEA collaboration. And they were conducted in Italy, Greece, Japan, North America, through CALGB/SWOG, the UK, Denmark, Spain, Australia, Sweden, and New Zealand, as well as France. So data came from, really, around the world.
The median age of people in the studies was 64 years of age. And these people had a really good performance status, so almost all of these patients had an ECOG performance status of 0 or 1. So they were healthy patients that were in the study.
And so some patients received CAPOX, and some received FOLFOX. That wasn't part of the randomization scheme. Other than the CALGB/SWOG study, this was up to the discretion of the investigator or patient. In the SWOG/CALGB study, only FOLFOX was given.
And the authors planned a prespecified subgroup analysis to look at differences between CAPOX and FOLFOX. There was also a prespecified analysis to look at differences based on stage.
What they found when they looked at the results was that, overall, the difference between groups in terms of the three months versus six months was that the hazard ratio between these two was 1.07, meaning a small difference between the groups in terms of recurrence or death between three months and six months overall. But because the prespecified confidence interval, noninferiority interval, for the difference in outcome was 1.12, the 95% confidence interval for the hazard ratio was above this. So it was 1.15, indicating that this prespecified noninferiority margin was exceeded.
And so the study did not prove noninferiority of the three-month regimen. So we're left with an inconclusive result. So that's why our guidelines don't have a strong recommendation for the three months, because we can't rule out a small but potentially important difference between the two groups in terms of recurrence or death.
Now, interestingly, when they looked at the prespecified subgroup analysis, which was looking at CAPOX versus FOLFOX, a difference was found. So they actually found that for FOLFOX chemotherapy, three months of therapy was inferior to six months of therapy, while for CAPOX, actually, three months and six months were the same. So it met the criteria of noninferiority. So these are kind of two different conclusions based on which type of chemotherapy was used.
This was surprising to the investigators and was not expected. And certainly, it was not consistent with the randomized trials that we have comparing these regimens. So we therefore did not make any conclusions in our recommendations about CAPOX versus FOLFOX. But this is certainly something that requires further investigation in the future.
In terms of stage, we did not find that there was an interaction between T stage or end stage when you looked at the differences between the three and the six month. And that was the prespecified analysis. But in non-prespecified analysis, which was the higher risk versus lower risk categories, you did find this difference where the patients with high-risk disease had inferior disease-free survival with three months versus six months of therapy, while those at low risk of disease, it seemed quite safe to give three months versus six months.
So that's a long story. But essentially, because the high risk versus low risk analysis was not prespecified, there's a limitation to how strong our recommendations can be to have three months of therapy. However, given that the hazard ratio associated with three months versus six months of therapy for this lower risk group was only 1.01, indicating they were the same, and the risk of neuropathy was substantially higher with six months, this has led to us making recommendations that the three months of therapy is adequate for patients with low-risk disease after discussion with patients about the possible pros and cons.

And what are the key recommendations of this guideline?

Well, so the recommendations of this guideline do depend on the pathology, so how high risk the patient is. So based on the evidence from the IDEA collaboration, the researchers found that patients who had a high risk of recurrence-- so had T4 disease or heavily node-positive disease, N2 disease-- the six-month duration of therapy was better than the three-month duration of therapy.
These studies and the meta-analysis were designed as noninferiority meta-analyses. But it was clear from the results that the three-month duration was inferior when compared to three months for these high-risk patients. So that seems clear, although we know that those patients will also be at more risk of neuropathy. And so that needs to be discussed with patients, as well.
So for the second group, which are patients who are at lower risk of recurrence, what we found was there was less of a clear benefit of six months of therapy. The recommendation was that patients who are in this low-risk category-- so T1, T2, or T3 cancers that are N1, so not heavily node-positive-- clinicians can offer three months versus six months of therapy after having a discussion with their patients about the pros and cons of that. So the clinicians can go ahead and offer that to patients and still be within the common guidelines based on evidence for treatment of stage III colon cancer.
So because there's some uncertainty after analysis of the IDEA collaboration, one of the really important recommendations that we make is about this shared decision-making approach. So the third recommendation that we make is that oncologists should discuss these factors with their patients who have stage III resected colon cancer and that the duration of therapy needs to take into account the tumor characteristics-- the surgical resection, the number of lymph nodes examined, the comorbidities, the patient functional status, all of these various things-- and there needs to be a discussion of the potential for benefit and the risk of harm based on the duration of therapy.
And oncologists definitely discuss these things with their patients. And this just emphasizes how this is yet another component of the discussion that needs to be included, particularly when speaking with low-risk patients who are at substantial risk of harm from neuropathy and are unlikely to benefit greatly by extending chemotherapy to six months.

So why is this guideline so important? And how will it change practice?

Well, I think, until now, the standard recommendation has been six months of FOLFOX or six months of oxaliplatin-based chemotherapy. And again, there are many patients who have quality of life-affecting neuropathy because of this. So for a substantial proportion of patients who present to us with stage III cancer-- so those that are low risk-- I think this provides some options to them.
So they can opt for a shorter duration of chemotherapy with a lower risk of toxicity. This saves time. This saves cost to the patient and to the system and potentially improves their quality of life without a great impact on outcome in terms of disease recurrence.
So that's a substantial number, a substantial proportion of our patients, who can be treated in this way. So I think that this is a real benefit. Again, oncologists need to have a conversation with their patients about the pros and cons. But this is an option for their patients, whereas from an evidence-based perspective, it wasn't before the publication of the IDEA collaboration.

Finally, how will these guideline recommendations affect patients?

So for patients who have heavily node-positive disease-- so high-risk patients with T4 or N2 disease-- it's not going to affect care. So the expectation would be those patients would be treated with six months of therapy, similar to previous recommendations.
So this will be for people who are at lower risk of disease recurrence, so patients with T1 to 3 tumors that are N1 positive, so not heavily node positive. So these patients will have the opportunity to opt for a shorter duration of therapy. So that's a major benefit to patients.
Again, it's important that there's a discussion and that patients understand the pros and cons. But this is now an option for them, which is excellent.

Thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/gastrointestinal-cancer-guidelines.
And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Alejandro Lazo-Langner from Western University in London, Ontario, senior author on Management of Cancer-Associated Anemia with Erythropoeiesis-stimulating Agents, ASCO/ASH Clinical Practice Guidelines Update. Thank you for being here today, Dr. Lazo-Langner.

Thank you very much for the invitation to present the new guidelines.

So this guideline has been updated now three times since its original publication in 2002. So how has this guideline changed over time?

Since initial publication in 2002, this guideline has undergone a number of different changes. If you look at the initial series of recommendations in the 2002 guideline, it was really limited and it was fairly upfront recommending the use of erythropoiesis-stimulating agents in this setting.
But during the last two updates in 2007 and 2010, that has changed significantly. And in the current guidelines, we have added some additional evidence that has been published in the last eight years. And now, in general, what we can tell is that the use of erythropoiesis-stimulating agents is now more restrictive than in the original guideline and is basically recommended for only one or two situations.
There has been some other updates in the last iteration of the guideline that I can certainly discuss in more detail later. But basically, in general, the guideline has now, in the last iterations, restricted the recommendations that were much more general during the first edition of this guideline, almost all of them based on available and emerging evidence regarding the onset of their side effects with these medications.
And can you give us a general overview of what this new guideline update covers, especially that new evidence that's emerged?
Yeah. So the new guideline has changed a few items. And indeed, we-- the committee did a little bit of an overhaul in the recommendations that are not in the same order as they were in the previous editions. We can say that there is a couple of important updates.
The first one would be addressing the use of biosimilars, which were not available in the previous guidelines. And we have addressed that in the current edition. The biosimilars have not been extensively studied in cancer, but they have. And so far, the committee considered that they were equivalent in terms of effectiveness and safety to the originator agents, both epoetin and erythropoietin.
And the second most important update on the guideline is the recommendation of the concurrent use of iron supplementation in patients who are receiving erythropoietin-stimulating agents. The previous versions of the guideline just recommended the use of iron supplementation in patients with documented iron deficiency. However, in the last eight years, there's been a number of studies that have suggested that the concurrent use of iron supplementation, irrespective of the baseline iron status, does increase the efficacy of the agents.
Third point is that, although this is not new, there's been more emerging evidence supporting the notion that all of the erythropoietin-stimluating agents increase the risk of thromboembolism. And this has been very consistent across all studies, and in particular derive from Julia Bohlius's systematic review and meta-analysis that was published a few years ago. And she's the lead author on these guidelines now. This has been confirmed, and I think that at this point this is probably the main limiting factor on the use of these medications.
And the final minor update was that regarding the use of erythropoietin in patients with myelodysplastic syndrome. This guideline now suggests baseline serum erythropoietin level cut-off that might actually increase the chances of the erythropoietin-stimluating agents of being effective. This has been updated from the previous guidelines based on recent research.

And what are the key takeaways of this guideline update?

Well, the key takeaways is that if a clinician is deciding to use erythropoietin-stimluating agents, in agreement with the previous guidelines, the first thing that you have to consider is that you should not use these agents in patients that are receiving chemotherapy with a curative intent.
And it should be reserved to patients in whom the chemotherapy is being given with a palliative intent. It should be only used to decrease the use of red blood cell transfusions. And if a clinician is to make a decision as to whether to use these agents or not, they should consider concurrent use of iron supplementation.
But basically, the other consideration that needs to be made is that because of the confirmed increase in the risk of thromboembolic complications, in the last eight years, there's been a myriad of new treatments that may potential increase the risk of these complications, specifically and most importantly in patients with myeloma in whom the use of immunomodulators such as lenalidomide or thalidomide does increase the risk of thromboembolic events per se.
And in those patients, if they were to be considered for treatment with erythropoietin-stimluating agents, that should be done in a very, very careful fashion. The risk of thrombosis is significantly high in these patients, and the concurrent use of erythropoietin-stimluating agents is probably not a very good idea.
So if one were to summarize the guidelines, I would say that, one, consider very carefully whether your patient actually needs these agents, and if they do need the agents, whether they should be receiving them, specifically if they are only being given chemotherapy with palliative intent with a short time life expectancy. Some patients would be considered to be in palliative.
However, in conditions such as myeloma, for instance, although they are not curable, the patients may go on living for many years. So that's probably not a very good idea to use these agents if they increase the risk of complications. And if one is going to be considering these, they should consider also the concurrent use of iron to improve the efficacy of these agents.

And finally, how will these guideline recommendations affect patients?

Well, the guideline recommendations won't have a particularly high impact on patients. The most important thing is that, if patients require ongoing transfusional support due to the palliative chemotherapy or the nature of the disease they have, the use of erythropoietin-stimluating agents might decrease the need for these transfusions at the cost of increasing the risk of complications.
The new updated guidelines are probably going to result in-- if they are considered when a clinician is using these agents, they are probably going to result in lower complications for patients due to the more restrictive nature of the recommendations.
And in general, the only other consideration would be that under special circumstances related to, for instance, access to transfusional support or other personal considerations from certain patients and groups, these guidelines might actually help to overcome those barriers for transfusional support. But those were the two major impact points that would be considered based on this updated guideline.

Great. Thank you for your work on this important guideline and thank you for your time today, Dr. Lazo-Langner.

Thank you for the invitation.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. 

Dr. James Harding (Memorial Sloan Kettering) is a board-certified medical oncologist specializes in caring for people with liver cancer, gallbladder cancer, and bile duct cancer, as well as other gastrointestinal cancers. In this week's episode, he discusses a new checkpoint inhibitor with monoclonal antibodies to programmed death receptor 1 (PD-1) for patients with Hepatocellular Carcinoma (HCC). He presents a clinical case and to highlight several aspects of immunotherapy for liver cancer.

Dr. Amy Comander, a hematologist-oncologist specializing in breast cancer at Mass General Hospital, and Dr. Rachel Jimenez, Associate Program Director of Harvard Radiation Oncology Residency Program, have a personal discussion about burnout and practical ways to combat it. 

Dr. Karen Autio, a medical specializing in the treatment of prostate cancer at Memorial Sloan Kettering Cancer Center in New York, discusses additional treatments beyond Anti-PD-1/PD-L1 therapy.

In this episode of ASCO eLearning Weekly Podcast Dr. Alessandro Fichera, Division Chief of Gastrointestinal Surgery at University of North Carolina at Chapel Hill, discusses clinical choices in managing rectal cancer. When is surgery the correct choice? When can we put down the knife?

Rona D. Yaeger, MD is a Medical Oncologist at Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY. In this special Annual Meeting 2019 episode, she discusses recent biomarker and targeted therapy treatments for colorectal cancer management.

Dr. Tarita Thomas is a radiation oncologist in Chicago, Illinois. She received her medical degree from Northwestern University Feinberg School of Medicine and has been in practice between 6-10 years. In this episode, Dr. Thomas discusses the role of adjuvant radiotherapy in nodal disease.

The ASCO eLearning Weekly Podcast is an educational series focused on helping learners identify knowledge gaps and stay up-to-date with the latest in new drug developments, cancer treatments and patient care approaches. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO eLearning. Subscribe to the podcast through a mobile device by clicking the Apple Podcasts link (iOS devices) or the Google Play Music link (Android devices). We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO eLearning Weekly Podcast, email elearning@asco.org for more information.

Age is a main factor when determining cancer care. In this ASCO Education podcast we speak to one of the top leaders in treatment for older patients who has also credited mentorship as a foundation for his career. Dr. Hyman Muss describes his childhood in Brooklyn, serving as a general physician for troops in Vietnam (6:18), the doctor who influenced his choice of hematology and oncology (7:48) and creating one of the first geriatric oncology fellowships in the country (21:58). 

Speaker Disclosures
Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University
Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical
Dr. Hyman Muss: None

More Podcasts with Oncology Leaders 
Oncology, Etc. – Devising Medical Standards and Training Master Clinicians with Dr. John Glick

Oncology, Etc. – Rediscovering the Joy in Medicine with Dr. Deborah Schrag (Part 1)

Oncology, Etc. – In Conversation with Dr. Richard Pazdur (Part 1)

If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org.

TRANSCRIPT

Pat Loehrer: Welcome to Oncology, Etc., an ASCO Education Podcast. I'm Pat Loehrer, director of Global Oncology and Health Equity at Indiana University. 

Dave Johnson: And I'm Dave Johnson of Medical Oncology at the University of Texas Southwestern in Dallas, Texas. If you're a regular listener to our podcast, welcome back. If you're new to Oncology, Etc., the purpose of our podcast is to introduce listeners to interesting and inspirational people and topics in and outside the world of Oncology. We have an inspirational guest today. Pat? 

Pat Loehrer: If you ask anyone who's achieved any level of success and how they've achieved it, most likely they'll mention a number of people who've influenced them along the way. Quite often, these people reflect on their mentors, and after a certain time of accomplishment and reflection, they begin to mentor others. This is very much what our next guest has done. Dr. Hyman Muss has been a mentor to me and to Dave, and he's one of the most outstanding, wonderful people in the world, and we're so excited to have him today.  

Dr. Hyman Muss served in the US Army in Vietnam, where he was awarded the Bronze Star Medal. He's an experienced Clinician Scientist, the Mary Jones Hudson Distinguished Professor of Geriatric Oncology at the University of North Carolina School of Medicine, and the Director of Geriatric Oncology Program at the UNC Lineberger Comprehensive Cancer Center Program. His interest in education and research is focused on cancer and older patients, and he is internationally recognized in this area. He's been the co-chair of the Alliance Committee on Cancer and Older Adults and won the BJ Kennedy Award from ASCO in Geriatric Care. His particular interest in research expertise is in the care of breast cancer patients, with a focus on the management of women who are of older ages. He's had a major interest in breast cancer survivorship and long-term toxicity of treatment and also served as the co-chair of the Breast Committee for the Alliance Group. He serves as a mentor for medical students, medical residents, junior faculty, and more recently, his Geriatric Oncology fellows. He served on the Board of Directors of the ASCO Foundation and on the ABIM, the American Board of Internal Medicine, where both Dave and I were privileged to work with him and witness his leadership and his deep breadth of knowledge. 

Dr. Muss, thanks for joining us today.

Dr. Hyman Muss: What a pleasure to be here. Thank you so much for inviting me. My mother would have loved the introduction. 

Pat Loehrer: Well, speaking of that, tell us a little bit. You grew up in Brooklyn, so tell us a little bit about your parents. Your father was a dentist, I think, and your uncle was a general practitioner. So give us a little bit of the early life of Hy Muss.

Dr. Hyman Muss: So I grew up in Brooklyn, New York. I was born and bred there. I went to Brooklyn Technical High School. I almost went to Brooklyn College, but I came back and went to Downstate Medical Center, which was just terrific. My tuition was $600 a year, but that's another story. My parents lived in the same neighborhood. My dad was a dentist, so we knew all the people. My uncle was the GP. You came into their office, sat down, and they saw you anytime, day or night, almost 24/7, something we're probably not going back to, but they had a profound influence on me. My uncle, as a GP, used to take me on house calls in Brooklyn when they were done, and he had an old Buick with MD plates. And I would go into these families, and they loved him, and they would give me ice cream and things. Maybe that's what made me a doctor. But it was a terrific and indelible experience. I had terrific parents. In those days, doctors and medical people usually lived in the same neighborhoods as their patients, so they really knew their people well. It was a terrific upbringing. I got to love medicine and have never had a look back.

Dave Johnson: So your inspiration for a career in medicine obviously started at home. Tell us more about your formal education. You mentioned your high school education. What about college? And shortly thereafter? 

Dr. Hyman Muss: Yeah, well, I went to Lafayette College. I was not the best high school student, but I had good college board scores or whatever they called them then. And I went to Lafayette and I thought I was going to be a chemist, a chemistry major. But I took enough premed courses and I spent a summer in a lab building cyclic ketones. And everybody was outside sitting on the lawn of the campus. And I was in there with all these distillation apparatus, and I said, “I don't think I can do this the rest of my life.” So I applied to medical school, and I got into several medical schools. But my father at that time was dying of metastatic bladder cancer. He had been a heavy smoker, and he was still working as a dentist. He worked until the day he unfortunately died. But I got into Downstate. We lived in Brooklyn, and my uncle, the GP, said, "Hy, you need to come home and help take care of your dad." I'm an only child, so I did. And I had a wonderful experience at Downstate.  

Several years ago, I was listening to NPR and heard that one of my professors had won the Nobel Prize. Dr. Furchgott in physiology, one would have never thought. And I had a wonderful education and subsequently got into what was then Peter Bent Brigham in Boston, did my internship and residency there, joined the army and medical school, so I wasn't drafted, it was a program then. And then after first year of residency, I went to Vietnam, worked with an artillery battalion, a mystical experience, but no regrets. And then subsequently came back and did hematology and oncology at Brigham and at what was then the Jimmy Fund and Sidney Farber Cancer Center. And Tom Frei had just come. And I did hematology with a guy named Bill Moloney in Boston at Harvard. I'll tell you, a wonderful man. He was like a surrogate father. My dad had died by then, and I just feel I've had every opportunity to have a wonderful education and terrific mentors along the way.

Dave Johnson: So we want to ask you about both of those gentlemen, but I would like to just, if I may, drop back to your experience in Vietnam. What was that like? 

Dr. Hyman Muss: Well, I was 27 years old and I was put as the doctor for 500 men in artillery. My job was to take care of the general health of the troops. Fortunately, we didn't have many casualties. It wasn't a front war like my uncle, who was a GP actually in World War II, landed in Normandy about a week later and went all through World War II as a doctor. But Vietnam was an unusual war, there wasn't really a front. So my experience was I would go out to fire bases, which were units of about 100 men in the jungle, go out three days in a week in a helicopter, do sick call, check people. I dealt with really alcohol problems, unfortunately, a lot of drug problems. You had young people with really not a lot to do during the day, nothing much to do, and no real goal of being there. I did that for a while, and actually, the reason I got the Bronze Star was because I set up– It was nothing like standing in front of a machine gun. I'm not that kind of brave guy, but I set up a drug amnesty program so I got a lot of support from our regular field people to do this, so we didn't have to keep sending kids home with dishonorable discharges. And I learned a lot. I think we were reasonably successful. I learned a lot about artillery. I think overall it was a great experience in my life.

Dave Johnson: Tell us how your interest in hematology and oncology originated. Where did that come from? 

Dr. Hyman Muss: When I was an intern at the Brigham, Dr. Moloney was a very famous Harvard professor. He had studied war casualties after Hiroshima, he was one of the people that found the Philadelphia chromosome in CML. He was a guy that rounded on every single one of his leukemia patients every day. So I was an intern. So in those days I would go and see all the hematology people rounding because all the acute leukemia patients and all the serious cancer patients were right on the floors, right on the wards. We had 17-bed wards, and then we had some private rooms. And he loved what he did. And before I left for Vietnam, we didn't have Ara C and daunomycin. So every leukemia patient I saw died. This is '68 to '70. Yet we tried all these different regimens. Occasionally you got someone who did well for six months, a year. But his bedside manner was absolutely wonderful to me. He knew all the patients. He'd ask them about where they lived in Boston. His humanism was terrific, and yet I loved the diseases he treated. The stakes were high. We didn't have good treatment, and I decided that that's probably what I want to do.  

So when I was in Vietnam, I applied and got back in the Hematology Fellowship and came back and did that. I saw Ara C and daunomycin. I gave the chemotherapy to them, and he'd say, "Go up and treat Harry Smith with Ara C and daunomycin." I had the syringes in my pocket, guys. Forget about hoods and mixing. And I'd go up and treat them and the marrow would be gone within four or five days. I did a bone marrow. They published their regimen in the New England Journal called COD, C-O-D because they also gave vincristine. So it was cytarabine, vincristine, and daunomycin, the COD regimen. It fit Boston. And I saw it was like the emergence of cisplatin after Larry Einhorn. You saw people that never survived going into remission and I saw some remissions in AML and it cemented it. 

About my second year of residency, we had a child. I was running out of money. I was being paid $6,000 a year and I had the GI Bill. I went into Dr. Moloney and he talked with Dr. Franny Moore, who was head of surgery at the Brigham, and they made me the Sidney Farber Research Fellow, doubled my salary and I had to go to the Jimmy Fund and see cancer patients. And it so happened that was when Tom Frei came to Dana-Farber. And so I started rounding with Dr. Frei and seeing those patients. And I think the first day I walked in, I knew I wanted to do more than just leukemia because I saw groups of patients with every disease. We treated everybody with CMFEP, it didn't matter what cancer they had. And I just loved it and said, "My God, there's so much we can learn. What a great career." And so that got me into the oncology portion.  

And then I was offered to stay at Harvard. They were going to make me an assistant professor, but they wanted me to do lab work. And I knew my personality, it just wasn't for me. I worked with a lovely guy named Frank Bunn, one of the world's great hem guys in his lab, and he's still a close friend in his 80s. And he told me one day, he said, "Hy, I don't think the lab is for you." And he actually helped me get my first job at Wake Forest University, which turned out to be wonderful. So that's how I ended up with my circuitous in HemOnc. And it's really from great mentors, it's from Bill Moloney, it's from Tom Frei, Dave Rosenthal, tons of wonderful people along the way that not only taught me a lot, but they seemed to love what they do, which is a gift in life to love what you do and love the people you're doing it with. They instilled that in me.

Pat Loehrer: From there you went to Wake Forest and there’s a couple of colleagues down there, I believe, that inspired you, Charlie Spurr and Bill Hazzard, who was the founding founder of geriatrics. Tell us about that experience and how’d that shape your life. 

Dr. Hyman Muss: I was looking for a clinical job and I looked at Rochester, and I got snowed in one night in Wake Forest, and I said, “Where's the contract?” And I signed it. And my mother, who was living in New York City, didn't know where North Carolina was. My mother was from a family, was born over a candy store in Greenwich Village, and said, “Where are you going?” And then I showed her where it was, and she says, “They're going to kill you down there.” And it turned out to be one of the best decisions of my life. My wife Loretta, who both of you know so well, we got out of our VW with our dog and our daughter when we moved here, and VW bug, by the way, not a van, and she cried. It turned out it was one of the best opportunities. 

Charlie Spurr was an iconic oncology leader. He actually did some of the early work on nitrogen mustard in Chicago during the war, the first chemotherapy drug. He was a terrific leader. He had patients programmed in on those IBM punch cards. He had little cards for the protocols, CMFEP, CMF, AC on little laminated index cards. I learned so much from him, and he was to me, great leaders and great mentors morph from things they do themselves to teaching other people, and whose brains have the ability of having the same dopamine shot when you see one of your fellows or young faculty present a wonderful study as you do. And your brain isn't saying, “I wish I was up there.” It's saying, “Isn't this so cool that this young man or woman or fellow or medical student is doing such a wonderful job?” And I had something to do with providing the soil for this seed to grow. That's the kind of guy he was. And so it was wonderful there. 

And as I moved on, we got a new Chief of Medicine, Bill Hazzard. And I still hear from Bill on rare occasions, but Bill was one of the first geriatricians in the United States. He wrote the textbook, and his wish was that all the faculty and all the specialties get involved in a geriatric project. And so I had all those little index cards, and I looked and saw how many older people with metastatic breast cancer we'd given chemotherapy to. And these were little protocols, nothing like the protocols today, no 50-page consent forms, 50 pages of where your data is stored. They were like, here's the treatment, here's the dose mods. And I looked at those 70 patients with one of our residents, Kathy Christman, she may be retired now, but in any event, we wrote a paper and showed the old people did as well as the young with breast cancer. And we published it in JAMA. And it's one of the few papers in my career, I got no reviewers. They accepted the paper. I got no reviewers. So because I'm from Brooklyn, and my English is not what it should be, I had my friends read it to just make sure I didn't say anything egregious. But it got published and the next thing I know, my friends in medical oncology in the state were calling me. They said, “I got a 75-year-old woman here.” I'm saying, “Guys, I just wrote this paper. I really don't know anything about older people.” But slowly, with Bill Hazzard and others, I got more and more interested. I started reading about Geriatrics and I ended up making it a focal point of my career. It was kind of happenstance. And Bill was a wonderful mentor. 

And then as I subsequently moved on, I worked with terrific people like Harvey Cohen, Lodovico Balducci, and Martine Extermann, all of them heavily involved with ASCO over the years as well, and B.J. Kennedy. They were wonderful to work with. And BJ was inspirational because BJ would get up at an ASCO meeting and he'd say when he saw the age cut off, he'd say, “How come you didn't let old people on that study? There'd be 1000 people in the audience.” And so he really was a great mentor. And I had the bittersweet opportunity of writing his obit for JCO years ago and kept up with his family a few years, but he was a wonderful man.

Dave Johnson: I'm just reflecting on the fact that today, patient registries are sort of mainstream, but certainly in the ‘70s, ‘80s, even into the ‘90s, having a list of patients with a particular disorder seemed almost novel in many respects. And to have that was a godsend. 

Dr. Hyman Muss: It was a godsend. I still remember those little file cards. And he called it the Oncology Research Center and it was a godsend. And you’ve got to remember, this is like ‘74, ‘75, it's a long time ago.

Dave Johnson: So many of our listeners may not be as familiar with Wake Forest as they are with Duke and North Carolina, the other medical schools located there. But you were at right at a point where I mean, it was one of the top oncology programs in the country at that time. Still is, I don't mean to diminish it, but there was a who's who of people there at the time. And you were also involved in creating, I think, one of the first cooperative groups of sorts. It was the Piedmont Oncology Group. Tell us about that. 

Dr. Hyman Muss: Oh, yeah, well, that brings back memories. So the NCI at that time wanted to get more, I think, rural and other smaller places involved in research. And they put out an RFA to form like regional cooperative groups. And we formed the Piedmont Oncology Association, the POA. We actually did well for a few years. We wrote some really good studies. We got one or two New England Journal articles. I worked with all the people, mainly in the community, community docs who would go on, and put people on the protocol. I mean, I looked at all the X-rays and scans in a lot of these patients myself as part of the studies we did. And it turned out to be a wonderful organization and it's still run today by Bayard Powell, who is one of our terrific fellows who's the head of Oncology at Wake Forest. 

But after a while, we just couldn't compete with CALGB, of which I was a member of also, and ECOG and SWOG, even North Central Group, which was kind of formed in a similar venue, eventually merged. So we did a wonderful job for a while but the truth is we just didn't have the manpower to write studies for every disease site. So eventually we kind of petered out as a clinical trials group. But it's been maintained for educational programs and it's really served as a good resource for a lot of good education for the community oncologists who give most of the care in this country in the state. So it's been good. I think Pat kind of exceeded us with HOG, the Hoosier Oncology Group, which was in a similar vein. But it was a great experience and it was all Dr. Spurr, who thought of doing this and built it. 

Dave Johnson: Certainly, it was inspirational in many people in and outside of Wake Forest. So with such an idyllic life, what in the world possessed you to move north to Vermont? 

Dr. Hyman Muss: Well, you get this urgent life. You want to be a leader, you want to be a chief. Now, I tell younger people, if they love what they do, don't do it. So I got a wonderful opportunity at the University of Vermont to go up there and be Head of HemOnc. Chief of Medicine was a terrific guy, Burt Sobel. The university at that time, at one time it had a wonderful Oncology program. It had a federally funded cancer center with Irwin Krakoff and Jerry Yates, two other iconic guys. I don't know what the politics were but it had lost a tremendous amount of faculty, especially its clinical faculty, and they needed to rebuild it. And I went up and I thought, “Well, I'm in my 50s. This is going to be a great opportunity. If I don't do it now, I may never get the chance.” So I went up there and actually, it was a great opportunity. We hired terrific people. We got CALGB and we participated. We had actually a very good accrual for a small place and we had a very small but very effective cancer center. So it turned out to be a really good experience. 

I worked with wonderful people. I recruited some wonderful people. But over time, the issues of the business of medicine, all the issues that happened, I'm saying I'm kind of losing my focus on clinical care and clinical trials, which I love to do. I don't need to tell either of you. I mean, Dave, you've been chief and department chair and Pat has run cancer centers. After a while, the administrative tasks just were so overwhelming and I didn't enjoy them, that I said, “I've got to get back in some type of more clinical focus.” And that's when I decided to look around and fortunately found what's turned out to be a dream job at UNC. 

But it was a time of life. Maybe my ego got in the way of my logic. I don't regret it. I met and I think we rebuilt a wonderful clinical program. But you realize some of the resources of big places with-  we never had the research infrastructure to hire a lot of people and get big programs going on and great translational programs, just didn't have the funding. But it was great, and I have no regrets. And I learned how to tolerate the cold weather. And I have a lovely daughter, Sarah, who still lives up there. So we get back occasionally. And I've kept up with a lot of the people there. There are some wonderful people at UVM. 

Pat Loehrer: From there, though, you were pulled down to North Carolina, where you've, again, built an incredible breast program there is outstanding. But you've created a Geriatric Oncology program, one of the first geriatric fellowships in oncology in the country. So tell us a little bit about that and what you feel may be your legacy is there at North Carolina. 

Dr. Hyman Muss: Well, I had the opportunity over the years when I was at Wake, really, I got to know Shelley Earp, who's our cancer center director. I think maybe you were close to him, Pat. The longest surviving cancer center director on the planet, or among them. And we were good friends. And North Carolina's legislature actually gave the University of North Carolina substantial funding to improve cancer care in North Carolina, not just research. And so I had talked with Shelley about maybe moving, and because of the generosity of the state, really, he was able to really get me going, start a Geriatric Oncology program. And what I wanted to do was develop trials. As Dave says, I built a registry in 2009 here for older cancer patients using geriatric assessment. I have 2000 patients, which has been a resource for all types of faculty and fellows, and students to write papers. But I was able, with the support, to do things like this right from the get-go. And plus, I joined probably one of the best breast groups on the planet with Lisa Carey and Chuck Perou, and Larry, terrific people, Claire Dees. I had great luck in doing this, so I was able to really focus, get great support from my colleagues to build studies focusing on older people. 

And then I had the great fortune of meeting Ned Sharpless, our prior NCI director. And Ned is one of the world's great aging biologists. And I don't mean aging as an adjective, he's really been a master on why we age, the biology of aging, cell senescence. So Ned taught me all about cell senescence and the mechanisms, especially the gene expression p16, which is like our own CDK inhibitor. And so I was able to start using his lab, collect samples, treat people with chemotherapy, follow them off with geriatric assessment. It was a great opportunity to do that here, and we got a lot of studies going and we showed what the pediatricians have known for years, that chemotherapy dramatically ages people, not just children, but adults. But it also allowed me to work with my colleagues in lymphoma and lung cancer to do little studies along the way. 

And we eventually then built a T32 program. We got a T32, which we're kind of completing now our first five years to train oncology specialists in geriatrics. So the way we do it is they can be surgical oncologists, GU, we had a GYN oncologist, medical. With their HemOnc training, they do a year where they work with the geriatricians, so they go on geriatric inpatient service for a month and they really learn about older people. And part of it is a project. So we've been able to build that and develop a lot of programs with that. And I should say we've been very successful with mentorship and with ASCO support for things like YIAs, the late and great Arti Hurria, who absolutely an amazing woman. Some of her legacy at ASCO, the YIAs, and things. We've been successful in applying for some. So we've been able to build a whole spectrum of med and hematologists. We have an interest in Myeloma and AML focusing on older people. We've been able to build a whole team approach, including translational projects related to older people. And it's just been a great opportunity, and hopefully, my legacy here will be, too, and I'm working on it. 

We have a wonderful guy, Bill Wood, who is very effective and has built this incredible coaching program to continue this legacy. Like many of us in this field, we are bothered because we all know the stats, we all know that first slide of the demographics of cancer, and yet it's been very hard in our culture to provide a lot of the services and build the clinical trials we need to best care for older people. It's still a major problem in this country. So as I cut back on my clinical care, I'm going to still advocate to try to improve the care of older people. Do geriatric assessment, build it into your clinical programs, get your hospitals to support you, convince them, build business plans, et cetera. And hopefully, that'll be my ultimate legacy, that we've made greater awareness of the older people, other than the usual stats, and we're really trying to care for them in a much more global sense, in a much more holistic sense than we've done. I hope we'll be successful. It's a slow haul, but we've got lots of great young people coming up through the pipelines, ASCO has been a great player in this. Many of you know people like Supriya Mohile and William Dale, Heidi Klepin, people, the next generation that's going to keep building this. So I hope the legacy will be that we get more buy-in, more interest, more trained people in other oncology-related subspecialties RadOnc, SurgOnc that will really focus on the care of older people.

Dave Johnson: I don't think there's any doubt that that will be a part of your legacy Hy, but I think your legacy will be much broader than the world of geriatric oncology. Your mentorship leadership, your clinical skills, your educational capabilities, all of that will certainly last for many, many years in the future. 

Well, I don't want to bring up a touchy topic, but you yourself are geriatric and we're wondering what your plans are for your semi-retirement. I recognize you're not retiring, but what do you like to do outside of medicine?

Dr. Hyman Muss: I'll tell everybody who's interested in hearing this. On Tuesday, I had my 80th birthday. 

Dave Johnson: Congratulations. 

Dr. Hyman Muss: And I think I'm one of the most blessed guys. I'm pretty healthy. I married up -  my wife Loretta, who both of you, Pat Loehrer and Dave Johnson, know well. 

Dave Johnson: Yeah, you definitely married up. 

Dr. Hyman Muss: Yes. It's really carried me most of my life. She's great and so she flew up our three kids and we celebrated and I'm very fortunate. I have the enthusiasm and strength to do more clinical medicine. But I think the time has come for me to cut back my clinical medicine, so I'm going to do that in June. The hardest thing I've done is say goodbye to so many of my patients here. 

We've been blessed. We have a lovely family. We're pretty close. I'm never bored, probably you two know well, I love to do things like fishing, outdoor stuff. I've really gotten into woodworking, so I'm not going to be bored. But there will be a small piece out of me when I walk out of that clinic in June. I know that and my two close psychiatry friends think it's going to really be a hard fall, but I don't think so. I still have some grants. In fact, I'm working with a fellow in City of Hope, Mina Sedrak, who's been very involved in ASCO, too. We are hoping to get an R01 looking at senolytic drugs that may prevent aging, and exercise in older women with breast cancer to see if we can reverse the trends of chemo. So my brain is still on that stuff, but the clinical care is going to be tough. 

I had a note and for some reason, we talked about so many things. I wanted to mention that one of my great opportunities was joining the CALGB and then the Alliance and getting the support of Dr. Schilsky, Rich Schilsky, who's been one of the icons of ASCO to build cancer in the elderly working group with Dr. Harvey Cohen at Duke. And Harvey is one of the world's great geriatricians. And using that to get studies done, to incorporate studies with Arti Hurria on geriatric assessment, and really have it as a place where a lot of younger investigators could get started on a career in geriatric oncology. And that was really a great opportunity. It was kept on by Dr. Bertagnolli, who now is our NCI director, and I think was really the first group to really give good support for this.

Dave Johnson: So we want to thank you very much for being our guest today. 

We also want to thank our listeners of Oncology, Etc. This is an ASCO Educational Podcast where we talk about oncology medicine and much more. So if any of our listeners have an idea or a guest they would like for us to interview, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, visit ASCO's website at education.asco.org.  

Thanks again for being our guest, Hy. 

Dr. Hyman Muss: My pleasure. Thank you so much.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Daniel George is Professor of Medicine and Surgery, Director of GU Oncology for the Duke Cancer Institute, and Co-Chair of the DCI Center for Prostate and Urologic Cancers. Dr George’s primary areas of interest are in drug development and optimizing care for patients with GU cancers, particularly prostate and kidney cancers. In this episode, Dr. George reviews disparities in prostate care.

The ASCO eLearning Weekly Podcast is an educational series focused on helping learners identify knowledge gaps and stay up-to-date with the latest in new drug developments, cancer treatments and patient care approaches. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO eLearning. Subscribe to the podcast through a mobile device by clicking the Apple Podcasts link (iOS devices) or the Google Play Music link (Android devices). We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO eLearning Weekly Podcast, email elearning@asco.org for more information.

Alexander Menzies, a Medical Oncologist and Associate Professor of Melanoma Medical Oncology at Melanoma Institute Australia (MIA), The University of Sydney, and Royal North Shore and Mater Hospitals discusses appropriate biomarkers and treatments for Stage IV Melanoma.

Lora Black, RN, MPH, OCN, CCRP, Senior Director of Clinical Research at Sanford Health highlights two key points for building a sustainable oncology research program in an oncology-based setting.

Komal Jhaveri, MD, FACP, is a breast medical oncologist with dual appointments in the breast medicine and early drug development services at Memorial Sloan Kettering Center in New York. In this special Annual Meeting 2019 episode, Dr. Jhaveri discusses two patient cases that relate to adjuvant treatment for breast cancer.

Click here to visit ASCO's Annual Meeting website to learn more about the education session. Come back after the meeting for more videos, links and information from relevant sessions.

An interview with Dr. Paul Celano from the greater Baltimore Medical Center, lead author on "Safe Handling of Hazardous Drugs: ASCO Standards."

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Paul Celano from the greater Baltimore Medical Center, lead author on "Safe Handling of Hazardous Drugs: ASCO Standards." Thank you for being here today, Dr. Celano.

Thank you for having me. I'm certainly glad to talk about these standards. They're very important to our employees and our patients.

So first I want to make the distinction that this publication is not a guideline like we usually cover on this podcast. So can you tell us what standards are and how they differ from guidelines?

Well, guidelines really are intended to guide practitioners around recommended care options. They give obviously a lot of latitude to clinical judgment and circumstances. Standards, on the other hand, are really meant primarily for the organization of care and are intended to have a higher level of obligation to help drive either practice or policy or even legislative efforts. So that's really the distinction.

And what are the standard statements that are made by ASCO in this publication?

The publication really is about safe handling of hazardous drugs. This all came about is because recently there have been a number of national guidelines or standards that have been offered by other organizations, but not specifically oncology or certainly ASCO or the ASCO organization. We felt a need to address the standards that have been put out on the basis of the evidence, so that best practices can be offered.

Initially, we did collaborate with other societies, such as the Oncology Nursing Society and the Hematology Oncology Pharmacy Association. That was really the impetus behind making sure that we are, in a sense, congruent with standards that are already being published and discussed, but also to also place in our interpretation of these standards so that they're based on the best evidence that's available.

And what qualifying statements are there to note about these standards?

Well, I think the best way to look at these standards is there has been recently published or offered what's been called the UST 800 standards, which really incorporate other previous standards by the Pharmacy Association as well as OSHA, the Occupational Safety and Health Association, as well as NIOSH, the American Society of Hospital Pharmacists, Oncology Nursing, etc. So there's a lot of standards that have been offered.

And in fact, the ASCO review of this really in a sense agrees with many of the standards that have already been published and offered-- types of exposures, the responsibilities of personnel handling the drugs, the personal protective equipment, how we communicate the hazardous drugs, the training of compounding personnel, how the drugs are dispensed and even transported. So there's lots of things that we really do agree with.

I think it's also important to understand that the objectives of this is really to protect personnel and the environment to make sure the standards apply to all personnel who compound hazardous drugs and preparations, all places where hazardous drugs are prepared and stored, transported and administered. So that's really a key part of this. These are a comprehensive program really to prevent worker environmental exposure and to provide the most practical safety environment for all involved.

So finally, why are these standards so important? And how will they affect practice?

Well, they effect practice in many ways. I mean, the key thing is making sure that our employees, meaning the nurses, pharmacy, the technicians, really everyone involved that they're not unduly exposed to these hazardous drugs. And so that's really the key thing that we're all trying to achieve by this.

Now, what really makes the sort of ASCO standards somewhat different or the things that we came into a contention with has to do with the differences that ASCO has come up with in contrast to some of the other standards. And these have to do with really four main areas within these standards. They have to do with medical surveillance, external ventilation, closed system transfer devices, and also proper assignment of our personnel while they may have either trying to conceive or pregnant or nursing.

So those areas that in our review, the ASCO review, have come under some question. As an example, medical surveillance, there in some of the standards offered-- not ASCO's-- that there's a number of medical surveillance procedures that have been elucidated, that really we find, number one, have really not any proven value for our employees and generate a lot of confusion in terms of how this process is supposed to be done. Obviously, if one of our employees has some undue exposure, such as a spill of chemotherapy or even just have flat out a concern, then obviously those things will be clearly investigated. But to have general medical surveillance of all employees, really we did not feel was of great value.

But also further, we really feel that this is an area where more research needs to be done to better elucidate really what should this process look like and what value are we providing to our employees.

Another aspect of this is the use of what are called closed system transfer devices. Currently, there are a number of these devices available that there is interestingly no standard way that these devices have been evaluated. And so it's hard to recommend one device over another, because there is no standards for which they're really being compared. And there certainly have been no studies looking at really any form of health outcome that really help us to direct this to how best to use these devices. And so really, a lot of these objections are more around let's do things in an evidence-based way so we can better know how to best direct our practices.

Another area of concern in terms of ASCO standards have been the implementation of external ventilation in either containment secondary engineering controls or other situations. And the challenges is that HEPA filters are probably appropriate for collecting solid or aerosolized particles, but don't capture vaporized drugs. But there's little data available on the ability of hazardous drugs to vaporize within the workplace environment and what those hazards really are. And so again, it's is a call for more research to have an optimal environment for preparing these drugs and without having to place undue burdens in terms of external ventilation.

Another area is options for alternative duties for workers who are actively trying to conceive or are pregnant or breastfeeding. And these we recognize can be special burdens to small practices looking to implement alternative duty programs. There is a lot of controversy regarding the potential level of risk that really these workers really have. And basically our stance has been that we should have a policy that identifies alternative work options for workers who are trying to conceive, are pregnant or are breastfeeding, and that this information needs to be conveyed to these employees at the time of their hire so they understand what their risks are and what their options are within the workplace.

Again, trying to make sure everyone is well informed and aware of what the work environment they're in and as their life circumstances change what they can do to change with this. I think the key is that we all feel that this is an area that we should have continued research on. And our standard, certainly ASCO's standards will continue to evolve as more and more research and evidence becomes available.

Thank you so much for taking the time to explain these standards to us today, Dr. Celano.

You're welcome.

And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague

Dr. Noelle LoConte, associate professor of medicine at the University of Wisconsin, presents two patient cases regarding cancer prevention.

TRANSCRIPT

Hello. My name is Noelle LoConte. I am a physician and associate professor at the University of Wisconsin Carbone Cancer Center in Madison. I am a GI medical oncologist in my clinical practice, and also the principal investigator of my state's Comprehensive Cancer Control program, and an implementation science researcher in cancer prevention and screening. 

Today, we will compare two patient cases that relate to cancer prevention. These two cases have similarities yet the recommended treatments may be different. Let's look at our cases. 

Patient case number one is Harold. Harold is a 55-year-old man with a history of head and neck cancer treated with curative intent with chemotherapy and radiation, which was completed about six months ago. He is seeing you for a follow-up surveillance visit. He reports he is currently drinking three to four beers per day, most days of the week. He had quit smoking at diagnosis, but prior to diagnosis had a 45 pack-year history. He recently reports that he started vaping or using e-cigarettes. 

Our second patient case is Susan. Susan is a 44-year-old woman with node-negative, ER-positive, PR-positive, HER2 neu-negative breast cancer. She has also been treated with curative intent with surgery, chemotherapy, and radiation, and has completed her treatments about six months ago. She is seeing you for a routine follow-up visit and reports no new symptoms. She tells you she is drinking two glasses of wine per day, and she denies any history of smoking. 

As you can see, both cases are very similar, but there are some differences. How would you counsel each patient about their use of alcohol? And in the case of Harold, about his use of e-cigarettes? Do either of these affect the risk of recurrence for the patient? And what are the alcohol-associated cancers? 

For background, the cancer burden attributable to alcohol is significant. In 2012, an estimated 5.6 percent of worldwide cancer deaths were attributable to alcohol-associated cancers. In the United States, alcohol accounted for about 3.5 percent of cancer deaths in 2009. Both of these numbers are increasing over time as alcohol use is becoming more common both in the US and globally. 

Upper airway and squamous cell esophageal cancers accounted for the majority of alcohol-attributable deaths among men. Breast cancer accounted for the majority among women. Additional cancers causally linked to alcohol include hepatocellular carcinoma and colorectal cancer. Cancer risk correlates with increasing alcohol consumption for cancers in which alcohol is implicated. 

E-cigarettes are currently approved for adults as a way to decrease the harms from combustible tobacco products, but much about their risk remains unknown, particularly for cancer survivors. Although the risk appears to be lessened with e-cigarette use, they are not proven to be safe and can often serve as a gateway product for youth and nonsmokers to more traditional combustible smoking products. 

In both cases, each patient has an alcohol-associated cancer. However, it is unclear for all but head and neck cancers and esophageal squamous cell carcinoma if cutting down on alcohol intake after cancer diagnosis reduces the risk of recurrence. E-cigarette use among cancer survivors is an emerging issue for clinicians, who often do not know how to counsel their patients about these products. 

For Harold, with his head and neck cancer, there is clear data that supports that patients with that diagnosis who continue to drink do have higher rates of recurrence and also secondary head and neck cancers. Thus, the oncologists should counsel him to stop, or at least cut down on his alcohol drinking. 
The current guidelines recommend no more than two servings of alcohol a day for men and no more than one per day for women. As a reminder, a serving of alcohol varies dependent on the product being consumed. It is roughly one 12 ounce bottle of regular beer, five ounces of wine, or 1 1/2 ounces of distilled spirits. 

For Susan, who has an estrogen and progesterone receptor-positive breast cancer, the data is less clear. There is a suggestion in some studies that ongoing alcohol use for hormone receptor-positive patients may increase the recurrence rates. However, the data is not definitive. It would be prudent for all health risks related to alcohol to counsel her to stick to the recommended amounts of alcohol use, however. So for her, this would be one drink per day for women. 

For e-cigarette use, a 2015 ASCO and AACR statement on ENDS, or electronic nicotine delivery systems, concludes that oncologists should not recommend e-cigarettes to their patients as first-line treatment for quitting smoking. Oncologists should also be aware that more and more cancer survivors are using e-cigarettes and similar products, and they should ask about use at each visit. The unclear health risks of e-cigarettes should be discussed with patients. 

Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. For more information on cancer prevention, including additional patient cases and opportunities for self-evaluation, visit the comprehensive eLearning center at elearning.asco.org. 

[MUSIC PLAYING] 

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 

To stay up to date with new treatments and standards of care medical oncologists in the United States are required to take the ABIM Maintenance of Certification exam, a ten-hour test, every ten years. This ASCO education podcast focuses on the Longitudinal Knowledge Assessment. An alternative test that offers more flexibility in medical certification.    

Our guests are Dr. Suresh Nair Physician-in-Chief of Lehigh Valley Cancer Institute in Allentown, Pennsylvania and Chair of the ABIM Medical Oncology Board and Dr. Olatoyosi Odenike, Associate Professor of Medicine at the University of Chicago and member of the ABIM Medical Oncology Board.  

Speaker Disclosures 

Dr. Suresh Nair:  

Research Funding - Bristol-Myers Squibb Recipient; Merck; Nektar Therapeutics; Mirati Therapeutics; Strata Oncology  

Dr. Olatoyosi Odenike:  

Consulting / Advisory Role – Abbvie; Impact Biomedicines; Celgene Recipient; Novartis; BMS; Taiho; CTI Biopharma; Threadwell therapeutics; Blueprint Medicines; SERVIER; Kymera; Bristol-Myers Squibb/Celgene 

Research Funding - Celgene; Incyte; Astex Pharmaceuticals; NS Pharma; Abbvie; Janssen Oncology; Oncothyrapy; Agios; AstraZeneca; CTI BioPharma Corp Recipient; Kartos; Aprea AB; Bristol-Myers Squibb; Daiichi Sankyo; Loxo; Novartis 

Resources 

• To find out more about the ABIM LKA, go to https://www.abim.org/lka/ 
• For a video walk-through, visit https://www.youtube.com/watch?v=C0-qaUQmQXc 
• Sign in to the ABIM Physician Portal to sign up for LKA by June 30, 2023: https://portal.abim.org/  
• To find out more about how ASCO supports physicians engaged in ABIM MOC, go to https://old-prod.asco.org/meetings-education/continuing-education-moc 
• If you are interested in joining the ABIM Item Writing Task Force for Medical Oncology, find out more and submit your application at: https://www.abim.org/about/boards-and-committees/openings/medonc-iwtf-physician/ 

If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org.

TRANSCRIPT

Disclosures for this podcast are listed in the podcast page. 

Dr. Suresh Nair: The medical profession is one where new treatments and standards of care are being discovered and applied frequently, especially in oncology. Staying up to date with such practices allows the physician to provide the highest quality of care. How is this accomplished? By taking part in the Maintenance of Certification, or MOC. The traditional MOC assessment takes about 10 hours to complete and gives you ten years to be reported as certified before your next assessment is due. But given today's world where new treatments and standards of care are advancing rapidly, a more continuous assessment approach is warranted to help oncologists stay up to date. 

This ASCO Education Podcast explores a new alternative to the every decade MOC exam for medical oncology. It's known as the Longitudinal Knowledge Assessment or LKA. I'm Suresh Nair MD, the Physician Chief of the Lehigh Valley Topper Cancer Institute in Allentown, Pennsylvania, and Chair of the American Board of Internal Medicine Medical Oncology Board. I will guide you through a general overview of the LKA, what it is, how it works, what the advantages are, and top-level need-to-know information. Joining me is my medical oncologist colleague, Dr. Olatoyosi Odenike, who's a professor of medicine and director of the Leukemia Program at the University of Chicago and serves as a fellow member of the ABIM Medical Oncology Board. 

To begin, here are the essential differences between the ten-year maintenance of certification exam or MOC exam and the Longitudinal Knowledge Assessment, the LKA. Both are being used to help medical professionals maintain a working knowledge of the latest treatments and standards in use in their field. The MOC is administered every ten years at specified locations, lasts about 10 hours, and the results are available after two months. The LKA is another option. It has a five-year cycle during which you answer questions on an ongoing basis and receive regular feedback on how you're performing. Dr. Odenike has taken the LKA and the MOC. 

Toyosi, please describe the preparation and the actual experience of taking the traditional MOC test. How much time did you take to prepare for the exam and how did you fit that prep time into your busy schedule?

Dr. Olatoyosi Odenike: Thank you so much, Dr. Nair. For the traditional MOC, I started preparing about six months ahead of time and it was challenging to find time to prep and to fit that into an already busy schedule. It came down to blocking out any available time, particularly on the weekends, in the few weeks leading up to the actual examination date. It was also challenging to find time to dedicate a whole day to taking the exam and traveling down to the test site to do so.

Dr. Suresh Nair: Today, the LKA is another option for busy oncologists. In 2022, the American Board of Internal Medicine launched the LKA after years of working with and listening to the physician community to understand their needs. As long as you're meeting the LKA participation requirement and other MOC requirements you'll continue to be publicly reported as certified for your entire five-year LKA cycle. The LKA is designed to provide greater flexibility, more convenience, and more immediate feedback, helping physicians stay current. Dr. Odenike, what has been your experience so far with the LKA?

Dr. Olatoyosi Odenike: So far, I have found the process far easier to navigate than the MOC. Registering for the LKA on the ABIM physician portal was very easy. There are 30 questions per quarter, and I chose to get weekly reminders of the due date, along with a link to access the portal and the LKA questions. I find this to be so convenient, I can determine when to access and complete the questions, which I have often done on block closer to the due date. You are able to do this and fit this in your schedule any way you choose, which is a big improvement on the traditional MOC.

Dr. Suresh Nair: Is the LKA a big time commitment for you? 30 questions per quarter seems like a lot. How does it compare to the traditional ten-year model?

 Dr. Olatoyosi Odenike: There's a four-minute time limit per question. So technically, you can answer all 30 questions in one afternoon. Some physicians report doing this in two hours. Data gathered over the last year have shown that most participants answer questions in under two minutes. And how they approach it is unique to each person. Some set aside a little time each week to answer questions until they're finished. Others, like me, will do it all at once or over the course of one week near the end of the quarter. You could do one a day with your morning coffee if you wanted to. We have found the structure to be significantly more flexible than the traditional MOC. 

We have a question for you, Dr. Nair. Can physicians sign up for the LKA now, even if they're not due for an assessment?

Dr. Suresh Nair: You can only sign up in the year that you're due, or rather, starting in the December prior to your due year. So, physicians due for an assessment in 2023 were able to enroll starting December 1, 2022. Physicians who are recently certified or who are not due for a few more years have to wait until their due year to sign up for the LKA.

Dr. Olatoyosi Odenike: What is the last date to sign up for the LKA?

Dr. Suresh Nair: The last day to enroll in 2023 is June 30. If you missed the enrollment date for the LKA this year, you can still opt to take the MOC exam in the fall without letting your certification lapse. MOC registration closes August 15.  

Dr. Olatoyosi Odenike: What happens if you don't pass after five years?

Dr. Suresh Nair: If you don't pass after five years, you enter the grace period as long as you're meeting your other MOC requirements and will continue to be reported as certified during that time. You'll have one calendar year to pass the traditional MOC exam. In some ways, this is somewhat risk-free going with the LKA in that regard. Can physicians still take the MOC exam if they prefer to?

Dr. Olatoyosi Odenike: The MOC exam is still available in spring and fall each year for most certificates, including med ONC and hematology, the LKA is just another option. Many physicians prefer to take the traditional exam or if they're certified in multiple specialties, they use both the exam and the LKA to balance their time and areas of expertise better. Some physicians take the LKA in hematology and/or medical oncology while using the exam to remain certified in internal medicine, for instance, or vice versa. 

I have a question for you, Dr. Nair. Who is eligible to take the LKA? How can physicians know if they're eligible?

Dr. Suresh Nair: LKA is offered in 15 specialty areas. All board-certified physicians in their assessment due year, except those in a grace period, are eligible. All physicians certified before 1990, all physicians with a lapsed certification. In fact, I had trained in both hematology and oncology 30 years ago, and I practiced medical oncology at two academic community hospital systems. I actually signed up for the LKA this past year to regain certification in hematology that had lapsed after my first 10 years, and I've had a great experience. I have finished a year of taking the test. I've gotten assessments. I see what my strong points and weak points are. I've actually ordered the ASH_SAP and I'm reading up on my weak points and I'm continuing this process. It really starts growing on you.

 I'd like to thank Dr. Odenike for sharing your real-time experience in taking both the MOC and the LKA. I would like to extend an opportunity for all listeners interested in keeping their certifications through the LKA by going to the ABIM Physician portal www.abim.org. That's www.abim.org or go to the notes on the podcast page to access the link, as well as other resources. There you can keep track of assessment deadlines and progress, and it allows you to set reminders for assessments, points, and payments.

 I want to thank all of you for listening to this ASCO Education Podcast. The ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncology well-being and professional development. If you have an idea for a topic or guest you'd like to see on the show, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. Thank you. 

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  

Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and I'm interviewing Dr. Joe Mikhael from the City of Hope Cancer Center and International Myeloma Foundation, lead author on "Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline." Thank you for being here today, Dr. Mikhael.
It's a pleasure to be with you.
So first, can you give us some context as to why this guideline was developed?
Well, we had a lot of ideas when we put together this guideline, but most importantly, multiple myeloma continues to be a rare disease in the cancer world. It really only accounts for about 1% to 2% of cancers. So for the practicing oncologist, they spend perhaps 3-ish percent of their time doing multiple myeloma.
And when you add to that there has been really a revolution in myeloma with new drugs approved, new treatments, new approaches, it really leaves the general oncologist with a complexity of how to treat this disease. And so we wanted to create a very practical guideline that would give very precise advice to walk through how one would care for a multiple myeloma patient, right from their diagnosis to indeed relapse disease.
We felt this approach was so important now, more than ever, because of the fact that myeloma has really changed so much, and now, thankfully, we're seeing our patients live so much longer that the treatment options can become a little bit more complicated over time. Furthermore, we partnered with Cancer Care Ontario, because this was really felt to be not just an American phenomenon, but really a full North American phenomenon of how we could work together to really give practical advice as to how to treat this disease.
So what are the key recommendations of this guideline?
In this guideline, we focused really on the treatment of the disease itself. There have been other guidelines that have focused on supportive care and bone disease and multiple myeloma, but we really focused on the treatment of patients really from induction therapy through to relapse.
So we spend time helping guide the decision around whether or not a patient is transplant eligible or ineligible, because that's really the first dividing marker in myeloma, because we know that transplant still has a role in myeloma, and eligible patients should have a transplant, or at least have access to a transplant. And historically, this was really done on the basis of age.
But the guidelines helps the clinician see that it's really not just an age phenomena. It's really a decision based on comorbidities and really what's best for the patient. So we spend time helping making that decision, and then provide very practical advice as to how to treat a patient who's going to transplant versus a patient who's not going to transplant.
We also, then, after the transplant, or in lieu of a transplant, we discuss the importance of continuous therapy, or sometimes called, maintenance therapy in myeloma. Again, we've seen maintenance therapy, now, have an impact on both progression free and overall survival. And so we felt it was really important to be very practical in giving advice as to what maintenance therapy agents to use and how to use them.
And then lastly, the guideline provides a lot of practical advice as to a patient who has relapsed with multiple myeloma. We have so many choices now with three major classes of drugs of proteasome inhibitors, immuno-modulatory drugs, and now newer monoclonal antibodies, it can be difficult sometimes to know which combination to use.
We know that triplet combinations tend to be preferred. So we walk through a number of those triplets and provide advice as how to explicitly use them. We do emphasize the importance of supportive care and of risk factor analysis throughout the guideline, so that we can understand the difference between high risk and low risk myeloma, so that we can understand how important a patient's comorbidities, especially in a disease that primarily affects older patients, can be managed.
And so we try to do so in a comprehensive way, but one that really distills down to the critical pieces to allow the practicing clinician some real advice.
So why is this guideline so important, and how will it change practice?
There are several kinds of guidelines for multiple myeloma, but I really think this is a critical guideline because it is so clinical and practical in its essence. It's really designed to not just give the utopian view or the clinical trial view of a disease, but practically in the trenches, how do we use the drugs that we know are going to benefit our patients.
Myeloma is one of the few cancers where we have seen a doubling, if not a tripling of survival in the last decade, because of so many of these new agents. And so making sure that our patients are treated optimally really is important. And we want to be able to ensure that they receive the best therapy possible, so they can live a longer life, but also live it with a greater quality of life.
And so finally, how will these guideline recommendations affect patients?
Well, we really hope that this is going to help patients all across North America and the whole world, because it will give very concrete advice to the practicing clinician in how to approach the disease. And one of the things I think will directly impact patients, if you will, right away is one of the themes of these guidelines, which is that you don't treat a patient simply based on the biopsy or simply based on their age, but that it is really a complex network of comorbidities, risk factors from the disease itself, the potential side effects of certain drugs, and a patient's own very personal history.
It really fits in with the ASCO modality that we have of ensuring that we bring personalized medicine to our patients. And so this will allow the person who's reading it and who's applying it to their patient to recognize the importance of general guidelines, but also of applying it to the specific patient they care for. Because as I like to say, we don't treat multiple myeloma, we treat people. And so hopefully, this will allow the clinician to have that precision to care for their patient in the best way possible.
Great. Thank you for that overview of this guideline, and thank you for your time today Dr. Mikhael.
It's been a real pleasure. Thank you very much.
And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/hematologic-malignancies-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Susan Chang from the University of California San Francisco, lead author on "Anticonvulsant Prophylaxis and Steroid Use in Adults with Metastatic Brain Tumors: ASCO and SNO Joint Endorsement of the CNS Guidelines." Thank you for being here today, Dr. Chang.

Thank you so much for this opportunity.

So first, can you give us the general overview of what this guideline covers and about the endorsement process?

Absolutely. So one of the things we've noticed, of course, is that the incidence of newly diagnosed adult patients with brain metastases is now estimated to be in the range of about 20,000 to 40,000 per year. And this has really been increasing because of several factors. This includes improved imaging tools, the fact that there's an increase in the number of cancers that are prone to spread to the brain, and the improved survival of patients with cancer.
And so the Congress of Neurological Surgeons have developed a series of guidelines on the treatment of adults with metastatic brain tumors. That includes systemic therapy, as well as supportive care. There are two guidelines that address the role of anti-convulsant abuse and steroids in the care of patients with brain tumors.
Specifically, the guideline questions were do prophylactic anti-epileptic drugs decrease the risk of seizures in both non-surgical and post-surgical patients, who are otherwise seizure free? So these are patients who have never had a seizure, does it make any sense to use these drugs? The second is do steroids, which are commonly used in patients when there is increased mass effect and cerebral edema, could that help to improve neurological functioning or quality of life, compared to supportive care or other treatments? And if they are used, what sort of dose should be used?
So the process of endorsing these guidelines included an initial assessment by content evaluators from ASCO and members of the Society of Neuro Oncology, or SNO guidelines committee. And subsequently, it was determined that a detailed review of the guidelines should be pursued.
So in this joint effort of both ASCO and SNO, a multidisciplinary expert panel of medical and radiation oncologists and neurosurgeons, neurologists, and others providing care for adults with metastatic brain tumors reviewed the content to determine the appropriateness for endorsement by the two professional societies.

So what are the key recommendations of this guideline?

The key recommendations of this guidelines include the fact that routine use of prophylactic anti-epileptic drugs is not recommended for patients who are seizure free, either in the non-surgical and post-surgical settings, and that steroids could be used when patients had mild, moderate, or severe symptoms that were related to mass effect in the brain.
This choice of steroids that was recommended was dexamethasone, and the doses was about 4 to 16 milligrams, depending on the severity of the symptoms. Now, what they found was that there was insufficient evidence to recommend steroid use in asymptomatic patients, when they didn't have any mass effect.
And one of the additional aspects that the panel provided was that the minimal effective dose should be used, and that nighttime doses should be avoided. And this is because of the known side effect of insomnia that a lot of our patients experience when taking this medication right before they go to sleep.

So why is this guideline so important, and how will it change practice?

Well, these guidelines provide a basis for oncologists to avoid the over prescription of anti-epileptics and steroids in patients with brain metastases, particularly in those who are asymptomatic and those without signs of mass effect. It also highlights that if steroids are going to be administered, that clinicians should be very familiar with both the short and long term sequelae of steroid therapy, and they should have a plan to taper the steroids as fast as can be clinically tolerated.

So finally, how will these guideline recommendations affect patients?

Well, both anti-epileptics and steroids have a wide range of toxicities that can adversely affect a patient's quality of life. And so the routine use of these drugs in patients with incidentally discovered or asymptomatic brain metastases is not supported by the available medical literature. For patients with symptoms related to mass effect, the best evidence supports the temporary use of steroids are the lowest effective dose with the intent to taper them off, and if tolerated, and after a definitive treatment of brain metastases has been initiated.
And because of the well known side effects of insomnia and agitation, nighttime doses of steroids should be avoided. So the hope is that this will have a direct effect on how we care for our patients.

Great. Thank you for your work on these important guidelines, and thank you for your time today, Dr. Chang.

You're very welcome. It's such a pleasure to be able to provide this for patients and families.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/neurooncology-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Rachna Shroff from the University of Arizona Cancer Center, lead author on "Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Shroff.

Thank you so much for having me.

So what does this guideline recommend?

This is a guideline that is basically looking at the role of post-operative therapy in patients who undergo surgical resection for biliary tract cancers. Biliary tract cancers are a somewhat heterogeneous group of malignancies that include intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancer.
And so the question always in most cancers are, if you are able to undergo surgical and curative treatment, is there a role for post-operative chemotherapy or radiation therapy to help improve the chance of cure and decrease the risk of recurrence? So that is exactly what we investigated as an expert panel.
So our recommendations are actually twofold. The first one is that we are clearly recommending that patients with resected biliary tract cancer should be offered adjuvant chemotherapy with capecitabine for a total of six months. Within that recommendation, we do acknowledge that this is based on the BILCAP phase III randomized controlled trial and that there was a specific dosing and treatment schedule that was done in that study, but that we are allowing for institutional and regional variances that we've noted in terms of dosing of capecitabine. And so as a result, we're recommending adjuvant capecitabine, and we're allowing practitioners to determine what the best and safest dosing would be, based on their experience.
The second recommendation is more specifically for patients with extrahepatic cholangiocarcinoma or gallbladder cancer who undergo resection and have a microscopically positive surgical margin, which is an R1 resection. And in those patients, we are recommending that we could consider offering these patients chemoradiation therapy.
Now, again, this is not as strong of a recommendation, because we do not have prospective randomized phase III data to support it. This was based more on a prospective single-arm study out of the Southwest Oncology Group, as well as some other retrospective studies. And so we do go on to qualify that that recommendation should really be made in a shared decision-making approach, with a multidisciplinary conversation to decide the risks and benefits of radiation in these patients-- and that we acknowledge that a prospective study would really help clarify that question a little bit more.

So can you tell us about the research that informed these recommendations?

There have been a number of studies that have looked at the role of adjuvant therapy in biliary cancers. And up until very recently, a lot of these studies were small retrospective series, single-institution or multi-institution, but everything in retrospect-- no prospective or randomized data. And so I think a lot of the reasons that we decided to have these guidelines come out now is that in the last two to three years we do finally have prospective randomized data that helps guide the recommendations.
And the majority of the recommendations that we made are based on one randomized phase III, which is BILCAP study. This was a study that was done in the UK and was presented at ASCO in 2018 and is currently in press. And it is basically a randomized controlled trial that compares adjuvant capecitabine by itself versus surveillance alone in patients who undergo surgery for biliary tract cancers.
And so our recommendations, which include that study as well as a couple others, is primarily hinged on that, since that is the largest prospective data we have so far. And based on that study, we did in fact recommend that there was a role for adjuvant chemotherapy with capecitabine after complete resection for biliary tract cancers.
And based on that research that was done in that trial that was completed, we do believe that the role for capecitabine for six months is pretty strong and that the data supports that now.

So why is this guideline so important, and how will it change practice?

Well, I think it's going to be practice-changing because up until now there has not been a clear consensus on how we approach these patients. And I will say that even now, it's really just this one study that has helped guiding these recommendations. There were a number of other studies that we looked at as part of the expert panel. And these were all prospective studies as well that looked at things like gemcitabine and oxaliplatin in the adjuvant setting, or single-arm phase II studies that came out of the Southwest Oncology Group that also explored the role of radiation. But really, nothing was a positive study other than the BILCAP study.
And so up until now, I would say it was a little bit all over the place in terms of how medical oncologists approached resected biliary cancers. I think the majority of us felt that there was probably a role for adjuvant chemotherapy or perhaps chemoradiation. But there was no rules that we could follow, and there was no clear study that we could turn to that would tell us what we should give, how long we should give it for, and whether it should be a combination of chemotherapy or chemoradiation.
And so I think it will be practice-changing because now, as part of the expert panel, we are making a very clear recommendation that patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy for a total of six months, hopefully eliminating that kind of regional or specialist-based variation that has been happening up until this point.

And finally, how will these guideline recommendations affect patients?

Again, I think that the main way it's going to affect them is that there's going to be a little bit less gray area, in terms of medical oncologists having conversations with the patients and saying, well, you know, I think that there's probably a role for agent therapy here, but I can't show you the data that supports why I think that.
And as a result, I would hope that patients will have a little bit more faith and confidence in knowing that there is a large study that has looked at and proven the benefit of adjuvant capecitabine and that that decreases the chance of recurrence and improves overall survival. The improvement in overall survival was dramatic in this study. And we had not seen a survival of 51 months, which is what we saw in this study, in a very long time.
So for patients, not only does it make clear what they should be doing after surgery, but I would hope it also gives them additional hope that we have really changed the bar by doing this adjuvant capecitabine, and that the chance for cure is even higher when we can offer adjuvant chemotherapy.
I think the only other thing that may still be a gray area, and that is kind of what we allude to in our second recommendation, and that is in patients who undergo resection and have a microscopically positive margin or an R1 resection. And that's typically patients with extrahepatic cholangiocarcinoma or gall bladder cancer.
In those patients, we suggest that they could be offered chemoradiation therapy, but the evidence is not as strong there. Again, it's more retrospective studies that we looked at. There is no prospective study that answers the question of whether or not there's a role for radiation. And so as a result for patients, I think that is still the one area that's a little bit of a gray zone in terms of knowing whether chemoradiation would benefit them if they undergo surgery and have a microscopically positive resection.
But I do think that there is a definitive benefit to giving adjuvant chemotherapy, and that, hopefully, will clarify things not only from the physician perspective but also from the patient perspective.
Great.

Thank you for your work on these important guidelines, and thank you for your time today, Dr. Shroff.

Thank you.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

Wendy Vogel is a Nurse Practitioner and President of APSHO, the Advanced Practitioner Society for Hematology and Oncology. In this week's episode, she presents a self-evaluation question about the correct chemotherapy treatment of obese patients and provides an explanation of the correct choice.

Dr. Sparano is Professor of Medicine & Obstetrics, Gynecology, and Women's Health at the Albert Einstein College of Medicine, Associate Chairman for Clinical Research in the Department of Oncology at Montefiore Medical Center, and Associate Director for Clinical Research at the Albert Einstein Cancer Center. He also serves as Vice Chair of the ECOG-ACRIN Research Group and Vice Chair of the AIDS Malignancy Consortium. He is former director of the Hematology-Oncology Fellowship Program at Einstein/Montefiore,  co-directs the ECOG-ACRIN Young Investigator Program, and is a faculty member of the Calabresi K12 Oncology Training Program.  He is co-principal investigator of the Montefiore-Einstein Minority/Underserved National Community Oncology Research Program (NCORP) grant (in conjunction with Dr. Bruce Rapkin), which funds multicenter, NCI-sponsored clinical trials in cancer therapeutics, cancer prevention/control, and cancer care delivery research.  He is also the recipient of funding from the Breast Cancer Research Foundation that is supporting creation of a biospecimen bank designed to identify determinants of late relapse.

Dr. Sparano is a practicing clinician who specializes in medical oncology and clinical and translational cancer research. His research has focused on developmental therapeutic approaches for breast cancer, lymphoma, and HIV-associated cancers, and therapeutic application of molecular profiling in cancer.

TRANSCRIPT

Welcome to the ASCO University Weekly Podcast. My name is Joseph Sparano, and I am Associate Director for Clinical Research at the Albert Einstein Cancer Center, and chief of the section of breast medical oncology at Montefiore Medical Center in New York. Today, we contrast two cases on adjuvant treatment of breast cancer.
The standard treatment for hormone receptor positive, HER2 negative, early stage breast cancer is surgery, followed by endocrine therapy. Since the early 2000s, adjuvant chemotherapy has also been recommended to the majority of these women, but the added benefit from chemotherapy is modest for most.
Many different gene expression assays have been developed to determine prognosis and identify which woman may be more likely to benefit from chemotherapy. One commercial test that is recommended in clinical practice guidelines is a 21 gene recurrence score assay. Based on the recently completed TAILORx study, it was known that woman with low recurrence scores on the 21 gene expression assay do well with adjuvant endocrine therapy alone. Whereas woman with high recurrence scores benefit from adjuvant endocrine therapy and chemotherapy.
The TAILORx study clarified the best treatment option for women with an intermediate recurrence score, which was defined as a recurrence score of 11 to 25 in the trial. This is particularly important because the majority of patients fall in this intermediate risk category, up to 70%, in fact.
Before we discuss the new evidence reported from this study, let's take a look at two intermediate risk cases. These two cases are very similar, yet the recommended treatments may be very different. Can you identify the key differences between these two cases?
We begin with the first case. Case 1 is a 55-year-old postmenopausal woman with a node negative, ER positive, PR positive, HER2 negative breast cancer. The size of the tumor is 1.6 sonometers. The 21-gene recurrence score is 24, which is in the upper range of the intermediate risk category.
Which option would you recommend as the best systemic treatment. The choices in this case include endocrine therapy alone or chemotherapy followed by endocrine therapy. The correct answer to this question is, A, endocrine therapy alone. We will discuss the rationale for this recommendation shortly, but first let's move on to the second case.
The second case is a 44-year-old premenopausal woman with node negative, ER positive, PR positive, HER2 negative breast cancer. Like case 1, the size of the tumor is 1.6 centimeters and the 21-gene recurrence score is 24. Which option would be the best adjuvant treatment in this case? The choices here include endocrine therapy alone or chemotherapy, followed by endocrine therapy.
The correct answer in this case is chemotherapy, followed by endocrine therapy. Both of these cases had nearly identical clinical presentations. That is, they presented with ER, PR positive, HER2 negative breast cancer, associated with negative axillary nodes, a primary tumor size of 1.6 sonometers, and a 21-gene recurrence score of 24.
However, the key difference was the age at presentation, with one patient being in her mid 50's and postmenopausal, and the other patient being in her mid 40's and premenopausal. The TAILORx trial found that endocrine therapy was not inferior to chemotherapy plus endocrine therapy in the overall population with a mid-range 21-gene recurrence score of 11 to 25. However, there was an interaction between age, chemotherapy treatment, and recurrence score.
About 1/3 of women who participated in the trial were 50 or younger. These women seem to have some chemotherapy benefit if the recurrence score was between 16 and 25. For those who had a recurrence score of 21 to 25, the absolute reduction in the risk of distant recurrence was approximately 7% at 9 years. For a woman who had a recurrence score of 16 to 20, the absolute reduction in distant recurrence by the addition of chemotherapy was about 2%.
It remains unclear as to whether the benefit from chemotherapy in younger woman was due to a true cytotoxic effect associated with chemotherapy in eradicating micrometastatic disease, or a castration effect in inducing early menopause. Nevertheless, the findings from the TAILORx trial provide the highest level of evidence supporting the greatest level of precision in using the 21-gene assay to guide the use of adjuvant chemotherapy in early stage breast cancer.
Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on the adjuvant treatment of breast cancer, including additional patient cases and opportunities for self-evaluation, visit the comprehensive e-learning center at university.asco.org. Thank you for your attention.
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Arun Singh, Co-Clinical Director of UCLA Sarcoma Clinic and Assistant Professor of Hematology and Oncology at UCLA, presents a self-assessment question from an ASCO University course focusing on the treatment of non-small cell lung cancers.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Jennifer Griggs from the University of Michigan, senior author on "Adjuvant Endocrine Therapy for Women with Hormone Receptor Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update." Thank you for being here, Dr. Griggs.

And thank you for the opportunity to talk about this focused update to the guidelines on extended adjuvant therapy. I would, of course, like to thank all my co-authors in the ASCO guidelines team for their contribution to this effort.

So first, can you give us a general overview of what this guideline covers and their research which informed this focus update?

Yes. First of all, the goal of the guideline was to give an update to the previous guidelines on this topic. And we specifically focused on extended adjuvant therapy. In particular, the aromatase inhibitors in women who had completed five years of adjuvant endocrine therapy. And it goes without saying, but it's worth reminding our listeners that the guideline is restricted only to post-menopausal women with hormone receptor-positive breast cancer. And, of course, our guidelines are only as good as the data upon which we rely. So for this guideline, six phase III randomized controlled trials met the pre-specified eligibility criteria for the updated systematic review and provide the evidence base for the guideline recommendations on the duration of aromatase inhibitor therapy. Each of the trials used the standard doses of the drugs that we use in practice today. So I'm not going to say the doses of each of the medications. So I'm going to go briefly over those six trials and just describe them so everybody's up to date with how the studies were designed.

So briefly, the first trial I'll describe is MA17R, which compares letrozole to placebo for five years in over 1,900 women who had already received 4.5 to six years of adjuvant therapy with an AI, proceeded in most women by treatment with tamoxifen. The second study is NSABP B-42. And this also compares letrozole to placebo in nearly 4,000 women who'd completed five years of endocrine therapy with either five years of an aromatase inhibitor or up to three years of tamoxifen followed by an aromatase inhibitor, for a total of five years.

The third study that we looked at is the DATA trial, which stands for the Different Durations of Adjuvant Anastrozole Therapy. This trial compared six years of adjuvant anastrozole with three years of adjuvant anastrozole in over 1,600 women after two to three years of adjuvant tamoxifen. The fourth trial out of the six is the IDEAL trial, the Investigation on the Duration of Extended Adjuvant Letrozole. This study randomized over 1,800 women to either 2 and 1/2 or five years of letrazole after five years of tamoxifen, an AI, or a combination in sequence of tamoxifen and an AI. So very similar study designs.

The fifth study is the ABCSG-16 trial, the Austrian Breast Cancer Study Group Trial 16, which randomized nearly 3,500 women following four to six years of adjuvant therapy with tamoxifen and AI or a sequence of tamoxifen and then an AI, to either two or five years of anastrozole as extended therapy. And finally, the study of letrozole extension, or the SOLE trial, randomized over 4,800 women with node-positive breast cancer who had completed five years of adjuvant endocrine therapy to receive either continuous letrozole for five years or five years of an intermittent schedule of letrozole given nine months on and three months off in years one to four and on continuously for a year or five.

So I know that's a lot to take in, but I do think it was important for our audience to understand the six trials that were included. These were all large studies, randomized, and patients had completed five years of adjuvant endocrine therapy. And then, were randomized either to placebo or different durations of an aromatase inhibitor or a placebo. For all of these studies, it's important to know that the primary outcome was disease-free survival. Overall survival and adverse events where secondary outcome.

Great. So given that research and those trials, what are the key recommendations for this guideline update?

Five key recommendations are included in this focused update to the previous guidelines. And they are for women with node-negative breast cancer, extended adjuvant aromatase inhibitor therapy can be offered for up to a total of five years of adjuvant therapy. Recommendations are based on considerations of recurrence risk using our usual established prognostic factors. However, since the recurrence risk is lower, the benefits are likely narrower in node-negative patients.

The guidelines panel recommends that women with low-risk, node-negative tumors should not routinely be offered extended adjuvant therapy. Now, that might sound vague. We did not make recommendations using genomic profiling results because we don't have sound data to support such views that we felt were strong enough to integrate genomic testing results. Our second recommendation is that women with node-positive breast cancer should be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine therapy. And that means combined tamoxifen and aromatase endocrine therapy. That's the total that we meant to recommend.

Third recommendation is that women receiving extended adjuvant endocrine therapy should receive no more than 10 years of total treatment. The fourth recommendation is when given as prevention of secondary or contralateral breast cancer, the risk of second breast cancers based on prior therapy should inform the decision to pursue extended therapy. So what this means is specifically, a woman who has had a bilateral mastectomy will not reap the benefit of preventative therapy with endocrine therapy.

The fifth recommendation is that extended therapy carries ongoing risks and side effects, and these should be weighed against the potential absolute benefits of longer treatment in a shared decision-making process between the clinical team and the patient. Specifically, to date, none of the studies have shown improvement in overall survival with longer duration aromatase inhibitor therapy. As such, the recommendations, therefore, an extended adjuvant AI therapy are based on benefits that include prevention of distant recurrence and prevention of second breast cancers.

So why is this guideline so important and how will it change practice?

The importance of this guideline rests in the fact that it supports what many clinicians and patients are already doing in practice. The second is it recommends against durations of endocrine therapy longer than 10 years in the absence of data supporting such a practice. So it's our thought that doctors and patients and other care providers, nurse practitioners, physician assistants, primary care doctors, are already practicing what we're recommending, and it supports doing so. And the second is that for those providers and patients who aren't sure that 10 years is enough, this guideline suggests that 10 years is sufficient. We don't have any data supporting giving more than 10 years.

And the third recommendation is that this guideline really supports the need for shared decision-making, given the absence of data supporting an improvement in overall survival.

So finally, since you did mention shared decision-making, how does this guideline recommendation affect patients?

Well, the panel strongly believes that the tailored decision-making process is key in the decision to recommend extended adjuvant therapy. So tailoring on disease factors plays a role in the recommended duration of therapy. Obviously, since we stratified by high-risk and low-risk and what treatment's been received specifically. And if a woman's had bilateral mastectomy, she's not going to benefit from the risk reduction that's achieved with giving somebody extended therapy.

But in addition to disease factors, patient preferences and tolerance of therapy should inform clinician and patient decision-making. Again, since none of the studies have shown improvement in overall survival with longer duration of AI therapy, patients and their medical providers need to make decisions based on an awareness that the benefits include, specifically prevention of distant recurrence and prevention of second breast cancers. And the importance of those benefits is going to vary according to a patient and how she views her life going forward and how bad her side effects have been, how well she tolerates the therapy.

From my own personal point of view, as a breast oncologist, I believe two things. Number one, we should provide aggressive support for managing symptoms in patients who are most likely to benefit from extended therapy. That is, we should not stop therapy early if she is very likely to benefit if we haven't maximized control of her symptoms. There are many things we can do to improve symptoms and we shouldn't just stop therapy because she's not tolerating treatment if we haven't done the most that we can to improve her quality of life and her symptoms.

Conversely, my hope is that we are not doggedly persisting in recommending prolonged therapy in a patient who has a fear of recurrence but who has little to gain from extended therapy. In the latter case, high quality information support is more therapeutic than extended therapy with a medication that's proven, in randomized controlled trials and in her own personal experience, to decrease her quality of life with marginal, if any, medical benefit.

Thank you so much for the overview of this guideline today and thank you for your time.

Thank you.

And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

Dr. Daniel George is Professor of Medicine and Surgery, Director of GU Oncology for the Duke Cancer Institute, and Co-Chair of the DCI Center for Prostate and Urologic Cancers. Dr George’s primary areas of interest are in drug development and optimizing care for patients with GU cancers, particularly prostate and kidney cancers. In this week's episode, Dr. George presents two contrasting cases with nephrectomy as a possible treatment path. Can you determine the best course of treatment for each patient?

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

Welcome to the ASCO University Weekly Podcast. My name is Dr. Daniel George. And I'm a professor of medicine and surgery at Duke University. I'm also the director of GU oncology at the Duke Cancer Institute and co-chair of the DCI Center for Prostate and Neurologic Cancers.

Today we'll discuss two similar cases of patients presenting with metastatic renal cell carcinoma in our multidisciplinary management options. Without any standard screening procedures, 20% to 30% of kidney cancer patients today present with metastatic disease. Historically, debulking nephrectomy has been our standard of care. And this has been based on old trials from the interferon era of treatments.

Since then, many drugs have been approved for the management of patients with metastatic renal cell carcinoma, many of which have improved the progression free survival and overall survival of patients with metastatic disease, which may have had an impact on the landscape and role for debulking nephrectomy.

Furthermore, metastatic kidney cancer patients can be risk stratified. There's a number of criteria used. But historically the most commonly used criteria has been the Memorial Sloan Kettering Cancer Center criteria. Which included five factors, including KPS score less than 70, a calcium score greater than 10, A serum hemoglobin of less than the lower limit of normal, and LDH greater than 1.5 times the upper limit of normal, or having their primary tumor in place, meaning no prior nephrectomy.

If patients had zero of these factors they were considered good risk with the best survival. Patients with one or two of these factors are considered intermediate risk. And patients with three or more of these factors historically have been very poor risk, with median survivals of six months or less.

The Carmena Study was a prospective, multi-center, randomized, non inferiority trial comparing upfront nephrectomy followed by sunitinib therapy, compared to upfront sunitinib therapy alone in patients with metastatic renal cell carcinoma amenable to cytoreductive nephrectomy.

We'll get to these results in a moment. But the study population included, importantly, patients with e cog performance status zero or one. And 40% plus of these patients were considered poor risk, with the average sum of metastatic tumor burden being greater than five centimeters.

So now, let's get to some modern cases. The first case we'll discuss is George. He's an 83-year-old man who presented with gross hematuria and a hemoglobin of 13.8 in the normal range. A CT scan revealed an eight centimeter right renal mass and multiple pulmonary mets, up to two centimeters in size.
His e cog performance status is zero. And his calcium was 8.4, and LDH was normal as well.

Our second case, for comparison, is Philip, a 76-year-old man who was found to have a 16 centimeter left renal mass incidentally on a spine MRI. This was confirmed by CT scan, along with some pulmonary nodules measuring up to 1.8 centimeters, as well as enlarged mediastinal lymph nodes up to two centimeters, and an eight millimeter liver lesion. His calcium score was 10.4. And his hemoglobin was 12.5, which was below the limit of normal. He had a normal LDH and an absolutely zero performance status.

So for these two cases, we have four choices. The first choice is for both cases a nephrectomy followed by systemic treatment, our historical approach. The second is systemic therapy first, with plus or minus a subsequent nephrectomy for both cases.

Our third choice would be to treat case number one with a nephrectomy, followed by systemic therapy, and case number two with systemic therapy first. And our fourth option would be systemic therapy first for case one and a nephrectomy first for case two.
Now, to me, when I look at these cases, the correct answer is three. Nephrectomy first for case one, and systemic therapy first for case two. Let me explain.

Even though these cases are fairly similar in age, gender, performance status, and had the presence of a large primary tumor, for case one this is an intermediate risk patient. This patient has lung only disease that's relatively low volume, a good performance status, and normal labs. In addition, he's symptomatic with gross hematuria. For these reasons, a debulking nephrectomy is really indicated. And because of his good performance status, he's very likely to recover well from the surgery, despite the fact that he's 83 years old.

Case two is subtly different. This is actually a poor risk patient. Even though his e cog performance status is zero, he has an elevated calcium, a decreased hemoglobin, and he's got his primary tumor still in place. That puts him into a poor risk category. And some of these patients never recover from surgery well enough to get systemic therapy.

He also has multi organ involvement, involving his lungs and nodes, and possibly even his liver. This is a patient that really mirrors the patient population of Carmena. Based upon this, I think systemic therapy first is a reasonable treatment option for this patient.
If we actually look at the results of Carmena, the study confirmed that sunitinib therapy alone, systemic therapy, was non inferior, and actually trended towards improved survival compared to cytoreductive nephrectomy followed by sunitinib.

The results suggest that for poor risk or for high volume metastatic patients, that systemic therapy first should be the standard of care.
But, importantly, not included in a Carmena study were patients that had low volume metastatic disease and intermediate risk features, or good prognosis. These patients not included in the Carmena study might still benefit first from a debulking or cytoreductive nephrectomy.

So thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on the role of cytoreductive nephrectomy, including additional patient cases and opportunities for self-evaluation, visit the Comprehensive eLearning Center at university.asco.org.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Yosef Landman is a graduate of the Sackler School of Medicine, Tel Aviv University. He is currently a medical oncology resident at Davidoff Cancer Center, Rabin Medical Center in Petach Tiqva, Israel. In today's episode, he discusses the recent approval of larotrectinib for tumor-agnostic treatment of advanced solid tumors containing NTRK gene fusion. Dr. Landman, a co-author on the journal paper Rapid Response to Larotrectinib (LOXO-101) in an Adult Chemotherapy-Naive Patients With Advanced Triple-Negative Secretory Breast Cancer Expressing ETV6-NTRK3 Fusion (Clinical Breast Cancer, June 2018), provides background on the recent approval as well as a case-based example of larotrectinib treatment.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

Dr. Ian Flinn, Medical Oncologist specializing in hematologic malignancies at Tennessee Oncology, discusses the recent FDA approval of duvelisib for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

(Intro Music Playing)
As a background to today's discussion, the PI3K are a family of lipid kinases that sit at the crossroads of numerous signaling events that drive many malignancies, including certain lymphomas, and chronic lymphocytic leukemia. There are four isoforms of the PI3K-- alpha, beta, delta, and gamma. Isoform specific inhibitors are attractive because they may lead to efficacy without the toxicity of pan inhibitors.

Idelalisib, which is a delta isoform inhibitor, was the first PI3K inhibitor be approved for lymphoma in CLL. The delta isoform is a particular interest in B cell malignancies because its expression is normally restricted to cells of a hematopoietic origin. In data from gene knockout models, show that it has a key role in B cell signaling, development, and survival.
Selective targeting of the delta isoform should not alter insulin signaling, which is mediated by the ubiquitously expressed alpha isoform. However, narrow targeting could lead to mechanisms of resistance to upregulation of other isoforms. This has been demonstrated in mantle cell lymphoma where the alpha isoform is expressed in relapse patients.

Duvelisib is a dual inhibitor of both the delta and gamma isoforms of the PI3K. Inhibiting the gamma isoform may be important because of its inhibitory effect, not only in the malignant cell, but also in the micro-environment, which provides important survival signals to malignant cells. Both idelalisib and copanlisib, an inhibitor of the delta and alpha isoforms, are currently FDA approved for third line follicular cell lymphoma. And idelalisib is approved in combination with rituximab in relapse CLL.

On September 24, 2018, the Food and Drug Administration granted approval for duvelisib for patients with relapsed refractory chronic lyphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma after at least two prior therapies. The approval of duvelisib in CLL was based on the DUO trial, a large international randomized phase III trial comparing duvelisib, at 25 milligrams orally, twice daily, to ofatumumab, given according to the package label. The results of the duo trial have been published in Blood.
In a subset analysis of 196 patients receiving at least two prior therapies, the median progression pre-survival was 16.4 months in the duvelisib arm, and 9.1 months in the ofatumumab arm, with a hazard ratio of 0.40. The overall response rate of 78% with duvelisib was twice the 39% seen with ofatumumab.

The follicular lymphoma indication is based on the Dynamo trial, a single arm multi-center trial of duvelisib, which enrolled 83 patients with follicular lymphoma who are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The overall response rate, determined by an independent response committee, was 42%. Of the 35 responding patients, 15, or 43%, maintained responses for at least six months. And 6, or 17%, maintained responses for at least 12 months. The most common adverse reactions with an instance of greater than or equal to 20% were diarrhea, or colitis, neutropenium, rash, fatigue, pyrexia, cough, nausea, upper respiratory tract infection, pneumonia, muscle skeletal pain, and anemia.

Over the last decade, we've seen substantial advances in the treatment of low grade lymphoma and CLL, especially in the front-line setting. Unfortunately for patients with relapse and refractory disease, new agents are needed. The approval of duvelisib is an important addition to our armamentarium for these patients. And we'll have an immediate impact.

However, to have its greatest effect, strategies will need to be devised to move this drug earlier in the natural history of these diseases. Such approaches might include alternative dosing and scheduling, as well as combination regiments. Duvelisib is a novel PI3K inhibitor and is differentiated from other PI3K inhibitors, because it targets both the delta and gamma isoforms. Consequently, it is being studied in a broader array of diseases, including T cell malignancies, where promising activity has been seen.

(Outro Music Playing)
Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on drug approvals visit the comprehensive e-learning center at university.asco.org.

In this episode of ASCO Educational podcasts, we'll explore how we interpret and integrate recently reported clinical research into practice. The first scenario involves a 72-year old man with high-risk, localized prostate cancer progressing to hormone-sensitive metastatic disease. 

Our guests are Dr. Kriti Mittal (UMass Chan Medical School) and Dr. Jorge Garcia (Case Western Reserve University School of Medicine). Together they present the patient scenario (1:12), review research evidence regarding systemic and radiation therapy for high-risk localized disease (5:45), and reflect on the importance of genetic testing and (10:57) and considerations for treatment approaches at progression to metastatic disease (16:13). 

Speaker Disclosures
Dr. Kriti Mittal: 
Honoraria – IntrinsiQ; Targeted Oncology; Medpage; Aptitude Health; Cardinal Health 
Consulting or Advisory Role – Bayer; Aveo; Dendreon; Myovant; Fletcher; Curio Science; AVEO; Janssen; Dedham Group 
Research Funding - Pfizer

Dr. Jorge Garcia: 
Honoraria - MJH Associates: Aptitude Health; Janssen
Consulting or Advisor – Eisai; Targeted Oncology
Research Funding – Merck; Pfizer; Orion Pharma GmbH; Janssen Oncology;  Genentech/Roche; Lilly 
Other Relationship - FDA

Resources 
ASCO Article: Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019

ASCO Course: How Do I Integrate Metastasis-directed Therapy in Patients with Oligometastatic Prostate Cancer? (Free to Full and Allied ASCO Members)

If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org.

TRANSCRIPT

Dr. Kriti Mittal: Hello and welcome to this episode of the ASCO Education Podcast. Today we'll explore how we interpret and integrate recently reported clinical research into practice, focusing on two clinical scenarios: localized prostate cancer progressing to hormone-sensitive metastatic disease; and a case of de novo metastatic hormone-sensitive prostate cancer progressing to castration-resistant disease.

My name is Kriti Mittal and I am the Medical Director of GU Oncology at the University of Massachusetts. I am delighted to co-host today's discussion with my colleague, Dr. Jorge Garcia. Dr. Garcia is a Professor of Medicine and Urology at Case Western Reserve University School of Medicine. He is also the George and Edith Richmond Distinguished Scientist chair and the current chair of the Solid Tumor Oncology Division at University Hospital's Seidman Cancer Center. Let me begin by presenting the first patient scenario. 

Case 1: A 72-year-old male was referred to urology for evaluation of hematuria. A rectal exam revealed an enlarged prostate without any nodules. A CT urogram was performed that revealed an enlarged prostate with bladder trabeculations. A cystoscopy revealed no stones or tumors in the bladder, but the prostatic urethra appeared to be abnormal looking. Transurethral resection of the prostate was performed. The pathology revealed Gleason score 4+5=9 prostate cancer, involving 90% of the submitted tissue. PSA was performed one week later and was elevated at 50. Patient declined the option of radical prostatectomy and was referred to radiation and medical oncology.  

So I guess the question at this point is, Dr. Garcia, in 2023, how do you stage patients with high-risk localized prostate cancer and how would you approach this case?

Dr. Jorge Garcia: That's a great question and a great case, by the way, sort of what you and I in our practice will call ‘bread and butter’. Patients like this type of case that you just presented come from different places to our practice.  So either they come through urology or oftentimes they may come through radiation oncology. And certainly, it depends where you practice in the United States, at ‘X’, US, they may come through medical oncology.  

So I think that the first question that I have is in whatever role I'm playing in this case, where the patient has seen a urologist or a rad onc or me first, I think it's important for us in medical oncology, at least in the prostate cancer space, to talk about how do we think of their case and put those comments into context for the patient. It's very simple for you to tell a patient you can probably have surgery, radiation therapy, but at the end of the day, how do you counsel that patient as to the implications of the features of his disease is going to be really important. I use very simple examples that I relate to my patients, but really this patient is a patient that has very high-risk prostate cancer based upon the NCCN guidelines and how we actually stratify patients into what we call low-risk, intermediate-, and high-risk, and between those very low and very high risk. 

So his PSA is high, very high, I would argue. His Gleason score, now, what we call group grading is high. He has high-volume disease. So the first question that I would have is, what are the choices for treatment for a patient like this? But even before you and I may talk about treatment options, we really want to understand the volume of their disease and whether or not they have localized prostate cancer with high-risk features or whether or not they have locally advanced or hopefully not metastatic disease. So back in the days prior to the FDA approval for PSMA PET imaging, we probably will have a Technetium-99 whole-body bone scan, and/or we probably will actually use CT scanning. Most people in the past, we used to do just a CT of the abdomen and pelvic region. As you know, with the movement of oral agents in the advanced setting, I think most of us will do a chest CT, abdomen and pelvic region, and certainly we also probably will have a Technetium-99 bone scan. 

Now, with the utility and the use of PET imaging, I think most people like him will probably undergo PET PSMA, where you use F-18 PSMA or Gallium-68 PSMA. I think the importance depends on how you look at the approval of these two technologies. I think that PET PSMA imaging is here to stay. It's probably what most of us will use. And based upon that, we will define yet the truest stage of this patient. So right now, what we know is he has high-risk features. Hopefully, their disease is localized. We'll probably put the patient through an imaging technology. If you don't have access to a PET, then obviously CT and a bone scan will do. But if you do, the PET will actually help us define if the patient has disease outside of the prostate region, in the pelvic area, or even if they have distant metastases.

Dr. Kriti Mittal: I would agree with that approach, Dr. Garcia. I think in the United States, we've been late adopters of PSMA scans. I think this patient with high-risk localized disease, if insurance allows at our institution, would get a PSMA for staging. There are still some patients where insurance companies, despite peer-to-peer evaluations, are not approving PSMAs. And in those situations, the patient would benefit from conventional CTs and a bone scan. So let's say this patient had a PSMA and was found not to have any regional or distant metastases. He decided against surgery, and he is seeing you as his medical oncologist together with radiation. What would your recommendations be? 

Dr. Jorge Garcia: I think the bigger question is, do we have any data to suggest or to demonstrate that if in the absence of metastatic disease with conventional imaging or with emerging technologies such as PSMA PET, there is no evidence of distant disease, which I think you probably agree with me, that would be sort of unlikely with a patient with these features not to have some form of PSMA uptake somewhere in their body. But let's assume that indeed then the PSMA PET was negative, so we're really talking about high-risk localized prostate cancer. So I don't think we can tell a patient that radical prostatectomy would not be a standard of care. We never had a randomized trial comparing surgery against radiation therapy. This patient has already made that decision and surgery is not an option for him. If he, indeed, had elected radiotherapy, the three bigger questions that I ask myself are where are you going to aim the beam of that radiation therapy? What technology, dose, and fractionation are you going to use? And lastly, what sort of systemic therapy do you need, if any, for that matter? Where we do have some data maybe less controversial today in 2023 compared to the past? But I think the question is, do we do radiation to the prostate only or do we expand the field of that radiation to include the pelvic nodes? 

Secondly, do we use IMRT? Do you use proton beam or not? Again, that's a big question that I think that opens up significant discussions. But more important, in my opinion, is the term of hypofractionation. I think the field of radiation oncology has shifted away from the old standard, five, seven weeks of radiation therapy to more hypofractionation, which in simple terms means a higher dose over a short period of time. And there was a concern in the past that when you give more radiation on a short period of time, toxicities or side effects would increase. And I think that there is plenty of data right now, very elegant data, demonstrated that hypofractionation is not worse with regards to side effects. I think most of us will be doing or supporting hypofractionation. And perhaps even to stretch that, the question now is of SBRT. Can we offer SBRT to a selected group of patients with high-risk prostate cancer? And again, those are discussions that we will naturally, I assume, in your practice, in your group, you probably also have along with radiation oncology. 

Now, the bigger question, which in my mind is really not debatable today in the United States, is the need for systemic therapy. And I think we all will go back to the old data from the European EORTC data looking at the duration of androgen deprivation therapy. And I think most of us would suggest that at the very least, 24 months of androgen deprivation therapy is the standard of care for men with high-risk prostate cancer who elect to have local definitive radiation therapy as their modality of treatment. I think that whether or not it's 24 or 36, I think that the Canadian data looking at 18 months didn't hit the mark. But I think the radiation oncology community in the prostate cancer space probably has agreed that 24 months clinically is the right sort of the sweetest spot. 

What I think is a bit different right now is whether or not these patients need treatment intensification. And we have now very elegant data from the British group and also from the French group, suggesting, in fact, that patients with very high-risk prostate cancer who don't have evidence of objective metastasis may, in fact, benefit from ADT plus one of the novel hormonal agents, in this case, the use of an adrenal biosynthesis inhibitor such as abiraterone acetate. So I think in my practice, what I would counsel this patient is to probably embark on radiotherapy as local definitive therapy and also to consider 24 months of androgen deprivation therapy. But I would, based upon his Gleason score of group grading, his high-volume disease in the prostate gland, and his PSA, to probably consider the use of the addition of abiraterone in that context.

Dr. Kriti Mittal: That is in fact how this patient was offered treatment. The patient decided to proceed with radiation therapy with two years of androgen deprivation. And based on data from the multi-arm STAMPEDE platform, the patient met two of the following three high-risk features Gleason score >8, PSA >40, and clinical >T3 disease. He was offered two years of abiraterone therapy. Unfortunately, the patient chose to decline upfront intensification of therapy. In addition, given the diagnosis of high-risk localized prostate cancer, the patient was also referred to genetic counseling based on the current Philadelphia Consensus Conference guidelines. Germline testing should be considered in patients with high-risk localized node-positive or metastatic prostate cancer, regardless of their family history. In addition, patients with intermediate-risk prostate cancer who have cribriform histology should also consider germline genetic testing. 

Access to genetic counseling remains a challenge at several sites across the US, including ours. There is a growing need to educate urologists and medical oncologists to make them feel comfortable administering pretest counseling themselves and potentially ordering the test while waiting for the results and then referring patients who are found to have abnormalities for a formal genetics evaluation. In fact, the Philadelphia Consensus Conference Guideline offers a very elegant framework to help implement this workflow paradigm in clinical practice. And at our site, one of our fellows is actually using this as a research project so that patients don't have to wait months to be seen by genetics. This will have implications, as we will see later in this podcast, not only for this individual patient as we talk about the role of PARP inhibitors but also has implications for cascade testing and preventative cancer screening in the next of kin.

Dr. Jorge Garcia: Dr. Mittal, I think that we cannot stress enough the importance of genetic testing for these patients. Oftentimes I think one of the challenges that our patients are facing is how they come into the system. If you come through urology, especially in the community side, what I have heard is that there are challenges trying to get to that genetic counsel. Not so much because you cannot do the test, but rather the interpretation of the testing and the downstream effect as you're describing the consequences of having a positive test and how you're going to counsel that patient. If you disregard the potential of you having an active agent based upon your genomic alteration, is the downstream of how your family may be impacted by a finding such as the DNA repair deficiency or something of that nature. So for us at major academic institutions because the flow how those patients come through us, and certainly the bigger utilization of multi-disciplinary clinics where we actually have more proximity with radiation oncology urology, and we actually maybe finesse those cases through the three teams more often than not, at least discuss them, then I think that's less likely to occur. But I think the bigger question is the timing of when we do testing and how we do it. 

So there are two ways -- and I'd love to hear how you do it at your institution -- because there are two ways that I can think one can do that. The low-hanging fruit is you have tissue material from the biopsy specimen. So what you do, you actually use any of the commercial platforms to do genomic or next-generation sequencing or you can do in-house sequencing if your facility has an in-house lab that can do testing. And that only gets you to what we call ‘somatic testing’, which is really epigenetic changes over time that are only found in abnormal cells. It may not tell you the entire story of that patient because you may be missing the potential of identifying a germline finding. So when you do that, did you do germline testing at the same time that you do somatic testing or did you start with one and then you send to genetic counseling and then they define who gets germline testing?

Dr. Kriti Mittal: So at our site, we start with germline genetic testing. We use either blood testing or a cheek swab assay and we send the full 84-gene multigene panel.

Dr. Jorge Garcia: Yeah, and I think for our audience, Dr. Mittal, that's great. I don't think you and I will be too draconian deciding which platform one uses. It's just that we want to make sure that at least you test those patients. And I think the importance of this is if you look at the New England Journal paper from many years ago, from the Pritchard data looking at the incidence of DNA repair deficiency in men with prostate cancer in North America, that was about what,  around 10% or so, take it or leave it. So if you were to look only for germline testing, you only will, in theory, capture around 10% of patients. But if you add somatic changes that are also impacting the DNA pathway, then you may add around 23%, 25% of patients. So we really are talking that if we only do one type of testing, we may be missing a significant proportion of patients who still may be candidates, maybe not for family counseling if you had a somatic change, rather than germline testing, the positivity, but if you do have somatic, then you can add into that equation the potential for that patient to embark on PARP inhibitors down the road as you stated earlier. It may not change how we think of the patient today, or the treatment for that matter. But you may allow to counsel that patient differently and may allow to sequence your treatments in a different way based upon the findings that you have. So I could not stress the importance of the NCCN guidelines and the importance of doing genetic testing for pretty much the vast majority of our patients with prostate cancer.

Dr. Kriti Mittal: Going back to our patient, three years after completion of his therapy, the patient was noted to have a rising PSA. On surveillance testing, his PSA rose from 0.05 a few months prior to 12.2 at the time of his medical oncology appointment. He was also noted to have worsening low back pain. A PSMA scan was performed that was noteworthy for innumerable intensely PSMA avid osseous lesions throughout his axial and appendicular skeleton. The largest lesion involved the right acetabulum and the right ischium. Multiple additional sizable lesions were seen throughout the pelvis and spine without any evidence of pathologic fractures. So the question is, what do we do next?

Dr. Jorge Garcia: The first question that I would have is, the patient completed ADT, right? So the patient did not have treatment intensification, but at the very least he got at least systemic therapy based upon the EORTC data. And therefore, one would predict that his outcome will have been improved compared to those patients who receive either no ADT or less time on ADT. But what I'm interested in understanding is his nadir PSA matters to me while he was on radiation and ADT. I would like to know if his nadir PSA was undetectable, that's one thing. If he was unable to achieve an undetectable PSA nadir, that would be a different thought process for me.  

And secondly, before I can comment, I would like to know if you have access to his testosterone level. Because notably, what happens to patients like this maybe is that you will drive down testosterone while you get ADT, PSAs become undetectable. Any of us could assume that the undetectability is the result of the radiation therapy. But the true benefit of the combination of radiation and ADT in that context really comes to be seen when the patient has got off the ADT, has recovered testosterone, and only when your testosterone has normalized or is not castrated, then we'll know what happens with your serologic changes. If you rise your PSA while you recover testosterone, that is one makeup of patient. But if you rise your PSA while you have a testosterone at the castrated level, that would be a different makeup of a patient. So do we have a sense as to when the patient recovered testosterone and whether or not if his PSA rose after recovery? 

Dr. Kriti Mittal: At the time his PSA rose to 12, his testosterone was 275.

Dr. Jorge Garcia: Okay, perfect. You and I would call this patient castration-naive or castration-sensitive. I know that it's semantics. A lot of people struggle with the castration-naive and castration-sensitive state. What that means really to me, castration-naive is not necessarily that you have not seen ADT before. It's just that your cancer progression is dependent on the primary fuel that is feeding prostate cancer, in this case, testosterone or dihydrotestosterone, which is the active metabolite of testosterone. So in this case, recognizing the patient had a testosterone recovery and his biochemical recurrence, which is the rising of his PSA occur when you have recovery of testosterone, makes this patient castration-sensitive. Now the PET scan demonstrates now progression of his disease. So clearly he has a serologic progression, he has radiographic progression. I assume that the patient may have no symptoms, right, from his disease? 

Dr. Kriti Mittal: This patient had some low back pain at the time of this visit. So I think we can conclude he has clinical progression as well.

Dr. Jorge Garcia: Okay, so he had the triple progression, serologic, clinical, and radiographic progression. The first order of business for me would be to understand the volume of his disease and whether we use the US CHAARTED definition of high volume or low volume, or whether we use the French definition for high volume from Latitude, or whether we use STAMPEDE variation for definition, it does appear to me that this patient does have high-volume disease. Why? If you follow the French, it's a Gleason score of >8, more than three bone metastases, and the presence of visceral disease, and you need to have two out of the three. If you follow CHAARTED definition, we did not use Gleason scoring, the US definition. We only use either the presence of visceral metastases or the presence of more than four bone lesions, two of which had to be outside the appendicular skeleton. So if we were to follow either/or, this patient would be high-volume in nature. 

So the standard of care for someone with metastatic disease, regardless of volume, is treatment intensification, is you suppress testosterone with androgen deprivation therapy. And in this case, I'd love to hear how you do it in Massachusetts, but here, for the most part, I would actually use a GnRH agonist-based approach, any of the agents that we have. Having said that, I think there is a role to do GnRH antagonist-based therapy. In this case, degarelix, or the oral GnRH antagonist, relugolix, is easier to get patients on a three-month injection or six-month injection with GnRH agonist than what it is on a monthly basis. But I think it's also fair for our audience to realize that there is data suggesting that perhaps degarelix can render testosterone at a lower level, meaning that you can castrate even further or have very low levels of testosterone contrary to GnRH agonist-based approaches. 

And also for patients maybe like this patient that you're describing, you can minimize the flare that possibly you could get with a GnRH agonist by transiently raising the DHT before the hypothalamic-pituitary axis would shut it down. So either/or would be fine with me. Relugolix, as you know, the attraction of relugolix for us right now, based upon the HERO data, is that you may have possibly less cardiovascular side effects. My rationale not to use a lot of relugolix when I need treatment intensification is quite simple. I'm not aware, I don't know if you can mitigate or minimize that potential cardiovascular benefit by adding abiraterone or adding one of the ARIs, because ARIs and abiraterone by themselves also have cardiovascular side effects. But either/or would be fine with me. The goal of the game is to suppress your male hormone. 

But very important is that regardless of volume, high or low, every patient with metastatic disease requires treatment intensification. You can do an adrenal biosynthesis inhibitor such as abiraterone acetate. You can pick an androgen receptor inhibitor such as apalutamide or enzalutamide if that's the case. The subtleties in how people feel comfortable using these agents, I think, none of us – as you know, Dr. Mittal - can comment that one oral agent is better than the other one. Independently, each of these three oral agents have randomized level 1, phase III data demonstrating survival improvement when you do treatment intensification with each respective agent. But we don't have, obviously, head-to-head data looking at this. 

What I think is different right now, as you know, is the data with the ARASENS data, which was a randomized phase III trial, an international effort looking at triple therapy, and that is male hormone suppression plus docetaxel-based chemotherapy against testosterone suppression plus docetaxel-based chemotherapy plus the novel androgen receptor inhibitor known as darolutamide. This trial demonstrated an outcome survival improvement when you do triple therapy for those high-volume patients. And therefore, what I can tell you in my personal opinion and when I define a patient of mine who is in need of chemotherapy, then the standard of care in my practice will be triple therapy. So if I know you are a candidate for chemotherapy, however, I make that decision that I want you to get on docetaxel upfront. If you have high-volume features, then the standard of care would not be ADT and chemo alone, it would be ADT, chemo, and darolutamide. 

What I don't know, and what we don't know, as you know, is whether or not triple therapy for a high-volume patient is better, the same, equivalent, or less than giving someone ADT plus a novel hormonal agent. That is the data that we don't have. There are some meta-analyses looking at the data, but I can tell you that at the very least, if you prefer chemo, it should be triple therapy. If you prefer an oral agent, it certainly should be either apalutamide, abiraterone acetate, and/or enzalutamide. But either/or, patients do need treatment intensification, and what is perplexing to me, and I know for you as well, is that a significant proportion of our patients in North America are still not getting treatment intensification, which is really sub-optimal and sub-standard for our practice. 

Dr. Kriti Mittal: Thank you, Dr. Garcia, for a terrific discussion on the application of recent advances in prostate cancer to clinical practice. In an upcoming podcast, we will continue that discussion exploring management of de novo metastatic prostate cancer.  

The ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  

Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello, and welcome to the ASCO Guidelines Podcast Series. Is my name Shannon McKernin and today, I'm interviewing Dr. Elena Stoffel from the University of Michigan, lead author of "Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion.” Thank you for being here today, Dr. Stoffel.

I'm delighted to join you.

So first, can you tell us what a professional clinical opinion is and why this topic is so important to ASCO?

Well, a provisional clinical opinion is a statement that ASCO puts out when we are seeing trends that are relevant to the care of our patients but that may not necessarily have the level of evidence needed to include in a true clinical guideline. This particular provisional clinical opinion that deals with the management of patients with pancreatic cancer and their families is based on some new data that has been published regarding the prevalence of inherited factors influencing pancreatic cancer risk.

So what are the key statements of this Provisional Clinical Opinion or also known as a PCO?

This particular provisional clinical opinion, which is about just the inherited susceptibility to pancreatic cancer, was prompted by several recent publications, which found that the prevalence of genetic predisposition among patients with pancreatic cancer was much higher than we had originally anticipated. And this is relevant because in talking about pancreatic cancer as one of the deadliest cancers in both in the United States and worldwide, we are very interested in finding ways to reduce the morbidity from this cancer to patients and their families. And this particular provisional clinical opinion addresses the role that genetic risk assessment should have in the care of pancreatic cancer patients and also the role for clinical genetic testing, as well as the risks and benefits of pancreatic cancer screening for at risk family members.

What considerations are there for having these conversations with patients and their families?

Well, many times when we see families affected with cancer, one of the questions they have is what is the likelihood that this will happen to other individuals in our family and what can we do to prevent cancers in other family members. And I think what's important here is that review of the data from multi-gene panel genetic testing in unselected individuals diagnosed with pancreatic cancer identified pathogenic germline variants in 1 out of every 10 individuals. And this is really important because when you think about it, if 1 out of every 10 patients with pancreatic cancer develop their cancer in the setting of a genetic predisposition syndrome, this has tremendous implications for management both for them as well as for their family members.

One of the most common inherited cancer syndromes identified in families affected with pancreatic cancer is hereditary breast ovarian cancer associated with mutations of BRCA1 and BRCA2. As you know, there are definite screening recommendations we make for individuals who carry these genetic alterations. And certainly if a family member is diagnosed with a genetic alteration, then that has an impact for cancer screening and management.

Furthermore, there are emerging data about the utility of pancreatic cancer screening in high risk individuals. And while there's still some controversy about how to screen individuals at risk for pancreatic cancer, certainly there are some emerging data suggesting that this may have a role for early detection.

And finally, the panel included a discussion section on the limitations of the research and future directions. So what are the key points of this section?

I think that what we're learning is with genetic testing, and particularly with multi-gene panel testing, we are we often find unexpected results. Certainly variants of uncertain significance are not uncommon when multi-gene panel tests are used. And being able to interpret the clinical significance of some of these genetic test results can pose some challenges, especially for clinicians who don't have specific expertise in genetics. Certainly being able to deal with the volumes of patients who need genetic testing who are also battling pancreatic cancer, we want to make sure that we have the resources to be able to offer genetic testing to everyone who needs it.

And finally, in talking about screening for pancreas cancer, while there are some studies that have demonstrated that screening with MRIs and/or endoscopic ultrasounds has led to early detection and down staging of cancers in some cases, larger studies are needed to be able to refine more specifically who and how to screen individuals at risk for pancreas cancer.

Great. Thank you so much for taking your time today to discuss this PCO with us, Dr. Stoffel.

Thank you very much for having me.

And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. If you've enjoyed what you heard today, please rate and review the podcast and refer the show to a colleague.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Scott Morgan from the Ottawa Hospital and University of Ottawa, lead author on "Hypofractionated Radiation Therapy for Localized Prostate Cancer: an ASTRO, ASCO, and AUA Evidence-Based Guideline.” Thank you so much for being here today, Dr. Morgan.

It's my pleasure, Shannon. I'm happy to take part in the podcast and hopefully share the highlights of the guideline with your listeners.

So first, can you give us a general overview of what this guideline covers?

Yeah. So the guideline covers really hypofractionated external beam radiation therapy, which is a treatment for localized prostate cancer, and for the non-radiation oncology folks in your audience, I think it's important to begin by placing the guideline sort of in its context and going over some of the terminology that we use as radiation oncologists. So external beam radiotherapy, it's a standard treatment-- standard local treatment option for men with localized prostate cancer. It gives outcomes which are really equivalent to those of radical prostatectomy or brachytherapy, which are the other two standard local treatment options.

And traditionally, it's given in small daily fractions over several weeks and the usual daily fraction size is 1.8 to 2 Gray per day. And this is called conventional fractionation. And that really translates into a course of about seven and a half to nine weeks of treatment. And so that total dose which is delivered in those daily treatments, five days a week, is about 76 to 80 Gray. And that's what we call conventional or standard fractionation.

And there's a theoretical framework in radiation medicine and there's some evidence to accompany that that suggests that prostate cancer is quite sensitive to radiation fraction size. And just to give a brief primer, for any tissue, cancerous or non-cancerous, there's a sensitivity to fraction size and it's characterized by something called the alpha-beta ratio. And for prostate cancer, that's felt to be low compared to most other cancers, the alpha-beta ratio, and indeed, it's thought to be lower than the adjacent dose-limiting normal structure, which is the rectum.

And so an implication of that is that hypofractionation, and by that we mean daily fraction size of more than 2 Gray, might improve the therapeutic ratio of radiation therapy in localized prostate cancer. Now the guideline-- and I think it's important to emphasize this-- it draws a distinction between what we call moderate hypofractionation and ultra-hypofractionation. Clearly, fraction size is a continuous variable, so any subdivision that we might make is necessarily a bit arbitrary, but it turns out that at least in clinical practice, there's been really two distinct approaches to hypofractionation that have arisen.

And one of these is moderate hypofractionation and that's an approach where the fraction size is modestly higher than 2 Gray per fraction, and in the guideline, it's been defined as a fraction size between 2.4 and 3.4 Gray, whereas ultra-hypofractionation, this is defined in the guideline as a fraction size greater than 5 Gray. And it's also been referred to in the literature as extreme hypofractionation or Stereotactic Body Radiation Therapy, SBRT, or SABR, Stereotactic Ablative Radiation Therapy.

But in any case, we are talking here about, with ultra-hypofractionation, with radical courses of treatment that are often delivered over as few as five fractions, often on an alternate day approach over two or two and a half weeks. And so the guideline really was largely motivated by the publication of a number of randomized trials, including four large-scale trials in the past two years that have compared conventionally fractioned radiation therapy and moderately hypofractionated radiation therapy. So that is really what stimulated the guideline, which was the evidence concerning moderately hypofractionated radiation therapy.

But at the same time, there has been an increasing use in routine clinical practice that's been observed of ultra-hypofractionated radiotherapy, so the decision was made to make recommendations on it as well. So ASTRO, American Society for Radiation Oncology, in collaboration with ASCO and the AUA, convened a panel of radiation oncologists, medical physicists, urologists, radiation oncology resident, patient representative, and a systematic review of the literature was conducted and their recommendations have been made on the basis of this systematic review. So the aim was to provide recommendations on use of both moderate hypofractionation and ultra-hypofractionation, in particular with reference to oncologic outcomes, toxicity, and quality of life. So we didn't directly consider health economic endpoints, though clearly the very nature of hypofractionation is such that there are potential advantages in terms of cost and convenience for patients.

And what are the key recommendations of this guideline?

We separated the key recommendations into three main groups and the first set of recommendations pertains to moderate hypofractionation, and these are generally based on the highest-quality evidence. So they could be viewed as the strongest recommendations in the guideline. And the second set of recommendations concern ultra-hypofractionation. They're somewhat less strong given they're based on somewhat weaker evidence. And then the third set of recommendations relate to some of the technical aspects of the planning and delivery of hypofractionated radiation therapy.

So, dealing with the moderate hypofractionation recommendations first, arguably the most important recommendation of the guideline is that the panel has recommended that in patients with localized prostate cancer who are candidates for external beam radiation therapy, moderate hypofractionation should be offered. And this is graded as a strong recommendation. It's based on high-quality evidence and it applies to patients across all risk groups.

So it applies to patients with low-risk prostate cancer who require active treatment or who have declined active surveillance and it also applies to patients with intermediate-risk or high-risk localized prostate cancer. And why really does it apply to all these groups? It's essentially because these groups are well-represented in the trials of moderate hypofractionation. And the trials have shown that moderate hypofractionation really gives similar outcomes in terms of efficacy to conventional fractionation.

Now one caveat I guess that I should say is that the trials generally only looked at radiation therapy to the prostate rather than radiation therapy to the prostate as well as the pelvic lymph nodes. So the panel's recommendations regarding moderate hypofractionation don't apply to the scenario where the clinician has decided to include the pelvic lymph nodes in the radiation therapy volume. The panel also made recommendations with respect to toxicity and quality of life, and specifically, they did recommend that men should be counseled about a small increased risk of acute gastrointestinal toxicity, typically rectal toxicity, with moderately hypofractionated radiation therapy. And they should also be counseled that moderately hypofractionated radiation therapy has a similar risk of late GI toxicity and also has a similar risk of both acute and late GU toxicity compared to conventional fractionation. The only difference was seen in acute GI toxicity.

And I think it's probably worth dwelling on this a little bit more. Probably the most granular data on acute GI toxicity comes from the CHHiP trial. This was a trial from the UK. It was far and away the largest randomized trial of moderate hypofractionation versus conventional fractionation.

And they followed the amplitude of GI toxicity very carefully over the short and long term and what they did found was that in the early weeks, there was greater peak acute GI toxicity with moderate hypofractionation, but this difference had really disappeared by about 18 weeks after the start of radiotherapy. So within a few months, there was no difference, and afterwards, there was no consistent difference in long-term GU or GI toxicity across these trials. Now I guess I should mention that, at the current time, that the median follow-up of most of these trials is between five and six years, so arguably, the last word hasn't been written.

The panel also offered conditional recommendations on particular moderate hypofractionation regimens. There were multiple different regimens that were evaluated but most were not compared head-to-head. And the panel preferred two particular regimens-- 60 Gray and 20 fractions over four weeks or 70 Gray and 28 fractions over five and a half weeks, as these were the two regimens that were evaluated in the largest populations. And of these two, likely the strongest evidence supports 60 Gray and 20 fractions, given it was used in two different trials and it was used across all risk groups and with or without concomitant hormonal therapy. So those were the recommendations regarding moderate hypofractionation.

So moving to ultra-hypofractionation, again, this is talking about fraction size of at least 5 Gray, typically a course of as few as five fractions over perhaps two or two and a half weeks. I think it's important to say that, at the time we were preparing this guideline, there were no published efficacy or toxicity data from randomized trials comparing ultra-hypofractionation and conventional fractionation. So the strengths of the recommendations made by the panel is correspondingly lower than was the case for moderate hypofractionation.

But having said that, there are several prospective non-randomized studies that have been published and have documented safe delivery of ultra-hypofractionation for appropriately-selected patients and pretty good biochemical control and low toxicities have been observed in these studies. But again, relatively few have follow-up beyond five years.

So what the panel recommended was that in men with low-risk prostate cancer-- and the bulk of the data to date for ultra-hypofractionation has been in this group-- panel conditionally recommended that in those who decline active surveillance and choose active treatment with radiation therapy, that ultra-hypofractionation may be offered as an alternative to conventional fractionation. Again, this is a conditional recommendation.

In men with intermediate-risk prostate cancer, the panel has conditionally recommended that ultra-hypofractionation may be offered as an alternative to conventional fractionation but it's strongly recommended in this group that these patients be treated as a part of a clinical trial-- and there are several clinical trials ongoing-- or as part of the multi-institutional registry. And then finally, in patients with high-risk localized prostate cancer, there was really insufficient comparative evidence for the panel to suggest offering this outside of a clinical trial or outside of a registry.

Regarding particular regimens, that the panel again made a conditional recommendation that a schedule of 35 Gray to 36.25 Gray and five fractions delivered to the planning target volume could be offered and that it recommended against consecutive daily treatments for this schedule. So I think it's again important to note that compared to moderate hypofractionation, the ultra-hypofractionation literature is really substantially less mature and it is evolving rapidly. And therefore, a short-term update of this guideline to address new data pertaining specifically to ultra-hypofractionation is likely going to be necessary.

And then I mentioned there was a third set of recommendations and these pertain to the technical aspects of planning and delivering radiation therapy. And these probably are not of core interest to your audience, but briefly, the guideline recommends that in the planning of hypofractionated radiotherapy, that normal tissue constraints and target volumes derive from published reference standards the use and that image guidance and intensity modulation at one form or another are recommended in delivering hypofractionated radiotherapy.

Great. Thank you for the overview of those guideline recommendations. So why is this guideline so important and how will it change practice?

Yeah. I guess the first point to make is that the guideline potentially can inform the care of a very large number of patients. Across North America, about 200,000 patients a year are diagnosed with prostate cancer and its far and away that the most prevalent non-dermatologic cancer in men and it's the third-leading cause of cancer death in men, at least in North America. So the vast majority of those 200,000 men are diagnosed with localized disease at the time of presentation and therefore they're potentially treatable with radiation therapy and therefore the guideline is relevant to these patients.

Prior to the publication of the trials that motivated this guideline, the overwhelming majority of these men who chose external beam radiotherapy as their primary treatment have been treated with conventionally fractionated therapy. In other words, seven and a half to nine weeks of treatment. And already, since the publication of these trials-- the trials of moderate hypofractionation-- we're talking really about moderate hypofractionation because I think that is where the guideline will have its impact, at least in the short term. In the jurisdiction where I practice in Canada, practice has already substantially changed in light of these trials, and I think a large majority of patients with localized prostate cancer choosing external beam radiation therapy are now typically being treated with a moderately hypofractionated approach, typically a four-week schedule. So it will be interesting to see if a similar change is occurring or will occur over time in the United States, particularly informed or potentially informed in part by this guideline.

And then finally, with respect to ultra-hypofractionation, I think again I have to note that this is a very dynamic space in terms of evidence and there are a number of large-scale trials looking at ultra-hypofractionation and comparing it to either conventional fractionation or moderate hypofractionation that are in progress or near to reporting. And so again, an update of the guideline in the short-term as data emerges from these studies will likely be important and it may ultimately influence practice as well on a large scale.

And finally, how will these guideline recommendations affect patients?

So I think in the short term, that the recommendation that has the potential to impact patients in the greatest way is the recommendation regarding moderate hypofractionation. And the guideline really recommends that this is a management approach that substantially reduces the treatment burden without compromising treatment efficacy and without increasing the risk of long-term side effects. So in my view, the move to moderately hypofractionated radiation therapy is a win for patients with localized prostate cancer who choose radiation therapy as their primary treatment modality.

And so moderate hypofractionation really represents about a halving of the overall treatment time in some patients. And those who live, for example, in rural or remote areas and who need to travel considerable distance to have their treatment, a halving of treatment time is significant. But I think even more generally, halving of treatment time is significant for patients regardless of where they live. And clearly there are also benefits potentially in terms of cost and also benefits in terms of for the health care system but those really weren't specifically studied in the guideline.

Great. Thank you so much for your time today, Dr. Morgan, and thank you for your work on this important guideline.

My pleasure, Shannon, and thank you for having me.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Dr. Axel Hauschild, professor of dermatology and head of the dermato-oncology department at the University Hospital of Kiel in Germany, discusses the recent FDA approval of cemiplimab, a PD-1 antibody treatment for patients with metastatic or locally advanced cutaneous squamous cell carcinomas.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

[MUSIC PLAYING]
Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Axel Hauschild. I'm a professor of dermatology and head of dermato-oncology at the University Hospital of Kiel in Germany.
Today, we will discuss the approval of cemiplimab, a new PD-1 antibody for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas. As a background to today's discussion, immune checkpoint inhibitors are active therapies in patients with other cutaneous malignancies, like melanomas and mucosal carcinomas already.
So far, chemotherapy was given as a routine for patients with advanced or metastatic cutaneous malignancies, and occasionally, cetuximab, an EGFR inhibitor. However, in almost all of these patients, the responses were short-lasting. The analysis of the tumor mutational burden indicated a high sensitivity of more or less all UV-induced cutaneous malignancy for immune checkpoint inhibitors. Therefore, theoretically, cutaneous squamous cell carcinomas are ideal tumors for the treatment with PD-1 or PD-ligand 1 antibodies.
On September 28 of 2018, cemiplimab was approved by the FDA for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas who are not candidate for curative surgery or curative radiation. These data led to the approval of a flat dose of 350 milligrams cemiplimab infused over 30 minutes every three weeks.
The approval of cemiplimab was based on a high number of clinically meaningful and durable objective responses observed in patients with two different clinical trials. The results have already been published in 2018, in June, in the New England Journal of Medicine.
Both clinical trials were non-randomized, multicenter studies in patients for whom surgery or irradiation was not recommended. Among 108 patients with advanced cutaneous squamous cell carcinomas, including 75 metastatic patients, the overall response rate was 47%, with 4% complete and 44% partial responses. There were no significant differences in the response rate between patients with metastatic and those with locally advanced disease.
The median response duration was not reached. And 61% of the responses were durable for six months or longer. Response rates and durability results were consistent across the advanced squamous cell carcinoma subtypes. For patients with locally advanced cutaneous squamous cell carcinomas, the radiographic response rate correlated with clinically relevant shrinkage of visible and often disfiguring tumors demonstrated in the photographic data obtained in these clinical trials.
Safety data were evaluable from 434 patients who received cemiplimab in both clinical trials. Serious adverse events were typically immune-mediated, such as colitis or pulmonitis. And in some patients, infusion reactions were observed. The most common adverse events were fatigue, rash, and diarrhea. The treatment discontinuation rate was 12%.
The approval of cemiplimab marks a significant advancement in the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas. Cemiplimab is considered as a new standard of care in these patients, since not only an impressive response rate of almost 50%, but also durable responses were observed.
As mentioned before, previously, chemotherapies and cetuximab have been used for these patients with limited efficacy, particularly because most responses were only short-lasting. Important to mention is that the approval is not going along with a biomarker test, such as the measurement of PD-ligand 1 expression. Therefore, cemiplimab can be used for all comers with metastatic or locally advanced cutaneous squamous cell carcinomas.
So far, there are no data available when cemiplimab has been combined with other agents or irradiation. Also, data from the adjuvant of PD-1 antibodies in high-risk cutaneous squamous cell carcinoma patients are outstanding. However, clinical trials on cemiplimab and other PD-1 antibodies are already planned.
In conclusion, cemiplimab adds significantly to the success story of PD-1 and PD-ligand 1 antibodies in cutaneous malignancies. The approval of cemiplimab for cutaneous squamous cell carcinomas leads to changes in the current guidelines for this tumor.
Thank you very much for listening to this week's episode of the ASCO University Weekly Podcast. For more information on immune therapy and the treatment of cutaneous squamous cell carcinomas, visit the comprehensive eLearning Center at university.asco.org.
[MUSIC PLAYING]
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a moment to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

[MUSIC PLAYING]

Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Valerie de Haas from Princess Máxima Center for Pediatric Oncology in the Netherlands, lead author on "Initial Diagnostic Workup of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the CAP and ASH Guideline.”

Thank you for being here today, Dr. de Haas.

Thank you.

So first, can you give us a general overview of what this guideline covers?

Well, yes. The laboratory evaluation of patients who are suspected of having acute leukemia is very complex, and it has evolved significantly with the incorporation of advanced laboratory techniques. The traditional backbone of initial workup of AL, of acute leukemia, is composed of ctyomorphology, cytochemistry, immunophenotyping, and molecular cytogenetics.

These techniques are the backbone of the initial diagnostic workup of acute leukemia. This is leading to risk stratification and fine tuning of the therapy by molecular signatures. The advanced molecular diagnostics, such as next-generation sequencing, has become more important in the diagnosis and in the risk stratification of acute leukemia.

This guideline is meant for both pediatric and adult patients, and it was initially published in 2017. This year, we reviewed this guideline, and we have taken into account two important developments.

First, since 2017, we've seen that there are major advances in molecular techniques and also that we can identify and validate new molecular markers. And those two events have contribute to a better risk stratification. And the second development is the effect that the WHO classification was revised in 2017 which also has led to new risk recoveries and refined subclassifications.

So what are the key recommendations of this guideline?

Well, in total, we have reviewed 27 guideline statements by the ASCO endorsement expert panelists. And discussion points are used to summarize issues that were identified from the updated literature. The ASCO expert panel determined that the recommendations from the guideline as published in 2016 are clear, thorough, and they are based upon the most relevant scientific evidences.

We fully endorse the CAP-ASH guideline on initial diagnostic workup of acute leukemia. And we decided to include some discussion points according to clinical practice and according to the updated literature. In fact, we identified four categories of key recommendations. The first one is the initial diagnostics focusing on basic diagnostics and determination of risk parameters.

This concerns, in total, about 11 guideline recommendations, and they give an overview of the initial workup varying from the collection of the clinical history of the patient to initial basic diagnostics by cytomorphology, flow cytometry and molecular cytogenetic analysis of peripheral blood, bone marrow, and cerebrospinal fluids.

Secondly, the second category were molecular markers and MRD detection, and they were addressed by 10 of the recommendations. And these recommendations give a structural overview of the molecular and cytogenetic workup for acute lymphoblastic leukemia versus acute myeloid leukemia identifying different prognostic markers.

Also, the detection of MRD is taken into account in this recommendation. There is a major difference between children and adults, and this part is given most attention in the discussion part as the developments have been major during the past few years.

The third one is the context of referral to another institution with expertise in the management of acute leukemia. This is addressed by four recommendations, emphasizing the point that referral to an institution with specific expertise is of major importance for the central workup of acute leukemia.

And finally, the final reporting and report keeping is reflected in three recommendations, mainly supporting conclusions from 2017 which were describing the fact that the complete report with basic diagnostics in one central report should be available within 48 to 72 hours. And this should be followed by complete, final, comprehensive report in one or two weeks.

So can you tell us about those discussion points that were made and why the panel decided to include these?

The discussion points include mostly issues regarding diagnostics that involve flow cytometry and molecular techniques as addressed in part one and two of the guidelines. We think that the cytomorphologic assessment is essential for initial diagnosis of acute leukemia.

Multicolor flow cytometry using 8 to 10 colors has led to a better distinction between myeloids, lymphoid, and mixed lineage blast origin. Even when the number of cells are limited, for instance in CNS involvement, fine needle aspirate of extramedullary leukemic infiltration, or skin biopsy for leukemic cutis.

Also, it was suggested to better assess the central nervous system involved in leukemia. The expert panel recommends the immunophenotyping studies as an additional detection technique next to the cytomorphological examination of cytospins and particularly for those with a low level involvement of acute leukemia that cannot be well addressed by a morphologic examination only.

The TDT immunohistochemistry staining of cytospins has alternatively been used for detection of CNS disease in AML and evaluation of CSF by multicolor flow cytometry has been recently adopted in some centers. Flow cytometry, using at least six, but we now use in some laboratories, even 8 to 10 colors has led to a much more specific in tentative diagnosis. And this has improved the detection of CNS involvement.

The use of molecular tools, for instance, polymerase change reaction, PCR, NGS for low-level CSF involvement is still under study, and therefore, we did not recommend this in our discussion.

Regarding the molecular markers and MRD detection, the discussion here was mainly based upon the results of translational research supported by better molecular detection techniques. And those molecular diagnoses have been developing in the past few years with the inclusion of many more molecular markers. And they included one of the key diagnostic criteria in the revised WHO classification, which was revised in 2017. And we made substantial changes that have been made in the ASH-CAP guidelines concerning molecular diagnostics.

Those newly identified targets by advanced molecular techniques give possibilities for better risk stratification. Some examples of better molecular characterization of acute lymphoblastic leukemia are, for instance, additional testing for MLL translocations. Furthermore, we can look in patients with T-ALL for NOTCH1, and FBXW7 mutations.

The Ikaros family zinc finger gene, the IKZF1 gene is frequently deleted in adults as well in children with B-ALL. And it was shown to have an independent prognostic significance and was also associated with poor clinical outcome.

In the current text of the current risk that the protocols IKZF1 should be regularly included in the screening panels for all ALL patients.

If we look for examples for better characterization of AML, acute myeloid leukemia, we have found an increasing number of additional cytogenetic aberrations, like for instance FLT3 ITD which is associated with poor outcome.

Another example is appropriate mutational analysis for kids, which can be detected both in adult patient as pediatric patients with a confirmed core binding factor acute myeloid leukemia. So this is myeloid leukemia with a translocation A21, RUNX1, or inversion 16.

This recommendation is very strong in adults, whereas in children, this prognostic fact impact remains unclear. So there have been proven several publications which refer to a similar prognosis for children and others who refer to a poor prognosis in comparison to known mutated genes. So we suggest to test for this mutation in adults, especially, but also in children to learn from it.

Finally, emerging evidence supports molecular studies as principle test for monitoring minimal residual disease of acute leukemia. And there are several key molecular markers that are included in the initial workup, which will be carried on for monitoring MRD, for instance, PML- RAR-alpha, RUNX1-RUNXT1, CBFB-MYH11, and NPM1, CEBP-alpha and others.

Beside those aforementioned markers, it's very important to screen for other molecular markers that have predictive or prognostic value in the individual. And it is possible to use them for MRD. We have found a recent consensus from the European Leukemia Net MRD Working Group, who was proposing that for detection of molecular MRD, and they refer the RT PCR platform to NGS and digital PCR platforms.

Although all those molecular techniques have been developed very quickly and it is very tempting to use them for initial diagnostics, currently, not all laboratories will have all those techniques available. So the expert panel strongly advises understanding to make distinction between diagnostic that are needed in the first phase to start treatment and subsequently, treatment stratification, in contrast to the usual dose findings in a broader research.

For instance, available karyotyping, FISH, PCR techniques, if possible, NGS can be used in the initial start of treatment, whereas techniques like whole exome sequencing, whole genome sequencing, RNA sequencing, and epigenomic studies are meant for a broader research.

And finally, how will these guideline recommendations affect patients?

Well, in the end, the patients will receive better and especially, more personalized treatment. If we have results available within two weeks from diagnosis, it will be possible to better identify which basis will better benefit from more intensified and more personalized treatment, whereas others may need less intensive treatment with less toxicity.

If you use traditional techniques to do this supported by molecular techniques like karyotyping, FISH, and PCR techniques, and in the end, following MRD to see which patients are responding to treatment, MRD detection will help to identify these patients and stratify them finally to the best treatment.

Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. de Haas.

OK. Thanks a lot.

And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

In this week's episode, Dr. Danielle Shafer, Medical Director of the Clinical Trials Office at Massey Cancer Center at Virginia Commonwealth University, explores the recent FDA approval of ivosidenib for the treatment of relapsed or refractory acute myeloid leukemia. Dr. Shafer's primary clinical focus is leukemia & lymphoma in adult patients. Her research focus is limited to the same population, with a particular interest in relapsed/refractory AML.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

[MUSIC PLAYING]
Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Danielle Shafer, and I'm an assistant professor at the Massey Cancer Center at Virginia Commonwealth University. My area of specialty is leukemia and lymphoma. Today, we will discuss the approval of ivosidenib in patients with relapsed and refractory AML with a susceptible IDH1 mutation.
As a background to today's discussion, somatic mutations of IDH have been identified in multiple tumor types, including AML and MDS. As a result of the mutation, there is impaired hematopoietic differentiation, as well as epigenetic alteration. IDH mutations occur in approximately 20% of adults with AML, and 5% of adults with MDS. IDH1 mutations occur in approximately 6% to 9% of adult AML patients. Enasidenib was approved by the FDA in 2017 for adult patients with relapsed and refractory AML with an IDH2 mutation.

On July 20, of 2018, ivosidenib was approved by the FDA for the treatment of adult patients with relapsed and refractory AML with a susceptible IDH1 mutation, as detected by an FDA approved test. The approval of ivosidenib in the relapse to refractory setting was based on the results of a phase I dose escalation and dose expansion study published in the New England Journal of Medicine.
The primary objectives of the study were to assess the safety, maximum tolerated dose, and recommended phase II dose. Of the 258 patients receiving study drug, 179 patients had relapsed and refractory disease. The median age was 67, with a range of 18 to 87 years. Patients had a median of two prior therapies, 24% had relapsed after transplant, and 59% were refractory to induction or re-induction.

59% had favorable cytogenetics. The most common co-occurring mutation was NPM1 in 26% of patients. A maximum tolerated dose was not defined, and ivosidenib 500 milligrams was selected for dose expansion. The most common adverse reactions were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, Q/T prolongation, rash, pyrexia, cough, and constipation.
In the overall population, 30 day all-cause mortality was 7%. The majority of deaths were related to disease progression or complications of underlying AML. No treatment-related adverse events leading to death were seen in patients with a starting dose of 500 milligrams.

IDH differentiation syndrome is of special interest, as early identification is necessary. It is similar to what has been described with ATRA and arsenic trioxide. In this study, IDH differentiation syndrome was reported in 19 patients, and was of grade 3 or higher in nine patients. Leukocytosis grade 2 or 3 accompanied differentiation syndrome in 7 of the 19 patients.

Median time to onset was 29 days, with a range of 5 to 59 days. Treatment included glucocorticoids, diuretics, and hydroxyurea, if leukocytosis was present. With intervention, 17 of the 19 patients had resolution. The two remaining patients had differentiation syndrome at data cutoff. In the relapsed refractory population, the rate of complete remission or complete remission with partial hematologic recovery was 30.4%.
The median duration of complete remission, or complete remission with partial hematologic recovery, was 8.2 months. The median time to response was 2.7 months. With a median follow-up of 14.8 months, the median overall survival was 8.8 months. ivosidenib is the first IDH1 inhibitor to enter the clinic for relapsed refractory AML, and clearly represents a step forward for this population. The drug is, overall, well-tolerated.
Differentiation syndrome represents a unique toxicity, as early recognition is critical. Practicing physicians may encounter difficulties differentiating disease progression from differentiation syndrome in some patients. Given the success of the drug in the relapsed refractory setting, it is now being combined with other therapies and moving earlier in the treatment course. Based on the encouraging results of a phase I study, ivosidenib is currently being combined with intensive chemotherapy in a phase III study, for newly-diagnosed AML patients with IDH1 mutations.

Although the drug is termed a success, the majority of patients are still dying of their disease. While some patients were bridged to transplant in the New England study, the benefit is not yet entirely clear. Additional questions emerge regarding co-mutations and IDH1 mutation clearance. Not surprisingly, in this study, there was some preliminary data to suggest that patients with IDH1 clearance had longer durations of remission and survival. We anticipate better understanding as more patients are treated with the drug.
Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on the treatment of AML, visit the comprehensive e-learning center at university.asco.org.

[MUSIC PLAYING]

Dr. Shaheenah Dawood is the Head of Medical Oncology and the Head of the Breast Cancer Program at Dubai Hospital in the United Arab Emirates. Dr. Dawood completed her M.B.B.Ch at Dubai Medical College in 1998 and a Master of Public Health degree at the Harvard School of Public Health, Boston, USA in 2008. Her postgraduate medical training programs include a Fellowship at McGill University in Canada in 2006, and the Susan Komen Breast Cancer Fellowship at the University of Texas M.D. Anderson Cancer Center in 2007. Dr. Dawood is a member of various professional organizations, including the American Society of Clinical Oncology (ASCO), the American Association of Cancer Research (AACR), the Canadian Association of Medical Oncologists, the Emirates Medical Association, and the Inflammatory Breast Cancer Research Group. She is also the co-director of the Middle East Research Network.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

[MUSIC PLAYING]

Welcome to the self-evaluation episode of the ASCO University Weekly Podcast. My name is Shaheena Dawood, and I am a consulting medical oncologist and lead of the Oncology Research program at the Comprehensive Cancer Center at the Mediclinic City Hospital in Dubai, United Arab Emirates. Today, we feature a self-evaluation question looking at the predictive and prognostic role of pathological complete response attained in the treatment of breast cancer.

Let us begin by reading the question stem. Here, we have a 55-year-old woman who presents with a 4 centimeter right breast mass and palpable right axillary lymph nodes. A needle biopsy of the breast mass and a lymph node are both positive for infiltrating ductal carcinoma negative for hormone receptors and negative for HER2/neu expression. The patient is interested in breast-conserving therapy, and she is referred to you for consideration of neoadjuvant chemotherapy. Which of the following do you tell her? Your choices are, A-- patients having a complete response to neoadjuvant chemotherapy have lower local and regional recurrence rates, B-- mastectomy will be required regardless of clinical response to chemotherapy, C-- chemotherapy will be administered before and after surgery, or D-- randomized trials have shown that radiotherapy is not necessary following surgery and chemotherapy if she has a complete response.

At this point, please feel free to pause the recording before we discuss the correct answer.

[MUSIC PLAYING]

The correct answer to this question is A. Pathological complete response in the breast and lymph nodes is associated with lower local and regional recurrence rates. A combined analysis of the NSABP B18 and B27, two large trials that evaluated the role of neoadjuvant chemotherapy, revealed that the rate of local regional recurrence decreased amongst patients who initially presented with positive lymph nodes prior to neoadjuvant chemotherapy, and who become pathologically node negative after neoadjuvant chemotherapy, especially if they also achieved a pathological complete response in the breast.

Briefly, the other choices presented in this question do not represent the most appropriate answer for the following reasons. The decision regarding type of surgery in the form of mastectomy versus breast-conserving surgery is dependent on multiple factors. One of the early established benefits of neoadjuvant therapy is that it increases the probability of breast-conserving surgery, making more women candidates for lumpectomy and breast radiotherapy, who otherwise would have been treated with mastectomy.
Studies have shown that chemotherapy before surgery in the neoadjuvant setting versus chemotherapy after surgery in the adjuvant setting is associated with similar outcomes. And finally, attaining a pathological complete response currently does not preclude the need for adjuvant radiation therapy, the decision of which would be made on clinical stage of disease at presentation. The NSABP51 RTOG phase III trial is ongoing to evaluate the role of regional radiotherapy in women presenting with clinical N1 axillary node disease before neoadjuvant chemotherapy, and who become pathologically node negative at the time of surgery.

Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on the treatment of breast cancer, including opportunities for self-evaluation and board review, please visit the comprehensive e-learning center at university.asco.org.
[MUSIC PLAYING]

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

This week's host, Dr. Thomas Karasic, is an assistant professor at University of Pennsylvania specializing in the treatment of gastrointestinal malignancies. In this episode, Dr. Karasic discusses the recent FDA approval of lenvantinib for patients with unresectable hepatocellular carcinoma.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

[MUSIC PLAYING]

Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Thomas Karasic, I'm an assistant professor at the University of Pennsylvania, specializing in the treatment of gastrointestinal malignancies. Today, we will discuss the approval of lenvatinib for the treatment of patients with un-resectable hepatocellular carcinoma. As background to our discussion today, the only FDA approved therapy prior to 2017 for hepatocellular carcinoma was sorafenib. This is based on results of the SHARP trial published in the New England Journal in 2008, which demonstrated an overall survival benefit of 10.7 months in the sorafenib arm, versus 7.9 months in the placebo arm.
In the 10 years after the approval of sorafenib, a number of phase III trials attempted to establish additional drugs or combination regiments in both the first line and the second line setting for advanced hepatocellular carcinoma. But all trials failed to meet their primary endpoint, and no other treatments were approved.
However, in 2017, two new drugs were approved for the second line treatment of hepatocellular carcinoma-- regorafenib, a drug similar to sorafenib, as well as the PD-1 inhibitor, nivolumab. Lenvatinib is an anti-angiogenic tyrosine kinase inhibitor that targets VEGF-1 3, FGFR 1 through 4, PDGFRA, KIT, and RET. On August 16, 2018, lenvatinib was FDA approved for the first line treatment of un-resectable hepatocellular carcinoma. Two different doses were approved-- 12 milligrams for patients with actual body weight greater than or equal to 60 kilograms, and 8 milligrams for patients with actual body weight less than 60 kilograms.
The approval of lenvatinib in the first line setting was based on the results of a non-inferiority study comparing lenvatinib to sorafenib for unresectable hepatocellular carcinoma. The primary endpoint of the study was overall survival.
A total of 1,492 patients were recruited, and 954 patients were randomized one-to-one between lenvatinib or sorafenib. Lenvatinib was given at a dose of 12 milligrams daily for patients of at least 60 kilograms actual body weight, or 8 milligrams for those below 60 kilograms-- while sorafenib was given at the FDA approved dose of 400 milligrams twice daily.

This trial met its primary endpoint of non-inferiority for overall survival. Overall survival was 13.6 months in the lenvatinib arm, and 12.3 months in the sorafenib arm. While it met its endpoint for non-inferiority, it did not establish superiority in terms of overall survival. The hazard ratio for overall survival was 0.92.
Lenvatinib did demonstrate a statistically significant increase in time to progression-- 8.9 months in the lenvatinib arm, versus 3.7 months in the sorafenib arm. It also showed a statistically significant improvement in overall response rate.

Using the study endpoint of modified RECIST criteria, the objective response rate with lenvatinib was 41% versus 12% with sorafenib. Using more standard RECIST 1.1 criteria, the overall response rate of lenvatinib was 19%, versus 7% with sorafenib.

Adverse events were common in both arms of the study, with 57% of those treated with lenvatinib experiencing grade 3 or greater toxicity, compared to 49% of those treated with sorafenib. Toxicities that were more common with lenvatinib included hypertension, proteinuria, hypothyroidism, weight loss, anorexia, nausea, and vomiting-- while sorafenib more commonly had hand/foot syndrome and alopecia. Toxicities, such as fatigue and diarrhea, were similar between the two arms.

The approval of lenvatinib marks the first positive front line study comparing an agent to sorafenib in the first line treatment for HCC. Lenvatinib demonstrated improvements in overall response rate, as well as progression-free survival, and a modest trend towards improved overall survival, although this was not statistically significant.

The toxicities of sorafenib and lenvatinib were largely comparable, although some toxicities-- such as hand/foot syndrome are more common with sorafenib-- whereas hypertension and proteinuria are more common with lenvatinib.

These study results established lenvatinib as a reasonable firstline option for the treatment of HCC, and choice of sorafenib versus lenvatinib can be made based on toxicity profile, as well as the symptoms of the patient that may dictate the need for an agent with a higher response. Pending results from the CheckMate 459 study, as well as other ongoing immunotherapy front line studies, may well change the sequence of immunotherapy and anti-angiogenic therapy for HCC. But for now, lenvatinib is a reasonable front line option.

Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on lenvatinib and the treatment of hepatocellular carcinoma, visit the comprehensive e-learning center at university.asco.org.

[MUSIC PLAYING]

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

Welcome to the Self-Evaluation episode of the ASCO University weekly podcast. My name is Dr. Karen Winkfield, and I am Associate Director for Cancer Health Equity and Director of Hematologic Radiation Oncology at the Comprehensive Cancer Center at Wake Forest Baptist Health in Winston-Salem North Carolina.

Today, we feature a self-evaluation question on the treatment of multiple myeloma and other plasma cell dyscrasias, and we begin by reading the question stem.

A 65-year-old woman was found to have free light-chains in her urine after she presented with proteinuria. A 24-hour urine collection contained 0.6 grams of monoclonal lambda light-chains, and the urinary sediment was normal.

She had normal complete blood count, renal function, and serum lactate dehydrogenase and calcium levels. Serum protein electrophoresis was normal with no monoclonal component. Subsequent free light-chain, or FLC, studies revealed kappa at 68.5 milligram per liter and lambda at 16.7 milligram per liter with FLC ratio of 4.1 with a normal range of 0.26 to 1.65.

The bone marrow aspirate revealed 6% of mature-looking plasma cells. Bone marrow biopsies failed to demonstrate any amyloid deposits. Both conventional and fluorescent in situ hybridization cytogenetic analyses were normal. Skeletal X-rays, as well as spinal access MRIs were normal.

The diagnosis is light-chain monoclonal gammopathy of undetermined significance, or LC MGUS. Which of the following is an accurate description of this disease? A, around 30% of cases present with kidney disease. B, around 3/10 of 1% per year of cases progress to light-chain multiple myeloma. C, around 30% of all MGUS is comprised of this condition. D, around 3% of the general population older than 50 years has this condition.

[MUSIC PLAYING]

The correct answer to this question is B, around 3/10 of 1% per year of cases progress to light-chain multiple myeloma. This answer reflects the natural history of LC MGUS.

Briefly, the other choices presented in this question are incorrect for the following reasons. Approximately 23% of LC MGUS cases have or will develop renal disease. Therefore, answer A slightly overstates the incidence at 30%.

Similarly, LC MGUS comprises only 19% of total cases of MGUS. This is consistent with the proportion of light-chain multiple myeloma cases among newly-diagnosed multiple myeloma patients. An estimated 0.8% of the general population age 50 years and older has LC MGUS.

Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on the treatment of multiple myeloma and other plasma cell dyscrasias, visit the comprehensive E-Learning Center at university.asco.org.

[MUSIC PLAYING]

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT

[MUSIC PLAYING]

Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I'm the clinical director of the early drug development service at Memorial Sloan-Kettering Cancer Center, and editorial board member for ASCO University. Today, we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel.

[MUSIC PLAYING]

Hello, and welcome to the ASCO Guidelines podcast series. My name is Shana McKernan, and today, I'm interviewing Dr. Antonio Wolff from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, an author on HER2 Testing in Breast Cancer, American Society of Clinical Oncology College of American Pathologists Clinical Practice Guideline Focus Update. Thank you for being here, Dr. Wolff.

Thank you for the opportunity. It is really a privilege to be here today on behalf of all of my colleagues in the ASCO/CAP HER2 testing panel, which truly represents not just a multi-disciplinary, but a multi-society effort over many years.

First, can you give us a general overview of what this guideline covers?

The recommendations by the ASCO/CAP HER2 testing expert panel were first released in 2007 and updated in 2013. And this is now a 2018 focus update. The aim was to improve the analytic validity of HER2 testing and the utility of HER2 as a predictive biomarker for potential responsiveness to therapies targeting the HER2 protein.

In fact, in late 2017 at the San Antonio Breast Cancer Symposium, we finally had data from the NRG trial B-47, which confirmed the lack of benefit from adjuvant trastuzumab for patients whose tumors lack gene amplification and were IHC 1+ or 2+. As a result, HER2 gene amplification assessed by In Situ Hybridization-- ISH, or I-S-H, or protein overexpression assessed by immunohistochemistry, IHC, remained the primary predictors of responsiveness to HER2-targeted therapy in breast cancer.

We have seen over the years a great communication among health care providers, especially pathologists and oncologists, but also much-needed infrastructure support by administrative teams regarding specimen handling in lab facilities. And they have resulted in meaningful improvements in the analytic performance and accuracy of HER2 testing.

We also have had greater clinical experience with the efficacy and safety of HER2-targeted therapies that resulted in a meaningful reduction in the high frequency of false-positive HER2 test results that were observed in the mid 2000s. And this led to the 2013 guideline update panel to provide further guidance regarding less-common clinical scenarios to allow greater discrimination between positive and negative results.

Since 2013, since the 2013 update, several labs and clinical investigators have reported on the practical implications of the guideline update and the observed frequency of equivocal cases. And these results have allowed the panel recently to evaluate the observed frequency of less-common HER2 testing patterns, the apparent prognostic and predictive value when retrospectively analyzed within clinical trial data sets, and the critical need to understand the underlying distribution of HER2 immunohistochemistry test results in cases that were submitted for additional tests, specifically In Situ Hybridization by a reference lab. This all led to the ASCO/CAP HER2 testing panel to prepare and now issue this 2018 HER2 testing focus update that includes five key recommendations.

What are the key recommendations of this guideline?

The HER2 testing guideline panel identified five clinical questions that formed the core of the 2018 focus update. Clinical question one is, what is the most appropriate definition of IHC 2+ or IHC equivocal. And clinical question two asks whether HER2 testing must be repeated on a surgical specimen if initially negative tests on a core biopsy. And these two questions were addressed in a previous correspondence by the panel that was published in the JCO in 2015. And they referred specifically to Figure 1, the algorithm for immunohistochemistry testing, and Table 2, the histopathologic features suggestive of possible test discordance.

Clinical questions three, four, and five address less-common patterns observed when performing dual-probe In Situ Hybridization testing, and are now graphically summarized in four different figures, Figures 3 to 6, that focus on the algorithm for dual-probe In Situ Hybridization testing. And these three questions help clarify the 2013 recommendations that led some labs to adopt the use of multiple alternative chromosome 17 probe testing as the sole strategy to resolve equivocal HER2 test results by In Situ Hybridization, despite limited evidence on analytical and clinical validity of such strategy.

The three additional questions of the 2018 focus updates are clinical question three, should invasive cancers with HER2/CEP17 ratio of 2.0 or higher, but an average HER2 copy number of less than 4 signals per cell, be considered ISH-positive. Clinical question four, should the invasive cancers with an average HER2 copy number of 6.0 or greater signals per cell, but a HER2/CEP17 ratio of less than 2.0 be considered ISH-positive? And finally, clinical question five, what is the appropriate diagnostic workup for invasive cancers with an average HER2 copy number 4.0 or higher, but less than 6.0 signals per cell, and a HER2/CEP17 ratio less than 2.0, and initially found to have an equivocal HER2 ISH test result.

The recommendations regarding dual-probe ISH testing also led to a change in figure 2 that describes the algorithm for single-probe ISH testing, and includes a new footnote with a recommendation that concomitant immunohistochemistry review should become part of the interpretation of single-probe In Situ Hybridization results.

The 2018 HER2 testing focus update also includes a new Table 3 that describes the patterns of HER2 ISH testing using dual probe assays showing a clear impact of the underlying distribution of HER2 immunohistochemistry test results on the frequency of these less common patterns of In Situ Hybridization.

As we expect, in total, groups 2, 3, and 4 will represent no more than 5% of all cases tested by In Situ Hybridization. And the majority, 95% of cases, tested for HER2 by dual-probe In Situ Hybridization will consist of group 1, which are clearly HER2-positive , and group 5, HER2-negative. And ultimately, the available clinical outcome data from related trials, although of limited statistical power, have allowed the panel to more carefully define this expected prognostic and predictive behavior of cases tested by dual-probe In Situ Hybridization that will fall in groups 2, 3, or 4.

What are the major changes from the 2013 version of this guideline?

Most important, after consideration of the available evidence and expert opinions, the ASCO/CAP HER2 testing panel revised the diagnostic approach to groups 2, 3, and 4 to include more rigorous interpretation criteria for dual-probe In Situ Hybridization testing, and to require concomitant immunohistochemistry review to arrive at the most accurate HER2 status designation, positive or negative, based on the combined interpretation of the ISH and the IHC assays.

The panel therefore recommends that such concomitant review be performed in the same institution to ensure parallel interpretation and quality of the two assays. As a result, most group 2 specimens will not be confirmed as HER2-positive, as very few will be immunohistochemistry 3+, and most group 4 specimens will be confirmed HER2-negative without the need for additional testing, use alternative probes, which happen a lot since 2013.

At the same time, group 3 specimens will be a mixed group of results with a small number of cases shown to be amplified, and a larger number shown not to be amplified. And so for these dual-probe ISH group 3 cases, the panel allows specimens that are IHC 2+ to be considered HER2-positive. And the rationale is described in greater detail in the manuscript.

And finally, how will these guideline recommendations affect patients?

While the main focus was to clarify the less common test results observed with the two-probe ISH assays, the recommendations do impact users of single-probe ISH assays. As such, the panel now recommends that concomitant immunohistochemistry review should become part of the interpretation of single-probe In Situ Hybridization results to allow a more accurate HER2 designation. And this is nicely described in Figure 2.

And the panel also preferentially recommends the use of dual-probe instead of single-probe ISH assays, while it recognizes that several single-probe ISH assays have regulatory approval in many parts of the world. At the end, and to conclude, these actions, we hope, will reduce the already small number of cases that have HER2 test results that are unresolved, will reduce the frequency of alternative group testing, and will remind us all of the importance of integrating the information provided by both types of assay platforms, IHC and ISH, in difficult cases, as we expect these results to be concordant in the vast majority of cases, when expertly performed.

Thank you for your insights on this guideline, and thank you for your time today, Dr. Wolff.

Thank you so much.

And thank you to all of our listeners for tuning in to the ASCO guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

[MUSIC PLAYING]

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

The early 1970’s saw the start of the medical specialty we now know as oncology. How does one create standards and practices for patient care during that time? Dr. John Glick is a pioneer during the dawn of oncology. He says that early work involved humanity, optimism, and compassion, all of which were the foundation of his career. Dr Glick describes the clinical experiences that drove him to oncology (4:28), his rapport with patients, which was portrayed in Stewart Alsop’s book Stay of Execution (9:21), and his groundbreaking work developing the medical oncology program at the University of Pennsylvania (12:22).

Speaker Disclosures
Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University
Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical
Dr. John Glick: None

More Podcasts with Oncology Leaders   
Oncology, Etc. – In Conversation with Dr. Richard Pazdur (Part 1)
Oncology, Etc. – HPV Vaccine Pioneer Dr. Douglas Lowy (Part 1)
Oncology, Etc. – Rediscovering the Joy in Medicine with Dr. Deborah Schrag (Part 1)

 If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org.  

TRANSCRIPT

Disclosures for this podcast are listed in the podcast page.

Pat Loehrer: Welcome to Oncology, Etc. This is an ASCO education podcast. I'm Pat Loehrer, Director of Global Oncology and Health Equity at Indiana University.

Dave Johnson: And I'm Dave Johnson, a medical oncologist at the University of Texas Southwestern in Dallas, Texas. If you're a regular listener to our podcast, welcome back. If you're new to Oncology, Etc., the purpose of our podcast is to introduce listeners to interesting people and topics in and outside the world of oncology. Today's guest is someone well-known to the oncology community. Dr. John Glick is undoubtedly one of oncology's most highly respected clinicians, researchers, and mentors. I've always viewed John as the quintessential role model. I will add that for me, he proved to be a role model even before I met him, which hopefully we'll talk about a little bit later.  

To attempt to summarize John's career in a paragraph or two is really impossible. Suffice it to say, he is to the University of Pennsylvania Cancer Center what water is to Niagara Falls. You can't have one without the other. After completing his fellowship at NCI in Stanford, John joined the Penn faculty in 1974 as the Ann B. Young Assistant Professor. Some five decades later, he retired as the director of one of the most highly respected comprehensive cancer centers in the nation. Among his many notable accomplishments, I will comment on just a few. He established the Medical Oncology program at Penn and subsequently directed the Abramson Cancer Center from 1985 to 2006. Interestingly, he established the Penn Medicine Academy of Master Clinicians to promote clinical excellence in all subspecialties across the health system. He's been a driving force in philanthropy at Penn Medicine, culminating in his role as Vice President Associate Dean for Resource Development. 

Over the past several decades, he has helped raise over half a billion dollars for Penn Med. We need you on our team, John. As a clinician scholar, John's research has helped shape standards of care for both breast cancer and lymphomas. For example, he pioneered the integration of adjuvant chemotherapy and definitive breast irradiation for early-stage breast cancer. In 1985, he chaired the pivotal NCI Consensus Conference on adjuvant chemotherapy for breast cancer. He also was a driving force in a clinical landmark study published in The New England Journal some 20 or so years ago about the role of bone marrow transplant for advanced breast cancer. Most impressive of all, in my opinion, is John's legacy as a mentor to multiple generations of medical students, residents, and fellows.  

So, John, we want to thank you for joining us and welcome. Thought we might start by having you tell us a little about your early life, your family, your parents, where you grew up, and how you got into medicine.

Dr. John Glick: Well, thank you for having me on the podcast, Pat and David, it's always a pleasure to be with you and with ASCO. I grew up in New York City in Manhattan. My father was a well-known dermatologist. He was my role model. And from the age of eight, I knew I wanted to be a doctor. Nothing else ever crossed my mind. But having seen my father's many interests outside of medicine, I realized from very early that there was much more to medicine than just science. And that really induced me, when I went to college, to major in the humanities, in history, art history, and I actually took the minimum number of science courses to get into medical school. That probably wouldn't work today, but it was the start of my interest in humanism, humanities, and dealing with people outside of the quantitative sciences. 

Dave Johnson: So that's reflected in how we all view you, John. You're one of the most humanistic physicians that I know personally. I wonder if you could tell us about your interest in medical oncology, and in particular, as one of the pioneers in the field. I mean, there wasn't really even a specialty of medical oncology until the early 1970s. So, how in the world did you get interested in oncology and what drew you to that specialty?

Dr. John Glick: Well, I had two clinical experiences that drove me into oncology. The first, when I was a third year medical student at Columbia PNS, my first clinical rotation in internal medicine, I was assigned a 20-year-old who had acute leukemia, except he was not told his diagnosis. He was told he had aplastic anemia, receiving blood and platelets, and some form of chemotherapy. And I spent a lot of time just talking to him as an individual, not just taking care of him. And we became friends. And he was then discharged, only to be readmitted about two weeks later. And in the elevator, the medical assistant had his admission sheet, and unfortunately, it was facing the patient, and it had his diagnosis, acute leukemia. So he came into the ward and he confronted me. "Why didn't you tell me I had acute leukemia?" Well, I couldn't say the attendees forbade me to do that. So I took what today we would call ‘the hit’, and apologized. But it stimulated me to reflect that honesty with patients was extremely important, and that oncology was just in its infancy. We knew nothing about it. It was not considered even a specialty. I don't think we used the word "oncology." 

But that inspired me to take an elective in my fourth year at PNS, at an indigent cancer hospital called the Francis Delafield Hospital. It only took care of indigent cancer patients, and there were wards, twelve patients in a ward, six on each side, and nobody would go see the patients. It was almost as if they were afraid that if they were to touch the patient, they would get cancer. And I started talking to the patients, and they were human beings, but nobody had told them their diagnosis. Nobody had told them if they were terminal. And there were a few patients who were getting a new drug at that time for multiple myeloma called melphalan, and they actually had relief of some of the symptoms, of their bone pain. But I realized that there was a huge void in medicine that I could possibly help to fill. 

And that was the era of Vietnam, and so I applied to the National Cancer Institute to become a commissioned officer in the Public Health Service to avoid the draft, to be on a service with, at that time, some very notable oncologists Vince DeVita, Ed Henderson, Paul Carbone. I had read some of their papers, and I was lucky to be accepted. And I was a clinical associate at the National Cancer Institute. And that was life-changing because there every patient was considered to be potentially curable. The advances at that time using MOPP for Hodgkin's disease, C-MOPP for lymphoma, some treatments for leukemia. George Canellos pioneered the use of CMF for metastatic breast cancer. It was an amazing, amazing experience. That was in 1971 to ‘73. Oncology did not become a true specialty till ‘73, but my two years at NCI were formative. 

However, I realized that there was something missing in my training. Everybody was considered curable, but I had never seen a patient with metastatic colon cancer, metastatic lung cancer. The radiotherapists there did not like to teach clinical associates, and I knew that there was a place called Stanford. And Stanford had Saul Rosenberg in medical oncology for lymphomas and Henry Kaplan in radiotherapy. So, everybody was going to California, and my wife and I packed up and went to California and spent a year at Stanford, which, combined with my training at the NCI, led me to the principles that guided my career in oncology; humanity, optimism, reality, compassion, and a love for clinical trials. 

I was very, very fortunate to be there at the dawn of medical oncology shortly after I decided to go to Penn, which at that time did not have a medical oncologist. In fact, I was the only medical oncologist at Penn for four years and did every consult in the hospital for four years, much to the chagrin of my wife. But I was fortunate to have great mentors in my career: Paul Carbone, Vince DeVita, Saul Rosenberg, Henry Kaplan, among many, many others. And that impressed me about the importance of mentorship because my career would never have been where it was or is without these mentors.

Pat Loehrer: John, just to echo what Dave said, you've been such a tremendous mentor for us. Dave and I particularly, you took us under your wings when you didn't know who we were. We were people in the Midwest. We weren't from any place shiny, but we really appreciate that.

Dave Johnson: So, John, I mentioned at the very beginning that I met you before I met you, and the way I met you was through Stewart Alsop's book, Stay of Execution. He portrayed you as an extraordinarily caring individual, and it tremendously impacted me. It was one of the reasons why I chose oncology as a specialty. I realize it's been 50 or more years ago and most of our listeners will have no idea who Stewart Alsop was. And I wonder if you might share with us a little bit of that experience interacting with someone who was particularly well-known in that time as a columnist for The New York Times. 

Dr. John Glick: His brother Joe Alsop and Stu Alsop were two of the most famous columnists at that time. Joe Alsop was a hawk right-winger who lived in the Vietnam War. Stewart was charming, was a centrist Democrat, wrote the back page for Newsweek for years. He and I had very similar educational backgrounds and interests. And we functioned on two different levels—one as a physician-patient, and then we became friends. And he and his wife adopted us into the Georgetown set. 

And I received a lot of criticism for socializing with a patient. But over the years, I've been able to become friends with many of my patients, and I've been able to compartmentalize their medical care from our friendship. And I use the analogy if I was a doctor in a small town and I was the only doctor,  I'd be friends with people in town, with the pastor and likely the mayor. But I have always believed that patients can become your friends if they want it and if they initiated it.  

Taking care of Stewart Alsop was an amazing, amazing experience. We didn't know what he had. People initially thought he had acute leukemia. In reality, he had myelodysplastic syndrome, but that hadn't been described yet. He had a spontaneous remission, which I rarely see, probably due to interferon released from a febrile episode, all his blasts went away in his marrow.

One of my children's middle name is Stewart. But professionally and personally, it was an incredible experience. It taught me the importance of being available to patients. They had my home phone number. We didn't have cell phone numbers in those days. We had beepers, but they didn't work. And from that point on, I gave my home phone number to patients, and I actually trained my children how to answer the phone. “This is Katie Glick. How can I help you? My father's not home. You need my father? Can I have your phone number? I'll find him and he'll call you back.” Patients still remember my children and their way of answering the phone.

Pat Loehrer: One of the things you did do is create this medical oncology program at Penn, which has graduated some incredible fellows that have become outstanding leaders in our field. But can you reflect a little bit about the process of creating something that was never created before, like a medical oncology program?

Dr. John Glick: Well, I came to Penn, my first day. Person who recruited me was on sabbatical. I asked where my office was and there was no office. There was an exam room. There was a clinic for indigent patients which we scrubbed by hand. There was another office for patients who paid. Within two months, I had abolished that. We had one– I hate to use the word clinic, people still use the word clinic today, but one office that took care of all patients, irregardless of means.  

I saw every oncology consult in the hospital for four years. But I had a mentor, not only Buz Cooper, but fortunately, Jonathan Rhoads was Chairman of Surgery, and he was also Chairman of the President's Cancer panel. And what he said at Penn in surgery became the law. And then when we introduced lumpectomy for breast cancer and radiotherapy, he endorsed it immediately. All the other surgeons followed suit. I don't think there's any hospital in the country that adopted lumpectomy and radiotherapy for breast cancer as quickly. And the surgeons were instrumental in my career. 

Now, I was taking care of gliomas, head and neck cancers, and it was difficult. If I had a colorectal patient, I'd call Charles Moertel at Mayo Clinic and say, “What do I do?” I was there when Larry Einhorn in 1975 presented his data on testicular cancer with the platinum. Unbelievably inspiring, transformational. It also showed the importance of single-arm studies. You didn't have to do randomized studies because the results were so outstanding. And so in my career, I did both single-arm studies, proof of principle studies, and then many randomized trials through the cooperative groups. 

But the first four years were very difficult. I didn't know what the word ‘work-life balance’ meant in those days. If somebody was sick, I stayed and saw them. It was difficult introducing new principles. When I first mentioned platinum after Larry's presentation, I was laughed out of the room because this was a heavy metal. When patients were dying, they died in the hospital, and I wanted to hang up morphine to assist them. The nurses reported me to the administration. I had to fight to get the vending machines for cigarettes out of the hospital. So there were a lot of victories along the way and a lot of setbacks. 

It took me several years to have an oncology unit of six beds, and now I think we have 150 or 160 beds and need more. So it was an interesting and, in retrospective, a wonderful experience, but I didn't know any better. Fortunately, I had a great wife who was working at Penn and then at Medical College of Pennsylvania, and she was incredibly understanding, never complained. And I think my kids knew that on Tuesdays and Thursdays, don't bring up anything difficult with dad because he's had a really tough day in clinic.

Dave Johnson: We were not in that era, but we were very close. And many of the struggles that you had were beginning to dissipate by the time we were completing our training. But it was still a challenge. I mean, all those things. I gave my own chemotherapy for the first few years I was in practice. I don't know that our colleagues today who have trained in the last, say, 10 or 15 years, actually realize that that was what we did. Most of the chemo was given in the hospital. It was not uncommon in the early days to have 20, 30, 40 inpatients that you would round on because there just wasn't an outpatient facility. But the corporate mind made a big difference, allowing us to give drugs like platinum in the outpatient arena. You span all of that era, and so you've seen the whole panoply of change that has taken place. 

John, the other thing you did that has impressed me, in part because of my time as a Chair of Medicine, is you created this Academy of Master Clinicians. Can you tell us a bit about that and what was the motivation behind that? 

Dr. John Glick: Ben had a strategic plan, and one of the pillars was talking about valuing clinical medicine and clinical excellence. But there was no implementation plan. It was sort of just words and left in the air. And I was no longer director of the cancer center, and I realized we had a lot of awards for research, awards for education, and no awards for clinical excellence. So I created the idea of having an academy and master clinician spend six months talking to all constituencies, chairs of various departments, directors of centers to get a buy-in. Wrote a three-page white paper for the dean, who approved it immediately. And then, as typical at Penn, I raised all the money for it. I went to one of my patients who was an executive at Blue Cross. I said I need $500,000 to start this program. And then subsequently, I raised $4 million to endow it. Today, it is the highest honor that a Penn clinician can receive. 

You could be on any one of our multiple tracks. You have to see patients at least 60% of the time. You not only have to be a great doctor, you have to be a humanist. So the world's best thoracic surgeon who has a demeanor in the operating room that is not conducive to working with a nurse as a team doesn't get in. We emphasize professionalism, mentorship, citizenship, teaching, national reputation, local reputation, and clinical excellence. And so we've elected over 100 people, maybe 3% of the Penn faculty. We give an honorarium. We have monthly meetings now by Zoom. We have monthly meetings on various topics. We never have a problem getting any dean or CEO to come talk to us. 

We were the first to do Penn's professionalism statement. The school subsequently adopted, and it's become the highest honor for a Penn clinician. It's very competitive. It's peer-reviewed. The dean has no influence. And we're very proud that 40% of the members of the academy are women. We have a high percentage of diversity compared to the numbers on our faculty, but you really have to be elected on merit, and some people that you might expected to be members of the academy aren't. It's one of the things I'm proudest of. It will go on in perpetuity because of the money we've raised. I think many of my accomplishments as a researcher will fade, as they typically do, but I'm very proud of the Academy, and I'm very proud of the people that I've mentored.

Dave Johnson: It speaks to your values, John, and I think it's one of the reasons why you're so widely admired. Thank you for creating that. It proved to be a model for other institutions. I know that for a fact. One would think that valuing clinical care would be preeminent in medical schools, but in fact, it's often ignored. So again, I know that your colleagues at Penn appreciate your efforts in that regard. 

Tell us a little about your term as ASCO president. What are you most proud about and what were your most difficult challenges?

Dr. John Glick: Well, the most difficult challenge was that ASCO was in transition. I had to fire the company that ran the meeting. We had to decide that ASCO was going to hire a CEO. We hired John Durant, made a small headquarters, tiny staff, and did a lot of the work as being chief operating officer myself. It was the year that email was just getting started, and ASCO wasn't using it. So every Saturday from 8:00 to 6:00, I came into the office and my secretary wrote letters inviting people to be on the program committee or various committees. But it was a society in transition. The growth of membership was huge. The meeting sites had to be changed. We emphasized science. Some of the things that we did are still in existence today. 

We formed the ASCO ACR Clinical Research Methods course. It's still given. That's one of our real highlights. We forged relationships with other societies, the National Coalition for Survivorship. We made the ASCO guidelines much more prominent. And I remember that we were going to publish the first guidelines on genetic testing for breast cancer, and the MCI went up in absolute arms, so I arranged a meeting. I was at the head of the table. On my right were Francis Collins, Richard Klausner, Bob Wittes, and a few other people. Then the ASCO people who wrote the guideline were on the left, and they didn't want us to publish it. They thought it was premature to have a guideline about genetic testing. And what I learned from that meeting is that you can agree to disagree with even the most prominent people in oncology and still maintain those relationships. But we did what's right, and we published a guideline on the JCO. There were so many wonderful things that happened at ASCO that I can hardly restate all that happened I guess 27 years later. It was exciting. ASCO was still young. There was a lot we had to do, and we could do it. You could just go ahead and do it. It was exciting. It was gratifying. It was one of the most fun years of my life.

Dave Johnson: I mean, that transition from an outside company in many respects, controlling the premier activity of ASCO, its annual meeting to ASCO, taking that on, that defined ASCO, and that's what I remember most about your time as president. It was a bold move, and the hiring of John Durant was brilliant. I mean, he was such an incredible individual, and it was great that you guys were able to pull that off.

Pat Loehrer: Thank you for what you've done. 

You've had a number of your mentees if you will, and colleagues that have gone on to prominent positions, including, I think, at least three directors of NCI Cancer Centers. Can you just talk briefly how you would describe your mentoring style because you've been so successful?

Dr. John Glick: First, there are two aspects. One is when people come to you, and then when you go to people, you sense they're in need. The key aspect of mentoring is listening. Not talking, listening. Looking for the hidden meanings behind what they're saying, not telling them what to do, presenting options, perhaps giving them clues on how to weigh those options in pros and cons, being available for follow-up. Mentoring is never a one-time exercise. Not criticizing their decisions. You may disagree with their decision, but it's their decision, especially if they've considered it. Being proud of the mentee, being proud of their accomplishments, following them over the years. And when they've gotten in trouble or failed to get the job that they wanted, always be there for them, not just in the good times, but in the times that are difficult for them professionally. I think that's one of the most important things. 

Even today, I mentor three or four clinical department chairmen, and people ranging from full professors to newly appointed assistant professors. Now that I'm retired, mentoring is the one activity that I've really retained. It's extraordinarily satisfying, and I'm proud of the people that I've mentored. But it's their accomplishments, and the key aspect of mentoring is never to take credit.

Dave Johnson: I'll give you credit for mentoring me, and I appreciate it. You were very instrumental at a very decisive point in my career when the old Southeast Cancer Group disbanded, and we were looking for a new cooperative group home. And you were instrumental in helping my institution come into the ECOG fold, and not just as a very junior member, but really as a player. And I'll never forget that, and we'll always appreciate that very much.

Pat Loehrer: Ditto on my side, too.

Dave Johnson: John, you mentioned that you're retired. What do you like to do in your "free time” if you're not mentoring?

Dr. John Glick: Life is good. My daughter says I have a disease, O-L-D. My grandson says, “He's not old; he's almost 80. Look how well he's done.” “Here's $20.” I'm having fun. We are fortunate to have homes in different places. We spend the summer up in the Thousand Islands on the St. Lawrence River, spring and fall down in Charleston, then lots of time in Philadelphia. We travel. I play golf poorly. I'm getting a chance to read history again, go back to one of my great loves. I'm with my children and grandchildren more. I lost my first wife. I've been remarried for about twelve years, and I'm enjoying every moment of that. I'm not bored, but I do wake up in the morning with no anxiety, no realization that I have to herd sheep or herd cats. I have no metrics, I have no RVUs,  not behind of the EMR. 

Dave Johnson: You're making it sound too good, John. 

Dr. John Glick: We're having fun. And I have not been bored. I've not been down in the dumps. Each day brings a different aspect. We see a lot more of our friends. I exercise. I deal with the health problems that people get when they get older, and I have plenty of those. Seeing doctors takes a lot of time, but I'm grateful that I'm having these few years of retirement. I'm one of the people who is most fortunate to have attained everything they wanted to do in their professional life, and now I'm trying to do some of the same in my personal life.

Dave Johnson: John, Pat and I both love to read. We love history. You mentioned that you're reading some history. Is there a book that you've read recently that you might recommend to us?

Dr. John Glick: “the Last of the Breed” {With the Old Breed} It's about a private in the Pacific campaign who was not a commissioned officer; it’s just a grunt on the ground. It brings the horrors of the Pacific island campaigns to life. But there's a huge number of books, some historical fiction. I'm a great fan of Bernard Cornwell, who's written about the Medieval times, Azincourt, 1356. I'll read two or three books a week. I'm devoted to my Kindle.

Dave Johnson: If you could go back in time and give your younger self a piece of advice, what would that advice be?

Dr. John Glick: Try and achieve more of a work-life balance. I didn't have any choice. If I didn't do the consult, it didn't get done. That's not the situation today. But I have a second piece of advice, don't treat medicine as a 9 to 5 job. If a patient is sick, stay with the patient. Give the patient your home or cell phone number. Remember, medicine is not just a profession, but it can be a calling. Too few of our physicians today regard medicine as a calling. And even if you're employed, as most of us are by an academic or other institution, do what's right for the patient, not just what's right for your timesheet or the EMR. Remember that the patient is at the center of all we do and that medicine is a calling for some people, as it was for me.

Dave Johnson: Great advice, John. Great advice. 

Well, I want to thank Dr. Glick for joining Pat and me. This has been a delight. You're one of our role models and heroes. 

I want to thank all of our listeners of Oncology, Etc., which is an ASCO educational podcast where we will talk about oncology medicine and other topics. If you have an idea for a topic or a guest you'd like us to interview, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content of ASCO, please visit education.asco.org. Thanks again.

Pat, before we go, I've got an important question for you. I've been trying to school you recently, and you’ve failed miserably. So I'm going to ask you, why is it that McDonald's doesn't serve escargot?

Pat Loehrer: I can't do it. I don’t know. I give up. 

Dave Johnson: It's not fast food.

Pat Loehrer: I like that. It's good. 

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  

Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

TRANSCRIPT

Welcome to the Self-Evaluation episode of the ASCO University weekly podcast. My name is Apar Kishor Ganti, and I'm the Associate Director for Clinical Research and the co-leader of the Thoracic Oncology Service at the University of Nebraska Medical Center, Fred and Pamela Buffett Cancer Center.

Today, we feature a self-evaluation question on locally advanced non-small cell lung cancer. I will begin by reading the question stem. A 58-year-old man with a 50-pack year history of smoking presents to your clinic with worsening cough and shortness of breath. His comorbidities include irritable bowel syndrome and coronary artery disease.

A CT scan of the chest, abdomen, and pelvis reveal a two-centimeter right lower lobe mass with no evidence of lymphadenopathy in the chest. A positron emission tomography scan confirms a hypermetabolic right lower lobe mass and mildly avid mediastinal nodes. An MRI of the brain was performed and was negative.

A biopsy of the right lower lobe mass was positive for squamous cell carcinoma of the lung. The patient was taken for a mediastinal lymph node evaluation by a thoracic surgeon. Additional biopsies of multiple lymph nodes were taken. Pulmonary function tests revealed that a right lower lobectomy would be feasible if warranted.

Which of the following would lead you to recommend definitive chemoradiation rather than surgery as the most appropriate treatment for this patient? The answer choices are, A, metastatic squamous cell carcinoma identified in a left hilar lymph node, B, metastatic squamous cell carcinoma identified in a right hilar lymph node, C, the absence of squamous cell carcinoma in a left paratracheal lymph node, and D, the absence of squamous cell carcinoma in a right hilar lymph node?

[MUSIC PLAYING]

The correct answer to this question is A, metastatic squamous cell carcinoma identified in a left hilar lymph node. In the eighth edition of the AJCC TNM classification system, this tumor would be classified as T1B.

The presence of cancer in a contralateral hilar lymph node represents N3 disease and thus, stage 3B. Surgery is not recommended in this setting, and definitive chemoradiation is considered standard of care.

What about the other choices? Involvement of an ipsilateral hilar node would only represent N1 and stage 2B disease, for which a right lower lobectomy and mediastinal lymph node dissection are appropriate.

The absence of involvement of the left paratracheal node would confirm the absence of N3 disease, while the absence of involvement of the right hilar node would confirm the absence of N1 disease. In both these scenarios, the patient would be considered resectable if other lymph node stations are not involved.

Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on lung cancers, including important release for self-evaluation, visit the comprehensive E-Learning Center at university.asco.org. Thank you.

[MUSIC PLAYING]

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

TRANSCRIPT

[MUSIC PLAYING]

Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I'm the clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University.

Today we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel.

[MUSIC PLAYING]

Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Davendra Sohal from Cleveland Clinic, lead author on Metastatic Pancreatic Cancer American Society of Clinical Oncology Clinical Practice Guideline update. Thank you for being here today, Dr. Sohal.

Thanks for having me. It's a pleasure.

So this update is focused on revising the recommendations on second line treatment for metastatic pancreatic cancer. Can you tell us about the studies that informed this update?

Certainly. The first study is a paper published in Science on PD-1 inhibition and solid tumors. This study included 86 patients with mismatch repair deficient tumors, also known as microsatellite instability high tumors.

In this study, 53% of the patients had an objective response with a disease control rate of 71% across multiple histologies. The study also included eight patients with pancreatic cancer, two of whom had complete responses with a disease control rate of 75%. This is the study that informed our recommendation for checkpoint inhibitor therapy in the second line setting.

The second study is the PANCREOX trial published in JCO, which randomized patients to 5-fluorouracil or FOLFOX. With 108 patients, the primary outcome of overall survival was 9.9 months in the control 5-fluorouracil arm, and surprisingly, only 6.1 months in the FOLFOX arm. This study informed our recommendation for chemotherapy regimens in the second line setting.

And what are the new and updated recommendations for second line treatment?

For second line treatment of metastatic pancreatic cancer, our first recommendation now is to consider testing for mismatch repair deficiency or microsatellite instability in patients who are candidates for checkpoint inhibitors therapy. Any standard form of testing is acceptable, whether IHC or PCR or next-gen sequencing.

Patients who have mismatch repair deficient or microsatellite instability high tumors should be treated with pembrolizumab given the excellent responses noted in the study we just discussed. For patients who do not meet these criteria for checkpoint inhibitor therapy, second line therapy with gemcitabine plus nab-paclitaxel can be offered to those who received FOLFIRINOX in the first line and meet other criteria for aggressive chemotherapy as detailed in the guideline.

Now, for patients who receive gemcitabine plus nab-paclitaxel in the first line, fluorouracil plus nanoliposomal irinotecan is the preferred second line therapy. Where nanoliposomal irinotecan is not accessible, fluorouracil plus regular irinotecan is an acceptable alternative.

As I mentioned the combination, of 5-fluorouracil plus oxaliplatin can be considered as an option in this setting, but we have noted a qualifying statement about the PANCREOX study whose results are inconsistent with the CONCORD-3 study using the same agents as the off regimen. Given these conflicting results from different studies of 5-fluorouracil plus oxaliplatin, the recommendation for its use in the second line setting has been softened.

Can you also give us an overview of the recommendations from the original 2016 version that the expert panel decided were still valid?

Sure. In 2016, the expert panel made recommendations which span from initial assessment through to follow up and surveillance. For every patient with metastatic pancreatic cancer, a multi-phase CT scan should be performed and baseline performance datas and comorbidities should be evaluated. Goals of care should be discussed with a multidisciplinary team, and all patients should be offered information about clinical trials.

Outside of a clinical trial, standard first line treatment options include FOLFIRINOX, gemcitabine plus nab-paclitaxel, or gemcitabine alone. And the full guideline provides details on which treatment is appropriate for which patients. The panel also recommended that every patient should be offered palliative care early in their treatment. These recommendations were endorsed in the update and are reprinted in totality in the bottom line box on the second page of the article.

And finally, what are some important things to note about communicating with patients with pancreatic cancer, especially in the metastatic setting?

Excellent point. It is important to communicate that participation in clinical studies is strongly encouraged. These studies could include new treatments, or supportive care measures, or collection of blood and tumor samples for further research, et cetera. While chemotherapy forms the backbone of treatment, it is only one component, and that is an important point to make.

The use of supportive care or palliative care is strongly encouraged for all patients with metastatic pancreatic cancer in order to maximize not just the quantity, but also the quality of life.

Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. Sohal.

Sure. Thank you very much. I'd like to thank our panel for diligent data review and dedicated discussions and the ASCO staff for all their support in producing the update. Thank you.

And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

[MUSIC PLAYING]

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.