JCO Oncology Practice Podcast – Détails, épisodes et analyse

Dr. Chino talks with Dr. Erin Roesch and patient advocate Julia Maues about pregnancy associated cancer with a focus on breast cancer, the most common cancer diagnosed during pregnancy. This discussion is based off an JCO OP review article published in late 2024 called "Multidisciplinary Management of Pregnancy-Associated Breast Cancer."

Dr. Fumiko Chino:
Hello and welcome to Put Into Practice, the podcast for the JCO Oncology Practice. I'm Dr. Fumiko Chino, an assistant professor in radiation oncology at MD Anderson Cancer Center with a research focus on access, affordability, and equity.

The incidence of early-onset cancer—new cancers in adults under the age of 50—is rising by 1% to 2% annually. Young women appear to be at particular risk, with cancer incident rates over 80% higher than similarly aged male counterparts. Collectively, that means that more patients are being diagnosed with cancer during their childbearing years. Pregnancy-associated cancer occurs in 1 in every 1,000 to 3,000 pregnancies and refers to cancer that is diagnosed either during pregnancy or within 1 year of delivery.

On today's episode, we'll be talking about pregnancy-associated cancer, with a focus on breast cancer, as it is the most common cancer diagnosed during pregnancy. This discussion will be based off of a JCO OP article published in late 2024 called "Multidisciplinary Management of Pregnancy-Associated Breast Cancer."

I'm excited to welcome both the first author of this review article and a patient advocate to the podcast today. They are both passionate about improving outcomes for people with breast cancer.

Dr. Erin Roesch is an assistant professor of medicine at Cleveland Clinic Lerner College of Medicine and a medical oncologist at the Cleveland Clinic Taussig Cancer Institute specializing in the treatment of breast cancer. She is involved in clinical trials research, and some of her specific interests include the care of young women diagnosed with breast cancer, fertility in oncology patients, and women's health and survivorship.

Julia Maues is a patient advocate working with researchers, clinicians, and other stakeholders to ensure research is patient-centered, innovative, accessible, and inclusive. She was working as an economist when she was diagnosed with breast cancer while pregnant in 2013. After delivering her son, she found out that cancer had already spread to her bones, liver, and brain. Julia co-founded GRASP (Guiding Researchers and Advocates to Scientific Partnerships), an organization that connects and fosters collaborations between researchers and patient advocates. She is also active within the Metastatic Breast Cancer Alliance and helped write the ASCO guideline for brain metastasis.

Our full disclosures are available in the transcript of this episode, and we've already all agreed to go by our first names for the podcast today.

Erin and Julia, it's really wonderful to speak to you today.

Dr. Erin Roesch:
Thank you. I appreciate the opportunity to be here and discuss this really important topic.

Julia Maues:
Thank you for having me. It's very important to include the patient voice on this topic, and unfortunately, I have a personal experience with this.

Dr. Fumiko Chino:
Our topic today is pregnancy-associated cancer. Erin, can you give us a quick overview of the background for pregnancy and breast cancer? I know in the recent era, breast cancer rates for those under the age of 50 have been rising faster than for other cancers, up to 1.4% per year since the mid-2000s. I'd always thought that pregnancy-associated cancer was pretty rare, and so I was really shocked to read in your paper that for women younger than 35, 1 in 6 with breast cancer are diagnosed around pregnancy.

Dr. Erin Roesch:
Yes. So, a cancer diagnosis during pregnancy is rare, with the incidence, as mentioned, of about 1 in 3,000 pregnancies, with pregnancy-associated breast cancer, or PABC, representing about 7% of all breast cancers diagnosed per year. Among women under the age of 45, PABC accounts for roughly about 2.5% to just over 6% of breast cancer cases. And for women less than 35 years, this rises to about 15.5%.

Studies have shown a rise in PABC in recent years, and this is anticipated to continue with the trend of delayed age at childbearing. In regards to the pathophysiology of pregnancy-associated breast cancer, various hypotheses have been proposed to kind of try and shed more light on how this occurs and the driving factors for PABC. So these include hormonal changes that occur during pregnancy and lactation, immunologic changes that can lead to the immune tolerance of tumor cells, and also breast tissue involution that occurs after delivery and breastfeeding, which can lead to a proinflammatory state.

In regards to risk factors, these include a positive family history, which is one of the strongest risk factors for breast cancer development, this includes pregnancy-associated breast cancer, pathogenic germline mutations—specifically BRCA1 or 2—and older maternal age at time of birth. We also know that breastfeeding has been shown to have a protective effect against breast cancer development.

Dr. Fumiko Chino:
So what I'm hearing from you is that just given the incidence rising in younger people and also delayed pregnancy, that this is really something that we're unfortunately going to be facing more and more frequently in our clinics and something that patients unfortunately will find that they have to face as well.

Dr. Erin Roesch:
Yes, yes, I think that's accurate. And just again, I think points to the importance of awareness of this particular topic.

Dr. Fumiko Chino:
Now, Julia, your lived experience in this space is really invaluable. Do you mind sharing it with us?

Julia Maues:
Yeah, of course. I was pregnant at 29, and I found a lump in my breast. I had an excellent OB-GYN and team, and they took it seriously. I think she wanted to watch it for a few weeks, but as soon as it didn't go away, she ordered an ultrasound, and that turned into a biopsy, and that turned into a cancer diagnosis.

I lived near a comprehensive cancer center. I had multidisciplinary care, really excellent team, and was treated with chemotherapy during the pregnancy, which was very surprising to me and hard to accept. But they did provide me with a lot of evidence that that is the best treatment for both my baby and me. And so I did four cycles of Adriamycin-Cytoxan during the pregnancy and delivered my son at 37 weeks. He was healthy and full of hair, even though I was bald. That was very important, I think, for many reasons, but it showed visually that the placenta did its job and he was protected.

After he was born, I could do scans that I couldn't do while pregnant. I had a lot of back pain and things that were thought to be pregnancy-related, or maybe they knew, and they just didn't go there because it really wouldn't have made a difference at that point, like, the treatment couldn't be any different. But I did that scan and found out that it was metastatic, and that changed the treatment that I did after the pregnancy, and instead of eventually surgery, I just stayed on systemic therapy for that long. And spoiler alert, this is 12 years later. That baby is in sixth grade and thriving. And I am very grateful for the privilege that I have to have received such excellent care and have access to the treatments that I have had, and also the luck to have had good response to treatments.

Dr. Fumiko Chino:
I love how you've taken your story and the successes, but also the horror and the terror, and really used it to galvanize your life in a mission to try to improve patient care for others. So I've always really thought that was phenomenal in terms of your mission and your drive.

Julia Maues:
Thank you. I'm very, very happy that it helps other people, but selfishly, it helps me to deal with my own difficult experience, and it's been a way to make something good out of this.

Dr. Fumiko Chino:
I feel very aligned with you on that in terms of my own personal story as a caregiver. It's one of the reasons why I became a physician. So I feel like you and I have a common touchstone there. And I think so many people in medicine and so many patient advocates are really trying to give back into a system to try to improve it for all because of either the ways that it helped them or the ways that they thought that it could be doing better. So thank you for sharing that with us.

Now, Julia had mentioned that the staging scans were delayed until after delivery due to some appropriate safety concerns. And I certainly know that those diagnosed during pregnancy often have diagnostic delays. Erin, do you mind discussing what delays may occur in pregnancy-associated breast cancer and if there are any solutions to improve those delays?

Dr. Erin Roesch:
Sure. And I'd like to echo and certainly, you know, thank Julia for sharing her story. And I think as an oncologist, we learn so much from our patients, and so it's really, really important for us to understand, to be able to appreciate everything you've gone through. So I just, I really thank you for that.

So in terms of, you know, the delays that we see—and I think, Julia, your story through this really kind of outlines much of what we see in terms of some of these delays and challenges related to the diagnosis and the workup of pregnant women with suspicion of breast cancer. So although the majority, about 80%, of breast cancers or breast masses, rather, detected during pregnancy will be benign, any palpable mass present for a couple of weeks or more in the breast or axillary region should really be clinically investigated, you know, as your doctor did. Additionally, any other breast changes—less common things such as an asymmetry, thickening of the skin, redness of the skin, nipple changes—those things should also be investigated, you know, as they raise clinical suspicion.

Pregnancy-associated breast cancer often remains undetected in pregnant women until later stages due to potentially symptoms being masked by the physiologic breast changes during pregnancy. Studies have shown that a relatively high proportion, you know, over 80%, of pregnancy-associated breast cancers are self-palpated. We know that later stage at presentation and a delay in care can lead to an inferior prognosis or affect someone's prognosis.

So I think in terms of the challenges, in terms from a diagnostic evaluation standpoint, typical imaging modalities that we use for breast cancer, we know some can have harmful effects on a growing fetus. So the evaluation should begin, as Julia mentioned, with an ultrasound. That would be the initial gold-standard diagnostic test. And then subsequently, a mammogram with abdominal shielding can and should be used to provide additional details regarding the breast mass.

In terms of systemic staging, so I think again, as Julia pointed out, the traditional evaluation for metastatic breast cancer typically includes CT scans with IV contrast of the chest, abdomen, pelvis, and a bone scan or a PET scan. However, these imaging tests should be avoided during pregnancy, particularly during the first trimester, due to the harmful exposure of radiation and IV contrast to the fetus.

In regards to some of the solutions, I think from a systemic staging standpoint, alternative imaging can be used. So when indicated or appropriate, things such as a chest x-ray with shielding, an ultrasound of the liver, an MRI of the spine without contrast could also be considered, again, in the appropriate setting. But I think, you know, Julia certainly highlights the challenges that we face from a diagnostic standpoint.

Dr. Fumiko Chino:
Julia, you had said something probably that was the most important, which is that you felt the mass and that your physician actually took it seriously. And I certainly have heard from other patients that when they were pregnant and they felt something, it was sort of just 'pooh-poohed', for lack of a better term, as, you know, normal changes in the breast, and it wasn't followed up to the extent that it should have. Do you have anything to add in terms of delays? I know you are certainly very active in the advocacy community, so I feel like you've probably heard every good and negative story about delays to diagnosis or care.

Julia Maues:
Yeah, unfortunately, we hear these stories all the time. The clogged milk duct, which may be very plausible, but needs to be investigated, right, is not always the case. And unfortunately, anecdotally, and I know you all have been part of evidence on this, women that are Black experience this at a much higher rate. And then we see younger women with doctors that just tell them that, "Women your age don't get breast cancer."

Dr. Fumiko Chino:
Which is patently false, as we know, because the rates of breast cancer in younger women are rising. So I feel like we need to be standing on top of rooftops trying to make sure we're advocating for our patients and educating our colleagues about the early-onset cancer risk.

Julia Maues:
And I'll say one more thing that I think patients also have a wrong understanding of this statistic about pregnancy protecting from breast cancer after menopause. The only thing that translates is 'pregnancy equals lower rate of breast cancer', right? So that is not necessarily the case while you're pregnant or in the short years after the pregnancy. It is a statistic about postmenopausal breast cancer, which won't affect the pregnant person for many years.

Dr. Fumiko Chino:
Julia, this review highlights the role of the multidisciplinary team for optimal management of pregnancy-associated breast cancer. And from the article, it says, "At the time of diagnosis, multidisciplinary teams should be consulted, including breast surgery, plastic reconstructive surgery, medical oncology, radiation oncology, maternal-fetal medicine, genetics, and psychosocial services." Can you speak to who was involved with your care, including what really worked well in this incredibly stressful situation or lessons learned for what could be improved? I know you said you did have the benefit of a comprehensive cancer center and a multidisciplinary team.

Julia Maues:
Yes, absolutely. A team that came from many angles at this problem was very important. I did see a surgical oncologist, a radiation oncologist, a plastic surgeon, the medical oncologist, of course. And then I had two OB-GYNs, my first OB-GYN and a high-risk OB-GYN, and I did see genetic counseling. And I think after those first appointments, the surgeon and the radiation oncologist and the plastic surgeon didn't play a role. They were going to come back into my care after the pregnancy; that was the plan. But the OB-GYN, and especially the high-risk OB-GYN, was very important. And the fact that they were in touch with my medical oncology team and they were complementing each other in terms of medications and what treatment I needed, that was very important.

Dr. Fumiko Chino:
Erin, do you have anything to add in terms of coordinating these large teams? I know that the medical oncologist often works as sort of the quarterback in this scenario for these teams.

Dr. Erin Roesch:
Yes, and that's exactly how I typically describe myself to patients, is kind of as that quarterback. I think that Julia's description certainly highlights the importance of multidisciplinary care, and it's really crucial for pregnancy-associated breast cancer. And it's important to recognize that it's not a one-size-fits-all approach either, and that not all patients' needs might be the exact same. But that being said, it's helpful to have, you know, an algorithm that outlines the general steps, diagnosis, and management of our patients with pregnancy-associated breast cancer. And it's really important—it's an overwhelming time for patients and their families. So it's really, you know, essential to make sure that our patients have knowledge of and access to all of the resources that are available, you know, during their diagnosis, treatment, and in survivorship. I think that again, just stressing that multidisciplinary care from the beginning is really key.

Dr. Fumiko Chino:
That segues nicely into the next topic, which is: I really found the figure in your article to be particularly helpful as a flowchart for decision-making in pregnancy-associated breast cancer. How do you approach shared decision-making, patient autonomy, and informed consent with your patients when faced with some of these really heartbreaking decisions?

Dr. Erin Roesch:
So, you know, just as I said, it's certainly, you know, it's very individualized, but it is very helpful to have a guide that we can follow and that we can also use for educating other providers on what are modalities that are safe during pregnancy, what we have data on, where we're lacking, et cetera. So I think that when I talk with my patients in this type of situation, you know, I think open lines of communication, transparency, super important. And I think recognizing that breast cancer diagnosed during pregnancy often occurs during a time when a woman is figuring out their life plan. They could be finishing school, family planning, you know, career goals, establishing relationships, just to name a few things. So it's helpful to be aware of these things when we're counseling our patients so that we can better really appreciate, understand their goals and, as much as possible, help them achieve their goals while also effectively treating their breast cancer. So I always really, really strive to involve my patients in the decision-making regarding their care, but also advise them that I'm there to provide full support and whatever information that I can to be helpful.

Dr. Fumiko Chino:
I love that thing to highlight—that cancer doesn't define someone's existence, and they were a whole human being before their cancer diagnosis, and they should be a whole human being after their cancer diagnosis. And so making sure that we are talking to a person, not to a cancer diagnosis and a treatment plan. It's an individual on the other side.

Now, Julia, I know that you said that your stage IV diagnosis came after you delivered. I'm sure that there was a shock and horror related to that. Do you have anything to add in terms of the multidisciplinary team or how it pivoted once you got that diagnosis?

Julia Maues:
I completely agree with the 'quarterback' name to the medical oncologist. They definitely have, even today, this role in my life, and I definitely benefited from really wonderful quarterbacks in my years. But I think another very important connection there is being able to connect to other patients with a similar experience. I did - at different times, I was able to connect to people who had just had a baby after treatment during pregnancy, or who had a child that was maybe a little bit older and they were thriving, and just knowing that that was a possibility or a likely possibility for my child, even though I was making him go through these treatments while inside me.

Dr. Fumiko Chino:
Now, pregnant women, human fetuses, and neonates have additional protected status under the federal government that mandates special IRB review. This means that pregnant women are often excluded from research, often without actually clear justification, even when the research really poses minimal risk. Erin, how do we improve the body of evidence to support best care for patients with pregnancy-associated breast cancer, understanding some of these concerns?

Dr. Erin Roesch:
Yes, so I think it is really important to utilize the research means that we do have. So an example of this could include retrospective analyses, you know, looking at registry data. We can really gain important, valuable information this way. Additionally, learning from thought leaders in this space and experts in this field can help providers and patients better understand the data that we do have and where our gaps may exist.

I think, furthermore, various institutions have niche programs that are dedicated to education and research for young women with breast cancer and, within that umbrella, pregnancy-associated breast cancer. So it's really important, I think, to be aware of those resources as well that do exist.

Dr. Fumiko Chino:
You really highlighted something important, which is that in this situation of pregnancy-associated breast cancer, it likely is best to go to a specialty center, you know, a comprehensive cancer center of some variety, or a center of excellence so that you can really rely on both the expertise of the team but also their capacity for building that multidisciplinary team that is, I think, really required to treat a patient with cancer and pregnancy well.

Now, Julia, I personally see some parallels here with exclusions for people during pregnancy and also the exclusions for metastatic breast cancer from research studies. Do you mind speaking about that? I know you've been a strong advocate about inclusion.

Julia Maues:
Yes, absolutely. We see a lot of clinical trials that include metastatic breast cancer patients when it comes to the actual treatment and the new drugs. But when it comes to survivorship trials, and let's say, what is the effect of exercise on your outcome? Patients with metastatic breast cancer are often excluded. And we are surviving too, right? We need to be studied in that scenario as well. And I think we're fortunately seeing some change in that. And there are a few trials, for example, open right now looking at diet and exercise for specifically metastatic breast cancer.

Dr. Fumiko Chino:
It's amazing to think about how you've really straddled both high-risk groups, you know, the pregnancy-associated breast cancer, metastatic breast cancer, and really dedicated your life to making inroads and positive changes for both of these communities. So I really am so grateful for you for that.

We are sort of wrapping up this podcast. I wanted to give a little bit of space at the end to have any open topics, if there's anything that we feel is under-addressed or unaddressed in this topic. I know that we could probably spend, you know, five hours talking about it.

Julia Maues:
I will say one thing that is perhaps the most difficult decision. When I discovered my diagnosis, I was very happy to be pregnant, but I was faced with the question of, I now have a disease that is life-threatening. Am I going to be alive by the end of this pregnancy? And in order to be alive by the end of this pregnancy, do I need to terminate this pregnancy? I think that is a question that was the most difficult one during that moment and is one that I discussed with my team. And fortunately, in my case, it was possible to give me treatment during the pregnancy and still not harm my baby. But I think this is the first thing that we're faced with at that moment of the diagnosis.

Dr. Fumiko Chino:
And I think that concern is certainly even more relevant in the climate where, depending on where you live, that may not even be an option. And even, I have definitely heard some concerns about even chemotherapy while being pregnant could be potentially something that would be at risk. Erin, do you have anything to add?

Dr. Erin Roesch:
Yeah, no, I think that's a valuable point too, is that again, it's a very, very challenging, scary time at initial diagnosis. And just like Julia mentioned, many women are very happy they're pregnant. And even to Julia's point earlier about receipt of chemotherapy during pregnancy, you know, many women might not think that that's possible. We have data that has shown relative safety of certain chemotherapies during pregnancy, you know, after the first trimester. And so I think it's important that again, with the shared decision-making, that women know all of this information so they can process and come to the best decision for themselves.

So, and I think also, not that we can predict the future—I always tell my patients I wish I had a crystal ball that I could tell what was going to happen in the future for people. But I think that we've had a lot of advances in terms of breast cancer treatment, and this includes for metastatic disease. And so our patients are living longer and living better. So I think that's important to remember too. And just again, make sure that we, as much as possible, have these conversations upfront with what we know and what we don't know so our patients can feel supported through this process.

Dr. Fumiko Chino:
That's a really good, positive note to end it on. So I'm so grateful for your time. Thank you for this wonderful conversation today. Thanks to Dr. Roesch and Ms. Maues, as well as our listeners, for your time today. You can find the links to the papers that we discussed in the transcript of this episode.

If you value the insights that you hear on the JCO OP Put into Practice podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. I hope you'll join us next month for Put Into Practice's next episode. Until then, please stay safe.

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.

Conflicts of Interest:

Erin Roesch:

Honoraria

Company: Intellisphere

Consulting or Advisory Role

Company: bioTheranostics

Company: MDedge

Company: Seagen

Julia Maues:

No Relationships to Disclose

Dr. Chino talks with Dr. Atif Khan and Dr. Lola Fayanju about the shift in breast cancer management from reducing locoregional recurrence and improving breast cancer mortality to deintensification, shared decision making, and improved quality of life. This discussion will be based off a JCO OP editorial published in late 2024 called "Contextual Framework for Understanding Treatment De-Escalation in Patients With Breast Cancer."

Dr. Fumiko Chino: Hello, and welcome to Put into Practice, the podcast for JCO Oncology Practice. I'm Dr. Fumiko Chino, an Assistant Professor in Radiation Oncology at MD Anderson Cancer Center with a research focus on access, affordability, and equity.

Breast cancer treatment has made significant strides in the past century, with the five-year survival rate rising from less than 5% in the early 20th century to around 90% in the present day. In today's episode, we'll be discussing the shift in breast cancer management from reducing local-regional recurrence and improving breast cancer mortality to deintensification, shared decision-making, and improved quality of life. This discussion will be based off of a JCO OP editorial published in late 2024 called "Contextual Framework for Understanding Treatment De-escalation in Patients with Breast Cancer."

I'm excited to welcome two breast cancer experts as guests today: the first author of this editorial and radiation oncologist, as well as a health services researcher and breast surgeon. They're both engaged in research to improve outcomes for breast cancer, including treatment optimization.

Dr. Atif Khan, MD, MS, is a full attending breast cancer disease site leader and Service Chief in the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center. He is also on the steering committee of the Clinical Research Innovation Consortium, as well as on the Research Council at MSK. Dr. Khan is the chair of the breast section of oral examiners for the American Board of Radiology and is active in NRG, helping develop and lead key clinical trials to optimize radiation delivery for breast cancer. Dr. Khan is also a translational science investigator of novel radiosensitizers.

Dr. Oluwadamilola "Lola" Fayanju, MD, MA, MPHS, is the Helen O. Dickens Presidential Associate Professor and Chief of the Division of Breast Surgery at the Perelman School of Medicine at the University of Pennsylvania. She is also Surgical Director of the Rena Rowan Breast Center at the Abramson Cancer Center, Program Director for Implementation Innovation at the Penn Center for Cancer Care Innovation, and a Senior Fellow at the Leonard Davis Institute of Health Economics at Penn.

Our full disclosures are available in the transcript of this episode, and we've already agreed to go by our first names for the podcast today.

Atif and Lola, it's wonderful to speak to you today.

Dr. Atif Khan: It's a pleasure to be here. Thank you for inviting me, Fumiko.

Dr. Lola Fayanju: Yeah, thanks for having me.

Dr. Fumiko Chino: The topic today is treatment de-escalation for breast cancer, loosely based on the editorial that Atif wrote in JCO OP outlining a conceptual framework, which is primarily focused on local-regional therapies, i.e., radiation and surgery for breast cancer. The concept of rightsizing treatment has really been developing over the past three decades, spearheaded by surgical de-escalation. Lola, do you mind giving me a brief overview of surgical de-escalation as you have seen it throughout history and as currently realized in your practice?

Dr. Lola Fayanju: Happy to. So, you know, it's one of those things where I think increasingly we recognize that breast cancer is a heterogeneous condition that shares an anatomical space. And with that refined understanding of treating breast cancer, we're no longer using a very blunt and large hammer to deal with what is actually a constellation of nails. So originally, when people used to treat breast cancer, the idea was that you wanted to take as much tissue as possible. And this originated the Halstedian mastectomy, which was a radical mastectomy that often involved removal of not only all the breast and axillary tissue but also the pectoralis muscle, even some accessory nerves, that really left people with incredibly deformed body habitus as well as compromised function. And in part, that was not an unreasonable approach given that disease was often presenting in a locally advanced fashion.

However, as we have been increasingly able to detect disease at an asymptomatic, pre-palpable state, but also as our ability to treat disease at a systemic fashion has become more effective, we've been able to move from the Halstedian mastectomy to then the modified radical mastectomy, and then ultimately to even less axillary surgery, as well as less breast surgery, such that there was the advent of the lumpectomy pioneered by Bernie Fisher in the 1980s, as well as sentinel lymph node biopsy pioneered by Armando Giuliano and Don Morton in the 1990s and early 2000s. And what this allowed us to do, again, is to achieve similar if not better outcomes, because we were again catching disease at an earlier state thanks to screening mammography, but also able to provide more personalized, less morbid care that focused on just the cancer at hand with the additional adjuvant therapy of radiation to provide comparable survival to mastectomy.

What this has allowed us to do is also think about the order in which we do treatment, that is allowing people to potentially get systemic therapy first in order to convert from a more morbid procedure to a smaller, less morbid procedure. So, we've made a huge number of strides both with regards to surgery in the breast as well as surgery in the axilla, and that's been facilitated by a combination of knowing more about disease, being able to be more systemic and holistic in its treatment, and also recognizing that more is not always more. The last thing I will say is that we've also been aided not only by the adjunct radiation and systemic therapies, but also by the ability of our radiologists to localize pre-existing cancer such that we can target the area and just the area of concern, whether it's through targeted axillary dissection or through sampling a previously positive area of the breast, such that we can again be more selective in terms of the surgery people get after systemic therapy.

Dr. Fumiko Chino: Thanks for that great overview, and I really love it how you have highlighted that it's all of these advances that allow us to customize the treatment to the individual. So it's not one size fits all with cancer care. We're really trying to make a customized plan and really rallying all of the modern technologies to make sure that we're rightsizing the treatments for the individual. And I think that provides a lot of benefits for patients.

Atif, can you highlight some of the key steps to de-escalate radiation for breast cancer?

Dr. Atif Khan: I think thematically, we're seeing a very similar sort of trend in radiotherapy. Just as a reminder, radiotherapy is a critical component of breast conservation therapy and also in the post-mastectomy context for high-risk patients. Radiation has been shown to sterilize or reduce the risk of microscopic residual, reduce the risk of local-regional recurrence, and in high-risk contexts, you know, by extension, reduce the risk of all recurrences and even improve survival, for example, in the seminal post-mastectomy radiation therapy trials.

Now, we existed in a time when there was perhaps only one right way to do radiation therapy, and that's not the case now. We have many different ways that we can deliver radiation therapy. And that's important because our, as Lola said earlier, our understanding of different risk strata of breast cancer has also improved, meaning we can stratify breast cancer patients into low risk, intermediate risk, high risk, maybe even very low risk. And therefore, we can tailor the intensification of our local-regional treatments to match the background risk that may exist for that particular patient.

Now, if we consider five weeks of whole breast radiation or five weeks of post-mastectomy radiation to sort of be our historic norm, we now know that we don't have to protract the course of radiation out like that. We can treat that same target volume, for example, the whole breast, with a shorter course of radiation that generally is given over three weeks. Now, I do want to pause here for one second just to clarify for everyone listening: taking five weeks of whole breast and doing that over three weeks is not necessarily a de-escalation per se, because really the same biologically effective dose is being given. It's just being given faster. So it's not really a treatment deintensification or de-escalation per se. Now, it is less disruptive to patients, it might be less, say, financially toxic, for example, in terms of like missed days of work, etc., but it's not a de-escalation with respect to the intensity of the treatment. It's just the same treatment being given shorter, but we know that it's safe to do that.

In contrast, partial breast radiation is, in fact, a de-escalation because now our target volume is no longer the entire breast, rather, we're just treating a part of the breast, that part of the breast where the risk primarily is, which is in the index quadrant where that original breast cancer was. And at the, let's say, at the low end of the risk spectrum, we now have very good evidence, you know, 14,000 randomized women, demonstrating that, in fact, partial breast radiation in those contexts is just as good as whole breast radiation. And I always sort of half-joke that whenever this treatment is possible, we should use it because for a fibroblast sitting in the breast somewhere minding its own business, a day without radiation is a good day, right? So if we can spare that treatment to uninvolved normal cells, we should try to do that.

And then, of course, the ultimate de-escalation is to identify patients who don't need radiation at all and just omitting radiotherapy. And really across the risk spectrum, whether it's in breast conservation or whether it's in PMRT/regional nodal radiation, we are seeing the emergence of these different types of treatments, meaning kind of like the high-risk treatment, the intermediate-risk treatment, and then at the very low end of the risk spectrum, no treatment at all. But that's sort of the practice that we're living in now, and I think it's a good one. We're making progress.

Dr. Fumiko Chino: I appreciate that. The whole idea is if we can potentially omit treatment to certain areas of the body or if we can omit it completely, we're certainly doing a favor for our patients if it's not going to increase their overall risk. We had talked, I think between the two of you, about some of the benefits of potentially omitting or reducing morbidities from, for example, surgeries or comprehensive treatments. Atif, do you want to take it first? What are the actual de-escalation risks? What are we potentially putting at risk when we talk about de-escalation or deintensification?

Dr. Atif Khan: Yeah, great question. I mean, I think the primary risk, which is, you know, a scary thought, is that we de-escalate or we do it too quickly or we find that, in fact, reducing the intensity of treatment leads to an increase in the recurrence risk of breast cancer. That's a very scary thought. I will say that this process of creating options, you know, treatment options, de-escalated treatment options, has been quite successful. For example, I'll open it up to Lola and you, Fumiko, but I can't really think of a clear example in which the de-escalation trial went in the wrong direction. Like, they've all sort of gone in the same direction, which is that the de-escalation or deintensification studies have generally been successful, meaning that we were able to preserve the excellent oncologic outcomes that we are used to seeing with less treatment. That's a testament to kind of how careful, you know, the scientific process is with respect to these practice-defining trials. They go through multiple levels of scientific review. It's a multidisciplinary group of individuals that's looking at this. And I would say the endeavor overall has been quite successful.

Dr. Fumiko Chino: Lola, anything to add?

Dr. Lola Fayanju: Yeah, I think when we're thinking about the risk of de-escalation, I would put them into three categories of risk. So, there are risks to the individual, that is, you know, we're actually de-escalating in the wrong person because we have an insufficient amount of information about whether they meet the criteria for de-escalation.

There's, I think, risk to the population in terms of are there groups of people who are systematically not benefiting from the de-escalation or who should not be benefiting from de-escalation because again of an underappreciation of how disease might work in that group or because the practice patterns where those people are getting care will not be amenable to de-escalation ultimately being of a good thing for them because they're not getting the other components of care that frankly are needed for de-escalation of one modality.

And then three, I think there's a risk to our collective knowledge about cancer because when we're not collecting information about what happens after six weeks of radiation or how many lymph nodes are positive, we just know a little bit less about the natural history of the disease and the natural sequelae of treatment. Again, that knowledge may be worth forgoing given the morbidity to patients and the non-benefit with regards to recurrence and survival, but it's real. It means that our retrospective reviews look different. It means our ability to have preliminary data for other types of things look different. With regards to the populations, it means that whenever we're thinking about de-escalation, we need to think hard about how to translate what we see on the podium at San Antonio or ASCO into clinical practice. And that requires, I think, more care than is often administered.

Dr. Fumiko Chino: Yeah, I'll quote directly from the manuscript of the editorial that we are basing this podcast on, and it said basically, "American women ascribe a high utility to remaining without evidence of disease." And that really sticks with me in that, even though there may not be a survival benefit, an increased risk of recurrence is not without a personal, financial, and physical burden on patients, even if that difference is small, it may be meaningful for the person in front of you.

Now I'll also shift focus slightly and just mention that we're primarily talking about local therapy here, but I'd be remiss to not highlight that there are gains in de-escalation for systemic therapies from, for example, RxPONDER, allowing us to safely omit adjuvant chemotherapy for many node-positive patients; B21, showing that monotherapy with radiation may be actually even better than tamoxifen monotherapy with no metastatic or survival differences; and of course, the PERSEPHONE trial that demonstrated that six months of trastuzumab was non-inferior to 12 months, although, granted, there were many caveats leading to poor adoption of this in practice.

Now, Lola, I know you've already mentioned this, but there are maybe some concerns that you see about broad adoption of these practices into, for example, surgical de-escalation. Based on what I know is stark disparities in clinical trial enrollment in certain populations or in maybe even clinical trial protocol adherence, are there any specific populations that you want to highlight that might be hesitant to apply this clinical trial podium data to?

Dr. Lola Fayanju: That's a great question. So, as an example, when we think about the SOUND trial, which was recently published and demonstrated that in women with early-stage breast cancer who were undergoing breast-conserving therapy and had normal axillary evaluation prior to surgery, that sentinel lymph node biopsy could be safely omitted without detriment with regards to long-term outcomes, you need to think about the context in which that preoperative ultrasound is being done. So, at different institutions, whether or not an ultrasound is routinely done, whether or not that ultrasound is done prior to biopsy, all of these things have implications for how likely you are to have a false positive after biopsy (so it's preoperative, but it's post-biopsy) and also what you're going to do about it, whether you're going to act on it, whether you're going to go ahead and proceed with sampling that node if it looks enlarged, putting something in it that means you retrieve it. If it demonstrates a small amount of cancer, potentially consigning someone to either an axillary dissection or preoperative systemic therapy that they might have forgone had you had the full picture of surgical pathology.

So that's just one example of how the context in which implementation occurs is really important because you have to take into account local practice patterns and what that means with regards to how we interpret the data that was used in the trial to then implement this practice in real life.

With regards to populations that need to be considered, I think in terms of centering equity, both domestically but also at a global level, thinking about, for instance, how we stage the axilla, how we map the axilla. What's the facility for lymphoscintigraphy as well as for localization of a previously positive node? So, there are many countries, many quite wealthy countries, in which use of radiocolloid is not routine, where it is primarily that people are using some type of tracer blue dye, for example, and therefore would not strictly be meeting the criteria for optimal sentinel lymph node mapping that would allow for a low false negative rate after neoadjuvant systemic therapy.

In the United States, we might be in places where you have patients who are having surgery with people who don't do that much breast surgery and who are less likely to have a successful and correct yield of lymph nodes at time of sentinel node biopsy. And so, you know, these are people for whom there might be actually clinically significant disease that's being left behind if not being done by someone who has a lot of experience working with dual tracer as an opportunity to localize a preoperatively positive lymph node. So again, thinking about both the availability of materials as well as the expertise of the local practitioners means that people in less or differently resourced settings may not benefit from implementation in a way that actually leads to appropriate outcomes.

Dr. Fumiko Chino: Yeah, I love it how you highlight that there's global differences, but there's also just in the US differences in capacity and skills within doing these, some of these presurgical and surgical evaluations. All three of us work at world-leading cancer centers, and I recently just transitioned from two top cancer centers in the United States, but I was actually kind of shocked about the differences even between the two major centers about how we do ultrasounds, for example.

Now, Atif, I've noticed that some providers don't really feel comfortable combining the information from various de-escalation trials in practice, i.e., so for some patients that might have had sentinel lymph node biopsy omitted per SOUND, they may be less likely to actually get PBI and instead, you know, prefer to treat whole breast radiation to cover the axilla. So, in this respect, it seems like we're kind of taking like one step forward, one step back. And are we de-escalating surgery to just escalate radiation?

Dr. Atif Khan: Fumiko, I agree with you. It'd be very counterproductive if we found that de-escalation in one domain was leading to escalation in another domain. I think the example you cite is a good one. If we are moving to a world without sentinel node biopsy and let's say clinical staging only, does that then mean that we have to, for example, give up on partial breast irradiation and treat everybody with whole breast radiation on the notion that low axilla, for example, is going to get some therapeutic effect? And I would submit for everyone's consideration that no, we in fact should not do that. We spent years developing the partial breast irradiation literature. We know that PBI has less acute toxicity. In every single trial, it has less fatigue, and it actually has less late toxicity in some studies, which is not surprising because remember, you're treating less tissue, you're treating less stuff, and that's a good thing.

Now, coming to SOUND and INSEMA, on the sentinel node arms of both of those studies, the rate of additional positive nodes is very- around, 10%, and that's pretty low. So I would submit for everyone's consideration the idea that if your patient is node-negative by SOUND criteria, let's say, right? They're very likely to be pathologically node-negative. And you can actually treat them as if they were pathologically node-negative. And that's kind of how we've adopted the findings of both SOUND and now also INSEMA from San Antonio, meaning that if a patient is eligible for PBI based on everything else, and she is node-negative by SOUND criteria, then we will offer them PBI in exactly the same way as we were before these trials were reported.

I also wanted to make one observation on your prior comment, Fumiko, if I may, about the de-escalation of systemic therapy. One thing that has been on my mind quite a bit is, particularly with, let's say in the elderly group where we have been struggling with kind of like the best monotherapy, right? Should it be five years of endocrine therapy? Should it be a short course of radiation, or do patients really need both of these treatments? And this is topical because the EUROPA trial, one of the endpoints was reported at San Antonio, the quality of life endpoint. Not surprisingly, a short course of radiotherapy was sort of associated with better quality of life than the endocrine therapy.

But I think we may be missing one potential opportunity in this sort of idea of like, we have to either do the radiation or the endocrine therapy, which is we might be able to give a little bit of systemic therapy and a little bit of radiation therapy. This line of investigation or line of thinking doesn't really exist right now. Like that conversation is interesting. So for example, can we give, for number one, can we go from AI back to TAM, right? Because AIs are just, there's just, the quality of life is worse. And can we give a lower dose of the TAM, monitor for compliance, and then give a little bit of radiation, you know, let's say PBI or something? And maybe that's the way to do that. And you could take that idea and you could apply it across different contexts even in breast cancer. And I'll note that that is how kind of the Hodgkin's lymphoma treatment evolved over time. At the low end of the risk spectrum, they kind of said, "Okay, a little bit of chemo and a little bit of radiation is better than just giving a lot of chemo or certainly a lot of radiation." And you know, that worked. And I think at the low end of the breast cancer risk spectrum, we might start thinking about that kind of line of investigation.

Dr. Fumiko Chino: You want to 'Goldilocks' this situation. You want to try to find something that's just right. And I love that. And I think that sort of out-of-the-box thinking is very helpful when we think about how omission seems very clean, "you just don't get this," but deintensification, simultaneous deintensification, I think has a lot of appeal there.

Lola, do you have anything to add about that?

Dr. Lola Fayanju: I have to acknowledge the bias of three local-regional therapists on this podcast, I'm outnumbered by our two rad oncs. But just wearing my medical oncology ally hat, I think one of the challenges is also that for many of them, the ability to prescribe effective forms of systemic therapy, including CDK4/6 inhibitors, for example, is sometimes predicated on information we obtain at surgery. So, when we think about implementation, which is really, you know, an area of research for me, whether it's trying to implement the SOUND trial, again, in an institution where everyone's getting an ultrasound prior to biopsy, absolutely. But in an institution where either it's completely ad hoc, so it's kind of the 'wild, wild west', you have no idea from radiologist to radiologist who's doing ultrasound before or after biopsy, and also frankly, what is the kind of false negative rate at that institution, recognizing not everyone's working at the kind of places we work at. Are we doing patients a disservice?

But then, in addition, thinking about working with insurance companies, right? If we're trying to say, "Okay, we are no longer going to do sentinel node biopsies," but that's actually required for the administration of certain medications, we put our medical oncology colleagues in a bad position in terms of their ability to actually get certain types of treatments paid for and approved. And so again, thinking about the consequences of our choices for patients, I think it really points to the fact that multidisciplinary consultation is increasingly going to be needed because we can't de-escalate everything. I think we all agree most cancers need to be treated in some fashion. But, you know, if we take away surgery, we take away radiation, we take away systemic therapy, suddenly we have a cancer that's just sitting there. And for some people, that's the right thing. Again, thinking about shared decision-making, for some patients with other morbidities and/or older age where they're unlikely to have any kind of meaningful threat from disease being left in place, well, that is the right thing potentially. But for a majority of our patients who actually want some form of treatment, I think we do need to think about the implications for our other prescribing providers, what that means, how we can help them, even as the clinical trial data suggests that there aren't major changes in adjuvant therapy or radiation prescription when you omit sentinel node biopsy, at least in the trials that have so far been shown.

Dr. Fumiko Chino: This is a nice segue to my last point, which is to talk about how these discussions of de-escalation, these decisions should really be made after the full multidisciplinary input. And yet, I feel like I've seen our specialties get increasingly disconnected in this kind of era of Zoom conferences. There seem to be less face-to-face meetings. There seems to be decreasing space for our co-shared clinics. And I just wanted to ask both of you what you think our responsibility is to each other and to our field to ensure that we're really working on these things synergistically.

Lola, you just mentioned some of your thoughts, but do you mind speaking about the multidisciplinary conversation or even how we're designing research?

Dr. Lola Fayanju: I think, with regards to the research, I'll start with that first, it means that, I think we're less going to have trials that fit in certain kind of cooperative groups that are more geared towards radiation or what have you. I think, increasingly, we should be having MPIs, you know, co-PIs who are from different modalities. I think that that's going to allow us to bring our different lenses to constructing the trial, to ultimately interpreting the result. I think we'll only grow from that. I think the era of having a bunch of medical oncologists or surgeons or radiation oncologists as the primary authors really should probably shift.

I think we need to think more globally about multidisciplinary care and what those, quote unquote, "tumor boards" should look like. And thinking beyond our own institutions, again, we're relatively privileged in terms of being at places where we all have at least weekly, if not bi-weekly multidisciplinary tumor boards. Most cancer care in the United States is happening in the community where a patient walks into, often a general surgeon's office, and that person will get surgery upfront whether they need it or not, or whether they should be getting systemic therapy or not first. And then from there, they will then be referred to a medical oncologist who may have had no input as to which procedure should have been omitted or discussed or vetted prior to meeting that person. And so, I think our greater challenge is how to bring in the global oncology community, and by global, I mean truly across the globe, across the United States, across the world. And it might be that ASCO and JCO, places like this for discussion, is an opportunity for us to connect people, connect our communities, and not having us work in silos, both at the institutions in which we currently are employed, but also at a broader level.

Dr. Fumiko Chino: Wonderful statement. Atif, anything to add to that?

Dr. Atif Khan: Yeah, I think you're pointing out an important thing, Fumiko, which is, you know, we are somewhat more fragmented since the pandemic, and we're kind of in our own spaces, and that is potentially a problem. I think in breast cancer, the different specialties are often existing in kind of a very cooperative matrix, and I think that ends up meaning that we're able to really provide high-level care to our patients. I think there are other specialties, I know, where the specialists may be existing in a somewhat more competitive matrix with each other, and I think that ends up potentially being counterproductive for patient care. So I think this is probably a thing that we need to have more conversation around and sort of thinking about how do we bring the different vantage points together in the interest of the patient and not lose that multidisciplinary care that we'd become so used to and that's provided such excellent outcomes.

I think on the research side, I don't want anyone to sort of be left with the idea that there's just one specialty that's sort of driving, you know, the design of these trials. From my own first-hand experience, both at Alliance and NRG, there's a lot of scientific review that happens, and I spent quite a bit of my energies over the past decade and a half kind of convincing medical oncologists that a certain local-regional question is warranted. And, and you know, that's part of the process. I appreciate that because they're not just experts in their field. You know, we all eat, breathe, and live breast cancer. So, you know, they have keen insight into the local-regional management as well.

Dr. Lola Fayanju: Yeah, I have to say I love the cooperative group meetings. That's kind of where the sausage gets made. And I think it is really exciting that you have people from different disciplines sitting together, proposing trials, vetting them. It feels like you're seeing the future in the present, which is really exciting. And, you know, I think what we're all striving to do.

Dr. Fumiko Chino: I love that hopeful conclusion, and I really am so grateful for both of you for this wonderful conversation today. Many thanks to both Dr. Khan, Dr. Fayanju, as well as our listeners for your time today. You will find the links to the papers that we discussed in the transcript of this episode. If you value the insights that you hear on the JCO OP Put into Practice podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. I hope you'll join us next month for Put into Practice's next episode. Until then, I encourage everyone to continue doing the work that they find meaningful for their patients, for their community, and for themselves.

Dr. Atif Khan: Thank you.

Dr. Lola Fayanju: Thanks 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.

Disclosures:

Atif Khan: Stock and Other Ownership Interests: Novavax, Xtrava; Research Funding: Clovis Oncology, Merck KGaA, Varian Medical Systems; Patents, Royalties, Other Intellectual Property: Use patent for the drug riluzole awarded to Rutgers University with me as inventor.

Oluwadamilola Fayanju: Research Funding: Gilead Sciences

Dr. Pennell talks with Dr. Daniel Richardson discuss physician burnout and the author's curriculum designed to mitigate burnout and foster solidarity among fellows.

Support for JCO Oncology Practice podcasts is provided in part by AstraZeneca, dedicated to advancing options and providing hope for people living with cancer. More information at AstraZeneca-US.com.

Hello, and welcome to the latest JCO Oncology Practice podcast, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all recordings, including this one, at podcast.asco.org. My name is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JCO OP.

Today, I'd like to talk about a topic that's at the front of many people's minds, burnout. With what seems like constant stress and increasing demands on our time, many clinicians are feeling increasingly exhausted, cynical, and like their work lacks meaning. These elements are part of a condition known as burnout. And it feels like everyone's feeling it to a greater or lesser extent these days. While employers and training programs are increasingly aware of the issue of burnout, what are they doing to reduce it or to prevent it from happening in the first place?

With me today to discuss this topic is Dr. Daniel Richardson, hematology/oncology fellow and AHRQ postdoctoral research fellow at the UNC Chapel Hill Lineberger Comprehensive Cancer Center. We'll be discussing his and his colleagues' paper, "Development of an Art of Oncology Curriculum to Mitigate Burnout and Foster Solidarity among Hematology/Oncology Fellows," which is part of a special series at the JCO OP on physician wellness burnout and moral distress. Welcome, Daniel, and thank you for joining me on the podcast.

Thanks for having me. It's really a privilege to speak with you today. I'll start off just by noting my conflicts. I have no financial conflicts of interest to disclose. However, my institution was involved in the study that we'll be talking about.

All right, thanks for that. So burnout is something I think most physicians and other clinicians can relate to. But would you mind just kind of giving our listeners a little brief overview of what exactly is burnout in physicians and how big of a problem is this right now?

Sure. So burnout was first described really as a metaphor to talk about an extinguishing of a fire or smothering out of a fire. And it related to this loss of capacity that many feel to make a meaningful and lasting impact with one's life or career.

More recently, it's been further clarified to cover several domains of this initial concept, including emotional exhaustion, depersonalization, and loss of meaning or purpose at work. And burnout really has been shown to lead to profound of personal and professional consequences-- anxiety, depression, and in the professional realm, attrition among physicians and oncologists and decreased quality of care. And the problem is pretty pervasive, as most of us are aware. Our most recent studies show that nearly half of practicing oncologists are experiencing burnout and about a third of residents, fellows, and medical students even are experiencing burnout.

Yeah, this is what, I think, a lot of our listeners might be interested to hear about. There may be a conception out there that burnout is a function of time-- you know, being exposed to something over a long time maybe later in your career. But what you're saying is that this is something that people can start to experience almost immediately, even in medical school and during residency. And I find that really interesting, although potentially disturbing as well.

Yeah, I agree. And I think what we're seeing is probably the results of a larger change in our culture. We're seeing kind of a loss of sense of meaning and purpose and connectedness to the community in the larger culture. Increasingly, we're seeing that medical students, residents, and fellows are lacking a deeper sense of meaning and purpose in the broader community. And that's really playing out in their role as an oncologist as well.

So I'm curious what led you and your fellowship program to developing this kind of a curriculum to try to combat burnout.

Sure. Prior to medical school, I completed a master's degree in philosophy of religion and ethics. And it allowed me the opportunity to think a lot about virtue ethics and also the moral foundation of medicine. And virtue ethics is really focused on human flourishing and really claims that the path to human flourishing is developing character and virtues that can lead to that.

And so I thought a lot about who I was becoming as a medical student, who I was becoming as a physician in medical school and then into residency. During my first year of fellowship, I was thinking a lot about the culture of medicine and how I was developing in the midst of that. And I really became aware that there was a clear lack of direction on how to help fellows develop into oncologists that would be able to thrive in their careers.

We didn't really talk about calling. We didn't talk about purpose. We didn't talk about who we were becoming. We were being trained as oncologists with the right answers about treatment. But as one of my favorite authors, C.S. Lewis, puts it, we were at risk of developing into oncologists without chests-- that is, without a deeper understanding of the meaning and purpose of what we did each day. It really kind of started with this bigger understanding that we were going through this big process, and we were becoming oncologists without really thinking about what that process was looking like and how that was happening.

Wow, I think that is-- that's fascinating. Well, in any case, since this led you to design the program, can you take me through the design of the Art of Oncology program that you designed? And what are you hoping to show as a result?

Sure so as I had mentioned, I was really thinking a lot about who we were becoming as oncologists. And so one of the first things that I thought about is, how can we foster a sense of meaning and purpose in our fellows. I thought that this was really a place where we are seeing a lot of burnout is that there is this lack of meaning and purpose among fellows and oncologists in general. And so we wanted to target that. So we landed on a curricular intervention that used narratives, really to promote a shared mental model of meaning and work, which all that really means is helping all of us have a discussion to understand where we are coming from, our experiences, and how we are being shaped in the midst of kind of caring for patients. And our hope in kind of starting from that point and developing a narrative model was really that we could help fellows understand where they sat in caring for patients, their calling in doing that, and then also their position as a part of a broader community that had a bigger vision for caring for patients as well.

So we decided that we would use personal and published stories, mostly about caring for cancer patients, to spark discussion, reflection, and then really a deeper understanding among fellows of this shared calling. And we had faculty or, often, patients come and share their story or one of the narratives in those sessions. We planned eight sessions throughout the year, which took place during the traditional didactic lecture times. And the narrative took place over the first 15 minutes or so. And then the point was really to foster this deeper discussion and reflection on meaning, identity formation, and moral development in medicine.

So a lot of this really was based, then, upon selecting the different essays and other pieces of literature that you were discussing. So how did you end up picking those?

That's a great question. And I think we wrestled with it a lot. I think initially, we, as a group, found those essays that were most meaningful to us. And we felt like they would really speak to the fellows. But as we thought about it more, we really wanted to collect them around a few themes. And as I've been talking about, I fundamentally believe that finding meaning in caring for suffering patients is essential to mitigating burnout. So this was kind of the primary theme that I focused on.

But we also, in the midst of the program, wanted to equip fellows with skills to foster their sense of purpose in medicine. So we had a session focused on cultivating virtues of resilience and self-care, as well as sessions on caring for dying patients. And we really understood that the experiences of most fellows were very hard, given the immense amount of suffering that they experience.

So our initial hope would be that really, this session and this program would be an avenue to redeem some of the suffering that the fellows were experiencing through their patients. We hoped that it would lead to a deepened sense of community or solidarity is the word I use in the paper, among our fellows, and that this sense of belonging in one's profession really becomes vital for the sustained success. And I was really hoping that this would be fostered in the program as well.

You had mentioned earlier about what you were hoping for. Although we knew that we wanted to target a reduction in burnout among fellows, we recognized that burnout is really a multifaceted concept. So we knew that a small pilot program would be unlikely to see a substantial improvement in burnout. But we wanted to really shoot our or our aim our intervention really at the roots of developing burnout over a career.

So how did you try to measure that? So I mean, first of all, I've got to say, this sounds amazing. And I could say it may have value just in and of itself, because it's such an interesting and cool concept. But as scientists and trying to study things, how would you measure this kind of improvement?

Yeah, so that is probably the fundamental challenge, to be honest. And I, first off, want to say, I 100% agree with you. I think it's a first principle of medicine that we need to, as a community, think deeply about how to care for patients well. And we need to help each other to thrive in medicine. So I don't know how you'd necessarily capture that on a scale.

There are well-developed burnout scales, the NBI being the most prominent. We worry a little bit about having our fellows go through extensive surveys in the curriculum. So we used a couple surrogates. So there are three one-item measures that we used at the beginning and then the end of the curriculum.

And then we really wanted to capture the experience of the program as well. So we had fellows fill out basically subjective surveys about their experience with the program. And then also, we captured their attendance in the program. Our aim was really to establish, first off, is this something that is possible to do, good fellowship programs do this. And then really, did fellows enjoy and participate in the program as well.

You mentioned about not wanting to put a bunch of surveys on top of people. And so one of the first things that occurred to me when I was reading this paper is, were you concerned when discussing adding this that fellowship curriculums are already quite busy and filled with lots of sessions and other duties and whether this might actually make their burdens worse by adding extra sessions and requirements?

Yeah, for sure. We didn't really know what to expect. And we didn't even know if the Fellows would show up and participate. There is fear within our culture of being vulnerable, of owning that the suffering of our patients is getting to us and that we need some help. And I was really afraid that fellows would feel like the sessions were cheesy or forced and that the fellows would be uncomfortable being honest in the sessions.

There is a perpetual concern about adding more into the lives of fellows that will lead to greater burnout. You know, it's the running joke about filling out a weekly 25-question burnout survey among our fellows. So we really wanted to design a program to limit the requirements. Fellows really just had to show up and participate. There is no required readings or homework.

And we limited a few didactic sessions that used to be in the place where the Heart of Oncology sessions were in order to make room in the schedule. And we tried hard to make the sessions adaptable to any environment so that it was really just having a narrative prompt, getting people who care for cancer patients together, and thinking deeply about some of these issues that was really at the heart of the program. So we tried to limit a lot of those extra requirements for the program.

Well, it sounds like you definitely thought about that and tried to make it as least burdensome as possible. And it sounds like you were able to do that. So tell me, what did you learn from this first year of the program?

Well, it was really fun at first. And so as a fellow myself, I was able to participate with the other fellows. And that was really wonderful. I had a great time with them and learned a lot about them and felt like it was really enriching for me.

We saw, really, that the fellows really enjoyed the curriculum as well. They really loved the opportunity to think more deeply about these issues and also to hear how their colleagues were wrestling with them and to dialogue about some of the issues that we often don't talk about. They felt it improved the sense of community among the fellows and helped with some of the daily challenges of dealing with the suffering of their patients.

They pointed to some practical skills that they took away from the sessions, including managing work-life balance, communicating bad news, and having a better understanding of the challenges faced by patients. Surprisingly, many of the sessions were really emotional for the fellows, where they were able to share their stories about losing patients or family members to cancer.

We didn't see a statistically significant improvement in burnout. And as I mentioned previously, this is a pilot intervention. So this is not wholly unexpected. As you mentioned prior as well, that with such positive comments from the fellows that the sessions were beneficial in and of themselves, and really that we would hope that there would be long-term benefit as well. I don't know if such programs to foster moral development would actually be expected to result in immediate improvements in burnout. So the goal was really to begin to cultivate the virtues that will have lasting impact over a career in medicine and not necessarily to impact the burnout that follows were experiencing in that moment.

So you are describing the first year in your paper here. So what are the next steps? And based on what you've learned, are you planning any changes?

Yeah, so Dr. Collichio and I sit on the ASH ASCO Milestones committee, which are working to develop some metrics to capture fellow well-being at each fellowship program. And so we are hopeful that these metrics begin to lay a foundation to expand the art of oncology programs and other fellowship programs. We've been in contact with other programs that are eager for such an intervention and to get it rolling. And so I welcome other fellowship programs to join in as well.

The ideal study design to test this intervention is a multi-institutional cluster randomized trial. But really, I think we're still at the nascent stages of the development of such interventions. So this will likely be something that will happen years from now. And again, I think we realize that while we want this intervention to really impact on burnout, we want the intervention to have something deeper in terms of developing the character of our fellows. And so rolling it out among fellowship programs is going to have benefit across the board.

So what changes are we making to the program? We're in the second year of the pilot. And we haven't had too many changes, apart from, again, limiting the amount of requirements that we have for the fellows. Last year, the fellows really loved having patients come and speak and share their stories and how they interacted with the health care community. So we increased the number of times that patients would be coming. And we started to have more of our senior oncologists come and share their journey in medicine, kind of a career perspective to the fellows, and allow them to really begin to build some mentoring relationships.

Well, Daniel, I think this sounds absolutely fantastic. I wish we had something like this when I was going through fellowship training. So Daniel, any closing thoughts before we wrap up?

I'd like to comment that programs like these are simply part of a larger whole. Much of the increase in burnout we are seeing in medicine, as I mentioned, is part of larger societal epidemic of the loss of meaning and purpose for individuals. I believe that the epidemic of burnout in medicine is not going to simply be reversed by programs, but rather by a deeper change in the culture.

As an oncology community, we need to recapture our calling of service to suffering patients. We need champions who can lead the way in this and serve as mentors for fellows on how to care for patients well and to model how to find joy in their careers despite the suffering and losses they experience. It is only by recapturing this deeper calling that we can inspire and train fellows to do the same. And I'm hopeful that programs like this one and other similar programs across the country to bring fellows together to think deeply about their calling, their personal calling, and then also their calling in the midst of the oncology community, will serve to do this as well.

So Daniel, thanks so much for joining me on the podcast today.

Once again, this is such a privilege. Thanks so much for having me.

And until next time, thank you for listening to this JCO Oncology Practice podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode.

JCO Oncology Practice podcasts are just one of ASCO's many podcast programs. You can find all recordings at podcast.asco.org. The full text of the paper is available online at ascopubs.org backslash journal backslash JCO OP, posted in February 2020. This is Dr. Nate Pennell for the JCO Oncology Practice signing off.

Dr. Pennell and Dr. Lisa Lowenstein discuss decision coaching in the LDCT setting and how it provides an opportunity for patients to confirm their screening decision by ensuring they are truly informed.

Hello and welcome to the latest JCO Oncology Practice podcast, brought to you by the ASCO Podcast Network, a collection of nine programs, covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all recordings, including this one, at podcast.asco.org. My name is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JCO OP.

Lung cancer is a huge public health issue. It's our number one cause of cancer-related mortality, and a big reason for that is the lack of a widespread screening tool which results in most of our patients ending up with advanced disease at diagnosis. Although, low-dose CT screening has been proven to reduce deaths from lung cancer for a number of years now, uptake among eligible patients in the United States is very low, well under 10%. Part of the problem may be a poor understanding of the risks and benefits of screening CT, despite broad recommendations for shared decision-making between providers and patients.

Why is uptake such a big problem, and can shared decision-making be improved to help increase screening rates? With me today to discuss this issue is Dr. Lisa Lowenstein, assistant professor in the Department of Health Services Research at the University of Texas M.D. Anderson Cancer Center. We'll be discussing her paper, Implementing Decision Coaching for Lung Cancer Screening in the Low-Dose CT Setting, to be published in the February 2020 JCO OP. Welcome, Dr. Lowenstein, and thank you for joining me today.

Thank you. It's wonderful to be on.

So can we start out by telling our listeners a little bit about the landscape of screening for lung cancer today and the role that shared decision-making plays in this process?

Yes. I think we're in a very exciting time in terms of lung cancer screening, because this is the first time that we have a screening test for lung cancer which is the number one cause of cancer deaths among men and women in the United States. It's really notable that CMS included shared decision-making in their policies for lung cancer screening, because they recognize that, unlike breast cancer and colon cancer screening, we're changing the game a lot of bit here. So we're saying that only high-risk individuals should be screened. So it's not all-comers, and I think telling people about the potential benefits and harms is beneficial. So they go in being a little bit more informed about what the next steps will be, and it is a complex process, and overall, it's still in its infancy.

Yeah. I think a lot of people found it interesting that, in order to reimburse for lung cancer screening, that CMS required this documented shared decision-making visit which on the surface seems like a very reasonable thing. But do you think that's really helping, or is it hurting?

Lung cancer screening is really in its infancy, and it's a complicated process. So we're not just talking about you just show up, and you show up for a scan. Right? We're not where breast cancer screening is. We don't have mobile scans out there. It's taken decades for those programs to get where they are, and I think shared decision-making is just adding one more step and just emphasizing that it's really a program that you're committing to.

And the other aspect is that we really want to highlight that it's not lung cancer screening is enough to prevent lung cancer. Right? It's just detecting it, if you have it. But the best way you can reduce your lung cancer risk is by not smoking, and I think by inserting the counseling and shared decision-making visit, we're reiterating that message to our high-risk smokers and former smokers. Primary care providers, or any providers, aren't even talking about lung cancer screening.

Two, not a lot of facilities may be listed in the American College of Radiology Lung Cancer Screening registry, but their volumes are very low, and they may not actually have the proper equipment or machines to conduct the lung cancer screening. Third is that, if there is to be something to be found on the scan, we don't have processes in place to deal with all the abnormal findings. So I think those are all the things that providers and networks are trying to figure out, and they're trying to figure out like the cost benefit from the reimbursement issue. Because CMS reimburses this scan for a very low cost, and it's lower than what's reimbursed for breast cancer screening.

That's interesting, and in your paper, you mention that, as of right now, something around 6% of eligible patients are getting screened for lung cancer. Which is disappointing, because the studies have been out for a while now. You mention about some of the institutional issues and awareness and providers. Are there any other reasons out there that are limiting this? Because this is something that should be saving lots of lives, and so far, it just seems like it's not making much impact.

I think so, and I think it's misguided in some sense. The reimbursement is not-- you don't have to submit a reimbursement for the counseling and the lung cancer screening. A screening facility can still be reimbursed for the scan without the 1 to 1 ratio of a counseling in shared decision-making billing code, if that make sense.

That's interesting. I didn't know that.

Yeah. So the reimbursement is definitely not going on 1 to 1. I just think, it's a complicated process, and if you were doing a study in Texas and we're serving as many screening facilities as they can in Texas, and I can tell you, a number of them are not doing a high volume of scans. And a lot of primary care providers are trying to find screening facilities that are doing low-dose CT, and it's really hard to navigate the American College of Radiology Lung Cancer screening facility to find a facility. It's about 15 to 20 clinics or something like that.

Wow.

So we tried to look for it on a number of occasions, and it takes us multiple tries every single time.

Well, it's obviously a complex issue, and there's more than one reason for the low uptake. What was the specific issue that led you to do this particular study, and do you think that improving shared decision-making can improve uptake on lung cancer screening?

I think the main issue that we were trying to address here is that, one, we recognize that primary care providers may not be the best-suited individuals to provide the counseling shared decision-making visit. Instead, they may just want to do more of a referral process, like what they're doing in the Cleveland Clinic. Right? Where they say, somebody's potentially eligible, so I'm going to send you to a one-stop shop type of setting. And our radiologists who are leading our lung cancer screening program really wanted to start building this and test it out as an alternative delivery model for the counseling shared decision-making visit which wasn't proposed by CMS or the task force recommendations.

So can you take us through your study design?

Sure. So it was really a pre/post kind of study, really with a quality improvement mindset, as well as using some elements of implementation science, so we can make it relevant more generalizable in our findings. But we first had our period of where they just did what they normally do, where the patients show up. They go and have their scan. They have their normal intake process, and that's it for the lung cancer screening. Then, in our post, we embedded a tablet interactive decision aid, decision coaching module.

So what happens is the patient has the iPad in hand, and they have some patient-facing education talking about the benefits and harms. It's very fast and quick. Patient can get through it and two to three minutes, five minutes if they're not tech savvy. And then we have an advanced practice provider sort of talk about what do they know about the benefits of lung cancer screening? What did they know about the harms, and what are their primary reasons for wanting to be screened, just to kind of confirm their issue, confirm their decision to be screened.

And so what did you end up finding with the intervention?

What they found is that, one, with the decision coaching aspect of it, the advanced practice providers can deliver all the key elements that are required for the counseling and shared decision-making to defer CMS reimbursement. So I think that's really important, in the sense that so much of what we already see in the literature, providers talk a lot about the benefits of screening, but they don't note any potential harms. And it's really important to notice that screening is not without its downsides, and that with an abnormal finding, there is inherent risk. It's not like you're just getting a picture taken. There are steps that need to be followed afterwards.

And the other thing is that what we really like and what our clinical operations people appreciated is the fact that this embedding entire new process did not increase the throughput time for the time that the patient checks in to the time that that patient checks out. Because every institution is paying a lot of attention in money, as to what is throughput time and making sure that it's not too long. And from a patient's anecdotal evidence, the patients appreciated that additional process, because it broke up the time between the waiting periods in between each step.

Yeah. I think that's an incredibly important point that you point out, that they didn't really increase the visit time, but how did that work? The intervention took place during a time that they'd normally be waiting or doing something else?

That's basically what it is, because we did time-motion studies in the pre and in the post. So we followed patients from the time they checked into the time they checked out, and we cataloged what they were doing. And what we saw when we looked at that data in more granular level is that the time was shifted from waiting periods to active time.

That's great. That's really important that you were able to show that. I thought it was interesting that you commented in your paper about the different elements of the shared decision-making visit. That in fact, what we might think of as the primary reason for doing it, which was the element of reducing mortality or their chance of dying of lung cancer, was actually the least important part of the shared decision-making visit. Why do you think that was?

I don't know if it was the least important part. It's just that we had some slides dedicated to it for the decision coaching, but there are so many more harms to talk about, and it's also an artifact of the context to where this intervention took place. So we took it, we were dealing with patients who had already been scheduled to be screened. So we were just confirming their decision, and I think the advanced practice providers knew that. So they might have glossed over the benefit, because otherwise, the patients wouldn't be there, if they didn't value the screen.

Mm-hmm. I guess that makes sense. They knew why they were there. Is there a next planned follow-up study for this?

Good, I'm glad you asked that. So using this data, we're testing this more centralized model and using it in a different setting. So now, we're taking this into a quit line setting. So we have a Cancer Prevention Research Institute of Texas, or CPRIT, grant that's looking at the decision coaching being delivered by tobacco treatment specialists via phone.

So a primary care provider identifies patients with upcoming appointments that might be eligible based upon age and being a current smoker. And then they get contacted with our quit line folks, here at Anderson, and we deliver the counseling and share decision-making visit, in addition to the cessation, and we give a report back to the BCP. And well, we're hoping that increases individuals to get screened and also have proper follow up, if there is something abnormal on the scan.

So I'm curious if you have any other suggestions outside of your program of ways we might improve the uptake of lung cancer screening in the US.

Oh, I think we could do a number of things. So I think we have to think about each step of the pathway. Right? So one, we have to increase awareness of it. So that's through social media, social marketing, that kind of stuff for both patients and providers and caregivers.

Then, two, we need multiple avenues, where we talk about lung cancer screening, like how we do with breast cancer and colon cancer. Like at church, at your beauty parlor, at your grocery store, and have those kind of public health interventions to get out the information. And three, we really need to train up our health care workforce and help programs. Where it's possible to either have the PCP do it in a robust manner or have a more linked program, where they can refer to a centralized program. Where the counseling and shared decision-making visit can be delivered by their pulmonology or in the radiology scan, and the patient can get scanned that day.

So I think there's a lot of different questions and different delivery models that can be asked, and this is a great area to be working in right now. Because with the release of the Nelson study, it's even more exciting to show that lung cancer screening can be very beneficial, and with using the lung rads, the false positives are much lower. So I'm pretty excited, and I think there's so much opportunity, and we can learn so much from what we're doing in breast cancer and colorectal cancer screening.

No, I completely agree with you. I think it's very exciting that the Nelson study was finally just published, and so hopefully, this will overcome any residual skepticism about the benefits of lung cancer screening. And obviously, continuing to improve on the screening tools themselves, maybe using some kind of companion diagnostic, maybe blood or breath-related, that might improve the-- or using artificial intelligence to better tell benign from malignant nodules. Ways that you can reduce the false positive rates would be very helpful. Well, Dr. Lowenstein, thank you so much for joining me on the podcast today.

Thank you. It's a pleasure.

Until next time, thank you all for listening to this JCO Oncology Practice podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts, Google Play, or wherever you listen. While you're there, be sure to subscribe, so you never miss an episode.

JCO OP's podcasts are just one of ASCO's many podcast programs. You can find all recordings at podcast.asco.org. The full text of the paper will be available online at ascopubs.org/journal/op, in February, 2020. This is Dr. Nate Pennell for JCO Oncology Practice signing off.

Dr. Nathan Pennell, Dr. Muhammed Beg and Ms. Erin Williams discuss improving the time-to-activation of new clinical trials at an NCI-Designated Comprehensive Cancer Center.

Read the article: https://ascopubs.org/doi/full/10.1200/OP.19.00325

TRANSCRIPT

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DR. PENNELL: Welcome to the latest Journal of Oncology Practice podcast brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all recordings, including this one, at podcast.asco.org.

My name is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JOP. Today, I'd like to talk about clinical trials, specifically the complex process that goes into opening a clinical trial and the surprising amount of time and individual steps that go into what might otherwise seem like a straightforward process. And while we all agree that trials are critically important for patient care and making scientific advances, as a clinical investigator, I can tell you that they can be quite a challenge to open and sometimes take a surprising amount of time and resources, which can be frustrating.

With me today to discuss this topic are Dr. Shaalan Beg, associate professor of medicine in the division of hematology and oncology at the University of Texas Southwestern Cancer Center, and Ms. Erin Williams, associate director of clinical research operations at the Simmons Comprehensive Cancer Center. We'll be discussing their paper, "Improving the Time to Activation of New Clinical Trials at an NCI-Designated Comprehensive Cancer Center," to be published in the November 2019 JOP.

Welcome, Shaalan and Erin, and thank you for joining me on the podcast.

DR. BEG: Thanks for having us.

DR. PENNELL: So can we start off by talking a little bit about what's involved in the clinical trial opening process and why this ends up being such an important issue that leads to projects, like what you describe in your paper?

DR. BEG: Yes. It's a pretty complicated process. And I think I say it a lot, like, how a bill becomes a law. So how does a trial protocol become an open clinical trial available to our patients? So when you have a document which embodies the principles for the clinical trial or the clinical trial protocol, you have a consent form that will be a patient-facing document that the patient sees, which summarizes, in layperson's terms, what the procedures will be for the study. And then these documents have to go through multiple steps of approval within individual institutions.

For example, the institution review board will look at the document in terms of risk management or risk assessment for the institution. Scientific committee will review the scientific integrity and see whether it suits the patients that that specific center is taking care of. And then, in parallel, you have a group of experts who want to see if that trial is something which they can feasibly execute. So hypothetically speaking, if a trial needs treadmill tests, do we have a treadmill to actually do that? So really the rudimentary, sometimes, feasibility questions.

And then, as the studies are becoming more complicated, some of these studies have biomarkers which we want to identify patients for, and we need to test patients before we can find the right patients for the clinical trial. So that entire process is becoming more and more complicated.

DR. PENNELL: That all sounds like it makes perfect sense, but I know a lot of our listeners might be surprised to learn that this entire process from beginning to end can take a long time-- sometimes six months or longer. What are the consequences to an institution of taking a long time to activate a trial?

MS. WILLIAMS: So this is Erin. Well, the consequences can mean our access to clinical trials, right? So it can also mean access for patients to the clinical trials. So both of those things. If we take too long to open the study and a lot of other centers around the country or around the world have a study open-- and specifically, there are a lot of trials that are open internationally, and sometimes it's easier to open trials internationally more quickly-- then our patients lose access to those trials as the spots for enrollment fill up and the study goes closer and closer to its enrollment target.

But in addition, sponsors, industry sponsors, pharmaceutical companies that are bringing trials to their cooperative groups in which we participate-- these are NCI-funded large-cluster groups for phase III clinical trials, we participate with those as well-- they're looking at how long it takes us, as an institution, to activate a new study. And if we start to take longer than most other institutions, they may not favor us for a particular trial to offer that trial to us.

DR. PENNELL: This is such an important process, and I think this is really going to resonate with lots of people who work at centers that open clinical trials. So why don't you take us through the process? So what exactly did you do there?

MS. WILLIAMS: So this is Erin again. We convened a group of stakeholders, along with a leader from our institution's Lean Six Sigma program, to really map out the process. So we convene about four or five hours of a day for everyone to come in. And it didn't just include cancer center stakeholders, but it included stakeholders from our sponsored programs administration office at the institution, our institutional review board, human research protections office, our hospital review committee. We really wanted to gather together all those people who touch the process in some way throughout the course of the time to activation.

And so really with Patrice's help, who is our Lean Six Sigma expert, she really kind of started the process out, and we did kind of what your traditional Lean Six Sigma mapping might look like-- use sticky notes and words on sticky notes, mapping out the process on the long board, and then ultimately creating what the map looks like. And I think what it did was allowed everyone who was in the room to really take a look at the process and how sequential everything came out to look.

One of the biggest impacts that we identified and that we highlighted in the paper is what you really saw was this gap between our scientific review committee submission and the IRB review, and then everything else in the process, because a lot of steps hung on IRB approval and didn't want to move forward, including hospital review, contract execution, things like that, until the IRB had given their stamp of approval, which of course is the review board for patient safety.

So what we tried to do is, immediately, you could kind of see this visible gap in-between the steps, and that really showed us that potentially aligning that scientific committee review with the IRB review and allowing that IRB approval to happen more quickly might trigger some of the other steps.

DR. PENNELL: One of the things that I found really interesting when you were talking about the various steps in the process was when you chose to start the clock, because I know that there is a lot of attention paid to how long it takes to open trials. And, you know, in my experience, I have heard that there are institutions that somewhat game their numbers by not starting their clock to opening until they've actually gotten a lot of steps already done before they do, say, a regulatory submission. And then it looks as though they're opening the trials quite quickly, but they may have already had the protocol for many months ahead of time, working on things ahead of this.

And you guys chose to start from the time you actually receive the regulatory packet and the protocol to start, which makes sense. I mean, that's really when, I think, you, as an investigator, would think the clock would start. But did you ever get any pushback from your leadership or others to starting that early?

DR. BEG: No. I think it's a matter of being consistent with how we report our numbers. Similar to you, we are an NCI-designated center. We report these to our advisory boards and to the NCI in regular intervals.

I think whenever we're measuring numbers and we set metrics for any target, we run the risk of people trying to cut corners and gaming the system to make the number look good. I think that's pretty well-documented in any industry. And our time-to-trial activation has become this shared quality metric across the cancer center, across the institution. And we were worried that it may start being that way, that folks are trying to, "well, should we take out the weekends, those aren't really work days, or how about the time the sponsor has the packet, or--," you know?

And I think, as humans, we all have tendencies to try and come up with ways to make our numbers look better. But the advantage of publishing this to a journal like the JOP with transparency on how we're measuring it, and, you know, I think we had faith that our audience would recognize when our time is-- when our time clock is starting. And there wasn't any pushback.

MS. WILLIAMS: I'll just add to that. The reason why I think it's so important to be transparent with these numbers is because-- being in an administrative role and an operational in a clinical research office for a long time, investigators who are bringing a trial forward for us to activate, the calendar has started as soon as they bring me a trial that they want to open. And if I tell them that a study only took 60 days to open, and their recollection is nothing near what I'm telling them my metric is, then they're not really going to trust what I'm telling them overall. And I think it's important that I recognize, and that we recognize as an operation, that what really matters is that once we get the study, we're starting the process.

It just makes the numbers more useful to you, internally. It makes it more useful to the outside companies or organizations that you're working with. And, you know, even the non-value added time that's not in your control can sometimes-- you can intervene in that. You could potentially escalate things if you haven't heard from a company in a certain period of time. So I completely agree. That makes perfect sense.

DR. PENNELL: So, well, why don't we dig into your results? So what did you find through the mapping process?

DR. BEG: I think one of the issues was how we can move some of the steps that happened in parallel or that happened sequentially to try and make them work in parallel. And like Erin mentioned earlier, just mapping out the process and having the different offices represented on campus that are a couple blocks away from each other really think about how they-- when they start their clocks and why they wait for specific milestones to start a review process was very helpful.

So one of the steps was to really move from a sequential process of scientific review followed by an institution review board review into a process where we move that in parallel to each other. And different centers have grappled with this question in different ways. The way we decided to address this, we didn't want the IRB to be bogged down by a study that wasn't scientifically valid, that may have concerns, or is not novel enough. But we have internal data that our scientific review committee-- and this is published data-- that our scientific review committee very rarely changes the design or the structure of an industry-sponsored clinical trial, for example.

So we decided that we would come up with a process where the IRB will physically review the study at a time after the scientific committee has reviewed the study. If the study is disproved, then it falls off the IRB's docket. But if it's approved, then they will be ready to review it. And we were able to shrink that time from scientific review to IRB quite significantly by modifying that process.

We talked about institutional studies, so studies that our own investigators are developing. Those studies do tend to get more criticism at the scientific review committee. Our committees review them much more closely and have much more impact on those. And we decided to move them forward on a case-by-case basis. So it really required some restructuring.

MS. WILLIAMS: One of the other things that we outlined in the paper, one of the other outcomes, was that our hospital review committee agreed to review the study in parallel with the IRB and in the PRMC review process and just hold their approval until those approvals had been received. And that happened. And if you looked at the individual time to getting that hospital review committee approval immediately following the intervention, it went down significantly.

As with anything, it takes consent kind of massaging and working with those groups. And some of the offices and the infrastructure around clinical trial changed subsequent after we had our time to activation. And so with any of that change, processes start over, people start looking at things over again, and they decide, well, wait, why are we reviewing this in parallel? Or these other groups of people need to be reviewing this in more detail.

Having said that, as those processes have changed, what we've heard and what we've experienced with those stakeholders in the institution is that their eye is always on the activation timeline. And that if we report to them, hey, this time to review committee approval has kind of gone back up, it's creeped back, and we really need to look at this again, you can see their immediate response is, oh, absolutely, we understand, these are kind of some shifts that we made, but let's get together, let's look at it, we really are hoping to push it back down.

DR. PENNELL: Well, I think that's a great point to point out, that this is not a one-time thing. And whatever changes you institute, you can't just do it once and then expect it to be a permanent change if you don't follow up and ensure that it's still working.

DR. BEG: One of the other things which came up when we were looking at our numbers was to figure out how to staff different positions. And there are some steps of the activation process that are very nuanced, really require special expertise. And an example for that is the coverage analysis evaluation, where a third party independent of the investigator's team decides whether every procedure or blood test or scan gets billed to insurance or is that something that gets billed to the study. So is it a research procedure or is it a standard of care procedure? And in oncology, where philosophically we view research as embedded within standard of care, that can be a pretty tricky determination to make.

So the people who do this come in with a really unique set of expertise from their clinical-- that have clinical expertise and research expertise. And one of the things we noticed was for positions like those and for positions other than that, it's really important to have redundancies in those positions, so if there is staff turnover of any kind, that that process can keep moving forward. Because those are steps that-- it's hard for a consultant to come in and fill in and those people don't really just hang out on campus for us to be able to tap their time and to start processing those studies.

So other than looking at our processes, it did come down to staffing those positions and making sure that we create some redundancies in those positions so that we're not completely dependent on, for example, one person for a task like that.

DR. PENNELL: And that is such an obvious issue that I think maybe a lot of people may be shocked to hear that institution's administrations don't always agree that you need more than one person to do a task. But again, this is really resonating with me personally, because we went through this same issue. And there are so many important things that for some reason there's always just one person who can do it. And if they're out for whatever reason, or they leave and there's staff turnover, things just grind completely to a halt. And so I think that that's a wonderful illustration that hopefully will be convincing.

Did all of this work end up making a difference in your time to opening trials?

MS. WILLIAMS: It is making a difference. We are seeing improvements in certain steps of the process. We've definitely seen an improvement in our time to both scientific committee review approval, our time to IRB approval. Our coverage analysis timeline has been very steady. Our time to activation for our national cooperative group studies has been very stable at around 90 to 100 days, since instituting just kind of these simple-- well, not so simple-- but since instituting this whole process.

Where we still have challenges is in our budgeting and contracting process. However, again, since we've got that institutional buy-in, it was actually our sponsored programs administration office contract director who approached me about two or three months ago and said, you know what, we really need to talk about the workflows between covered analysis, budget negotiation, and contract, because I see things kind of being an issue for us, as far as getting expedited approval and execution of contracts.

So we had another about 2 and 1/2 hour meeting just about a month ago to sit down and go through that workflow and identified, again, a couple of key places where we can bring previously sequential steps into a parallel-step process.

And so once again, I think the take-home of the exercise that we performed is that we have institutional stakeholders who aren't necessarily just waiting to hear from us to figure out how we can do better, but are coming to us and identifying timelines and being able to work together to continue to make those happen.

DR. PENNELL: And it sounds like this has worked very well for your institution. But you point out in your manuscript that a lot of the processes are so unique to individual institutions that it's hard to make blanket recommendations that apply everywhere. So what can other sites who are also worried about their time to activation take from your process?

DR. BEG: I think one message is to know what your internal process is. And I think a lot of folks who are listening to this podcast will admit that at their centers there's no one document that really maps out the entire process. So for us, the process of mapping out the trial activation process was probably the most transformative bit, the rest sort of just fell into place.

DR. PENNELL: Shaalan and Erin, thank you so much for joining me on the podcast today.

DR. BEG: Thank you very much.

MS. WILLIAMS: Thank you.

DR. PENNELL: Until next time, thank you for listening to this Journal of Oncology Practice podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode.

JOP's podcasts are just one of ASCO's many podcasts programs. You can find all recordings at podcast.asco.org.

The full text of this paper will be available online at ascopubs.org/journal/jop in November 2019.

This is Dr. Nate Pennell for the Journal of Oncology Practice signing off.

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Dr. Nate Pennell talks with Dr. Joel Segel about "Coverage, Financial Burden, and the Affordable Care Act for Cancer Patients."

Article available online at Journal of Oncology Practice.

TRANSCRIPT

Support for Journal of Oncology Practice podcasts is provided in part by AstraZeneca, dedicated to advancing options and providing hope for people living with cancer. More information at astrazeneca.us.com.

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Welcome to the latest Journal of Oncology Practice podcast, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all recordings, including this one, at podcast.asco.org.

My name is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor at the JOP.

Medical care can be very expensive in the United States. And a diagnosis of cancer can be a huge shock, both physically, mentally and financially. Medical expenses don't just impact financial lives, but may also impact treatment outcomes, as even patients who are cured of their cancer may be left with a significant amount of debt.

One of the primary goals of the Affordable Care Act-- so-called Obamacare-- was to increase the number of citizens covered by health insurance, so that these financial burdens would be lessened. And we know that as the result of the Affordable Care Act, overall insurance coverage did increase. But how well did this work for patients with cancer specifically? And what impact has it had on financial burdens?

With me today to discuss these issues is Dr. Joel Segel, assistant professor of health policy and administration at the Penn State University. We'll be discussing his paper, Coverage, Financial Burden, and the Affordable Care Act for Cancer Patients, to be published in the October 2019 JOP. Welcome Dr. Segel. And thanks for joining me today.

Thank you for having me.

So can you start, for our audience, just by putting the general landscape into perspective for us. What are the financial burdens that cancer patients go through, especially those who are in lower incomes?

Sure. So there's certainly been a lot of evidence that cancer patients face, obviously, a number of medical care and health burdens, but also financial burdens. And in some cases, the financial burden can be pretty significant.

We also know that certain groups are probably disproportionately affected. So we know lower income, especially sort of racial and ethnic minorities, and especially some of the younger cancer patients can face significant financial burdens, but it also varies quite a bit. And so the evidence is certainly mixed in terms of how it's measured, how a financial burden is experienced by these different patients, but it can be as extreme that there is evidence that 2% to 3% can experience financial bankruptcy. So these can be pretty significant financial burdens.

And I guess the last thing would be there's probably two ways in which a patient can face a significant financial burden. So one is, and the one that we actually focus on most in our paper will be, the financial burden that results from medical care costs. We can also think about that, obviously, cancer can affect an individual's ability to work. So there can also be an additional financial burden if they're unable to work or they have to cut back on their hours, and that leads to a reduction in their income.

And is there evidence that patients' insurance status factors into their financial strain and burden?

Yes, there's certainly evidence that patients that have more comprehensive coverage, especially those that are higher income, that may help to mitigate much of the financial burden, whereas patients-- and that's one reason why younger patients sometimes have less comprehensive coverage. And they also may have less in savings and be less prepared to deal with some of the financial burdens.

And I think that makes perfect sense. And so what was in the Affordable Care Act that was designed to help patients deal with this?

The Affordable Care Act is an extensive law with a whole bunch of different features. I think there are several that are probably particularly relevant for cancer patients. So one is the one that's probably talked about a lot, which is the Medicaid Expansion. So initially, states were required to expand Medicaid. Due to a Supreme Court case, it became optional. So certain states decided to expand Medicaid, and that meant that they expanded who would be eligible. So primarily lower income adults, particularly ones without children, became eligible for Medicaid in certain states. So that's one piece.

I think the other one that's come up a lot, especially in a lot of the news stories, would be the restrictions on preexisting conditions. So certainly leading up to the Affordable Care Act, one major concern was that individuals, particularly-- cancer was one of the prominent examples would be if they had previously been diagnosed with cancer, they might have trouble either obtaining health insurance coverage or being renewed for health insurance coverage. So the Affordable Care Act made it so that regardless of what health care conditions an individual had, they were guaranteed renewability of the health insurance or the ability to purchase a health insurance plan.

And I think the last two general sections that might also affect cancer patients would be, one, they set up a number of state-based health insurance exchanges to allow individuals to purchase health insurance, and particularly for individuals who are buying individual plans and not through their employer, prior to the Affordable Care Act, especially for those with cancer, might have had difficulty purchasing a health insurance plan. So these state-based exchanges were an opportunity for individuals to purchase health insurance, and depending on their income with subsidies. So there were both subsidies for the premiums, or what an individual would pay each month for their health insurance plan, as well as cost-sharing subsidies. So for lower income individuals, they could become eligible for additional assistance to help cover some of their medical care costs.

And then, I guess, the last part would be that the Affordable Care Act placed limits on what an individual would have to pay out of pocket, both in terms of within a given year, and also, they got rid of some of the lifetime limits to health insurance.

OK. So it's obviously a complex law with a lot going on. But fundamentally, ultimately, the hope was that more people would be insured and that fewer people would suffer the consequences of having to pay for expensive medical care without having the insurance to help them with that.

So with that now put into perspective, take us through your study. How did you design this? And what were you hoping to look for?

So what we wanted to do was to take a look at, in particular, the non-elderly population who had been diagnosed with cancer. So what we did is we took a look at a large nationally representative data set, the Medical Expenditure Panel Survey, which follows a random sample of individuals across the United States for a period of two years. And within that, we then try to identify a non-elderly-- and by non-elderly, that'd be ages 18 to 64-- who had been previously diagnosed with cancer, or who, in the data, we could observe that they had some utilization for which there was a diagnosis of cancer.

And we then further restricted it, for much of our sample, to the lower income population. So that would be individuals who lived in a family that was at less than 400% of the federal poverty level. I guess to give a bit of a sense of that, that would be about $48,000 for an individual or $100,000 for a family of four currently. And we specifically chose that threshold, because that's the threshold by which individuals qualify for premium subsidies on the state-based exchange.

In particular, what we're going to look at is, first, we're going to look at coverage, so the number of months an individual spent either uninsured with Medicaid coverage or with private coverage. Among those with private coverage, we also took a look at whether they were enrolled in a high deductible health plan. We also looked at spending in terms of both their overall spending and also their out of pocket spending. And then, finally, to get a better sense of some of the financial burdens that families might face, we looked at both the change in what this family had to pay out of pocket for their health insurance premiums, so just the part that the family or individual pays as well as the fraction that a family pays for their health care costs, and that would be both the medical costs as well as the out of pocket premium.

And our last one, in addition to the fraction of income spent, would be whether they crossed a threshold of 20% of their family income spent on health care costs, which is a commonly used measure of high medical burden.

OK. So I think that makes sense focusing on that group. So what did you find?

So we look at a couple of different samples, both the lower income cancer population as well as the higher income cancer population. And we look at sort of how those outcomes changed from before the Affordable Care Act to after the Affordable Care Act. And in addition, we were going to make some comparisons to try to get a better sense of whether these changes looked different for different groups, so whether the higher income cancer group, how do they compare to the lower income cancer group, how the different cancer groups might compare to a population with a similar income level, but without cancer.

Similar to other studies, we see a significant improvement in health insurance coverage among the low income or the lower income sample with cancer. We find that that's driven largely by both an increase in Medicaid coverage as well as an increase in the high deductible health plans. So people seem to be enrolling in either Medicaid or private coverage, and that tends to be with some of the higher deductible health care plans. We see similar changes for individuals who what we'll call current cancer, and those are the ones who not only have been diagnosed with cancer, but show some utilization in the current year.

And then, I guess, in addition, what we find, we find something slightly different in the higher income cancer sample, and that's that they also experience an increase in the enrollment in high deductible health plans, but they also see a significant increase in their out of pocket premiums as well as the fraction of family income spent on health care. And so that's what we see in terms of just comparing pre and post. But we also do a number of comparison to some different groups to try to tease out sort of what might be driving, and sort of how similar the cancer population might look in terms of their improvements to some of the other population.

You mentioned that a lot of this had to do with the expansion of Medicaid, but of course, that that was rather sporadic because not every state expanded Medicaid. Did you look regionally at these numbers or is this basically nationwide?

So it's nationwide. In some of our adjusted analyses, we're able to control for region. But actually, one of the limitations of our study is that in the data that we have available, we can't identify an individual's state. So we don't know whether or not they're necessarily in an expansion state or a non-expansion state.

Yeah, because one of the first things that occurs to me is that if everyone had expanded, would the number be larger? And is there any evidence of the Affordable Care Act improving coverage and financial burdens specifically in states that didn't expand Medicaid? But I think that would be an interesting thing to look at maybe in the future.

Absolutely, and there's certainly some evidence to suggest that within cancer populations, generally, there does seem to be improved health insurance coverage, in particular, in some of the Medicaid Expansion states precisely for the reasons that, I think, you're mentioning.

One of the other things you looked at is you looked at a comparison group with a higher income level, what did you find in that group sure so one of the comparisons we make is that some changes in our outcomes between the lower income cancer sample and the higher income cancer sample what we see is maybe not surprisingly there's less of a change in health insurance coverage among the higher income cancer sample part of that is that they've had they had higher coverage rates to begin with. But what we also see is an increase in the out-of-pocket premium of about $800 per year for the higher income sample relative to the lower income sample. And we also see it relative to lower income sample that day they experience about a two to three percentage point increase in the fraction of their income spent on health care costs. What we find seems to be driving that is actually

more of a modest increase in the fraction spent among the higher income cancer sample along with sort of a very modest decrease in the lower income sample where are you going to go from here with these data what future studies do you have planned and what ideas can you pull from this to try to help reduce future financial burdens on cancer patients. So part of it is trying to get access to some of the restricted data where we would actually be able to identify what state people are and so we could get a much better sense of whether we're seeing some of these changes differentially in expansion states versus non-expansion states.

Also, with some additional restricted data, we'd able to get a better sense of how these patients might be transitioning across different types of health insurance plans once they're diagnosed with cancer. So right now, we've got a mix in terms of patients who are in active treatment and more recently diagnosed, along with patients who may have been diagnosed further back. I mean, unfortunately, in the data we currently had, we're not able to accurately distinguish exactly when they were diagnosed. But again, we'd be able to better tease out some of those differences between people who had maybe been diagnosed longer ago versus more recently.

So one of the things that everyone is worried about today, of course, is the rapidly rising cost of medical care, especially drugs in patients with cancer. That probably poses a challenge to doing this kind of research showing pre and post expenses when the actual cost of care is going up during the study period.

It's certainly an important thing to consider. Obviously, during this time period, the cost of, in particular, some of the cancer therapies has gone up significantly. We try to account for it, I guess, in a couple of different ways. One was going to be we're comparing some of the higher income and the lower income populations to get a sense of whether they differentially experience some of the financial burden. So to the extent that both lower income and higher income cancer patients are facing the same increase in drug prices, we would control for that to some extent.

I guess the other comparison we made was to compare, in particular, the lower income cancer sample to a lower income sample that did not have cancer. And actually, interestingly, what we find is we don't really find much of a significant difference between those two samples. So what that suggests is that the Affordable Care Act improves coverage and may help to mitigate some of the financial burden, but it does similarly for both cancer and non-cancer patients who are low income.

And that makes sense. As much as we pay attention to cancer because that's our field, it's only one of major health issues. Especially in a non-Medicare age population, I would think there'd be a lot of other competing risks. But still, it sounds like that is a good control over the overall rising costs of health care.

Well, Dr. Segel, thanks so much for joining me for the podcast today.

Thank you for having me.

Until next time, thank our listeners as well for listening to the Journal of Oncology Practice podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe, so you never miss an episode.

JOP's podcasts are just one of ASCO's many podcast programs. You can find all recordings at podcast.asco.org. The full text of the paper will be available online at ascopubs.org/journal/jop in October 2019. This is Dr. Nate Pennell for the Journal of Oncology Practice signing off.

Dr. Nate Pennell discusses "How to Know if a Somatic Tumor Mutation is Targetable" with Suanna Bruinooge, the director of research, strategy, and operations at ASCO's Center for Research and Analytics, or CENTRA, and Dr. Richard Schilsky, senior vice president and chief medical officer at ASCO.

Read the related article "Determining If a Somatic Tumor Mutation Is Targetable and Options for Accessing Targeted Therapies."

[DR. NATHAN PENNELL]

Welcome to the latest Journal of Oncology Practice Podcast brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all recordings, including this one, at podcast.asco.org.

My name is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JOP. Today, I want to talk to you about an increasingly common scenario encountered in clinical practice. Molecular testing for biomarkers to help guide treatment of patients has now become a standard part of treatment for many types of cancer. For example, HER2 testing and breast cancer or EGFR mutation testing in lung cancer.

But testing is also increasing in other cancer types often using broad, multiplex assays surveying hundreds of genes. Clinicians are being presented with a report that may seem dauntingly complex and hard to interpret. And even when you have a drug recommended, that may be off-label for its use or even experimental, leaving patients and clinicians perplexed as to how to access them.

With me today to discuss these issues are Suanna Bruinooge, the director of research, strategy, and operations at ASCO's Center for Research and Analytics, or CENTRA, and Dr. Richard Schilsky, senior vice president and chief medical officer at ASCO.

We'll be discussing their paper, "How to Know if a Somatic Tumor Mutation is Targetable-- Options for Accessing Targeted Therapies" published in the August 2019 JOP. Welcome Suanna and Rich, and thanks for joining me today.

[DR. RICHARD SCHILSKY]

Thanks for having us, Nate.

[SUANNA BRUINOOGE]

Thanks.

[DR. NATHAN PENNELL]

So Rich, give me a little background on the problem that you were hoping to address with this paper. Why did ASCO feel it was important to provide a guidance to oncologists about interpreting testing reports and accessing these drugs?

[DR. RICHARD SCHILSKY]

Well, I think you actually framed the problem very well in your introduction. Obviously there's a lot of tumor genomic profiling that's going on these days, oftentimes for very good reason to identify actionable alterations that are known targets of effective anti-cancer therapies.

And what we've been seeing, of course, in more recent years is the more widespread use of genomic profiling, oftentimes for people who have advanced cancer, who no longer have any standard treatment options available. And the physician is looking to see whether or not there's something that might be considered actionable in the tumor genome that could provide a therapy option that wasn't considered.

We're also seeing that the testing itself has become much more expansive. So instead of testing for a few genes, many tests are now testing for hundreds of genes. And, of course, they can be many different alterations that could occur within any given gene. So the amount of information that's being provided to oncologists in these test reports is enormous and very difficult to interpret.
The nomenclature is difficult to understand. The biological relevance of the alterations is difficult to understand. And whether or not they really lead to a potential course of therapy is oftentimes difficult to figure out, because a lot of what turns up in the reports is difficult to understand and difficult to interpret.

So one of our goals in putting this short paper together was to try to provide resources to oncologists to help them navigate these test reports to help them have resources available to, in essence, look up the abnormalities that are being detected and try to figure out whether or not that's something that might be targetable with a particular drug. And then, of course, secondarily as you pointed out, to help walk them through the various strategies they can use to actually obtain the drug that seems like it might be a good choice for their patient.

[DR. NATHAN PENNELL]

So if I'm looking at one of these reports now and seeing these alterations, how do I decide if that truly is actionable or not? And how do we decide what level of actionability, whether this is something that's really a standard of care now or something that's much more lower level of evidence?

[DR. RICHARD SCHILSKY]

Yeah, it's a great question. So, I mean, there are actually some conventions regarding the level of evidence to assign to genomic alteration to determine its actionability. And in fact, ASCO working together with the College of American Pathologists and the Association of Molecular Pathology published a paper a couple of years ago, now, sort of assigning levels of evidence.

But the convention goes something like this-- if the alteration is the target of an FDA-approved drug, then that's a high level of evidence that the alteration is of clinical importance. It may or may not be of the same level of importance in a histology that is outside of the FDA-approved indication for the drug.

Best known example that is often described as BRAF mutations in patients with colorectal cancer, which do not respond nearly as well to BRAF inhibitors, as the same mutations respond when they occur in patients with melanoma. But nevertheless, a BRAF mutation occurring outside of the melanoma indication has still might be considered to be sort of level two evidence of potential actionability.
Then as you get further and further away from FDA-approved therapies or FDA-approved indications, then you get into lower levels of evidence. So you have, as you mentioned earlier, variants of unknown significance. These generally are alterations that are detected in the genome that truly are of unknown significance.
They have not been well-characterized. It's not clear what their biological relevance is with respect to being related to tumor initiation or progression. It's not clear whether they represent markers of response or resistance to therapy. They're just alterations where really more research is necessary to determine their actionability.

Nevertheless, I can tell you that we often find that many physicians think that it might be worthwhile to target APUS sort of just to give something a try. Then at the lowest level of actionability are the germline alterations. Now, even there, it's complicated because, of course, there are some germline alterations that actually direct you to use an FDA-approved drug, like germline BRCA mutations used to direct therapy with PARP inhibitors.

But generally speaking, germline alterations or alterations that have been well characterized and known to be functionally benign, there, the evidence for actionability would be considered to be very low.

[DR. NATHAN PENNELL]

I've certainly seen people treated with targeted drugs for variants of unknown significance and, otherwise, actionable genes, such as EGFR mutations but well outside the tyrosine kinase domain. And it really depends a lot on how well it's presented in these reports as to how easy it is to figure out what's actionable and what's not.

[DR. RICHARD SCHILSKY]

Well, that's right. And one of the reasons we included in the paper that quite expansive table of knowledge bases that are available is to help oncologists help participants who have elected a tumor board determine where to go to look up an alteration that might actually give them useful information as to, has it ever been reported before in human cancer?

If so, is it an alteration that is likely to be biological significance based upon the nature of the alteration and where it's located in the DNA? How close it is to other known ontogenic alterations and so on. So hopefully, readers of the article will find one or more of those knowledge bases' valuable resources, particularly in the context of a molecular tumor board discussion.

[DR. NATHAN PENNELL]

Absolutely. This is a fantastic resource. And I've got a couple of these bookmarked on my own desktop so that I can look things up, such as mycancergenome.org, for example. So I think our readers hopefully will check into that. So now that we have identified an actionable alteration, and we have a recommendation for a particular drug, what are our options for going about accessing these drugs for our patients?

[SUANNA BRUINOOGE]

Thanks, Nathan. This is a really good question. And I think we created a figure in the manuscript to really help clinicians and patients walk through what the options are laid out in front of them. And as you can see from the figure, it really does depend on the initial question being, does the targeted drug have FDA approval?
And as Dr. Schilsky mentioned earlier, it may depend on whether the indications specifically include the cancer type or histology that your patient has. But let's just say, then that case, it would be considered an on-label indication, and largely be reimbursed by insurers.

But let's say, the indication-- the cancer type is not specifically mentioned in the label. In that case, it would be considered an off-label indication. And so in that situation, there is a chance that the company or other researchers are already looking at whether the drug works for that same alteration and other cancer type. In other words, research on off-label indication.

And in these situations, as trials have been completed and results are published, they might be noted in either clinical pathways or drug compendia. Or it might be published in scientific journals, like the Journal of Clinical Oncology and Journal of Oncology Practice.
So in those situations where there is published data, and that supports the use in a different cancer type, then, you might be in a situation where Medicare or private payers might provide coverage for that off-label use. So in those situations, contacting the insurance companies is what we reference in the article to obtain authorization to prescribe the medication and get coverage.

In situations where there isn't published data, there might be clinical trials that are under way. And in those situations, obviously, the clinical trial-- you'd have to look at the eligibility criteria for the clinical trial. Is it something that's available at your clinic? If it's not available at your clinic, is it something that the patient could travel to obtain enrollment in the clinical trial?

So that's really on all along that left side of the figure related to whether the cancer type is mentioned on the drug label, whether there's published data. And the payer might cover it off-label, or if the patient would qualify for a clinical trial. If none of those are a possibility, then there still might be an occasion in which the patient would still be interested in accessing the therapy. And then you might want to look into financial assistance options for the patient. And in the manuscript, we talk about, there's recently been a compilation of patient assistance programs. And we include the website in our manuscript. And that does allow a clinician and a patient to look across multiple pharmaceutical companies to see if there might be patient assistance options available if it's already an FDA-approved approved drug.

[DR. NATHAN PENNELL]

Oh, that's great. So what about for patients who want to access drugs, but for whatever reason, don't have either an approval for off-label use, or there's no trial available? How would patients access drugs in that setting?

[SUANNA BRUINOOGE]

In that setting, you're probably thinking about a drug that's an investigational use if it does not have an FDA approval. And in this situation, there certainly may be circumstances in which a clinical trial isn't available. Or maybe your patient is not available at your site. Or maybe your patient doesn't qualify and meet the eligibility criteria or isn't able to travel for the clinical trial.

And in those situations, there may be options that you and your patient could explore through something called expanded access program. And there's really three options that are sort of broadly described as expanded access program. A company might offer a large or mid-sized expanded access program.

It's essentially like a clinical trial, although it may be collecting less data in the course of the clinical trial. It might be for a broader patient population who might not otherwise qualify for the clinical trial. And typically the company might conduct this as a broader access for patients who don't qualify for a clinical trial.

Or perhaps in the interim period between which a company submits its application to the FDA, and they're waiting to hear about the FDA review of the drugs. So these are often sort of in that interim time period before a drug might be approved.

The third type of expanded access program is an individual patient use. And this is something that is there's actually new resources that are available on a couple of different locations. There's an organization called the Reagan Udall Foundation. So that's Reagan as in the former president. And Udall-- U-D-A-L-L.

This is a foundation that supports the work of the FDA in a broad sense. And they have something that's called the Expanded Access Navigator Program that's available on their website. You are a patient Google Expanded Access Navigator. The Reagan Udall website will certainly become available in the listing.

And what this does is list all the companies that provide expanded access program. So this is a good starting point to see if a company might be offering either a large or midsize expanded access programs and also list the company context at the company so you can also figure out how to contact the company to find out if your patient qualifies.

If there isn't a program. Then fortunately, in oncology, we also have another option that clinicians can explore. The FDA Oncology Center of Excellence recently launched a program that's called Project Facilitate. And this provides both web-based resources, as well as a phone line that is available during business hours which are largely East Coast business hours.

And it's a resource for clinicians to contact related to individual patient access requests. And the FDA has staff who are very knowledgeable about the individual patient access pathway. They can help with contacting companies and sort of serve as an intermediary to help navigate those situations.

And the FDA role is actually in any of these three expanded access programs. The FDA plays a very important role in reviewing requests from clinicians. And they provide sort of a third-party review of the circumstances. And they're very quick to respond to inquiries in this regard and really do approve virtually all of the requests for access that they receive.

And so long as the company provides access to the drug, ultimately, the decision about whether to provide access to the drug is up to the company.

There is another avenue, which is described in our manuscript as well. Some states have also passed right-to-try laws. In these circumstances, these laws are at the state level. So not all states have passed them. But they provide a pathway that bypasses FDA review and assessment. They do not require that a company provide the investigational drug. So that circumstance is really still up to the individual company, whether they want to make the drug available outside of clinical trials.

[DR. NATHAN PENNELL]

I think a couple incredibly important things that I want to make sure everybody got out of this. One is that all of this relies on the pharmaceutical company actually being willing to provide these drugs. So even the right-to-try laws on the state and federal level don't require that the companies give access to the drugs to the patient. So both of those are necessary.

And second of all, that the FDA is incredibly helpful in providing access to these drugs. I've personally gone several times through compassionate use single patient's drug access through the FDA. And they've been tremendously helpful and never were in any way a barrier to getting access to the drug. They're fast and responsive.

And so I actually haven't personally heard much in terms of the use of the right-to-try laws to access drugs. I don't know if that's something that there was a lot of attention, of course, when the federal government passed the law. But I haven't heard much about it since then.

[DR. RICHARD SCHILSKY]

Nor have we. I don't think we're aware of any circumstances in oncology where patients have access to investigational drugs through the right-to-try pathway. That may be because the companies are reluctant to make drugs available. Or it may be because appropriate drugs just haven't been on the radar screen.
I think all of us, though, would agree that a much better way of providing access to drugs would be to do it in a way where you're actually collecting the information on the efficacy of the drugs and the toxicity of the drugs where you can learn about that process and help lead to an eventual approval. So what is ASCO doing that can help provide access to promising drugs, perhaps, an off-label setting for patients?

Many people know the TAPUR is an acronym that stands for Targeted Agents and Profiling Utilization Registry. So it's a quite a mouthful. And so we like to call it TAPUR. So TAPUR is a prospective multi-arm phase II basket trial, which is matching commercially available targeted drugs used to off-label against a genomic alteration in a patient's tumor.

So, in essence, we set up TAPUR to be able to learn from the off-label prescribing of targeted drugs to patients who have advanced cancers. And the study has been ongoing now since March of 2016. There are about 1,600 patients who have been enrolled at about 120 sites around the country.

We've started to report out both negative and positive results. And we think that negative and positive results are equally important in this setting, because, for example, if a doctor could prescribe a drug off-label, but there's no evidence that the drug actually is beneficial, then those patients are better served by being directed to other clinical trials.

So for example, last year, we reported that palbociclib is not effective in either pancreatic or biliary tract cancers that have a CDKN2A alteration. So the implication being, of course, that the next time a doctor sees that alteration showing up on a tumor genomic test report for a patient with one of those cancers, they probably should look for something other than palbociclib.

Now, alternatively, we've also begun to identify signals of activity that either have been already reported in more formal clinical trials. And we're just able to affirm that the therapy works in a more real world population or in some cases haven't really yet been identified.
So, for example, at this year's ASCO annual meeting, the 2019 meeting, we reported that pembrolizumab has activity in patients with breast cancer that have a high tumor mutational burden. And we think that's an exciting observation. Some of those patients actually had quite prolonged disease control and that the abstract has been presented.

The poster is available on the TAPUR website, tapur.org, for anyone who wants to look at the details. And there are some manuscripts of preparation. So TAPUR we hope over time we'll continue to report out both positive and negative results. They can't really help to guide the use of these well-sampled therapies. And, of course, it's also a mechanism, whereby the drugs can be provided to patients at no cost to them, because all the drugs in the study are being provided by the participating pharmaceutical companies.

[DR. NATHAN PENNELL]

Yeah, it really is a win-win situation. The patients get access to the drugs without having to worry about whether their insurance will cover the off-label use. And the companies learn whether their drugs may have expanded indications outside of where they're currently used.

Well, Suanna and Rich, thanks so much for joining me on the podcast today.

[DR. SCHILSKY AND MS. BRUINOOGE]

Thank you.

[DR. NATHAN PENNELL]

And until next time, thank you for listening to this Journal of Oncology Practice Podcast. I hope you enjoyed what you heard today. And if you did, don't forget to give us a rating or review on Apple podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode.

JOP's podcasts are just one of ASCO's many podcast programs. You can find all recordings at podcast.asco.org. The full text of the paper will be online at ascopubs.org/journal/jop in August 2019. This is Dr. Nate Pennell for the Journal of Oncology Practice signing off.

Dr. Pennell and Dr. Kircher discuss the push for increased price transparency among stakeholders in an effort to control the rising costs of healthcare. Read the related article on ascopubs.org.

TRANSCRIPT:

Welcome to the latest Journal of Oncology Practice podcast, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all recordings, including this one, at podcast.asco.org.

My name is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JOP. Americans are very familiar with comparison shopping for goods and services based on the price. I can buy anything from a car or a television to life insurance to hiring a contractor to remodel my home.

And I could expect that the price of that good or service is going to be easily available. It's going to be accurate. And then I can compare it to their competitors prices. So I can then make my decision based on that price and the quality of the goods or services.

But what if you wanted to shop around for your health care? How easily can we determine the true out-of-pocket costs for, say, a hip replacement or a screening colonoscopy? In truth, I bet aside from a purely cosmetic procedure, most people don't ever recall being told what the price is of a medical procedure before having it done.
So why is medicine different? And how does this impact the cost of health care? And what can we do to improve price transparency? With me today to discuss this issue is Dr. Sheetal Kircher, associate professor and GI medical oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Dr. Kircher is a member of the ASCO Health Equity Committee and was a recent ASCO Health Policy Fellow from 2018 to 2019.

We'll be discussing her paper, "The opaque results of federal price transparency rules and state-based alternatives", to be published in the August, 2019 JOP. Welcome Dr. Kircher, and thanks for joining me today.

Thanks for having me.

So first of all, can you briefly kind of review why aren't health care costs like other goods and services? And why isn't it easy to understand and compare between them?

There's a lot of reasons that health care costs are really just fundamentally different than really almost any other goods or services that I can think of. Taking your example of shopping for a TV, when you know which TV you want, you to go to multiple stores. You check to see if there's free online shipping. And you choose the lowest price.

Even if you don't know what TV you want, you can see what the cost is going to be. And this cost is going to be inclusive of tax, shipping. And you can even see what that cost will be if you had a coupon or promo code.

In addition to the cost of these TVs, we will see ratings, hundreds, thousands of people with commentaries on their experience with that exact product. So many times, you could even return it. So as we can see, health care is just really different. The stakes are higher.

So even when we use this word, cost, shopping around for health care, and things like that, already that kind of seems like a misnomer. For the individual case and the actual cost of a service, it's complicated. It's difficult to figure out because almost nobody pays what we think of as like the list price.

The literal list price for hospitals is called a charge master. A charge master is really just the list prices out the gate that a hospital comes up with and becomes a starting point for negotiation for payers. And then each plan will have a different contracted rate for that service.

And this is problematic, isn't it? Because the charge master is sort of the-- when people start, at least say with the federal regulations, that's the price that they're sort of trying to get people to put out there. But that's not necessarily all that helpful.

Exactly. And you know, in addition, because there's such variation in what the patient will actually pay at the end of the day after their insurance coverage kicks in, when you look at the hospital list of prices, it's difficult, even for myself with a medical degree, to understand what I'm looking at. For example, if I'm thinking of a single service, like a colonoscopy, there could be many components to a colonoscopy, such as the doctor fee, facility fee, pathologist, anesthesiologist. So even if you saw the word colonoscopy on one of these lists, it's impossible to really know if that's inclusive of all the components of that procedure.

So say a patient was able to actually get a hold of these contracted rates instead of the lowest prices. And then they were able to know all the components of that service. They would still need to understand the specific cost sharing details of their insurance plan, such as like how much the deductible is, what's their copay, what's their coinsurance. In my experience, and I think it's well-published in the literature, that most patients even struggle to just know what the definition of those things are, like your deductible, let alone what their actual amounts are.

You know, it does sound complicated. And obviously, I think a lot of doctors are familiar with the multiple different charges and whatnot. But at the same time, given the complexity of modern technology and whatnot it doesn't sound to me undoable for a particular hospital to bundle all of the costs of a single procedure together and to somehow link to what your insurance company should cover for that kind of thing. It does not seem to me like this is an undoable technological fix if someone wanted to do it.

I agree. There's been a lot of attempts, both at the state level and federal, to really address this issue. I mean, even taking a step back even further, institutions have tried to, at least for their patients, provide more accurate down at the patient level estimates of their costs. And as simple as it sounds, it is actually quite difficult. And the reasons are because a lot of people contracting from payers as well as insurance it still is very opaque, even in people that are highly skilled and trying to figure this out.
So if you are an actual patient, I mean, I think that the challenges just become even greater. But some states have taken some more kind of in the weeds active approach to improve price transparency in health care as a whole, including oncology. [INAUDIBLE] states have implemented or at least passed laws where they create something called an all-payer claims data set or APCDs.
What these are it's still a list of prices. I think it tackles some of these issues that we just talked about, because what these lists are, they account for the negotiated price, as opposed to the pre-negotiation charge master. So basically, it's the price after the coupon. You know, it's like the real price.

Most of these data sets, or at least many of them, have incorporated quality metrics. Now, I would have to say that the quality metrics between states is all over the map. Nobody has agreed on these quality metrics. But it's at least one more tool to help the patient in addition to cost to make decisions.
I think a kind of interesting point this all brought up as we were doing this work is almost like a bigger question of do patients want to comparison shop for their health care. So I mean, if my primary care doctor, who I trust and I know, and I've known for 15 years, recommends a procedure, so say a colonoscopy, I'm likely to choose the doctor and the facility that she recommends.

I don't even remember if you go to get a procedure, they usually don't even tell you ahead of time what the cost is and ask you if that's something you're interested in paying. Usually you just schedule it, and you do it. And you get a bill after the fact.
That would have to be a pretty big shift in the culture of how we approach paying for health care if we were going to start comparison shopping. You'd have to understand that you needed to do that to begin with. You'd have to know how to do it and how to compare these things. It's certainly not undoable. It's something, again, that we do for almost every single other thing that we buy, but it would require quite a major change.

Absolutely. And there's an even larger price transparency kind of movement going on. In relation to we were just saying about a patient-- say an oncology patient is starting chemotherapy. Federally, there's multiple different efforts that are trying to improve price transparency. So the oncology care model, one of the 13 kind of pillars of that care plan, one of them is delivering out-of-pocket costs before treatment starts.

Now, in oncology specifically, this is problematic and very challenging. You know, kind of trust me, we've tried. And we continue to try because when you think of the drugs we give oral chemotherapy, targeted agents, and then IV chemotherapy, we're not only dealing with totally different modes of treatment. We're talking about different payment structures of how cost sharing works.

So typically, IV chemotherapy is on our hospital outpatient benefits, while oral chemotherapy is covered by our prescription drugs. Now, both of those, in say Medicare for example, are completely different cost sharing structures. So the experience for a patient picking up their oral chemotherapy is at essentially a retail pharmacy or if it's perhaps a specialty pharmacy. But there's a cash register. And you're paying for it there.

The experience of paying for your IV chemotherapy is just like you described with the procedure, where you get it done. You get the bill at home. And just the experience alone is really different.
So federally, for this specific charge master display, so as of January 1st, all hospitals must publicly display their charge master. You know, like I said, these were never intended for consumer viewing. So they were first mandated to exist in the actually the Affordable Care Act. And the Trump Administration has really built upon this and said, why make patients ask for the charge master. How about we just require the hospitals to publicly display these? So that's where this kind of mandate came through.

It's interesting because as we went through this exercise in the publication, and the codes they use, the abbreviations, even with a medical degree, I had a hard time deciphering what they said.
Yeah, it does seem as though a lot of hospitals did not take this as a mandate to try to make this a transparent and useful thing. They said, well, the requirement is we're going to put it up. And here's our Excel spreadsheet or our PDF with all of the jargonese there. And you can do with it what you will.

Absolutely. And I wasn't surprised when we saw that even within four months of this being mandated, 88% of the hospitals we looked at in Chicago had it published. They were right on it. They had published it. And it was on their website. Because the ACA had already required that they have it. So really, they just took it out of the file folder and put it on the website without much thought that they were trying to make it helpful for patients.

A lot of disclaimer that a lot of, I think, hospitals overall did a really good job of putting kind of the fine print on there and saying that please speak to your doctor and facility to actually get the real cost. So I think the hospitals overall did a pretty good job of that.
As you and your authors point out, if someone actually did try to use that information to comparison shop, or what I would think perhaps would be more common, they would look it up just to see what the price is going to be forwardly placed they've been told they're supposed to go. They might see a $3,000 charge for their CT, which might have been completely covered by their insurance with no out-of-pocket expense to them at all and decide not to get it because they're afraid they're going to be charged $3,000.
Right. So in the hopes of having this transparent playing field, my major concern is even I, if I saw that amount of money, maybe that would make me pause a little bit actually. And I think the last thing we need to do, especially in these screening tests that there is no shortage of data saying that they improve survival. I want my patients to get them. There's enough barriers, I think, to getting someone a colonoscopy, that I would hate for that to be an unintended consequence of showing people the cost, especially in this inaccurate kind of forum.

So what can we do about this? What do you and your co-authors recommend to try to address cost transparency moving forward?
I think it's exciting that there is momentum here. I mean, I think price transparency, although has become a buzz word, it is going to continue to be an active issue at the state and federal levels. What makes this exciting to me is that it is bipartisan. So we all care about health care, to a different degree, and we all have different strategies.

But I do feel that this is a bigger discussion about transparency, not only here at the patient level, provider level, hospital level even. I really think I hope we're moving to a place where there is a bigger discussion of transparency at all levels. I'm talking even starting up at the manufacturer level.

But from a very practical patient level standpoint, we all encourage people to develop APCDs. There's interesting results that have been shown in some states that there is a good way to show people cost. And by doing so, programs, such as California's program, has actually shown that utilization of lower priced facilities has increased. And most importantly is that when patients are shown a cost and have some sort of way to impact or influence the amount of cost sharing that they will have based on their decision making, there is an opportunity perhaps for patients to choose lower cost facilities.

Now, even as I'm saying this out loud, my first concern and worry is making sure that outcomes are the same. And so I, first and foremost, care about complication rates for surgery and things of that nature. But there are state level programs that have shown that we can have both. It can be a dominant solution.
So I encourage states to especially have the flexibility to accommodate variations in state level health care markets, the states is really where these databases belong. And they should take it the next step further to make them interpretable, inclusive of all cost. And I encourage states and federally to work together to say if we're getting a colonoscopy, that includes services A, B, C, and D. So when patients are comparing, they're actually comparing apples to apples.

Evidence-based standardized quality metrics incorporated into these cost models will help us at least keep thinking about getting to this ultimate goal of value. And it's like hard not to plug when we're talking about cost and everything is this concept of value. And making sure that no matter what structure we choose to show people cost to have it impact their out-of-pocket cost sharing, those services as we have deemed in the evidence to be high value, the screening lung CT, the colonoscopy, really should be at a minimal cost sharing for patients, no matter what sort of structure that we have.

No, that makes perfect sense. One of the things that jumped out here, if you actually have data that using an APCD increase the number of patients moving to lower priced facilities from here, you mentioned from 68% up to 90%, the first thing that would occur to me is that that might actually end up driving down prices from competition, which is something that has never been a successful strategy in medical care for some reason.

Absolutely. The specific program I'm talking about from California is called CalPERS. And it's the government 1.3 million state employee programs. And really, the premise of that program is so interesting because it's the assumption that we can never really decrease the cost of care unless individual consumers are aware of the prices and have some sort of input into their cost sharing and decision making.
Oh, yeah. This is everybody is looking for ways to reduce costs. And when you see success like this, you'd think people would jump all over this. You'd think even hospitals and health systems would want to market that they have lower costs procedures to get more business. It's just very interesting that this is flying so under the radar.

Absolutely. And I do think, though, that there are more and more states actually jumping on board. So I'm hopeful in the next five, 10 years that as the real discussion of the value and value based care continue, this will really, I hope, will become more common.
And Dr. Kircher, thanks so much for joining me on the podcast.
Thank you for allowing me to discuss the paper.

Until next time, thank you for listening to this Journal of Oncology Practice podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode.

JOP's podcasts are just one of ASCO's many podcast programs. You can find all recordings at podcast.asco.org. And you can also find the full text of Dr. Kircher's paper online at ascopubs.org/journal/jop in August, 2019. This is Dr. Nathan Pennell for the Journal of Oncology Practice signing off.

Dr. Nathan Pennell and Dr. Jennifer Ligibel discuss weight management and physical activity programs for patients with cancer.

TRANSCRIPT:

Hello, and welcome to the ASCO Journal of Oncology Practice podcast. This is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JOP. I'm sure everyone who listens to this podcast is aware that obesity and lack of physical activity are major health problems in the USA, and they contribute to multiple medical conditions such as heart disease, diabetes. But how much do patients and oncologists know about how obesity and lack of physical activity impact cancer incidence or treatment or outcomes? And how do physicians manage these issues in their practice?
With me today to discuss this issue is Dr. Jennifer Ligibel, associate professor at Harvard Medical School and medical oncologist at the Dana-Farber Cancer Institute, where she also serves as director of the Leonard P. Zakim Center for Integrative Therapies and Healthy Living. We'll be discussing her paper, "Oncologists' Attitudes and Practice of Addressing Diet, Physical Activity and Weight Management with Cancer Patients, Findings of an American Society of Clinical Oncology Survey of the Oncology Workforce." Welcome, Dr. Ligibel, and thanks for joining me today.
Thank you so much for having me.
So just to set the stage for our listeners, how big of a problem is obesity and physical inactivity among cancer patients? Is this something that is generally mirroring the larger problem we see in America, or is there anything different about our cancer patients?
Well, we know that obesity and inactivity are risk factors for developing a number of different malignancies. The International Agency for Research in Cancer and the World Cancer Research Fund have both analyzed observational data linking obesity, inactivity, poor dietary quality to the risk of developing malignancy, and have demonstrated really consistent evidence that there is at least 13 different malignancies where obesity, in particular, increases the risk of developing the malignancy. So if you think about the fact that obesity and inactivity are pretty prevalent in the United States, in general, and that these factors also increase the risk of developing malignancy, we find that an even higher proportion of cancer survivors are obese and inactive as compared to the general US population. We also know that treatment that patients get for some malignancies can contribute to weight gain, and also can contribute to inactivity. So you put all of these factors together, and a very large proportion of cancer survivors are at risk for obesity, inactivity, poor dietary quality, or all of those factors together.
I mean, the number that you and your co-authors mention is that almost 1/3 of cancer survivors are obese. That seems like a huge number. So clearly a major problem.
Yes, that's true. And that number has increased significantly over the last decade.
So I know that obesity contributes to cancer risk. But is there data that even treatment of cancer can be impacted by these issues?
Yes. So we know that obesity has an impact on treatment-related outcomes and, likely, on the risk of recurrence and mortality in many different diseases. Breast cancer has been the best studied, where we know that women who are obese when they're diagnosed with breast cancer actually have a 35% higher risk of dying from breast cancer compared to women who are of normal weight when they were diagnosed with breast cancer.
Similar data are emerging in other malignancies. Colorectal cancer, there has been a strong link with obesity and cancer outcomes. Prostate cancer, gynecologic cancers, there's emerging data as well. So we know that these factors can impact the risk of recurrence and mortality. But there's also evidence that suggests that people who have excess adiposity, have metabolic complications of obesity, are at higher risk of complications like poor wound healing after surgery. They're at higher risk of lymphedema and some malignancies. They may be at higher risk of things like peripheral neuropathy related to chemotherapy. So there are a lot of poor outcomes associated with body weight in cancer patients.
Now, I know even dosing of chemotherapy, I believe, obese patients are at risk for under-dosing because people are afraid to give them proper weight-based dosing. So lots of reasons to pay attention to this issue. Is there data, though, that changing that-- intervening with helping patients lose weight or patients at risk losing weight, or increasing their physical activity-- mitigates these risks?
That is a great question, and one that will hopefully be answered within the next few years through a number of large-scale, ongoing phase III trials that are looking at the impact of weight loss, increased physical activity, better dietary quality on cancer recurrence and mortality. We don't have data from randomized trials, at this point, looking at the impact of lifestyle change after diagnosis on outcomes. But we do have a lot of observational data that suggest that individuals who are physically active are at lower risk of recurrence in malignancies like breast cancer, colon, and prostate cancer. And we do also have a lot of information from randomized trials that are smaller in scale that demonstrate that losing weight, exercising more has an impact on shorter-term outcomes, like quality of life, cancer-related and treatment-related side effects like fatigue, neuropathy, joint pain. So we know there are benefits of lifestyle change after cancer diagnosis, but we're still awaiting these large-scale trials that will show us whether changing these behaviors actually reduces the risk of recurrence and mortality.
So already enough evidence that it's important that we address it, but hopefully, we'll have more convincing evidence soon. Can you take us through the ASCO survey? What was the background to doing the survey, and what did it try to assess?
So in 2014, ASCO launched an obesity initiative that really sought to educate the oncology workforce about the connections between obesity and related factors in both cancer risk and outcomes, and to provide tools and resources to help oncologists talk to their patients about physical activity, weight management during and after cancer treatment. There was also a part of the initiative that focused on research and advocacy.
We were interested, given that 2014 was a number of years ago, to look at what were the current attitudes of oncology providers toward these topics? What was their practice? Were they talking about weight? Were they talking about physical activity and diet with their patients?
And what did they perceive as barriers to really implementing behavior change after cancer diagnosis? And so we designed a survey that would be delivered to individuals that were currently seeing oncology patients. And they could be physicians, they could be nurse practitioners, they could be dietitians or anyone that was currently working with oncology patients and was an ASCO member. And then we asked them questions about their practice, about the attention that they paid to these topics, about what they felt got in the way. And then thinking more broadly about how important did oncology providers think that these topics were in the scope of their practice.
Why don't we just jump right into the results? So what were the results from the survey?
So first of all, we found that the people that filled out our survey were pretty typical for the general ASCO membership. So about 2/3 of the people that filled out the survey were based in the US. The other 1/3 were international. We did have a higher proportion of medical oncologists, partly because this was limited to people that were actively seeing patients. We had a nice balance of private practice and academic centers, and we had individuals that were treating all different kinds of cancer. So we were happy with the population that filled the survey out as being fairly representative of oncology providers in the US and more broadly.
We found, when we asked the providers what were their perspectives on issues related to obesity and cancer, that there was a very strong agreement that obesity impacts treatment outcomes in cancer patients. And in fact, more than 90% of the survey respondents strongly agreed or agreed with that statement, which we were very excited to see. There was also high agreement with addressing a patient's weight should be a standard part of cancer care. And most of their respondents felt that it was the responsibility of the treating physician to recommend healthy diet, regular activity, weight management for patients in whom that was relevant.
But there was much less agreement that the oncology workforce felt that they were prepared to be either delivering those interventions or that they had enough information or enough training to really feel comfortable in their skills to help patients start to make these changes. So I thought that was very important that there was high agreement that these things were important, but also a feeling of there needed to be other parts of the health care team that could help patients once these issues were identified in really helping them to make the changes that needed to after diagnosis.
We then asked providers about what they were doing now, and we found that the vast majority of providers that completed the survey indicated that they were asking patients about their physical activity patterns, about their diets. They were assessing patients' weights. And this was both during and after cancer treatment. There was a much lower proportion of survey respondents that were actually making referrals to dietitians, to weight management services for their patients. So although there was a lot of discussion and there was an assessment, there wasn't necessarily the next step, which was helping patients actually incorporate these changes through a referral to a skilled provider.
And then, the last piece was looking at barriers. And I think that this was something that we were actually a little bit surprised about some of the responses. The last part of the survey focused on looking at the respondents' perceptions of barriers. What did oncology providers feel like was getting in the way of patients changing their diets, exercising more, losing weight when it was relevant?
We found that, not surprisingly, lack of time for counseling was something that many providers noted, lack of available resources. So even if you identified that a patient wanted to lose weight or meet with a dietitian, there wasn't necessarily someone that was available. Lack of training or expertise on the part of the oncology provider was also noted. We also found that the majority of participants felt that patients' resistance to behavioral interventions was also a large barrier to helping people make these changes. And this really led us to think start thinking about, well, what is the patient's perception?
And I think that's something that we did not cover in this survey, but that is really critical. Because if we find that oncologists are talking about these topics and are trying to reinforce the importance, but patients aren't hearing that or aren't making these changes, then we're really not accomplishing what we want to. So I think from this survey, we now can see what oncologists feel is important and what they're doing in their practices. And we need to figure out, what are the patients hearing and what is the result of the advice that the providers are giving to patients?
Yeah, that really is an interesting and kind of a surprising piece. So the first part resonates with me. So I certainly address, you know, in my patients that are in follow-up and survivorship, exercise and trying to maintain a healthy weight. And I also feel that I'm not super comfortable with trying to intervene in that myself, but rather try to suggest that they look for SilverSneakers or some sort of local exercise gym or other opportunities or, perhaps, refer them to a dietitian.
But I don't know that I have a perception that the patients wouldn't welcome that advice or that they might be resistant. Is there any plan to try to get an assessment of cancer patients' attitudes on this?
So this is something that we are planning at this time. We are trying to develop a survey and partner with some patient advocacy groups to really better understand what the patients' perceptions of these topics are. There is not much currently in the literature, but there have been some assessments. There was a large study that was done in the UK that looked at patients with colorectal cancer and the attention that was paid on the part of their provider to exercise. And if patients remembered hearing about exercise, they were much more likely to do it.
So I think that something that we really need to better tease out is, what is the patients' receptivity to this type of information? And are the suggestions that oncologists are making enough to get patients, on their own, to seek out a program? Or do we really need to try to educate providers about effective ways of making referrals?
I think the reality is that we also need more programs that patients can be referred to. And something that I think is a real need within the oncology space is programs that help people lose weight that are able to help people become more active, and recognizing some of the limitations that many patients have as a result of their therapy. Things like lymphedema, things like neuropathy, that can be barriers. How can we manage those in oncology patients to help them successfully achieve these behavior changes?
And this is, I think, such a great topic because patients really care about interventions that they can do themselves to help their cancer care and their health. And there's so much out there, in terms of complementary therapies and whatnot. But we have real data on things like diet and exercise, and I think more attention being paid to this within cancer centers would really be welcomed by patients.
I think so too. You know, we, right now here at Dana-Farber, are leading a trial called the Breast Cancer Weight Loss Trial that's a phase III study looking at the impact of a weight loss intervention on recurrence in women who are overweight or obese when they're diagnosed with breast cancer. And when we started this study, we weren't sure what the uptake would be. It's a very different type of model. But we've enrolled now more than 2,000 patients in less than three years. So there's definitely a very, very significant interest in this topic amongst patients.
There's a similar trial going on in ovarian cancer that just enrolled 1,000 patients with a disease that's much less common than breast cancer over just a few years. So I think that the interest on the part of patients in this topic is large and we want to be able to provide them with evidence-based recommendations. There's a lot of stuff out there that's not so evidence-based, especially about diet, and I think that, as oncology providers, we really owe it to our patients to get them the best information that we have about things that they can do to help improve their outcomes and to make themselves feel better during and after their cancer treatment.
And we're very lucky to work at institutions like the Dana-Farber Cancer Institute or here at the Cleveland Clinic, where we've actually got a lot of resources devoted to these efforts. But what can people who work at smaller institutions, or really don't have a lot of infrastructure for this, where can they access data or suggestions on how they can counsel patients or help their patients address problems with obesity and lack of physical activity? Is this something that ASCO can help with?
So as part of the ASCO Obesity Initiative, we developed toolkits for oncology providers and for patients about the role of weight management and physical activity in cancer. And so those are available at cancer.net. They can be downloaded. You can give them to your patients to start a conversation about the importance of these topics in oncology care.
The American Cancer Society also has diet and exercise guidelines for cancer survivors that oncologists can use as a guideline. The American College of Sports Medicine also has a website where they have oncology-trained exercise professionals in different communities. So if a patient wants to work with a trainer that has an understanding of the complications of cancer treatment and the side effects that patients have, that's another good resource.
The other thing that is available in many communities is the Livestrong at the YMCA program, which is a free exercise program that's offered for cancer survivors. This is offered now in more than 700 YMCAs across the country. It's a 12-week program that includes both aerobic exercise and strength training. And this is a resource that I send a lot of patients to, and that is available to people not everywhere, but increasingly more places. So that's another good resource for oncologists and for patients across the US.
Well, that's fantastic. So good, I'm glad we got to plug that on the podcast. And Dr. Ligibel, thanks so much for talking to me today.
Thank you.
And I also want to thank all of our listeners out there who joined us for this podcast. The full text of the paper will be available online at ASCOpubs.org/journal/JOP in June 2019. This is Dr. Nate Pennell, for the Journal of Oncology Practice, signing off.

Dr. Pennell talks with Dr. Patrick Conner Johnson, hematology oncology fellow at the Dana Farber Cancer Institute Massachusetts General Hospital fellowship program about his and his co-authors' new study titled "Potentially avoidable hospital readmissions in patients with advanced cancer."

Hello and welcome to the ASCO Journal of Oncology Practice podcast. This is Dr. Nate Pennell, medical oncologist at the Cleveland Clinic and consultant editor for the JOP. Potentially avoidable hospital readmissions are a major target for reducing costs in the health care system. However, for cancer patients, the issue goes way beyond cost.

Many of our advanced cancer patients have a limited lifespan. And every unnecessary day they spend in the hospital is one less day they spend at home with their loved ones. The reasons behind cancer patient readmissions may differ from other types of patients. And so broad efforts to reduce hospital readmissions may not apply quite as well to this population unless we understand the specific reasons behind readmissions for our vulnerable population.

Today we're going to be talking about this topic with Dr. Patrick Conner Johnson, hematology oncology fellow at the Dana Farber Cancer Institute Massachusetts General Hospital fellowship program about his and his co-authors' new study titled "Potentially avoidable hospital readmissions in patients with advanced cancer," which was published in the May 2019 JOP. Welcome, Conner, and thank you for joining me today.

Nate, it's truly an honor to be on the podcast. I appreciate your time and [INAUDIBLE].

So first of all, can you give us a little bit of background on why hospital readmissions are a topic that people are talking about? How big of a problem is this and what's the scope of the issue?

To start with, just hospital admissions period are a major topic within cancer care and all of medicine. If you go back to the health care cost and utilization project report since 2009, more than 4.5 million cancer related hospitalizations amongst adults. So that's hospitalizations.

Some percentage of these are potentially avoidable both in the general medicine literature and in the oncology literature. and both from a cost and value standpoint and from quality of cancer patients' lives, I think these are important issues to think about in terms of addressing.

And then when we looked, particularly in our study, we focused on readmissions by which we define having a panel of patients who already had admission once and then looking at subsequent admissions after that.

There is a fair amount of literature out there looking at causes of hospital readmissions as a target for improving value based care. What do you think is different about cancer patients that makes this something we need to study uniquely in them?

I think, in general, amongst a variety of different subspecialties, there's an importance in focusing on targeting each individual population to understand the nuances of that population, whether that's a literature on COPD or heart failure. And oncology in particular is still a wealth of drugs with a wealth of potential consequences and with a sub-population within oncology of advanced cancer patients who have defined limited lifespans.

There's a whole host of factors and different unique circumstances that could potentially affect their readmission profile a little bit different than other general medicine populations. And I think the greater understanding we have of each subset of patients within a number of disciplines is probably going to target our interventions to be more likely to be successful.

And I think that makes perfect sense. One of the other things you mentioned in the background section of your paper is that many of the studies looking at potentially avoidable readmissions have not incorporated patient reported outcomes. And why do you think that would be an important thing to include in the study?

I think looking across oncology care, the study by Dr. Schrag and Dr. [? Basch ?] and colleagues comes to mind. There's been an increasing interest in incorporating patient reported outcomes in order to better pair these with our other outcomes.

And I think that our hope with this was to gain a greater understanding of what kinds of symptoms and other things patients report and trying to identify if there is any correlation with admissions. And the same thing's being done across a number of different facets of oncology care.

Yeah. I'm not sure people outside of oncology understand that there's a significant percentage of our inpatients are admitted for symptom control specifically as opposed to general medicine problems like pneumonia or blood clots.

And so definitely in that case being able to assess their symptom burden makes perfect sense when you're trying to do the kind of study that you're doing. So speaking of your study, can you walk us through the design? How did you put this together?

So this was a longitudinal cohort study of consecutive patients that were admitted to the hospital. And patients were enrolled. And as part of their enrollment, their symptoms were assessed at the time of their enrollment.

So this was a one time symptom assessment within two to five days of their hospitalization when they completed a symptom burden questionnaire essentially. We took available data that we had.

And we had two coders go back, review the medical record with a focus on the discharge summary to try and understand the reason for hospital admission. And then we had a peer review system to try and identify which readmissions were potentially avoidable.

And we used some adaptive criteria, which has been utilized in some other studies in leukemia an GI cancer. And that process was essentially two physicians doing an initial coding review using these criteria. And then anything that was considered potentially avoidable by either of those physicians went to a panel that included two board certified oncologists.

Yeah. I'm curious about this. I know that there are published methods for how they do this. But can you give us an example? How do you determine if a patient had an a potentially avoidable readmission? What's an example of something they might find.

There's no question that it's a challenge. And it's rife with some subjectivity at times. In order to try and minimize that, we have defined criteria. For an example, one of those is premature hospital discharge, which in this study was defined as being readmitted within seven days of discharge with identical symptoms to the prior admission. And that's by a review of the hospital discharge summary.

OK. That makes perfect sense. And you would think that that would be a significant risk for patients since the length of stay is such a big target for hospitals to try to reduce costs. And also our patients typically want to go home.

You know, we have to sometimes convince them to stay when we think they need to stay. OK. So if they were readmitted within seven days with the same symptoms that's how you determine that. So tell us some of what you found.

Thanks, again. Major points from our paper are, first, similar to some other studies that try and look at potentially avoidable hospitalizations at large. More than 30% of the admissions were qualified as potentially avoidable readmissions, which I don't think is anything that has ever been described.

Again, that's fairly consistent with actually the general medicine and with some other oncology literature, but it speaks to the importance of the topic and the sizable possibility of interventions down the road. And the two major important risks that we identified in a multivariable model were marital status, and which we think is a proxy for social support and was protective against potentially avoidable readmissions, and higher physical symptom burden.

And those with higher physical symptom burden were more likely to have potentially avoidable readmissions. And finally, when we looked at the most common reasons as using our criteria for potentially avoidable readmissions, those were premature discharge from a prior hospitalization and also not having what's called a timely follow up, which was a seven day follow up. And so that speaks in our mind to the hazardous time period that is the discharge is fraught with a lot of possibilities of difficulty in terms of making that transition.

Yeah. I think that makes perfect sense. I know our institution in particular has instituted a mandatory call from the outpatient team to a patient the day after they're discharged to just check and see how they're doing. And then we try to get everybody an appointment within seven days although that's not always possible. Are there any other interventions that you think would come out of what you found that might help reduce potentially avoidable readmissions?

I think from the social support side of things, given that social support can be challenging, there is an idea that if we identify patients with that limited social support that that might be the patients that we target for patient navigation programs, more intensive social work involvement programs, or a specially designed care transition programs at hospital discharge as well as potentially patients who have a higher physical symptoms.

And the association with higher physical symptoms also makes perfect sense, although that's always a challenge to address appropriately. I know that there's a lot of focus certainly in solid tumors about integrating palliative medicine and [INAUDIBLE] of medicine support for patients with solid tumors to control that. Is that something that you think could be helpful in this setting as well to help reduce readmissions?

Absolutely, Nate. I think that the hope would be that this also raises a possibility of identifying a patient population that may already be plugged in with palliative care. But if they're not, this could help identify another group of patients that can benefit from integrated palliative care with the hope being that we can identify interventions that can reduce their hospitalization burden.

And where do you think we're going to go here in terms of research. So you've identified some nice potential associations. And there's some low hanging fruit in terms of arranging fast follow up. But what's the next steps in terms of trying to reduce potentially avoidable readmissions for our patients?

I think an integrative palliative care interventions for those with high physical symptom burden. And I think that targeted interventions such as more intensive social work involvement or care transition programs for those with limited social support would be potentially good intervention based studies to start with.

I also think that, as you mentioned, you raised good points about there's still a good bit of research to having a greater understanding within the world of oncology. What is the ideal follow up after discharge for each sub-population even within oncology? And there's probably a great deal more research into understanding that as well as more about the physical symptom burden of hospitalized patients in oncology.

I don't know what your opinion is. Do you think we'll ever be able to avoid almost or all potentially avoidable readmissions?

No. I don't think so. I think that it's a patient population that has a high symptom burden and has a high complexity of care. But I do think that any interventions to reduce the burden of hospitalizations could potentially have far reaching consequences.

I know. I agree with you. I mean there's no way we'll ever be able to avoid this completely. And we all have experience with patients who we can tell when we're getting ready to discharge them that they're at high risk of not successfully transitioning home and yet they want to try.

Perhaps they might be better off in a facility where they could have a higher level of care. But they really want to try to get home. And we want to give them the chance to succeed. And it's just not always successful. So giving them every resource that we can sounds like the right thing to do.

[INAUDIBLE] I agree with you totally. I think the other point to mention is just that the care transition time is a very fragile one. And other interventions to try and improve that transition period as well are something that would be of interest for us or other folks to explore around this topic.

Yeah. It sounds like that would be ripe for a quality of care study to look and see if really intensive interventions in that first few days or a week after discharge can reduce this. I know that we've moved forward with doing that, but I'm not sure if we have any data that it's effective. But it certainly makes sense that it would be helpful. Connor, thank you so much for talking with me today.

Thank you so much for having me.

And I also want to thank all the listeners out there who joined us for this podcast. The full text of Dr. Johnson's paper is available online at ASCOpubs.org/journal/JOP in the May 2019 issue of the JOP. This is Dr. Nate Pennell for the Journal of Oncology Practice signing off.