Dr. Manish Shah (Host): Welcome to Weill Cornell Medicine CancerCast, conversations about new developments in medicine, cancer care, and research. I'm your host, Dr. Manish Shah. And today, we'll be talking about cancer survivorship.

Our guest today is Dr. Emily Tonorezos. Dr. Tonorezos is the Director of the Iris Cantor Cancer Survivorship Program at Weill Cornell Medicine, where she helps individuals transition from active cancer treatment to long-term wellness.

Prior to joining Weill Cornell, she served as Director of the Office of Cancer Survivorship within the Division of Cancer Control and Population Sciences at the National Cancer Institute where she led efforts to support investigators and survivorship-related research.

Dr. Tonorezos has published widely on the multitude of issues facing people who have been diagnosed with cancer, including cancer delivery, and emerging areas of survivorship science, such as side effects from newer therapies. Welcome, Dr. Tonorezos.

Dr. Emily Tonorezos: Thank you so much for having me.

Dr. Manish Shah: So more people are surviving cancer than ever before. According to the American Cancer Society, the overall five-year survival rate across all cancers in the United States has reached a historic 70%, translating to nearly 19 million cancer survivors worldwide.

People both live longer with and after cancer, but also more people are being diagnosed at an earlier age. By any metric, the field of cancer survivorship is growing and will only continue to grow. We need to have better tools and research in caring for people who survive cancer.

Dr. Tonorezos, let's begin with the basics. So, what is cancer survivorship and what does it mean?

Dr. Emily Tonorezos: This is an excellent place to start the conversation, because we've struggled as a field with this word cancer survivor, and we've talked about whether we should be using different terms, but the diagnosis of cancer is really life-altering for many people. And we got this word cancer survivor actually several decades ago from the cancer survivor advocacy community, where they told us that they wanted to be referred to that way.

And the definition says that a person is a cancer survivor from the time of diagnosis through the balance of life, and that cancer survivorship is all of the things that happen to a person and their family and their job and their life during and after the diagnosis of cancer.

Dr. Manish Shah: It seems all-encompassing. Do you want to expand on that a little bit?

Dr. Emily Tonorezos: A few years ago, actually, my predecessor in the Office of Cancer Survivorship, Dr. Deb Mayer, she clarified that a person is a cancer survivor, whether they are on treatment or off treatment, and whether they are living with cancer or free of cancer.

So, we had always said it's from the time of diagnosis forward. But with that additional language, it really called out this growing population of people who have been diagnosed with advanced or metastatic cancer and who are living for many years after that diagnosis. And as a result of that change, we really pushed for more research in that population, which has happened over the past few years.

Dr. Manish Shah: That's amazing. And I think that's so important. Once you have a diagnosis of cancer, your life changes. And there are different phases. There's an active treatment phase. There's a phase for life after treatment. And both of those need survivorship care. The other question that this brings up is then who provides that care? When you're in active treatment, often your closest healthcare provider is your oncologist. But after the treatment of cancer, it may or may not be your oncologist. What are your thoughts on that?

Dr. Emily Tonorezos: You're absolutely right. And one of the things that we've realized as a field is that having primary care providers and generalist providers involved in cancer care from the time of diagnosis is very important for many people. One of the reasons for that is that their cancer is expected to be treated and even cured. And so, that is a person who needs comorbidity management, who needs surveillance for other types of cancers, who needs maybe support in health behaviors like exercise or quitting smoking. And all of that is in the realm of primary care and really should be managed, even during treatment, by primary care clinicians or physicians.

Dr. Manish Shah: I think sometimes as oncologists, we don't realize the importance of this. There was just last year a publication in the adjuvant treatment setting for colon cancer, where they prescribed active physical activity as a treatment in addition to the standard treatment of chemotherapy in the adjuvant setting.

And remarkably, there was truly a survival advantage in patients who had an exercise program prescribed to them. In that study, they had to reach 10 met hours per week, which is effectively brisk walking for 10 hours a week. But they had to maintain that and get to that goal. And that was associated with a survival benefit on the similar range of what the chemotherapy itself was getting. So, it's actually not a small thing. This additional impact of how you live your life.

Dr. Emily Tonorezos: I really appreciate that example.

Dr. Manish Shah: The scope of this is actually quite enormous then in terms of cancer survivorship. You recently published on how many people are cancer survivors either with rare diseases or people who are diagnosed at a young age. Do you want to talk about that?

Dr. Emily Tonorezos: Those two papers that you mentioned were part of this overall effort where we've been trying to describe some emerging populations of cancer survivors that have not gotten as much attention historically. So, we published a paper on the prevalence of people surviving rare cancers in the United States, and we published a paper on survivors of adolescent and young adult cancer. And we found that for the AYA population, there were over 2 million survivors in the United States with a history of a diagnosis of cancer between the ages of 15 and 39.

Dr. Manish Shah: That's just an enormous number of people. And of course, not all of them will need additional support. But even, let's say 5% or 10% of them, that's a huge number. That's 200,000 people that may need additional support from the diagnosis and the management of their cancer.

Dr. Emily Tonorezos: Yes, absolutely.

Dr. Manish Shah: What kind of challenges do cancer survivors face, once they've finished treatment and what are the common things that people complain about in your experience?

Dr. Emily Tonorezos: Well, there are categories of issues that people can face. There's the category of side effects from treatment. So, that might be something like fatigue or dry mouth. It could also be something related to maybe going through menopause as a result of cancer treatment. So, that could be symptoms of menopause or osteoporosis or related to that.

And then, there are the psychological and psychosocial effects. So, those are things like loneliness, distress, sometimes anxiety, maybe concerns about why am I here? The thoughts of what is the purpose in life?

And then, there are a whole bunch of things related to how your life is being lived. So certainly, we would put in that category, return to work, the effect that cancer diagnosis has on people's relationships, romance, financial distress, all of those things related to the roles that you have in your life.

And then, there is the category of subsequent cancer. So people, either as a result of their treatment or just because of aging and other environmental factors are at-risk for cancers besides their primary cancer. And so, all of those things need either surveillance or screening after treatment. There is even more, there’s things related to genetic risk, health behaviors like we talked about, but those are kind of the general categories.

Dr. Manish Shah: That seems all-encompassing. So, maybe give us a sense of that, because new treatments and targeted therapies or immunotherapies are able to have so much success, and especially if you apply them early, even patients with very advanced cancers, maybe their cancer can sometimes be eradicated.

So, the problems that you've been discussing are those that are related to the treatment in part, as well as other things. Are there different prevalences? Because, for example, germ cell tumors are treated with a lot of platinum-based therapy. And I know, there's a study that suggests that people that receive platinum-based therapy, they age earlier and their actuarial survival might be a little bit less. And some thoughts are that treatment for cancer essentially causes aging to happen earlier and there's a decrease in telomere length and things like that. So, there's some science behind this, as well. Can you speak to that?

Dr. Emily Tonorezos: So, this is actually a very important emerging area of research, which is the idea that being treated for cancer somehow contributes to accelerated aging or maybe aging processes. And what we understand or what we've learned so far is that there are some mechanisms like telomere length, like inflammation, some of the other hallmarks of aging that are affected by specific cancer treatment. And then, we have some ways of assessing people's age that relate to how many comorbidities do you have, or what kind of illnesses are you suffering from.

For example, we would think of osteoarthritis as a disease of aging. It's something that happens to older people with wear and tear on the joints. But we see it in young cancer survivors as well. So, there are lots of ways to think about that idea of accelerated aging. And, it's actually a very exciting and interesting place to be doing research.

I will also say this is a place where those health behaviors become so important because we know that, for example, exercise has effects on the hallmarks of aging and can improve or reduce or even eliminate a lot of those aging-related effects.

Dr. Manish Shah: So, some of these issues or medical aspects of the treatment, like cardiac issues or aging or chronic fatigue or neuropathy, are there things that we can do to reduce their impact for patients who are survivors or maybe even reduce their prevalence as we treat patients?

Dr. Emily Tonorezos: I think, across the board, we know that exercise is beneficial. There is a lot of current research on what aspects of exercise we should be encouraging, what type of exercise or what intensity and duration. But we know that moving is better than not moving across the board for every person, whether at-risk of cancer or diagnosed with cancer.

So, exercise for sure is beneficial. And we are still even learning all the ways that it's beneficial. But for me, I think from a health behavior perspective, the best exercise is exercise that the person will do. So, if there's something that you like or that appeals to you, that you enjoy doing, then that's the exercise you should be doing.

There are also some things we know about other health behaviors. Certainly, it's to your advantage to avoid alcohol or drink alcohol as little as possible. We don't know exactly what dose of alcohol seems to be dangerous for people who've been diagnosed with cancer, but we do know that generally speaking, less is better.

And also, some elements of diet seem to be beneficial, particularly for a cancer survivor. So, plant-based diet seems better than a diet with a lot of meat, especially grilled, smoked, and barbecued meat seem to be detrimental to cancer survivors. We think that eating during the day is better than eating at night, and there are some ongoing studies on intermittent fasting and time-restricted eating with the question of whether those are extra beneficial for people who've been diagnosed with cancer.

And also, a major feature of the American Institute of Cancer Research or World Cancer Research Fund Recommendations for cancer survivors is a focus on fiber. That does seem to be very important for cancer prevention and for cancer survivors, as well. There's the most research in breast cancer, but it's probably true for other cancers as well that a diet that's higher in fiber will have a lower risk of cancers, whether it's your first cancer, or a second or later cancer.

Dr. Manish Shah: That's really remarkable. So, exercise is critical, limiting your alcohol intake. How about medical therapies? Like, if someone has chronic fatigue or treatments for neuropathy? I know that there's some work on nerve stimulators for neuropathy, as well.

Dr. Emily Tonorezos: Yeah, that's an excellent point. And some of that work is going on here at Weill Cornell in our rehab and physical medicine program where they are testing interventions for cancer survivors. We certainly see a lot of neuropathy, decreased range of motion; as I mentioned, osteoarthritis, all kinds of musculoskeletal side effects after treatment. So, it's possible nerve stimulators will be part of those treatment paradigms in the future. It's really exciting work going on for sure.

Dr. Manish Shah: It occurs to me that all of these things, if you're not thinking about it as a healthcare provider, seeing a patient who had a history of cancer, you may chalk it up to other things and not appreciate that this is a real thing that can happen from the treatment of cancer or its management. I guess that's a key argument for the real impact of actually having someone who's a cancer survivor maybe see a specialist, in conjunction with their primary care doctor. What are your thoughts on that? There must be different models.

Dr. Emily Tonorezos: Yes. And you're struggling with the exact debate that's going on in the research as well, which is what is the best model for cancer survivors? We know that about two-thirds of cancer survivors are seen in primary care settings, and primary care clinicians are the backbone of our healthcare system in this country.

So if we could somehow, make sure that primary care clinicians are informed on the issues related to cancer survivors, that seems to be the best method in terms of reaching the largest number of cancer survivors. But the fact is that there is not a lot of awareness across the board, whether in oncology or in primary care about what people are at-risk for after diagnosis and treatment of cancer. So, that's something we're actively working on.

I'll also say that historically most of what we've done as a country to try to care for cancer survivors relies on the survivor themself. So, we do things like give the survivor a treatment summary and survivorship care plan, and then that survivor is supposed to take that information to each provider who they see and share it with them. And those sorts of interventions really do not work very well, quite honestly, because we shouldn't be asking the survivor to coordinate their care. We should have the system in place that coordinates the care for them so that they don't need to be responsible for remembering what tests they need or what specialists they should see. But there is a huge need, and a lot for us to figure out.

Dr. Manish Shah: Yeah, I find that actually very challenging. Because in my practice, when I'm seeing someone who has had cancer, has had their treatment, and now we're in a surveillance mode, I routinely will see them every six months or sometimes every year. And the healthcare system isn't set up in a way to hold the hand here, I feel like.

Dr. Emily Tonorezos: Yes, you're right.

Dr. Manish Shah: I think that's where patients often lean on their families or their loved ones to try to make sure that things are on track. But it is challenging. And I think another area that's challenging, we practice in a large metropolitan area where there's access to super specialists. But that may not necessarily be the greatest thing, because the specialists are focused only on the thing that they super specialize in. And we need someone to take a more holistic view, because there's so many different processes that could occur that need follow-up.

Dr. Emily Tonorezos: You're absolutely right. I'll just point out that, in my practice, so mostly I'm seeing breast cancer survivors, and especially among women who are over the age of 70. Many of them, if they weren't coming to this program, would not be getting a breast exam. So, we have something that, at one point, could have been part of sort of generalist care, but has become part of specialty care. And what that means is that, if you're an older woman, maybe you're no longer seeing a gynecologist, even though you're a breast cancer survivor, you're not getting a breast exam, what would be considered a very basic component of follow-up care.

Dr. Manish Shah: Let's talk about some of the emotional and social aspects of survivorship care. What are the common themes that occur in those realms?

Dr. Emily Tonorezos: Mental health is a huge gap. Our patients are experiencing distress. They feel worried. They maybe are depressed. And we have very little resources for getting them mental health care just from a general perspective in this country. And even in New York City, it can be quite difficult. So, I find that to be especially challenging.

Historically, the psychological and psychosocial effects of cancer diagnosis and treatment have been the largest part of the NIH portfolio on survivorship research. So, it's actually been quite a long time that we've been studying things like fear of recurrence and the whole field of psycho-oncology, which was started by Jimmie Holland at MSK. That is a field that has been around for many decades. But still, it's a huge need and we just don't have enough providers. It's a huge gap across the board.

Dr. Manish Shah: Are there support groups for cancer survivors to talk about these things and to raise awareness and things like that?

Dr. Emily Tonorezos: Yes. That is one thing that Weill Cornell and NYP do very well, which is we do have social work-led support groups that are available here for our patients. And they have support groups also available in some situations through the surgery departments, as well. So, we have one here in breast cancer surgery. They are divided into younger survivors and older survivors. And sometimes by other characteristics as well, depending on the need.

Dr. Manish Shah: That's so critical. The variety of issues and concerns that can arise are so wide that it almost feels that it is also helpful to have the specialist. So, what I'm speaking about is, for example, we have a program in cardio-oncology and patients, with regard to cardiac risk or arrhythmias, that might be one area of specialty that is unique. And then, the other area is infertility where we have a leading program. And I wonder, is that something that you see in your younger population of survivors?

Dr. Emily Tonorezos: Oh yes. In terms of both how cancer impacts their fertility and how they want to plan their family building, during and after, yes, definitely a huge issue.

Dr. Manish Shah: It's something that needs to be proactively managed. I mean, at least in the cancers that I treat, for example, if you're a young woman with rectal cancer, radiation might be a key component of that. And then, that does affect potentially fertility, because, you know, the radiation could impact the ovaries.

So, there are procedures to move the ovaries out of the way of the radiation field. So, that's proactively thinking about it. But then even afterwards, having access for infertility clinics and things like that may be very helpful as you think of life after treating the cancer.

Dr. Emily Tonorezos: Yes. One of the great strides that has been made in breast cancer treatment was the recognition that some patients can safely come off their endocrine therapy to try to get pregnant. And that is some research that we've only just had in the last few years, but it has made an enormous difference for those young women who are diagnosed and treated for breast cancer and historically have been on endocrine therapy and told, "If you come off, you're at-risk of your cancer coming back." And now, we know that at least for some of those patients, it is safe for them to stop treatment and try to get pregnant. And that has been an amazing step forward for those patients and for this field.

Dr. Manish Shah: Let's talk about how survivorship care is integrated in oncology practices. We can speak of the program that you lead in breast cancer. But then, maybe, what are the other models of how it could be integrated for different practices?

Dr. Emily Tonorezos: So, there are so many different ways that this can be done, but the way that it happened here in breast medicine oncology is that there was a provider, Anne Moore, who is a breast oncologist, who had been practicing in New York City for many decades. She's a very well-known and well-respected medical oncologist, and she decided she wanted to retire. And the team here said, "Could you please work part-time?" This was now eight or nine years ago. She agreed to transform her practice into a survivorship program where she would see just people who had finished treatment and who were in the surveillance stage. And of course, because of her vision for this program and also, the vision of the Division of Hematology and Oncology, the program was very successful and grew.

And I joined a couple years ago as part-time faculty while I was still at NCI. And then, a year ago, when Dr. Moore decided she wanted to retire, I moved into this full-time role. What has been amazing is that I'm not a breast medicine oncologist. I'm a general internist. But I was really embraced by this division and by this organization, as the right person to be in this role and taking care of these patients.

So, my position is in the Division of Hematology and Oncology, but I am a general internist. And for this group and for these patients, it's been a wonderful fit, and I think the program is really thriving, but that required a lot of steps and a lot of foresight on the part of the leadership.

So, I think that can work very well where you have what's called an onco-generalist who is taking care of the survivors who fit into the right category for that provider. In other places, there are medical oncologists and even surgical and radiation oncologists who have said this is an interest of theirs, and they follow the patients prospectively. And in a lot of places, actually, it's nurse practitioners who are embedded in the disease management teams, but who are taking over the long-term follow-up aspects of care for survivors.

All of those programs, at some point, there does need to be either a transfer or an integration with community providers or providers who are outside of the cancer center. We're very fortunate here at Weill Cornell and NYP that we have highly respected primary care and internal medicine groups who are available to our patients. And that's been a wonderful collaboration for me, working with those primary care providers inside our system who are taking care of the same patients. But I have my role, which is survivorship, and they have their role, which is primary care. It works great.

Dr. Manish Shah: That's terrific. And your impact has been enormous for the program and for all of us. I'm just wondering, a breast cancer survivorship program probably has very unique and specific health concerns that commonly come about, and it might be different than prostate cancer or rectal cancer. Is that the sense or do you think that a survivorship clinic could exist for all of solid tumor? And then, correlated to that question is I imagine that someone with a lymphoma or leukemia that had a bone marrow transplant, their survivorship program might be also very, very different.

Dr. Emily Tonorezos: Absolutely, you're right. So, every disease management team or every diagnosis needs to figure out for themselves what is the survivorship program that will best serve the needs of their patients. Because it is very different in breast than in other types of cancers.

At my old job, one of the things that I did was adult survivors of childhood cancer. So, that's where you see a very heterogeneous cancer diagnosis population, but where a lot of the exposures are similar across disease types or cancer types. So, that worked well. But for the most part, these programs are growing up in sort of disease-specific or cancer-specific settings.

Dr. Manish Shah: So, we talked in the podcast previous episodes about targeted therapy and bringing them earlier into the forefront of treatment, and that has had a bigger impact. Combined with that targeted therapy, is a move to deescalate treatment. And there are other ways to deescalate treatment by using new technology like circulating tumor DNA and things like that. I imagine that deescalating treatment may make survivorship care a little bit better for at least some patients. Are you experiencing that or do you see that moving forward?

Dr. Emily Tonorezos: Absolutely. One of the places I've seen it in my own career is with Hodgkin lymphoma survivors, where we went from radiation all the way from the bottom of the jaw to the tip of the pelvis and high doses of very toxic chemotherapy, to now where patients can get targeted therapy to maybe not require chemotherapy. It's amazing. It's remarkable. It's happened in the 20 years that I've been in this field and truly changed the face of survivorship without a doubt.

Dr. Manish Shah: A recent publication that you had was on the late and long-term effects of immunotherapy. And I mentioned that because this might be one area where there could be a unified survivorship clinic because, in immunotherapy, late side effect that happens in a patient with breast cancer might be very similar to someone that had immunotherapy with bladder cancer. Do you want to talk about any of those side effects that we should think about or have come to the forefront?

Dr. Emily Tonorezos: So, there is a program at Roswell Park, which is just for people who've gotten immunotherapy, but my understanding at least is it's all different kinds of cancer diagnoses. So, you're absolutely right that could be the future of survivorship after immunotherapy.

The common side effects that are seen during treatment kind of relate to inflammation. So, it tends to be either rheumatologic or systemic sort of inflammatory syndromes or symptoms. The name of that paper actually is "Where is the data?" Because we don't really always know what patients are at risk for those inflammatory conditions coming back, and what patients may have smoldering, undetected inflammation that could be affecting their health. So, we really actually need much more observational research on people who have gotten immunotherapy, just to be able to know even how closely or under what circumstances should we be watching these patients.

Dr. Manish Shah: Where are the areas of research that are really at the forefront for survivorship care?

Dr. Emily Tonorezos: I think we've covered a lot of those areas, certainly these emerging populations. So, that would be people who've been treated with newer therapies like immunotherapy, like the checkpoint inhibitors and other targeted therapies.

There are these growing populations of survivors, like the people who have a history of a diagnosis of metastatic or advanced cancer, people who've been diagnosed with rare cancer, where historically those populations just were not included in survivorship research. But now that they are growing in number and we know that these survivors are living longer periods of time after those diagnoses, we need to be capturing them in our studies and studying them to the fullest extent possible.

I also think there's been a growing acknowledgement of all of these secondary ways to measure the burden of going through cancer treatment. So, we talked about financial toxicity. We talked about changes in relationships and roles. But there is also this emerging idea of time toxicity, which is to say how much time do you spend going back and forth to appointments related to your cancer diagnosis? And for some patients, that may be a limiting factor in their desire to pursue treatment. So if you find out that you are eligible for a therapy, but you have to come to the hospital every single day for the next six weeks, depending on the circumstances, you may say, "That's just not something I want to participate in." And up until recently, we haven't really even had the ability to measure that potential time toxicity and use it in our conversations with patients about treatment options.

Dr. Manish Shah: That's such an important point. This has been an incredible discussion. There are so many key takeaways. I think, for me, it's really critical that healthcare providers are aware of the medical issues, health issues and social issues that can occur, both during the active treatment of cancer, but also after the cancer is treated and how best to manage it. I think awareness is a critical aspect of this. And then, offering support where there's so many options available. And our breast cancer service is really fortunate to have access to the Breast Cancer Survivorship Program. I think that similar programs across oncology would be really quite helpful. Are there other takeaways that you'd like our listeners to have?

Dr. Emily Tonorezos: I would just say from a provider perspective, if you're someone who's taking care of these patients, there are lots of resources available including on the Office of Cancer Survivorship website. But also, the American Cancer Society and the American Institute of Cancer Research.

And from a patient perspective, I think, as I mentioned, this whole field came into existence because survivors told us we're experiencing things after treatment is over and we want more research in this area.

This is a field that really owes a huge debt of gratitude to the patients and survivors and their families themselves, and they should always be the ones who are leading the way for us.

Dr. Manish Shah: Well, that's wonderful. Thank you so much for your time today. You can download, subscribe, rate, and review CancerCast on Apple Podcast, Spotify, YouTube, or online at weillcornell.org. We also encourage you to write to us at CancerCast at med.cornell.edu with questions, comments, and topics you'd like to hear us cover in the future. That's it for CancerCast, conversations about new developments in medicine, cancer care, and research. I'm Dr. Manish Shah. Thanks for listening.

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