By Mark Elfers
In early 2021, Blue Note Therapeutics was joined by Dr. Patricia Ganz, MD, Dr. Areej El-Jawahri, MD, and Dr. Michael Antoni, PhD, to discuss advances in the field of psycho-oncology.
Moving Forward - A Blue Note Therapeutics Oncology & Psycho Oncology Expert Panel Discussion
Patricia Ganz, MD - Jonsson Comprehensive Cancer Center
Areej El-Jawahri, MD - Mass General Hospital
Michael Antoni, PhD - Sylvester Comprehensive Cancer Center
Mark Elfers (ME) - Hello everyone, happy Monday. I hope Spring is returning to wherever you are. On behalf of all of us at Blue Note we want to say thanks to you and to our panel for joining us. Real quick though, if you have any questions as we go through please put them in the chat and we’ll make sure we get them into the rotation, and let’s plan to stay on mute throughout just to ease down on any static that’s on the line. So why don’t we kick off and say hello to our panelists and let them introduce themselves. Is Dr. Antoni on?
Dr. Antoni (MA) - Yes I’m here, can you see me?
ME - We sure can, Dr. Antoni. How are you, Sir?
MA - Very good, very good. My name is Mike Antoni and I’m a professor of psychology and psychiatry at the University of Miami and I’m in the cancer control program at the Sylvester Cancer Center. I work in an area called Behavioral Medicine, a branch of psychology, and we do studies of stress and coping and have also developed interventions to facilitate medical patients' ability to cope with the challenges of their treatment. So it’s a pleasure to be here today and I’m happy to answer any questions.
ME - Thanks Dr. Antoni. Appreciate you being here. Dr. El-Jawahri, how are you, Ma’am?
Dr. El-Jawahri (AE) - I’m good, thanks. Good afternoon thanks for having us. My name is Areej El-Jawahri. I’m one of the oncologists at Mass General Hospital in Boston. I specialize in caring for patients with blood cancers, so leukemias, lymphomas, myeloma, and treatments used to treat these blood cancers, particularly stem cell transplantation and cellular therapy. That’s my clinical hat and my research hat involves developing and testing supportive and palliative care interventions that span the illness continuum for patients with blood cancers to improve their lived experience and their overall outcomes, as well as the outcomes of their caregivers. Glad to be here and also happy to answer any questions.
ME - Thank you. Dr. Ganz, do you want to take a second and introduce yourself please?
Dr. Ganz (PG) - Greetings from Los Angeles. I am Patti Ganz. I’m a medical oncologist and I am both a professor in the school of medicine and in the school of public health at UCLA. And I am the associate director for population science at the Jonsson Comprehensive Cancer Center. I’ve been involved in psychosocial and behavioral research for cancer patients for over 30 years, and I’ve been focused on how we can improve the outcomes for patients both in clinical trials research that I do, as well as my own research focused on the toxicities of cancer treatment. So it’s great to be here with you today.
ME - Thanks, Dr. Ganz. Dr. Ganz, maybe I’ll start with you, please. You and your colleagues with the Institute of Medicine co-authored two reports on the needs of patients and survivors in 2006 and 2008, emphasizing the gaps in delivery of Psychosocial Services, and then published five years later another report called “Delivering High-Quality Cancer Care: Charting a New Course” what drove you and your co-authors to this topic initially and then to return to it?
PG - So first of all, maybe some of you are familiar with the Institute of Medicine which is now called the National Academy of Medicine. This is an independent body that is often commissioned by either the government or other nonprofit organizations to do what we call consensus studies on a topic of interest. The first report, which was focused on cancer survivors in 2006, really was demanded by the cancer patients survivorship community because they felt that their post-treatment experience was being neglected by the medical community and that they had many concerns about not only their physical well-being but their emotional well-being in recovery, and returning to the new normal. So that report is famously called “The Lost In Transition” report where survivors, who at that time were about 10 million and are now 17 million today, really felt that the healthcare system was neglecting their needs.
Then in 2008, again advocated by many of the professional organizations in psychology and psychiatry being very concerned about the fact that cancer patients and survivors had unmet psychosocial needs that were not being addressed adequately by the oncology system of care, and that a report was needed to call attention to this. And this was caring for the whole patient. Again having served on that committee, the emphasis there was really to deliver patient-centered care we had to deal with both the physical and the emotional needs of patients along the cancer journey, and that the healthcare system was not taking advantage of a lot of resources that were available. Many support groups, many psychosocial delivery systems that were available, interventions such as the ones being developed by Dr. Antoni and others, and it wasn’t getting to the persons who needed it. But that important report led to a call for systematic screening for depression, anxiety, distress in cancer patients, which over time has become a mandate from the College of Surgeons, which accredits many cancer programs in the United States, that everyone with a cancer diagnosis needs to be assessed for cancer-related distress. That again is a work-in-progress, we know that while everybody says ‘yes, this is important,’ it is not universally being done.
So what happened in 2013 was I was actually able to chair one of these consensus reports where we talked about the deficits in delivering high-quality cancer care and basically the first two recommendations from that report were that every patient and their family were the center of our focus, in terms of delivery of high quality care, in addition to understanding their diagnosis and its prognosis needed to receive psychosocial assessment and care as well as palliative care being available. This was for newly diagnosed patients as well as patients with recurrence and that this should be presented to them in a systematic way. Again, why do we have all these reports and why are we continuing to request that these things be a part of care? It’s because they’re not being done and they’re not being delivered. So maybe I’ll stop there and if there are any questions or others want to add something, I would welcome that.
ME - Thanks for leading us off there, and there is a question: does cancer-specific psychosocial treatment that you just described really improve medical outcomes or does it simply make the patient feel better? Where does that medical versus behavioral line sit? And maybe Dr. El-Jawahri, can you help us with that first?
AE - Absolutely and obviously being with Dr. Antoni and Dr. Ganz is an absolute honor and I’m sure they have a lot to comment on that as well. I will say that first and foremost improving the experience, the lived experience, of patients with cancers and cancer survivors is in itself noted a noble goal and should be our primary goal with a lot of these interventions. I’m a strong proponent that people who are actually feeling better mentally lead a more fulfilling life and a more fulfilling life with their loved ones. That being said, I will say several things. One is we know that psychological distress and depression has been associated with a lot of negative outcomes in the context of various cancers. Different populations I can tell you in stem cell transplant, depression has been associated with mortality, risk of graft-versus-host disease, higher risk of hospitalization and intensive healthcare utilization. And this is just one population but we’ve seen this over and over again across multiple multiple populations.
In fact, depression and psychological distress is an important comorbidity that is used in a lot of our comorbidity indices, to describe the risk of patients for future medical complications. So I think all of us who are in this field do wholeheartedly believe that intervening on the psychological well-being of our patients with cancer not only will make them feel better, but will lead to actually downstream impact on healthcare utilization, potentially survival, and other health outcomes. It is important to know that these outcomes such as survival require large studies with big sample size to really demonstrate these benefits.
But the known consistent association between psychological distress and these negative health outcomes, including hospitalization, length of stay in the hospital, survival, mortality, complications, have been shown so consistently that everyone in our community really does believe that intervening on the psychological well-being of our patient will lead to better medical outcomes.
ME - Thank you. And Dr. Antoni, I know you’ve done some research in this field and published. Can you maybe add a little bit of color?
MA - Okay, a little bit of color. So, my work is restricted primarily to breast cancer that I can talk to. That’s significant given that we have at least three and a half million or so survivors of breast cancer in the United States at this point in time. We found that if you measure their depression just in the post-surgical period, right at the front end of treatment, that’s a predictor of how long they will live. So if they had no depression they lived maybe thirteen years, if they had moderate depression, they lived 11, and if they had more marked depression, they lived 9 years. So it was very convincing there seemed to be a linear association between distress and a long-term outcome.
An intervention that we developed that was designed to target anxiety and depression by teaching stress management skills that you’ve heard of, such as cognitive behavioral therapy mixed with relaxation and mindfulness, that the women who were in our trials back in 1998 to 2005 we followed forward in the tumor registry for the state of Florida. And we found that the women who had received this intervention called cognitive behavioral stress management (CBSM), if we followed them for 8 to 15 years, those who were in our groups lived longer, and they went longer before they had a recurrence. When we looked back at our data we found that the more they improved their psychological, what we call adaptation, as well as the more they reduced inflammation and other immune related phenomena during our groups. That was correlated with the number of days that they lived forward without a recurrence.
So this putting together the experimental pieces has made what used to be in many of the data sets simple correlations, made it really come to life for us to see that intervening on some of these mental health or mood-related phenomena could have an impact on physical outcomes.
ME - Okay, thank you for that answer. Let me just go back to Dr. Ganz real quick. So you and your colleagues published these reports from 2006-2013. One of the questions we have is what was the response from your community? Open arms, or was there push back, or were people immediately on board? How did those reports land?
PG - I think the survivorship report had some challenges in the sense that one of its central recommendations was that patients should be given a care plan at the end of treatment that would tell them how they should be followed. In many ways this was a discharge summary to say you need to see your oncologist three times a year, you should check back in with your primary care doctor, you need to be on the lookout for these late effects and we need to take care of health promotion and disease prevention including mental health. But the push back from the medical community was ‘who is going to pay me to do this’, and ‘what’s the proof that this will make a difference’, and a lot of hostility was presented associated with this. And I would say there’s never been any evidence that a discharge summary from the hospital does any good, but we rely on it. JCAHO [Joint Commission on Accreditation of Healthcare Organizations] relies on it. How could we ever review every note in the hospitalization and figure out what went on if we didn’t have a discharge summary? So I don’t want to dwell on this, but it’s been a long time getting this into real world activity. And the American College of Surgeons has tried to do this, but it has not really flown.
With regard to the distress screening, I have already mentioned that, again that is a requirement. I would tell you that the US Preventive Services Task Force gives a ‘B’ rating to depression screening and everyone, but I can tell you oncologists are not doing depression screening, and that is something that I’m very passionate about now just having completed a study in younger breast cancer survivors and looking at the severity of depressive symptoms in those young women.
So what happened in 2013 was very very exciting. We wrote this report, we had 10 recommendations, I left it feeling this is blue sky, it’ll never happen. But it turned out lurking in the corners of the healthcare system were actually champions for a lot of the things that we recommended - one of them was a learning healthcare system as an example, which we know a lot of people are very interested in. But what happened within 9 months of our report was that the Center for Medicare and Medicaid services (CMS) Innovation Center (CMMI) picked up our recommendations for a 13-point plan that should be part of every patient’s initial encounter with their doctors and in their program called the Oncology Care Model (OCM) where they provided a bundled payment for Medicare patients who were starting chemotherapy of any sort, and many private insurance plans also joined this as well. They said if you participate in this program, we will give you $160 per beneficiary per month to improve that experience, to do the psychosocial assessments, to do navigation, to do all the things that we know are the extras that keep people out of the hospital and improve their wellbeing. Now I have to say I was extremely excited about this. There is actually a trial or evaluation study that’s being done; there are about 170 clinical sites around the country that participated in the OCM and they picked, in a quasi-experimental design, other sites. It’s now struggled because of what’s happened with the pandemic this past year, but CMS was really going to go forward with an expansion of this to Oncology Care For All [[Oncology Care First]](https://innovation.cms.gov/files/x/ocf-informalrfi.pdf), the new plan with the bundled payment, because they saw that practice redesign occurred in many of these things that were considered extras were integrated into the practice. So this is a to-be-continued, but it was extremely exciting to see implementation, at least in an innovative model, to occur.
ME - Okay, great. Let me ask our other panelists, in that same time period, have you seen in your regions a similar change towards the integration of holistic care? So how are we doing so far from Miami and Boston’s perspective?
MA - I think one evolution in our cancer center has been a stronger number of faculty and emphasis put on cancer survivorship. So often cancer centers get their stripes by having great cures and things that they can say they were the first to come up with precision medicine, genomics, etc, but I think the Sylvester is really putting a lot of money where its mouth is in terms of cancer survivorship, and I think reports like the ones that Dr. Ganz has done have had an impact by way of how the NCI construes the proportion of support that they give for cancer centers that is dedicated toward quality of life and quality of care to cancer patients. So by having an influence on the NCI, it’s had an impact on the culture of cancer centers which is where a lot of oncologists get trained and do their thing and so that’s carrying forward all the way through the newest generation of oncologists who now have this proportion of their mindset focused on cancer survivorship maybe in a way that wasn’t there 15 years ago.
AE - I completely agree with Dr. Antoni. I do think things, while progress has been slow as Dr. Ganz has mentioned, I do think there has been substantial progress. I think there is more research into the survivorship care needs and developing innovative interventions to address the needs of survivors and actually patients actively living with cancer. I think our survivorship paradigm also is obviously changing as we have more and more patients living with cancer for many many years, which is a great success story for cancer treatment I should say. In addition I will say that I think from a research infrastructure there has been more funding than ever that has been put into these types of programs from a research perspective, trying to understand mechanistically what happens, and how is intervening on the stress improving patient outcomes? There is a huge movement of palliative care research focused on enhancing the quality of life and lived experience of patients with cancer and their caregivers.
And then politically, I will say that 10-15 years ago, discussing screening for cancer-related distress or psychological distress in cancer clinic, was probably something that was discussed in a small circle of people that care about this issue including people on this panel, and now it’s actually more mainstream. While we have challenges in terms of system-based barriers to integration that are honestly true across all of medicine, and not particular to this type of integration, we’ve always had challenges in terms of scalability and dissemination of successful models of care and care delivery interventions. I think we see it definitely in survivorship care and psychosocial care, but I do think it’s becoming essentially mainstream and it’s one of the things that all of our cancer centers are investing resources and infrastructure in.
ME - Okay, let me follow up with a question from the group. The first question is ‘has survivorship care planning had an impact on patients? And that idea that survivorship care planning should be done; has that moved the needle?’ Maybe Dr. El-Jawahri, do you want to start?
AE - Sure, again, I do think there has been from a research perspective, as some of you may know, there has been mixed research on the potential benefits of survivorship care plans. I think what we are learning more and more and it seems intuitive, that providing a survivorship care plan without guidance doesn’t really help, that we need to provide survivorship care plan with really appropriate counseling and education to reduce patients in distress and to really discuss the long-term management of health that can actually improve the quality of life and the stress of patients with cancer. I can tell you in the stem cell transplant population, one of my colleagues, Karen Syrjala of the Fred Hutch Cancer Center, has done a lot of work in survivorship care plan in stem cell transplant recipients, and integrating survivorship care plans along with psychological counseling to help patients really cope with the impact of their treatment and understand what we mean by ‘late affects,’ or what do we mean by ‘monitoring for long-term health outcomes.’ And in those trials, survivorship care plans have been incredibly effective at reducing the stress, enhancing a sense of patient self-advocacy, and making them feel empowered to really address their health care concerns, and ultimately leading to better management of long-term help outcomes. So, yes I do think that survivorship care plans do have an impact, but I think we have to be thoughtful about how to integrate them and scale them into the cancer setting.
ME - Okay, great, and I’ll ask Dr. Ganz for any additional color, and if anyone knows if there are metrics in place now on providers or clinics that measure the integrations of an interdisciplinary management team beyond nursing or advanced practice, into social work or any lay support? So Dr. Ganz, over to you.
PG - I did want to say one thing about the challenges of screening for psychosocial distress or depression. It’s a little bit of a don’t-ask-don’t-tell kind of thing because many clinicians are afraid to actually do those screenings because if somebody does screen as being depressed or suicidal or whatever, unless they have somebody that they can immediately turn to, or know how to deal with that, they’re not going to do it. It’s a little bit like asking about sexuality and intimacy; i’ve actually lectured on this and did a whole study on this 25 years ago. And again, if you ask about that as a problem and you don’t have someone to refer the patient to, or you do not know how to address those symptoms, you’re just going to freeze because it will take up the rest of the time in the clinic.
So I think one of the issues is how well resourced clinical oncology practices are, and I want to get to this, because those of us who work in tertiary, quaternary places where we have largely philanthropically supported psychosocial support teams, we can turn to those people urgently or semi-urgently if we need help, but if you’re a doctor in an office and you don’t really have a social worker who is affiliated with your practice or anyone or you’re not part of a hospital system, it becomes very difficult. So that even if you were to screen for distress, where would you refer those individuals? And I think that’s a problem with implementation wide-spread.
And, again, I don’t have to tell all of you but 80% of oncology care is given in the community, not in tertiary centers like ours where even where we’re trying, we’re not always completely effective. I think those are important things. For my own practice, I see survivors of all types in consultation, I see people treated for lymphomas; in an example, young folks, who I am also very concerned about, young folks who are survivors, where they’ve had extraordinary curative care for their high grade lymphomas, but there’s not a single note in the chart that tells me if they’re married, if they’re working, what their psychosocial situation is, and I have to figure that out when I see those patients for a survivorship consult. So this gets back to the fact it’s not just a piece of paper with a plan, it’s actually an evaluation that meets the needs of the patient where they are.
ME - If I just put together a couple of these thoughts that we’ve just heard. It should not wait until survivorship, right, we should be thinking about that, like Dr. Antoni was saying, as early as we can and integrate this treatment along the way and then through - you’re taking the patient all the way through survivorship with this kind of care, right? Is that fair?
PG - Yes and also I think what’s really important is that physicians often don’t know that the patient has a history of depression. Anyone who’s had a history of depression is much more likely to become depressed during their treatment. And I would venture to say that the patients in Dr. Antoni’s study who he talked about probably were people who had a history of this. So cancer doctors are just focused on the tumor, its characteristics, there’s so much we need to know, there’s so many subtypes of every type of cancer, and then we have to match it with a targeted therapy and the patient is overwhelmed, their family is overwhelmed, and the level of distress and anxiety is extremely high and it’s seldom addressed when we’re trying to get a treatment plan for the patient in terms of the cancer focus.
ME - Okay, so let’s talk about these types of interventions. So Dr. El-Jawahri, you’ve created and collaborated on creating some cancer specific behavioral and psychological interventions, and coming to it as a medical oncologist and hematologist, were you trying to solve a problem that had no solution? Or were you saying we could do incrementally better? Help us understand. Was there just a gaping hole here that you wanted to fix, or you were trying to incrementally get a little bit better at something we were doing OK at in the first place?
AE - Yeah, it’s more of the gaping hole model, Mark, I will say it’s definitely that. I will use DreAMLand and our experience in thinking about patients with acute leukemia as an example.
Just to orient you to this population. Imagine you’re a 25, 26, 27 year old patient who is doing well, very healthy, going about their daily business, going to work, doesn’t have time to really think about even going to the primary care doctor. And they just notice that they’re more short of breath as they go up a flight or two of stairs. They think nothing of it, they wait a couple of weeks, it gets worse, they go to a walk-in clinic or an urgent care clinic or sometimes their primary care doctor if they have one, and say hey I’m just been feeling more short of breath when I do things. And usually they say well we’ll do a couple of tests to see how things are, maybe it’s your thyroid, maybe you’re just tired, maybe you’re overworked. And typically that patient is going to get a call at 6 or 7 o’clock at night, saying ‘hey your blood counts are abnormal, you need to go to the hospital, you have leukemia, and this is life threatening, and you need to go now!’ And that is the most common way we know, documented in the literature, patients with acute leukemia present to medical care. Someone frantically calling them, telling them that they could die from this illness and they have to acutely come to the hospital. They come to the emergency room and they need the emergency room physicians, who to be honest with you are pretty scared of acute leukemia, and they look like ‘oh my gosh you have leukemia you have to come in immediately.’ And then they’re told ‘you’re coming into the hospital you’ll be in the hospital for the next six weeks to receive intensive chemotherapy, some of the most intensive treatment that we have to offer and oncology, and on top of it this is just the beginning of a very long journey.’ In the first 48 hours from diagnosis, these patients receive an overwhelming amount of information about what this disease is, how we’re treating it, what are we doing, the expected side effects. Patients often describe being abducted by this illness and their lives are flipped upside down, and I have to say we see a lot of peoples’ lives get flipped upside down in oncology, but as a resident and as a fellow and junior faculty, the story, this dramatic presentation has always been one of the hardest for me to watch people suffer through.
Taking into account this and understanding the idea that in medicine in oncology we’ve been used to this model of providing medical informations all in a bolus fashion. So patients are diagnosed. We have a visit. We talk about all the potential treatments. We start treatment and we kind of talk about even their prognosis during that visit often. And the reality is these patients probably hear about 10% of what we say in that first visit. Developing an illness understanding really requires a lot of information given over a period of time to allow patients to cognitively process what we’re dealing with. So needless to say, acute leukemia is one of the most traumatic diagnoses in oncology and it’s been actually strongly associated and has been shown to be related to clinically significant post-traumatic stress disorder similar to what we see in veterans. And this medical trauma if you will, the social isolation, the abduction, along with the physical side effects of treatment, you can imagine as you show up to the hospital everyone looks at you like you’re dying, and then you feel like you’re dying, you think you’re actually dying. In fact the rate of death during that acute hospitalization is less than 5%, but the experience itself creates that trauma and that culture that makes you feel like this is all coming to an end. So, what we decided to do was really develop an intervention that targets acute trauma, this acute distress, psychological distress, paired with the idea that these patients require education about their illness to be more informed about what to expect during the hospitalization for that induction intensive chemotherapy that they receive early in the course.
And in many ways to the question that was asked earlier, are we just trying to make people feel better, this is a population where moving depression anxiety and PTSD is actually easy because the rates of clinically significant depression is 50% and the rate of clinically significant PTSD symptoms at 6-months post-diagnosis is about 30-35%. So, these metrics are actually easy to move in some ways because the bar is so low and there’s so much that we can do to support these patients acutely as they’re diagnosed. But to the question that was asked earlier, this is also population where theoretically if you intervene on that psychological trauma, if you provide patients with an extra layer support at the time of diagnosis as they’re dealing with this acute traumatic illness during that first four to six weeks of their initial diagnosis experience, there’s a huge potential for moving very very significant healthcare utilization metrics. These are patients who spend approximately 50% of their life in the hospital from diagnosis until death. These are patients with high healthcare utilization, they spend a lot of time in the hospital, they’re at high risk for re-hospitalization and there is a potential for improving some of these healthcare realization outcomes.
So, we developed an intervention really pairing our psychologist Dr Joe Greer, who unfortunately is not here, and myself working together trying to address both the medical and the psychosocial needs of these patients during the acute hospitalization. And we relied on mobile technology particularly based on what Dr. Ganz just shared with you all that we simply just do not have enough mental health clinicians to care for all of our patients with cancer, and thinking about innovative strategies to address the needs of these patients in a way that is patient-centered, the idea to allow patients engage with a mobile app during a difficult, long hospitalization at their own convenience during a time that they want to interact with this mobile app provides them with that patient centered approach to care. DreAMLand is structured in such a way to allow patients’ information about their diagnosis that really matches and aligns with their own course. So they are able to process cognitively the medical information, set the expectations for the hospitalization, how to manage physical and emotional side effects and also set the expectations for the future, and at the same time provide a layer of coping and support to really address the psychological trauma associated with this diagnosis. Some of the same principles that Dr. Antoni spoke about, cognitive behavioral therapy skills, mindfulness based strategies, and some focus on self-efficacy and self-care. And I should say this was inspired really honestly by a palliative care intervention that we did in this population. A lot of the components of the app came from this in person intervention where we took palliative care clinicians with expertise in physical and psychological symptom management in promoting patients coping and integrated them in the care of these patients at Mass General and other institutions, and found that these patients with that extra layer of support did a lot better from a quality of life and psychological distress perspective. So we took the lessons learned from that and try to really utilize them in a mobile application, so I do think this idea of developing population specific cancer interventions is important. We need to understand that these patients’ experiences differ across cancers, and our ability to tailor these and adapt these interventions to their needs are probably critical to their success.
ME - Thank you for that background. And it brings to mind a question that we received, and maybe I’ll give this one to Dr. Antoni. Dr. Antoni, there’s so much need out here, couldn’t a more generic or a generalized or homogenized behavioral therapy work? Couldn’t we give - and I don’t mean “just” because I know there’s a lot behind cognitive behavioral therapy - but couldn’t we just give all cancer patients pretty straight-stick CBT?
MA - Well, just to step back, the CBSM intervention that I can speak to empirically, is a combination of relaxation techniques and CBT techniques. And it’s true that muscle relaxation, deep breathing, mindfulness, meditation, can be disease agnostic. These can be behaviors that you train people with the CBT, however, requires that people apply the techniques of cognitive restructuring, coping skills training, interpersonal skills, to their real lives. So if you were teaching a person CBT for a neurotic depression that they have had for many years or a marital issue that they were having for many years, you would be addressing things that were neurosis related, longer-term patterns.
The cancer patient arrives with a diagnosis and is overwhelmed, as we just heard, with decision-making and many different steps of treatment. When we treat a cancer patient we’re going to treat them multiple times with multiple treatments, and those treatments are going to last sometimes for decades when you talk about hormonal treatments. So the CBT has to be based on the nouns of their life, CBT may be verbs, but you’ve got to apply it to the nouns of their life, the topics that are most set on the front of mind. That’s why before we created CBSM for breast cancer patients we interviewed a ton of patients who were on the eve of surgery and asked them what was on the front of their mind. There were things like fear of recurrence, fear about their children, fear of what chemotherapy was going to do to their bodies. This allowed us to know what the biggest challenges were for these patients, and that gets built into what the CBT techniques are addressing. And so the techniques that get used in our intervention are designed to raise awareness of where stressor cues are in their life, how to handle decision-making better, how to allocate their energy resources better by the way they cope, restructuring their thoughts so they can improve their transactions with the healthcare team and their family, and then teaching them interpersonal skills to help communicate their needs to their doctors, nurses, as well as family members so they can build the resources they need to get through the journey. So that’s one point I want to make.
Another point I want to make is although our intervention was really designed to handle a lot of the stress and challenges that happen right around the period of surgery and the starting of adjuvant therapy, we’ve learned that what we taught those patients early on is associated with better adherence to hormonal therapy out to seven or eight years later, to depression levels 11 years later, and as I mentioned already to physical health outcomes years later. So we have to take a longer perspective I think on where these interventions might carry over to. From that point of view they are very efficient. If you can help a person with the journey navigate through the 12 months of primary treatment and then you get a bonus that you improve their health behaviors long-term, their mood, and possibly their physical health long term, these interventions can have a lot of durability because you’re hitting patients at the point when they couldn’t be more open to thinking about change, to thinking about what do they want to tune up in their life to be stronger as it’s already been mentioned that we give patients not only skill efficacy, teaching them tools, a toolbox, but we give them self-efficacy which is a much broader concept of if stress management is the skill efficacy, then stress confidence is the self-efficacy.
So a lot of powerful things can happen in this period of time, and I think the moving toward digital delivery is going to be able to reach more patients. It’s going to be able to free up the hours of the mental health team so that they can then work on the things that maybe bubble up from using the digital tools and it’ll focus the therapy sessions - the mental health therapy sessions - in a way that the patient is already prepared, they’re already facile with the skills of talking about stress appraisals and coping skills, and they can help identify where they need a laser treatment from the mental health professional. So I think those are several ways that the efficiency is going to change as medicine moves a little bit more toward self-management and self-care in tandem with guides, navigators, and very enlightened healthcare professionals that allow that proportion of time for the survivorship quality of life focus.
PG - Mark, I just wanted to say one thing. You know I’ve been at this for a long time, and I was very fortunate I had a young postdoc in my lab, who is now one of my collaborators, who came to work with me in our psychoneuroimmunology Norman Cousins Center. And I had a lot of skepticism about inflammation and some of these mind-body techniques, and as a leader in my cancer center I would often present our research to groups of people, and the basic scientists really woke up one day when we were able to show biological correlates of the symptoms and the problems that we were seeing, as well as the interventions that we were using to mitigate some of these symptoms. And it was like, ‘I always knew you were doing good things but now it’s real’.
And I have to say that all of these mind body techniques, the ones that we have studied in our research group, are associated with reductions in inflammation. So not only do you see improved symptoms, but reductions in inflammation, which we know is likely to contribute to better disease control over time, reduction in other chronic diseases that many of these patients will be at risk for - cardiac disease, diabetes and so forth - and so the fact that we can not only communicate to the patient this is not just for how good you’re going to feel, but for your overall health and well-being is a very powerful message.
And again, the idea is that this will contribute to adherence and better outcomes are really emerging from all the research that is being done. I think the big issue is disseminating these techniques has been the big problem, and again there’s just not enough good therapists and centers that have these kinds of individuals or even in the community to both detect people who need help as well as deliver the services.
ME - Thanks for saying that, Dr. Ganz. I think that links to the moment when a patient says ‘I feel better’, and you can say from a blood test ‘I’m seeing it here’. Dr. El-Jawahri, you were nodding. Can you maybe just double click on that for us?
AE - Yeah, I think Dr. Ganz said it perfectly. I do think the way you get our basic scientist excited about the work we do is by showing the mechanism, right, by really demonstrating the conceptual and theoretical framework of what we’re talking about. And the reality is these links are absolutely real and we’ve seen them not just from a correlation perspective as you heard from Dr. Antoni, but in a mechanistic way coming out of intervention work like his, that has really shed the light on the importance of these mechanisms. We should note that these mechanisms are also relevant for other aspects outside of psychosocial distress and the link to medical outcomes including now we’ve told you that psychological distress is linked to survival, to how long people live, to morbidity, to physical health and physical well-being, to relapse.
And I want to highlight that that was the point that Dr. Antoni is making that it has been associated to cancer recurrence and then Healthcare utilization. So a lot of hard medical outcomes that matter here, but we should note that a lot of what we are learning from this actually could apply to patients with no psychological distress. I’ll give you just one example. In our field in the blood cancer world, Car-T therapy is the new and hot thing around the block. It’s adoptive cellular therapy, it’s cellular therapy that essentially engineers the patient’s immune system to attack cancer, and in the process it creates this incredible inflammatory milieu. And one of the most effective drugs to manage that inflammation is a drug called tocilizumab, which is an anti-inflammatory drug that blocks one of the cytokines that’s responsible for inflammation. Well lo and behold this drug has been used for treatment of refractory depression and there’s a lot of literature on its use in refractory depression. So these links become relevant outside of even what we’re thinking about within the context of a distressed patient, but have important implications on how we think about cancer, about how we think about tumorigenesis, about how we think about how inflammation impacts these medical outcomes as well.
ME - Thanks for sharing that. We’ve got about 10 minutes left. If there is a question on the tip of your tongue please jump into the chat. I want to give Dr. Antoni a second. Dr. Antoni, I think your team has published on this very topic , the links between your intervention and some of the biology, you want to just take a minute and describe those links while some of these last questions come in?
MA - So the women who’ve gone through the stress management have decreased their afternoon and evening levels of cortisol, a stress hormone. They’ve shown improvements in their immune cells’ ability to respond to challenges, they’ve shown reductions in the inflammatory proteins floating around in the bloodstream, but also, thanks to our collaboration with a great investigator from UCLA, who I know Patty knows, Steve Cole, we’ve been able to show that the white blood cells circulating through the body, which talk cancer cells, are showing less inflammatory gene expression in the women who go through the stress management intervention over a 12-month follow-up period. And the more those genes stop yelling out inflammatory signals, the longer the women went without a recurrence over the next 11 years. So to me that was powerful that at the level of gene expression we were seeing the intervention move the gene expression, and that was linked in a dose-response fashion with how long the women went into the future without a recurrence. So, that’s probably the most ‘wow’ thing that I’ve had the chance to observe in the past few years.
ME - Thanks, Dr. Antoni. And I’ll send it back to dr. Ganz as it sounds like you and Dr. Cole there at UCLA are looking at this. Is there any more recent research that has supported that hypothesis that you can share with the folks on the call?
PG - Certainly. For the last 5-6 years we’ve been working with a mindfulness intervention that we first piloted at UCLA in younger women who are breast cancer survivors. In that particular study, the women who received the mindfulness intervention in the randomized trial actually had that same kind of signal in their gene expression profiles. So a different intervention, a different patient group, but highly depressed and stressed and anxious, and that was beneficial. And we’ve now just done a three institution randomized trial in younger women at Dana-Farber and Johns Hopkins and at UCLA, and in this much larger sample we I have a similar outcome in terms of mindfulness actually reducing depressive symptoms, fatigue, insomnia, and hot flashes, and being persistent out to six months. We are just waiting - Dr Cole is now just doing the gene expression profiles - but we’ll be looking at the inflammatory markers and the gene expression to really see if the women who are benefiting from this, compared to the controls, have the same kind of inflammatory response benefit. Again, this is the mechanistic approach to looking at not only does something work, but how does it work? What’s associated with the benefits from the intervention?
ME - Thanks for sharing that. Let me shift gears a little bit. Now we’ve said these things help, and we’ve proved that they help, why isn’t US healthcare and US oncology as an ecosystem all over this? Why aren’t people falling all over themselves to implement these kinds of face-to-face interventions that have been so successful? First one who has a thought.
PG - Let me just say that I’m a rare bird, and as is Dr. El-Jawahir. Most medical oncologists know nothing about behavioral medicine, about psychological interventions, they may know if they got a patient who’s combative and won’t take their treatment, or isn’t showing up and that they need to get psychiatry or a social worker involved, but these are parallel streams of education. Unless you are very early in your career as a physician sort of linked at the hip with a psychiatrist or a psychologist who is rounding with you when you’re on the transplant service or some other setting, you don’t even know what they do, you don’t know the benefits of what they do are and it’s just completely siloed. And again it’s only for the extreme and desperate cases will you actually do something. Of course that’s until maybe somebody in your family has a problem and you realize how missing this is. So it’s just not part of mainstream oncology. Palliative care, which Dr. El-Jawahri is heavily involved in, has had terrible time making inroads and the palliative care physicians are marvelous in terms of dealing with pain and symptoms, but there was a wonderful interview with Diane Meier yesterday in New York Times magazine and I just want to bring it up. When Medicare changed its reimbursement, particularly around 2006-2007 where they reduced the remuneration per visit, and people went to high volume and less time with patients, all of those kinds of things that were starting to be put into oncology care in terms of cognitive services disappeared, and so now it’s tests and procedures and high volume giving drugs and very little that deals with the whole person. And that’s just the business model, I hate to say it, but those are my concerns and I think these remain barriers for us in terms of introducing these kinds of clinical services into everyday clinical care.
AE - I just want to say I agree and echo, obviously, with what Dr. Ganz said. I agree there are major major system based barriers that we need to overcome as a field, and that’s true across the spectrum of psychosocial supportive care and palliative care services across the illness continuum. And again I do think this is becoming more of a conversation, I think there has been more of a focus, I think you cannot have a comprehensive cancer center now without having a survivorship program and that’s noteworthy, and I do think the field is changing, but I think as we know culture and system takes a while to change.
I do also want to highlight as we have mentioned in this call several times that there is a shortage of mental health clinicians and palliative care clinicians to meet the needs of patients with cancer. So currently if our entire system changed around and said, ‘great I want every single patient to have a psychologist or a psychiatrist who is going to be there with them from diagnosis until survivorship, or until end of life for those who are less fortunate,’ the answer is we can’t deliver on that, and we can’t deliver on that even in academic tertiary care centers at the current pace. And this will take awhile to fix from a system based perspective there are a lot of issues with how we actually reimbursing and discussing psychology, social work, all of these supportive care services and how we’re actually valuing these clinicians on the clinical side, but beyond that I do think that shortage is here to stay for the near future and likely the state will be here for the next decade or so. And so we do have to be innovative in terms of thinking about how we can scale and disseminate services to patients with cancer.
ME - Okay thank you, and I’m going to pause there, everyone. This hour has gone by so quickly, we’re super grateful for all of our panelists for participating and thanks for everyone for attending and asking these great questions. Let me pass it over to Geoff Eich, our CEO, for any last thoughts.
Geoff Eich - I would also just echo thanks to the three of you for presenting this foundation, and we’re obviously pleased and honored to be working with you. As you know, cancer is personal to us at Blue Note, it’s something we’ve seen in our families and have experienced the ripple effects that you have described, and we’re really privileged to be in a position to help and to partner with you. So just want to echo Mark’s thanks for your insights and all of your work over the last many years in this field.
ME - Thanks Geoff. And listen, everyone, this has been extraordinary. If anyone wants to stay on and continue the conversation - I know our panelists all have a hard stop - but I’ll be on it til the last person dials off. So, once again thanks Dr. Ganz, Dr. Antoni, Dr. El-Jawahri we really appreciate you and look forward to talking to you all soon.