Cancer Stories: The Art of Oncology

"Warm Companion," by Meaghann Weaver: a palliative care doctor shares her story of a gun-shy dog and a daring rescue. TRANSCRIPT Narrator: 'Warm Companion' by Meaghann S. Weaver, MD, MPH, Ph.D. We were introduced at the front desk of a small town diner. By the time we reached the parking lot, we had committed to cohabitation. I pulled over to a small town's sole restaurant. Standing at the long counter, I waited for a carry-out dinner for the long drive home from a rural hospice visit. As a closing weekend in hunting season, I was the only one in scrubs and a mask in a diner filled with camouflage and deer antler de´ cor. The guy next to me was loudly complaining to his hunting buddy how his new puppy was gun shy and let the birds go. "Good for nothing." I mumbled that as a pediatrician familiar with gun violence and firearm accidents, I'm also gun shy. He pointed to his truck and jokingly suggested, "Welp, maybe you'd be a better pal for that whelp." One look at those puppy eyes from the cargo bed, and I emptied my wallet, handed him my uneaten to-go-boxed dinner, and carried his pup to my car. "No more guns," I whispered as we hit the highway. She joined our little family at the onset of COVID-19, snuggling close to us in the midst of the pandemic's physical distancing. I had planned to name her Agape. Her first collar tag jingled with the idea of a universal, unconditional love that transcends and persists regardless of circumstances. My kindergarten-age daughter insisted on calling out "Lovey" as she followed the new pup, all paws, around the house. The name persisted until the puppy responded only to "Lovey." Her collar tag was soon replaced with the vernacular: Lovey. Lovey represents a bonded attachment, a security and safety, and a held comfort. She is Lovey. Lovey nuzzled into our relationships and roles. My dad added milkbones to his right back pocket since his left back pocket was already filled with peppermints and lemon drops for my daughter. Lovey quickly tripled my pedometer footsteps. She motivated me back into early morning jogging. She introduced us to new parks. She taught us persistence with tennis ball retrievals and a dogged perseverance for finding frisbees. Lovey wagged her tail at kind strangers with sureness of future friendship and was on guard and protective when needed. She mastered the Labrador lean, offering my shins a counterpressure under the telehealth tabletop. She reminded us of the power of instinct and interaction. She represented goodness. One chilly morning after a night shift, I took Lovey to visit a lake further than our usual landscape. Walking through tall grass with the harsh prairie winds whipping around us, Lovey suddenly started barking an unfamiliar howl. She wouldn't let me check her paws for nettles or fur for burrows as she frantically lunged toward the lake. Far off, I then saw what she witnessed. A lone ice fisher's dog had been walking on thin ice 60 feet from the edge, crashing through, while the angler stood sturdy. The ice fisher went to rescue his dog but instead also crashed through. They both thrashed and struggled in the freezing water. They gasped and clawed at the slippery, growing ice ring around them. Without a sense of locale or direction, I pinged 911 to my cell phone and tracked their 11-minute arrival. Racing to the lake edge, I yelled out that help was coming. I prayed for a protective bradycardia, fearing a hypothermic-induced arrythmia would kill sooner. If I entered the broken ice waters to reach them, we'd all just freeze together. Helpless. I tried to throw Lovey's leash to them. Useless. Without a rope and without ability to reach out, I felt "Good for Nothing." Except I was present. Fully present. I was bearing witness to suffering without shying away. I couldn't rescue. I could just remain. The presence of another human served as an antidote to aloneness. I instructed the fisherman to look at me. I asked him to trust me. I told him to protect his strength by stopping the struggle. Just be with me. Just hold on. I assured him that his dog knows how much he is trying to help. "Tell me about your pup." Teeth chattering, he told me about how they met. Then, a sacred silence. I asked if he wanted to keep talking. He told me about how he named her. Silence. He told me he rescued her, but he's pretty sure she rescued him. We talked about the reciprocity of such relationships. As the minutes dragged on, his breathing changed. I suggested, as I have done time and time and time again between covering COVID-19 comfort care night calls in New York during the pandemic surge to rural home visits during relentless variants, that we breathe together. As in palliative clinical practice, I heard myself telling him to trust his strength. I suggested he curl to protect his core. I found myself instructing him to protect his heart. Then, true to medicine's focus on what matters most in life, I reminded him to remember love, forgiveness, and peace and to truly trust his body. He rallied. He lifted his dog's back legs. The dog slippery-sprinted over to join Lovey in a victory jig. Downward dogs bowed. Paws pranced. Collars jingled. We heard the sirens. Rope and rescue floaties reached him. The Sherriff turned his back while I switched his bib overalls for my sweats and fleece. Without guidance or prompting, Lovey and her new-found canine friend covered the fisherman with their bodies. They covered his core and licked his face. Our faithful companions warmed him. They remained silent and still as he started to stir. Their patient presence and warmth brought healing. After a prolonged silence filled with just gentle presence, his chattering teeth started to form words. His dog barked in recognition of a familiar, favorite voice. Companioning represents sacred stillness, not frantic fixing. Companioning means being present to another's grief, pain, or suffering. Companioning represents profound presence rather than rescuing. A primary tenet of companioning is bearing witness to the struggles of others without shying away. As I tried to add warmth to the pile of pups, I thought about how we've all been walking on thin ice in medicine, especially during the pandemic. Companioning applies to contingency or crisis phase. Companioning has meant holding up the iPad for telehealth hospice goodbyes during visitor restrictions. Companioning has meant tirelessly advocating for vaccinations and masks without judgment or unkindness. Companioning has meant pivoting to telehealth to continue to caringly check in on patients with immune system vulnerabilities while protecting them from clinic exposures. Companioning has meant wiping the brow of a colleague when they can't reach past their protective layers. We haven't been able to rescue the curve or fix the surges. Still, companioning means being present for each other and our communities to offer healing warmth in a cold world. Dr. Lidia Schapira: Welcome to JCO's Cancer Stories: The Art of Oncology, 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 of the shows, including this one at podcast.asco.org. I'm your host, Lidia Schapira, Associate Editor for Art of Oncology, and Professor of Medicine at Stanford University. And with me today is Dr. Meaghann Weaver, a lead regional ethicist at the National Center for Ethics in Health Care, and an adjunct associate professor at the University of Nebraska. We'll be discussing her Art of Oncology article, 'Warm Companion'. The views expressed in this podcast are those of the author and do not necessarily reflect the position or policy of the US Department of Veterans Affairs, the US government, or the National Center for Ethics in Health Care. Meaghann, welcome to our podcast. Dr. Meaghann Weaver: Thank you. It's a joy and privilege to be with you this morning. Dr. Lidia Schapira: So, tell me first a little bit about your writing process. How does a story present itself to you? When do you know that it's time to put it on paper or on screen? Dr. Meaghann Weaver: It's interesting the way that narrative medicine evolves in a really different way than research and summarizing data in written form. In many ways, I think of that as a cognitive process, where you can be planful and structured. Whereas narrative medicine, it occurs as a story that just has to be told. It's beating so profoundly in your heart, that even if you want to contain it, and hold it as personal, I think for me, it's really an uninhibited moment. So, funny enough, I tend to do research during day hours or very structured hours, whereas narrative medicine is very much waking up in the middle of the night saying, 'This has to pour out. I can't continue to contain the truths from this narrative.' Dr. Lidia Schapira: It's a lovely description. Tell me a little bit about how you decided to share with others? I totally understand the need to reflect and tell a story, but how do you decide what is private in what you want to share? Dr. Meaghann Weaver: I would say that in clinical experience, and even in ethics consults, there are so many stories that are quite profound, but are so intimate, are so personal, even if you de-identified them, they border on sacred and so those for me remain really untold. Those are held by the participants of the story. For me, it's this particular narrative in one of our staff meetings, we had a couple of extra minutes. And so, I just shared, you know, what had happened over the weekend. And my colleagues said, 'You have to write that.' And a number of them followed up and said, 'Have you written that? You need to write that.' So, in many ways, it's if the narrative resonates with others, in many ways, they think sharing can be selfless. It can be hard to share. But my colleagues really said, 'You might have a duty to share this one because it resonated with our experience and COVID.' Dr. Lidia Schapira: It's a lovely story. So, tell us the story of how you met Lovey? How does the pup become your family's own? And how Lovey led you to this moment that is so amazing that you describe so beautifully in your story? Your story, unlike many other narratives in the Art of Oncology, has so much suspense to it. I mean, the reader will hold their breath, to try to see how the story ends. Dr. Meaghann Weaver: Thank you. Well, I met Lovey in really spontaneous circumstances. I, as many during the pandemic, anticipated adding a family pet to our family, was starting to prepare, but Lovey in many ways was a little bit impulsive, because I met her where she seemed particularly vulnerable. And I just experienced a time of seeing her, seeing that she might have been in an environment that wasn't actually drawing out her strength. So, she wasn't living up to the hunting dog persona. And so, in her community, she was maybe perceived as not useful or not productive, that I was encountered her at the end of a hospice visit, and we know from oncology, we know from hospice, from palliative care, presence and being and really living into your strengths, like your core identity. So, I encountered her and noted that she's really gentle, and she might not be a hunting dog, but she would have such joy and contribution to the right community in the right setting. And so, in many ways, it was an impulsive attachment. And then she so quickly nuzzled right into our family and brought so much comfort and truly brought companionship, and she helped us to re-engage and live life with a deeper level of fullness. That's Lovey. Dr. Lidia Schapira: Sounds absolutely wonderful. How old is Lovey, now? Dr. Meaghann Weaver: She just turned two. Dr. Lidia Schapira: In your essay, you talk a lot about companionship. You also mentioned the concept of bearing witness to another's suffering or crisis. And you talk about presence. Can you tell us a little bit about these three concepts and how they came to you so clearly, as you reflected on this incident, and perhaps you should tell our listeners also, what actually happened, and what the story is about? Dr. Meaghann Weaver: So, the story is about after a particularly challenging night shift, I took Lovey for a walk at a lake which is of further distance from our usual geography, and it was deep winter, there was an ice fisherman out about 60 feet from the lake edge. And it's very common in our community for ice fishers and hunters to bring their dogs with them. It's just a partnership. This particular pup fell through the ice. Lovey and I were walking quite a distance from the lake and she just had this really impulsive shrieking. I thought she was wounded. She had this really strong instinct of another animal's injury or needing rescue. So, she was really pulling and lunging me. So, I followed her, actually pretty nervous because she was acting so out of character. I followed her and she brought me to the lake's edge, and then I saw the fisherman had also fallen through in his attempt to rescue his dog. They were too far out. I tried to throw her leash, but there was no way for me to rescue, which as you can relate in our calling in medicine, we're trained to rescue, we're trained to fix, to intervene, it felt so counter natural. It felt so counter to training. And so, just calling out connecting with him, trying to let him feel that I was really close, even though I was at quite a distance. I called for help. I pinged 911 to my phone. I had no idea really where I was other than somewhere very rural area like a frozen lake. So, I pinged them to my phone. I just continued to reassure him that help was coming. And I just asked him to stay connected with me. It was clear that his dog gave him such meaning, you know, the fact that he would sacrifice his safety to rescue his animal. So, I tried to engage him in narrative. And it seems what was most helpful for him was less when I asked about him as the fisherman or as a human and more when I asked about his dog, and how he was connecting him back to what mattered to him. And so, very long story short, he was able to rally just like we see at the end of life for many of our patients, this final rally, so he rallied, and lifted his dog who came to us, and then we had a really sweet reunion with his pup. So, the sheriff arrived, it took about 11 minutes, and I was quite concerned physiologically, whether we would sustain life in that time gap. So, the sheriff arrived; he was able to throw ropes and rescue floaties, and that patient was able to then be retrieved. He was pretty obtunded when he came out of the water, but was able to hold on to the rescue equipment and to just be then pulled to safety, then warmed really with our two dogs just laying on him licking him, very instinctually, they just covered him, and it was just their warmth and being present. I think that's what we see in medicine often when disease has progressed, and we are sort of past our biomedical ability to intervene. In many ways, there is still profound healing. And for me, in this narrative, the healing was human warmth and the presence of living beings, and companioning, remaining present, bearing witness to someone who is really struggling, bearing witness without thrashing around, feeling like the only help you could offer is fixing. I think that the story would have been more exciting if it were a palliative care doctor ethicist dives into freezing water, but we wouldn't have helped him. So, it's really saying, 'I'm gonna bear witness, stay with you, companion with you as part of your healing.' I think there's a message in there for medicine, too, staying with our patients. There's actually a narrative there too, because of course, in hypothermia, you need to change the person's clothing. And so, probably the humorous part of the story is the sheriff turning around and me putting the fisherman in my fleece and my scrubs, and me putting on his bib overalls. I think that's probably quite the visual. Dr. Lidia Schapira: I must say, I saw that. I didn't know what you looked like, but I could just imagine the scene. Tell me a little bit about that moment, when you have to do this cognitive switch from, 'I'm diving and I'm rescuing to I'm bearing witness and I'm present?' Dr. Meaghann Weaver: That's such a powerful cognitive switch because, in many ways, it's instinctual to fix and to rescue. So, I almost would say that is a practice that has to be in some ways predetermined. And so, I think it's a commitment and it takes practice outside of the clinic space to really say, 'My role in this patient's life is to help them ask the questions they need to ask, help them explore the answers without me forcing the answers upon them', and help them in some ways you could think establish the safety net that they need. So, foster that, without forcing it, without thinking my sense of rescue would be the same that would be most beneficial to them. So, I think that is really a practice that requires contemplation and commitment because the impulse is to rescue. The impulse is to fix, and so, it really takes strategizing. Dr. Lidia Schapira: Meaghann, I'm sure you've given this some thought, how would you have felt if the story had a different ending? If the sheriff didn't arrive in time? Dr. Meaghann Weaver: I tried to protect myself from thinking in that way. I think I would have experienced immense guilt, and I perceive it would be natural to feel that I then should have gone into the water even if I couldn't have made a difference. I anticipate that there would have been a significant weight. And so, it takes thinking in a logical way because my heart would have said, 'Well, just dive in and be with him.' And also, I think the emotive experience of guilt would have been really heavy. I thank you for asking. I think that's a courageous question and one that I've have to reflect on. Dr. Lidia Schapira: You've written about guilt before, so I know that you are certainly not shy in thinking about the emotional landscape of our work. But let me end this with a little bit more of a playful question. And that is about the pups here, the role that the dogs played because the dogs are all about instinct and impulse. We can't ask the dogs about their cognitive experience, but we can watch their behavior. And I was certainly moved, I laughed and felt this incredible energy and warmth when you describe both pups were on the body of the fisherman, warming him up. So, tell me a little bit about this bonding with dogs and using dogs both for therapy for oneself and therapy for others. Dr. Meaghann Weaver: Yes, it's amazing to me the way that our pups have a way of connecting with us and with our core self… Oops, my pup is participating. Connecting us with our core selves. I noticed even in my work, that the respite and the sense of connection that we have, with our animals, with our pups, there's something so instinctual and uninhibited about it. And I also think much of our work is so serious, but their playfulness, and then their unconditional and really uninhibited celebration, when we're sort of reunited after a long day or there's something, it's really hard to describe it just this profound feeling of warmth and of belonging, and companionship. Dr. Lidia Schapira: Well, thank you so much for the conversation today for this absolutely beautiful essay, for sending us your work, and for sharing this experience with the broader community of readers. Thank you, Meaghann! Dr. Meaghann Weaver: Thank you! I'm grateful and I do turn quickly when I receive the journal to this section. So, thank you, I find that it resonates with my head, my heart, and my spirit. So, thank you for fostering that. Dr. Lidia Schapira: You're very welcome! Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology 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 of JCO's Cancer Stories: The Art of Oncology podcast. This is just one of many of ASCO's podcasts. You can find all of the shows at podcast.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.

"Dose-Painting," by Shivani Sud: a resident creates visual narratives within two patients' dose clouds. TRANSCRIPT Narrator: 'Dose Painting' by Shivani Sud, MD. (10.1200/JCO.21.01524) When asked to describe radiation oncology, my first recollection is watching chart rounds as a medical student. Sitting along the conference room periphery, I observed as dosimetrists projected patients' scans, residents presented histories, and attending physicians reviewed treatment plans. Far from the usual hospital rounds with plans consisting of procedures, consults, and medication changes—here, treatment plans are scans overlaid with intricate colorful lines denoting the amount of radiation traversing internal structures to arrive at the target (ie, tumor) volume. This dose visualization is our primary method of conceptualizing and articulating radiotherapy treatments. Recent technological advances enable delivery of radiation with immense precision to the extent we dub some techniques as "dose painting."1 Starting with our planning scan consisting of computed tomography images of the patient in the treatment position, we delineate areas of tumor and likely microscopic disease to compose our target volumes. In collaboration with dosimetrists and physicists, we adjust various parameters including multileaf collimators—movable metal leaves that sculpt the x-ray beam as it departs the linear accelerator to enter the patient—and beam angles such that we cover the intended target with radiation while avoiding delicate neighboring organs. We evaluate and iteratively optimize our radiation plans and the resultant dose distribution. Balancing the correct radiation dose, treatment field size, and shape are critical for preventing recurrence, minimizing toxicity, and improving survival. At the first glance, our peer review reduces the patient to a spectrum of grayscale pictures a few millimeters thick as we scroll through their bodies searching for tumor and ask whether our colorful delineations will adequately treat the cancer. Controversial plans elicit the most discussion as we glean insights into patients' lives and decision making. Why this shorter course of radiation? His priority is quality of life and maximizing time at home. Why no concurrent systemic therapy? She is too frail for chemotherapy—we are escalating radiation dose as an attempt for more durable local control. Why are you sparing a sliver of the scalp? She fears children will tease her for balding. Answers live within a broader narrative. These rainbow-colored three-dimensional dose clouds represent the complex convergence of patient history, goals of care, humanity, medical judgment, and cautious control of our treatment medium—radiation. As a resident, I view the dose clouds denoted by the color wash of the computationally optimized radiation distributions through the lens of the patient-physician relationship—literally and figuratively. During late nights and unrushed moments, my mind drifts back to my favorite childhood pastime—spotting shapes in the clouds. This activity is a form of pareidolia—the human tendency to perceive meaningful imagery amid a random or ambiguous pattern. As a child with a sweet tooth, I pictured popcorn and cotton candy in the sky. Now, this manifestation of my imagination was centered on my most salient thoughts—caring for an older woman (Ms V) with lung cancer and a child (Lilly) with Ewing's sarcoma. I grappled with whether our treatment plans were adequate, too little or too much. I turned to painting to articulate my angst as art is part of how I reflect on complex situations. For both Ms V and Lilly, I traced the isodose lines defining the radiation dose distributions to maintain fidelity to the original radiation plan. I then folded those dose distributions into the visual narrative of the paintings to create a reflection of their journeys amid their dose clouds. Ms V (Figures 1 and 2) had countless admissions for chronic obstructive pulmonary disease, heart failure, valve replacements, and now cancer. Ms V longed for quality time until the sun sets. Her case was complex—she had an early-stage lung cancer, but because of multiple comorbidities, she was not a surgical candidate. She projected courage and resolve in conversations about her goals of care while accepting death as inevitable. We treated her with definitive intent linear accelerator-based stereotactic body radiation therapy. Months later, she died from a heart failure exacerbation. I was heart-broken and humbled. Ms V taught me that prognostication is an elusive art for physicians—I was naively optimistic about curing her early-stage lung cancer. She was pragmatic about embracing the trajectory of her comorbidities. As I scrolled through her treatment plan, the beams enveloped the tumor in warm tones denoting high dose as it floated through a sky of trapped air. I imagined her wishes for quality time expressed as colorful, vibrant brushstrokes of light emanating from a sun setting into a calm, reflective ocean overlaid on my target volume. Lilly (Figs 3 and 4) was a bald, spunky and vivacious four-year-old girl whom I met after multiple rounds of chemotherapy for a chest wall Ewing sarcoma. As we talked about radiation therapy, Lilly flapped her arms while proclaiming herself a butterfly. Weeks later during a status check, she cried in agony from radiation esophagitis. Her mother solemnly whispered "I wish I could take the pain instead of her." That evening as I was looking for a picture book for my niece, I came upon the story of a baby giraffe on quest to find his spots until one day while he slept, rays of sun shining through the leaves of a tree tanned his skin with perfect spots. Curiously, I searched for the evolutionary rationale for giraffe spots—they are a trait passed between mother and offspring with size and shape predicting fitness for survival. My mind wandered attempting to create meaning amid these random coincidences as I wrestled with uncertainties about how Lilly would fare after radiation. I sketched Lilly as a baby giraffe—her spots, much like the storybook, sculpted by leaves (of tungsten metal) distilling rays (of photons) to sizes and shapes reddening her skin but designed to improve her chance for survival, spots shared by a mother wishing to take her daughter's suffering upon herself. The painting's striking visual of mutually shared bold, whimsically colorful patterns inspired by the axial, coronal, and sagittal views of the radiation plan set against a stark dark matte background aimed to capture the vibrancy of the love I saw connecting Lilly to her mother and their resilience in the most trying times. Witnessing their journey underscored the permanence of the mother-child bond filled with tenderness and compassion that moved me as I was then caring for my own mother who was receiving radiation therapy. When my mother's radiation oncologist showed us her treatment plan, I was engulfed by the same questions. Is the dose and field size appropriate for tumor control? Will there be irreparable damage? Will her symptoms improve or get worse? Is this what she wants? I viewed her treatment plan through the lens of a meticulous radiation oncologist in training, but this time, I was sitting in the chair along the wall reserved for family members. Like the patients I care for every day, as we scrolled through the intricate colorful isodose lines, I trusted they were the optimal intersection between science (dose) and art of medicine (painting) we strive for as radiation oncologists. Dr. Lidia Schapira: Welcome to JCO's Cancer Stories: The Art of Oncology, 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 of the shows, including this one at podcasts.asco.org. I'm your host Lidia Schapira, Associate Editor for Art of Oncology, and Professor of Medicine at Stanford. My guest today is Dr. Shivani Sud, a resident in radiation oncology at the University of North Carolina. We'll be discussing her Art of Oncology article, 'Dose Painting'. Our guest today has no disclosures. Shivani, welcome to our podcast. Dr. Shivani Sud: Thank you so much for having me. It's a pleasure to be here. Dr. Lidia Schapira: So, I'd like to start this by asking our authors to tell me what's on their reading list right now, or to recommend a book that has been interesting and inspiring to you that you read in the last year? Dr. Shivani Sud: That's a good question. I'll be completely honest, I've been a bit boring at the moment with copies of clinical essentials of radiation oncology, and a few of our other handbooks. Frankly, during the pandemic, and especially with current events, I think I've been more in the nonfiction realm, especially just trying to submerge myself in the news articles and the ground level journalism that's been coming out and so I would actually say that these days kind of a local newspaper and things of that nature have been a bit refreshing. Dr. Lidia Schapira: Let's turn to your essay and your art. You're very unusual in that you bring to us in your narrative, not only the beautiful narrative and written word, but also visual art. Have you always been a writer and a painter? Dr. Shivani Sud: I have enjoyed painting for a long time. It was one of those things that started by, I think I was just copying my sister, she once got an acrylic paint set, and she was painting on canvas. And there I was doodling something on paper. I was always one of those kids who couldn't help but try to fit the whole rainbow into a coloring book page, or any art assignment. And I think that as I went throughout school, and the multiple levels of training that we encounter, as physicians, that painting just became my outlet, whether it was expressing myself, decompressing, feeling like I was channeling my thoughts and my energy into something, while not necessarily kind of sitting idle with those thoughts. Dr. Lidia Schapira: Your essay helps those of us perhaps, who don't paint as a way of expressing ourselves to understand your process a little bit. And you start by saying that you've always enjoyed looking at shapes and finding connections. Can you talk to us a little bit about the way that you view shapes and find connections? And tell us how you see that in nature, and then in your work as a radiation oncologist? Dr. Shivani Sud: Certainly, I think a lot of this goes back to that word we mentioned, pareidolia, and this human tendency to want to find meaning in randomness. And so, that was that childhood memory where you're on the playground with your friends, and you're lying on a grassy hill, and you're looking up at the clouds, and somebody sees a bunny, and somebody sees popcorn. And then someone says, 'Well, it reminds me of cotton candy.' And so, I think as I then look forward to these late nights, these unrushed moments when frankly, you're maybe a little bit tired, maybe a little bit delirious, who knows, but you're looking at your work, you're seeing these shapes, you're looking at the plan, those memories of what the patient said was important, your abilities and limitations to control radiation dose, and seeing them merge together. And I think it was really that immersion of, here are these dose lines, they're not random. They reflect meaning, they reflect what I am trying to accomplish and what we as a team are trying to accomplish for this patient. And so that was really what gave rise to these visual narratives in trying to take the dose lines, take the patient's narrative, and essentially create that visual narrative within their dose clouds. Dr. Lidia Schapira: I found your essay so moving and so clear in helping somebody who is not a radiation oncologist think through all of the steps of the treatment planning and the delivery of the treatment, but what I appreciate so much about your writing is the humanity you brought into this. One of the lines I found so beautiful was when you're describing the scene of this older woman who has so many comorbidities and now is facing lung cancer, and you're trying to palliate and treat with your treatment. And you say, you imagine and I'm quoting you now, 'her wishes overlaid on my target volume'. Can you tell us a little bit about how you imagine the patient's wishes and aspirations as you are crafting a treatment plan and delivering that plan? Dr. Shivani Sud: It all starts with the consultation. I think oftentimes, even myself before I became a trainee in radiation oncology, I thought it would be a very impersonal field. I imagined just plans and computers and scans, and that it wasn't a field where you necessarily interfaced with patients as much as I learned that we do. And so, the consultation is an amazing opportunity to get to know the patient. You have reviewed their medical record, you've scrolled through their scans, and you started to think about how you want to treat things. And all of that comes into reality when you actually meet someone. You actually talk about what is important to them. Who did they come with? What does the person who was with them say about them? And what's important to them? How do they advocate for them? And so, a lot of it is that merger of this is what I've trained to know. This is what the guidelines say. This is what the studies say. And now I'm meeting you, and I have an opportunity to learn about you. So, how can I take this information? And how can we embrace it in what you want to come up with the best plan? Dr. Lidia Schapira: That's beautifully stated. You tell us in the narrative that this patient told you that she longed for a quality time until the sun sets, and then you drew or you painted this oil painting, right? It's an oil on canvas, that you titled 'Until the Sun Sets', and you said that you then use the art as a way of expressing yourself, but then also sharing it with others, perhaps gifting it to a loved one. Talk a little bit about how this art helps you to reflect, process, express, and then share? Dr. Shivani Sud: I think, for me, a lot of the expression has to do with both the patient's journey, as well as my journey here. I started out as an outsider. I didn't understand what these plans meant. How they came together. And then as a trainee, working with Ms. V, I was able to understand, how do we actually use radiation to give her a short course of treatment, so she can get back to that vibrant life that she was enjoying, that quality life that she wanted, until the sun sets? And in her case, especially, beyond just the radiation, she taught me so much about what we strive to do as providers and where our limitations are. So, I found myself very enthusiastic about treating this early-stage tumor. I had all the statistics about what the control rates were, and everything of that nature. I remember her being very pragmatic about her multiple comorbidities and whether or not she felt she would derive a lot of benefit from treatment. And indeed, in the end, she was right. You could argue there might not have been a lot of benefit from treatment, because she passed away, a few months after we treated her, from those other comorbidities. But I remember after she passed away, and I saw that chart notification, it made me rethink all of our conversations, and that was one of those moments where you pause and you say, 'What did she want? And what was I trying to achieve? And where is the overlap between the two of them?' And so, my target in the moment was that gross tumor volume. It was that nodule in the lung that I had circled, it was the hot spot in that dose cloud. And what I was trying to achieve for her was short treatment so she can get back to her day-to-day life. That meant I needed a hot dose in the center. I needed things to be cool and calm around the periphery. So, I didn't damage too much lung. And then I thought about this sunset, and there was this target volume. There was light because she was so light, so bright, so vibrant. And I had that sun setting into a calm ocean, not a turbulent one, to reflect her pragmatism, her ability to stay calm, cool, collected in the face of not only lung cancer but all of these other comorbidities. And so, really, it was meant to be 'What does she want? What is she stating? How do we accomplish it for her? And how do we put that forward in a visual narrative that someone else can understand and appreciate aside from, here are some colorful isodose lines that happened to look nice?' Dr. Lidia Schapira: I must say I find it very inspiring to hear you talk because you talk about radiation oncology, being a technical field and I hear in your voice, everything about connection and mission-driven work. So, I think it's beautiful. The idea is that you're sort of translating and applying what you hear from the human being who is bringing you this disease into your thinking and crafting your dose and your delivery. That's really very beautiful. I wonder if you can share with us a little bit about your comment about the importance of the caregiver story. And in the essay, you say that perhaps some of your response to your patients was also impacted by your experience as a caregiver for your mom when she was undergoing radiation. Can you share a little with the readers and listeners? Dr. Shivani Sud: I think this is part of the reason why Lily's situation and her journey resonated so closely with me. She and her mother were an inspirational duo, regardless, but I think there was this extra level of connection, as we took care of Lilly because my mother was about to start her radiation treatments herself. This is another one of those examples, where, as a trainee especially, it feels like you start off as an outsider, and then you're part of the system. And then here, I was, not necessarily, you know, I wasn't part of my mother's radiation treatment delivery team, but I was still a radiation oncologist in training. And here I was sitting there by her side, trusting the system that I was once an outsider to, and then was once part of, but from a different vantage point. And so that's kind of those shifts in where the chair is located. And in chart rounds, it was along the periphery for the medical students, and then you're sitting in the main seat as the radiation oncologist. And now you're sitting in the chair along the wall reserved for family members. I think the role of a caregiver is tremendously important in terms of caring for patients. First, of course, for the patient's well-being for them to have someone to speak with, at least that was the case with my mother. We would often talk about her symptoms, and what she was afraid of, what she wanted out of treatment, the parts of radiation that were scary and nerve-wracking to her. And it was interesting to now be on this cusp and, had her tumor arisen five years before, I wouldn't be able to speak both languages of daughter and radiation oncologist. But given the point in time, there were many moments where I could reassure her. And there were also many moments where, after I reassured her, I would then sit there and say, 'Oh, dear, is this actually going to work?' You have all this training, but then you kind of pause and you say, 'Well, do I believe it?' And you think about things a little bit differently, again, when you're not necessarily in the system, but you understand the system, but you're sitting in a different position. Dr. Lidia Schapira: You're clearly inside the system. Now, my final couple of questions are these, one is what motivated you to write and publish the story? Dr. Shivani Sud: The paintings themselves arose from seeing these visual narratives. And essentially the same way that a writer likes to put thoughts to paper, I wanted to put paint to canvas, because that was the way that I was going to remember this connection that I had made. And this was the best way that I would be able to share the connections that I had made with others. In terms of wanting to pen the story, part of it was giving light and continuity to these experiences of taking care of these two patients who had taught me so much and clearly struck a chord with me in terms of wanting to craft these paintings and to also share with others that there is humanity in our field, there is such a deeper connection that we make. And even though these computer-generated lines might seem so impersonal, and you see us scrolling through scans and things of that nature, there is very much a human connection, a human cause, and purpose behind all of that, and everything we do is centered around the patient. And this for me was just my way of showing a way in which I bring my mind, body, and soul to the work that I do. And take home this work and say, 'This is where it's a part of me.' Dr. Lidia Schapira: Have you shown your artwork? Dr. Shivani Sud: I have shown my artwork to a few of my co-residents. A few of my attendings have seen it as well, I haven't widely circulated it at this point in time. Dr. Lidia Schapira: Shivani, thank you so much for sending us your work, and please remember to keep your humanity about your work. It is inspiring. It is inspiring to hear you. It was really moving to read your essay and to appreciate your artwork. Thank you so much. Dr. Shivani Sud: Well, thank you so much for having me. Thank you for accepting the piece, for encouraging us to embrace our humanity in the work that we do, and for having the Art of Oncology section. It's a pleasure to be able to join. I really appreciate your taking the time to include me. Dr. Lidia Schapira: Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology 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 of JCO's Cancer Stories: The Art of Oncology podcast. This is just one of many ASCO Podcasts. You can find all of the shows at podcast.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.

"A Note of Gratitude" by Austin J. Price: A senior resident honors his grandmother and expresses gratitude to a doctor who had a long lasting influence on him and his family. TRANSCRIPT Narrator: "A Note of Gratitude" by Austin J. Price, MD-MPH (10.1200/JCO.21.01781) Mary Ann Richards-Elbrader was many things. Born in rural Kansas in 1936, she was a product of the pre-War Depression Era. That fact, I am sure, had an impact on the type of person she would become—a hard worker to a fault and a fiercely loyal family woman. She was the mother of five, the grandmother to 13 including me, and a friend to all, rarely knowing a stranger. Only a high school graduate herself, she believed wholly in the value of education, something that no other person could ever take away. Owing to that belief, all of her children earned college degrees, something that made her immensely proud. She was quick to anger and even quicker to apologize. Devoutly faithful, she taught her children to believe in something greater than themselves. On a more lighthearted note, she was known to lay back in the recliner after a hard day with a stiffly poured vodka. I recall the kindness ever present in her eyes, seen through large, clunky, 80's style frames and the lines on her face that easily divulged to the world she was someone who loved to laugh. The fact that she became a patient with cancer in 1995 is quite likely the least interesting thing about her. My grandmother's journey with cancer began, as many things did for her, in the service of others. She was a frequent blood donor. After giving blood once, she was found to be anemic and instructed to see her primary care doctor. The diagnosis came swiftly— colorectal cancer. From what I have been told, the goal initially was cure. I was very young and hardly able to grasp the nuances of her clinical course. Nonetheless, I know she had surgery and chemotherapy, and for a while after that, everything seemed fine. My mother and aunts recall a discussion when there was mention of age spots in her liver that would be monitored. That probably seemed harmless at the time, but it sounds so ominous to me now. Indeed after a 1.5-year remission, my grandmother experienced a roaring recurrence, this time in the liver. As tragic as it was, I share these details merely as a prelude to something wonderful. It was 1998, and my grandmother found herself seeking a second opinion at the University of Nebraska from a medical oncologist named Dr Tempero. As my family recalls, there was a clinical trial for patients with colorectal cancer metastatic to the liver ongoing at that time. My grandmother initially qualified but was soon disqualified for medical reasons. Despite that, our entire family quickly came to thoroughly appreciate this oncologist. What it was about her that resonated so deeply is difficult to express in words. In my mother's terms, it was her confident, no nonsense, but never cold, demeanor that provided assurance that she knew her stuff while still having her patients' best interests at heart. She was also very honest from the outset in a compassionate, preparatory way, without becoming bleak. Perhaps most striking, my mother recalls, was their last meeting in Omaha, when she explained that there was no more she could do from a medical prospective. There were tears in her eyes, but she did not cry. She exuded both empathy and resolve, which made her more human but no less professional. My grandmother succumbed to cancer on September 20, 1999. I was 8 years old. I never spoke to her specifically about Dr Tempero, but I remember hearing stories about that doctor in Omaha who was so acutely aware of the human experience. A decade later, I was about to start my freshman year of college. I had always been reasonably smart, fairly ambitious, and done well in school. However, as an 18-year-old, I shall admit that I was more preoccupied with the social aspects of college than I was with what might happen in 10 years. Slowly, I became more interested in the prospect of going on to medical school. Much of my early childhood had been fraught with my grandmother's illness and I recalled the various roles physicians had played in her life. My mother always told me, "If you are going to be a doctor, be like Dr Tempero." I realized early on becoming such a physician would require much more than good grades and perseverance; it would require a constant commitment to being present, humble, and empathetic, without losing the confidence that allowed others to find comfort and value in my assessments. Ultimately, I decided that was a challenge I wanted and needed to pursue. With the unending support of my family and friends, I got into medical school and graduated in May 2019. I am now an internal medicine resident in San Francisco. My residency experience has been greatly different from what I anticipated. As the COVID-19 pandemic descended on our hospital, I found myself as an intern charged with facilitating end-of-life discussions through FaceTime, fully clad in personal protective equipment. Continually, I had to explain to families of the critically ill why they could not visit their loved ones. There was no instruction manual on how to have such conversations, but I know every day I channeled what I had garnered from my own family's experiences with the health care system. I am unsure if I succeeded in the ways that Dr Tempero did, but I have never stopped trying. In December 2020, I was triaging patients from the emergency department. While gathering the history on one patient, I asked "who is your oncologist?" When he replied, "Dr Tempero," I froze. Surely it could not be the same doctor, the same one I had heard about since I was 8 years old? The one whose unique abilities I would always tried to emulate? When I left the room, it did not take much time on Google to realize it was. I shared portions of this story with my patient, who was extremely complimentary of her. That evening, when I got home, I called my mother to share this truly cathartic experience. Ultimately, it was she who implored me to personally reach out. I sat down at my desk and wrote her a note of gratitude. The following day I got an email notification while at work. I waited until I had a few minutes to read her response in privacy: Dear Austin, Your letter is, without a doubt, the most touching letter I have ever received. I know how busy you must be right now, and I was doubly honored to know that you took the time to write this thoughtful message. Thank you from the bottom of my heart. I have had the privilege of helping so many patients over the years and each one becomes a gift. I may not be able to turn the course of their disease but I can always make the journey easier. On a Wednesday evening in early May 2021, a little over 23 years after she was my grandmother's doctor in Omaha, I met Dr Tempero for the first time. I joined her and her husband at their apartment in San Francisco for a glass of wine. We discussed medicine, our mutual love of travel, and of course the unique situation that precipitated our meeting. I could easily perceive the qualities my family had always admired about her. She was interested in my story and my goals, but yet forthcoming about her life, family, and career. Her persona was welcoming, but yet demanded respect. Two hours later, she walked me downstairs and waited until my Uber arrived at her door. As I rode across the city, I contemplated the miraculousness of these events. I wished, as I always will, that I had more memories of my grandmother that did not center upon her illness, but the reality is I do not. What I do have is the memory of this encounter that has left me with a sense of inner peace and optimism, reassured that I am exactly where I am meant to be. I write this in gratitude to a doctor, who had no way of knowing her kindnesses would have such lasting influence. Of course, I also hope to honor my grandmother's legacy. I know she would be honored to see how her own misfortune somehow managed to be the genesis of such positivity in my life. I believe she would also challenge us all, as do I, to be like that doctor in Omaha. Dr. Lidia Schapira: Welcome to JCO's Cancer Stories: The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows including this one at podcast.asco.org. I'm your host Lidia Schapira, Associate Editor for Art of Oncology and Professor of Medicine at Stanford University. With me today is Dr. Austin Price, a senior resident in internal medicine at California Pacific Medical Center, soon to be an infectious disease fellow at the University of Kansas. We'll be discussing his Art of Oncology article, "A Note of Gratitude". Our guest has no disclosures. Austin, welcome to our podcast. Dr. Austin Price: Thank you very much. Thanks for having me. I'm happy to be here. Dr. Lidia Schapira: Let me start by asking if you are, in addition to a writer, also an avid reader? Dr. Austin Price: Yes, in the past at least I have been somewhat stymied by going into residency, but in the past, I liked to read a lot. Dr. Lidia Schapira: So, tell me a little bit about your past readings and maybe favorite authors or books, something you'd like to share with our listeners. Dr. Austin Price: I like to read about medical history. And so, one of my favorite books actually is by Dr. Paul Offit, and it talks about the early days of vaccines and how there was, I think it's called The Cutter Incident, but it's a great book. I may be misquoting the actual name, but great book. When I was in Baltimore, and doing my master's, he gave some guest lectures. And that's where I became acquainted with some of his work, I like reading that. So, those are the kinds of things that I really enjoy. And then I think, of course, I have always really enjoyed F. Scott Fitzgerald, even from high school, and Hemingway. Dr. Lidia Schapira: Very classically trained. Tell me a little bit about writing. Writing is a way of sharing an experience or perhaps processing a difficult encounter with a patient, is that something that you routinely do or have thought of? Dr. Austin Price: Yeah, it's definitely become something that's been more robust as I've gone through residency. I think part of that certainly had to do with the pandemic, and just not being able to be as close with people and have those personal relationships. And I found myself kind of cut off, maybe from a support system that I would have otherwise had, being in California with most of my friends and family in the Midwest. And so, I used writing as a way to kind of compartmentalize my feelings and my interactions with patients and to check in with myself. And I find that it's therapeutic and also enjoyable. Dr. Lidia Schapira: That's fantastic. Let's talk about the essay that you submitted and we published in Art of Oncology, which is a way of honoring the memory of your grandmother, who had cancer when you were a child, and also talks about your sense of vocation and this ideal that was held up to you by your family of aspiring to be as empathic and wise, as a doctor, who is an oncologist who helped your grandmother. Let's start a little bit with your grandmother's illness and how you remember that now that you are a physician. Dr. Austin Price: Yeah, certainly. I mean, I just remember as a child, her getting very sick, and finding out that she had cancer, and knowing that that was a bad thing, but not really knowing any of the details of it. As it turned out, she had colorectal cancer, and had surgery, for a short time she seemed okay. And then she got sick again, this time with metastatic disease to the liver. And of course, she was very sick then and ended up seeking out a second opinion from an oncologist who becomes the person in the story that I write about, in Omaha. At that time, there really wasn't anything that could be done to save her life, essentially. But the interactions that they had were very impactful to both her and the rest of our family. So much so that all through my life, my family members said, if you want to become a doctor, which I thought kind of early on, I did, that I should be like this particular person, Dr. Tempero. And so, she had just always been this kind of person on a pedestal, if you will. Dr. Lidia Schapira: Let's talk a little bit about the impact that Dr. Tempero and her consultation had on your family. Can you tell me a little bit more about how they talked about that particular meeting? Many of us who are in oncology and have been for a long time often talk about the fact that there can be a therapeutic relationship between the oncologist and the patient and the family that can actually help during difficult times and even through bereavement. But it's so interesting to me to hear you speak about it from the perspective of a family member. Tell me a little bit about how that relationship impacted the way the family understood the illness and how they went through their loss? Dr. Austin Price: I definitely think that there was a therapeutic relationship established. And I think in a way, Dr. Tempero managed to be preparatory in the sense that she knew that the outcome was likely not going to be good. I think she did that without ever being bleak or ever losing hope, in doing so she really kind of helped, in her own way, move us slowly towards accepting reality, and then learning how to move forward and enjoy the time that we had left together. I think all of my mom's siblings remember her in the same way, they really trusted her in such a robust way that her assessment that there really wasn't anything else medically that could be done, really helped them to come to terms with it and to refocus their goals, and those goals being to spend as much quality time with my grandmother that they could. Dr. Lidia Schapira: And as you've gone through your medical training, I imagine that they'll have to dangle this idea of this ideal doctor in front of you more than once. How have you interpreted or internalized this aspiration to also be wise, empathic and so kind to your patients? Dr. Austin Price: Yeah, it's definitely something that my mother in particular is always reminding me to do, because it's not always easy, as we all know. And there are times when I'm frustrated and tired and all those sorts of things. So, she and I've had many conversations where I'm maybe lamenting about feeling overworked or this or that. And she's always reminding me to be present and to realize that, although I'm tired that I'm oftentimes interfacing with people at bad points in their life. So, I always try to keep that at the forefront of my mind and try to decompress before each patient interaction, in hopes that I can be at least to some degree like Dr. Tempero was for my family. I'm sure that I don't always succeed in the ways that she did, but I hope that I do most of the time. Dr. Lidia Schapira: I assume Dr. Tempero would reassure you that even she may have a bad day or a bad hour in a day. Your essay has a moment of suspense and a twist in the plot when you find yourself now as a physician in an emergency room looking after a patient who tells you that their oncologist is none other than Dr. Tempero. Tell us a little bit about what that felt like? Dr. Austin Price: Well, I mean, it was just altogether shocking, honestly, because I had never met her and I really had never even Googled her name in the past. She was just always this person that my mother talked about so much. And then I had come to a kind of honor but I assumed for all I knew that she was still in Omaha. And so, when I heard this name, I thought, well, how many oncologists named Dr. Tempero are? Well, there's probably more than just her, but I immediately left the room and started to Google and realized, just quickly, that it was her or that I assumed that it was because she had done her training in Omaha at the University of Nebraska. It was shocking and emotional too, I will say. I immediately remember texting my mom and being like, oh my gosh, this patient just told me that Dr. Tempero was their oncologist. And I have to go back in there and finish the assessment because I kind of had to leave the room to just decompress a little. Yeah, it was a wonderful feeling and also just one of those moments where you're just like, life is so interesting in the way that you come into contact with people and in situations that are just so unique. Dr. Lidia Schapira: And then you reached out to her? Dr. Austin Price: I did. Yeah, my mom told me, she said, she may not have time to get back to you about this but you should at least reach out and explain how this made you feel. And thank her for the way that she treated our family and thanked her for the ways in which she or the idea of her has kind of impacted the type of physician that you aspire to be. Dr. Lidia Schapira: So, you wrote to her, and she wrote you back. What was that like and what happened after that? Dr. Austin Price: Well, I just remember being shocked that she wrote back so quickly. I know that she's incredibly busy. And so, I was very happy that she'd written back so quickly. Honestly, when it was written, this all happened at Christmas time. So, I wasn't able to be there because of COVID and working through the holidays. It was just the first time in 30 years that my mom hadn't seen me for the holidays. So, she was emotional about that. And so, getting to read Dr. Tempero's response to the family over FaceTime on Christmas, really was kind of like the best gift that they could have gotten. They really enjoyed it. That kind of helped to stifle the blow a little bit of me not being able to be there for the first time. Dr. Lidia Schapira: I'm just getting teary just thinking about that scene of you're reading this message to the family over FaceTime, and then talking Dr. Tempero invited you to meet her, and you had a long conversation, tell us a little bit or share with us what you feel is appropriate so that we can understand how important that reunion was for both of you? Dr. Austin Price: Yeah, sure. From the first response email, she said, 'I would like for us to get together and for us to meet in person when it's safe to do so', because when this interaction initially happened, none of us had been vaccinated yet, and so we're still in the throes of COVID and still petrified and all those things. And so, once we had been vaccinated, I reached out to her and said, I actually have started to write this essay, and I just wanted to know your thoughts on it. And she read it and she said, and this was many iterations ago when it wasn't as good as I think it is now, but she was like, 'Oh, I'm very much in support of this and I'm very honored, and by the way, we're vaccinated now and it's time for us to finally meet.' So, we did. It was great. I met her and her husband at their apartment in Mission Bay in San Francisco. We just had a lovely evening, had a glass of wine, some hors d'oeuvres, and just talked about this unique situation that had brought us together, and also talked a lot about my life and what I want to do in my career and my future. She was more interested in me than sharing so much about her life, but was very forthcoming when I would ask her questions as well, then also just had this kind of commanding aura, but welcoming at the same time, just very likable. I don't know how to explain it, other than that it was amazing and I was so thrilled to experience it. Dr. Lidia Schapira: I think you've explained it very well. It's a beautiful story for us to read, for all of us who have been in oncology for all these years, and those who are just starting, it's really inspiring. We think a lot about mentoring our students or junior faculty, but the idea that we in our clinical roles, can also have sort of in a way an indirect mentorship, relationship with or an influence with other young members of the families is really beautiful and moving. I thank you so much for having sent it to us and for sharing that experience. Is there something else, Austin, that you would like our readers and listeners to know about the essay itself, your family, or the intention that you had that brought you to not only write but share your writing so publicly? Dr. Austin Price: Yeah, I hope to honor my grandmother, because I think it's been interesting, this experience brought me a lot of joy, and I think it brought our family a lot of joy. The fact that that came from such a sad place and sad reality, I think is really great. For clinicians, it's just really important to realize how far-reaching our interactions with patients can be because we are seeing them, oftentimes, really in bad times of their lives, times that they're going to remember for a long time. And so, we can then be remembered in kind of good ways and bad. I think it's so unique in the situation that in an interaction that Dr. Tempero had with my family, nearly a quarter-century ago, it only took the mention of her name, to bring back this whole flood of memories and spawn all of this. I think that's really cool and something that we should always be cognizant of. We have very far-reaching impacts for our patients. I just think that that's cool, and a good thing to be reminded of. Dr. Lidia Schapira: I think it's very cool too and I thank you so much, Austin, for sharing your essay and for taking part in this conversation. Dr. Austin Price: Thank you for having me. Dr. Lidia Schapira: Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology 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 of JCO's Cancer Stories: The Art of Oncology Podcast. This is just one of many ASCOs podcasts. You can find all of the shows at podcast.asco.org The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.

"Questions for the Oncologist," by Barry Meisenberg: an oncologist struggles to answer a patient's "Why me?" question. Transcript Narrator: Questions for the Oncologist by Barry R. Meisenberg, MD (10.1200/JCO.22.00158) Go ahead, ask me anything. Decades of meeting beseeching eyes has prepared me. Ask me anything except that one thing. That one thing that neither colleagues nor study has helped me comprehend. Ask me instead about prognosis; I will be honest, but gentle. Ask me about side effects; I will use a small spoon so as not to overfill your vessel. Unfold your notebook. Ask me anything: "-how many cases like mine have you seen before? -what is the nectar of the bone marrow? -what (and how) should I tell the children? -is it wise to lay in the sun? -is it safe to have sex? -should I get the vaccine? -what's next if this doesn't work? -what if it were your wife?" Go ahead, ask me anything. But please, don't ask me that one thing. Don't ask, "why me?" You wouldn't like the answer. I don't. I could fill your notebook with a tale of random errors in the genes. Tiny rivulets of mutation that flow into a tumultuous river. But, I don't think of them as errors. Rather, they are Nature's engine of biodiversity. Individuals suffer, so that species survive. "Bad luck" is a second-rate explanation, I know. So please, don't ask me that one thing. Search for a better answer within, as I have. Unsuccessfully, so far. Dr. Lidia Schapira: Welcome to JCOs Cancer Stories: The Art of Oncology 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 of the shows including this one at podcast.asco.org. I'm your host, Lidia Schapira. And with me today is Dr. Barry Meisenberg, Chair of Medicine and Director of Academic Affairs at Luminous Health. We'll be discussing his Art of Oncology article: Questions for the Oncologist. Our guest has no disclosures. Barry, welcome to our podcast. Dr. Barry Meisenberg: Good morning. Thank you very much. Dr. Lidia Schapira: It's a pleasure to have you. And before we start to talk about your poem, and the reason for your wanting to share this with a broad readership, mostly of Clinical Oncologists, let me start by asking if you are a poet and if you often write to reflect on your experiences as a physician, or for other reasons? Dr. Barry Meisenberg: Well, I will never give myself that label of poet. I have written several, what I would call reflections on what it is to be an oncologist, which this section of the JCO covers so well. Sometimes I've submitted work and said it was a poem and the editor said, 'No, this is a vignette.' Another time I thought it was a narrative and someone said, 'We liked your poem.' So, increasingly, I've entered this area reflecting a career's worth of introspective thoughts about what it is we do. Dr. Lidia Schapira: So let me ask you, given your very particular vantage and your experience, why do you think it's important for us to write and read reflections? What does narrative give us as physicians, as cancer doctors? Dr. Barry Meisenberg: Well, I think it gives us the other parts of our brain and the other parts of our personality as humans. The most humanistic of all the sciences is medicine. We can't neglect that. Mostly for our own health. But also, I think it makes us better physicians when we think about what we're doing. You know I think it was a physician author, who said that we walk around in the midst of stories. Every one of our patients has a story, sometimes multiple stories, and if we miss that, and don't really capture that, then we're just sort of functionaries. Dr. Lidia Schapira: Such an important thought. There's definitely plot. There are characters. There's the scenery. There's all of this very rich life and human content and I couldn't agree with you more. So, before I ask about this particular essay, what are you reading now or what have you read in the last year that you would recommend to your colleagues? Dr. Barry Meisenberg: Well, it's interesting you say that because, recording here in April of 2022, I've talked to many of my neighbors about their pandemic hobbies, both medical and nonmedical, and they're, you know, learning to bake, reteaching the piano, and working on developing their rhomboids. I've been doing a deep dive into the history of other pandemics. I may be little obsessive, but I've been reading about pandemics throughout history, and just appreciating the fact that human nature hasn't changed very much, nor has medical behavior. So, in Defoe's book, I think it's called Journal of a Plague Year, which by the way, is not history, is a fictional journal but based on reality. We have the same sort of medical charlatanism. We have false hopes. We have people trying to beat the quarantine for their own good. At the same time, we have just public-oriented behavior as well, feeding those who couldn't be fed or who would become orphaned by the plague. The same thing is true of the 14th-century plague. It's just remarkable how little we've changed as a species, all the behaviors on display today, both good and bad, were on display then. And so, I've been reading quite a bit about pandemics. Dr. Lidia Schapira: It's so interesting. Now, with that, let's focus on your beautiful poem, the question that you can't answer after all your scientific work and after your decades of clinical experience, "Why me?". Tell us a little bit about what inspired this poem that I found so moving, and I'm not a great reader of poetry. But this one message was so clear that I think most of our readers will understand the sentiment. What inspired you to write it? Dr. Barry Meisenberg: Well, I woke up with this one. Sometimes that happens, you wake up with a poem that is nearly fully formed, or a narrative is nearly fully formed in your mind. Although I did get some excellent suggestions from my reviewers that I do appreciate. And I realized only after it was on paper, that seven years ago, I wrote a piece for a different oncology journal about this issue of random chance. And you may remember, in 2015, there was an article, or a science magazine published an article by Thomas Heti and Bert Vogelstein about their mathematical calculations of errors in stem cell division. They didn't do any new experiments. They accumulate what was already known, and they were able to correlate that with the incidence of cancer from the cancer databases. And their conclusions were, when stem cells make random errors, there's more likely to be cancer. Now, they didn't cover every type of cancer. They covered several. And they came up with this idea that cancer is stochastic, that is a random process. Now, stochastic is not a poetic word. And so, we didn't use it in the poem, but random, and that was covered extensively in the New York Times and other media, and a big debate about what it meant. So, I wrote an essay about that, and I realized it's been on my mind all this time, and whether it's a helpful notion or a harmful notion. Helpful in that patients can understand you didn't do anything to give yourself cancer, despite all the media noise about that, but harmful, potentially harmful, in this idea that maybe my life doesn't have meaning if this is just a random process. And so, I talk to patients about this when appropriate, because many of them have thought about it. So, it's sort of been on my mind since this article I wrote in 2015. And I must say, it disturbs me that I don't have a good way of explaining that or helping patients overcome this. Dr. Lidia Schapira: So, when a person asks you why me in some way, I mean, you, first of all, you tell us that you have answers for most of the other questions, what is my prognosis? You can answer. How do I tell the children? You can answer. Is it safe to have sex? You can answer. But the "why me" question is still with you and still troubles you. What is it, in your view, that a person is really asking you? What is the question behind the question when they say 'why me?' Dr. Barry Meisenberg: Well, that is the question. And then I think what they're saying is what does my life mean? Yeah, if the answer to Dr. Vogelstein is correct, that it's stochastic, doesn't mean my life doesn't have a meaning. I hope people wouldn't draw that conclusion. So, random things happen to people, both nice people, and mean people all the time. I remember when I was in New York doing a year of research at Sloan Kettering, there was a helicopter accident, and it didn't just kill the people in the helicopter, but a piece of the blade broke off and spun out over Manhattan, killing someone who was about to walk into a retail store, totally random. It had an impact on me in how all our lives hang by a thread, or it can, and cancer is like that. Dr. Lidia Schapira: What I hear in the "why me" question is also sort of a plea for, please reassure me and keep me safe, because this happened, and you have no explanation, I have no explanation. So, it's interesting that you talk about life's meaning. I see it more as a cry for help. If I can't deal with the uncertainty and the chaos of the universe. Dr. Barry Meisenberg: That's an excellent perspective. And you may well be right, at least for many people. It's almost like a real issue of faith and religion, or more faith and religion. When I say in the piece, 'you have to look inside for that answer, why me and what your life means?' Yeah, people ask questions for a reason. Some of it is just fact downloading, the risk of mucositis, how to treat mucositis, and so on. But other, the more important questions are these. Dr. Lidia Schapira: And that's one of the beauties, I think, of poetry and why we love to publish great poems because it's almost like a bit of a Rorschach too, right? You can read into it, you can interpret, you can use a poem as a way of exploring an important topic, and bringing perhaps to the surface some of the questions that you also deal with, as a human, instead of only your skill, as an oncologist or as a physician used to counseling people. Dr. Barry Meisenberg: I think that is one of the values of poetry. I run a program here at this health system that we call the Diastole Hour because it's important for relaxation. You can't live your whole life in systole. That's the message. And we use poetry a lot, mostly written by patients about their medical experiences, sometimes written by doctors about what it means to be a doctor or be a better doctor. And then, of course, some art that covers medical topics. And the whole goal is to train that other part of our brain to make us better at the business part of being a doctor, and I think the two are related. Dr. Lidia Schapira: Do you read poetry with your fellows or with your trainees or junior faculty? How do you incorporate this kind of thinking in their professional life? How do you use it to build a community? Dr. Barry Meisenberg: Well, that's a great point. I wish we could do more. So, I read some poetry. I am not trained in it and I tend to look for poems that one doesn't need to be an expert in the classics to understand and we use them at this event I've told you about. But also, I've been known to sneak them into Grand Rounds presentations and other venues, trying to make people pause and think a little bit about it. There's some wonderful poetry about the physician experience, for sure. And I sort of collect them. Dr. Lidia Schapira: What are some of your favorite pieces? Dr. Barry Meisenberg: There's a neurologist named Ginsburg, who has written, I remember one poem, in particular, called "Line Drive". And it's about a man, presumably, based on a true story, who is explaining to someone their brain tumor anatomy during a hospital visit, and pointing at shadows, but recognizes that he doesn't actually do any touching. He doesn't enter their lives. He doesn't answer all their questions like the one we just talked about. And then he's driving home, and he stops at a little league Park and watches some boys play baseball. And one of the boys is struck by a line drive. And he's so moved, by the way, his teammates gather around him and offer support and touch him and help him that he drives back to the hospital to redo the consultation he had just finished doing, but this time with the touching. I thought that was a wonderful poem. Dr. Lidia Schapira: It's an amazing poem. Dr. Barry Meisenberg: I read that poem in Abu Dhabi, actually, to an audience, few of whom knew baseball, so I sort of had to explain it to an audience of oncology professionals. I might have missed my mark, I don't know, but I wanted them to understand certainly the importance of entering patients' lives. Dr. Lidia Schapira: Have you always felt this way about using narrative and poetry as a means of reflection, self-expression, and dialogue? Or is it something you came to later in your life as a more mature professional? Dr. Barry Meisenberg: Definitely the latter. I mean, I was fortunate in that I had good cultural capital growing up, but I didn't really incorporate it into my other life, my professional life until I'd say the last 10 years or 15. I've always been an admirer of Shakespeare, by the way, he wrote about the plague a little bit too, indirectly. And then one time I actually wrote an essay about this: I was given a poem by a patient, who was from Ireland and this is sort of like the national poet of Ireland. And it was his way of telling me, he didn't want any treatment. And the poem is about loss and lamentation that accumulates through life, and all his friends were in the graveyard. He wasn't interested in therapies that are designed to induce a response rate. He didn't want any treatment. The way he communicated that was through a poem. And I began to understand that really in a more realistic way that poem can do that. Dr. Lidia Schapira: Well, thank you so much for your insights. It's been a wonderful conversation. Is there something else you would like to tell our listeners and perhaps even a thought for future readers of the poem? Dr. Barry Meisenberg: By the way, I should say that the name of that poem I just referred to is called "Oft, in a Stilly Night". It's the first line of an Irish folk song. But I would hope people take the time to indulge. Many medical journals have sections like this, they're usually short. And I will tell you, that's the first thing I read in these medical journals. I hope people will follow that pattern. Dr. Lidia Schapira: Thank you so much, Barry. It's been a lovely conversation. Thank you for your work, and thanks to the readers. And more next episode of Art of Oncology. Until next time, thank you for listening to this JCOs Cancer Stories: The Art of Oncology 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 of JCOs Cancer Stories: The Art of Oncology Podcast. This is just one of many ASCOs podcasts. You can find all of the shows at podcast.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product or service organization, activity or therapy should not be construed as an ASCO endorsement.

"Wall Street doesn't believe in this target," by Dario Altieri. A scientist shares his 12-year journey that led to the discovery of a drug now in clinic. TRANSCRIPT Narrator: Wall Street Doesn't Believe in This Target by Dario C. Altieri, MD (10.1200/JCO.22.00180) March 2, 2009. Just published in the Journal of Clinical Investigation.1 And we even got the cover. Twists and turns of heat shock protein-90 (Hsp90), the chaperone, the evolutionary capacitor. Great name and important cancer target. People smiled when I talked about this at the Hsp90 conference. No, no, really there is a lot of it in mitochondria, and only in mitochondria of tumor cells. And, I don't know why, but Hsp90 drugs don't touch it: somehow, they don't get to mitochondria. So, I made my own. Took an old Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin and attached it to triphenylphosphonium, a carrier that basically gets anything into the mitochondria. No, of course, I didn't do the synthesis in my laboratory. What do I know about medicinal chemistry? Outsourced it. Like sneakers and sweaters. And after three months, there it was: an Hsp90 inhibitor that only goes to the mitochondria, causes aggregation of a lot of proteins, and kills tumor cells in minutes. Makes sense, right? Mitochondria must control protein folding, especially in cancer, and they do it with chaperones. Inhibit the process and tumor cells can't cope. Normal cells don't seem to mind. So, strong preclinical activity, and against a lot of different tumor types. Better than any other Hsp90 inhibitor. Good safety. Totally different mechanism of action. And even a cool name, Gamitrinib. Tired of curing mice. What if this were to work in people? Ideas are made in academia; drugs are made in companies. Okay, fine, then I'll launch a startup, spinout, whatever they are called. The (former) doctor-turned scientist now turns entrepreneur, and then captain of industry. Problem is, I am not like that. More like an (aged) boy scout. The inner soapbox says: it belongs to the American taxpayers; they funded it; it's theirs. Excellent start. What else? If doctors and scientists become businessmen (or businesswomen), who will take care of humanity and discover new things? Perfect for a campaign ad. Sold. Bring it to the patients solely from academia: no pharma, no biotech, no investors, no nothing. Soapbox meme for the day: Yes, we can. It's going to cost. So? I'll write a grant, that's what I do for a living anyway. And the fact that I know zero about drug discovery? Or drug development? Laboratory-Clinical Transition Award from the Department of Defense. Great title. Three years of funding. Perfect for me. Pass-through money, nothing for the laboratory, but it pays the bills of outsourcing. First things first. Synthesize Good Laboratory Practice (GLP) Gamitrinib. Already getting a pretty good hang on the acronyms. Hey, we made this drug lots of times before and has never taken this long. It's almost a year and counting. The Department of Defense (DoD) is on my case because I am already behind. What's going on? Yes, I understand that we don't make anything in this country anymore. New import permits that need to clear the Indian government? The what? This is just a chemical, not an international incident. Yes, I get it, nothing I can do about it. My new job is mailman. And telephone operator. Finally shipped the GLP drug for the toxicology. Two animal species, says the US Food and Drug Administration (FDA). Rats and dogs sound good to me. Should I feel sorry for the dogs? Rats not so much. But what if Gamitrinib poisons the mitochondria in the brains? Or hearts? Wait, you said it's just perfect? Animals are doing great, all of them. And no toxicity at all, like giving them…water. Wow, that's some news. Feeling quite pleased with myself. See? I said it all along: mitochondria are wired differently in cancer. That's why the drug is safe for normal tissues. Maybe I should write a review article about that. Serious boost of the citation index. I am sorry, what? Yes, of course I know that the drug is purple. Okay, you filtered it before giving it to the animals and instead of purple it turned white? And you did that to all animals. For the entire time. Oh, what do I think it means? I think it means that you filtered out the drug and we have been giving animals…water. Yes, I get it. I need a new formulation. And start over. Note to self: find a new Contract Research Organization (CRO) that doesn't give water to the animals. Formulation experts. Big pharma ex-pats who now have their own CRO. Everybody is an entrepreneur here. Is this drug oral? Nope. Is it soluble in water? Not at all. So, it's an intravenous (IV) infusion? Yes, that's what it is. Sorry, then it's not a drug. It's not? And what about things like, you know, paclitaxel or doxorubicin? Aren't they also insoluble and given IV? Last time I checked, we used them for half a century and saved millions. Oh, now we think differently? I see, Fail Fast: that's how we think now. And mine, whatever it is if it is not a drug, has already failed. Nobody likes to take risks. Soapbox meme for the day: If nobody takes risks, how do we make progress, exactly? So, maybe I am in good company: paclitaxel and doxorubicin would also Fail Fast today. It's doable. Nobody likes it but it's doable. Sterile-filter the emulsion components and then bring the particle size below 200 nm. Nice. How do I do that? With a microfluidizer. And why nobody likes it? Oh, because the microfluidizer is a dirty machine and where you make Good Manufacturing Practice is called a clean room. Impeccable logic. But a place in California may do it. For a fee, of course. Oh, and you have to buy the machine. Buy what? Or lease it, whatever. People may not like it, but the whole thing works like a charm. Except, of course, when the microfluidizer stops for no reason in the middle of the run. Media fill looks good. Drug is stable for months in the new formulation. Release testing coming together nicely. I am running out of money. Burned through not just one but two DoD grants and all my research kitty. Nothing saved for the swim back: talk about risk-taking. At least the repeat toxicology is paid for and looks good. The drug, the real thing this time, is safe. They even did ECGs on the dogs. Thank goodness I didn't have to read those, but they are normal: no QTc liability. Can't drop the ball now, but I really need money. Here is how you do it: silence the inner soapbox and enchant the big pharma suits that are coming over. Use the right words. It's not early stage anymore. Asset totally derisked. Sure it's ready for prime time. It works. I am a natural. Maybe I should have done this before. A lot of nodding around the table. The suits must be in awe with the great pharmacokinetics, long half-life, and fabulous safety. A hand goes up. I am sorry? Sales data? Sales of what? What is the unit price? No, no, no, we are not there yet. I haven't even filed an Investigational New Drug (IND) application. Something different now. Analysts who advise big-time investors. They don't wear suits. Sweaters for sure. Maybe black tees a la Steve Jobs. They like new things and totally live by risks. Sounds like my crowd. And don't forget, they can get tons of money from people who already have tons of money and want to make even more money. My crowd? Voices out of a polyphone. Yes, it is Hsp90. Yeah, the chaperone. Sure, I know, it has been around for a long time. But this is a completely new story: nobody ever tested a cancer drug that goes to a subcellular organelle: that's really where the action is. Yes, Hsp90. And mitochondria, they used to be bacteria two and a half billion years ago, but they turned out to be important in cancer. I know that too, Hsp90 drugs didn't fare well in the clinic. Lot of toxicity, basically no efficacy. Yes, very unfortunate. But this one has a completely different mechan…Sure, I would like to hear that perspective. I am sorry, did you say, Wall Street doesn't believe in this target? Triaged the first time but funded on the resubmission. Could have been worse. This one is a grant from the National Cancer Institute. And a nice award from the Gateway Foundation is coming too. Enough to pay for the clinical trial. Single site, standard phase I. Accelerated dose escalation. Up to 35 patients with advanced cancer. All comers. Drug vials ready to go. And a fantastic clinical investigator to run the trial. You really don't want me in the clinic. The only thing missing is IND approval. Right, there is that. No, not a commercial IND, investigator-initiated IND, thank you very much. The FDA people are the nicest in the world. Super-helpful, don't believe otherwise. Or maybe they just feel sorry for the clueless applicant. Thirty days to respond to the questions. Totally getting a promotion to a higher rank of telephone operator. And publisher of FDA modules. And certifier of United States Pharmacopeia (USP) . recommendations. And fixer of Chemistry, Manufacturing, and Controls deficiencies. Oh, and let's not forget the specs for polytetrafluoroethylene filters. Then the examiner mutters two words at the end of a phone call. Good luck. Then, nothing. No more questions, e-mails, or phone calls. Right on the thirty-day mark. Were you expecting this? It's a letter; it says study may proceed. What would the day look like? The first patient to be dosed. Maybe I should go to the clinic: it's in town, not far from where I am. I don't think I can pass muster as one of those confidence-inspiring docs in pharma ads. But I do well as chief executive officer. The cufflinks look good, and so do the shoes. I can impress the family. My Italian accent can pass as straight from South Philly, so I have that also going for me. And I can more than hold my own if I need to talk about Philadelphia Eagles football and worries with Jalen Hurts' arm for next season. I used to be good with my patients. Or at least I convinced myself of that. Yes, this is an experimental drug straight out of our backyard, right here in Philadelphia. No, I don't know if it will work, but I sure hope it will. And thank you, thank you so much for being part of the trial. What if I make these people even sicker than they are? I took an oath a long time ago. Anyway, I know the literature on phase I studies, chances are it just won't do anything, so nobody gets hurt and I am finally done with it. I never thought this moment would arrive. There is none of that. January 10, 2022. It's just a late-night e-mail on the anniversary of my mom passing from lung cancer. Hey, the first patient did great at the starting dose of Gamitrinib. No problem whatsoever. The next patient will now get twice the dose. I hope we get that started this month. Happy new year. And that was that. Twelve years, 10 months, and nine days from that Journal of Clinical Investigation paper.1 Affiliation: 1The Wistar Institute, Philadelphia, PA Dr. Lidia Schapira: Welcome to JCO's Cancer Stories: The Art of Oncology. I'm Lidia Schapira, Associate Editor for Art of Oncology, and Professor of Medicine at Stanford University. And I'll be the host of this show. Cancer Stories is 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 of the shows including this one at podcast.asco.org. With me today is Dr. Dario Altieri, president, and CEO at the Wister Institute. We'll be discussing his Art of Oncology article: Wall Street Doesn't Believe in This Target. Our guest is a named inventor for patent number 2,699,794. Titled: Mitochondria Targeted Anti-Tumor Agents. Dario, welcome to our podcast. Dr. Dario Altieri: Thank you so much for having me, Lidia. It's a great privilege. Dr. Lidia Schapira: My first question to you and to our authors is this, people who enjoy writing are usually also readers, what are you reading now? Dr. Dario Altieri: Well, absolutely it has been a passion of mine since the floods. I am an absolute avid reader of novels, and history, in particular, contemporary history and modern history. Those are my favorite topics. Dr. Lidia Schapira: Do you read in English, Italian, or other languages? Dr. Dario Altieri: I typically read in English, even though some of the Italian literature is best read in the native tongue. And so, I am still attached to that. Dr. Lidia Schapira: You're clearly a very accomplished scientist. But tell me a little bit about your writing in this particular area in what I'll call creative nonfiction. How has this writing helped you perhaps process experiences or communicate with others? Dr. Dario Atieri: It has been, it's been a passion of mine for a very long time, I think. In finishing up college, of course, my major was contemporary literature and philosophy. The question was whether to continue on in a classic literature career or go to medical school, probably the wrong choice was made. But it has remained with me for a very long time, and it's a form of expression that I truly enjoy. In writing, this particular contribution was a bit transformative for me. It doesn't happen every time that you write a scientific article to express a little bit about yourself and your passions and dreams. Dr. Lidia Schapira: Let's talk a little bit about your passions and dreams in this article. You described an intensely personal journey of 12 years that led to the discovery or the availability of this drug now in the clinic. When did you think that you wanted to share this story with your colleagues? And tell me a little bit about the process of writing this article? Dr. Dario Altieri: It has certainly been a roller coaster experience. I would like to describe it as life-defining and life-changing. I've learned so much and so many things, not just about the process, but also a little bit about myself. I recognize reaching the clinic, especially in a phase one trial, is really just the beginning. But for me, as a basic scientist, somebody who has seen his last patient in the 13th century. As a basic scientist, that was a little bit of a milestone, and I wanted to share what it took, the experiences that I lived through, especially with our youngest colleagues, scientists, and doctors, starting their own careers in oncology, whether it's basic research, clinical research, translational research, I really don't think it matters. And so, issues of resilience, staying the course, passion, and not really giving up are the parameters that I had hoped to convey with this contribution. Dr. Lidia Schapira: In your article, I was so impressed by how you used humor, often self-deprecating humor, and the particular narrative style and writing style that you chose and defended as you were revising it. You know, this choppy phrasing, a staccato, and you said, this is what it feels like, how can I pack it into a small number of words and describe it all? Tell us a little bit about how you allowed your imagination to take over and how you found the proper voice and style for this particular narrative. Dr. Dario Altieri: Again, it's been a thrilling experience and it's been a thrilling experience to answer to the editors and the reviewers of the JCO, who provided incredible insightful comments. The challenge was, how do I tell a story without sounding obvious, fright, or expected, and more importantly, without sounding boring? And I think to paraphrase one of our reviewers about this journey. What the reviewer said, the author, that would be me, has encountered many of the absurdities of the path in drug development, something that we don't talk about too much because it's been the realm of a drug company for the longest time. And so, I wanted to try to capture that absurdity in a positive way. Things that the reviewer indicated, may be second nature to the pharmaceutical industry, but for academic investigators, that's been publicly funded for 30 years, is not second nature and is unusual, and is a world all in itself. And so, that was the impetus of trying to use literature advice on short sentences that are really intended to convey the impression of the moment that was what I tried to accomplish. Dr. Lidia Schapira: Well, you certainly picked a catchy title, and we have not published this sort of article in Art of Oncology before. For our listeners, tell us a little bit about why Wall Street doesn't care about your discovery? Dr. Dario Altieri: Unfortunately, I think, I mean, I don't know for sure. But I think that dealing with this particular molecule, heat shock protein 90 in the clinic has been difficult. Hsp90 has long been recognized as an important cancer target. There have been several generations of small molecule inhibitors that have been tested in the clinic. And unfortunately, I hope I'm not offending anybody, but unfortunately, the clinical results of those studies, and some of them moved all the way to really large phase two trials have been disappointing. And so, that is the idea that perhaps this was a dead target. And therefore, trying to leverage industry or biotechnology interest around it was quite a remarkable challenge. Dr. Lidia Schapira: What message do you want the young investigators to take away from your story in terms of the collaboration between academia where thoughts start, as you say, in your article, and all of the rest of the partners that you actually need it to bring this discovery and this idea to fruition? Dr. Dario Altieri: Lydia, this may sound trite, I really hope to convey one simple notion. It's not even a message, it's a very personal account. And that is don't give up. If you have run the controls. If you have done your experiments enough time. If you're convinced of the results, if you explore alternative explanations, and you keep coming back to the same conclusions, go for it. That has been a little bit of my own personal experience and if there are things that you don't know about, that's perfectly fine. Actually, that is the fun of the process, and the things that I didn't know about drug development, I can fill in the encyclopedia. I've learned some of them through people who have been doing this for a living, for a very long time. And that has been truly inspiring for me, a life lesson and professional lesson about how we can think of a drug target that has been discounted and remain true to the core value of strong basic research and try to advance that to the clinic, whether this will ever become something useful for our patients? I don't have the faintest idea. I certainly hope so. But that would be the experiment that is being done right now in the clinic. Dr. Lidia Schapira: In your article towards the end, you just give us two little glimpses into something that is personal and meaningful to you by telling us that there's an anniversary of a loss, the passing of your mother from cancer. Can you tell us a little bit more about that, and why you chose to put that sentence just where you did? Dr. Dario Altieri: I didn't know if anybody would have noticed, frankly, so I appreciate you bringing it up, Lidia. It's been a very personal journey for me as well. Both my parents died of lung cancer. They were a different generation. Both were heavy smokers. I remember those dates very well and I remember the void that they're passing is created. And so, I thought it was an interesting circumstance, that in fact, the first patient was enrolled in a clinical trial, the notion about that and of course, I am technically conflicted. So, I am not supposed to know anything about what is happening in the clinic. But it was interesting that the first notion about the first dosing came on that day, on January 10. Dr. Lidia Schapira: Well, I'm sure other readers will notice that too, the timing of that in the article and the fact that there was some emotion implied, I think, in how you chose to end your story by saying that this had happened in the clinic, but somehow, you were not there, that you had to be removed. Tell us a little bit more about that, about why you needed to be removed from the clinical site and why do you talk about yourself as a former doctor? In my mind, once you are you always are, but somehow you feel that you need to make the distinction. What does it all mean to you? Dr. Dario Altieri: Well, Lidia, let me just say you don't want me in the clinic right now. At 64years of age, like I said that the last patient was a very long time ago. I have to say, sometimes I miss those days, just as a personal account. I need to be removed because I'm technically conflicted on the trial, I was the IND holder, and then the FDA asked me to transfer the IND to the clinical investigator as proper because I'm not involved in patient care or research, in this particular case. And technically, because I am the inventor on a patent, I could potentially stand to benefit financially from the results of the trial, something that is certainly not on my mind, but that I have been reminded of. And so, I try to stay away as much as I can. Obviously, I think about this every day. But whatever information I can gain, that I can gather from my colleagues across town will be wonderful, but I'm not the one initiating those calls. Dr. Lidia Schapira: So back to the humorous side of your essay, you say that you've learned to be a telephone operator and a mailman, and a whole bunch of other things. Have those lessons been useful to the other aspects of your life? Or do you see that as a total waste of your time? Dr. Dario Altieri: Not at all. Not at all. I have been an incredible component and I think I was trying to be humorous and to take myself seriously, but not too seriously. But in fact, maintaining that level of interaction, particularly with aspects of the work that I've never encountered, for instance, regulatory aspects of an early-stage clinical trial with the Food and Drug Administration, that has been part of the life journey and I only have very good things to say about my experience. You know, it's been interesting, Lidia, being part of the experience of being a telephone operator and a mailman. I had this sense, and I could be completely wrong, but I had this sense that people out there want to see us taking small risks. They want to see testing new drugs, they want to see new targets being somehow examined, developed, if at all possible. I had the sense that there was support, you know, for the idea, and this was an entirely publicly funded program. I funded both the preclinical and now the clinical trial of Gamitrinib out of the American taxpayer's commitment and in many different study sections, in dealing with the FDA, in dealing with other regulatory consultants, I always get the sense people who wanted to help, then had perhaps the mindset, okay, we don't know whether this is going to work or not but let's give it a try. Let's give it a shot. It was wonderful, that was an absolutely awe-inspiring experience. Dr. Lidia Schapira: I'm glad they did and I'm glad you shared your experience with all of us. Is there something else that you'd like our listeners or your readers to know about you or this story? Dr. Dario Altieri: I just would like to say that I would do it again, 12 years, I would do every step of the way but I think I'm done. If I were to start over, I'll do it again, but I don't think I'm ready to do it again with another target. Dr. Lidia Schapira: And with that, I want to thank you and I want to thank our listeners. Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology 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 of JCO's Cancer Stories: The Art of Oncology podcast. This is just one of many of ASCO's podcasts. You can find all of the shows at the podcast.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product or service organization activity or therapy should not be construed as an ASCO endorsement.

A physician attempts to ease a patient's pain, a painful moment somewhat eased by the joy of music. TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] RICHARD LEITER: Ode to Joy. "Is now an OK time?" I asked as I quietly entered the dimly lit room on a Saturday afternoon. "Yes, we've been waiting for you," my patient's wife Julie responded in the same calm, composed voice she had maintained all week. "Before we start, what questions do you have?" "I think you answered all of them this morning. I'm ready. Tom is ready. We just don't want him to suffer anymore." "OK, we'll get started." When I was in training, I had seen my preceptors initiate palliative sedation, but this was my first experience doing so as an attending physician. After being dormant for so long, my impostor syndrome returned. Though I was confident that I was taking the clinically-appropriate next step, I was nervous. I asked Tanya, our charge nurse and the nurse who was primarily caring for him over the last few days, to draw up the syringe. She did so with practiced confidence and handed it to me. I held it between my fingers, wondering how slowly I would need to push it to ensure the 2 milliliters of midazolam went in over a full five minutes. Tanya cleaned off the side port of his IV. I twisted the syringe into place. I looked up at Julie. She squeezed Tom's hand. I had first heard about Tom nearly a week earlier, when my colleague was handing off the service to me. "He's in his 50s, metastatic cancer. He was home on hospice and came in yesterday with uncontrolled pain. We started him on ketamine and he looks much better. The plan is to wean his ketamine, increase his methadone, and get him back home, hopefully in the next day or two." Stoic from years of pain from cancer eating away at his bones, Tom lay in bed with his eyes closed, his furrowed brow the only sign of his ongoing agony. When the nurses tried to move him, he screamed. After we weaned his ketamine, his pain quickly worsened. We increased methadone and hydromorphone. Neither gave him adequate relief. We restarted ketamine, but it proved to be no match for his pain. On rounds one morning, Julie asked if Tom could make it home. I told her I didn't think so and explained how worried I was about his pain. If we sent him home, I was concerned the pain would force him to come right back. Julie told me her kids would be disappointed, but that they'd understand, as she did. Easing Tom's suffering was more important. The hospital bed his family had set up in the living room would remain empty, a physical manifestation of cancer's unending cruelty. The hospital bed his family had set up in the living room would remain empty, a physical manifestation of cancer's unending cruelty. We talked about what would come next. If further titrating his medications proved ineffective, which I worried it would be, we would need to consider palliative sedation. "Whatever you need to do," Julie responded, her voice barely betraying the exhaustion I imagine she was feeling. Palliative sedation is a procedure used to relieve refractory suffering in a terminally-ill patient. Clinicians carefully sedate the patient, often to the point of unconsciousness, to relieve symptoms such as pain, nausea, shortness of breath, or agitated delirium. It is a procedure of last resort, and in our hospital, requires the approval of two attending physicians and the unit's nursing director. Though palliative sedation may shorten a patient's life, ethicists and clinicians have long regarded it as acceptable because its goal is not to hasten death but rather to relieve suffering. This is known as the doctrine of double effect, by which an action with at least one possible good effect and at least one possible bad effect can be morally permissible. Back in his room on that Saturday afternoon, I looked over at Tanya, the nurse, then at Harry, my fellow, who had been caring for Tom all week. I took in a breath under my mask, then slowly began to inject the contents of the syringe into his IV. In the quiet, I could hear the music coming from Julie's phone, which she had placed on the pillow beside his head. A pianist played a slow, mournful rendition of the final movement of Beethoven's Ninth Symphony, the Ode to Joy. In my head, I sang along. (SINGING) Joyful, joyful, we adore thee. I went to a traditionally Anglican school. 600 boys of all faiths and backgrounds, we'd rise each morning in assembly and sing hymns together. We cheered, yelled, and thumped on our pews-- a few minutes of raucous togetherness before we devolved into the usual bullies and cliques for the rest of the day. Tom's room couldn't have been more different. He remained completely still. Though Julie held his hand, he was alone, as we all felt in that room. (SINGING) Hearts unfold like flowers before thee, opening to the sun above. I felt the soft resistance of the syringe's plunger hitting the barrel. I looked back up at Tom. His chest fell, but didn't rise. I waited. He didn't breathe. The music slowed down. I felt Harry's eyes pivoting back and forth between my face and Tom's chest. I fixed my eyes on Julie's hands wrapped around her husband's. Despite the tension of the last week, she was calm, gentle. I matched my breath to hers. If she could exude such peace, so could I, I thought. I noticed Tom's hands. He had a piano player's fingers, long and slender. I pictured him sitting at the piano in their living room. I wondered who would take his place on the bench. I wondered if he could hear the song playing beside him. Had he and Julie chosen it for this moment? Did it bring back joyful memories, as it did for me? (SINGING) Melt the clouds of sin and sadness, drive the dark of doubt away. He didn't breathe. Did my first attempt at palliative sedation become euthanasia? Even if so, was this OK? I rehashed our conversations from the last few days. We talked about the risks. I went over the dose. Double effect, I reassured myself. Even so, as bedside nurses have told me, it's easier to talk about philosophy when you're not holding the syringe. I thought about how I would explain Tom's death to Julie. I wondered if she would be angry, upset, relieved? With the help of my outpatient colleagues, they had spent years preparing for his death. His financial affairs were in order, and he had done legacy work with his kids. More than nearly anyone I had cared for, they were ready. Were we? Was I? (SINGING) Mortals join the happy chorus which the morning stars began. He breathed in. Not a grand gasp, a slow, soft inhalation. Tom's hand flexed ever so slightly around Julie's. In my head, I thumped a pew. [MUSIC PLAYING] SPEAKER 2: Welcome to "JCO's Cancer Stories-- The Art of Oncology," 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 of the shows, including this one, at podcast.asco.org. SPEAKER 3: The guest on this podcast episode has no disclosures to declare. [MUSIC PLAYING] LIDIA SCHAPIRA: Welcome to "Cancer Stories-- The Art of Oncology" podcast series. I'm your host Lidia Schapira. And with me today is Dr. Richard Leiter, physician and member of the Psychosocial Oncology and Palliative Care team at Dana-Farber Cancer Institute in Boston and the Brigham and Women's Hospital. Welcome to our podcast. RICHARD LEITER: Thank you so much for having me. LIDIA SCHAPIRA: It's a real pleasure. You submitted a beautiful narrative piece called "Ode to Joy." And I'd like to start today, Richard, by just focusing first on the case that you present to us. Let me tell you how I understand Tom's history, and then you can correct me if this is not the way that you'd like him to be understood. And remember, Tom is a man in his 50s who's lived with metastatic cancer to bones for years. In your narrative, you're very careful and document the fact that you've worked with many members of your palliative medicine team for a long time, that there had been many efforts to control his pain, his suffering, and he had to be hospitalized for pain management. He was already receiving home hospice care. There was a bed in the living room in the center of the family home. And he had a very supportive family and a wife that we'll call Julie at bedside. Is that the proper framing for the story? RICHARD LEITER: Exactly. Yep. Yeah. I think what I would add is that the goal was really to control his pain and get him back home. LIDIA SCHAPIRA: So now you're there as the fresh attending in palliative medicine, and you're called in, and it becomes quite clear to you after a few days of changing his medications that the pain is refractory. And that it-- you note here that he screams when he is moved, that the level of pain reaches what you have called agony. So tell us a little bit more about how a palliative medicine consultant or physician approaches this kind of situation in hospital today. RICHARD LEITER: Yeah, no. Great. Thanks so much. So we were, I would say, lucky enough to have him on our intensive palliative care unit, where we're caring for patients with difficult and sometimes refractory symptoms at any stage of the disease. So not only for end of life. But we do see a number of cases like his every year, every few months, where someone is getting closer to the end of life. The goal is to really focus on intensive symptom management. And their symptoms are challenging to control. So I think the first step, always, is a good history, right? Where is this pain coming from? What treatments have they tried already? What's worked? What hasn't? We're going to titrate medications, but select medications based on that and titrate them. I think someone who has been involved with my outpatient colleagues and has been receiving hospice services at home has often gone through many treatment modalities. So it's really taking what they've been on before and starting to add to it. So for Tom, I had inherited him from one of my colleagues, who had admitted him a couple of days earlier. And at that point, he was already on a hydromorphone infusion and ketamine, as I talk about in the piece. Ketamine had been started, hopefully, as a bridge to get him back home. And he had been on methadone, which is one of our most potent agents for, not only nociceptive pain, so our basic kind of bony pain or visceral organ pain, but also if there's pain with a neuropathic component. Methadone is an opioid that can be particularly effective there. So I think it's saying, OK, well, have we hit all of our receptors in managing their pain? Are we managing the anxiety on top of that? Are we doing everything we can? Are there procedures that we could do to help with their pain? Sometimes we're talking about intrathecal pumps for instance. And obviously, that's a more involved discussion. How much time does someone have left? Are the goals really to put them through a procedure in order to get their pain under control? But we frequently work with our interventional pain colleagues to tease out whether a procedure would be helpful for a particular patient. So those are the thoughts that always go through my mind when I'm approaching someone with severe cancer-related pain. LIDIA SCHAPIRA: So this is a very thoughtful approach. And I think one of the messages is that it seems palliative medicine and pain management are integrated into the care of patients with advanced cancer, which is a very important message for our listeners and our readers. And here you are, you have all of this, you have good communication, it seems, with your team members, with the patient's family, and there's nothing more that you can think of doing. And you're now starting to think about interventions that we normally don't think of, except as a last resort. Bring this to the bedside. Tell us a little bit about the recommendation for palliative sedation and when that's indicated in care. RICHARD LEITER: Yeah. So palliative sedation, as I write in the piece, it's a measure of last resort. And certainly, in our hospital's protocol, it explicitly states it's when all other options have been tried. As we start to integrate more options, it's always a conversation we're having among our team-- is when is palliative sedation truly indicated. How many boxes do we need to check before going down the palliative sedation route? And I think-- so we started to think about-- we had him on ketamine. We tried to wean him off, it didn't go well. We restarted ketamine. We started dexmedetomidine, which can be useful. Precedex, the brand name, they oftentimes use it in the ICU for sedation, but we find that it can be helpful in cases of refractory pain as well. And my practice has been-- and though I haven't gotten to palliative sedation until this case-- when I'm thinking about Precedex, I'm also starting conversations with the patient or their family, and certainly our team, about palliative sedation to say if this doesn't work, this is where we're headed. LIDIA SCHAPIRA: And why is this situation so difficult, so personally anxiety-provoking for you? You do use words that convey that you are feeling nervous, or perhaps even anxious. Tell us why. RICHARD LEITER: I think it's-- relieving our patient's suffering, relieving their families suffering is certainly the core of much of medicine and very much the core of what we do in palliative care. And I think to have someone in just such a terrible situation-- putting aside the pain, right? This is a man who's dying of his cancer, has a relatively young family. That alone is an awful situation. And my job is to make that situation a little bit less bad, is to ease the suffering. LIDIA SCHAPIRA: And there's something about this particular procedure, however, that adds a level of intensity and nervousness for you, and that is that perhaps-- you can describe this better than I-- but the fact that in some cases, this could have the unintended effect of actually causing respiratory depression or even hastening death and something that you have explained in your piece, if I understood you correctly, as the double effect. Did I get that right? RICHARD LEITER: Yeah, that's right. So the worry or one of the considerations with palliative sedation is that it could hasten someone's death. Oftentimes, the doses of the medications that we're using, if we're titrating them slowly, there are studies that show that it doesn't necessarily. I do think, though, when we tie it into withholding artificial nutrition and hydration, in that case, had the person been awake enough to eat and drink before, we do know that it would probably hasten their death, right, from that part of it, but not necessarily the sedation aspect. So double effect is basically saying this is ethically OK-- and there are a number of criteria. But if we are intending the good effect and not the bad effect and that it's proportional to the gravity of the situation so that not every patient who comes in with bad pain undergoes palliative sedation. LIDIA SCHAPIRA: My favorite line, Richard, in the piece-- and one that I now have read probably dozens of times-- is this-- "the double effect, I reassured myself. Even so, as bedside nurses have told me, it's easier to talk about philosophy when you're not holding the syringe." And that just gives me goosebumps thinking about it. What did you feel when you were holding the syringe? RICHARD LEITER: Exactly as I wrote about. There's all of the cognitive processes going on. And I ran it by another attending, I ran it by the nursing director, I ran-- everyone was on the same page, that this was medically indicated in this situation. And yet, when I'm standing there in the room-- patient, his wife, my fellow, and the nurse-- and I'm the one holding the syringe, watching the medication go in, it felt completely different to me. And there's a power that comes with it. In one sense, I felt like I was there for my patient. Here I am, standing here doing this to ease his suffering. And then the other, the unintended consequences of the sedation are real, and that feels different when you're the one physically doing it. LIDIA SCHAPIRA: I think one of the incredible gifts you've given us as readers is to share this with us and really adds a different dimension to the discussion of the complexity of what it is to be present, not just as a witness, in this case, but as somebody, as you say, with a power to really control so many things in the situation. And I thank you for sharing that with us. And question to you is, did writing about it in any way help you process this emotional, very powerful experience? RICHARD LEITER: Absolutely. I write to process. I write when I feel like I have something to say. And oftentimes, I write when a particular moment struck me. And I think that that moment, sitting there, pushing the medication, waiting for that breath while the music was playing was so poignant for me that I walked out of the room and I remember thinking to myself that night as I was decompressing on my walk home from work, I think I need to write about this. LIDIA SCHAPIRA: So thank you for writing about it, and then, of course, for submitting for review and to share it with people. Let me bring the music in. Music is such an important part of our sensory experience. So as you were holding the syringe, Julie, Tom's wife, puts the phone on the pillow and she plays the piano version of Ode to Joy from Beethoven's Ninth Symphony, which I want to play for our listeners now. [MUSIC PLAYING] So Ode to Joy meant something, clearly, to Tom and Julie. And you said that you watched-- perhaps you were watching for his reactions. But tell me a little bit about what it meant to you. You sprinkled your essay with the lines for the choral for Ode to Joy, which has a religious significance as well. So tell us a little bit about that. RICHARD LEITER: Yeah. So I grew up in Toronto. I went to an all-boys school there that had a traditionally Anglican background, though I'm not-- I'm Jewish. We would sing hymns. And over the course of my time there, the hymns became less denominational and more multicultural and inclusive. And it was a moment-- it was a nice moment where everyone got into it. It's 600 boys singing, and so I still remember the words to Ode to Joy vividly. Anytime I hear it, I can replay the words in my head. And I found myself, in those moments in the room, really thinking about it. And the words were still-- as I was processing and watching Tom and Julie and making sure I was pushing the medication at the right speed, there was this soundtrack. It's a strange moment too, because they're good memories for me, and yet I'm in this incredibly solemn, intimate moment in my patient's room. LIDIA SCHAPIRA: And so as we're getting to the end of the piece and there's all of this tension that you've built up in the writing and the narrative-- and here you are, you're waiting and you hear the music and so on-- and then you finally let the tension out and he breathes. It's not a huge breath, but it's a soft, slow inhalation. And you see that the hand is flexed slightly around his wife, so he's still breathing. And you finish with this line that you say, "In my head, I thumped a pew." And I have to ask you about that. What does that mean to you? RICHARD LEITER: Yeah. So in that moment, it was relief, is what it was. Just the sense of, OK, this went-- it's my first time doing this, and this went OK. He appears more comfortable. He is still breathing. This is OK. And it just brought me back when we would thump the pews as we were singing the hymns. Our principal did not like it, but-- [LAUGHTER] But I think it was just that it was relief. I hesitate to say it was joy because I don't think there's joy in a situation like that, in the room. But there was a sense of satisfaction maybe, or professional satisfaction, the, OK, this is what we can do. And as bad as the situation is, there was something that we could do to make him somewhat more comfortable. LIDIA SCHAPIRA: Well, I certainly learned a lot. I wonder if now that some time has passed since this event, if you have any additional reflections on how this story has impacted your professional delivery of care, or perhaps the way you teach others, and if there are any parting comments that you'd like to leave us with. So I haven't had another case where I've needed to do palliative sedation, though we've thought about it in a couple of cases. I do think it's helped me, when I talk about palliative sedation with our trainees, to add the emotional valence. I think I was pretty good at talking about the importance of making sure everyone's on the same page and talking to the patient and the family and nursing staff. But to really talk about the significance of that moment for us as clinicians and how it does feel different-- at least it did for me-- and I think drawing on my personal experience is helpful in teaching it to the fellows that it's OK to feel like that when you're doing this. LIDIA SCHAPIRA: There are moments in medicine-- certainly in what you do-- that are really difficult. And this, probably, I would imagine, ranks as one of the top things. And it should never be easy. It will never be easy. The day that you think it's easy, you need to find something else, right? RICHARD LEITER: I think that's right. I think that's right. LIDIA SCHAPIRA: Well, thank you so much, Richard. You made me laugh, you made me cry reading this, and I thank you very much. My last question is, have you had a chance to talk with Tom's widow Julie about what that moment felt like to her? RICHARD LEITER: I have not, although I hope to in the near future. LIDIA SCHAPIRA: And that will be your next piece for us. [CHUCKLES] All right. Well, thank you very much and until the next time. Hope you all enjoy reading Ode to Joy. RICHARD LEITER: Thank you so much. SPEAKER 1: Until next time, thank you for listening to this "JCO's Cancer Stories-- The Art of Oncology" 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's Cancer Stories-- The Art of Oncology" podcast is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org. [MUSIC PLAYING]

A mother mourning the loss of her daughter discovers that she has lost something else important to her. TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. SPEAKER 2: Welcome to JCO's Cancer Stories, The Art of Oncology, 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 of the shows, including this one, at podcast.asco.org. ELIZABETH CONROW: Access Denied, by Elizabeth Conrow. I lost my daughter, Amanda, in 2015. She was diagnosed with a brain tumor at age three and was in treatment for 2 and 1/2 years. Less than two weeks after she died, friends and family were getting on with their lives, but I was still in shock. I couldn't believe that Amanda was really gone. Early in the day, I looked at my kitchen table and tried to imagine her eating a bowl of rice, an unusual breakfast for a five-year-old. But that was Amanda. My eyes filled with tears as they rested on the empty chair. She was really gone. In that moment, standing in the kitchen, I struggled to remember every detail of who she was. It felt like the memory of her was slipping away. My heart beat quickened, and my mind raced with compulsive nagging thoughts. How tall was she the last time we were in the outpatient clinic? How much did she weigh? I realized I would never be able to put her on a scale again or mark her height on the cupboard door. I fear that this information would be lost forever, just like Amanda. I moved to my computer and started to log on to our hospital's online patient portal to see if I could find answers to my questions. How many times had I logged into this system looking for Amanda's test results or to message one of her doctors? How many times did it serve to confirm appointment times or remind me of medicine doses? I clicked the Sign In button, and my heart stopped. I couldn't get in. Instead of viewing her chart, I saw an alarming red stop sign and a message saying "access denied." I stared at the screen in disbelief. Just two weeks after losing my daughter, I faced yet another heartbreaking and unexpected loss. I no longer had access to Amanda's medical records. I no longer had a connection to her medical team and the hospital family I had grown to love and care for. Everything Amanda had been through for the last 2 and 1/2 years was gone. It was as if she never existed. She had vanished. I was caught off guard, deeply saddened, and utterly unprepared to have this connection to the hospital and this connection to Amanda ripped away. I was confused and embarrassed by my emotions. I certainly didn't need this access. But I was devastated that it had been taken away. I reached out to my daughter's oncologist to ask how and why the patient portal had been turned off. I let him know that it was really important to me to be able to view Amanda's records, at least for a time. It had never occurred to him that a parent might want to see this information again. He explained that it was a system designed safety measure that automatically turned off access to an account once a patient had died. I was the first parent to reach out to him with this question. Amanda's oncologist immediately contacted the online records office to reactivate her chart so I could search out answers to some of my questions. It brought me so much comfort to be able to go back in and revisit her medical journey. As I thanked her doctor, I shared with him how important it was to protect families from this type of trauma. I didn't want another family to experience this pain. He listened and helped put a manual reactivation system in place. Going forward when a child died, the online records office would manually reactivate each pediatric account individually. It wasn't a perfect solution, but it was a step in the right direction. It has been six years since Amanda's passing. I am now the bereavement coordinator at the same hospital where she received care. When I started in this role, I was surprised to learn of several families who, like me, had been denied access to their child's medical record. Hadn't the hospital resolved this issue years ago? I was frustrated that our institution hadn't found a better solution in the six years that passed. Last spring, as I followed up with bereaved families from our hospital, I had a conversation with a mother, Diane, that was hauntingly familiar and heartbreaking. Diane and I spoke on the phone shortly after the loss of her son, Evan. As we wrapped up our call, almost as an afterthought, she sheepishly asked about Evan's medical records being deactivated. I was immediately brought back to my kitchen table and the pain I felt when I experienced this secondary loss just two weeks after losing Amanda. I knew why Diane felt silly asking about this. And I deeply understood her need to log in. Diana explained that she was creating a record of everything Evan had been through, every transfusion, every chemo treatment, every inpatient and outpatient visit. And she could no longer complete that task. She shared her experience with me. I know for me, it was really difficult to wake up that very next morning, literally only about 12 hours since he died and not be able to look at it. Even though I know there had been no additional tests run since the last time I had checked, it was my morning routine to look at it. I would check it each morning, even before I got up. It had been that way for months while we were inpatient. First, looking at his ANC and counts, and then in the final month and a half, checking his bilirubin and liver numbers. There was always that hope that things were going to improve. This would be the day. So that first and subsequent time was just a blunt reminder that he was gone and there would be no more checking. I wanted to go back and look at his results, too. Oddly, I thought it would make me feel closer to him and closer to the routine I had while he was alive. Diane wanted to feel closer to her son. I wanted to feel closer to my daughter. Accessing a child's online medical portal is one way a parent begins to come to terms with this impossible loss. Snaman, et al, 2016, suggest that parents who are grieving significantly benefit from the creation and continuation of bonds with a child who has died. Revisiting a child's journey through the lens of the medical portal helps strengthen that bond. As I looked through Amanda's chart and remembered various times we visited the hospital, it helped me picture her more clearly. And it helped me feel a connection to her that I was deeply longing for. Looking through a child's medical record, while painful, can be part of healing and connection. In addition to creating bonds with a child who has died, the medical portal helps parents stay connected to the hospital and the medical team that cared for their child. According to additional research by Snaman, et al, 2016, bereaved parent's benefit from the ongoing support of a hospital throughout a time of grief. When a child dies, the secondary loss of the medical community can leave families feeling abandoned by those they have come to trust and depend on. Anyone who had taken care of Amanda felt like family to me. Sending messages to Amanda's medical team after she died provided a feeling of familiarity when everything else around me was spiraling out of control. A continuing connection with the medical team through the online portal can positively impact grief outcomes for bereaved parents. Accessing a child's medical record provides a grieving family with an easy way to communicate with, and ask lingering questions of the medical team. Access to medical records should not end when a child dies. The 21st Century Cures act acknowledges the need to provide patients with open notes and immediate access to medical information. As we implement real-time access for living patients, continuing access after a loss should also be considered essential. Dr. Alan Wolfelt, from the Center for Loss, discusses the need to say hello to one's grief and welcome it before saying goodbye to the person who died. In those early months, saying hello to grief meant reading through Amanda's medical records, communicating with her medical team, and uncovering every connection I had to her while she was alive. In some small way, logging into Amanda's medical portal and discovering that she was 42 inches tall and weighed 41.2 pounds brought me immeasurable comfort. As parents grieve the loss of a child, comfort and connection should be readily available without having access denied. SPEAKER 3: The guest on this podcast episode has no disclosures to declare. SPEAKER 4: Welcome to Cancer Stories, The Art of Oncology podcast series. With me today is Elizabeth Conrow, bereavement coordinator at the University of Rochester Medical Center and the author of Access Denied. Welcome to the program, Liz. ELIZABETH CONROW: Thank you so much for having me here. It's an honor to be here. SPEAKER 4: It is our pleasure. And first of all, let me start by saying I was very moved by the piece. And I'm so sorry that you lived through this experience. And really interested in knowing how you transformed your personal grief into now, your profession. ELIZABETH CONROW: Sure. Well, it's definitely been a process. Obviously, as a family, we never thought we would be down this road. I never thought I would have a child who had cancer. I never thought that I would have to go through the grief of losing a child and then comforting my own family, and my husband, and those around us through that experience. And I can tell you that for the first couple of years, I really didn't feel equipped to do anything. I felt like I lost my confidence in anything that I had an ability to do prior to this. Simple things like making a meal for someone who was sick became way too overwhelming to even consider doing. So it was definitely a process of years. But when the opportunity came up to work at Golisano Children's Hospital, the same place where Amanda had been cared for, the timing was right. And I knew that it was a great step to take and a way to honor Amanda's life, and really in some way, offer just a little bit of support and comfort to bereaved families, because I understood a little bit of what maybe they were going through. So it just seemed like a really good fit and a really good match for my experience at that point and a way to help and honor Amanda. SPEAKER 4: Let's start by talking a little bit about Amanda. Tell us a little bit about her and her story. ELIZABETH CONROW: Sure. Amanda is one of five children. So she was the fourth of the five. Very silly, loved to wrestle with daddy, had the biggest blue eyes that anyone had ever seen. She was just a delight and a joy. And when she was 3 and 1/2, she was diagnosed with a brain tumor. And we were in the hospital for a number of days. She had surgery and a full resection. And we were told that if after a resection and radiation it never came back, that we would be good. But that if it came back, it would likely be terminal. So we knew at the outset that this was-- we're not dealing with a cold or a headache. We're dealing with something pretty serious. So she went through the surgery beautifully. She went through all of her radiation treatments. We did a clinical trial of chemotherapy. And six months from when she was diagnosed, we really felt like we did well. She did amazing. And we were ready to walk away from everything and just celebrate really, kind of getting through this. And her very first follow-up scan two weeks after she was done with treatment-- her doctor, Dr. Koronas, called us and let us know the very devastating news that the tumor had returned, and it was all in her brain and down her spine and too many places to count. So six months from diagnosis, we knew that this was not going to end well. And we kind of had to struggle to prepare for that, as well as to recognize that in that moment, she was still Amanda. And she was still doing really well. But we knew that time would be limited. And so we had actually a very good year and a half with her, as much as you can say that. She went through additional radiation treatments. And we continued to try other chemotherapies to do what we could. But ultimately, in February of 2015, surrounded by her family in our home she passed away. And we then had a whole new struggle with grief and really, coming to terms with a new life and a devastating loss. But she was a joy. And she was a joy throughout it. So it was not all terrible. SPEAKER 4: She sounds like an extraordinarily little girl. And in your essay, you start by telling us that just after she died, I think a few days or weeks, you're thinking about her, and you want to access her medical record through the portal that you had gotten used to using all the time. And then as you're logging in, you get the signal that says "access denied." And that triggered a tremendous wave of grief for you or something. Tell us a little bit about that and what you did with that. ELIZABETH CONROW: Sure. I think I didn't realize at the time that I was really just trying to hang on to who she was, that I was trying to connect with her in some way. I mean, it was just two weeks after she had died. And I just-- I wanted access to see, what did she weigh? Goodness, if I could recreate her in the form of a stuffed animal, how long would she be? How much would she weigh? And when I went to log in, it was a horribly devastating loss. It really felt like all of the sudden, I knew in my mind she was gone, but logging into this wealth of information that contained all of her blood counts and numbers and information that we had access so often, to all of a sudden have that gone. It was just a punch in the gut reminder that she truly was gone and that her records had disappeared. And she just wasn't here. And I wasn't prepared for that. I really thought that I'd be able to go in and find the things I wanted to find and have peace about that. It was shocking to me. And I remember feeling so embarrassed like, how can I call her doctor and say, I lost this access and I really need it? When she's not here, there's no reason. I don't need it. He's going to think I'm crazy. But it was important enough to me that I reached out to him. And I said, you've got to help me. How can I still access this? SPEAKER 4: So what happened next? ELIZABETH CONROW: So he-- actually, I was pretty surprised. I was the first parent he said, that had ever reached out to him with this issue. And I thought, how is that possible? How is that possible? And I'm guessing other parents had experienced it, but didn't know what to do, didn't know where to turn. And he was very compassionate. And he reached out to our online medical team, our portal team, and tried to figure out a way to reactivate the account for me. And got that done very quickly. And I said, well, it's not enough that it's been reactivated for me. No other parent can go through this. We have to come up with a plan. And so he really did work very hard with our team here to come up with something that would hopefully fix the problem. And it did. I know many families then, had their access turned back on manually, through a manual process that they put in place here. But I know that in the last six years, there have been several families who went to log in and had this experience. And unless you've been there and unless you've been the parent on the end of losing a child and then going in and having more taken away that you didn't expect, you don't understand the pain of that. And so I think the driving force behind me really wanting to write this article was to say, I know that this isn't just my institution. I know this is happening across hospitals. I know that when a child dies, this access is turned off. And that really hurts families. And if there's a way to bring attention to that and say, hey, we can do better, we need to. SPEAKER 4: Now that you have this perspective, I know that you have actually developed some training for oncology fellows and staff to train them a bit to talk with bereaved parents. What are some of the lessons that you want people to learn? ELIZABETH CONROW: That's a great question. I'm working with another doctor here. It's an advanced communication training where we're helping young doctors share bad news for the first time. And it's amazing to me how afraid people are to approach the bereaved. And I guess, having been through it, I see now how poorly we really do bereavement and how afraid we are to kind of approach someone who's lost a child and just wrap our arms around them and say, I'm so sorry. I'm here with you. Everybody wants to fix it. And there's no fix. And people don't want to approach a bereaved parent and bring up their child, because they don't want to make them sad. And what many people realize is that our children are always on our mind. You're not reminding us of anything we're not already thinking about. I was pretty surprised after losing Amanda that someone could be on my mind all the time-- all the time when they're not here anymore. You know, you think about people here and there, time to time, people in your life. But once she was gone, she was right at the front of my mind and still is, every moment of every day. And so if you see a bereaved person, it's OK to mention their child's name. I actually-- I go to the dentist. And the woman who cleans my teeth, every single time I go, will mention Amanda. And I know it's intentional. And I know it's because she wants me to know that she cares. And so those kinds of simple acts that people do as a way of recognizing and honoring the child whose passed means so much to a bereaved parent. SPEAKER 4: Just listening to you and the emotion in your voice, I imagine it must have been difficult in a way to go back to the same place where Amanda was treated and now, work with the staff and the clinicians who treated her. Tell us a little bit about how you've managed those relationships? ELIZABETH CONROW: One of the things I've learned, and that's partly through the role I have now in supporting other bereaved parents is that everyone grieves differently. And I know there are some parents who, the first time they come back to the hospital, it's really, really hard for them. And it's almost like a PTSD moment. For me, I appreciated and cared about all of the medical staff so much that coming back here to me, was a need. I needed to get back here and find a way to connect with these doctors and nurses and the people who cared for Amanda so beautifully while she was here. In those first months of grief, I showed up at the hospital-- I remember there was one day I showed up, and I felt so lost. But I just needed to see those nurses and give them a hug. And I felt awkward and out of place, because suddenly, I'm here and she's not with me. But I just needed to be in a place where she had been and a place that meant so much to us. So coming back here for me, certainly had its hard moments. And there have been challenges with it. But it's been a place of comfort. And being able to talk about Amanda with other parents has really been a gift for me, because it's not an opportunity you have all the time, especially six years later to talk about the child who died. So it's been a gift. SPEAKER 4: What is it like for you to be with other parents now who are going through what you experienced? How does your experience of loss influence your role as a counselor for a newly bereaved parents? ELIZABETH CONROW: I do a lot of listening. I do a lot of listening. And there are some parents who I'll call and follow up with and check in on. And they're good. And they don't need anything. And to be honest, I think when we first lost Amanda, if someone called me and I had never met them before, I might say I'm good. I don't really need any support right now. I've got my family. But there are some parents who I will call, and they will talk to me for 45 minutes. And they will cry. And they will say, you're the first person I've been able to talk to about this, because you understand and you've been through it. And so I'm able just to listen. And when they say things that they think are crazy, I wandered into my son's room and I slept in his bed last night, I say, I understand that. I once found Amanda's socks in a travel bag. And when I found them, I pulled them out and I slept with her socks. So there are things that people think are crazy that I'm able to help them normalize some of those feelings and understand that it's OK. SPEAKER 4: I don't think it's crazy at all. You speak with such knowledge and also such empathy. I wonder if you can help us also understand how you see the clinicians now-- the doctors and nurses who are actually are caring for these patients-- how you see them react to the death of a patient and how they maintain their relationships with what the parents once the kids are gone? ELIZABETH CONROW: It's been very interesting, I guess you could say to be on the other side of this, right? I was on the parents side before, where I was able to receive kind of the love and comfort and support of those who cared for Amanda. And I was able to see them showing up at the funeral and the ways that they would reach out and send notes and cards. But now, being on this side working with many of those same people, I've been really struck, even during our weekly meetings when they talk about different cases and different families and the losses that they've had, how significantly it does impact them, and how much those families and those children really do mean to them. And you know, I've often sat there now wondering, well, what did they say about my family? What did they say about us? And not a conversation I can go back to and sit in on. But I'm just struck by how much they really do care and how much it extends beyond this just being a job for most of-- all of them. SPEAKER 4: Yeah, in your role now, in your professional role, what kind of changes have you implemented in the way clinicians and parents communicate, or the way the system communicates with parents? ELIZABETH CONROW: At our hospital where I work, we have probably around 80 or 90 losses a year. And I came into this and said, I can support these families. And I can follow up with 80 or 90 families in a reasonable manner. But really, we need more parents doing this. We need to expand kind of what we're doing. So I've been trying to work toward implementing a mentoring program of sorts, where bereaved parents who are a few years out in their grief can come alongside newly bereaved parents and really support them, one on one for a year or a year and a half to help them get through that time, so that it isn't just me. And as great as I am, I really know that we can do much, much better by parents if we expand kind of the support network that we have. So I've been trying to grow some of our bereaved parent base. And those who can give input on some of the things we're doing-- because I know bereaved parents have so much wisdom and so much they can share from their own experiences. SPEAKER 4: You sound like a force. I wonder, have you connected with other hospitals, other teams? Or is your-- are you concentrated on your hospital and your community? ELIZABETH CONROW: The greatest support to me, actually has been St. Jude. They have such a fantastic program. Their bereavement, their parent support is really outstanding. Actually, just this week, I was able to sit in on one of their parent mentor trainings to kind of learn, well, how do you train your people, and what do you do? And so that was fantastic. So I'm really grateful-- grateful for their support. So they've been really wonderful. SPEAKER 4: I imagine Amanda's passing really affected your entire family and the other kids. Can you tell us a little bit about how all the other kids dealt with their grief? ELIZABETH CONROW: Sure. I know at the time when Amanda was diagnosed, my oldest was 9, and my youngest was 9 months. So everybody was pretty little. And they went through that at a really young age. And then when she passed, my oldest was 11 and my youngest was 3. So they were still little. And they had been through what I consider to be significant trauma in those early years. And when things first happened, I mean, I had a therapist describe it to me as a children's mobile that hangs over their bed you know, that once it becomes imbalanced, it just tips on its side. And that's the way things felt at home for quite a while. You know, just nothing felt right and things felt out of order. But kids are so resilient and so forward looking. And my kids really did beautifully through it. And I had someone tell me, well, kids are going to revisit grief. And they're going to come back to it from time to time. And it'll surprise you. And I will say, that's so true. You know, I would think everything was going along OK and everyone was coping well. And then, my daughter Jessica, who was closest in age to Amanda, would come down at 10 o'clock at night in tears because she was thinking about her sister. And that would catch me a little bit off guard. And my oldest just went away to college. And she's now 18. And she's had some conversations with me lately just about everything they went through and really revisiting some of her feelings about it all. And so they don't really get over it. But helping them to kind of process it and work through it and really, just talk about her. We talk about her constantly. She's a part of everything we do. We still make her a birthday cake. So we just keep her memory alive and celebrate her life together. But grief for kids is certainly different, and it doesn't end. But they are definitely forward looking and really can handle more than I think sometimes we give them credit for. SPEAKER 4: And your husband and you I hear have also been involved in some activities to talk about this publicly or teach others. What was that like for you as parents? ELIZABETH CONROW: There are a few things that we've really wanted to help move forward in terms of childhood cancer awareness and things that people can do to really help bereaved parents. And I think there's just so much that people don't know or understand. Many people don't realize how underfunded childhood cancer is. So it just means a lot to us to be able to kind of get that message out now. SPEAKER 4: I imagine there's so much work to do. And as we've had this great opportunity to chat about Amanda to remember her, to think about your experience and the amazing work you seem to be doing-- are there any final comments that you want to share with our listeners? ELIZABETH CONROW: It's an honor for me to really share this experience. And that bereaved parents need support, and they need to know that people care and remember, even as time goes on. So just take good care of those who know who are grieving. And love one another. SPEAKER 4: Thank you so much. This is Liz Conrow, author of Access Denied, published in Journal of Clinical Oncology. Thank you very much. Until next time. SPEAKER 1: Until next time, thank you for listening to this JCO's Cancer Stories, The Art of Oncology 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's Cancer Stories, The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org. [MUSIC PLAYING]

Dr. Hayes interviews Dr. Breitbart on his research addressing psychiatric, psychological and existential adjustment as well as symptom control in advanced cancer. Dr. Daniel F. Hayes is the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center. Dr. Hayes' research interests are in the field of experimental therapeutics and cancer biomarkers, especially in breast cancer. He has served as chair of the SWOG Breast Cancer Translational Medicine Committee, and he was an inaugural member and chaired the American Society of Clinical Oncology (ASCO) Tumor Marker Guidelines Committee. Dr. Hayes served on the ASCO Board of Directors, and served a 3 year term as President of ASCO from 2016-2018. TRANSCRIPT SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] DANIEL HAYES: Welcome to JCO's Cancer Stories-- The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insights into the world of cancer care. You can find all of their shows, including this one, at podcast.asco.org. We have a special treat today in our podcast series in that I have the opportunity to interview Dr. William Breitbart. Dr. Breitbart is the Jimmie Holland Chair of Oncology at Memorial Sloan Kettering and the Professor and Vice Chair of the Department of Psychiatry at the Weill Cornell Medical College. And as far as I can see, Dr. Breitbart, you've never left New York City. But I will get the background. And you can tell us if you took a vacation or something one time outside the city. Dr. Breitbart grew up in the Lower East Side of Manhattan. He went to Brooklyn College, graduated in 1973, then medical school at the Albert Einstein College of Medicine. And then he did his residency in internal medicine at the Bronx Hospital and trained basically at Memorial Sloan Kettering. Joined the faculty there, and has been on the faculty ever since. He has a number of accomplishments, too many for me to really review it carefully. But he's been president of the International Psycho-Oncology Society and received their Sutherland Lifetime Achievement Award. He's been president of the Academy of Psychosomatic Medicine and received their Hackett Lifetime Achievement Award. And on a personal basis, my brother was also the president of the Academy of Psychosomatic Medicine. So I'm very proud of my brother and equally proud of Dr. Breitbart. He really is responsible for a number of enormous steps forward in our field, including psychotherapeutic approaches for palliative care of patients with terminal illnesses, especially cancer. He has been involved with what I saw you call, Dr. Breitbart, "hastened to death." I had learned it as assisted suicide. I'm going to ask you a question about that. I'm interested in your comments. And more recently, meaning-centered psychotherapy for the terminally ill And we'll talk more about that, too. So in addition, I have asked Dr. Breitbart if he would also give us insights into Dr. Jimmie Holland's life and her career. Sadly, she passed away before we had an opportunity to chat with her. She was one of my favorite people in the whole world. And I think everybody that knew here said the same thing. So we'll get some insights for those of you who didn't know Dr. Holland from this call as well. Before we start, Dr. Breitbart wants to declare that he's received honoraria from Novartis and has a consulting or advisory role with Novartis. Dr. Breitbart, welcome to our program today. WILLIAM BREITBART: Thank you Dr. Hayes, pleasure to be here. Can I make just one slight correction? I actually trained in both internal medicine and psychiatry at the Bronx Municipal Hospital, which is the Albert Einstein College of Medicine, in New York City Health and Hospitals Corporation's Public Hospital. So I trained in both psychiatry and internal medicine, jumping back and forth between the two, out of a state of confusion. And then I landed in Dr. Holland's fellowship at Memorial Sloan Kettering for a variety of reasons. The main reason was though that I had developed a thyroid cancer when I was a medical resident in the middle of my training. And then I went back to finish up more of my psychiatry residency training, I became the liaison to the Oncology Clinic at Jacobi Hospital, the Bronx Municipal Hospital. I did consultations for cancer patients. I ran groups for cancer patients and also ran groups for the oncologists and oncology nurses. And I was trying to educate myself on the subject of psycho-oncology or psychiatric oncology. It actually hadn't been named yet in those days. And the only literature I could find were papers written in oncology journals by Dr. Julie Holland. And so that's where I knew where I needed to go to become more expert in this area. That's the most superficial version of how I ended up at Memorial Sloan Kettering. I could tell you the more interesting version if you're interested. DANIEL HAYES: Well, actually, what you just covered was my first question. I was going to say this is about you, not about me. But my brother also did training in internal medicine and decided to go in psychiatry, and ended up in psychiatry liaison. And I think that's what makes you two, and others like you, powerful, is that if you go to France and you don't speak French, you're not going to be listened to. And if you come to a bunch of oncologists, and you don't speak internal medicine or oncology, we're not going to listen to you. And I think clearly to me, Jimmie Holland always knew what I did. And I think you have the same strength. I'd love to hear how you actually got involved with her. Yes. Please begin. WILLIAM BREITBART: I agree with you actually about that comment. It's very helpful to have had the training in both medicine and psychiatry. And, in fact, we've trained a few fellows who've done oncology fellowships and then done our-- and a psychiatry residency and then done our psycho-oncology fellowship as well. But the real story of how I ended up in this field starts in childhood, where a lot of stories start. But my parents were both Holocaust survivors from Eastern Europe, from Poland in particular. When the war broke out, my mother was 14 years old and my father was 17 years old. And my father's family were all killed. But he ended up surviving, hiding in the woods. And he became-- Polish forest-- and he became part of a partisan fighter group, lived in the Polish forest. And one day he went looking for food and broke into this farmhouse. And as it turned out, my mother and her parents were being hidden by a Catholic woman, who hid them in a hole underneath the stove in her barn. And my father broke into this farmhouse and discovered my mother and my maternal grandparents. It turned out they were related. They were second cousins. My father said, you can't stay here. It's not safe. You should come into the woods with me and 150 other people. My grandparents were too afraid to go. But they let my mother go. So at the tender age of 14 and 17, my parents were hiding in the Polish forest, where they lived for about three years, hiding from the Nazis, and then Ukrainians, and all sorts of people who were interested in killing Jews. And they finally, after the war, crossed over to Germany. They actually found my grandparents alive. And they crossed over the border to Germany, went into this displaced persons' camp outside of Munich and got married there. And then came to the Lower East Side in late 1949, early 1950. And I was born several years later. And I grew up in this home on the Lower East Side, as you pointed out. And I grew up in a home where the Holocaust also lived. I lived in this home where the Holocaust was in every room-- didn't have a room of its own. It was in all the rooms, on all the walls-- and all the pictures that had been saved of my family, that had perished, on all the religious articles that might have been saved, et cetera. So I grew up in this environment where I understood at a very early age, maybe four or five years old, that death and suffering were very real. And that we all lived in this space between life and death. My mother would ask me every morning-- when she gave me breakfast, she would ask me the question, why am I here? And the full question really was, why am I here and everyone else is dead? Basically, what evolved out of this was the transmission of this responsibility or I guess a burden-- for me, it was an inspiration-- for me to accomplish something of such significance and impact-- in the world of suffering in particular-- in the arena of people who suffer in the face of death. And it's going to be up to me to achieve something of such significance that my parents would be able to-- my mother would be able to turn around and say, well you see we had to survive because if I hadn't survived, there wouldn't be Bill Breitbart in the world. [LAUGHTER] So that was the mission. That was the burden. That was the inspiration. And I wasn't fully cognizant of it. But I was traveling this journey-- this route that took me through college, and loving science and poetry, ending up in medical school, thinking I'd be a psychiatrist, but then falling in love with medicine. Loving both psychiatry and medicine. What I realized what fascinated-- what fascinated me was how a human being can live a mortal, finite life. How do you-- as a person who develops a life-threatening illness, how do you continue to live? How do you have the strength, the courage, to keep on living? And what gives you purpose and meaning? And so I got myself to Sloan Kettering by reading the work of Dr. Jimmie Holland and Dr. Massie. And I found myself at Memorial. I put myself in a place, with a mentor-- a group of mentors-- a place where I would breathe the same air of my patients, who were breathing the air of a human being confronting death, confronting the real prospect death being closer than-- closer than it was farther away. So that's how I ended up at Memorial. That's the real story. And I went to Sloan Kettering to do a fellowship, just to become a good clinician. I wanted to be a clinician. I never had the expectation of being a clinical researcher or an academician. I never had the ambition or aspiration to be an academic, a teacher, an advocate; never thought to be a professor of anything. I never thought I'd write books, or scientific articles, or become president of organizations, et cetera. All that happened because of my exposure to Jimmie. And my interest in research ended up being a result of one conversation that I had as a fellow. Dr. Holland, who was supposed to be my supervisor-- she's deceased now-- she was my inpatient supervisor-- my outpatient, inpatient supervisor. So we made rounds one day, which was very rare. But we made rounds one day. And I was the liaison. I was very fortunate enough to be the liaison to the Neuro-Oncology Unit and to the Pain Service at Memorial, which were both within the Department of Neurology. When Dr. Holland was recruited to Memorial Sloan Kettering in 1977, it was by the chair of the Department of Neurology, Dr. Jerome Posner-- Jerry Posner-- who recruited both Jimmie to be the Chief of the Psychiatry Service and he recruited Kathy Foley to be the Chief of the Pain Service. So I basically held on to these two meteoroids. Jimmie Holland and Kathy Foley, those are the two people who helped-- helped pull me along the road. So on the Neuro-Oncology Unit, I had done a consult on patient with brain tumors, on high-dose steroids. And he had a severe psychosis. And I asked Dr. Holland, why is it that these patients on steroids develop these neuropsychiatric syndromes? They develop depressions. And they can get delirious, and psychotic, and manic. And this was the advice that my mentor gave me-- Dr. Holland gave me-- which turned me into a scientist. And her response was, well, gee, Bill-- in her Texas twang-- well, gee, Bill, I really don't know. I really don't know. I guess you'll just have to go figure that one out yourself. [LAUGHTER] And that's what I ended up doing. I then pursued figuring it out myself. And that's what I did for the next 30 years, trying to figure out clinical problems-- when the AIDS epidemic exploded. My first research study was to study looking at patients with epidural spinal cord compression, those who had high grade versus lower grade compression. One group got high-dose steroids, the other didn't. And I did a comparison study of psychiatric syndromes in both populations. I was at Memorial when the AIDS epidemic exploded. And so I started to do studies of delirium. I did the first double-blind randomized controlled trial of neuroleptics for the treatment of delirium in the AIDS population because they all got demented and delirious. I did the first studies of pain in HIV. I did the first studies of desire for hastened death in patients with advanced AIDS and in patients with advanced cancer. And then I started to do a lot more work in inflammation and depression in pancreatic cancer patients. And eventually, everything kind of culminated. As I evolved from being a psychiatric oncologist to a psychiatric oncologist and palliative care clinician, that kind of bridged the two worlds of psychopharmacology and palliative care. And I started really looking at issues of desire for hastened death and the loss of meaning. And then developed interventions for meaning, which we call meaning-centered psychotherapy, which has been a real advance I think in our field. DANIEL HAYES: You must have been Dr. Holland's first trainee at Memorial. WILLIAM BREITBART: Well, her story-- basically, she was this young country girl in Nevada, Texas. She grew up on a farm, a cotton farm apparently. She was most influenced by the country doctor who would visit when people were ill. And when he passed away, he gave her a set of medical books, which inspired her. And she told her family, I think I want to be a doctor. And they said, well, gee, that sounds unreasonable, Jimmie. But whatever you feel like doing, go ahead. She ended up going to Baylor. And I think she was one of only three women in medical school class at Baylor. She started her residency I think at Baylor as well. And then eventually, she got married. Her first husband died tragically. I believe it was a suicide, which I think got interested in psychiatry. She ended up, I think, doing her residency at-- finishing her residency at MGH, along with Tom Hackett, people like that. And somewhere along that route, that's where she met James Holland. So James and Jimmie were, as you say, a power couple. James told me that Jimmie was his secret weapon, his secret power. But Jimmie told me the exact same thing about James. I think they fed off each other in terms of creativity and ideas. So when James moved to Roswell Park, I guess, Jimmie started a special clinic. And she called it "special" because nobody would come to a psychiatry clinic. But they would come to a place that was special because it made them feel special. And I guess it was around that time that James started collaborators-- CALGB. On the drive to work one day, Jimmie said, you ask patients every kind of question, like how many bowel movement does he have? You're very invasive in your questions. But you never ask them how they feel. And so she insisted that James do something about that. And so in order I guess to not get nagged on the car ride every day, he started a quality of life committee in CALGB. And Jimmie chaired that for quite a while. Eventually, I think James went to Mount Sinai. And Jimmie came along. And she worked at Albert Einstein-- College Hospital-- at Boston College of Medicine. And she was there with actually a bunch of pioneers of psychosomatic medicine. There was a guy named Herb Weiner, and Sig Ackerman, and Jim Strain, and Myron Hofer. These are very important names in our field of psychosomatic medicine. Jerry Posner at Memorial, Department of Neurology, was looking to bring psychiatry into-- consultative service to Sloan Kettering. And Jimmie often says they couldn't get Ned Cassem from MGH. So they picked her in second tier. And in 1977, she came there, along with a resident who graduated from Einstein, Mary Jane Massem. And the two of them had an office, with a card table-- as she described-- and a stack of index cards with the patients on them. And they set about starting a consult service. So in '77, she was the chief of the psychiatry service. And then about '78 or '9, a clinical fellowship was established. The NIMH had an initiative at that point to develop consultation liaisons, psychosomatic medicine fellowships around the country. And so she benefited from that initiative, and started a fellowship. That continued through '78 or so. And there are a couple of classes of fellows before me. I came to do the fellowship 1984 to '86. And it was during my fellowship, I think, that Jimmie and a woman named Julia Rowland, a psychologist, who's at the Smith Center now-- but was around the NCI's survivorship program for a long time. DANIEL HAYES: I actually worked with Julia at Georgetown for five years. WILLIAM BREITBART: At Georgetown, exactly. So she and Julia wrote the first-- edited the first textbook of psycho-oncology. It was called the Handbook of Psychooncology. And that's the first time I think the term "psychooncology" was used. I think it might have been 19-- late 1980s. It might have been 1989 or so that book came out. And the term psychooncology was not hyphenated at that point. There was no hyphen between the two O's. Jimmie asked me to write about six chapters. I knew a lot about delirium. I wrote that chapter. I knew a lot about suicide and cancer, which was an early interest of mine. And I knew a lot about neuropsychiatric issues and AIDS. But I didn't know very much about neuroendocrine phenomena that caused neuropsychiatric syndromes or the psychiatric aspects of head and neck cancer. I said to Jimmie, I don't know anything about these subjects, Jimmie. Do you think I'm the person to write this chapter? And she said to me, well, Bill, there are no experts in the world in this field. [LAUGHTER] So after you write the chapter, you will be the expert. So that was the philosophy. And so as a mentor, I would basically say the greatest thing about her as a mentor was that she gave you the confidence that you could achieve whatever you wanted-- whatever you were driven to achieve. She had that faith in you. The idea was that the only person who really had to believe in what you were doing was you. And if it was important to you to find the answer to that question, that you would be able to do it. She had a knack for finding people who were very driven, who joined this mission. It was really a mission. It was a calling to provide the human side of cancer care, to provide whole person care, to take care of the person who had cancer while they were going through all the cancer treatments. And the combination therapies that James Holland had come up with. DANIEL HAYES: Two stories about Jim, who I had more association than with Jimmie. Although Jimmie told me the thing she tell you, which is you got to figure out what you want to do. And then you'll be great at it, because I wasn't sure. But with Jim Holland, two things. I was the very young guy in a field to be. And I was named chair one of the committees. And he was sitting in the back. And I was talking about, well, we need a statistical plan, and that sort of thing. And in the back of the room, as only he could do without a microphone, "Well, Hayes, if you need a statistician, it's probably not worth doing." And other is, I once asked him, between you and Dr. Frye, who was my boss, Dr. Frye White-- the three guys, who actually came up with the idea of combinational therapy? And I might as well have let a fuse to a bomb because he was-- "Well, I did. I was there before they did. They came in. They were in the minority." And he sent me the protocol. That was David. So to be sure I understood that he had written it before those guys got there. He was quite a character. And I have to say, your comments about Jimmie, and being married to Jim, were like oil and water. It's unbelievable to me that they actually had a very loving, long-term relationship. She had five children with him, who are all accomplished in their own right. WILLIAM BREITBART: Yes, they are. DANIEL HAYES: And they just they just managed to make it work because he could be hard to deal with. But everybody loved him because of it. WILLIAM BREITBART: Yeah. I think the secret ingredient there is dedication. They were both people of great dedication and commitment. And they were committed to two things. They were committed to the work they did. And they were committed to each other and their family. And so I think that was the secret-- the secret ingredient. DANIEL HAYES: There are a number of things in your own career that struck me as I was going through it. That one of my own interests would be your work with hastened death. And again, I actually wrote a little sort of term paper kind of thing on this. And it was called assisted suicide. And I think we're talking about the same thing. Talk more about that, and what you've been involved with, and where you think that's going. WILLIAM BREITBART: Right. Well, my interest in that all started during the AIDS crisis, the AIDS epidemic, in the mid-'80s to mid-'90s or so. And I was right in the thick of it, in Manhattan, in New York City. And Sloan Kettering had a large population of AIDS patients, because of their interest in Kaposi's sarcoma and lymphomas. And they ended up taking care of a lot of patients. And I saw a lot of patients. And I was that age-- I was often the age of the patients-- many of the patients who I was treating. It was very difficult work, but very inspiring work. You really felt like you were doing important work, obviously. And because of many of the patients were younger men, men in their 30s, who I could relate to in many ways-- like you, I'm sure there are many patients that you treat. There are some that you feel closer to, you identify a lot more with, right. And these were-- that was the case here. And at the time, I was treating patients with AIDS. And there was no treat-- there was no therapy at all. And people were dying very difficult deaths. And I had many, many patients who asked me if I could help them die, if I could assist them in the suicide, could I prescribe their medicine, could I somehow hasten their death? And so for me, it was a clinical problem. What do I do? How do I understand this? What drives this desire to hasten your death? I knew it came out of a sense of despair. I knew it came out of a distress and a sense of despair. But at the time that this was happening, clinically there was also a big debate in our society about legalization of assisted suicide. And, in fact, I think that was the Supreme Court case of Vacco versus Quill, which was also being adjudicated at that time. And states, like Oregon, were starting to have a referendum about whether to legalize these things. So I thought, does one create policies based on popular opinion, or whatever, or a public opinion? Or do you create policies by understanding of the problem and that's informed by research? So I thought I needed to understand this. If I was going to be helpful as a psychiatrist, in this kind of a setting. And it came up occasionally with cancer patients, too. But it was just so dramatic. And it confronted me for the first time, mainly during the AIDS crisis. I felt I needed to understand it more, so that I could know how to be helpful or useful. Was I going to be able to eliminate the suffering? Or was my only option to eliminate the sufferer? And so we set about doing a set of studies, both in terminally ill AIDS patients and terminally ill cancer patients. And I actually developed and validated a scale that measured desire for hastened death. It's called the Schedule of Attitudes towards Hastened Death. Up until that point, people didn't really have a way of measuring it. They just asked the patient, yes or no, do you have-- or they might qualify it on a 0 to 4 scale or something. And so what was really interesting-- and one of my early fellows, my first fellow, the first surgeon attending from oncology, Chasnoff, who went back to Canada-- Winnipeg. And he starts to do a study. He did studies around the same time. But he didn't have a validated measure. But we ended up finding very similar things. As it turned out, about 40%-- 45% of folks who had high desire for hastened death, had a depression. About 17% of patients that had cancer-- we'll stick to the cancer data. About 17% of cancer patients have a high desire for phase. These are patients with advanced cancer, in a palliative care unit, or a hospice, whatever. And about 45% of those patients have a depression that was undiagnosed, untreated. The other factors that seem to contribute to desire for hastened death were things like lack of social support, uncontrolled pain, and severe physical debilitation. So I said, well, we can treat pain. We can increase social support. I gave a presentation one day at-- Kathy Foley had worked with George Soros and the Open Society Institute, to develop something called Project on Death in America. And I gave a talk to the board of the Project on Death in America. I was in the class of the first faculty scholars of Project on Death in America. It included a lot of people who are at the forefront of palliative care these days. But I gave a talk on this, on patient death. And one of the ethicists in the room, a famous ethicist, asked me, well, what happens to desire for hastened death if you treat the depression? And before answering that question, I said to myself, make a mental note. That's your next ROI grant, Bill. And so what I did after that, is I wrote several grants and did two studies looking at what treating depression in patients with high desire for hastened death. And I did both in AIDS and cancer patients, terminal cancer patients, two different studies. As it turns out, if you treat-- if someone who has high desire for hastened death and they have a depression, and you treat the depression, 90% of those patients, when their depression remits, the desire for hastened death remits. But there was still this segment of population of advanced cancer patients, were not depressed, did not have uncontrolled pain, or lack of social support. There were about a 40%-- 35%, 40% of the group, I didn't have the element, the factor that contributed to this desire for hastened death. So I figured there's something there that I haven't found. So we went back and did further studies. And we looked at other variables, like anxiety, hopelessness, loss of meaning. And what we discovered was that hope of hopelessness and loss of meaning were independent and synergistic factors that contributed to the desire for hastened death, and made up an additional 30% of the so-called variance. So between depression and hopelessness, independent of depression, and loss of meaning independent of depression, you could account for about 85%, 90% of the reasons why patients wanted to desire for hastened death. Based on my research and the research of others, there's still about a 10% group who are probably not in great despair. But the issue for them is, I live my life in a pretty authentic way. I've been able to control how I live my life. I should be able to. And I want to control the circumstances of my death. And they're not impaired by depression or anything like that. But when we had the findings of hopelessness and loss of meaning, I said to myself, OK, now I've got to find an intervention for loss of meaning and hopelessness. And I was looking for a drug. I went through every page of the PDR. And there was no drug for loss of meaning or loss of hope. So I had to turn to psychotherapy. Our CL psychiatrist-- you know, psychosomatic medicine psychiatrists, we like to give drugs. If there's a drug solution, we've got it. I'm your guy. So I had to force myself to turn towards psychotherapy rather later in my career, after doing all of these stimulant trials for fatigue and things like that, and other pharmacological trials for pain-- neuropathic pain, et cetera, delirium trials. There I was, starting to figure out what kind of psychotherapy can I develop to help enhance sense of meaning and hope? And that's when I turned to, ironically, a Holocaust survivor named Victor Frankl-- and turned to the work of Victor Frank, who wrote the book, Man's Search for Meaning. His big idea was that meaning is a primary motivating force for human behavior, similar to the idea of libido, and instinctual drive, and things like that. He thought meeting was another important drive. "Better" instinctual, he called it. And he thought that there were predictable sources of meaning that one could tap into. And so we basically developed-- just sat down in a room with a couple of my fellows. And we hacked out a seven-- or at the beginning, it was group intervention. So it was an eight-session intervention. And then we developed an individual format, seven sessions. And we basically developed this brief, structured psychotherapy that involved teaching patients the importance of meaning, both didactically and experientially; teaching them the various sources of meaning; and relating it to their cancer experience and living with cancer. And the whole purpose was to be able to get through cancer, and even facing death, by sustaining a sense of meaning for as long as you possibly could. And that's what we called meaning-centered psychotherapy. I ended up doing four randomized-- NIH-funded, randomized controlled trials of both individual and a group format. And now we have a-- we're in the seventh year of an R25 training grant. We're training a national and international cohort of clinicians to provide meaningful psychotherapy in the manuals and textbooks that are published. DANIEL HAYES: I'd like to segue this-- WILLIAM BREITBART: [INAUDIBLE], I designated it as a evidence-based intervention for palliative care. DANIEL HAYES: Well, I'd like to segue, that as you were talking, most of people listening to this are probably medical oncologists. And my impression is, we don't get a lot of this training that you're talking about. And the people you're training, they're probably a psychiatrist, not a medical oncologist. How have you translated that over to our world? WILLIAM BREITBART: Now, so actually the people we're training-- a few psychiatrists, not too many. We train psychiatrists, social workers, nurses, nurse practitioners, oncology nurse practitioners, oncology nurses, oncologists, chaplains, palliative care docs. We're expanding the training. And it's quite simple. And it's actually-- but we're working with a group to develop this into a digital app. It might be able to be prescribed by oncologists so that you don't even need a therapist. DANIEL HAYES: Are you in the weeds with the medical oncologists at Memorial, at Sloan. I mean, do you make rounds with them and help train them? WILLIAM BREITBART: Yeah. Jimmie started out with one psychiatrist. By the time the Psychiatry Service became a department in 1996, I think there were 12 psychiatrists and psychologists. And as of last count, I think we have 43 faculty, 25 psychiatrists and the rest psychologists, and around 200 staff, including research staff, and research faculty, and psychiatry services. So I took over as chief when Jimmie became the first chair in the Behavioral Sciences Service. And we had a cancer disparities in the Immigrant Health Service. So it's grown quite a bit. And all of us, we work in a sort of a disease management embedded model. So I originally was the psychiatrist for the Neuropsychology and Pain Service, and moved to the hepato-pancreato-biliary disease management team. But all of my psychiatrists and psychologists are embedded in the Breast Center, and in the GI group, hepato-pancreato-biliary groups, and hepato-neck, and thoracic, and all that. So we're all interacting there. DANIEL HAYES: How do you translate that outside of Memorial in New York? I mean, most oncologists don't have access to those kinds of resources. And you've got to have thought about that. WILLIAM BREITBART: About 1996, the National Cancer Center Network, the NCCN, got established and started developing guidelines. And so they asked Jimmie to head up of their guidelines for distress. And I was part of that group, and still am. And what came out of that was screening for distress, using a distress screening tool. DANIEL HAYES: The distress thermometer-- the distress thermometer. WILLIAM BREITBART: The distress thermometer, that's exactly right. And that came out of the pain work. The pain guys had the 0 to 10 scale. We didn't want to rip them off too badly. So we didn't want to do the 0 to 10 visual analog scale. So we had to come up with a different metaphor. So we called it "pain throughout." So the Distress Screening Commission on Cancer, I think, accredits cancer centers through either the Academy of Surgery-- Surgical Oncology or something like that. They mandated that for a cancer center to get accredited, you have to have a distress screening program. And if you have a distress screening program, then you have to have people who respond to these algorithms that get developed for people who they identify with high distress. So as a result of that one move, that one move of establishing distress stress as the sixth vital sign, which was Jimmie's idea, and developing distress screening, you now have-- every designated NCI-designated cancer center has to have a psychology program of some sort. Now, a lot of them aren't as big as ours. Some of them basically involve a half-time psychiatrist, a chaplain, a psych nurse practitioner, and a couple of social workers. But every cancer center has psycho-oncology present in it now as a result of that. DANIEL HAYES: I was having dinner one time with Jim and Jimmie. And she said, you two know the blood pressure, the temperature, the weight, pulse. But you have no idea, she said, how they feel. So it wasn't the last time she asked Jim on that question. And I went, what do you mean? She goes, you need a distress thermometer. She'd already published it. Of course, I didn't know that-- and pulled it out of her purse. And so she had to show the distress thermometer. WILLIAM BREITBART: That's correct. That's correct. That's correct. One of the big problems is when Jimmie started-- and you can attest to this-- that in the beginnings of oncology, it wasn't always the case that patients were told exactly what they had. Cancer was very stigmatized. The only thing that's more stigmatized than an illness like cancer is mental health, right. God forbid, you should have a problem with depression, or coping, or panic, or something. DANIEL HAYES: It's a sign of weakness. WILLIAM BREITBART: A weakness, moral weakness. Actually, we've come a long way in terms of truth telling and being transparent. And my patients now know exactly all the genetic mutations of about the tumor and stuff like that. They know everything. And they even know how their tumor is-- mutations are evolving and changing over time. But cancer was-- the idea of needing psychosocial counseling-- psychiatric help, psychological help, it was very stigmatized. So even the word "distress" was chosen out of a concern to not stigmatize patients. DANIEL HAYES: I will tell you that when-- I was at the Dana Farber. And there was a push for the Dana Farber to develop its own hospice program. And Dr. Frye, who was physician-in-chief, absolutely drew a line, and said no way because that means we've given up on those patients. We're not going to have a hospice program at Dana Farber because we don't want patients to think they're coming here to die. And I remember thinking that some of them do. And it would be very helpful if we had a way to help them figure it out. And I have to say, in preparing for this podcast, I've read several your papers. And thought, God, I wish you'd been at the Dana Farber when I was there. Or I wish I'd been at Memorial to get to work with you. But you can see I'm kind of tying things up here. Because I could listen to you for hours,but But we only have 20 or 30 minutes. And this has been terrific. WILLIAM BREITBART: I appreciate the opportunity. DANIEL HAYES: I'm sure our listeners will say, maybe-- I wonder how we can get him to come speak to our program. But I already wrote down here, we're going to invite you to Michigan. WILLIAM BREITBART: Well, in this era of Zoom-- in this era of Zoom, I'm a very cheap date because all you have to do is just connect me by Zoom. You don't have to pay for the air fare or anything. I go everywhere. DANIEL HAYES: I want to thank you for lots of reasons. One is for filling our listeners in-- many of them are young-- about who Dr. Holland was and what she did. Because we all owe her an enormous debt of gratitude for the contributions she made-- and you personally, as well. So thank you for taking your time to speak with us. And we really appreciate it. And I hope our paths cross again in the near future. Thanks a lot. WILLIAM BREITBART: Absolutely. Thank you so much. It was my pleasure. Appreciate it. [MUSIC PLAYING] DANIEL HAYES: Until next time, thank you for listening to this JCO's Cancer Stories-- The Art of Oncology 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. JCO's Cancer Stories-- The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]

Dr. Hayes interviews Dr. Sarah Donaldson and her pioneering work in pediatric radiation oncology. Dr. Daniel F. Hayes is the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center. Dr. Hayes' research interests are in the field of experimental therapeutics and cancer biomarkers, especially in breast cancer. He has served as chair of the SWOG Breast Cancer Translational Medicine Committee, and he was an inaugural member and chaired the American Society of Clinical Oncology (ASCO) Tumor Marker Guidelines Committee. Dr. Hayes served on the ASCO Board of Directors, and served a 3 year term as President of ASCO from 2016-2018. TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] DANIEL HAYES: Welcome to JCO'S Cancer Stories: The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of these shows, including this one, at podcast.asco.org. Today my guest on this podcast is Dr. Sarah Donaldson. Dr. Donaldson has really been instrumental in much of the development of both, in my opinion, modern radiation oncology and especially related to pediatric radiation oncology. Dr. Donaldson was raised in Portland, Oregon. She received an initial undergraduate and nursing degree at the University of Oregon in Eugene and ultimately in Portland. After a few years working as a nurse with Dr. William Fletcher, who I hope we'll get a chance to talk about later, she elected to go to medical school and spend her first two years at Dartmouth and then finished with an MD from Harvard. She was planning to do a surgery residency at the Brigham Women's in Boston but then elected to do an internal medicine internship at the University of Washington and ultimately then a residency in radiation oncology at Stanford. After a residency and a few side trips along the way, she joined the faculty at Stanford and has remained there since. Dr. Donaldson has authored nearly 300 peer-reviewed papers, probably more than that by now. That was when I last looked at her CV a couple of weeks ago, and it seems like she brings them out every week. She has served as president of the American Board of Radiology, the Radiology Society of North America, and the American Society of Therapeutic Radiation Oncology, ASCO's sister organization, of course-- ASTRO. And she also served on the board of ASCO, the board of directors, from 1994 to 1997 and, in my opinion, perhaps as importantly, on the board of directors of the ASCO Foundation for over a decade. She has way too many honors for me to lay out here, but a few that caught my eye. Named after a distinguished scientist in the past, the Marie Curie award for the American Association of Women Radiologists, the Janeway Award from the American Radiation Society, and the Henry Kaplan Award for Teaching from Stanford. And she was the inaugural recipient of the Women Who Conquer Cancer Award from our own Foundation, the Conquer Cancer Foundation. Dr. Donaldson, welcome to our program. SARAH DONALDSON: Thanks so much, Dan. It's a privilege to be talking with you today. DANIEL HAYES: I hope I got all that right. It's pretty tough to cram the distinguished career you've had into about a minute. [LAUGHS] Anyway, I'm going to start out. So I've interviewed a lot of the luminaries and the people who really started our fields or even the subfield within our field, and you yourself had quite a journey. I know you started out as a nurse. Can you just give us some background about going to nursing school and then who and what influenced your decision to become a physician? SARAH DONALDSON: Yes, I did. I can, Dan, and it's an interesting story. Because when I grew up, girls that wanted to go on to college-- and it wasn't all girls didn't go to college, but I did. The three areas that one could do in that era were become a teacher or maybe a librarian or a nurse. And so I elected to become a nurse, and I went to nursing school. And I loved nursing school. I had a terrific time in nursing school, and along the line, I met the house officers and such and ultimately got to know a surgical oncologist. That was before surgical oncology was a field, but a young man from the Boston City Hospital training program, which was a very good surgical training program at the time, who was recruited to the University of Oregon to start a cancer program. His name was Bill Fletcher-- William S. Fletcher. And when I graduated from nursing school, Bill Fletcher was looking for a right arm assistant. He was looking for somebody to help him develop a cancer program. And he offered me a job, and the job was to work with him in the operating room, either scrubbing or circulating, to run his tumor board-- and that meant just scheduling it and taking notes and such-- and working with him in his tumor clinic. And in the tumor clinic, he was at that time beginning clinical trials, and Oregon was part of something that was called the Western Cancer Chemotherapy Group, which ultimately merged with SWOG. But at that time, his helper-- me-- filled out the forms, and we sent them to patients that were entered onto the study and got consents and measured lesions and that sort of thing. And I worked hand in hand with him. In addition to working with him in those clinical parameters, he gave me a little laboratory project, and so I worked with him in the lab and learned a little bit about small animal oncologic research, et cetera. And after a couple of years working with him, he suggested that I would be a better employee if I took some additional courses, and he suggested that maybe I should take physics because at that time he was doing isolation perfusion. I was running his pump oxygenator. He asked me what I would do if there was a pump failure. I didn't know. And he said, well, I think it would be good if you took physics. Well, the prerequisite to physics was organic. I hadn't had organic, and he was also working with radioisotopes in the lab. And he said, you could really be more helpful to me if you could work in the lab. That meant I had to take organic, and the prerequisite to organic was inorganic. To make a long story short, I took these series of classes in night school while I was working for Dr. Fletcher in the daytime. And then one night, I was working on my hamster project, and he said, I think you should go to medical school. I said, I can't go to medical school. And the long and the short of it was Dr. Fletcher thought I should go to medical school, and he made that possible for me. It's a very, very interesting story, but what it means is that I was mentored by somebody who was a visionary, and he could see a lot more than I could see. And he got me excited about medical school and everything that I knew about medical school is what he had taught me, so I of course wanted to be a cancer surgeon. And then after I went to medical school and I went to the same medical school he did, I just followed his advice. Every time I needed some guidance along the way, I asked Dr. Fletcher what I should do, and he told me what I should do, and I applied. And that's what I did. And so when I came time to choosing a specialty, I decided I would train in surgery, and I applied at the Brigham and was accepted into their surgical program. It was run by Francis Moore at the time. And that was a big deal because they hadn't had women in their surgical field, and I was very excited about all of that but feeling totally inadequate because I didn't think I knew enough medicine. And so I went to Dr. Moore and said, I think I'd be a better house officer if I knew some medicine. He says, OK, well, go take a medical internship, and we'll hold you a spot. So I went to the University of Washington and took general medicine, which was a very vibrant program, a really exciting program, and I just came alive in my internship. I loved everything about it. And then I decided I wanted to be an internist. So at this point, I was offered a position in Washington, and I had already accepted Dr. Moore in Boston. And I didn't know what to do, and I asked Dr. Fletcher what I should do. And he said, Sarah, the world of-- he called it radiotherapy at the time, but what we would call radiation oncology-- needs more surgically oriented physicians. I think you should go down and talk to my friends at Stanford. So I came down to Stanford. I met Henry Kaplan and Malcolm Bagshaw and the leaderships in the department, and including Saul Rosenberg, who was one of the people who interviewed me, and I left that day visiting at Stanford making a commitment that I would come to Stanford as a radiation oncologist. So I wanted to do everything, and I met some very inspiring people along the way, perhaps like you have in your own career. And it's for that reason that I am now excited about mentoring because it's a little bit of payback because somebody opened the door for me and made it possible for me to have a most gratifying professional career, and I would like to do that for as many people as I could. DANIEL HAYES: I love that story. And there were two things about it that came out. One is I normally don't like people who namedrop, but when you can namedrop the names you just dropped-- Bill Fletcher, who I consider really one of the early surgical oncologists, Henry Kaplan, Saul Rosenberg, Franny Moore. I was in Boston of 15 years, and he was a legend. He was not the chair anymore by any means. In fact, he passed away. But it was legendary. You should be doing these interviews instead of me. [LAUGHS] You've been there. SARAH DONALDSON: Well, it's all about where you are at the time you are and meeting the right people. I think so much of my gratifying career is just because I happened to be at the right place at the right time and met the right people. DANIEL HAYES: Well, the other thing I want to say is I always believed I don't trust people I interview who say they know exactly what they want to do. And the reason I say it that way is I have a young woman who's been a technician in my lab that just got into med school, and she sat with me and said, now, when I go there, should I tell them I know exactly what I want to do? Because she's interested in the oncology. Or should I go through my rotations and see what I like? And I said, I forbid you from going there knowing what you want to do. Go to your rotation. See what you like. You're going to run into somebody who just inspires you beyond words who-- I don't know-- maybe selling shoes. But whatever it is, become like her, and you'll be extraordinarily successful. So if there are young people listening to this, I think that your story, Dr. Donaldson, is a classic for that, the way you kicked around. And actually, you didn't tell us, but I'm going to have you tell us about your trip to Paris and that experience too and how that influenced you. SARAH DONALDSON: Oh, that was another wonderful opportunity. When I finished my training, it was 1972, and that's when America was in the Vietnam War. All of my classmates were being recruited to a mandatory draft and were having to go to Vietnam, and I felt like I too should be just like all of my best friends and I too should join the military and go to Vietnam. But that wasn't possible. Women couldn't do that. So I looked for things that I could do where I could do something useful, and I thought about joining the ship Hope and all sorts of fanciful things, but basically I was lost, and I didn't know what I wanted to do. And at that time, there wasn't a carve-out of pediatric oncology as a specialty. It hadn't been defined, but there were people that were doing pediatrics. And as a resident, I had had a little rotation at the M.D. Anderson, and when I was in medical school, I had spent a fair amount of time at the Boston Children's, so I kind of knew a little bit about those institutions. But the thing was at Stanford, I knew that I wanted to be at Stanford. But Stanford didn't have a cancer program either. And so again, I went to Henry Kaplan and Malcolm Bagshaw-- at that point, Kaplan was head of the department, and Malcolm was his associate director. But they changed positions about a year after that. So I trained under both of them, really, but I went to Dr. Kaplan and said, I'm interested in pediatrics. And I said that because we didn't have a program at Stanford and that was like a carve out that nobody had addressed yet. And he said, oh, well, if you want to study pediatric cancer, you have to go to the Institute Gustavo Roussy and train under Odile Schweisguth. And I said, no, I don't speak French. I can't do that. I'd like to go to London because I like the theater. And he said, no, no, no, no, no, that's not the way it is. If you want to be a pediatric doctor, you have to go learn pediatrics and learn to think like a pediatrician, and that means you have to go and train under Odile Schweisguth. She was at the Grand Dame of pediatric oncology. She took care of all the children in Western Europe. And so I went to Institute Gustavo Roussy to be a fellow in pediatric oncology, although I did spend some time on the radiotherapy unit as well. But that's where I learned pediatric cancer because I learned from Odile. And in French, there's a formal and an informal, and I never understood the formal because when you talk to kids, you talk in the familiar form. So I was just talking to and not [SPEAKING FRENCH]. I would just say, [SPEAKING FRENCH] and such. [INAUDIBLE] French. And that's how I learned French. More importantly, I learned the biology of cancer from Odile. It was largely observational. And I learned a lot of late effects of children who were cancer survivors. So when I came back to Stanford, at that time Mal Bagshaw was chair, and he said, well, why don't you work on starting a cancer program? We'd like to have a cancer program. So I worked with the pediatric cancer doctor at Stanford. His name was Dan Wilber, and he had just come from the M.D. Anderson. And the two of us started a cancer program at Stanford. And so I've been kind of doing that ever since, of doing pediatric cancer. So I would say my skill set came along just because the right people told me where to go at the right time. DANIEL HAYES: Were the pediatricians welcoming, or did they resent the fact that you'd never been a pediatrician? SARAH DONALDSON: Malcolm Bagshaw gave me the clue to that by saying the only way the pediatricians will accept you is by having them accept you is one of their own. So you have to learn to think like a pediatrician, and then they will accept you onto their team as one of theirs because pediatric doctors are very possessive about their patients, and pediatric cancer doctors are possessive about their patients. So it worked for me. But it worked because I had had this special training under Odile Schweisguth, who was a general pediatrician, and so I was accepted because I was at that point thinking like Odile thought because that's what she taught me how to do. So I always felt like I was accepted by the pediatric cancer doctors who then became the pediatric oncologists because that field didn't really open up for a couple of years later. DANIEL HAYES: For our listeners, Dr. Donaldson and I have not met before, and I certainly have never worked with her. But she's talking, she's glossed over that when you work with the French, you really have to speak French. When you work with the pediatricians, you really have to speak pediatrician. And you've managed to do both of those. I don't know anybody who's been that successful. I should take a sabbatical and come work with you. [LAUGHS] SARAH DONALDSON: Well, I'll tell you, Dan, there was one wonderful thing that happened because shortly after I was working at Stanford doing pediatrics, our dean wanted to recruit some more people and buff up our pediatric cancer unit. And he recruited Michael Link, who had just come out of his training at the Dana Farber. And so Michael and I started working together his first day as an assistant professor at Stanford, and pediatric oncology is a team sport. Pediatric radiation oncology is a team sport. And I had a wonderful teammate, Michael Link, with whom I worked very well, and we became very fast friends. And we did pediatric lymphoma and sarcoma, bone sarcoma, and soft tissue sarcoma, and all sorts of stuff. And I had a wonderful, wonderful colleague working with Michael Link. So one of the keys to my most gratifying part of my career at Stanford has been working with Michael Link and his associates. DANIEL HAYES: As an aside, by the way, Michael and I overlapped just a little bit at Harvard, but then he proceeded me as president of ASCO by two years, and we got to be pretty close friends during that period of time. And I echo your fondness for him. He's just an amazing human being, as far as I was concerned. And he's one of the-- he may be-- I'm trying to think, has there other pediatricians that have been president of ASCO? I'm not-- SARAH DONALDSON: No, he was the first. Yeah, he's the only one to date. DANIEL HAYES: Yeah. And he left a big stamp on the society in terms of-- we always had some pediatrics involved-- you, especially-- during the years, but as president, he was able to leave a big footprint of what we do. So he was terrific. I'd also like you to talk a little bit about the early days of the co-operative groups. You threw out that you were in the Western Group that became part of SWOG, and what were the hurdles and obstacles to getting all these folks to work together? And what do you see the pros and cons of the cooperative groups in the country? SARAH DONALDSON: I know the cooperative groups mainly through the lens of the pediatric cooperative groups. I mean, I can tell you about the adult ones, but I really know the pediatric ones. And at the beginning, there was one, and then there were two. And we worked competitively, and then ultimately the pediatric doctors learned early on that the children they took care of had rare tumors, and no one physician had a whole lot of experience with any cancer. For example, this tells the story well. When Hal Maurer was chairman of Pediatrics at Virginia, he had a child with rhabdomyosarcoma. And he called his friend Ruth Hein, who was at Michigan, and said, Ruth, I've got this child with rhabdomyosarcoma. Have you ever treated a child like this? And Ruth said, oh, I had one patient, but I think you should call Teresa because Teresa, I think, had a patient. And so Teresa Vietti was at Washington University, and so Hal Maurer and Teresa Vietti and Ruth Hein and a few other really, really pioneers started to throw their lot together and decided that the way they could answer a question about these rare tumors is by deciding what was the question of the day and working collaboratively. And then Hal Maurer became the first chair of what was then called the Innergroup Rhabdomyosarcoma Study, which has now been merged into the other pediatric groups. But that same process that worked for rhabdomyosarcoma was then employed for Wilms tumor, and then subsequently down the line, brain tumors and all the other solid tumors. And of course, St. Jude was doing this with their leukemia studies and Dan Finkel, and then Joe Simone did it with leukemia. They got everybody to join in on their team, decide together around the table by consensus what is the question that we want to have an answer for, and then just treat all the patients in a consecutive fashion, analyze those, and then take that step and go on and build to the next step. That's how the pediatricians have done it because their cancers are so rare that one person doesn't have very much experience. They have to throw their lot together and work collaboratively. So they don't work competitively. They work collaboratively. DANIEL HAYES: This is very similar to the stories I of course heard from Drs. Frei and Holland that they came ultimately to CALGB to be after a couple of mis-starts. But it's one of the things I worry about COVID. It's not the same Zooming with somebody or talking on the phone as it is sitting around dinner and just saying, maybe we could do this and make it work. So I'm hoping young people are listening to this and saying, OK, maybe we can start something new that a bunch of us work together and get things done. That's a really great story. You were early on and ended up taking both diagnostic and therapeutic radiology boards, correct? When they were combined? SARAH DONALDSON: No, no I didn't. Radiology was combined at that time, but Stanford was one of the few institutions that had a carve-out for radiation oncology without diagnostic training, and I wasn't in the first class. I was in the fourth or fifth class, so my formal training was only in what was called radiation therapy, now called radiation oncology. So it was one department, and I worked collaboratively with a diagnostic radiologist because I knew nothing about image interpretation-- nothing at all. So I'd see an X-ray. I didn't know how to interpret it, and I'd have to go and ask for some help. But they were like our best friends. But the diagnostic people could take the picture, but the therapists had access to the patients. So that made all the difference in the world because we really had access to the material, the clinical material or the blood or the bone marrow or the biopsy specimens or whatever it was, and allowed us to do studies. But to clarify, no, I was not. I do not have formal training in diagnostic radiology, although I have worked with them so closely now that I feel like they're all my brothers because you cannot do radiation oncology without collaborating closely with the imagers. DANIEL HAYES: And my first interview was with Sam Helman. This has been three or four years ago. And he was still lamenting the split because he thought it was to learn both-- and for the reasons you just said. If you don't know where it is to shoot your bean, you can't shoot your bean. That's not exactly what he said but something like that. On our side, they team hematology and oncology. Like you, I never got trained in hematology. I only trained in solid tumor oncology, which has not hurt me in any way. In fact, in many respects, I focus my efforts on things I seem to know about and let somebody else worry about blood clotting. Of all the things you're well known for-- and again, it was hard for me to get it all into a minute or two, but probably teaching and mentoring. And in this conversation, I see why. Tell me how you think that's evolved in your field, especially in radiation oncology, teaching and mentoring, and the importance of the things you've done-- and perhaps some of the people you have trained yourself and you're proud of. SARAH DONALDSON: Well, when I think of all the things that I love about my professional career, I love taking care of patients. And I've had very joyous experiences of watching pediatric cancer patients grow up and watching them in their process and treating them when they're toddlers and then getting invitations to graduations and wedding invitations and baby announcements and following through that. That's very, very gratifying. But the single most important and most gratifying part of what I do is the volumetric feedback and gratification from training residents because one patient is one patient, but one trainee then goes into academic medicine and that person has 30 or 300 or 3,000 trainees. And you see your impact is just explosive. And Stanford has had a training program in radiation oncology from the very, very beginning. It was one of the first programs that did train in radiation oncology, so a lot of talented people have come through Stanford. They need to have what Bill Fletcher did for me, which was open doors and help them with networking and giving them an opportunity and giving them some guidance and being their new best friend. When your trainees trust you like that, then you can really, really have a relationship, and you can really help them. And so I am very, very, very proud of our trainees that are now all over the place as cancer center directors or directors of departments or divisions that are doing what they're doing. You just meet the best of the best. That is the most gratifying part of-- maybe it's because that's what I'm doing now, but it's the most gratifying part of medicine that I've experienced. DANIEL HAYES: This is the third time I've said this on this call-- I hope there are young people listening, and I hope they're looking for a mentor and they can find someone as generous and trusting and helpful as you have been. SARAH DONALDSON: Dan, let me just say one little thing. DANIEL HAYES: Yeah. SARAH DONALDSON: It was extremely helpful to me-- and wonderful recognition for ASCO-- to provide the opportunity that I received the Women Who Conquer Cancer Mentoring Award. Because when I won that award, I was the inaugural-- but when I won that, all of a sudden people thought that I knew something about mentoring. I'm not certain I did know anything about mentoring, but I was asked to talk about it and asked to give advice, et cetera. And it gave me a carve out that was quite novel at the time, and now, of course, it's a mandated requirement in every training program, et cetera, but it wasn't then. And for me, it was just to return what Bill Fletcher did for me. The only way I can say is that it's a pay out, and it's so gratifying. It just makes you happy to get out of bed every morning and interact with the people you do interact with. DANIEL HAYES: He was pretty young when he began to mentor you. And I think having seen and been mentored and mentored other people, I always worry about a young person trying to mentor because you've got your own career to worry about, and it's hard not to be selfish when you're building a career in academics. He must have been a remarkable-- is he still active? Is he still around? He must have been a remarkable guy. SARAH DONALDSON: He was a remarkable guy, and no, he passed away. But that was true. And that is true because junior faculty are busy making their own professional career, and they don't have time. They're busy on their own path, and it's a hard path to go on. So most junior faculty don't really have very much time to do formal mentoring. But in Bill Fletcher's case, we worked hand in hand as sort of partners. And so I think, in some ways, I was helpful to him because I could do literature searches for him. I could write the first draft of his paper. I could write the first draft of his grant. I filled out the forms. I did a lot of things that were labor saving for him, but for me, what was he doing for me? He was teaching me to suture. He was teaching me how to resect normal [INAUDIBLE]. He was teaching me lymph node drainage from cancers. He was teaching me about drug metabolism, methotrexate, and phenylalanine mustard. And 5-FU was an experimental agent. So was vincristine-- those kinds of things. So I learned a lot from him just in the ordinary practice of taking care of the patients. DANIEL HAYES: By the way, two stories I read about you-- one is how you met Henry Kaplan, and the second is the first paper you wrote with him. Can you give us those two? And then I think we've got to sign off. SARAH DONALDSON: Well, let me tell you about the first paper I wrote with him because the other one is too funny. Everybody will laugh at me. The first paper I wrote with Henry Kaplan, I worked really, really hard on it. It had to do with bacterial infections in patients with Hodgkin's disease because we were doing splenectomies on everybody, and they were getting pneumococcal bacteremias and meningitis. And I was running the ward at that time. I was taking care of a lot of patients that were sick. So I was writing up this experience. And I wrote what I thought was the perfect paper because, see, Kaplan had a high bar, and you didn't want to disappoint him. So I wrote the paper that I thought was perfection. I had gone through a lot of drafts. And I gave it to him, and he returned it to me the next day. He read it that night. But I only looked at the first page because the first page looked like a blood bath. Everything he wrote, he wrote with a red pen. And there was red writing all over the first page. I couldn't see any white paper. It was all red comments. DANIEL HAYES: [LAUGHS] SARAH DONALDSON: And I went through-- I don't know-- 24 different drafts of that paper finally being published. And so one of the things I try to do with residents now is to teach them, you have to have a hypothesis. You have to make certain you have a database. You have to have a long term follow up. You have to understand statistics, and you have to write a paper knowing what you're doing. You don't just start writing. You do a section and a section and you build it with evidence. So I enjoy doing editing, and I think I can help some trainees focus their thinking in terms of writing a grant proposal or a manuscript that's worthwhile publishing. My introduction to Henry Kaplan-- there are many, many funny stories about them, but to end them all, I will have to say that he was very, very, very good to me. He provided a lot of opportunities and was a huge role model. He taught by scarification. We were all scared to death of him, but he was absolutely a wonderful, wonderful huggable person, if you felt like you could hug him. We didn't do that very often. We might have hugged Saul Rosenberg, but we didn't hug Henry Kaplan. But they were both helpful to me, especially in understanding lymphomas. DANIEL HAYES: For those of you listening who don't know who Henry Kaplan was, I think it's fair to say he was one of the first people to prove you could cure Hodgkin's disease with radiation. Do you agree? Is that a fair statement? SARAH DONALDSON: Yes, that's where his name came. But of course, what Kaplan did was he recruited Saul Rosenberg, and the two of those worked hand in hand, and they brought to Stanford what we call the Lymphoma Staging Conference, which was a combined modality conference where we talked together over each patient. And together, they wrote clinical trials that were institution-based clinical trials. So what Kaplan did was he did a lot of technical work with the linear accelerator, but that was just a tool. My way of thinking is his most important contribution was the importance of combined modality therapy and understanding what your colleagues can contribute and what you can contribute in doing it as a team. DANIEL HAYES: And I will encourage anyone who's listening to this to go back to the website and listen to my interview with Dr. Rosenberg who laid that out in spades. And the first few patients he treated, he had a chair outside his exam room. He would examine the patient, take them out, put them in the chair, start the IV himself, go mix the chemotherapy, hang it up, and then see the next patient in the room while the first patient was getting chemotherapy. It's a little different now. [LAUGHS] Anyway, thank you so much. By the way, I have a copy of Dr. Kaplan's book on Hodgkin's disease, which was the Bible when we were training. You can't see it because it's on my bookshelf behind my camera, but I still open it up quite a while, even for a breast cancer guy. It was a classic. I also want to say, it's very clear to me you're a nurse at heart. You've been a fabulous physician and researcher and mentor, but your love for people shines through, so congratulations. I think that's terrific. SARAH DONALDSON: Thank you so much. DANIEL HAYES: Thanks for taking your time to speak with me today. I'm sure people are going to be thrilled to listen to this, and thanks for all you've done to feel. It's just really remarkable-- and what you've done for ASCO and the Foundation, which is a big, big, payback. Thanks for everything. SARAH DONALDSON: Thank you. DANIEL HAYES: Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology 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's Cancer Stories: The Art of Oncology Podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]

Dr. Hayes interviews Dr. Pamela Goodwin on her work in metabolism and cancer. Dr. Daniel F. Hayes is the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center. Dr. Hayes' research interests are in the field of experimental therapeutics and cancer biomarkers, especially in breast cancer. He has served as chair of the SWOG Breast Cancer Translational Medicine Committee, and he was an inaugural member and chaired the American Society of Clinical Oncology (ASCO) Tumor Marker Guidelines Committee. Dr. Hayes served on the ASCO Board of Directors, and served a 3 year term as President of ASCO from 2016-2018. TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement [MUSIC PLAYING] SPEAKER 2: Welcome to JCO's Cancer Stories, The Art of Oncology 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 of this shows, including this one, podcast.asco.org. Today my guest on this podcast is Pam Goodwin. Dr. Goodwin was instrumental in the consideration of metabolism, exercise, and diet for prevention and/or treatment of breast, and for that matter, other cancers. Dr. Goodwin received her undergraduate medical degree from the University of Ottawa, and then she did a residency in internal medicine at the University of Toronto, where she also did a year residency in pathology, which I was unaware of. She went on to train in oncology at Princess Margaret Hospital in Toronto, and she spent a year as a research fellow with, in my opinion, the legendary Dr. Norman Boyd. She's on a clinical appointment at Mount Sinai Hospital in Toronto, where she directed the breast program for 15 years. And she's remained on faculty for the University of Toronto since 1986, where she is now the Marvelle Koffler Chair in breast research and a professor in the departments of medicine and clinical epidemiology. She's won many, many awards for her contributions to science, but perhaps most germane to this discussion-- and I was unaware-- she was named a star in nutrition and cancer by the United States National Cancer Institute a few years ago. She's authored over 200 peer reviewed papers. And she serves as the current editor in chief of the Journal of the National Cancer Institute Cancer Spectrum, and she's also deputy director of JNCI. By the way, she receives research funding in collaborations with Epic Science but has no other declarations of conflicts. Dr. Goodwin, welcome to our program today. PAM GOODWIN: Thank you. It's a pleasure to be here. SPEAKER 2: So let's start with a [INAUDIBLE] question that I ask almost everybody in this series. And that is, tell us a little about yourself and why oncology. Was there a light bulb that went on, or you knew you were going to be an oncologists from the time you were in kindergarten? PAM GOODWIN: Well, I was born in Ottawa. And when I was a young girl at five years old, we moved into the country. And it was just outside of Ottawa, but it's now called Kanata. But at the time, it was a very rural area. And I started my education in a one-room schoolhouse. By the time I was halfway through my schooling, they put a division down the middle of the room and it became a two-room schoolhouse. But from the very beginning, I remember in grade 1 sitting at the back of my row-- each grade had a row-- and I would listen to the lesson from my row. And the teacher would move to the next row, and I would listen to that lesson, and then I would listen to the next lesson. I always wanted to learn more. I became interested in oncology for a reason that many oncologists have. My mother had cancer and died when I was still in school. And-- jeez, still emotional. And it really made me realize that-- at the time, cancer was almost uniformly fatal. It made me realize that there was a lot of work to be done in the area of cancer. So I very early on decided that I was going to do medicine and that I was going to do oncology, and I never looked back. SPEAKER 2: So neither of your parents was a physician? PAM GOODWIN: No, no. My mother actually worked in the finance department on Parliament Hill for the government of Canada. And my father, in the 1950s, worked on computers for the Department of National Defense. So no medical people there at all. SPEAKER 2: Well, at least it sounds like there was some science behind you. And when you went into oncology then, were you just dedicated to breast cancer because of the history you just gave us, or was there somebody who talked you into being a breast cancer person? PAM GOODWIN: I think Norman Boyd had one of the biggest influences me. My mother didn't have breast cancer, she had myeloma. But Norman, at the time, was at Princess Margaret Hospital and was very interested in diet and breast cancer risk. And I was very interested in the role of the patient in cancer from the very beginning. I thought I might end up doing research in quality of life, because that was an emerging field at the time. But I became very interested in the host factors in obesity, metabolism. And I chose to focus on how these factors impacted the clinical course of cancer for the most part, and I focused on breast cancer. At the time, it was way, way out there to work in this area. And one of my biggest challenges as a new investigator and a new staff person was to be sure that people didn't think I was a little bit of a quack by working in this area. SPEAKER 2: Actually, I have two follow up questions for that, and I'll get to that in just a moment. But can you tell us a little more about Dr. Boyd. I mentioned him earlier as being legendary, but a lot of our listeners may not know who he is and what he's done. PAM GOODWIN: So Norman Boyd was a medical oncologist at Princess Margaret Hospital who became a clinician scientist over the years. He was very interested in the role of dietary fat in breast cancer and actually conducted a randomized trial of dietary fat reduction, which, unfortunately, didn't show a beneficial effect on breast cancer. But he was one of the grandfathers of the mammographic density breast cancer risk association. And he did a very large amount of work confirming that association, quantifying that association, and identifying how it made independent contributions to breast cancer risk over and above family history, for example. SPEAKER 2: I want to say, I have-- obviously, I think you can tell-- enormous respect for Dr. Boyd. He's truly a giant. However, he's caused more trouble in the United States than he knows, because every woman has a mammogram. If she has dense breasts, she gets a little piece of paper saying, speak to your doctor about this. And then we say, I don't know what to do about that. PAM GOODWIN: That's right. That's right. That happens in Canada sometimes too. SPEAKER 2: So you've talked about Dr. Boyd being a stimulus. And you sort of hinted on this. Were there obstacles? I can imagine mentors at the time at Princess Margaret or other places saying, are you crazy? This will go nowhere. You're wasting your career. PAM GOODWIN: Well, I think a lot of people thought that it was a little bit crazy. I think a lot of people thought that it was possibly these people were being under dosed with chemotherapy, that the obesity cancer link wasn't a true biologic association. And that's one of the reasons that I have practiced at a general hospital my whole life. At a general hospital, we have a very strong diabetes and endocrinology department. And they fully understood that these factors could be important. They had seen the impact of diabetes on a host of organs-- end organ disease in the kidney, for example-- and they were very open to this type of research. And I was actually recruited to Mount Sinai Hospital by a guy called Lou Siminovitch, who was a molecular biologist. He had just set up a new research institute at Mount Sinai Hospital. And even though he was not an MD, he wasn't a clinician, he would look at all of my grants and ask the most important question, find the fatal flaw that needed to be fixed before it went in. And Lou continued to support me throughout my career. He died just a couple of weeks ago just shy of his 101st birthday. SPEAKER 2: Oh my. That's great. So you mentioned your grants. Was it hard to get funded early on when you started this? PAM GOODWIN: With some organizations, yes it was. But I think because I always presented this as a biologic association and my focus, at least early on, was to try to identify what was the biologic link between obesity and breast cancer, I think my grants were somewhat better received. I think I always had hypotheses relating to the biomarkers and not just to the prognostic association. Now it wasn't always easy, because my first study was a prospective study of obesity and breast cancer. And towards the middle of the 1990s, we confirmed the association and we looked at biomarkers. We collected fasting blood during the study. We looked at biomarkers focusing on insulin, because there was some emerging evidence that insulin might be associated with cancer. And we actually showed that insulin was strongly associated with obesity and was a stronger predictor of breast cancer recurrence and death than obesity. So as a young staff person-- I think I was an associate professor at the time-- I wrote that up and I sent it to The New England Journal of Medicine, thinking that I really had a great finding there. And New England gave me three reviews. Two of them were glowing. They were fantastic, really nothing to change. And the third one said, I see nothing wrong with this paper, I simply don't believe the results. And New England rejected it. SPEAKER 2: It's always the third reviewer. PAM GOODWIN: That's right. But it took another three years to get it published in JCO. And it's now my most highly cited paper, so go figure. SPEAKER 2: That's interesting. So you talked a bit about the biology. Again for our listeners, my impression is not just that obese people get cancer, but that there is an underlying biology that connects them. Can you go through what your work to show that, and others for that matter. PAM GOODWIN: Yeah, so it's a really complicated association. And the biology of obesity is complicated. There is an alteration or a change in adipose tissue in individuals that are obese, and that's associated with a change in physiology. And both of those factors can then impact the development and prognosis or clinical course of breast cancer. We focused more on the physiology. We've looked at insulin, which I think is now accepted as a growth factor in breast cancer. Most breast cancers express insulin receptors on their surface and insulin that is circulating signals with those receptors to turn on the PI3 kinase pathway. Hyperglycemia, which is associated with obesity, may also change cellular metabolism. And there's a lot of people that have been focusing on inflammation in the adipose tissue. Andy Dannenberg's group in New York has probably been the main people in this area. We've recently looked at that, and we've actually found-- Martin Chang, a pathologist who worked with me at Sinai, and he's now in Vermont, he recently found that the type cellular response to obesity that occurs in adipose tissue may actually determine the physiologic response to obesity and whether obesity impacts breast cancer outcomes. So in other words, if there are CD68 positive macrophages in adipose tissue, you're going to have insulin resistance and you're going to have poor breast cancer outcomes. But for another woman who has the same BMI, if she has an absence of those CD68 positive macrophages in the adipose tissue, she will not have insulin resistance and she will not have worse breast cancer outcomes. So we're trying to focus there on what is the link between the adipose tissue response and the physiologic response and what drives that. SPEAKER 2: I think almost everybody listening to this podcast knows that over the last 15 or 20 years, we've really broken breast cancer into a number of different kinds of cancers. In fact, I really believe that they all happen to be different cancers that happen to start in one anatomic site-- the breast-- as opposed to being all breast cancers. Have you seen differences in the emergence or potential treatment of different subtypes related to obesity or obesity management? PAM GOODWIN: So in some of our earlier work, we actually found that obesity was "perhaps" a little bit more prognostically important in ER negative breast cancer. And I put the word perhaps in quotation marks there. I think more recent work has not shown that, and that obesity contributes across the spectrum of breast cancer. To the extent that obesity impacts are related to estrogen, then you're going to see a greater impact in hormone receptor positive breast cancer. But the association is really seen across the spectrum of breast cancers. SPEAKER 2: So another question that raises-- and others have addressed this-- do you think it's obesity or specific types of diets that are the culprit? PAM GOODWIN: I think it's obesity. I think diet contributes to body size, and I think the composition of the diet may play a role in the response to obesity. But I think that if you are normal weight and have non-obese physiology, the dietary composition doesn't matter quite as much. I think right now when people are looking at diet, they're no longer looking at the fat content of the diet. They're looking at whether it's a healthy diet, whether there are legumes and nuts and healthy oils, but they're also looking at the glycemic index of the diet. I think all of that contributes, but my read is that obesity is the primary driver of this association. SPEAKER 2: And do you think that once you have obesity, it's too late, losing doesn't help. In other words, this is something that's imprinted early on, because I do want to get into treatment too, but especially for prevention. PAM GOODWIN: So that's an unknown. Steve Hursting's group has actually done an experiment where they had mice that were either fed a normal diet and weren't obese, or were fed an obesogenic diet and became obese. And the ones that became obese, a group of them, half of them were put back on the normal diet and they became non-obese. And then they injected all three groups with cancer cells. And what they found was that the currently obese and the formerly obese mice had tumor growth that was the same and was much greater than the mice that were never obese. And they also found patterns of DNA methylation and gene expression in the mammary fat pad that was similar in the formerly obese and the currently obese mice and different from the never obese mice. That suggests that, perhaps, there may be some carryover after weight loss. But I think we need to be very, very careful. The tumor cells were injected almost immediately after the weight loss. And these were mice, they weren't people. People, I think, are a little bit more complex than mice. SPEAKER 2: I mean, this raises-- actually, I have to say that this entire series for me has been, what if I was in a cab with these people who have been experts and pioneers in a field and I can just ask ask them any questions I want to. These are questions I've been wanting to ask you for 20 years, but we never had the opportunity. So the other thing is it's a little bit like early pregnancy. We know there is something about early pregnancy that imprints a cancer reduction compared to late pregnancy. And as you know the Russos have worked on this for years and years. And I've wondered if that's the case with obesity, but now I'm going to [INAUDIBLE] myself instead of you. It's just something I've thought about for a long time. PAM GOODWIN: We're not going to know until we get the results of some studies. The BWEL study led by Jennifer Ligibel looks at weight loss after breast cancer diagnosis. It's fully accrued. It's a randomized trial. It will give us some definitive information. But our group did a small randomized trial called the LISA study, which were reported out about a year ago. And in that study, we actually showed that there was a reduced risk of breast cancer recurrence in women that were randomized to the dietary-- the weight loss intervention arm. The hazard ratio was 0.71. We'd hypothesized a hazard ratio of 0.76. So it looked good, but we did not complete accrual on that study. So we didn't have the power to conclude that the effect that we saw was actually significant. But I actually think that those results are-- I think they're going to lead us in the direction that we hope to see in the BWEL study. In other words, I think that the effect of obesity will not be fully baked in and that there may be some ability to reverse it. We know that losing even 10% of weight will reduce insulin, for example, by 20% to 30%. We know we can see major changes in physiology when we see weight loss. SPEAKER 2: So in your work with [INAUDIBLE], so go back to biology, and you had an opportunity then to look at things like methylation patterns before and after weight loss in cancer cells, or what's getting turned on. You talked about the CILs in macrophage infiltration, but are there things going on in the cancer cells themselves-- or the normal cells for that matter-- that make them more or less susceptible to going on to become nasty cancers? PAM GOODWIN: So that's a little bit beyond my focus. In the BWEL study, blood is being collected repeatedly. So we'll at least be able to look at those changes in lymphocytes, for example. When you're looking at the adjuvant setting, there's no tumor to rebiopsy. And I'm not convinced that the obesity link is the same in the metastatic setting as it is in the adjuvant setting. Once you get into the metastatic setting, the presence of tumor itself may alter metabolism and may impact a lot of the factors that we're looking look at. SPEAKER 2: I'd like to ask you to look forward a little bit now too, because especially in your early work with epidemiology and a focus on lifestyle changes and weight loss, do you think that's going to be where the magic bone will be, or will it be a drug that people can take? I know you've worked quite closely with the Metformin. And imagine you looked in a crystal ball here, I know it's cloudy, but maybe you can give us some insight. PAM GOODWIN: Well, we've looked at Metformin initially because it was an insulin lowering drug. And then Grahame Hardie identified the AMP kinase mechanism of action, and now there's a host of direct antitumor effects that have been reported with Metformin. I think that Metformin in many ways is an anti-obesity physiology drug. It improves much of the physiology associated with obesity. As you know, we've done work showing that it lowers insulin in non-diabetic patients who have breast cancer. We've also done a neoadjuvant window of opportunity study, where patients were given Metformin for the two weeks between diagnosis and definitive surgery. And we showed that Metformin actually lowered T67 and increased apoptosis in the cancer cell. So that was the time when we could look at the cancer cells before and after drug administration. So I think we may see some direct-- or we may see some tumor effects. As you know, we have the large MA-32 adjuvant trial-- 3,600 patients-- which is about to be analyzed. It will likely be analyzed in the next two to three months, and we'll have a definitive answer as to whether Metformin will improve breast cancer outcomes. And because we're looking at contralateral breast cancers, we can also look at whether it impacts the development of breast cancer. SPEAKER 2: At night, do you look up at the ceiling and worry about things like everolimus and alpelisib that actually block the insulin pathway, and then we see hyperglycemia? I don't know if you've treated many people with alpelisib, but hyperglycemia is one of the major consequences of that. Could we actually be in a vicious cycle with using these drugs, or am I reaching too far? PAM GOODWIN: No, I worry about it. I do. It's the same with the IGF1 receptor blockers. I think that sometimes we don't look at the impact of a drug that we believe targets the tumor on the patient's physiology, and the patient's physiology may then actually impede the ability of the drug to treat the breast cancer. If we look at the use of, for example, aromatase inhibitors in premenopausal women, they raise the estrogen levels and the tumor may progress more quickly. We have an example of that. And I think whenever we're doing anything, we need to look beyond the drug itself to the impact-- the drug and the tumor to the impact it has on the patients. I mean, one of the really interesting things that I've seen recently is that some of the PD-L1 inhibitors, when you look at them used to treat cancers other than breast cancer-- I don't think we have this information yet in breast cancer-- being obese actually predicts a better response. So there's something about the synergy between the PD-L1 inhibitor and the obese physiology that makes the PD-L1 inhibitor work better. And some people think it's leptin that is playing a role, but I don't think that's been definitively established. SPEAKER 2: I was not aware of that. Actually, when I was at the Dana-Farber, Chuck Scher, who discovered PD, Platelet-Derived, growth factor, was an endocrinologist. He's a PhD, but he's an endocrinologist by training. And he used to tell me the cancer is just endocrinology gone wild, so you need to understand endocrinology if you're going to be an oncologist. And I'm learning that in spades now 40 years later. PAM GOODWIN: Well, when it comes to breast cancer, yeah, that might be true. Only-- SPEAKER 2: Well, especially in breast cancer, I think. Let's get away from breast cancer for just a moment. I'm towards the end here. And what do you think the role for obesity and diet in other cancers? Do you see such a strong association? And do you have optimism that the kinds of things you're doing in breast cancer will spill over to the others? PAM GOODWIN: So I think obesity is important for cancer in general. I think obesity is associated with increased risk of most types of cancer. And I think it's even more important in cancers like endometrial cancer than it is in breast cancer. I think that what we're learning about obesity and breast cancer will be applicable to multiple other types of cancers. One of the big things we need to think about, though, is that we're in the midst of an obesity epidemic. And at some point, this becomes a societal issue. Obesity is a bad thing for cancer. It's a bad thing for many other illnesses too. And it's probably contributing to a shortened life expectancy for obese individuals. And we need, as a society, at least in the developed world, to start thinking about what we are going to do to try to reduce obesity, to try to get people to eat healthy and to eat proper portion sizes, and to become physically active or to be more physically active. I put that in a very blunt way, but I think these issues extend far beyond breast cancer, far beyond cancer, and really into our general health and well being. SPEAKER 2: Yes, I agree. I've been fond of saying that I think obesity is the smoking of the next generation. I think we're going to pay the piper for this. PAM GOODWIN: I think you're absolutely right. And I think we have a generation that's coming up that maybe has never known proper portion size and knows, at a theoretical level, about healthy eating but doesn't understand how to put it into place and follow a healthy diet and be physically active. And because the obesity epidemic is really just the last generation or generation and a half, we should be able to turn it around. This is not something that's baked into our genes. This is something that we, as a society more so than as individuals, [INAUDIBLE]. SPEAKER 2: Well, and I think when we finally do recognize that and understand how to treat the obesity, people will remember that you were at the forefront-- I don't want to age you-- but 30 or 35 years ago when the whole field got started. So thank you for your courage in going that way. Many of us took the path of least resistance. I don't think you did. Anyway, so thanks for taking time to speak with us today, very much appreciated. And thanks for all you do for the field, and most importantly for our patients. I'm fond of saying that to almost all of our speakers. Without the people who have been on this series, we wouldn't be where we are today. So I'm very appreciative of it. Have a good day. Buh-bye. PAM GOODWIN: You too. Buh-bye. SPEAKER 2: Until next time, thank you for listening to this JCO's Cancer Stories, The Art of Oncology 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's Cancer Stories, The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]