Podcasts about hope national medical center

I'm thrilled to sit down with Dr. Lorna Rodriguez, a medical doctor with a PhD in biochemistry and a true double doc!

Dr. Edward Kim, Vice Physician-in-Chief at City of Hope National Medical Center and Physician-in-Chief at City of Hope Orange County, joins the Becker's Healthcare Podcast to discuss the expansion of City of Hope's footprint, the importance of inclusive clinical trials, and the evolving landscape of cancer screening.

CancerNetwork® spoke with Natasha Bahri, MD, MS, and Daneng Li, MD, about their Hot Topics article titled Casting a Wide NET: When Is the Optimal Time for 177Lu-Dotatate Treatment?, which was published in the November 2024 issue of ONCOLOGY®. Their article focused on findings related to the use of 177Lutetium-Dotatate (177Lu-dotatate; Lutathera) in patients with neuroendocrine tumors (NETs) and whether these data supported the use of the novel radioligand therapy for this population. Bahri is a PGY-5 chief fellow in Medical Oncology and Hematology at City of Hope National Medical Center in Duarte, California. Li is an associate professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center in Duarte, California, and a gastrointestinal editorial board member of ONCOLOGY. Bahri and Li discussed findings from the phase 3 NETTER-1 trial (NCT01578239) assessing 177Lu-dotatate for those with inoperable, locally advanced or metastatic, grade 1/2 midgut NETs following progression on long-acting repeatable octreotide therapy. Although these findings established a significant efficacy signal with the radioligand therapy, Li noted that questions remained regarding the sequencing of 177Lu-dotatate alongside other therapies in the treatment landscape. The conversation also covered efficacy, safety, and quality-of-life (QOL) data from the phase 3 NETTER-2 trial (NCT03972488), in which investigators assessed high-dose octreotide with or without 177Lu-dotatate among patients with locally advanced or metastatic, well-differentiated, somatostatin receptor–positive gastroenteropancreatic NETs. Although data showed improvements in efficacy with the 177Lu-dotatate combination, there did not appear to be significant differences regarding QOL outcomes between arms. “We're waiting for further long-term follow-up information as there was no difference in the QOL metrics. It's important to think about how these patients' goals align with the therapy that we're giving, and if we're not seeing a difference in the quality of life quite yet, [we need to] look at individual patients, see what their goals are, and match them up to the therapy that we're giving them,” Bahri stated. Although the NETTER-1 and NETTER-2 trials demonstrate “great” results associated with efficacy end points such as progression-free survival, the authors noted that it is crucial to weigh these benefits with the potential toxicities when determining suitable candidates for treatment with 177Lu-dotatate. “There's a lot of nuances in terms of who is the ideal patient that's going to maximally benefit [while] minimizing any risk of serious toxicity in those patients. As a result of that, we're helping to improve their outcomes to the highest bars possible, whether it's quality of life or survival,” Li concluded. References 1.        Strosberg J, El-Haddad G, Wolin E, et al; NETTER-1 Trial Investigators. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. doi:10.1056/NEJMoa1607427 2.        Singh S, Halperin D, Myrehaug S, et al; NETTER-2 Trial Investigators. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2-3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. Lancet. 2024;403(10446):2807-2817. doi:10.1016/S0140-6736(24)00701-3

In this episode of SurgOnc Today, Alexander Parikh, MD, MPH, from the University of Texas – San Antonio and Chair of the SSO HPB disease site working group, and Laleh G. Melstrom, MD, MSCI, from City of Hope National Medical Center, are joined by Timothy Newhook, MD, from the University of Texas MD Anderson Cancer Center and Andreas Kaiser, MD, from the City of Hope. We will be discussing the management of synchronous rectal cancer with liver metastases.

During the 2024 Society of Surgical Oncology Annual Meeting (SSO), CancerNetwork® spoke with a variety of surgical oncology experts regarding the topline data they presented. Each conversation also expanded upon how these results can be implemented into the clinical space and the next research steps.  First, Adrienne Bruce Shannon, MD, a complex general surgical oncology fellow at Moffitt Cancer Center, discussed findings from her presentation highlighting responses to neoadjuvant immune checkpoint inhibitors among select patients with mismatch repair deficient (dMMR) gastroesophageal cancer.1  Looking ahead, Shannon described her aim to optimize treatment strategies for this patient population, which may include assessing whether single-agent treatment can be efficacious while avoiding toxicity associated with combination regimens.  Next, Sean Dineen, MD, an associate member in the Gastrointestinal Department, section leader for Peritoneal Disease, and the program director for the Complex General Surgical Oncology Fellowship at Moffitt Cancer Center, spoke about his session, which was aimed at determining appropriate conditions for using cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) for those with colorectal cancer (CRC) and peritoneal metastases.2  Dineen highlighted that there is “good evidence” in support of HIPEC as a “valid treatment option” and emphasized the need to encourage medical oncologists to refer patients for consideration of surgery. Additionally, he spoke about other advancements he hopes to see in this patient population, including the development of markers of various disease volumes that can help identify potential recurrence in those who receive surgery.  Finally, Muhammad Talha Waheed, MD, a research fellow in the Department of Surgical Oncology at City of Hope National Medical Center in Duarte, California, detailed findings from a retrospective analysis indicating disparate treatment access and cancer-related mortality based on racial-economic segregation.3  Specifically, data showed that those who lived in Black and poor majority areas were less likely to receive care that was in accordance with various treatment guidelines while having worse overall survival outcomes. Regarding the next steps, Waheed described his intentions of sharing his findings with policymakers who may create legislature intended to mitigate the disparities observed in the analysis. References 1.        Shannon AB, Mehta RJ, Mok SR, et al. Pathologic response to neoadjuvant immunotherapy in DNA mismatch repair protein-deficient gastroesophageal cancers. Presented at the Society of Surgical Oncology 2024 Annual Meeting; March 20-23, 2024; Atlanta, GA. Abstract 94. 2.        Dineen S. Optimal tumor burden for CRS/HIPEC in colorectal cancer. Presented at the Society of Surgical Oncology 2024 Annual Meeting; March 20-23, 2024; Atlanta, GA. 3.        Waheed MT, Sullivan KM, Haye S, et al. Impact of racialized residential segregation on guideline concordant cancer care and survival. Presented at the Society of Surgical Oncology (SSO) 2024 Annual Meeting; March 20 – 23, 2024; Atlanta, GA; abstract E126.

Charles Brenner, PhD is the chair of the new Department of Diabetes & Cancer Metabolism at the Beckman Research Institute of the City of Hope National Medical Center. He is a major contributor to work on nicotinamide adenine dinucleotide (NAD) metabolism. 15 Daily Steps to Lose Weight and Prevent Disease PDF: https://bit.ly/46XTn8f - Get my FREE eBook now! Become a Genius Life Premium Member! Learn more: http://thegeniuslife.com This episode is proudly sponsored by: LifeForce is a powerful, at-home biomarker testing solution (they test important biomarkers like ApoB, LDL, A1C, hormones, and more!). Head to MyLifeForce.com and use code GENIUS for 15% off.  AG1 is my favorite multivitamin. Enjoy a free 1 year supply of vitamin D and 5 free AG1 travel packs with your first purchase. All you have to do is visit drinkag1.com/GENIUS.

I got the opportunity to talk to Dr. Charles Brenner, an expert in aging research and Alfred E Mann Family Foundation Chair of the Department of Diabetes & Cancer Metabolism at the Beckman Research Institute of the City of Hope National Medical Center. We talked about if eternality and reverse aging is possible and how a Harvard scientist misled investors and companies and scammed people about an anti-aging product that didn't work.Thanks to the sponsors:Audible: Use my link for a 30-day free trial: http://audibletrial.com/diamondgoat Newsly: https://newsly.me promo code to receive a 1-month free premium subscription: EARLYMORNING Libysn: https://libsyn.com promo code: DGDubby Energy: https://www.dubby.ggpromo code for 10% off: DIAMONDGOATspikeview:https://www.spikeview.comhttps://www.instagram.com/spikeviewSwift Grips:https://swiftgrips.netPromo code for 10% off: Diamondgoat ----------------------------------------------------------------------------------Listen on: Podcast website: https://anchor.fm/diamondgoatSpotify: https://open.spotify.com/show/0EuhA6WyuerHtVAqcFrFeORadioPublic: https://radiopublic.com/dg-earlymorning-show-WoML4rBreaker: https://www.breaker.audio/dg-early-morning-showPodcast YT channel clips: https://www.youtube.com/@dgearlymorningshowReason: https://reason.fm/podcast/dg-earlymorning-showApple Podcast: https://podcasts.apple.com/us/podcast/dg-early-morning-show/id1575451533 Amazon Music: https://music.amazon.com/podcasts/f050b86c-1dad-4bc3-b12f-6aa5fa62438c Tiktok: @dgearlymorningshow--------------------------------------Check out my other stuff:Instagram: @itzdiamondgoatTwitter: @lildiamondgoatMain YT channel: youtube.com/diamondgoatTiktok: @lildiamondgoatSoundcloud: @Lil DiamondgoatSpotify: @Lil DiamondgoatMerch store: https://diamondgoat.creator-spring.com

In this episode, we chat with Cynthia Reddick, RD, CNSC. Cynthia is a home tube feeding expert, educator and strategist having worked in homecare for 25 years passionately facilitating patients' successful transition from hospital to home on tube feeding. She works to promote positive clinical outcomes and believes a patient's positive relationship with their feeding tube impacts compliance and quality of life. She developed her passion for nutrition support interning at the City of Hope National Medical Center in Southern California. Most recently, she worked for Coram/CVS Specialty Infusion Services as their National Tube Feeding Manager. Presently, she shares her expertise as a consultant in the realm of home tube feeding and enteral innovation. She enjoys presenting round tables, clinical posters, webinars, and case studies on home care tube feeding and has been a guest speaker for ASPEN, the Oley Foundation, CMSA, NHIA, and the Academy of Nutrition and Dietetics on a variety of topics related to home tube feeding. This episode is hosted by Christina M. Rollins, MBA, MS, RDN, LDN, FAND, CNSC and was recorded on 1/8/2024. Disclosures for Cynthia Reddick RD, CNSC include Speakers Bureau: Nestle Health Science, Nutricia North America, Cardinal Health, Moog Medical and General Consulting: Avanos Medical, Abbott Nutrition, Kate Farms, Danumed, Functional Formularies, and Rockfield Medical

“I don't know the meaning of life, but I know the purpose of life: to survive and procreate.” This quote was from a biologist on the podcast eight years ago, and it stuck with me because if he's right, I've achieved my biological imperative and I'm now on borrowed time. While that may sound soulless and even nihilistic, it's also a helpful frame (for me) as I attempt to make choices to optimize my life in the second half - my bonus time. On this week's podcast, you'll meet a researcher who debunks many pop longevity myths and also shares some compelling research around the supplement nicotinamide riboside. Will it make you live forever? No, but it might help you live better for the time you are here. Listen and learn: Why “biological age” tests are inaccurate How we're unlikely to experience “escape velocity” Metformin, rapamycin, and resveratrol debunked Why so-called longevity clinics giving TRT and HGH are almost certainly reducing - not extending - lifespan   Links Brennerlab.net ABOUT OUR GUEST Dr. Charles Brenner, the Alfred E. Mann Family Foundation Chair in Diabetes and Cancer Metabolism at City of Hope National Medical Center, discovered nicotinamide riboside (NR) as a crucial precursor to NAD+ in 2004 and a second NR-to-NAD+ conversion pathway in 2007, enhancing yeast cell lifespan. Currently, Dr. Brenner leads groundbreaking clinical trials on NR, focusing on its maternal and neonatal effects and translating animal model findings into safe, evidence-based clinical practices for human metabolic stress conditions. Like the Show? Leave us a review Check out our YouTube channel Visit www.yogabody.com

“We incorporate nurses and clinicians and users for any tool from the very beginning. They say, ‘You know, we need help with this.' And then we start ideation: We start understanding the problem, we meet with them, we try to see what is it that they're trying to do, is it feasible given the data we have? We go back, we do some research, feasibility study. We say we think this is something we can predict with decent performance. Now let's do it,” Nasim Eftekhari, MS, executive director of applied artificial intelligence (AI) and data science at the City of Hope National Medical Center in Duarte, CA, told Lenise Taylor, MN, RN, AOCNS®, BMTCN®, oncology clinical specialist at ONS, during a discussion about how the use of AI in cancer care affects an oncology nurse's daily work.  Music Credit: “Fireflies and Stardust” by Kevin MacLeod  Licensed under Creative Commons by Attribution 3.0  The advertising messages in this episode are brought to you by LUNGevity.  Episode Notes  Oncology Nursing Podcast:  Episode 281: Nursing's Role in AI in Health Care  Episode 131: NLM Is Changing Health Care Through the Power of Data  ONS Voice articles:  New Technology Tools Help Oncology APRNs Improve Patient Outcomes  AI Ultrasound Is Nearly 100% Accurate in Detecting Thyroid Cancers  Nursing Informaticists Are the Backbone of Technology-Driven Care  What ChatGPT Says About Belonging and Oncology Nursing  Clinical Journal of Oncology Nursing article: Technology and Humanity  Oncology Nursing Forum article: Artificial Intelligence for Oncology Nursing Authors: Potential Utility and Concerns About Large Language Model Chatbots  Primers for AI concepts and terminology:  Introduction to Artificial Intelligence for Beginners  12 Important Model Evaluation Metrics for Machine Learning Everyone Should Know  To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library.  To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.  Highlights From Today's Episode  “So, there is a lot of applications of AI in cancer care, so I can't possibly give you an exhaustive list. But the ones that come to my mind, at least the ones that we are actively working on are early detection and diagnosis, treatment planning, predictive modeling for predicting unwanted outcomes, remote monitoring, radiology applications, pathology applications, improving operations and helping the resource allocation, precision medicine, and research. And we also started a year or so incorporating AI and helping with drug discovery.” TS 2:13  “We've been using AI for a very, very long time. Recently, we just hear more about AI, but AI is in our lives, in health care or not, all day, every day. Google Maps, Google search, all of this is enabled by AI, but we may not realize even that we're using it.” TS 8:27  “So, for technical challenges, you have to always consider: Is this model performing in a decent manner for this application? And depending on the use case, that's different. If you're providing a decision support to someone that is impacting patient care, then you have to be very careful about model performance. So, model performance is one technical consideration, then how do you really technically integrate with the EMR system? It's not easy, EMR systems are not usually very open, and that's a whole challenge in itself to be able to read from any EMR system in real time and feed data back into it in real time.” TS 10:16  “For nurses to successfully approach and adopt this work, I think the most important thing is to keep an open mind to really realize that these technologies can, at best, take the mundane part of their work away so they can operate at the top of their license, but what AI does best is to do things that are repetitive and doesn't require a ton of human intelligence. I think that would be very helpful. Just that mindset could make things more collaborative and cooperative, and that's the only way that we can make these successful.” TS 12:37  “What could help is for nurses to learn the basic concepts that are involved in the development and deployment and testing of these models, so that they can really understand the limitations and capabilities and they can take an active part in the development as well. So, it's not like we build something for you and then we're trying to convince you this is good for you. We try to build together. As an AI and computer scientist, I'm always learning the medical language. I try to educate myself about the clinicians' workflows and language, and I think the same needs to happen on the clinician side for us to be able to build tools that really work in their workflows for their everyday life.” TS 13:58  “We incorporate nurses and clinicians and users for any tool that will be developed from the very beginning. So, usually, the need for something, like a predictive model, comes from nurses and doctors. They say, ‘You know, we need help with this.' And then we start ideation: We start understanding the problem, we meet with them, we try to see what is it that they're trying to do, and is it feasible given the data we have? We go back, we do some research, feasibility study. We come back and say we think this is something we can predict, you know, with decent performance. Now let's do it.” TS 14:30  “All of our models, even the ones that have been in production for the longest, we're still getting feedback, we're still improving, and we're still retraining models, not only with new data that becomes available but also with the feedback that we get from our users.” TS 17:43  “For example, after going live, we've had less ICU admissions because of sepsis or septic shock, or after going live had less sepsis mortality, which is very reassuring. So that seems like we're doing the right thing, and our model is working, but if you want to put your scientist hat on, you cannot say 100% this is the impact of the model because there is a lot of different workstreams that are trying to improve those same metrics. And unless you do a clinical trial or what we call in industry A/B testing, where you control for everything else and it's only the model intervention that is the variable, you cannot say for 100% that this is the impact of the model. That's why we combine our qualitative metrics that seem to be right in the right direction with the quantitative metrics.” TS 22:17  “I think for the first time, something has come up that can really make a big change in health care. I could not say this before generative AI. AI has always been helpful, but now I think it's the time to see real change. We're still experimenting. It's really new technology. We are experimenting with in-house development as well as third-party tools that we are testing and evaluating. Again, there's a huge potential in reducing manual labor and documentation, note taking, there are implications in billing and finance, data abstraction for research or whatever other purposes that we need them, tumor boards, predictive modeling, clinical trial matching is one big use case in oncology, and finding similar patients—something that we've been aspiring to for a really long time—seems to be very possible now with these technologies.” TS 25:30  “The users also weigh in. So, if you're considering it to improve clinical operations, the people who will be using the tool will have a say in, ‘Yes, we think this tool will be helpful.' So, it's not just looking at the technical and cybersecurity and ethical and legal aspects, but also is this something that our users will use because that's the ultimate goal. If they don't use it, it doesn't matter how good the tool is. It won't work.” TS 31:13  “Making it successful is not about the technology, but mostly about people and processes and operational support.” TS 33:33  “Helping people, helping clinicians, nurses to be more free of mundane tasks and be able to interact with patients, do patient care, which is what they should be doing, rather than the things that I know a lot of nurses hate. I think we have a very exciting time ahead of us.” TS 38:47 

“We really need to do our best to reach people who don't have access to palliative care in their communities, and this is an innovative way for us to do that,” Carey Ramirez, ANP-C, ACHPN, nurse practitioner and manager of advanced practice and supportive care medicine at the City of Hope National Medical Center in Duarte, CA, told Lenise Taylor, MN, RN, AOCNS®, BMTCN®, oncology clinical specialist at ONS, during a discussion about how telehealth is overcoming barriers and disparities that previously limited patients' access to timely oncology palliative care.  You can earn free NCPD contact hours after listening to this episode and completing the evaluation linked below.   Music Credit: “Fireflies and Stardust” by Kevin MacLeod  Licensed under Creative Commons by Attribution 3.0  Earn 0.5 NCPD contact hours of nursing continuing professional development (NCPD), which may be applied to the care continuum, coordination of care, nursing practice, oncology nursing practice, psychosocial dimensions of care, quality of life, symptom management, palliative care, supportive care, treatment https://www.oncc.org/ilnaILNA categories, by listening to the full recording and completing an evaluation at myoutcomes.ons.org by October 20, 2025. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation.  Learning outcome: The learner will report an increase in knowledge related to telehealth-based oncology palliative care.  Episode Notes  Complete this evaluation for free NCPD. Oncology Nursing Podcast:  Episode 251: Palliative Care Programs for Patients With Cancer  Episode 135: ELNEC Has Trained More Than One Million Nurses in End-of-Life Care  Episode 41: Advocating for Palliative Care and Hospice Education  ONS Voice articles:  Bipartisan PCHETA Legislation Reintroduced in U.S. Senate  U.S. Senators Introduce Legislation for Earlier Palliative Care  Help Your Patients Prepare for the End From the Beginning  APRNs Can Lead by Example When Integrating Palliative Care in Practice  Clinical Journal of Oncology Nursing articles:  Palliative Care: Oncology Nurses' Confidence in Provision to Patients With Cancer  Telehealth in Palliative Care: Communication Strategies From the COVID-19 Pandemic  Clinical Oncology Nurse Best Practices: Palliative Care and End-of-Life Conversations   Integrating Palliative Care in Hematopoietic Stem Cell Transplantation: A Qualitative Study Exploring Patient, Caregiver, and Clinician Perspectives   ONS Palliative Care Huddle Card  ONS clinical practice resource: Palliative Care Communication Strategies  ONS book: Integration of Palliative Care in Chronic Conditions: An Interdisciplinary Approach  Center to Advance Palliative Care (CAPC)  Hospice and Palliative Nurses Association (HPNA)  National Hospice and Palliative Care Organization (NHPCO)    To discuss the information in this episode with other oncology nurses, visit the ONS Communities.    To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library.  To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.  Highlights From Today's Episode  “If a person is uncertain of their prognosis or if a provider is uncertain of the goals that the patient has for themselves, that might be an appropriate time to consider palliative consultation. These are all important considerations for triggers that might make palliative a possibility for patients in those scenarios. The take-home message, though, is that the sooner that palliative care is involved, the more likely the patient and family are to benefit.” TS 2:51  “From a patient and family perspective, we frequently find that there are misperceptions regarding palliative care. Oftentimes, they'll conflate the word palliative with either hospice or end-of-life care. They unfortunately sometimes believe that they're one and the same. They demonstrate a lack of knowledge regarding the benefits, including the fact that palliative care can and should be provided alongside life-prolonging care.” TS 3:53  “Palliative providers do their best to help patients maintain hope throughout their disease trajectory, regardless of how well or how poorly things are going. I tend to view things in terms of climbing a sand dune: Living with cancer can sometimes feel like you're walking up a sand dune, either at the beach or at the desert, and there will be days where you take two steps forward and you might slide only one step back. There may also be days where you take two steps forward and slide three steps back. And you find, for example, that if you keep trudging toward the top, that because the winds are constantly blowing those dunes, the top you eventually reach might be different than the one you initially set out to reach. And I think that speaks to the changing nature of hope.” TS 6:08  “It's important to ensure that providers are aware of the local services available to them in their respective communities. [And] we often find that from an organizational or a structural barrier perspective, there are lack of access to palliative care in the community. We often find that outpatient programs may not be as robust, or you may find that there is great variation between outpatient programs with regard to quality.” TS 10:10  “We have multiple patient populations who unfortunately do not have equal access to palliative care. They include rural populations, those who come from low socioeconomic backgrounds. We find that male patients and/or patients who are older adults have lower access to palliative care. We find that those who might be either single or live alone, those who might have an immigrant status, those who don't speak English, those who might have certain cancer diagnoses. It may surprise some of you to know that those with hematologic malignancies actually have much lower rates of palliative referral than those with solid tumors.” TS 11:23  “There's a maldistribution of palliative care resources nationwide. We tend to see that many of the resources are in urban areas, and as a result, we find that a great many rural areas are left untouched. I think it's important for us to recognize that these social determinants of health exist. It's important for us to look intentionally at them and whether they affect some of our patient populations and to work together to overcome them.” TS 14:03  “Anecdotally, I've been doing telehealth for about five years and it's been quite well received. It decreases my no-show rates. It improves my ability to monitor patients over time, and it can be carried out safely.” TS 16:12  “It's important to recognize that telehealth can be utilized not only for a planned appointment that might be scheduled to surveil someone every two weeks or every month from a pain and symptom management perspective, it can also be utilized as a same-day possibility. So if, for example, we have a patient who's due to have an MRI tomorrow and their last MRI was stopped in part because they couldn't tolerate it due to pain or symptoms, we might have a primary team reach out to us and ask whether we can see that patient the day prior to their MRI and devise a plan with that patient so that they can tolerate the MRI more easily the next day.” TS 22:26  “Many of our patients no longer have the ability to get to and from their place of worship, and we can sometimes bring their clergy people to them via telehealth video. We also offer psychology services, psychiatry services, child life services, all via telehealth. And I think it's important to recognize that palliative care is actually made up of an interdisciplinary team, including all of the aforementioned specialists who can basically work together to improve the experience of the patient who is living with cancer and being treated for it.” TS 26:41  “Accept the inevitability of ups and downs. Learn from the downs and persevere. The outcomes are definitely worth it.” TS 28:11 

Dr. Supriya Mohile , Dr. William Dale, and Dr. Heidi Klepin discuss the updated guideline on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy. They highlight recent evidence that prompted the guideline update, and share the updated evidence-based recommendations from the panel, focusing on geriatric assessment-guided management. Dr. Mohile also reviews what the expert panel recommends should be included within a geriatric assessment, and Dr. Dale highlights the Practical Geriatric Assessment tool, aimed at helping clinicians implement a geriatric assessment. Dr. Klepin comments on the impact for both older adults with cancer and their clinicians, and reviews outstanding questions and challenges in the field. Read the full guideline, "Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update" at www.asco.org/supportive-care-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/supportive-care-guidelines. Read the full text of the update and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.00933. See also the Practical Geriatric Assessment tool and associated videos (How to do a Geriatric Assessment, What to do with the Results of a Geriatric Assessment) mentioned in the podcast episode. Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts.  My name is Brittany Harvey, and today I'm interviewing Dr. William Dale from City of Hope National Medical Center, Dr. Heidi Klepin from Wake Forest Baptist Comprehensive Cancer Center, and Dr. Supriya Mohile from University of Rochester Medical Center—co-chairs on “Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update.”  Thank you for being here, Dr. Dale, Dr. Klepin, and Dr. Mohile. Dr. William Dale: Nice to see you. Thanks for having us. Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensures that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including our guests joining us on this podcast episode today, are available online with the publication of the guideline in the Journal of Clinical Oncology linked in the show notes.  Diving into the content of this guideline first, Dr. Dale and Dr. Mohile, can you speak to what prompted an update of this ASCO guideline on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy, which was previously published in 2018? Dr. William Dale: Sure. Yes. In 2018, that was the very first guideline for older adults that ASCO had created, and that was based on work that had been done up to that time, focused on chemotherapy toxicities. And to summarize what was put out at that time, the evidence was thought to be strong enough for doing geriatric assessments. And these are specialized assessments across a number of domains, including functional impairments, cognitive losses, social impairments, etc. But to do these kinds of geriatric assessments with validated tools; that a certain selection of these domains to cover everything that was relevant; to conduct non-cancer prognostication so that for decision-making purposes, if someone were to have their cancer cured, what would be their prognosis, and help make decisions about giving chemotherapy and what doses; and then to enact geriatric assessment-guided target interventions was the fourth recommendation. And so that's where we were in 2018.  In 2020 at ASCO, there was an oral session that had four randomized controlled trials that enrolled older adults. And in that was kind of the signal that there was more coming. And in 2021, two big trials that are practice-changing were published. One led by Dr. Mohile in Lancet that we call the GAP70+ study, and another one was published in JAMA Oncology. And they essentially showed the same thing, which was that GA-guided interventions could change the primary outcome, which was to reduce chemotherapy toxicity up to 20%, and also to affect a number of other outcomes. That, along with a number of other trials that have since come out and are included in the upcoming guidelines, and made it a high priority to update these guidelines. So that's where we got from there to here. And I think it's worth saying a few words about these new trials, particularly the GAP and GAIN studies. So the GAIN study included patients who were 65 and older who were starting systemic chemotherapy and looked at the likelihood of having chemotherapy toxicity as described and looked at a number of other outcomes. Most importantly, it showed that chemotherapy toxicity could be reduced with these interventions based on the geriatric assessment from about 60% to about 50%. It also showed that the likelihood of completing advanced directives would go up by around 25%. And importantly, there was no impact after all of the use of the geriatric assessments on mortality. So patients were living just as long, but they were having less toxicity and they were having more goal-concordant care. And at almost the same time, the GAP study came out, which I would hand over to Dr. Mohile to describe. Dr. Supriya Mohile: Thank you, Dr. Dale. I agree that it was time for an update, and I'm glad ASCO partnered with us to do this. I'll also just mention that Dr. Dale, Dr. Klepin, and I lead the Cancer and Aging Research Group, and many of the original predictive models that showed that geriatric assessment could help us identify patients at highest risk for toxicity were designed by Cancer and Aging Research Group investigators. And that's what informed the first guideline. I'll mention Dr. Arti Hurria, who unfortunately passed away a few years ago, and she led some of the first large studies that developed these predictive models. We built on that data in both GAP and GAIN studies to show that the geriatric assessment—when you assess and provide management—can reduce chemotherapy toxicity.   Like GAIN, GAP70+ implemented a geriatric assessment intervention that both assessed and provided management to older adults. There were some key differences. In GAP70+, the patients had advanced cancer, whereas, in the GAIN study, it was a more generalizable population of patients with both curative intent and advanced cancer. And in the GAP70+ study, we enrolled patients who already had geriatric assessment domain impairments, meaning that these patients were more vulnerable because of those aging-related conditions. We were trying to enroll patients who are traditionally excluded from therapeutic clinical trials. The GAP70+ study was done in oncology offices by Community Oncology practices.  So this was what I think was really interesting, in that geriatricians were not involved in implementing the geriatric assessment in this study. Oncologists received the assessment information from their team, and they're the ones that implemented the recommendations. We found in GAP70+ that not only chemotherapy toxicity was reduced, that we were able to reduce the prevalence of falls and reduce the incidence of polypharmacy, which are important geriatric outcomes for older adults. We included patients who were receiving chemotherapy, but also patients who are receiving high-risk targeted agents in GAP70+, which also leads us to believe that these interventions are important for patients who are receiving treatments other than chemotherapy.  So we believe these two trials, plus others, really inspired the ASCO guidelines. Brittany Harvey: Absolutely. I appreciate you both for providing that context and background and some of the new evidence that's informed this latest update. So then I'd like to move into some of the updated recommendations of the guideline. So, Dr. Mohile, what is the updated recommendation from the panel regarding the role of geriatric assessment in older adults with cancer? Dr. Supriya Mohile: So the first guideline really focused on the assessment piece, what should be assessed, and why, which we still incorporate in this new guideline. This guideline extends now because of the randomized controlled trials into management. And when we think about geriatric assessment, we think about two pillars of management. One is how geriatric assessment influences cancer decisions, that includes what treatments to provide, what dose to provide. And then the second is how geriatric assessment can influence management recommendations that are supportive care based that address some of the geriatric assessment domain impairments.  I'll just give you an example of both. So when we see patients with advanced cancer who have geriatric assessment domain impairments who are presenting for treatment, often the doses of chemotherapy may be overtreatment because those doses were developed in therapeutic clinical trials in younger, more fit patients. And in our geriatrics world, we often think about going slow and starting low, and we may do a first cycle that's dose reduced a touch, to kind of see how the patient does physiologically with that first cycle. There are therapeutic clinical trials like FOCUS2 in patients with metastatic colon cancer that show the benefits of being careful with dosing in the first cycle.  So, in GAP70+, the oncologists who received information from the assessment were more likely to reduce the dose of the treatment in the first cycle which led to less toxicity but did not lead to a difference in survival, so do not compromise survival. And I think this is because we don't know the right doses for patients who have significant aging-related impairments. So that's one example of decision-making.  As examples for geriatric management recommendations that are supportive care, this can be done in almost like an algorithmic approach. So, if a patient has an impairment on a physical function test, then through the geriatrics literature we know of management recommendations that can improve outcomes like physical therapy, home safety evaluations, balance, training, fall prevention information. And if we implement those supportive care recommendations through that patient who's at risk for falls, we may prevent falls and we were able to show that in addition in GAP70+ as well as other trials showed benefits in some of those outcomes.  And so those are the two pieces that I think are newer with this guideline than with the previous guideline. We know more about how those management recommendations can improve outcomes.    Brittany Harvey: Understood. Yes. It's helpful to understand those examples of how integrating this geriatric assessment can help improve the management of care for these patients. So then you've mentioned some of the geriatric assessment domain impairments. So, Dr. Mohile, what does the guideline recommend should be included within a geriatric assessment? Dr. Supriya Mohile: This was a really great question for us to rise and think about, as part of this guideline and as a panel, we went back and forth with all of the authors to try to think about what is the most streamlined number of domains that should be assessed? What are the highest priority domains that, if you could only do a few things in a busy oncology clinic, which are the ones that oncologists should have to do because without doing them, they won't have relevant information to inform treatment decisions or to improve the outcomes of their patients?  And so when we think about geriatric assessment, there has been literature to show that almost all of the domains we do are important in identifying patients who are at risk of poor outcomes. These include physical function, cognitive function, emotional health, comorbidities, polypharmacy, nutritional status, and social support. That sounds like a lot, but we do many of those assessments sort of naturally in oncology clinics. There are just a few that are not done as standard. For example, it is not standard for oncologists to assess cognition using a validated screening test for cognition. And we know that recognizing patients who may have cognitive impairment is really important in identifying vulnerabilities and providing support systems in place so patients who are receiving treatment can go through treatment safely.   Other things, like just doing a formalized nutritional assessment, really bringing in the caregiver, are done not in a standard way. And so what the geriatric assessment allows is for us to assess each of those domains in a standard way. When we're communicating to our colleagues and tumor boards, we can describe vulnerabilities in a standard way. And we're moving now past the eyeball test, which is different for different clinicians, and having more objective ways of describing health status to be able to have a common language across studies and in clinical care. Brittany Harvey: That's helpful to understand moving past the less formal approach to geriatric assessment and making it more standardized.  So then, Dr. Dale, this guideline offers a specific tool, the Practical Geriatric Assessment, as an option for clinicians conducting a geriatric assessment. What is this tool and where can clinicians access it? Dr. William Dale: Very good question. Just to set the context a bit, after hearing about all the evidence that we've just described. We did do some work as a task force through ASCO and through some work that Dr. Klepin and her colleague have done to understand now that the guidelines in 2018 had come out, they weren't really being used. So when we asked, about 25% of people would say they were using them very much, even though we saw in these large studies that we did, that those who were using the guidelines were changing their practice significantly in the ways that Dr. Mohile mentioned. And this was among a large group of community oncologists.  So we have been breaking down the geriatric assessment into the most concise, most straightforward, and easiest-to-use version of the geriatric assessment, maintaining its validity and maintaining the number of domains. We really tried to make it simple. So the Practical Geriatric Assessment is not the only tool, but it is a tool that accomplishes this practical charge to make it accessible to community oncologists while also being valid. So those domains that Dr. Mohile mentioned physical function, functional status, nutrition, social support, psychological considerations, comorbidities are all in the Practical Geriatric Assessment.   But what we've done is boil it down to here's a very specific tool that we think is valid but easily applied. Here are the very specific thresholds that tell you when a deficit has been identified and then gives recommended actions to be taken, whether it's in decision-making or in other interventions like a referral to somebody, perhaps physical therapy, or a cognitive specialist, all of which come from the GAP. So this tool is designed to be very straightforward and practical, but still cover all the relevant domains. And it will be made available through both the ASCO website and through the Cancer and Aging Research Group website so that people can access it easily. Brittany Harvey: That sounds like a real challenge that the ASCO working group took on to create a comprehensive yet practical tool for clinicians to use. We'll also provide some links for people to access this in the show notes of this podcast episode.   So then I want to move on. Dr. Klepin, in your view, how will this guideline update impact both clinicians and older adults with cancer?  Dr. Heidi Klepin: Yes. Thank you. As was mentioned, for clinicians, the guidelines provide an overview of new evidence and concrete recommendations to address the challenge experienced every day in practice, that of providing personalized care in the context of age-related conditions to maximize benefits and minimize the risk for older adults with cancer. The evidence summary will educate clinicians on key outcomes that can be positively impacted by use of geriatric assessment, including decreasing treatment toxicity, enhancing decision-making, and improving communication and patient-caregiver satisfaction.  And this information on outcomes is really critical to informing the use of geriatric assessment in practice. We hope that the evidence-based recommendations with the provision of the practical geriatric assessment and the associated trigger table to guide management strategies will empower clinicians to incorporate geriatric assessment into their workflow by helping them overcome some of those known barriers that Dr. Dale mentioned, such as lack of time and uncertainty about which measures to use and what to do with the information once you have it. So, we anticipate that providing clear recommendations and accompanying readily available materials to support the implementation that clinicians in both community and academic practices will be able to use the geriatric assessment and incorporate it into routine care. For patients, we anticipate that the guideline recommendations would translate into increased use and access to this type of assessment as part of their routine oncology care. So, we hope that our patients will actually be able to access this regardless of whether they're receiving care at a specialized academic center versus a community oncology clinic. So, by doing this, we would extend the proven benefits of geriatric assessment, including lower rates of side effects, experiencing fewer hospitalizations, and improving satisfaction to older adults regardless of where they receive treatment.   And we feel like this is critically important, since currently, most older adults receive cancer care in community oncology clinics without access, as was mentioned, to any geriatric specialty care. So, as more older adults have the opportunity to participate in this type of assessment as part of routine care in their oncology clinics, they'll be able to discuss the results of the assessment with their healthcare providers, which can help them make better-informed decisions and engage, I think, more completely in what we would consider patient-centered decision making. And ultimately, we would hope that the guidelines would provide an evidence-based and practical strategy for improving the quality of care received by older adults with cancer.   Dr. Dale, would you be interested in commenting a little bit more on the patient perspective informed by our patient partners on the guideline panel? Dr. William Dale: Yeah. Thank you, Dr. Klepin. Very well said. Yeah, our guideline panel, just to fill out the picture of that, included our patient partners, along with a wide diversity of perspectives. We had experts in geriatric oncology, but we had community oncologists who take care of cancer patients. We have people from across the country. We had different backgrounds and different levels of experience. But to focus on the patients for a group that we've worked with for some time called SCOREboard, and they were some of the strongest voices on this.  Whenever people said, “Well, do we really need to require this?” The patient partners were insistent that this be included as a requirement as much as possible for what happens. I think one of the most important roles they've played is as advocates for this. If I can, when the community oncologists are having some concerns about how hard this would be or how difficult it might be, the patient partners have been the first to say, we need to find a way to do it and insist that we empower the patients to ask for it. So, one of the hopes for all of these guidelines is also that it get disseminated to patients who can self-advocate as they go forward and have tools that will be made available for them to use in this self-advocacy. Brittany Harvey: Definitely, that self-advocacy is important and the geriatric assessment is critical for optimal care for older adults.  So, then we've talked a lot about the new evidence regarding geriatric assessment and also making it easier for clinicians to implement the geriatric assessment, but Dr. Klepin, what are the outstanding questions and challenges regarding geriatric assessment in older adults with cancer?  Dr. Heidi Klepin: Thanks. So, while there's strong evidence and clear rationale to incorporate geriatric assessment into routine clinical care, there are outstanding questions and challenges that we have to consider. First and foremost, still remains a challenge of implementation. As mentioned, we hope that the Practical Geriatric Assessment, the detailed recommendations, and the associated educational materials on what to do with the geriatric assessment information will help overcome implementation barriers for many. But we recognize that more work needs to be done to both train providers to facilitate behavior change as well as to tackle clinic and healthcare system barriers to routine use.  And along these lines, we also recognize that it's important to educate patients and caregivers about the role of geriatric assessment and its value in order to optimize uptake in community clinics. We want all of our patients to be as enthused and recognize the importance of the geriatric assessment, as our colleagues on the recommendation panel did. Another consideration is the challenge of tailoring use of geriatric assessment to specific disease and treatment settings. And more research is underway testing geriatric assessment and management strategies in varied disease settings, as well as with varied treatment types and intensities.  And finally, I would suggest that another challenge is the lack of routine incorporation of geriatric assessment measures into cancer clinical trials. And this will really be necessary to interpret clinical trial data for older adults optimally and to reinforce the value of routine geriatric assessment in clinical care. Brittany Harvey: Absolutely. These are key points for moving forward and looking forward to additional research in this area and maybe future guideline updates down the line.  So, I want to thank you all so much for your work on updating this guideline and for your time today. Dr. Dale, Dr. Klepin, and Dr. Mohile.  Dr. Heidi Klepin: Thank you for having us.  Dr. William Dale: Yeah, thanks for having us here. We're delighted to be talking about this.  Dr. Supriya Mohile: Thank you.  And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store.  If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.  The purpose of this podcast is to educate and 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.    

In this episode, host Shikha Jain, MD, speaks with Edward Kim, MD about what it means to be a disruptive innovator, how to lead efforts in health care system changes and more. •    Welcome to another exciting episode of Oncology Overdrive 1:11 •    About Kim 1:19 •    The interview 3:00 •    What was your journey into oncology and the leadership roles you hold now? 3:27 •    Jain and Kim on changing specialties in medical school and in careers 10:45 •    Kim on family, his relationship with his daughter, and their viral Taylor Swift concert video  12:34 •    Jain on the upcoming Healio Disruptive Innovators Awards and how to register 17:46 •    What do you think disruptive innovation means? … Why did you agree to join this initiative? 18:07 •    Jain on framing disruptive innovation as a positive within the struggles of the health care system 23:34  •    How can we get our systems and delivery of health care to reflect the innovation that we see in medical technology advances, cancer care advances and other advances now to disrupt things for the future? 25:02  •    Jain and Kim on perceptions of certain treatments, and how it can prevent forward-thinking innovation 31:36  •    Why do we allow ourselves to fall into that trap in health care? … Why have we taken so many years to start addressing these innovations on a larger scale?  32:54  •    Kim and Jain on risk aversion for physicians and how questioning systems has evolved 37:36 •    If someone could only listen to the few minutes of this episode, what would you want them to take away? 43:02 •    How to contact Kim 44:27 •    Thanks for listening 45:10 Edward S. Kim, M.D., M.B.A., FACP, FASCO, is physician-in-chief and senior vice president, City of Hope Orange County, and vice physician-in-chief and professor, City of Hope National Medical Center.  Learn more about  Healio Disruptive Innovators Awards on June 3, 2023, and how to register.  We'd love to hear from you! Send your comments/questions to Dr. Jain at oncologyoverdrive@healio.com. Follow Healio on Twitter and LinkedIn: @HemOncToday and https://www.linkedin.com/company/hemonctoday/. Follow Dr. Jain on Twitter: @ShikhaJainMD. Kim can be reached via LinkedIn, Facebook, on Twitter @DrEdKim, or via email edwkim@coh.org.  Disclosures:  Jain reports no relevant financial disclosures. Kim reports affiliation with Boerhinger Ingelheim, Genentech and Mirati.

This episode features Stephen Gruber, Vice President at City of Hope National Medical Center and Director of City of Hope's Center for Precision Medicine, Stacy Gray, Chief of City of Hope's Division of Clinical Cancer Genomics and Deputy Director of its Center for Precision Medicine, Sumanta “Monty” Pal, Co-Director of the Kidney Cancer Program at City of Hope, and Rick Baehner, M.D., Chief Medical Officer at Exact Sciences Precision Oncology. Here, they discuss their experience building their precision oncology program at City of Hope and how it has improved patient care and clinical outcomes across the organization.This episode is sponsored by Exact Sciences

Winter snow impacting millions of people from coast to coast. Also, Rupert Murdoch acknowledges Fox News hosts pushed false 2020 presidential election claims. Plus, Vicky Nguyen shares some popular alternatives to a hotel or resort and perfect for your next vacation. And, Your Health: The City of Hope National Medical Center is using robotics to help detect lung cancer and save lives.

What causes aging? In a paper published last month, Dr. David Sinclair, Professor in the Department of Genetics at Harvard Medical School, reports that he and his co-authors have found the answer. Harnessing this knowledge, Dr. Sinclair was able to reverse this process, making mice younger, according to the study published in the journal Cell.I talked with Dr. Sinclair about his new study for the latest episode of Making Sense of Science. He said that turning back the clock on mouse age through what's called epigenetic reprogramming – and understanding why animals get older in the first place – are key steps toward finding therapies for healthier aging in humans. We also talked about questions that have been raised about the research by Dr. Charles Brenner, Department Chair at City of Hope National Medical Center, and Dr. James Timmons, Senior Fellow at Queens Mary University.Show links:Dr. Sinclair's paper, published last month in Cell.Recent pre-print paper - not yet peer reviewed - showing that mice treated with Yamanaka factors lived 9% longer than the control group.Dr. Sinclair's podcast.Previous research on aging and DNA mutations, noted in a critique by Dr. Charles Brenner.Leaps.org podcast with Dr. Brenner.Dr. Sinclair's book, Lifespan.Leaps.org is a not-for-profit initiative that publishes award-winning journalism, popularizes scientific progress on social media, and hosts events about bioethics and the future of humanity. Visit the platform at www.leaps.org. Podcast host Matt Fuchs is editor-in-chief of Leaps.org.

JCO PO authors Dr. Edward Esplin and Professor Heather Hampel share insights into their JCO PO commentary, “Universal Germline Genetic Testing for Hereditary Cancer Syndromes in Patients With Solid Tumor Cancer” and discuss practical implications of testing for patients, geneticists, and clinicians. Host Dr. Rafeh Naqash, Dr. Esplin, and Professor Hampel discuss standard of care guidelines, insurance coverage, and benefits of testing. Click here to read the article! TRANSCRIPT Dr. Abdul Rafeh Naqash: Welcome to ASCO's JCO Precision Oncology Conversations, where we bring you the highlights and overview of Precision Oncology. Episodes will feature engaging conversations with authors of clinically relevant and highly significant JCO PO articles. These articles can be accessed at ascopubs.org/journal/po. Hello and welcome. My name is Dr. Abdul Rafeh Naqash. I'm a medical oncologist and assistant professor at the OU Health Stephenson Cancer Center. I'm also the social media editor for JCO Precision Oncology, and you're listening to JCO Precision Oncology Conversations podcast.  Today I am thrilled to be talking with Dr. Edward Esplin and Professor Heather Hampel about their recent paper, ‘Universal Germline Genetic Testing for Hereditary Cancer Syndromes in Patients with Solid Tumor Cancers'. Heather Hampel is the associate director in the Division of Clinical Cancer Genomics and is a professor in the Department of Medical Oncology and Therapeutics Research at the City of Hope National Medical Center. Dr. Edward Esplin is a clinical geneticist and also the Head of Clinical Trials at Invitae in San Francisco, California.  For the purpose of this podcast, we'll be referring to each other using our first names. So welcome both Heather and Ed. Thank you for joining us today.  Dr. Edward Esplin: Thank you, Rafeh.  Professor Heather Hampel: Thanks for having us.  Dr. Abdul Rafeh Naqash: Well, first of all, I'd like to start by discussing some of the context behind this very interesting commentary. For the sake of our listeners, this is one of our first commentaries that we're doing a podcast on because this is very clinically relevant, especially for patients with cancer and without cancer, as I was reading through this commentary. So could you tell us, Ed, what prompted you to start this commentary, and what was the context of and the importance behind why something like this would make a difference in the clinical care of patients with cancer?  Dr. Edward Esplin: Yes, I'd be glad to. I think that we have seen over the past couple of years an ever-growing application and opportunity for application of precision therapies in patients with cancer of various kinds. And there has been with that a growing amount of evidence connecting germline genetic variants of a pathogenic nature with various types of cancer, breast cancer being one of the ones that is the most prominent. And as we've seen this evidence accrue in cancer types such as breast, which has probably got the longest history of a connection to germline genetics, but also accruing in other cancer types such as pancreatic cancer, prostate cancer, ovarian cancer, colorectal cancer, it became clearer and clearer that there is evidence to support a broader application of germline genetic testing than is currently the standard of practice. In part driven by the desire for access to these precision therapies that are driven in part by patients' germline genetic makeup and for the opportunity that germline genetic testing results have for affording patients potential access to clinical treatment trials - so the cutting edge of what is driving some of these treatment opportunities - and reviewing the amazing amount of work that has been done by a number of people across the country and across the world to support these opportunities and support this becoming more and more the standard of care really motivated us to do this project together, and we've been fortunate to have been involved in a number of the studies that we review in this commentary.  Dr. Abdul Rafeh Naqash: Thank you so much for that explanation, Ed. So, Heather, you, and both Ed, have obviously led and been part of a lot of work in this space and have developed guidelines in this space. For the sake of our listeners, whether they are clinicians or patient advocates, what are the current guidelines behind germline testing for patients with cancer and patients without cancer?  Professor Heather Hampel: That's a really good question, and that's a lot of what's driving it for me, just from a clinical perspective.  So currently, we mainly use the NCCN guidelines in the US for deciding when a patient is appropriate for germline genetic testing. And they only recommend or suggest considering germline genetic testing for all cases of three particular cancers: all cases of ovarian, pancreatic, and, most recently, this summer, all cases of colorectal cancer, they've said you could consider offering germline testing to. The other one that has a recommendation is prostate cancer, but that's restricted to patients with metastatic or advanced prostate cancer, so it's not all prostate cancers. When you look at the guidelines, you ask yourself, how did they decide that? Was it based on the prevalence of finding a germline mutation? Because if it was, there are several other cancers where germline mutations are just as prevalent, but that recommendation has not been made.  And what is happening really on the front lines is that some patients are not having access to genetic testing because we have very complex criteria requiring ages of diagnosis, certain tumor markers, particular family history constellations that make the criteria difficult to use for frontline primary care physicians and patients deciding who needs referred, and do I need to see cancer genetics? And how much more straightforward would it be if we just said everybody with cancer needs gene testing? At this point, we pulled the data together for this commentary. We feel like the odds of testing positive are high enough in every single solid tumor to support a change in the recommendations like that.  Dr. Abdul Rafeh Naqash: Thank you. And from the data that you highlight in this commentary, apart from the tumors that you mentioned, Heather, that have recommendations for germline testing, what other tumors would you try to incorporate this in subsequently as a first, second, third approach, maybe if you can't get to all tumors at the same time?  Dr. Edward Esplin: I would say that one of the ones that we would highlight, I think, also, is breast cancer, right? That's one that there's a clear link. And as Heather appropriately noted, while a universal guideline per se has not been established by the NCCN for breast cancer, about three years ago now, based on a publication in Journal of Clinical Oncology, there was the observation that the guidelines that existed at that time did not find a significantly increased number of pathogenic germline findings in patients who met the criteria as they existed at that time compared to those patients who did not meet the criteria. And based in part upon that data, the American Society of Breast Surgeons came out with guidelines that recommended, indeed, the time is now for universal germline genetic testing for all patients who have been diagnosed with breast cancer. So I think that one's another one that there's a great deal of opportunity for that to be implemented, consistent with what Heather has already noted.  And I think there is also data that's been presented at ASCO here very recently, suggesting that similar evidence supports testing not just for metastatic prostate cancer but possibly for a broader collection of prostate cancer patients as well, perhaps all of them with a similar finding where in a prospective observational cohort of unselected patients with prostate cancer. Again, when you applied the current guidelines for testing, there was no statistically significant difference in the number of actionable pathogenic germline findings in patients who met the current criteria compared to those who do not. Which unfortunately suggests that all those patients who are being excluded when we adhere to these guidelines are not able to access the genetic information that could be crucial to their treatment. And it's just because they're not being considered, even though there is a significant fraction of those individuals who do have germline genetic information that could impact their care and possibly the preventive care of their at-risk family members as well.  Professor Heather Hampel: And, Ed, let me add a study I did with you and your team on endometrial cancer. So the truth is, Rafeh, we don't want to pick. We want all solid tumor patients to get germline genetic testing through a multigene panel. But I think if we did have to pick, I would also add endometrial. We did a study of nearly 1000 unselected endometrial cancer patients in the state of Ohio and found just over 10% had a pathogenic variant in a cancer susceptibility gene. And you really could not predict, based on personal or family history factors, who was going to test positive.  Dr. Abdul Rafeh Naqash: And that was definitely something interesting that I caught in this commentary as I was going through it. One of the sentences that was definitely interesting for me was where you mentioned that these guidelines should include risk factors beyond family history and just testing for genes beyond BRCA1 and BRCA2, which are commonly identified entities associated with germline testing, that prompt germline testing.  But one of the other things is the financial aspect of it, which you have highlighted in your commentary. So, I wanted to briefly touch on that and understand what are the policies. It seems like different coverage policies cover different aspects of germline testing, so that's number one. Could you comment on that? And number two, a few years back, there has been an effort you might have heard of related to TMB or Tumor Mutational Burden Harmonization. Could there be some sort of harmonization to identify what are the most important testing genes that are or should be covered by some of these insurance policies? And could you highlight some of the aspects around that?  Dr. Edward Esplin: That's an excellent point. And what we have found has been the course this usually proceeds through is when the guidelines have established what the criteria should be for testing, then, over a certain period of time, naturally, the various insurance payers will then incorporate this into their medical policies. And, for better or for worse, this takes time. I think, in the opinion of most, the time that it takes is unfortunately prolonged for reasons that I don't personally understand.  But noting a bright spot, I'll highlight that UnitedHealthcare has actually taken the step of instituting a very patient-first medical policy. They did this back in 2020, where they recommend and consider medically necessary standard of care germline genetic testing for any patient who has a diagnosis of any cancer that is associated with Lynch syndrome. So meaning that any patient covered by their policy who has a personal diagnosis of colon cancer, endometrial  cancer, the long list of cancers associated with Lynch syndrome, qualifies for germline genetic testing. And that's covered as part of the standard of care, which is a great move in the right direction for this, the largest private commercial insurance provider in the United States.  Now, do we need to see more of that? We absolutely do, because, as Heather's already noted, there is an access issue, and there is a disparity issue for those individuals that don't meet the criteria of their own insurance policies, medical policy, they don't have access. And that requires them, if they choose, to get germline genetic testing, to pay an out-of-pocket cost of $250 or more, depending. And that may be something that is simply not accessible to individuals. And so there's a tremendous amount of effort that needs to be done to incorporate the guidelines as they currently exist into medical policy.  And I think, to your point as well, the discrepancies between various medical policies is certainly a challenge, and I don't have a good answer for how to address that. But it is frustrating, to say the least, that any clinician has to guess what their own particular patient that's sitting in front of them right now has in terms of medical policy coverage for germline genetic testing. And then that should in any way cause them to have to second guess ‘How am I going to get the standard of care to this patient?' One of the other challenges that that potentially raises is, as we noted in our commentary as well, unfortunately, even for those cancer types where there is an established recommendation for universal germline testing, there is nowhere near the implementation of that that there ought to be.  For ovarian cancer, I think it's in the neighborhood of 30% of patients with ovarian cancer are getting this testing. For breast cancer, I think it's 25%. I can't remember if this was cited in this paper or not, but in a recent publication that we did with collaborators from Optum Health, we found that 5% or less of colorectal cancer patients who fell under this very progressive UnitedHealthcare policy were getting testing where everyone qualified for it under the medical policy. And so it really raises concerns about these missed opportunities in the setting of not effectively implementing germline genetic testing even when it is already recommended as the standard of care for the guidelines as they currently exist and not to be available to many more patients with various cancer types, as we've already noted.  Dr. Abdul Rafeh Naqash: Thanks for highlighting some of those very extremely important points. And, to your point, it's not implemented as much as it should.  Heather, have you, or others in this field, tried to understand what are those exact barriers that maybe me, as a clinician who sees at least patients with cancer, should know, or any other community-based oncology practice physician, should know that these are patients where testing is important and will have clinical implications. But what would be the barriers that potentially do not result in as much of a higher implementation of this testing than one would expect?  Professor Heather Hampel: Well, you may be surprised to hear this coming from a genetic counselor, but I've become convinced over the years that requiring pretest genetic counseling is one of the biggest barriers that actually keeps patients from getting genetic testing when it's appropriate. And not that we're trying to be, but just that we have long wait times. Patients may have a lot of appointments because of a new cancer diagnosis, and they're overwhelmed. It just adds one more thing that's a little difficult.  And so, I really am interested in flipping the paradigm, and this is what we're doing at City of Hope now, currently, which is offering a precision medicine or a mainstreaming approach, where every single patient at the institution is offered germline genetic testing regardless of age, regardless of family history, regardless of tumor type. And then, believe it or not, this actually supports hiring more genetic counselors because you're dealing then with thousands of results that need to be hand-reviewed, and all positives, of course, get invited in for full post-test genetic counseling. And that saves that resource, that scarce resource of genetic counseling for the people who need it the most, the people who tested positive, whose family members need testing, who need to implement all the management that comes with testing positive.  I find those sessions much more rewarding because I can be much more helpful for the patient and the family, and our negative patients, or patients with variants of uncertain significance, get templated letters. We've got a team of genetic counseling assistants that are helping get those out because, of course, that's the majority of patients. But if they have questions or concerns or a strong family history, they can, of course, come in for post-test genetic counseling, too. But I think we're on the cusp of switching the paradigm of how cancer genetics is delivered, and that's really the only way to get it at scale to the large number of patients who actually need it.  Dr. Abdul Rafeh Naqash: Thank you. And, to that point, I wanted to say that, as cancer care becomes more and more multidisciplinary, it's right there in front of us that, I think, genetic counselors or clinical geneticists need to be part of these multidisciplinary teams, whether it's through molecular tumor boards or outside of molecular tumor boards. But I think that's where the gap is, at least from what I see on my end. And that's where communication gaps create issues. I recently had at least two patients in their 30s and 40s, one with a PALB2 and another with the CHEK2 alteration and initially identified on liquid biopsy, actually, and that prompted me to check for germline testing. And lo and behold, both were positive. And that resulted, as Ed, you mentioned, cascade testing and eligibility for trials, both ended up on different DNA damage-based trials. So, definitely a lot of clinical implications.  In your practice, when you were on the academic side, Ed, did you have instances where you definitely could see a lot of difference with respect to clinical management of a patient when such an event was identified when a pathogenic germline alteration was identified? And could you give us a few examples so that listeners maybe could try to understand better how some of these things can have significant clinical implications?  Dr. Edward Esplin: Well, I practiced when I was at Stanford in perhaps a little bit of a skewed environment, skewed to the better, where much of my interaction with patients with cancer and with molecular tumor board as well was in the setting of the Stanford Cancer Genetics Clinic. And so that's certainly highly enriched for well-informed individuals, very genetic-savvy medical oncologists. Obviously, the genetic counselors were the foundation there, and me, as a clinical geneticist, was actively involved in such a way that, yes, I think it made a lot of difference from the standpoint of patients with cancer, knowing what all of their options were. And in a number of cases also, the first thing, I think that at least from my standpoint, thinking about genetics a lot that many patients want to know is: why do I have this cancer? Did I do something to cause this? What's the underlying reason for this? And being able to either provide them reassurance that this was not something that was genetic, that this was not something that anyone in their family needed to be particularly concerned about, or that there was anything further that needed to be done about that. Versus the alternative, each of those answers was incredibly valuable to the patient and the patient's family for the reasons I think that you already alluded to.  If there is a genetic cause, then there are known actions that can be taken, whether it's an approved precision therapy or a clinical treatment trial. But then I think equally important, especially in those families where there was a known history of various cancers, and this is the first person who had any genetics done, then being able to share with that patient and with the patient's family that they're going through an excruciating disease course, but there is an opportunity for some of that to be mitigated, some of that risk to be mitigated in their family members; I think brought a certain amount of, I don't know if reassurance is the right word, but it was valuable and was greatly appreciated by those individuals.  One situation that I recall actually was a patient that– I can't remember what her age was, she was probably in her 40s or 50s, but she had developed a colorectal cancer. She had had appropriate germline genetic testing performed and had had a variant identified; I believe it was one of the Lynch syndrome genes, I'm not recalling exactly right now. But while she was undergoing her treatment, I mean, to her credit, she went right away to her family in particular, to, it happened to be her son who was one that got tested, and he was, I think, late teens, maybe early 20s, he had tested positive for the same thing. She made sure that he went in, he got his colonoscopy right away, and lo and behold, right, they find an advanced polyp in this 20-year-old kid that, had that not been done, that would have been identified in just a very tragic way. And yet, as a result of her taking charge and having the information that she needed to take charge for herself and for her family members, a cancer was literally prevented. And that individual's life was prolonged, if not saved, because of that action being taken on behalf of that individual who had the information they needed to do that.  Professor Heather Hampel: Yeah, I would just add I was talking to some of the docs at one of our network sites recently and talking about all of these benefits, which are 100% clear and really also hitting on the targeted therapy benefit quite a bit. And they reminded me of another benefit which we all often forget, and that is even surgical decision-making. So if we got this done early enough, there are certainly patients who have BRCA mutations who might elect to have bilateral mastectomies instead of a unilateral mastectomy or a lumpectomy and patients with Lynch syndrome who might elect to have a subtotal colectomy instead of a segmental resection. And again, this is where not only do we need to be offering this to everybody, but we need to be offering it early at the time of biopsy-proven cancer in some cases, where it could actually affect even their surgery.  Dr. Abdul Rafeh Naqash: Absolutely. And thanks, Ed, for highlighting some of those interesting and important examples.  Now, Heather, when we talk about 80%-85% of the places in the country, at least in the US, they may or may not likely have access to experts like yourself or elaborate, broad, experienced teams that you guys have been part of. So on the oncology side, in a clinic, we get a patient who gets next-generation sequencing done, a 500-600 gene panel where we may or may not have a geneticist, or the wait times are longer. What is your suggestion for individuals, both clinicians and for patients, in that setup? What are the things that one should think of to mitigate some of those delays in that setup where you may not get a geneticist to see that patient or a counselor to see that patient immediately? Looking at that sequencing panel, what couple of things would you think of should prompt a physician to refer a patient to a genetic counselor if it's on a need basis and not available for everybody?  Professor Heather Hampel: And you're talking about a tumor panel that's coming back.  Dr. Abdul Rafeh Naqash: Correct. I'm talking about NGS 600 gene panel because that's what gets done clinically every day, all day, when you're talking about patients with cancer. What are the few things that one should look out for?  Professor Heather Hampel: So there's some nice ESMO guidelines around this, and that's what we were using. Where I used to work, I would actually hand-review the tumor test that came in and kind of send an email to the docs when I said, "Hey, this may be germline. I think this patient needs a referral." Some of the labs are now calling those out themselves, which is nice. So if they're calling it out themselves, definitely pay attention to those boxes that say "Potential germline finding," and make sure you refer any patients with anything there. If you're using a lab that's not calling it out, certainly some of the rules—there's already guidelines - anyone with a BRCA1 or BRCA2 mutation found in their tumor should be referred, regardless of what kind of tumor they have. So that one's easy.  Some of the things I like to look at is what was the variant allele fraction. If it's around 50% or anything over 35%, you start thinking maybe that's germline, that's a nice red flag. Cautionary tales - every colon tumor has an APC mutation in it, so we don't want those referred to genetics. Most of them don't have familial adenomatous polyposis. So only send a patient with an APC mutation in their colon tumor if they– in the setting of polyposis. Same goes for TP53. You're going to find that in almost every tumor, and very few of them are going to have Li-Fraumeni Syndrome.  So in the ESMO guidelines, I believe in addition to having a TP53 and an APC around a VAF of over 35%, they want to see it in a young age tumor so that you have an indication that you might be dealing actually with Li-Fraumeni syndrome. The Lynch syndrome genes, I think the common genes, if you see a mutation in them, go ahead and refer. Consider the variant allele fraction and then beware of genes that are commonly mutated in all cancers because most of those won't be hereditary, and genetics can't handle seeing every single patient who has a TP53 mutation in their tumor. So we need to see an early age or some strong family history in those cases.  The other thing just to point out, because there are long waits and not everybody has a genetic counselor or geneticist on staff is COVID turned out to have a little silver lining for the genetics community, and that is cancer genetics transition very well to televideo medicine. And there are now multiple companies providing televideo medicine. And you can usually get your patient in within a day or two for a televideo genetic counseling appointment. And so, just be aware if you can't get them to an in-person clinic in a timely manner, there are many, many televideo companies now providing genetic counseling services remotely from the comfort of their own home within two days' notice, evening appointments, weekend appointments to make it convenient for the patient. I don't work for any of those companies, but I would say just that people should be aware that those options exist so that their patients don't have to have a long wait time. Dr. Edward Esplin: Just one quick thought along those lines. And in the context of the commentary that we talked about, I think there is a good rationale that if the patient that we're talking about with respect to receiving the tumor profiling NGS they're having any of those solid tumor types that we're discussing, it does make a lot of sense now to order that Germline genetic test at the same time that they're getting that tumor test. And doing that via what I've heard described in the literature is a mainstream approach where the clinical oncologist can be the person who is initiating both the tumor test and that germline genetic test. Get both those things cooking at the same time, such that when you're getting those results back, and in many cases, you'll probably get the germline results back sooner, then you don't have to ask those questions. And the referral to genetics can take place at the same time as well, potentially, where those results can then be discussed in detail. And I say that in part because testing all these patients with these tumor types that we've described and taking a more universal approach can make a lot of difference, for example, in patients having the information they need to actually prevent or mitigate the risk for a second primary cancer.  We did a retrospective here a little while ago where we looked at patients who had received germline testing as a reflex to the tumor testing they'd received already. And appropriately so, I think, these savvy clinicians doing exactly what Heather described and referring them for germline testing. The unfortunate thing we found is in about 10% of the individuals that had a positive finding in their germline genetic test that was done as a downstream effect from their tumor profiling test, they had had this done on the second cancer that they had developed. And the genetic result that they received in their germline test was consistent with their first cancer that they had developed. In fact, if they had the germline testing done with the first cancer that they had developed, they would have the opportunity to have had that second cancer either downstaged by screening or completely avoided in its entirety with that information being at hand. And of course, it's practically unconscionable that a patient who has successfully defeated cancer, beat it back into remission, would need to be at unknown increased risk of a second primary tumor simply for lack of getting germline genetic testing at the time when they were first diagnosed with cancer.  Professor Heather Hampel: And not to pile on, but I'm a big fan of paired tumor and germline testing as well. And I'll just mention a Memorial Sloan Kettering paper which showed that about 10% of the mutations found on germline testing had been missed on the tumor testing because they were large rearrangements or some other type of mutation that tumor testing is really not designed to detect. So you also can't feel reassured by a normal tumor test that there isn't a germline mutation because that's not the purpose of the test, and it doesn't find every type of mutation. And so I am also a big fan of paired testing when you can get it. I also think it gives you some potential for sorting out variants of uncertain significance because you can look for second hits, et cetera. So again, I think that's the future of cancer genetics. Dr. Abdul Rafeh Naqash: Absolutely. And I learned a lot from all the stuff that you guys mentioned. And one of the things that you just mentioned that was on my mind was VUSs or Variants of Undetermined Significance. And briefly, I wanted to touch on VUSs. If I have a BRCA1, BRCA2 VUS, what should I do?  Dr. Edward Esplin: Nothing. Absolutely nothing.  Dr. Abdul Rafeh Naqash: Should I refer to genetics or just wait and watch? Dr. Edward Esplin: Well, I'll speak with my Invitae hat on. The waiting and watching, like you describe, I think, is very relevant because Invitae and other labs are actively involved in interrogating these VUSs on a routine basis. We see thousands of patients every day, and we see these VUSs popping up, and we're combing the literature on an ongoing basis. We're depositing new variants into ClinVar all the time, and that is part of what we consider to be our responsibility to continuously review the evidence underlying these VUSs.  And in fact, in a paper published, I think it was in JCO Global Oncology here pretty recently, we noted that over the course of about, I think it was a five-year retrospective of patients who had undergone breast cancer testing, that we looked at how many of those individuals had a variant of uncertain significance, for example, in BRCA 1 and BRCA 2, and over that period of time how many of them got reclassified, and if so, what was the reclassification. There was some small fraction that over that time period got reclassified. I think I'm going to say it's in the order of like 10% or 20% and I'm saying that wrong. But more importantly, of all of the ones that got reclassified over that five-year period of time, 10% or less ended up being pathogenic or likely pathogenic. The vast majority of them ended up being benign or likely benign, which just underscores there's nothing that needs to be done for VUS when the evidence might ever accrue that would help to reclassify that. The vast majority of the time, it's going to end up downgrading it. That's not even the right term to use for a VUS. It's going to reclassify it as a benign or likely benign variant. And if it is something that should be actionable at some point in time, all of the reputable labs out there will notify clinicians of that change in status, and that is the time when action ought to be taken. Professor Heather Hampel: Yeah, I think that's one of the biggest cons people will have against offering germline testing to every patient is the high variant of uncertain significance rate and a fear that those patients will be mismanaged as positives, particularly in settings where there aren't genetics professionals on staff. And so I think that's a really important point. I remember when Mary-Claire King was with her Lasker Award recommending germline genetic testing for all breast cancer, all women actually, unaffected, to try and prevent breast cancer. She had suggested that in that setting, they maybe should not report variants out at all because of the risk of them being mismanaged, and I think it's an interesting idea. Most of the academic centers like to have them; sometimes, they like to work on getting some of them reclassified. But I think it's something we need to consider if we start doing testing at this large of a scale or just being sure that everybody knows that a variant of uncertain significance should be treated like a negative until proven otherwise. Dr. Edward Esplin: I'll pile on that just briefly to note that at ASHG American Society of Human Genetics just last year there was an entire session devoted to exactly that kind of topic, and it was broadly discussed, the potential opportunity to, for example, within a cancer gene multigene panel is that a panel where returning VUS is just not a useful thing to do, restricted to pathogenic, likely pathogenic. We do that on other panels already. We do that on panels for ostensibly healthy folks and other situations. So I think that is a very worthwhile approach to consider.  And at the same time, we've also seen in the literature, Heather brings up a concern that is broadly raised and repeatedly raised, we've seen evidence that clinicians are not acting inappropriately as much as they had done, perhaps in the past, that we're getting our house in order. Breast surgeons and other physicians are treating these things like the negative results that they, in reality, are, and so that in my opinion, the potential for increased VUS identification should not be an obstacle to folks getting clinically indicated testing because that's what's needed for them to have appropriate treatment and appropriate prevention. Dr. Abdul Rafeh Naqash: Absolutely. Well, this has been very engaging and very interesting, and hopefully, our listeners will feel the same. Thank you, both Heather and Ed, for joining us today and especially choosing JCO PO as one of the destinations for your very interesting commentary.  Thank you for listening to JCO Precision Oncology Conversations. If you like today's episode, please leave a rating and review. You can find all our shows, including this one, at asco.org/podcasts and continue to stay updated by following JCO PO on Twitter with the handle @jcopo_asco. All JCO PO articles and series can be found at ascopubs.org/journal/po. 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. Guest bios Prof. Heather Hampel, MS, is an Associate Editor of JCO Precision Oncology. She is the associate director in the Division of Clinical Cancer Genomics and is a professor in the Department of Medical Oncology and Therapeutics Research at the City of Hope National Medical Center. Dr. Edward D. Esplin, MD, PhD, FACMG, CGAF, FACP is board-certified in clinical genetics and internal medicine and completed his clinical fellowship training in medical genetics at Stanford University. He now works at Invitae. Guest disclosures (See also: Universal Germline Genetic Testing for Hereditary Cancer Syndromes in Patients with Solid Tumor Cancers) Heather Hampel Stock and Other Ownership Interests: Genome Medical, GI OnDemand Consulting or Advisory Role: InVitae, Genome Medical, Pomega, 23andMe, GI OnDemand, Natera   Edward D. Esplin Employment: Invitae Stock and Other Ownership Interests: Invitae Consulting or Advisory Role: Taproot Health Inc  

Dr. Shannon Westin and her guests, Dr. Paul Frankel, Dr. Judith Karp, and Dr. Robert Maki discuss how to better inform patients of the risks involved in phase 1 clinical trials. TRANSCRIPT Dr. Shannon Westin: Hello, everyone, and welcome to another episode of the Journal of Clinical Oncology After Hours podcast, where we do a deep dive on manuscripts that are published in the Journal of Clinical Oncology. We're so excited to have you all here today. I am your host, Shannon Westin, GYN Oncologist at MD Anderson Cancer Center, and it's my great pleasure to serve as the social media editor of the JCO and the host of this podcast. Today we are going to be discussing a very important manuscript titled “Ethics and Clinical Research: Improving Transparency and Informed Consent in Phase 1 Oncology Trials”. And I'm joined today by several of the authors, as well as one of our editors that helped to review this paper. But before I start, I'll note that none of our authors have any conflicts of interest to disclose. And with that, I'd like to introduce our guests. First is Dr. Paul Frankel. He's a research professor at the Division of Biostatistics, Department of Computational and Quantitative Medicine, at the City of Hope National Medical Center. Welcome. Dr. Paul Frankel: Hello and thank you. It's a great honor to be here today. Dr. Shannon Westin: Also with Dr. Frankel is Dr. Judith Karp, who is Professor Emerita of Oncology and Medicine at the Johns Hopkins University School of Medicine in Baltimore, Maryland. Welcome. Dr. Judith Karp: Thank you. And I echo exactly what Paul said. Thank you for having me. Dr. Shannon Westin: And then finally, our esteemed Associate Editor of the JCO, Dr. Robert Maki. He's a professor of hematology and medical oncology, a physician leader in developmental therapeutics, clinical leader of the Sarcoma program at the University of Pennsylvania. Dr. Robert Maki: Hi, Shannon. Thanks for having me on the program. Dr. Shannon Westin: Well, it's awesome to have this star-studded group of guests. We are going to try to cover as much details about this important paper as we can in a short period of time. But I encourage you also to check out the JCO to read the paper in full. So first, let's level set. As we start this discussion around phase 1 trials and ethics, maybe, Dr. Mackie, can you start by giving the basics of just phase 1 trials just to make sure everyone's on the same page? Dr. Robert Maki: Sure, absolutely. Since we have people who are listening from different walks of life, that's for sure. Clinical trials in cancer run anywhere from phase 1, 2 to 3. There are also such things as phase 0 and phase 4 trials. But the primary ones we'll discuss today are phase 1 trials. These are the initial tests, be there a brand-new drug never tested before in people, or it might be testing a new combination of treatments, or it might be looking at an already approved drug or an experimental drug in a new population of patients. Let's say you wanted to take a look at a drug in an elderly population. There aren't any data about that in people who are, let's say, 80 or older, and that would constitute a phase 1 trial. The idea of the trial is to start with low doses of a medication and increase the doses in a systematic way, tracking the side-effects that occur with treatment, and then come to an answer as to how you should move forward with the medication in future trials to determine whether the drug is actually active or not and in which setting. The important point, I guess, in that sense is that a phase 1 trial isn't necessarily looking at whether a drug is useful or not, really just looking at the toxicity of the agent or new combination or new setting overall. Dr. Judith Karp: If I could add one thing to that, and I think this is something that has evolved—well, it's evolved over the last 30 years, but in terms of practicality and application, it's really over the last 10 years, roughly speaking. It's also, I think, the opportunity to identify potentially informative biomarkers through a series of pharmacodynamic studies. I'm an old leukemia doctor, and so I've had that capability, if you will, with our diseases because they're so accessible. But I think there's been a new emphasis on that over the last decade. And it's an important one because it becomes a tool for stratifying in phase 2 and ultimately for identifying, hopefully, in a prognostic fashion, who is potentially likely to respond versus not. And if it's a versus not, then you go in a different direction once you got a bunch of—or if you're lucky enough to have a bunch of different directions. Dr. Robert Maki: It's a really important point about looking at so called pharmacokinetic and pharmodynamic markers. How long is the drug staying in the body? What is the body doing to the drug? What is the drug doing to the body? Judith is right on the mark. You can get leukemia cells right out of the body, oftentimes take a look at them directly, whether you're actually hitting the target you think you're hitting. This is a really great place to—and it's often mandatory to get pre- and post-treatment biopsies, even in solid tumor patients, to know if you're actually hitting your target of interest. So, yeah, if you're not achieving that much, then you shouldn't really be moving the drug forward. Dr. Shannon Westin: I agree. And it's so critical because, as we've seen, you know, to your point, Dr. Maki, about the true goals of a phase 1 trial, I think we've done a lot better job of trying to ensure there is efficacy or trying to clarify for whom we are getting efficacy. And I think we all are aware of several drugs that have gotten approvals from an extended so-called phase 1, right? An appropriately selected population. And certainly that's something new over the last five, six, seven years that we've been able to do that. But things like PARP inhibitors in BRCA-mutant populations and TRK fusion inhibitors like Larotrectinib and others in those with NTRK fusions just come to mind kind of quickly. And even more so, we're seeing these focus drugs, right, that are focused on abnormalities in a specific—Exon, like the G12C inhibitors and things like that. So it is interesting to see how drug development is kind of changing in the phase 1 space where we're trying to move that efficacy potentially up earlier and earlier, just to Dr. Karp's point about that biomarker development. So I think it's a really exciting time. Okay, so the next piece I wanted to just make sure, again, to ensure that we're all on the same page, is these are very common trials, I'd say, and certainly the foundation of drug development. Do one of you want to give an estimate of approximately how many phase 1 trials are ongoing currently and maybe how that's changed over time? Are we seeing more phase 1? Less phase 1? About the same? Dr. Paul Frankel: Yeah, I can take a look at that. The number of phase 1 studies that are currently accruing patients today in oncology is around 4500, something like that. I think there's 4451 open clinical trials and phase 1 clinical trials in oncology today. If you look at, let's say, in May of this year, there was 4263. So you're seeing it's increasing. But if you want to look at really the increase, you can look at between 2000 and 2010. There were a little bit over 5000 phase 1 clinical trials that had started in that period, that 10-year period. If you look at the next 10-year period, 2010 to 2020, it's over 10,000 that started. So the number of phase 1 clinical trials is very large, and it's increasing at a rapid rate. And these do set, as you mentioned, the foundation for all the studies that subsequently follow. Dr. Judith Karp: It's very interesting to me that Paul has these numbers in his head. I am not as quantitative as Paul, but we have these increasing numbers of trials, and yet the percentage of patients who go on those trials has not increased at the same rate. There's still that gap where now for children with leukemia—actually, for children with cancers, it's 90%. 90% of those children go on clinical trials. But for adults, it's still around 8 or 10%. It's unfortunate. Dr. Robert Maki: It's a really good point. There really should be more adults being put on clinical trials. But by the same token, not every adult is appropriate for a clinical trial. Let's say you have—there are things you can do that are clinical trials that aren't treatment either. And if it's data collection or patient-reported outcomes, something that we really don't have a lot of information of in a broad manner, there certainly are clinical trials, even if you're getting standards of care in which patients can be enrolled. So you're certainly speaking to a group of people who espouse and promote clinical research wherever it can be done. Dr. Paul Frankel: These clinical trials, I think, are often the best opportunity that patients have. And even though we're going to be talking about issues with consent and other issues with regard to phase 1 clinical trials, they still remain the best option for patients in almost every situation, if you can get on them. Dr. Judith Karp: Yeah. I just think of them as… Dr. Shannon Westin: Yeah, and I think we could have a whole ‘nother podcast of how to expand an exclusion criteria to allow for those patients, but maybe we'll bookmark that for another episode. Paul, you kind of started mentioning, I think, the last place to level set before we get into a little bit more detail from the paper that you all wrote is from regards to informed consent. Can one of you, or more than one, review the importance and challenges of this process for our listeners? Dr. Judith Karp: I'll take a stab at that one. I think the importance of informing a patient, however well we can do it, of what we expect to happen and what we know and what we know we don't know is a very important part of the contract between the physician and the patient. And it's really a partnership, especially for phase 1 trials, where we really know so little. And what we do know is that the patient—these are for treatment trials. We know that there is no therapy widely available for that patient that's going to do that patient any good. So we have to enter into a partnership with the patient to say, “We're going to try something. We know this little bit. We don't know this huge amount.” And so I think that that's really the importance, just ethically, to have the patient be informed. In terms of the challenges, I think that—this is certainly not politically correct, but were I on the receiving end, on the patient end, and somebody gave me a 35-page document to read, I would not for many reasons. In some ways, it's too much information. Most patients are not, by definition, medically sophisticated. That's one. Two, they don't want to read 30 pages. They're either going to sign it, or they're not. And it's confusing. And, yes, you can say to a patient, “Look, take this home, read it, come back in a week, call me in a week,” whatever. There are many instances, certainly in the leukemia field, where you can't do that. You don't have that luxury. So I think that that is a real challenge that we really haven't addressed. And in the good ol' days when all of us physicians really sat down and talked to the patient, then I think that the challenges were much less. And I think that that's key. Dr. Robert Maki: Yeah. I mean, Judith, AML over age 65. You're not going to get most people into remission, and you've got a captive audience because there they are with low counts. And what are you going to do next? We all, in our research, want to follow the Belmont report. We want to respect people. We're looking for studies that offer beneficence, that do no harm. We can't really do no harm a lot of the time, but we can at least minimize harm. And I think it's where the consent process kicks in. And justice, the third tenet of the Belmont report, being sure that we're using well-considered procedures as part of the research. All those are part of those beautiful words that you used, “partnership” and “contract,” that I think are really important in developing that bond with the individual patient who you're going to treat is super critical. Dr. Judith Karp: Yeah, absolutely. And in some senses, the only real informed consent is if the patient has been through it before. Dr. Shannon Westin: Right. Dr. Paul Frankel: So one of the things making it even more challenging, all these challenges exist throughout. And one of the focuses of our paper is that there's been an increasing trend to use designs that specifically target toxicity rather than limit toxicity during the dose finding of the phase 1 study. And so that introduces a whole ‘nother aspect to the consent process. So if you look at those studies, the most common toxicity target, as noted by others, is a 25% DLT rate. And if interpreted directly, that means that these risk-targeting designs, they claim to aim to find the dose where one in four patients are expected to experience a severe or a life-threatening adverse event in the first cycle of therapy, which is usually 28 days. And that's despite dose modifications. And further, most of these designs consider it a positive feature if a large percent of the enrolled patients are treated near the target. Now, whether this is really what the physicians want or not is separate. But one way or the other, what we have noted in our paper is that our collective experience that the actual toxicity target, the targeted risk, whether it's 20%, 25%, or even 33%, is not disclosed to the patient in the initially submitted consent forms that we see. That is a fundamental change in the way we've designed studies, but it requires that we adapt the consent process to this very challenging problem. Dr. Judith Karp: Along those lines, you're talking about toxicity. Any treatment that targets a non-itchy skin rash has got to be a lot less toxic than a drug that is targeting refractory ovarian cancer or leukemia or what have you. And the disease itself is toxic. So I think there has to be a way to approximate and weigh those toxicities, the toxicity of the treatment versus the toxicity of the disease, because the disease is not benign. Dr. Shannon Westin: One of my mentors, Dr. Razelle Kurzrock, used to always say, “The worst toxicity is progression of cancer.” And I completely—that's a very wise woman. But I think it's a really good point. And I think, just to kind of summarize what you all were saying, if we're targeting a certain toxicity level, we just need to make sure that patients are aware of that. And many of them might be willing and would probably be willing to take that for that potential benefit and things they might get out of it, but we need to be more transparent on that kind of individual protocol level. Would you say that's…? Dr. Paul Frankel: That's the critical thing is to be transparent about these things. And certainly certain different treatments which have maybe more curative potential, certain types of diseases, they're going to be more amenable to a higher toxicity threshold. But it depends on the intent of the therapy, and these need to factor into the decision of what's being used, what kind of target and kind of design is being used. That's kind of part of the issue of transparency is once you get that in front of the patient and the physician and they discuss it, you're likely to get people to agree if it's at least a reasonable target. Dr. Robert Maki: The toxicity targets up from some of these Bayesian designs, oftentimes they're kind of guardrails to ensure there's not too little or too much toxicity on a trial. I think people are using more of the rules-based designs, this risk-targeting design, than the classic three plus three simply from the inability to come up with an adequate dose-escalation scheme using three plus three simply from the fact that you're just looking at the prior three patients. If you look at a lot of the kinase inhibitors that have been approved over time, even when they're FDA approved, drugs like lenvatinib or cabozantinib, even in the phase 3 trials, patients had to have their dose reduced two times out of three. And it really speaks to something went awry in the development of these agents if they really were looking for a 16% DLT rate in a classical sense, which is what you get from that three-plus-three design, one out of six people. It's pretty crazy that two thirds of people in a larger population need that dose reduction. So perhaps by putting better guardrails with one of these rule-based designs, we'll actually end up with a schema for treatment of a patient that ends up being more appropriate. Dr. Judith Karp: It would be very interesting, actually, to examine how often we're wrong. It might be very easy. 100% of the time, I would imagine. But how often the so-called RP2D turns out not to be that. And even with phase 3 trials, you never really know a drug until it's out on the street and thousands and thousands and thousands have been treated with that drug or combination. Paul, maybe that's our next study. What do you think? Nah, I can tell you don't like it. Dr. Shannon Westin: This is kind of getting at what Project Optimus is trying to do, right, is getting away from that idea that we have to get to the max dose and instead look at long-term tolerability. And yeah, Robert, I've given quite a bit of lenvatinib and pembrolizumab in my clinic to patients with recurrent endometrial cancer. You can see that that max dose is not the ideal dose for a lot of patients. Now, there are some patients that tolerate just fine, but 70% grade 3/4 toxicity is legitimate, and making sure we're protecting patients from that is really critical. And I want to cover a few more things before we wrap up. I guess we've talked a little bit about what to do on an individual protocol level. Do you all have some recommendations about what can be done at the research/enterprise level to kind of address the issues that we've been discussing today? Dr. Paul Frankel: One of the issues is, if you look at, let's say, clinicaltrials.gov, you'll see that there's very few studies that have both a model consent form or the protocol on clinicaltrials.gov. And I think if you look at all the clinical trials, the number that have both, you can count on one hand. So the question is whether or not there's a way to systematically evaluate whether the consent form is appropriate, whether the target is reasonable, that kind of thing. And it's very hard to do when you don't have a way to assess that information in a systematic way. So one thing that can happen is that the registries could require a model consent form where they could ask for it, encourage it, one way or the other. It's just a simple document. The other thing that they can do is make sure that the protocol summaries, if the design uses a DLT targeting method to at least state what the target is in the protocol summary, that would help quite a bit. And then you can go through and see if this is reasonable or if this has been communicated in the consent form in particular. And so that's one thing that can happen on the enterprise level that would help considerably. Dr. Judith Karp: The only thing I would add to that is that I think a model consent form, a template, is it's surprising that it hasn't been done yet, although, as you say, it's not easy with all of these studies being done by government and pharma and other enterprises. But that has to be modulated for the disease that's being targeted and for the drug. You can't have the same thing for cell cycle cytotoxic agents and immunotherapy because they're totally disparate. And you can't have the same thing for leukemia and breast cancer. The pathogenesis may be the same, but the phenotyping is not. So that's the only thing I would add. Dr. Robert Maki: The patient population involved as well can certainly impact that. Greater or poorer performance status, susceptibility to complications, all that figures into that consent form. So it's not an easy thing to prepare, at least in a coherent way that a patient is going to understand, especially, as you were saying there, with a 40-page tome that reads at somewhere between grade levels 11 and 14. How do you expect a patient with, let's say, an 8th or 9th grade reading level to fight their way through that if they really wanted to understand the side-effects. It's kind of like the teacher in the Charlie Brown cartoons: “Wah wah wah wah, wah, wah, wah, sign here.” So there are many challenges. Dr. Paul Frankel: There's no question that this is a minimum requirement. Having a written consent form is just an absolute minimum. But the conversation that needs to take place, the communication, that's a whole ‘nother level that I think the physicians are better able to address. But it's just the minimum requirement to have something in the document, and it doesn't make the document longer to communicate the targeted risk in some of these studies. There's really no extra effort that's being asked. I mean, the model consents exists. The DLT targeting is stated in the protocol. It's all fairly simple. Dr. Robert Maki: Yeah, it'd be another line or two, wouldn't it? It's just saying here's what our expected rate of toxicity is. And uploading, whether you're a cooperative group, whether you're an industry, whether it's an investigator-initiated trial, some sort of redacted consent form makes a lot of sense. You may not have to have the grid of activities, which oftentimes is now included in one of these cumbersome documents, but at least the description of the treatment and the toxicity would be at least something everybody could agree to. Dr. Judith Karp: Yeah, some kind of a precede or a FAQs, frequently asked questions. What is this? Why are we doing this? Very simple. Dr. Robert Maki: And that's now mandated, I think. They said at NCI, they insist that we have a summary of the trial, and one page or page and a half at the beginning of that long document. That, to me, has been incredibly effective, as have been things like a little drawing of patient and going one randomization and things like that. Simple means can really be powerful, especially on those first two pages before the eyes glaze over. Dr. Judith Karp: Exactly, yeah, a little CONSORT diagram or something like that, very nice, schema. Dr. Shannon Westin: This has been a really awesome discussion, and I think the bottom line is we need to increase our transparency. And it seems—I don't know, after this discussion, I feel like it's a pretty straightforward ask. Are there any downsides to being transparent? I know we've already talked a little bit about patient burden and how we don't think that would add much to that piece. Dr. Judith Karp: The fear that might exist, that, “Oh, my God, if we really tell them what we're going to do, they're not going to do it. They're going to say no.” I don't think that's realistic. I think patients, especially for phase 1, we're dealing with a population of people for whom there is not a reliable, effective therapy available. These patients know that. Many times they've been through rounds and rounds of chemotherapy or immunotherapy or surgery already. So many patients say, “Just give it to me, and I'll sign it.” And you say, “No, no, no, you must read it.” So they say, “Okay, I'll read it. Where do I sign?” Dr. Robert Maki: Done. Exactly. But it's a really important point that I'd also like to highlight, that phase 1 trials aren't just for the patients with performance status 3, very sick. You can certainly impose those earlier in a patient's course, especially in situations where there is not a randomized trial, for example, showing evidence of survival benefit. Short of that, I tend to be more aggressive about putting patients in earlier lines on phase 1 trials simply because it provides more options for them. Dr. Judith Karp: Yes, and I think a good example, as you had brought up, Robert, earlier, the older patient with AML, maybe a myelodysplasia-related AML. There are lots of things you can do, but none of them work. And so is it an opportunity to look at improving the hypomethylating agents where you get a 25% response rate, not much in terms of complete remission, and a year survival, maybe a year and a half survival. Can you improve on that if you add a drug that interrupts the survival pathway targeting BCL? Can you do that? The answer has been yes, but the only way to get there is to do the phase 1 trial initially and then move up the trial schema. Dr. Robert Maki: To your question, Shannon, though, the administrative burden is a small one. It's uploading a document, adding a little bit more to a consent form. It should not be a deal breaker, I would think. Dr. Paul Frankel: There's plenty of burdens on the research team. We certainly don't want to increase that at all, and I don't think this does. One of the questions you mentioned are the downsides of transparency, but some of the upsides also: by having the physicians have more discussion with the patient on some of these issues in a more transparent and lay language, I think, increases the understanding between the physician and the patient. And the physician can take that back to the statistician who's designing the study with the physician and say, “Hey, maybe we need to reconsider this.” There's some upsides in a variety of ways. Transparency and discussion are only going to be improving the ultimate product. And we certainly don't want to find drug doses that end up being a program drug death or unnecessarily hurting patients. Either one are totally unnecessary and unacceptable. Dr. Shannon Westin: Well, great. I think you've made a very clear call to action. I think the last question is how do we get this done besides raising awareness and just kind of setting the bar, right? Because I know, coming from my standpoint as a clinical trialist, it's not something we think to put into the informed consent as we've transitioned to this more risk-targeting type of trial, which I think, as you mentioned, is becoming much more common and over, like, the three plus three and things like that. How do we implement this? Too big of a question? You're like, “You tell me.” Dr. Judith Karp: We, as physicians, have removed ourselves from patients in so many ways. And how do you get it done? You sit down with the patient. And listen, I'm no saint, and none of us are saints, and we all have other things that we have to do, and there are—you know, we're pressed for time and this and that the other. But much of this, yes, full transparency, you have a 20%, a 25% chance of having a dire consequence. That doesn't mean that you will. If you do, it's 100% in you, right? But there's got to be a communication part that goes with it. That's personal. You can't just do it on paper. You need to do it on paper, but you gotta do it with people, too. Dr. Robert Maki: And the discussion point around potential toxicity, all of the visits, extra visits you might have to make, what extra work you might have to go through, versus, let's say, supportive care only if you are at that point. That is an incredibly important point to make to patients, that you really have exhausted many therapies. Is it best just to go with supportive care for whatever time is left? Because this certainly is rolling the dice. You're going to have some side-effects. And what's the chance of benefit in a phase 1 trial? I think that it's higher now these days, simply from the ability of immunotherapy to intervene on so many different diseases. For example, our success rate is higher than the 5% that's quoted previously, but it's not a home run in any case. And we don't want to take away hope, but we also don't want to give false hope. And I think with Paul's paper and your paper have really pointed out how important it is to have that discussion around the degree of toxicity you might have to expect. Dr. Judith Karp: Absolutely. Absolutely. Dr. Shannon Westin: Well, great. I just want to thank you all for such a lively discussion. I learned a ton, and I hope that our listeners did, too. I do want to remind our listeners to check out this paper, “Ethics and Clinical Research: Improving Transparency and Informed Consent in Phase 1 Oncology Trials,” published in the JCO. And also check out other episodes of the JCO After Hours podcast to learn more. So thank you all again and have a wonderful day. 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.  

Charles Brenner, PhD is the Alfred E Mann Family Foundation Chair in Diabetes and Cancer Metabolism at City of Hope National Medical Center. In 2004, Brenner, then a faculty member at Dartmouth College, discovered nicotinamide riboside (NR) to be a vital precursor of nicotinamide adenine dinucleotide (NAD+), which is made available by nicotinamide riboside kinases (Nrks) that are conserved between yeast and humans. In 2007, Dr. Brenner's lab discovered a second pathway by which NR is converted to NAD+ and showed that NR can extend the lifespan of yeast cells by virtue of elevating NAD+ levels and increasing the activity of the NAD+-dependent Sir2 enzyme.   In the past decade, Dr. Brenner has made multiple seminal contributions to NAD+ metabolism, which include engineering a yeast strain to convert inexpensive NAD+ precursor vitamins into NR, solving the crystal structure of human Nrk1, developing the methods for quantitative NAD+ metabolomics, and demonstrating the activity of oral NR in animal models of fatty liver disease; obesity; type 2 diabetes; diabetic and chemotherapeutic neuropathy; heart failure; and central brain injury. Dr. Brenner also led the first clinical trial of NR, which established safe oral availability in humans. He is currently focusing on the maternal and neonatal effects of oral NR and translating animal discoveries into evidence-based safe, human clinical practice for human conditions of metabolic stress.

Meet Charles Brenner, the Longevity Skeptic. Brenner, a leading biochemist at City of Hope National Medical Center in L.A., has been attending the largest longevity conferences with one main purpose: to point out that some of the other speakers are full of it.Brenner is "throwing cold water" on several scientists in the field of aging, accusing them of hyping various fountains of youth, despite limited evidence for these therapies.In this podcast episode, Brenner sat down with Leaps.org to discuss his groundbreaking work on metabolism and his efforts to counter what he considers to be bad science.In addition to bringing his candor to conferences, Brenner is applying it in academic journals, publishing a paper in September, "A Science-Based Review of the World's Best-Selling Book on Aging," in which he pans the author of this bestseller, David Sinclair, a Harvard biologist, for talking up the potential for humans to live far past 100. These aspirations may sound nice, but they're not backed by science, Brenner says. He's had high-profile debates online with Sinclair and Aubrey de Grey, a prominent biomedical gerontologist.Meanwhile, in his own lab work, Brenner is credited with identifying a vitamin precursor called NR that seems to enable repair of cellular damage that happens as we get older - a major discovery that he's helped turn into a supplement, commercialized with a company called ChromaDex.Whether it's possible to extend human lifespan is a pressing question as investments in longevity startups are projected to increase from $40 billion to $600 billion over the next three years. Brenner is an intriguing figure in these debates. Although he's been introduced in public appearances as a longevity skeptic, he calls himself an optimist.Links:Charles Brenner, City of HopeCharles Brenner LabCharles Brenner on TwitterCharles Brenner's debate with Aubrey de GreyBrenner's paper, "A Science-Based Review of the World's Best-Selling Book on Aging"Leaps.org is a not-for-profit initiative that publishes award-winning journalism, popularizes scientific progress on social media, and hosts events about bioethics and the future of humanity. Visit the platform at www.leaps.org. Podcast host Matt Fuchs is editor-in-chief of Leaps.org.

Dr. Lorna Rodriguez-Rodriguez is a gynecologic oncology surgeon and Vice Chair of Faculty Development in the Department of Surgery at City of Hope National Medical Center, where she also serves as part of the Enterprise Leadership Team. She is a Professor in the Division of Gynecologic Oncology. Her research focuses on finding a cure for ovarian cancer and understanding the importance of racial and ethnic differences in clinical outcomes. She has served as a clinician, instructor, and researcher at several of America's leading medical institutions over the past 30 years. Most of all, she is a surgeon that wants to cure women's cancer by removing it when possible. She is a frequent speaker for conferences related to health and wellness, diversity in healthcare, and cancer research, and she has mentored many postdoctoral fellows over the years. She holds a Ph.D. in Bio-Chemistry and Molecular Biology and completed her Gynecologic Oncology Fellowship at the University of Michigan Medical School. She earned her medical degree from the University of Puerto Rico Medical School. --- Send in a voice message: https://anchor.fm/urcaringdocs/message

Endocrine-disrupting chemicals are pretty much everywhere, and all of us have some level of exposure. Today we will talk about research presented at ENDO 2022 on a group of EDCs called parabens. The title of that abstract is “Parabens Promote Pro-Tumorigenic Effects in Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry.” Host Aaron Lohr talks with one of the authors of that study, Lindsey Treviño, PhD, assistant professor at City of Hope National Medical Center. They talk not just about the effects of parabens as an EDC, but also about racial and ethnic disparities in risk and mortality, as well as research, and how Dr. Treviño and colleagues address these disparities. For more information, including helpful links and other episodes, visit our website at https://www.endocrine.org/podcast.

Endocrine-disrupting chemicals are pretty much everywhere, and all of us have some level of exposure. Today we will talk about research presented at ENDO 2022 on a group of EDCs called parabens. The title of that abstract is “Parabens Promote Pro-Tumorigenic Effects in Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry.” Host Aaron Lohr talks with one of the authors of that study, Lindsey Treviño, PhD, assistant professor at City of Hope National Medical Center. They talk not just about the effects of parabens as an EDC, but also about racial and ethnic disparities in risk and mortality, as well as research, and how Dr. Treviño and colleagues address these disparities. Show notes are available at https://www.endocrine.org/podcast/enp62-parabens-as-an-edc-and-addressing-disparities-in-risk-and-research — for more information, including helpful links and other episodes, visit our website at https://www.endocrine.org/podcast

Endocrine-disrupting chemicals are pretty much everywhere, and all of us have some level of exposure. Today we will talk about research presented at ENDO 2022 on a group of EDCs called parabens. The title of that abstract is “Parabens Promote Pro-Tumorigenic Effects in Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry.” Host Aaron Lohr talks with one of the authors of that study, Lindsey Treviño, PhD, assistant professor at City of Hope National Medical Center. They talk not just about the effects of parabens as an EDC, but also about racial and ethnic disparities in risk and mortality, as well as research, and how Dr. Treviño and colleagues address these disparities. Show notes are available at https://www.endocrine.org/podcast/enp62-parabens-as-an-edc-and-addressing-disparities-in-risk-and-research — for more information, including helpful links and other episodes, visit our website at https://www.endocrine.org/podcast

Dr. Shannon Westin discusses germline genetic testing in gastrointestinal cancer with Heather Hampel and Dr. Matthew B. Yurgelun.   TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours. This is our podcast where we get down in the nitty-gritty of articles that are published in the Journal of Clinical Oncology. I am your fearless leader and host, Shannon Westin, the Social Media Editor of the Journal of Clinical Oncology, as well as Professor of Gynecologic Oncology at The University of Texas, MD Anderson Cancer Center. And I am very excited to bring two guests in today to discuss a review article that was published in a special series on, 'Precision Medicine and Immunotherapy in GI Malignancies,' back in June of 2022, and this is, 'Point/Counterpoint: Is It Time for Universal Germline Genetic Testing for All GI Cancers?' And please note that our participants have noted no Conflict of Interest. So, without further ado, let me welcome our guests. First is Heather Hampel. She is a Cancer Genetic Counselor, and the Associate Director in the Division of Clinical Cancer Genomics, and a professor in the Department of Medical Oncology and Therapeutics Research at the City of Hope National Medical Center. Welcome, Heather. Heather Hampel: Thanks so much for having me. Shannon Westin: We're also accompanied by Dr. Matthew Yurgelun, he is a Senior Physician in Medical Oncology at the Dana-Farber Cancer Institute, the Director of the Lynch Syndrome Center, and Assistant Professor of Medicine at Harvard Medical School. Welcome. Dr. Matthew Yurgelun: Thanks for having me. Shannon Westin: And we have all decided we were going by first names. So, audience, don't be alarmed. Okay, let's get right into it. So, this is a really great review. I learned a ton and I think, you know, just to kind of get back to basics, I think we've been seeing an increase in the use of germline genetic testing across a number of different cancer types. As I mentioned, I'm a gynecologic oncologist, certainly this is something we're doing for patients with ovarian cancer. What are the reasons this has become so widespread across all cancer types? Heather Hampel: Matt and I probably agree on this one. I will, but I'll say you a couple of reasons, and see if Matt has any to add. I think that 2013 marked a major turning point in the field of cancer genetics for a couple of reasons. One was; the advent of next-generation sequencing, so that we could do multiple genes at the same time for a lower cost. The other was that that was the year the Supreme Court struck down the patent on BRCA1 and BRCA2, which allowed lots of different competitors into the market to offer sort of these pan-cancer panels, including, BRCA1 and BRCA2, among other genes. And the price has dropped precipitously since then, giving better access for patients. The competition, I think, has been good, so that a lot of the laboratories now will offer out-of-pocket maximums of $250. And then, we've seen a lot of research. Because of that, I think, where we've just done pan-cancer panels on different solid tumor cancers, just to determine what the prevalence of mutations is, all of this is sort of leading to, I think, just greater use of germline genetic testing across the board. I don't know. Matt, what do you think? Dr. Matthew Yurgelun: No, I fully agree. This is an example of the more you look, the more you find, and I think we've seen that both in the studies that have been done looking at multi-gene panel testing in virtually any setting across different cancer types and then I think people who use these in clinical practice, whether they are genetic counselors, oncologists, gastroenterologists, gynecologists, primary care physicians, I think as people have become more experienced and more comfortable using them in routine practice—I think it's not an uncommon phenomenon for those of us who use these to find things that were somewhat unexpected, which kind of naturally leads to the question, "Well, what else might I be missing if I'm not doing these tests further and wider?" What's made it a little bit difficult is that this is an example of testing that's become available commercially before we really understood how to use it. And so, we've been figuring a lot of this out kind of on the fly a little bit. Shannon Westin: Yeah. I think it brings up, and not to get too nitty-gritty right from the beginning, but to me, it brings up the whole idea around variance of uncertain significance, right? I think we've really struggled with this on the GYN space, and I don't know how common that is for you all in the colorectal space, but we get answers, we don't know how to tell a patient what to do with that information. And in fact, we've personally seen people get risk-reducing surgeries, probably not appropriately in response to these variants. Dr. Matthew Yurgelun: It's a real phenomenon, and it's the other side of the more you look, the more you find. You know, you end up finding a lot of these variants of uncertain significance. I think we've become a lot more comfortable and maybe even cavalier about them as panel testing has become so widespread. But there are data out there, and not to mention just anecdotes of people who are potentially being harmed by these variants of uncertain significance, as you said, whether it's through unnecessary surgery, whether it's even just psychological burdens and harms that come from the angst of those uncertainties. So, it is important that we be thoughtful about just how to use this technology. Heather Hampel: And really it is, "the more you look, the more you'll find." So, on a panel of about 50 genes, there's about a 30% rate of finding a variant of uncertain significance, increase that panel to 80 genes, you're up to probably a 40 to 50% chance of finding a variant of uncertain significance. A panel of 150 genes, maybe an 80% chance of finding a variant of uncertain significance, and it becomes almost the rule and not the exception. So, this is where genetic counseling becomes really important in terms of having people understand that these are sort of common, and usually, not anything, and setting expectations so that people don't over screen, or overreact, or get in a situation where they're mismanaged. And this is one of the things that Matt and I go back and forth a lot about when you start to think about testing all-comers because if you're testing all-comers, you kind of have to give up pre-test genetic counseling and kind of move to a post-test genetic counseling scenario more for the positives, or people with a strong family history or concerns. And I know Matt worries, and I do too, that that's where we've risked these variants of uncertain significance getting mismanaged, particularly in centers that aren't as used to dealing with cancer genetics. Dr. Matthew Yurgelun: I would just add one more concept on that. We're probably also, in the case of some of these larger panels, dealing even with genes of uncertain significance. At the end of the day, it's the commercial laboratories in many cases that are really setting the agenda on some of these panels as far as choosing which genes to include or not to include, and a lot of these genes are genes where the link to cancer risk is sometimes very preliminary. Shannon Westin: Those are some great points. I think just to kind of take a step back, since the paper's in GI cancers, and I want to make sure we have—we have a mixed audience out there, so I want to make sure we level set. So, can you tell us the current standard of practice for germline testing in GI cancers? What are you looking for specifically? What are some of the things that you know are of certain significance? Heather Hampel: Currently, the NCCN guidelines recommend that all pancreatic cancer patients be offered germline genetic testing. And what is very new in 2022 is that there's now a consideration recommendation that you could consider offering germline genetic testing to all colorectal cancer patients. That is logistically much more challenging than offering germline genetic testing to pancreatic cancer patients because there are so many more of them. And it comes with a page of caveats of things that you need to think about before you would consider offering testing to all colorectal cancer patients. And then, I'd say among the rest of the GI cancers, you're going to be offering testing in cases of early onset, multiple primaries, maybe three affected's on the same side of the family with cancers that could go together in a family, and raise a red flag that there could be hereditary, diffuse gastric cancer comes to mind when you think of the stomach, certainly, polyposis is an indication for testing as well. But for most of the GI organs, you're going to need early age, multiple primaries or some family history. The one clear exception being pancreas, and now, a lot of debate about colorectal. Dr. Matthew Yurgelun: And I would just add to that from some of Heather's own seminal work. Tumor testing is often used to drive a lot of this in day-to-day practice. Certainly, the presence of microsatellite instability, and/or mismatch repair deficiency. This isn't limited to GI cancers, obviously, but it is where we often think about it the most. But any finding of mismatch repair deficiency in microsatellite instability should really strongly trigger strong consideration for germline testing, at least for Lynch syndrome, which is often, at least a way in the door for germline testing a bit further and wider. Shannon Westin: Yeah, that's kind of what we've done in endometrial cancer, and it's definitely a less expensive way of kind of getting at that, and we use those same Amsterdam criteria for the full germline outside of that. But that's really how we've gotten to universal testing for endometrial is using the less expensive protein testing, you know, as a trigger to break down the door. Heather Hampel: But it's not necessarily less expensive anymore. So, that's where things are getting a little challenging. You know, at most hospitals, if you're going to do four immunohistochemistry stains, you're going to take whatever they charge for IHC times four, then you're going to have a reading fee for the pathologist times four, and believe it or not, that adds up pretty quickly, and can become a test that's $1,500+, compared to potentially a $250 germline panel. I find it an odd situation for me to be in, who I've spent 20 years of my career advocating for universal tumor screening for Lynch syndrome. But I do feel that we really need to relook at the cost-effectiveness analysis now that the cost of germline genetic testing has gotten so low, and we need to think about what we're missing with universal tumor screening. So, yes, it will detect most of the cases of Lynch syndrome, and it should detect anyone who could benefit from immune checkpoint blockade therapy. And those are very important points, and I think that's the reason we're never going to go away from tumor screening. But it's not going to detect mutations in any other cancer susceptibility gene. And that's what you risk missing if that's your only approach. Shannon Westin: Those are some great points. Again, bringing those of us that aren't GI experts, up to speed, what's the overall incidence of these germline genetic abnormalities in GI cancers? What are we looking for? Dr. Matthew Yurgelun: I think it depends on which cancer you look at, and it also depends a little bit on even just how you define the prevalence here. Where it's been a little bit difficult, or where it's been kind of moving goal posts is that the panels that we're using in day-to-day practice are getting bigger and bigger, and certainly, the panels that are being used in a lot of the studies that are examining this are getting larger and larger. And as far as the number of genes being tested-- and not surprisingly, as you test more genes, you find more stuff. We make a point in the paper that some of the older studies, these are all still relatively new studies, but some of the older studies that have looked at gene panels of say, 30 genes or fewer, you actually find germline prevalence rates that are maybe 10% or lower across most of the GI tract malignancies. But as you start getting into panels that are 50 genes, 60 genes, 100+ genes, that's when you start getting these prevalence rates that are 15%, 20%, almost across the board. But the prevalence is only part of the story, in my opinion, it's a matter of what you're finding, in addition to how many people you're finding stuff in. Because you know, finding a diagnosis of Lynch syndrome, finding a BRCA1 or BRCA2 abnormality, things that are high penetrance, clearly actionable that we understand reasonably well, I would argue is much more impactful than finding something like a monoallelic MUTYH pathogenic germline variant, which arguably has very little clinical significance for the person themselves, and is honestly, much more common than some of these other things too, and drives up some of these prevalence rates. Heather Hampel: I agree, Matt, completely. And I struggle myself, sometimes, with how people should report out the incidence of mutations in series like this because when you include those MUTYH heterozygotes, you include your APCI 1307Ks, you're padding the numbers, but are you finding something that's going to really make a major management change for that family? I don't know. The one thing though that has stuck with me as I look at this is that it appears that people who meet the criteria for testing aren't much more likely to test positive than people who don't meet criteria for testing. And as a genetic counselor who, you know, loves to take family histories, and for years, liked to believe that if I took a good family history, and assessed it, I could pick who was going to test positive appropriately, it's been a little bit of a dash to the confidence to see rates of positivity that are pretty similar in the patients who don't meet criteria. And I think that's been a challenge for all of us. So, if we could pick these cases well, it would be one thing, but I don't think we can all the time, outside of Lynch syndrome. Lynch syndrome, I think we can pick, to a large degree, through tumor testing more than family history. But the non-lynch genes are much harder to predict based on age of diagnosis, family history, or any other clinical criteria. Dr. Matthew Yurgelun: I totally agree, and for me, that's what moved the needle a handful of years ago with pancreatic cancer in particular, in my own mind, is that it was becoming quite clear that you could find some of these with clinical criteria or even just clinical intuition, but there were a lot that were just being missed. We were looking at age of diagnosis, we were looking at family histories of BRCA-related cancers, and family structures being what they are, in many cases, you know, the fact that pancreatic cancer, even in the setting of some of these germline variants is often diagnosed well after age 50, and often after age 60, or even after age 70, you know, our usual clinical criteria just weren't working. Shannon Westin: I think you kind of already started touching on this, but I'd love to get a little bit more, you know, what would be the additional benefits to doing this universal testing? I think one of the things you just mentioned, like, not being able to completely pick the right people to test. I mean, this is exactly why we started doing this in ovarian cancer is because, more than half of the women that were testing positive BRCA, did not meet the age criteria, they had no family history to note, you know. So, we were missing tons of people. What are the other things we can gain from universal testing? Heather Hampel: I think that's a key one. I think another one that Matt and I agree on is that from that proband there, are all those at-risk family members who get to benefit because of the cascade testing that begins from that first person who gets diagnosed in the family. And those are often unaffected at-risk people who you can really keep from getting cancer in the first place, and make a major impact in their health outcomes. So, not wanting to miss a potential hereditary family, and that ability to get to those at-risk family members, I think is a major benefit. I think the one that hasn't really panned out yet in GI, and I'll leave this to the oncologists in the room, is a change in treatment. But I think it's coming. I hope it's coming; we'll see what research all you oncologists can do. But I think that what moved the needle on ovarian and pancreatic was the fact that we had mutations in the homologous repair deficiency pathway, leading to a change in treatment, and the use of PARP inhibitors that just hasn't born out in GI cancers yet, outside of pancreas. And the one thing that you do see a treatment change for is mismatch repair deficiency, which you can find by doing IHC for the mismatch repair proteins or MSI testing, so, you don't really need the germline panel. In fact, some people with Lynch syndrome don't have an MSI-high tumor, and won't benefit from immune checkpoint blockade therapy. And so, I feel like that's the one benefit that maybe hasn't been fully realized in GI cancer, but I hope it will one day. I don't know. Matt? Dr. Matthew Yurgelun: No, I agree. I think the therapeutic actionability has been one that we've been hoping for more than what we've actually seen in real-world practice, the big exception being PARP inhibitors for pancreatic cancer. But even there, I think so far, the benefits have been maybe a bit more modest than people would've originally hoped for. I agree, I think the therapeutic benefits are ones that we're still trying to work towards. Shannon Westin: Yeah, and you kind of got around this before, and I think this is what we're experiencing in some of the gynecologic malignancies is like, not every gene is created equally. You know, we originally thought, "Oh, any homologous or combination gene will do. We could do PARP for all," and then realized, "Actually, no, it's probably just BRCA, maybe PALB2, RAD51." So, I think it's exactly like what we're seeing in honestly, frankly, across precision medicine, right? Where it's like, not every PI-3-kinase mutation will lead to benefit from a PI-3-kinase inhibitor. So, I think the science got ahead of us, or we got ahead of this science, and so, I do think that that's where the struggle is. Because I think once you've got therapeutic actionability, it becomes a no-brainer. And then, you've already hinted at this, but I just want to be really clear for everyone listening, why shouldn't we do it right now? What's holding us back from universal germline testing for everybody in GI cancers? Dr. Matthew Yurgelun: You know, I think if it were a perfect world, then it would be a no-brainer - test everybody. The finances, as Heather alluded to, are in some ways kind of the least compelling argument against universal testing, that the cost of the germline testing itself has come down tremendously. But it's more than just the cost of the test itself, at least in my opinion. I mean, first of all, I think we've got massive work to do just to figure out the care delivery here. As it stands right now, roughly half of colorectal cancer patients meet criteria for germline testing, putting aside the recent update to the NCCN, which says, "consider testing for all individuals." But even if you just look at colorectal cancer alone, if you expanded germline testing to all-comers with colorectal cancer in the US, that's another 80,000+ new diagnoses per year in the US, who are all over age 50, have mismatch repair proficient tumors, have no striking family history, you know, where the odds of finding something truly actionable in my mind, is exceedingly low. Then you add in all of the other GI cancer types. You add in the literal millions of GI cancer survivors that are out there, and you're talking about bringing this testing to a whole lot of people. On top of that, there's really all of the uncertainties and nuances that come from the testing itself, as we were talking about at the beginning of the chat here. Whether it's variance of uncertain significance, whether it's genes where there's really no link between the gene in which they have a germline variant and the cancer that they were ultimately diagnosed with, or whether they're genes we don't understand or don't have clear-cut management guidelines for, it's really all the unintended consequences in some ways of a lot of what we're doing. And I think too often out there, whether it's from the patients themselves, or us healthcare providers, or combination of the two, there's this misperception that genetic testing is giving black and white answers to what's going on. There's a whole lot of gray here, as far as understanding what needs to be done with this. Yes, if we could test everybody and get them clear-cut answers, and then get their at-risk family members in for testing, the benefits would supersede all of these concerns, but I don't think the real world is as simple and straightforward as that. Heather Hampel: And I find myself just in the struggle between-- when I get in a room with people who discuss this, most people feel like we should be doing it, and the thing that's stopping us is that it's difficult. And that doesn't seem like a good reason to not do this. If it's the right thing to do, I think we have to figure out how to do it. And you think of, you know, Mary Claire King's Lasker Award talk when she talked about offering BRCA1 and BRCA2 testing to all women at age 35, population-based screening. And one of the things she recommended there was, not reporting out variants of uncertain significance. I realize it's a different situation when you're talking about population testing and healthy people, but are we doing more harm than good with reporting out variants of uncertain significance even in cancer patients? Whereas, you know, we could just ask the lab to let us know if anything ever got upgraded and avoid risking mismanagement of patients based on a variant that you know is likely benign. So, I think there are things we can do. We've been working on some of them, I know Matt has done a little work with mainstreaming in pancreatic cancer patients. I did as well, my former job, because that was sort of the first new tumor outside of ovarian where we needed to recommend all patients get seen by cancer genetics. And the wait time often in cancer genetics is too long, given the prognosis for pancreatic cancer patients, we had to kind of come up with new service delivery models. And there's some great data out there, people are using genetic testing kiosks in the waiting room, videos at the oncology clinic. We can get creative, and the trouble is, I think we're learning while we're doing, which is coming full circle in our discussion here, that's a hard way to do things. Dr. Matthew Yurgelun: I would just add on top of that, in my mind, the reason why not to do this, is really why not to do it. I think we can recognize that more germline testing is going to pick up more people with inherited risk to cancer. There's the unintended consequences, and we need to figure out how to deal with them. And as Heather said, just because it's hard, that shouldn't be a reason not to do it. At the same time, I think it's okay for us to recognize that this is where the field is heading, but to also recognize that we don't yet have all the answers, and to say, "Well, let's be thoughtful about it. Let's figure out how to implement these types of things, how to study them," because it's not going to be one size fits all. What works in a major tertiary care academic medical center is going to be very different from what works in other settings and for other populations. What works for English-speaking patients versus non-English-speaking patients is probably going to be very different. And I think there's all sorts of permutations when you start breaking it down like that. And I think it's okay for us to say, "Well, this is where the field seems to be going, but let's really be thoughtful about it and make sure that we're not doing harm in the short term just because we think it makes more sense to just test everybody in a shotgun approach." Shannon Westin: This has been great; I've learned so much. I was like trying to frantically take notes for thoughts of what we're doing in our clinic right now. I just want to thank my two guests. I think that I remain hopeful that we will get here. I think that you all outlined some really clear steps that we need to take to get there. And audience, I just want to thank you all for being here with us. Again, this was a discussion of, ‘Point/Counterpoint: Is It Time for Universal Germline Genetic Testing for All GI Cancers?' Thanks again for joining us on JCO After Hours, and we will see you next time.   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.  

In this JCO Precision Oncology Conversations podcast, JCO PO author Dr. Thanh Dellinger of City of Hope National Medical Center shares insights into the research published in her article, “Hyperthermic Intraperitoneal Chemotherapy–Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.” Podcast host Dr. Abdul Rafeh Naqash talks with Dr. Dellinger about hyperthermic intraperitoneal chemotherapy (HIPEC) and the various challenges of the treatment of epithelial ovarian cancer (EOC). The study described in this JCO PO article discusses protein expression, RNAseq alterations and signature, and whole-transcriptome sequencing and signatures. Read here  https://ascopubs.org/doi/full/10.1200/PO.21.00239   TRANSCRIPT Dr. Abdul Rafeh Naqash: Welcome to ASCO's Precision Oncology Conversations where we bring you the highlights and overview of precision oncology. This podcast is here to provide interactive dialogue focusing on the excellent research published in the JCO Precision Oncology. Our episodes will feature engaging conversations regarding precision oncology with the authors of a clinically relevant and highly significant JCO Precision Oncology article. You can find all our shows including this one at asco.org/podcasts, or wherever you get your podcasts. Hello, I am Dr. Abdul Rafeh Naqash. I'm a medical oncologist and a phase one clinical trialist at the OU Stephenson Cancer Center. You're listening to JCO Precision Oncology Conversations. I have no conflicts of interest related to this podcast. A complete list of disclosures is available at the end of each episode. Today, I will be talking with Dr. Thanh Dellinger from the City of Hope Comprehensive Cancer Center, who's a gynecological oncologist, and we'll be talking about her JCO Precision Oncology article, ‘Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.' Dr. Dellinger does not have any conflicts of interest. Hi, Dr. Dellinger, welcome to our podcast! Dr. Thanh Dellinger: Hi, Dr. Naqash! It's such a pleasure to be on with you. Dr. Abdul Rafeh Naqash: We recently saw your paper published. It's one of those interesting, clinical translational papers that we felt needed to be highlighted in our Precision Oncology Podcast series. So, we're really excited to have you here today to take a deeper dive into the findings and some of the novel approaches that you used in your recent publication. So, for starters, could you give our listeners a brief idea of what HIPEC is, where it's used, and when it's used in ovarian cancer? Dr. Thanh Dellinger: Right! Thank you very much for this great introduction. So, HIPEC or Hyperthermic Intraperitoneal Chemotherapy has been used in ovarian cancer for quite some time. The most relevant data giving us an indication for ovarian cancer was published by Dr. van Driel in the OVHIPEC-1 randomized trial several years ago in the New England Journal of Medicine, which demonstrated that in stage 3 ovarian cancer patients who undergo an interval tumor debulking with HIPEC, that those patients appear to enjoy both progression-free and overall survival benefit. In fact, the overall survival benefit is nearly 12 months for those patients. So, with this in mind and a number of other data, the HIPEC treatment for those patients that interval debulking has been incorporated into the NCCN guidelines. Nonetheless, there have been some criticisms of HIPEC and it still remains to be seen who those patients are, the ovarian cancer patients who really best benefit from HIPEC, given the morbidity of HIPEC. We now know also that HIPEC is probably equivalent to just cytoreductive surgery alone in terms of morbidity. Dr. Abdul Rafeh Naqash: Thank you for that explanation. And especially for people like myself, who are not surgeons or gynecological oncologists, that was very helpful. So, my next question, and you probably partly answered it, but I'm going to still ask the question is: what is the reason you think that intraperitoneal chemotherapy overall, has not been as widely adopted? Dr. Thanh Dellinger: You touch on a very good point there. As many of the listeners may understand, IP chemotherapy has demonstrated a lot of efficacies in multiple clinical trials over the last decade or two decades even. And part of why, despite its benefit, it has not been taken up in the overall community may really be the difficulty and the complexity of doing IP chemotherapy in the community, especially the side effects are difficult sometimes to take care of. There's increased abdominal pain and there are catheter issues. And so, especially with more recent data, that with the presence of Avastin, IP chemotherapy may not necessarily be as beneficial. Unfortunately, IP chemotherapy hasn't been really taken up in daily oncologic care with ovarian cancer. Nonetheless, we know that there are a lot of theoretical benefits because of the peritoneal metastasis not being as best treated with intravenous chemotherapy as with regional therapy. Dr. Abdul Rafeh Naqash: Thank you! So, now going to the data that you published. I was very intrigued with some of the findings. And from what I understood, your main aim was to understand predictive biomarkers to identify patients or basically identify molecular characteristics for patients' selection for HIPEC. So, could you tell us more about why you initiated this study? And I understand this is one of the, I believe the first study in humans to evaluate some of these interesting biomarkers, both pre- and post-. So, what was the background of doing this trial? And what led to this interesting study? Dr. Thanh Dellinger: Thank you for pointing out this aim. There's a lot of criticism of HIPEC and part of it is that we may not exactly understand the mechanisms of HIPEC, why is it that it works so well in some patients? There's a lot of preclinical data supporting hyperthermia, especially with cisplatin. There's synergy between cisplatin and hyperthermia, and improving the DNA adduct formation. There's increased cytotoxicity seen when the temperature increases up to 43 degrees. And there's also a T-cell activation and immune response that occurs during hyperthermia. So, a lot of this, however, has been done in preclinical studies, in vitro data as well as preclinical mouse models. There hasn't been much or really anything published that, as far as I know, has been done in humans. And so, this particular study looked at both pre-treatments, pre-HIPEC specimens, peritoneal biopsies, as well as immediate post-operative peritoneal biopsies, tumors, and normal samples, and we wanted to look both at the whole transcriptomic sequencing profile, but also at the tumor microenvironment. Dr. Abdul Rafeh Naqash: From a logistic standpoint, from a trial design standpoint, was this a phase 1 study? I know you use the term pilot in the publication. So, were you trying to look at safety also, or was this primarily I would say, a biomarker, pharmacodynamic biomarker-driven study that you were trying to evaluate? Dr. Thanh Dellinger: You're correct. This was essentially a feasibility study. But we additionally looked at safety and feasibility with HIPEC at our institution. And in some respects, we also looked at the feasibility of giving intraperitoneal chemotherapy normothermically early after HIPEC, and so it was also an endpoint to look at safety. Dr. Abdul Rafeh Naqash: Understand! I believe there was some difference in the dose for the cisplatin, I believe, is the chemotherapy that you use. What was the rationale for the difference in the dose for 75 milligrams per meter square that you use in your study? Dr. Thanh Dellinger: The study was initiated at a time before the OVHIPEC-1 trial was published. And so, at that time, the HIPEC dose for cisplatin was still not established. 75 milligrams per meter square for cisplatin was actually used in other trials, and has been noted to be effective in other clinical trials. Dr. Abdul Rafeh Naqash: Thank you! Now going to the patient population for this trial. What type of patients were you enrolling? Was it just epithelial ovarian cancer patients, did these patients need to have peritoneal metastases when you were doing this cytoreductive surgery? What was the patient population that you were targeting in this trial? Dr. Thanh Dellinger: The majority of the patients did have epithelial ovarian cancer. We did enroll a few, actually 5, uterine cancer patients as well, which were not included in this specific publication. But the majority of them were epithelial ovarian cancer patients. Dr. Abdul Rafeh Naqash: Going to the interesting translational analysis. So, you had three subsets of patients based on the biopsy collection. What were your hypotheses, and what drove some of those translational studies to understand the biomarkers? Dr. Thanh Dellinger: The first translational analysis we conducted was the whole transcriptomic sequencing, and specifically, we wanted to look, one, for any potential transcriptomic signatures that may correlate with survival or improved response to HIPEC. The second one was to look at whole exome sequencing. Thirdly, we looked at whole transcriptomic sequencing differences before and after HIPEC treatment. And lastly, we looked at the tumor microenvironment through multiplexing of certain markers associated with T-cell response. Dr. Abdul Rafeh Naqash: From a clinical outcome standpoint - and we'll discuss the biomarkers in more detail - from a clinical standpoint, when I briefly looked over the PFS curves, were the results, as far as expected outcomes, were they similar to what you see with the current standard? Or were there any unusual safety signals? Or would you attribute any of the adverse events that you saw to intraperitoneal chemotherapy specifically? Because I believe some patients did have some chemotherapy pre-surgery, neoadjuvant if I'm correct. So, how would you attribute some of those AEs, and if at all, did you see any interesting safety signals of concern and outcomes as far as PFS is concerned? Dr. Thanh Dellinger: So, one of the major toxicities that we saw in the first half of our trial were actually renal toxicities. In fact, there were actually two patients who could not go on to adjuvant chemotherapy because they suffered chronic renal failure. And because of that, halfway through the trial, we did actually add a nephro protectant called sodium thiosulfate. And this actually dramatically improved those renal toxicities. And for the second half of our study, no patients suffered grade three or grade four renal adverse events. And so, that did change significantly. Dr. Abdul Rafeh Naqash: From a genomic standpoint, it's very interesting that you were able to do all these very cool and interesting translational biomarker studies, including multiplex immunofluorescence. From a genomic standpoint, though, would you say it's fair to say that there was no significant correlation based on the baseline genomics for some of the patients and their outcomes? Is that a fair assessment? Dr. Thanh Dellinger: Yes, that is a very fair assessment. I think that our cohort was really too small to make those kinds of assessments. I don't know whether you saw there recently was a paper published by the OVHIPEC-1 group looking at their cohort of over 200 patients that underwent the interval cytoreductive surgery in HIPEC and they did actually demonstrate benefit in patients who are HIV-positive but BRCA wild-type, but not necessarily in BRCA mutated patients. So, I think that I would point to that study to look for genomic effects with HIPEC patients. Dr. Abdul Rafeh Naqash: Understand. Now, again, going to the biomarkers that your team evaluated, it seems from among good responders especially, you saw an increase in tumor necrosis factor, alpha signaling, NF-kappa B signaling, KRAS signaling, and then you also saw some pathways that were downregulated, especially the G2-M checkpoint, and Myc targets. What would you say the correlation of these is in terms of future drug development in this specific setting? Dr. Thanh Dellinger: I think that we did see some increase in immune pathways in patients who did better in the end. And also, our multiplex results did demonstrate that E1 expression was increased in patients who had better responses after HIPEC. So, our hypothesis is that potentially, there's an activation of T-cell response with HIPEC and that potentially PD-1 inhibitor could be added in the future. This is a hypothesis that certainly would need to have more work, but it's something that is interesting enough to really look at in ways of how to improve HIPEC. Dr. Abdul Rafeh Naqash: Going to your point on the PD-1, I found really intriguing that you were able to see an increase in PD-1 expression on CD8+ T cells but no actual increase in the number of CD8+ T cells suggesting there's some sort of activation of this marker and this may not necessarily be a marker for T-cell exhaustion. So, would you interpret it in a way that in a different setting, perhaps a new adjuvant approach with immunotherapy, would perhaps somehow augment this and then you could see more upregulation? Is there any work being done in that field? How would you put this in the context of your findings? Dr. Thanh Dellinger: You bring up a really great point because to date HIPEC has been demonstrated to have benefit in the interval setting. But there was a more recent study done by, well not recent, a more recently published study by a Korean group that demonstrated no benefit in the adjuvant setting for HIPEC and still some benefit in the interval setting. And the question is, are these really two different types of cohorts who respond differently because of potential differences in immune response and tumor microenvironment? I think that that would be a great way of delving further into this. What are really the differences in tumor microenvironment changes in those two different settings? Dr. Abdul Rafeh Naqash: Definitely! It's very exciting. You've also shown upregulation of, as you mentioned earlier, immune pathways, as well as upregulation of genes related to heat shock proteins. Does that play into future drug development as far as HSP Inhibitors are concerned? Dr. Thanh Dellinger: That is a really great question. Certainly, in preclinical models, heat shock proteins are known to be elevated and they do activate dendritic cells and result in T-cell activation. Now, whether that can be spelled out into actually some future drug therapy definitely remains to be seen. To date, there hasn't been any success in using heat shock types of agents or inhibitors, unfortunately. So, I think while this is of great interest, I'm not entirely sure that this will translate into any drug therapy in the future. Dr. Abdul Rafeh Naqash: And I totally connect with you there as a phase 1 trialist. I completely agree that we see a lot of translational data, more often than not, going into the phase 1 site because many of these targets are not actionable. Now, from a DNA repair standpoint, you did see that there was interference with DNA repair, as far as some of the analyses that you did, but I did not specifically see any markers for DNA damage that were assessed on the biopsies such as Gamma-H2AX, RAD 51, or Phospho-NBS. Was there a reason why that was not looked at? Dr. Thanh Dellinger: I think that we did look at that and there weren't really any significant results. We did put some of the data into the supplementary data. I think that in the end, our cohort was really too small to really make any meaningful data. But I absolutely agree with you looking at HSP and DNA repair is really important. And as I mentioned that most recently published paper does address that. Dr. Abdul Rafeh Naqash: Excellent! Do you think that there could be any confounders in this analysis that could have led to the upregulation of some of these pathways and may not necessarily have been the intraperitoneal chemotherapy? Could you think of some other reasons that this could have been a confounding factor? Or would it primarily be attributed to the intraperitoneal chemotherapy that you guys have looked at in this interesting paper? Dr. Thanh Dellinger: Yeah, it is a rather small cohort. So, I think that more data is required to potentially repeat this in the larger cohort. But what is interesting is that we did have paired analysis. So, we had matched peritoneal samples from the same patients looking before the HIPEC and after the HIPEC, which is very unique and hasn't really been done in the setting before. And while you couldn't necessarily repeat the same exact peritoneal tumor it was very close. And so, in the best setting, I think that we did have a good paired analysis. Dr. Abdul Rafeh Naqash: That was one of the very interesting aspects of this study that I very much appreciated, that you were able to get some of those paired biopsies and do the analyses on samples and look at all these markers. So, this was all excellent work and definitely intrigues the mind into what other ways one could use some of these findings to develop future combination-based approaches, whether it's the neoadjuvant or the adjuvant setting for patients with ovarian cancer. Are there any next steps as part of this project that you are excited about that you can share? Dr. Thanh Dellinger: Right! I'm definitely very excited about trying to build on this and essentially developing a much larger predictive study using hundreds of ovarian cancer HIPEC-treated tumors in collaboration with others. We have definitely developed a great community of HIPEC investigators who are very interested in developing somewhat of a predictive signature for ovarian cancer undergoing HIPEC. So, I'm very excited to hopefully be able to develop this consortium of HIPEC transcriptomic research. And so, I'm looking forward to collaborating with my co-investigators on that. Dr. Abdul Rafeh Naqash: It was definitely exciting to talk to you about your work. Now, I want to ask you about you as an investigator or as a researcher. How did you end up in this field? What was your background while you were pursuing science and medicine? How did you end up in this field and how are you mentoring the next generation? Dr. Thanh Dellinger: When I was a fellow at UCI, my mentor Robert Bristow introduced me to HIPEC and that has really stuck. As a GYN oncologist, it is hard to really do both chemo and be a good surgeon. And in many ways, I have really specialized in surgical oncology more than in medical oncology. And HIPEC is really a very nice blend of the two. It allows you to do clinical trials while still doing surgery and giving some chemotherapy. Really, it was for the introduction of my more recent mentor, Elena Rodriguez, who really introduced me to genomics and applying this to HIPEC samples that this all came about. And so, I think that there are a lot of opportunities for surgical oncologists who do not give chemo and may think that clinical research is not for them, but there are a lot of translational opportunities and clinical trial opportunities for those who don't give chemotherapy, but are surgical oncologists. Dr. Abdul Rafeh Naqash: Thank you so much. We are really excited for all the work that you're doing and will continue to do and hopefully, we'll see more of this evolve as time progresses. Dr. Thanh Dellinger: Thank you so much, Dr. Naqash. It was such a pleasure meeting you and talking to you. Dr. Abdul Rafeh Naqash: Same here. Thank you for listening to JCO Precision Oncology Conversations. To listen to more, visit asco.org/podcasts, or find them on Google Play Spotify and Apple podcasts. To stay up to date, be sure to follow and share JCO Precision Oncology content on Twitter. The Twitter handle is @JCOPO_ASCO. All JCO PO articles and series can be found at ascopubs.org/journals/PO. The purpose of this podcast is to educate and 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.  Guest Bio Dr. Thanh Dellinger, MD, is a gynecologic oncologist and physician-scientist who specializes in ovarian and uterine cancer. She is an expert in hyperthermic (HIPEC) and pressurized aerosolized intraperitoneal chemotherapy (PIPAC), and is the primary investigator of clinical and translational studies focusing on these therapies. She received her medical degree at University of California Irvine, where she also completed a gynecologic oncology fellowship. She is leading the first U.S. clinical trial in PIPAC (pressurized intraperitoneal aerosolized chemotherapy), a novel therapy using pressurized aerosolized chemotherapy for ovarian cancer. Her current research focuses on innovative therapies for ovarian cancer using intraoperative chemotherapy, and novel antibody and nanoparticle therapies.

The eyes are the window to the soul, as the old saying goes, but are the eyes also the window to cardiovascular disease? Diabetic retinopathy is a common diabetic microvascular disease and a leading cause of blindness in diabetes patients worldwide. Defects in the blood-retinal barrier caused by increased production of vascular endothelial growth factor-A isoforms promote angiogenesis and permeability. Listen as Consulting Editor Dr. Shawn Bender (University of Missouri, Columbia) interviews first author Dr. Naseeb Malhi (City of Hope National Medical Center), senior author Dr. David Bates (University of Nottingham), and expert Dr. Jerome Breslin (University of South Florida) about the new study by Malhi et al, which investigated whether serine-arginine-rich protein kinase-1 (SRPK1) inhibition can attenuate the pathophysiology of diabetic retinopathy. The authors conducted a combination of mechanistic in vitro studies using human retinal pigment epithelial cells and studies in type 1 diabetic rats to investigate whether SRPK1 is activated in diabetes, and whether an SRPK1 inhibitor (SPHINX31) switches VEGF splicing in diabetic retinopathy to prevent increased vascular permeability into the retina. The novel intervention design of delivering the SRPK1 inhibitor via eyedrop in the authors' diabetic rat model was used preventatively at the outset of the diabetes phenotype. Does this unique treatment modality offer promise for treating established diabetic retinopathy? Listen and learn.   Naseeb K. Malhi, Claire L. Allen, Elizabeth Stewart, Katherine L. Horton, Federica Riu, Jennifer Batson, Winfried Amoaku, Jonathan C. Morris, Kenton P. Arkill, David O. Bates Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy Am J Physiol Heart Circ Physiol, published May 10, 2022. DOI: 10.1152/ajpheart.00001.2022

Private Medical physicians Dr. Jordan Shlain, Dr. Hadi Halazun and Dr. Natalie Walsh are joined by Dr. Charles Brenner, the Alfred E. Mann Family Foundation Chair in Diabetes and Cancer Metabolism at City of Hope National Medical Center. They discuss the role of the popular longevity coenzyme nicotinamide adenine dinucleotide, NAD, and how it maintains resilience and youthful function, the myths of anti-aging, what constitutes pro-aging, and what the science really tells us about how to feel better as we age.

Fred Claire is a former long-time executive with the Los Angeles Dodgers. He served numerous roles with the Dodgers from 1969-1998, including his position as Vice President/General Manager from '87 to ‘98.Fred began his career with the Dodgers as an assistant in public relations – and in 1975, he became the VP of Public Relations.  During this term, he was instrumental in creating the team branding that became known as the ‘Dodger Blue' campaign.A year after being named GM, Claire was instrumental in helping bring the Dodgers to a 1988 World Series win in 5-games over the heavily favored Oakland Athletics.In the spring of 2015, Fred was diagnosed with skin cancer that later migrated to his jaw. While odds were against his survival, Fred, along with this long-time wife Sheryl, fought the brave fight and found a great new championship team at City of Hope National Medical Center in Duarte, California. In the book, “Extra Innings,” author Tim Madigan provides us a look at what Fred's fight with cancer has meant.  When treatment at the City of Hope began to show success, Fred and Sheryl began dedicating themselves to raising money and awareness for the cancer research and treatment center.The Fred Claire Celebrity Golf Tournament continues to raise large amounts of money for the City of Hope.In addition, to help find new ways to fight cancer, Fred joined USC alumnus, Kurt Colicchio, to establish the Fred and Sheryl Claire Scholarship Fund to support medical students conducting a year of dedicated research in head and neck cancers. Between a highly successful 30-year career with the Dodgers and a heartwarming, winning battle against cancer, the May 11th episode of A Mick A Mook and A Mic with Fred Claire is one you won't want to miss.

My guest on episode 42 of the podcast is Dr. Charles Brenner Dr. Brenner is the Alfred E Mann Family Foundation Chair in Diabetes and Cancer Metabolism at City of Hope National Medical Center.  In 2004, Brenner discovered nicotinamide riboside (NR) to be a vital precursor of nicotinamide adenine dinucleotide (NAD+), which is made available by nicotinamide riboside kinases (Nrks) that are conserved between yeast and humans. In 2007, Dr. Brenner's lab discovered a second pathway by which NR is converted to NAD+ and showed that NR can extend the lifespan of yeast cells by virtue of elevating NAD+ levels and increasing the activity of the NAD+-dependent Sir2 enzyme. In the past decade, Dr. Brenner has made multiple seminal contributions to NAD+ metabolism, which include engineering a yeast strain to convert inexpensive NAD+ precursor vitamins into NR, solving the crystal structure of human Nrk1, developing the methods for quantitative NAD+ metabolomics, and demonstrating the activity of oral NR in animal models of fatty liver disease; obesity; type 2 diabetes; diabetic and chemotherapeutic neuropathy; heart failure; and central brain injury. Dr. Brenner also led the first clinical trial of NR, which established safe oral availability in humans. He is currently focusing on the maternal and neonatal effects of oral NR and translating animal discoveries into evidence-based safe, human clinical practice for human conditions of metabolic stress. Dr. Brenner is clearly a well-credentialed scientist, but my main impetus for inviting him to come on the podcast is his recent public criticisms of the longevity field. In particular, Dr. Brenner has several recent posts in which he has directly called out prominent longevity scientist Dr. David Sinclair for what Dr. Brenner describes as spreading misinformation regarding what we know about aging and whether or not we can slow or reverse aging. We spend the last 20 minutes or so of the podcast discussing his critiques and where he believes scientists in the longevity field may be overstepping. Other topics that we get into include some basics on human metabolism, nicotinamide adenine mononucleotide (also known as NAD) and the importance of the NAD system in physiology, what types of things perturb the NAD system and how this may contribute to diseases and aging, and ways we might be able to boost the NAD system through diet and supplementation. I will say that at times, we got pretty technical in this podcast, and Dr. Brenner gets into some of the more complex biochemistry surrounding metabolism and the NAD system. But I really encourage you to listen to everything we chat about, because Dr. Brenner is such an eloquent speaker about these topics and I think that even if some concepts are higher level, you'll learn a lot about biology and physiology through what he has to say — I surely did.  If you enjoy this podcast and would like to support it, there are several ways to do so. The first way is by becoming a supporter of Patreon. With Patreon, you can support the podcast with a monthly donation at any level you'd like. You can start showing your support right now by going to patreon.com/bradyholmer or checking the show notes for a link to my Patreon page. You can also make a one-time donation to help support the podcast through PayPal or Venmo. These support options can be found on my website by going to bradyholmer.com/donate. There's also a link in the show notes to the support page. Finally, checking out the podcast sponsors is also a fantastic way to show your support. There are two partners for today's podcast, both of which are products I use frequently and absolutely love. The first is LMNT electrolyte drink mix. LMNT is a sugar-free, carbohydrate-free and tasty drink mix containing scientifically-based amounts of sodium, potassium, and magnesium. The single serve packets are great to add to water for any time around a workout or just to have throughout the day. I'm routinely using about 3 of these each day. LMNT comes in a variety of flavors including citrus salt, raspberry, and watermelon. You can try a free 8 pack sampler of LMNT by going to drinklmnt.com/scienceandchill or checking the show notes for a link to this special offer. I've also partnered with health via modern nutrition (HVMN) to bring a special offer for my audience on their brand-new ketone IQ ketone drink. Ketones are sometimes called the “fourth fuel” and can be used by our muscles, heart, and brain for energy. With exogenous ketone drinks like ketone IQ, you can rapidly elevate your blood ketones and put your body into a state of ketosis. Studies have found — and I have experienced — that taking ketones can help with mental performance and clarity, athletic performance, and maintain energy levels throughout the day.  If you have not yet tried ketones, I really encourage you to give ketone IQ a try. You can get 10% off your order of ketone IQ by going to their website using the link in the show notes and entering the code BRADY10 at checkout. Again, use the link in the show notes to learn more about ketone IQ and when you order, enter BRADY10 at checkout for 10% off your order. Last but not least, if you enjoy my podcast, then you may also enjoy some of the writing that I publish on a weekly basis, which includes my weekly newsletter that I send out every Friday called Physiology Friday. If you'd like to check out my writing and subscribe to receive my weekly posts, please visit bradyholmer.substack.com. You can also find a link in the show notes.   Links Episode webpage: https://www.bradyholmer.com/pod/42  Watch on YouTube: https://www.youtube.com/watch?v=8h6O5jxu6Yk  Listen on Apple Podcasts: https://podcasts.apple.com/us/podcast/science-chill/id1494739189  Listen on Spotify: https://open.spotify.com/show/2ilq7P9OBAiqrxk4Ac4WQg  Brenner lab site: https://www.brennerlab.net/ Dr. Brenner's bio (Chromadex): https://www.chromadex.com/bios/charles-brenner/  Follow Dr. Brenner on Twitter: https://twitter.com/CharlesMBrenner  Support the podcast on Patreon: https://www.patreon.com/bradyholmer Other support options: https://www.bradyholmer.com/donate  Claim your FREE LMNT sample pack: https://DrinkLMNT.com/scienceandchill  10% off of H.V.M.N. Ketone IQ for the Science & Chill audience (use code BRADY10 at checkout): https://hvmn.com/products/ketone?rfsn=6449481.3c177c Subscribe to my Substack: https://bradyholmer.substack.com/about4:

In this episode, Edward S. Kim, MD, MBA, discusses his path to oncology, how he views disruption in health care, and the ways he’s innovating to help both patients and providers. Intro :13 About Kim :22 The interview 2:03 How did you end up in medicine and oncology? 2:20 What do you think it means to have disruptive or innovative health care strategies? 15:24 Oncology care provides the opportunity for disruptive innovation 21:10 How do you decide which risks to take? 25:59 Taking risks can help move the needle forward 37:52 Kim’s take-away from this episode 38:58 How to reach Kim 39:58 Edward S. Kim, MD, MBA, FACP, FASCO, is physician-in-chief at City of Hope Orange County and vice physician-in-chief of City of Hope National Medical Center. We’d love to hear from you! Send your comments/questions to Dr. Jain at oncologyoverdrive@healio.com. Follow us on Twitter @HemOncToday @ShikhaJainMD. Dr. Kim can be reached by email at edwkim@coh.org and on Twitter @DrEdKim. Disclosures: Jain reports she is a paid freelance writer for Lippincott. Kim reports no relevant financial disclosures.

Dr. Caligiuri describes his journey from being a liberal arts major at a college in upstate New York, to being a Stanford trained MD, to his current position as President of City of Hope National Medical Center. Along the way Caligiuri shares his thoughts on training to be a hematologist in the late ‘80s – at a time when there were no curative therapies, and such a calling was daunting at best – to his finding a cherished mentor that put him on the road to becoming one of the top NK cell experts in the world.

On today's episode, meet Dr. Michael A. Caligiuri. Dr. Caligiuri is President of City of Hope National Medical Center and the Deana and Steve Campbell Physician-in-Chief Distinguished Chair, a world-renowned physician, scientist, builder, innovator, leader and visionary at City of Hope. A leading researcher in immunology, lymphoma and leukemia, Dr. Caligiuri dedicates himself to developing the next generation of cancer therapies, rapidly delivering them to patients and curing their disease. His research team is currently focused on bringing natural killer cellular therapies to patients with any form of cancer. He also gives back to the communities he serves.

The treatment of prostate cancer is continually evolving as we look at new technologies and advances in managing the disease. Today, board-certified urologist and prostate cancer expert, Dr. Jim Hu, from Weill Cornell Medicine, in New York joins us. In this episode, Dr. Hu will be talking about targeted focal therapy. He will focus specifically on HIFU (High-Intensity Focused Ultrasound) as a treatment option for targeted focal therapy, for prostate cancer. He will also review who may and may not be a candidate for focal therapy.  Dr. Jim Hu completed his urology residency at UCLA and his urologic oncology fellowship at City of Hope National Medical Center. He got recruited at Weill Cornell Medicine in February of 2015 after establishing high-volume internationally renowned programs at Brigham and Women's Hospital, Harvard Medical School, and UCLA Medical Center, where he served as Director of the Prostate Cancer and Robotic and Minimally Invasive Surgery programs respectively. He is internationally renowned as a surgical innovator and health services researcher. His research interests have been funded by the Department of Defense, National Cancer Institute, and the Livestrong Foundation. He has authored more than 300 peer-reviewed papers. Dr. Hu has performed thousands of robot-assisted prostatectomies, among over 4000 laparoscopic, robotic and open procedures. He has been instrumental in helping drive some of the advances that have helped the field of urology, including working with the FDA to look at the outcomes of HIFU (High-Intensity Focused Ultrasound), a type of targeted focal therapy for prostate cancer.   Disclaimer: The Prostate Health Podcast is for informational purposes only. Nothing in this podcast should be construed as medical advice. By listening to the podcast, no physician-patient relationship has been formed. For more information and counseling, you must contact your personal physician or urologist with questions about your unique situation. Show highlights: Dr. Hu explains what targeted focal therapy for prostate cancer is. Dr. Hu describes some of the different technologies currently utilized for focal therapy. Dr. Hu explains what HIFU is and how it works in treating prostate cancer. When looking at targeted focal therapy, Dr. Hu describes the best potential candidates for the HIFU option. Dr. Hu explains the methods he is currently using to identify the targeted area to treat with focal therapy. Dr. Hu discusses one of the challenges with the localization of prostate cancer. Dr. Hu explains what a man considering HIFU as an option for targeted therapy can expect from the procedure. Some of the risks and potential advantages of using HIFU for focal therapy for prostate cancer. Dr. Hu describes his set protocol for following men after focal therapy with HIFU in terms of monitoring them for any recurrence or progression of prostate cancer. Dr. Wu discusses whether men are still candidates for other therapy if needed after HIFU, should they have a prostate cancer recurrence. What the future holds for the future of HIFU in the management of prostate cancer. Dr. Hu talks about whether he sees HIFU making its way into current guidelines and becoming more widely accepted as a standard of care for appropriate candidates. Most of the current guidelines continue to advocate for the templated biopsy rather than the MRI. Some tips for men considering targeted focal therapy for prostate cancer. Links and resources: Follow Dr. Pohlman on Twitter and Instagram - @gpohlmanmd  Get your free What To Expect Guide (or find the link here, on our podcast website)   Join our Facebook group  Follow Dr. Pohlman on Twitter and Instagram  Go to the Prostate Health Academy to sign up for the wait-list for our bonus video content.  You can access Dr. Pohlman's free mini webinar, where he discusses his top three tips to promote men's prostate health, longevity, and quality of life here.

ONS member Betty Ferrell, PhD, MA, FAAN, FPCN, principal investigator of the End-of-Life Nursing Education Consortium (ELNEC) project, director of the Division of Nursing Research and Education at City of Hope National Medical Center in Duarte, CA, and member of the Greater Los Angeles ONS Chapter, joins ONS President Nancy Houlihan, MA, RN, AOCN®, to discuss ELNEC's history and milestone of training more than one million nurses in palliative and end-of-life care. Then, ONS members share personal testimonies about ELNEC and how the training has enhanced their practice.   Music Credit: "Fireflies and Stardust" by Kevin MacLeod  Licensed under Creative Commons by Attribution 3.0  Earn 0.75 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at myoutcomes.ons.org by December 25, 2022. The planners and faculty for this episode have no conflicts to disclose, and the episode has no commercial support. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation.  Episode Notes  Introduction: 00:25  Interview: 01:36  Testimonies: 31:15  Jacqueline Boreland, MSN, RN, GERO-BC™, OCN®, CCDS: 31:28  Karin Elkins MSN, NPD-BC, OCN®: 33:46  Tracy Garrett-Reed DNP, APRN, AOCNP®, FNP-C: 38:34  Tiffany McConathy, MSN, FNP-C, APRN, AOCNP®: 40:38  Sara M Tinsley, PhD, APRN, AOCN®: 43:31  Jennifer Tschanz, RN, MSN, FNP, AOCNP®, ACHPN: 47:02  Check out these resources from today's episode:  Complete this evaluation for free NCPD.  ONS Voice article: ELNEC Milestone Marks Transformation of EOL Care for Countless Patients With Cancer  ONS Voice article: Palliative Care Resources Comfort Nurses Through COVID-19 Stress, Dilemmas, and Grief  ONS Voice palliative and end-of-life care topic pages  Oncology Nursing Podcast Episode 41: Advocating for Palliative Care and Hospice Education  Clinical Journal of Oncology Nursing article: Barriers to Hospice and Palliative Care Research: A Patient-Centered Approach to Intervention Studies  Clinical Journal of Oncology Nursing article: Providing Palliative Care: Oncology Nurses' Perceptions of Their Self-Reported Abilities  ONS Position Statement: Palliative Care for People With Cancer  ELNEC courses   ELNEC COVID-19 resources   ELNEC tools for trainers     

Charles Brenner, PhD is the chair of the new Department of Diabetes & Cancer Metabolism at the Beckman Research Institute of the City of Hope National Medical Center. He is a major contributor to work on nicotinamide adenine dinucleotide metabolism, who discovered the eukaryotic nicotinamide riboside (NR) kinase pathway.

For this special edition of Oncology Today, I met with Dr Tanya Siddiqi from the City of Hope National Medical Center in Duarte, California, to discuss recently published and emerging research in the use of chimeric antigen receptor T-cell therapy for patients with non-Hodgkin lymphoma. CME information and select publications here (http://www.researchtopractice.com/OncologyTodayCARTNHL20).

Cristiane Bergerot (@crisbergerot), PhD, health psychologist, City of Hope National Medical Center, discusses when patients should be involved with a psycho-oncologist, whether the psychological state of a patient has an impact on treatment outcomes, pre-diagnosis factors that may put a patient at higher risk of depression, and more.

Betty Ferrell of City of Hope National Medical Center has been a nurse for more than 40 years. She also leads the End-of-Life Nursing Education Consortium, which provides palliative care training for nurses worldwide. In recognition of International Nurses Day, Ferrell offers her Brief But Spectacular take on how medical professionals are showing up for us -- and how we can return the support. PBS NewsHour is supported by - https://www.pbs.org/newshour/about/funders

Betty Ferrell of City of Hope National Medical Center has been a nurse for more than 40 years. She also leads the End-of-Life Nursing Education Consortium, which provides palliative care training for nurses worldwide. In recognition of International Nurses Day, Ferrell offers her Brief But Spectacular take on how medical professionals are showing up for us -- and how we can return the support. PBS NewsHour is supported by - https://www.pbs.org/newshour/about/funders

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. 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. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. Greg Guthrie: Hi everyone, I'm Greg Guthrie, and I'm a member of the Cancer.Net content team. And I'll be your host for today's Cancer.Net podcast. As a reminder, Cancer.Net is the patient information website of ASCO, The American Society of Clinical Oncology. Today, we're going to be talking about some research highlights from the upcoming Supportive Care in Oncology Symposium. And my guests are Dr. William Dale and Dr. Joe Rotella. Dr. Dale is the Arthur M. Coppola Family Chair in Supportive Medicine at the City of Hope National Medical Center in Duarte, California. He is also the Cancer.Net Associate Editor for Geriatric Oncology. Thanks for joining us, William. Dr. William Dale: Thanks for having me. I'm happy to be here. Greg Guthrie: And Dr. Rotella is the Chief Medical Officer of the American Academy of Hospice and Palliative Medicine. Thank you for joining us as well, Joe. Dr. Joe Rotella: It's nice to be here with you today. Greg Guthrie: All right. Now, I also want to comment that William and Joe both served on the news planning team for this symposium, which means they helped select the studies that we'll be discussing on this podcast. So let's start off by discussing what is meant when we say “supportive care.”  William, what do you think when I say supportive care? Dr. William Dale: So supportive care medicine, and we have a Department of Supportive Care Medicine here at City of Hope, focuses on providing quality of life considerations for patients in a multidisciplinary way to emphasize functional status, to emphasize overall health for patients. Within supportive care, almost any part of the multidisciplinary team could be included outside of the cancer-directed therapy itself. As an example, palliative care exists as a division within our department of supportive care along with psychology, psychiatry, interventional pain, social work and some others. So when someone says supportive care, I think of everything outside of the cancer-directed therapy that we might do on a multidisciplinary team. Greg Guthrie: That's a great foundation to have before we jump into these studies. And the first one I'd like us to talk about is called “A pilot study of oncology massage to treat chemotherapy-induced peripheral neuropathy, also called CIPN.” So Joe, what is chemotherapy-induced peripheral neuropathy? Dr. Joe Rotella: Well, peripheral neuropathy is a nerve damage which is often associated with neuropathic pain which can be of 2 sorts: sort of a constant burning or a deep kind of pain, or it can be more of a sharp and shooting type of pain. But it's associated with the toxicity of some common chemotherapy drugs, particularly those related to platinum and the Taxol family of drugs. And so it's a pretty common side effect of pretty common chemotherapy that's given to people with advanced cancers and not an easy symptom to treat. The typical pain medications that we would use for any sort of pain, for example opioids, don't always work that well for neuropathic pain. And, of course, there are safety issues and other concerns around using opioids. The other medicines that are often used might fall in the class of the medicines like Gabapentin, or anticonvulsants. And they also can have quite a few side effects and are just not terribly effective. So this study looked at a nonpharmacological approach to managing the pain of chemotherapy-induced peripheral neuropathy. Very interesting, they looked at a standardized Swedish massage technique applied to the lower extremity, and then they had a number of other less intensive massage therapies that were used as a control. And they gave this 3 times a week over 6 weeks, and they were actually able to show a significant reduction in the symptoms related to the chemotherapy-induced peripheral neuropathy, and that it actually was sustained for up to 6 weeks after the massage treatment had been completed. So this was fascinating that we could apply what appears to be a low-risk treatment that seems to be free of significant side effects that falls in that category of complementary alternative medicine that is so appealing to patients, and that this actually showed results that lasted beyond the duration of the intervention. And the less intensive control interventions did not result in as much symptom improvement. So very interesting study. Greg Guthrie: Great. William, what do you think of this study? Dr. William Dale: You know, peripheral neuropathy is extremely difficult for patients to deal with in our treatments as Joe just pointed out, are kind of notoriously ineffective. It works for a few patients, but often it doesn't that well and the side effects are quite high. So looking for alternatives to medications is something that's on all of our lists. Too often patients, in some ways, either get medicines or they're left on their own devices. We don't really have good evidence base to tell them what to do. Even though this study is not huge, it was very well constructed. So we know what kind of massage was used, what kind of evidence we had, and that it had a longer-term effect. And I agree with Joe that it's really nice to have an alternative that we can say has evidence that we might let patients consider and that's outlined in a way that lets us say this was a causal relationship or at least seems to be that patients were put into these two groups and it really was the group that got this very specific Swedish massage that had these enduring effects. So it'd be great to see this in a larger group of patients and to know for sure if this will work from a wider group of patients, but as a starting point, to have an alternative to medications for such difficult-to-treat side effect with such quality of life implications is really exciting. The other thing I would mention and ask Joe about is they make the point that, these are licensed professionals. These were people who were expert at doing this kind of intervention. And patients sometimes ask, "Oh, can I get this?" And it would be nice to say just like any other intervention whether it was a medication intervention or a procedural intervention to say, "This is the way that this has to be done," and very specifically, what the outcome is expected. Too often we give vague information to people when it comes to so-called alternative therapies. But this was very specific to people trained to do this, presumably in patients who have cancer. Dr. Joe Rotella: Yes, I agree. It's actually important to have a sense of what the intervention is that is actually performing better, let's say, than control or better than placebo or better than no intervention. The more we can pin down exactly what works and what frequency, what intensity is needed to get the optimal results, the more we can treat this like we would a pharmacological therapy where we can say, "Here's precisely what I recommend for you. Here's the dose. Here's the frequency. This is where the evidence says you're likely to get the most benefit." And I think there are certain interventions in complementary alternative medicine where we're starting to get there, where we can actually say, "This technique works better than that technique." And I think that's when we can begin to bring it into the same sort of rigor that we do our pharmacological treatments. Greg Guthrie: Yeah, that's really great, just having an evidence-based approach to complementary therapies. So let's move on to our next study which is called “Anxiety, depression, pain, and social support in a large representative cancer population.” So what questions did this study set out to investigate? Dr. Joe Rotella: This study started with the recognition that pain is a very common symptom in patients with cancer and actually looked at what are some associations with pain? How does it relate to the presence of anxiety and depression? How does it relate to whether people have good social supports or not? Can we start to get a sense of how these things all interrelate to modulate the intensity and frequency of pain? And this study was interesting because it really looked at over 11,000 patients. And it was looking at patient-reported information. These were patients who were undergoing treatment for anywhere from stage I to IV cancer who were using a tablet to record their symptoms and information in a large academic center. And through this large database, a lot of analysis could be done to determine what were the key drivers of pain or modulators of pain. And what they found was a number of things were independently associated with the severity of pain in these cancer patients, included the site of the tumor. For example, head and neck cancer versus gastrointestinal cancer. The degree or severity of the disease, how advanced it was. Race and ethnicity was a predictor, lower income, all of these were independently associated with severe pain. But this study went a little further and looked at the effect of anxiety or depression and the level of reported social supports. And in all cases, if the patient reports high anxiety or high depression, it is associated with higher pain scores. But those could be further modulated by the degree of social support. So if a patient had low social support level as self reported, then the effect of the depression on pain was more. If they had anxiety and high levels of pain and the ones who had transportation issues, for example, tended to have even more pain. So with this really large database, we begin to get a sense of how these various factors interface. And it's not just a tumor type, it's not just a stage of the tumor, it's not just things like race, ethnicity, socio-economic status, but it's also the degree to which anxiety and depression are present and the degree to which there are social supports that can actually play a role in the level of pain that patients report. All of this would support this multidisciplinary holistic approach that we take in supportive care programs or when we're providing palliative care through a team. This really supports that concept that pain is not an island unto itself. The whole rest of the patients’ experience has a big impact on how they experience pain. Greg Guthrie: William, what are some patient takeaways from this study? Dr. William Dale: Yeah, to pick up on Joe's great summary of this, so overall, sometimes we have big studies but we don't have a reason for those studies to be big other than we happen to have a lot of data. What was nice in this study was they used the fact of a large dataset to show how the various variables interacted with each other. So in many cases, you can say well, if someone has a lower income or comes from a certain part of the world, whether a city or in an urban area versus a more rural area, they have worse outcomes. But, of course, those are very non-modifiable things. And it's perfectly fine to say it, but then what do we do about it? What made me feel good about this study was they said, "Well, if you have anxiety and depression, you can approach the problem this way. You can start to take care of those modifiable issues and that will help you with pain." Or if they live in a remote location, you could identify transportation. If you noted that they were living alone, for example, and they needed more help in the home, you could get that support. We all sort of feel that in our field, intuitively, that those things matter and are important. But this really started to connect the dots between pain and these other factors and how we might start to both take care of patients better, but to also start learning and putting the causal picture together about how this works. And to your question about patient outcomes, so the idea of patient-reported outcomes has become more common and I think for good reason to actually ask the patient, “What's going on? What's their experience? How are they feeling?” And this was nice because it put an emphasis on that. And in many cases as they reported—this was on tablet computers—patients and respondents to surveys will be more honest when they're talking to a computer than they were to people, especially if it's their oncologist. We know that they will often become nervous, that if they could tell the oncologist, "Oh, I'm having these other problems," that someone might stop their therapy. And so they don't want that to happen when they really need those outcomes so they can identify what's needed. So screening people for these problems, which we advocate for, this just emphasizes how important they are even for something as basic as pain management. And 1 other thing I wanted to mention, and Joe may want to weigh in on this as well, was this may help explain why we've had this so-called opioid crisis. And I don't want to overemphasize it, but if every time someone reports pain, our first instinct is to give them a medicine, especially an opioid medicine, and just increase the dose. Without identifying all these other factors, it's just an “If I have a hammer,” kind of solution to a problem, when really the multidisciplinary approach that palliative care and supportive care have always emphasized would do better even for something like the overuse of opioid medications. Dr. Joe Rotella: William, I really agree with you on that. Actually, the founder of the modern hospice movement who really started the whole palliative care movement as well, Cicely Saunders, had a concept she called “total pain.” And what it meant was that you may experience pain physically, but it is an experience that involves your physical being, your mental being, your social relationships, your spiritual concerns, that the whole person plays a role in how you experience pain. And whether we're prescribing an opioid or massage or a ride to the chemotherapy center, whatever else we're doing, that multidisciplinary approach that looks at all the experience of the patient, not just their physical experience, but what's happening not just in their body, but in their mind, in their heart, in their spirit. That's really the key to giving people the very best quality of life. And those interventions that are less physically oriented tend to be lower risk, they're tolerated well. It's just a question of getting that team engaged and providing that more holistic approach. Greg Guthrie: That's really great insight into this study. So let's switch to our third and last highlighted study for this symposium which is called “Racial/ethnic disparities in hospice utilization among Medicare beneficiaries dying from pancreatic cancer.” Before we delve deeper into the study, I think it's important if we define what hospice care is and what we may mean when we say disparities. So Joe, how would you describe these terms? Dr. Joe Rotella: Sure. Hospice care is a particular form of comprehensive palliative care that's provided to people near the end of life. Palliative care, supportive care is appropriate at any stage of illness when patients may experience stress or symptoms. But hospice care is designed for those patients that are near the end of life. And in our country, we have a Medicare hospice benefit which is in myriad insurance benefits, which means that it's generally a care that is accessible to almost everyone who is designated as most likely to be near the end of life. The Medicare benefit actually requires a physician to predict that it's probably the last 6 months or so. And it's a very comprehensive form of palliative care. It's really the gold standard of care for people who are nearing the end of life. And so what's interesting about hospice care though is even though it's comprehensive palliative and supportive care with a team right where you live in your home, wherever you call home, a lot of people don't access it at all or they don't access it until very late. Nationally, the trends are that about half the patients with Medicare who die actually get any hospice care before they die. And of those who do get hospice care, half of them get it for less than 3 weeks. And so it's really not fully utilized. And we could do a whole separate podcast on why people don't fully use it. But it's interesting then if it's sort of an underutilized service to try to determine either what drives that. And among other things, one way to try to understand it is to look at whether there are disparities. And by disparities, we mean, does 1 population seem to be treated or seem to be having outcomes that are different from another population who only differ, let's say, in race or ethnicity or gender? And so this study is trying to look at is there a difference in hospice utilization among Medicare beneficiaries who have a very specific condition? They're dying from pancreatic cancer. And again, large database looked at thousands of patients, and really, they were trying to see if there was an association between race or ethnic minority and the utilization of hospice before dying. Pancreatic cancer is a high mortality illness, and in fact, in this study, something like 64% of the patients did die during the course of the study. And there was a difference. Those from ethnic and racial minorities were less likely to initiate hospice care before they died. What's also interesting though is that disappeared if you looked at the very short hospice stay. If you looked at the patients who only got hospice for 1 or 2 or 3 days before they died. In that case, you don't see a racial disparity. But for that earlier hospice care, you do. This study can't explain why, but it really raises questions around why. Is it about how we present the option? Is it because there are different preferences for treatment near the end of life? Is it socioeconomic factors? Don't know from this, but what we can show here is just like with so many other parts of healthcare, there are in fact important disparities here that we should try to understand. Greg Guthrie: William, what are your thoughts on this study? Dr. William Dale: It's such a complicated story of why there are differences between groups. And this study has a great job of showing that we see these differences. I will reflect on my own personal experience of being in 2 different places with 2 different populations. First in Chicago where we had a mix of largely African-American patients and white patients, and now in Southern California where we have a group that's roughly one-third white, one-third Hispanic and one-third Asian. And just to take a simple thing like that, we all noticed differences in the communities with acceptance of the terms of hospice and end of life care. And I think we've all wondered gosh, it does seem like certain groups get it more often than others for a variety of reasons. And to have some data and a large dataset to show, that's really a good thing for us, so that we can advance to the next step of what are the reasons for that or as Joe just said, why is that? I note in the general population, about two-thirds of people when you ask them at the end of your life, what is your preferred location for dying? And two-thirds will say at home. And then when you look at the actual likelihood of where people die, it's about one-third that dies at home and about two-thirds that are in the hospital. Dr. Joe Rotella: Just to add a little bit more, there was something interesting kind of a side observation, and that is that in this particular study, although there was that disparity, overall, 74% of the patients actually did receive hospice care before dying. And so that's actually much better than that 50% or so that you see across the board for all people with all serious illnesses. And another set of disparities we might want to look at sometime besides race and ethnicity would be disease-specific disparities. Why do cancer patients have a higher rate of hospice utilization than patients with end-stage kidney disease, for example? Dr. William Dale: Yeah, that's a great point, Joe. And it makes me think of our ultimate goal when we talk about people having certain goals for their care including their end of life goals. And we use the term “goal-concordant care” so that people pass away where they want to. But boy, that is a moving target sometimes. And so it's helpful to just see well, where do we usually end up in terms of goal-concordant care. And cancer patients, I don't know what you think Joe, do tend to end up in hospice more often, but I still think the length of stay are pretty short even in the cancer population. Dr. Joe Rotella: I think that's true. And a lot of times, I think it may have to do with when the patient stops taking chemotherapy or some other direct cancer treatment. And in many cases, that's close to the end of life, and so then the stay is short. Dr. William Dale: Yeah, I think that's right. I do point out I'm at a cancer center. Our name is City of Hope. And so patients come here with that sense of their coming with hope for something. Usually some form of a new treatment or almost a miracle treatment that will rescue them. And we in the field are often trying to make sure patients understand hope for, can be hope for lots of different things. My old mentor, Bob Arnold, used to say hope for higher quality of life. Hope for meaningfulness. Hope for comfort. All should be part of the conversation. So broadening, again, beyond just the hyper focus on what can we do about this disease to a broader set of questions is probably the next thing we need to understand. Dr. Joe Rotella: Yeah, that'd be a great podcast [laughter]. Greg Guthrie: Well, I wanted to say I've heard the terms quality of life, multidisciplinary, and overall health a lot in our discussion today. And I think that that really just underwrites the role that supportive care plays in cancer treatments. And I think that that's just a great way to summarize the really interesting research that's coming out of this year's Supportive Care in Oncology symposium. So William, Joe, thank you for coming onto this podcast to talk about these studies and to show how they can help start to make improvements in patients’ lives. I really appreciate you taking the time to join us. Dr. William Dale: Well, thank you, Greg. We're looking forward to seeing these studies discussed at the conference. Dr. Joe Rotella: It was a pleasure. Thanks so much. Greg Guthrie: Thank you. ASCO: Find more research from recent scientific meetings at www.cancer.net.  And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content offering insight into the world of cancer care. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

Professor Kim Margolin (Department of Medical Oncology, City of Hope National Medical Center, Duarte, California) discusses in this podcast the different treatment strategies as well as the clinical challenge of handling melanoma patients with brain metastases. Brain metastases are a particular problem of melanoma patients, as this complication occurs early and frequently. Further, brain metastases are associated with a high symptom burden. Recently, systemic treatment approaches including immunotherapy and tyrosine kinase inhibitors have become increasingly important in the management of melanoma brain metastases patients. Indeed, some patients with small, asymptomatic brain metastases without edema and need for steroid treatment might be candidates for a primarily systemic treatment. https://esmoopen.bmj.com/content/4/5/e000579

Dr. Daneng Li, co-director of the neuroendocrine tumor program at City of Hope National Medical Center, offers his expertise and insight on diagnosis, treatment, and dietary practices for a patient with carcinoid syndrome. Patient on this episode is an actor, and represents a hypothetical case. Dr. Li is a paid consultant for Ipsen. ©2019 Ipsen Biopharmaceuticals, Inc. May 2019. SMD-US-002859

All of the conversations we have here at the Precision Medicine Podcast are focused on uncovering both barriers and solutions to realizing the promise of precision medicine. Having the opportunity to speak with Laura Holmes Haddad, an author, speaker, and breast cancer “thriver,” was especially meaningful, because it serves as a reminder that improving patient care—and giving every patient the best chance at beating cancer—is the ultimate goal. On this episode, Laura shares her experience with cancer and discusses her recently published book, This is Cancer: Everything You Need to Know, from the Waiting Room to the Bedroom. Laura begins by telling listeners about the inspiration behind the book, which she wrote to give cancer patients a sense of what to expect. She realized there had been many things about the cancer experience that she did not know before being diagnosed, and that her notion of what it would be like was vague and flawed. Laura wanted to provide people with a sense of comradery and comfort in the knowledge that many others shared their experiences. After the release of her book, she was pleased to learn that caregivers and friends of cancer patients were helped by her insight and could better relate with their loved ones facing the disease. Laura talks about her battle with stage 4 inflammatory breast cancer. The doctors who initially cared for Laura believed that after three rounds of chemotherapy nothing could be done to save her life; however, she continued to pursue a doctor whom she would like and feel comfortable with, and eventually found an oncologist who helped her get into the clinical trial that saved her life. This doctor had a strong grasp on current cancer research and was committed to supporting Laura. He applied to enter her in a clinical trial at City of Hope National Medical Center that would approach her tumor differently than traditional treatment. The trial was a form of precision medicine, and so it treated her in terms of her overall biology rather than merely considering her disease. Laura now feels quite strongly about the value of precision medicine, and she wants other cancer patients to understand both what clinical trials are like and how precision medicine can help with cancer treatment and screening. She is a public advocate for cancer patients and for precision medicine, and she is committed to seeing cancer stories told, cancer patients advocating for themselves, and barriers to care removed. More specifically, Laura hopes to see clinicians granted more access to innovative therapies, and she advocates for insurance companies to remove roadblocks to these treatments. The science of cancer detection and treatment develops quickly, she notes, and there is much for people to learn and put to use. Her experience and insights are truly inspiring, and well worth a listen.​ Don't miss the next episode! Subscribe here or in your favorite podcast app above. Please leave a review and share The Precision Medicine Podcast with your friends! ​ Download the full transcript here (pdf).

How does a Stanford University graduate with a MD/PhD that includes specialized training in one of the most aggressive, cure-focused specialties in medicine―Hematology and Bone Marrow Transplants―find her way to palliative care? By being still just long enough for her life to find her. Dr. Dawn Gross is uniquely qualified to lead a cultural revolution on end of life care. She holds combined degrees from Tufts University School of Medicine and the Sackler School of Biomedical Sciences, where she was trained rigorously as both a physician and scientist. Beginning her practice as a hospice team physician, Dawn was invited to attend on the palliative care team at the University of California, San Francisco (UCSF). She was subsequently recruited away to become the Arthur M. Coppola family chair for the Department of Supportive Care Medicine and clinical professor of hospice and palliative medicine at the City of Hope National Medical Center. Dawn wanted to be a scientist. She loved the science behind medicine and thought she would never aspire to become a practicing clinician. Yet, when her father was facing a serious illness, Dawn chose not continue on the scientific path she loved. That’s when she sat still long enough and allowed life to find her―and began to bake.Dawn didn’t just bake anything. She baked a batch of cookies from her grandmother’s old recipe books. “Watching my dad eat the cookie from his childhood, he was transported to a place of pure happiness and joy,” she recalls. “This made me realize how important the small things in life truly are at the end of life.” Upon her father’s admittance to hospice, dying only four days later, her grief took over. Throughout her medical training, Dawn was taught to separate her emotion, putting boundaries between her own self and the patients she served. As a hospice medical director, she knew one thing. She did not want to be a physician that chose not to relate with her patients facing end of life. She found that she simply could not take her heart out of her practice.Dawn returned to UCSF to join the newly formed palliative care committee within the San Francisco Department of Aging and Adult Services. In addition, she was invited to host a ground-breaking live, call-in radio program, Dying to Talk, broadcast on the oldest FM station west of the Mississippi, KALW 91.7 FM. Her experiences as a hospice and palliative care physician have given her an unequaled perspective on how to care for people in their own homes. Whether attending patients in trailer parks or penthouses, there is no ivory tower. Dawn’s personal encounters as a mother and as a witness to her father’s death and her mother’s simultaneous serious illness inspired her to write and speak extensively about the work she does today. Her writings have been published in a variety of medical journals, including: Science, JAMA, Annals of Internal Medicineand San Francisco Medicine. A recent piece, "The Error in 'There's Nothing More To Do,'" was featured in the “Opinionator” blog of the New York Times. Her recent work to develop a curriculum offering a "death-ed" class at Head Royce School in Oakland, CA, was also published in the New York Times. Dawn’s written words based upon her distinguished medical career have one mission: to show us how we can live fully until we die. She is determined, both through her writings and by example, to improve how the medical community and medical protocol communicate with people about their potential dire prognoses. Her undertaking is to assist patients and their families in dealing with the inevitable outcome of a life-ending health crisis with honesty and dignity. In the end, public policy must acknowledge and question incentives that prolong life with no appreciation for the impact on how we die. The public is just beginning to accept this dialogue and there is much more to be said.http://www.drasyouwish.com/ See acast.com/privacy for privacy and opt-out information.

Betty Ferrell, PhD, MA, FAAN, FPCN, director of the Division of Nursing Research and Education and professor at City of Hope National Medical Center, presents the ASCO Guideline on Integration of Palliative Care into Standard Oncology Care, originally published in the Journal of Clinical Oncology in January 2017.

In today’s podcast, Peggy Burhenn, a nurse and professional practice leader in Geriatric Oncology at City of Hope National Medical Center discusses several strategies for getting a better night’s sleep.   Quality of Life

Stephanie Hosford is the author of Bald, Fat & Crazy: How I Beat Cancer While Pregnant with One Daughter and Adopting Another (Nothing But The Truth, LLC, June 2015). She holds a Master’s Degree in Occupational Therapy from Tufts University as well as a black belt in taekwondo. She is also a member of the Speaker’s Bureau for the City of Hope National Medical Center. When not shuttling kids around town in her SUV, she can be found writing, at the gym, or shopping at Trader Joe’s for the items she forgot last time. She lives in Los Angeles with her husband and three children.   Please feel free to follow her at stephaniehosford.com.   Back Cover Summary Stephanie Hosford has a big decision to make. For her 20-year high school reunion, how should she style her hair? Little does she know, in a few months it won’t matter - she’ll be bald. And huge. What woman wouldn’t go a little crazy? After receiving a cancer diagnosis and a positive pregnancy test within days of each other, Stephanie, a happily married mother of one and in the midst of an international adoption, is suddenly fighting for her life, her children - and her sanity. Get ready to laugh, cry, gasp, and cheer on the ultimate 9-month roller coaster that takes us everywhere from the treadmill, to infusion rooms, and even across oceans. You will not forget this wild, true and ultimately satisfying story of love, motherhood and finding the inner strength we all hope is there when we need it.  

Our BlogTalkRadio show this week will focus on just what is involved in creating a good business plan. If you are a newpreneur, this show will show you the 5 essential elements of an effectice and actionable business and marketing plan. My guest is Carma Spence-Pothitt who has more than 20 years marketing and public relations experience under her belt. She has worked on campaigns for organizations such as City of Hope National Medical Center, The Marine Mammal Center and Champagne Deutz. She helps authors, speakers, coaches and other info-service professionals develop and nurture a business they love through better marketing, branding and web presence. We will be covering: What are the five essential elements you need to create a business and marketing plan that is easy to use and moves you toward your vision? What is the difference between the Vision and the Mission statements? What are the best types of objectives to include in your plan? How do strategies differ from the action plan? Once you've created you plan, what do you do next? Time permitting; we will open up the call for questions and answers. Please be sure to login to the chat room to ask questions during the call. We look forward to “seeing” you! We appreciate you tuning in to this episode of Your Partner In Success Radio with Host Denise Griffitts. If you enjoyed what you heard, please consider subscribing, rating, and leaving a review on your favorite podcast platform. Your support helps us reach more listeners and create even better content!Stay ConnectedWebsite: Your Partner In Success RadioEmail: mail@yourofficeontheweb.com

Thanks to medical advances, we now live longer, but living longer doesn’t necessarily make death any easier when it comes. Forget the good life, what in this world makes a good death? How does culture affect our choices? Palliative care offers some relief to suffering, yet it is our uncertainty about the end of life that keeps our dread alive. Experts visit Zócalo to share first-hand accounts and clinical insight: Dr. Susan Stone, the Director of Palliative Care at the Los Angeles County Medical Center; Dr. Betty Ferrell of the City of Hope National Medical Center; and moderator Dr. Michael Wilkes, Vice Dean for Medical Education at UC Davis, join us for an evening of big questions that demand courage, compassion, and a dash of wit. (This event is made possible by a generous grant from the California HealthCare Foundation.)