Journal of Clinical Oncology (JCO) Podcast

Host Dr. Davide Soldato and Dr. Shelia Garland discuss the JCO article "Randomized Controlled Trial of Virtually Delivered Cognitive Behavioral Therapy for Insomnia to Address Perceived Cancer-Related Cognitive Impairment in Cancer Survivors." TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Davide Soldato: Hello and welcome to JCO After Hours, the podcast where we sit down with authors from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato. I am a Medical Oncologist at Ospedale San Martino in Genoa, Italy. Today we are joined by JCO author Dr. Sheila Garland. She's a Professor of Psychology and Oncology at Memorial University, and she's the director at the Sleep, Health, and Wellness Lab and Senior Scientist at the Beatrice Hunter Cancer Research Institute. Dr. Garland will be discussing the article titled, “Randomized Controlled Trial of Virtually Delivered Cognitive Behavioral Therapy for Insomnia to Address Perceived Cancer-Related Cognitive Impairment in Cancer Survivors.” Thank you for speaking with us, Dr. Garland. Dr. Sheila Garland: Thank you so much for having me. Dr. Davide Soldato: So, Dr. Garland, you designed a study that relied on cognitive behavioral therapy to treat insomnia, and then you assessed whether improvement in insomnia would be associated with an improvement in cancer related cognitive impairment. So I wanted to ask if you could give us a little bit of context and explain the rationale between these studies. So how common are these symptoms among cancer survivors, and why do we think that improving insomnia would also improve cognitive function? Dr. Sheila Garland: Yeah, thank you very much. That's a really, really good question. And so cognitive behavior therapy for insomnia has been used to successfully treat insomnia in cancer survivors for quite some time. I think JCO was one of the first publishers to really demonstrate the potency of this intervention to improve insomnia. But as we know, patients will often present not just with insomnia, but insomnia comorbid with pain, fatigue, and very commonly cognitive impairment. If we take a look at the experimental research in sleep, we know that sleep quality and quantity is associated with very important cognitive functions. And so we've had clear sleep deprivation studies where if you're not able to successfully get sufficient quality or quantity of sleep, you're going to have impairments in attention and concentration and memory. So it really makes sense that if we're able to improve sleep in cancer survivors, that we're also able to address maybe some of the other concerns that they would have related to sleep. So this is an important clinical question for the patient's quality of life, but I also think it has important system implications where if we're looking at like resources and efficiency of allocating those resources, if we have an intervention that can treat multiple problems, that means that we can more effectively address lots of symptoms and use fewer resources in doing so. So that was the thought in designing this trial. Dr. Davide Soldato: Thank you very much. That was very, very clear. So you spoke about the intervention that you implemented in the clinical trial. So I was wondering if you could give us a little bit of context. How long was the intervention? What were the main points addressed? Because you said that, in the end, we already have some data regarding cognitive behavioral therapy for treating insomnia. So I was wondering, did you personalize in any way, the program or the intervention to fit more to the cancer survivors population? Dr. Sheila Garland: Yeah. So it is based on a protocol that has been well researched and has a great deal of evidence of efficacy. But we delivered this intervention over a course of seven weeks. So individuals had individual sessions with a trained therapist, and those sessions lasted about an...

In this episode of JCO Article Insights, Dr. Giselle de Souza Carvalho interviews Dr. Hatem Azim and Dr. Ann partridge on their JCO article “Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy,” TRANSCRIPT Giselle Carvalho: Welcome to the JCO Article Insights episode for the August issue of the Journal of Clinical Oncology. This is Giselle Carvalho, your host. I'm a Medical Oncologist in Brazil focusing on breast cancer and melanoma skin cancers, and one of the ASCO editorial fellows at JCO this year. Today, I will have the opportunity to interview Dr. Hatem Azim and Dr. Ann Partridge, two of the authors of the POSITIVE trial. We will be discussing their trial on “Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy,” which was published in May this year. Hello, Dr. Azim and Dr. Partridge. Welcome to our podcast. Dr. Ann Partridge: Hi. Thanks. Dr. Hatem Azim: Hello. Giselle Carvalho: So, beginning with our interview for breast cancer survivors, in addition to the treatment itself, aging is one of the major contributors to infertility. The optimal duration of adjuvant endocrine therapy in patients with hormone positive early breast cancer ranges from five to ten years, depending on patient and tumor characteristics. This time interval can be critical for women who wish to attempt pregnancy. One of the main concerns in daily breast cancer oncology practice is whether breast cancer recurrence rates are increased either by temporary interruption of endocrine therapy for pregnancy or by the use of assisted reproductive technologies. Dr. Azim, what about assisted reproductive technology is worrisome regarding breast cancer outcomes? And how do the POSITIVE study results address the concern about worsening breast cancer outcomes either with assisted reproductive technology or endocrine therapy interruption? Dr. Hatem Azim: So, in the primary analysis of the POSITIVE trial, we tried to address one of these questions, whether temporary interruption with endocrine therapy affects breast cancer outcome. And what we found was that interruption did not appear to have a detrimental impact at the median follow up of 41 months. So in the current manuscript, we addressed the second question, whether assisted production of fertility preservation has an impact as well on breast cancer outcome. And we did not find any worsening of outcomes in patients who underwent these procedures compared to those who had a spontaneous pregnancy. Of course, we have relatively short follow up, but at least the outcomes at the median follow up of around 3 to 4 years appears to be reassuring. Giselle Carvalho: I see. Thank you. These are really important outcomes regarding premenopausal patients. So, moving on, results from your study show that after 24 months, 80% of women under 35 years old had at least one successful pregnancy, while the same was true for 50% of women aged 40 to 42. These results are particularly impressive considering that over 60% of women over 35 had undergone chemotherapy. Dr. Partridge, other than age, what factors did you find were associated with a successful pregnancy? Dr. Ann Partridge: Yeah. The biggest factor, other than age, that was associated with successful live birth pregnancy was use of assisted reproductive technologies. So either having gone through IVF prior to diagnosis and banking eggs or embryos prior to diagnosis and then using them during the study, for undergoing stimulation of the ovaries during the study and then using it during the study. And that's what we also looked at in this most recent analysis of the initial POSITIVE data. Giselle Carvalho: I see. Thank you. The group of patients who underwent embryo oocyte cryopreservation at diagnosis were more likely to be nulliparous and treated with chemotherapy. Presumably these...

Host Dr. Davide Soldato interviews Dr. Sana Raoof to discuss the JCO article Turning the Knobs on Screening Liquid Biopsies for High-Risk Populations: Potential for Dialing Down Invasive Procedures. TRANSCRIPT Dr. Davide Soldato: Hello, and welcome to JCO After Hours, the podcast where we sit down with others from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, Medical Oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by JCO author Dr. Sana Raoof, Physician at Memorial Sloan Kettering, to talk about her article, “Turning the Knobs on Screening Liquid Biopsies for High-Risk Populations: Potential for Dialing Down Invasive Procedures.” Thank you for joining us today, Dr. Raoof. Dr. Sana Raoof: Thank you so much. It's lovely to be here. Dr. Davide Soldato: So, Dr. Raoof, I just wanted to start a little bit about the theme of your article, which is really centered around multi-cancer early detection tests. And this comes from the results of several studies that showed their reliability and efficacy in identifying cancer in the average risk population. But I just wanted to ask you if you could give us and our readers a brief overview of how these tests work and how they were designed for this specific population. Dr. Sana Raoof: Of course. Well, there's an interesting story. The origin of multi-cancer early detection tests actually begins with insights that come from the field of obstetrics and gynecology. So about six or seven years ago, in the peripheral blood of pregnant women, we discovered that you can actually find fetal DNA floating around. And that was an early discovery of cell free DNA coming from the baby into the mother's bloodstream. But in some of those young, otherwise healthy women, we also discovered that there's another clonal signal, unfortunately not coming from the fetus, but coming from an undiagnosed tumor. And that led to the entire field of circulating tumor DNA and all of its applications. Of course, scientists in the last six or seven years have harnessed the fact that DNA and the methylation patterns on the circulating tumor DNA, as well as other analytes like glycosaminoglycans, proteins, and other analytes, are secreted by tumors into the peripheral blood in order to try and screen for tumors, hopefully at early stages, when there are still curative, definitive interventions that are available. There's several different tests now that are providing the ability to detect cancers at many stages, including early stages. They're in different phases of preclinical to clinical development, and one is even commercialized and available by prescription in the United States. Dr. Davide Soldato: Okay. So I think that in most of these tests, they really look at the tumor DNA, so they identify mutations or, for example, methylation patterns. But do we also have some tests that integrate some other type of biomarkers that we can identify in the blood? Like, are they integrated all with the others, or are we just relying on circulating tumor DNA? Dr. Sana Raoof: It's a great question. There's a lot of really fascinating biology that different companies predominantly are using in order to find signs of early cancer. One of the analytes that I find really interesting, other than looking for small variants in circulating tumor DNA and looking at methylation patterns, as you mentioned, is looking at fragment length. So, for example, the company DELFI looks at the different patterns of the length of DNA fragments that are floating around in the peripheral blood. And not only is fragment length tissue specific, so in theory, a fragmentomics based multi-cancer early detection test could tell us what is the tissue that this aberrant signal is coming from, but they can also tell you if there's likely a cancer present, because there's a difference in fragment length patterns in cancer versus non cancer. There are also other...

In this episode of JCO Article Insights, Rohit Singh interviews Dr. Ticiana Leal on the editorial, "Back to the Drawing Board: Overcoming Resistance to PD-1 Blockade." TRANSCRIPT The guests' disclosures can be found in the transcript. Dr. Rohit Singh: Hello and welcome to JCO’s Article Insights. I am your host Rohit Singh and today we will be discussing the JCO article, “Back to the Drawing Board: Overcoming Resistance to PD-1 Blockade.” And we are joined by the senior author of the article, Dr. Ticiana Leal. Dr. Leal is an Associate Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, and she serves as director of Thoracic Medical Thoracic Oncology Medical Program and Multidisciplinary Thoracic Oncology Leader at the Winship Cancer Institute. She also served as a member of the Board of Directors at the Georgia Society of Clinical Oncology. Dr. Leal, welcome to our podcast and thank you for joining us. Dr. Ticiana Leal: Thank you, Rohit. Thank you for this interesting opportunity to discuss our editorial. My co-authors and I are very glad to be here today. So, Dr. Jennifer Carlisle and Dr. Liu were co-authors with me on this editorial. Dr. Rohit Singh: It's a really good article. And just for our audiences, the article again, titled “Back to the Drawing Board: Overcoming Resistance to PD-1 Blockade,” it discusses the challenges and the potential strategies for overcoming resistance to immune checkbox inhibitors in patients with non-small cell lung cancer. In this article, Dr. Leal and colleagues talk about the second line of drug when the patient developed disease progression while immunotherapy and they develop resistance and their definitions and what to do. So, to Dr. Leal, can you please explain the mechanisms of primary and acquired resistance to immune check prohibitors in non-small cell lung cancer? I also saw in your article you proposed the definition of immunotherapy resistance in solid tumors, distinguishing between primary resistance and acquired resistance. So, if you can please share your thoughts and explain their mechanism. Dr. Ticiana Leal: So primary resistance and acquired resistance are related to tumor intrinsic and tumor extrinsic factors. And this is mainly clinically defined as of now according to previous response patterns and timing of occurrence, and these definitions can be heterogeneous, and we certainly think that biologically they can be very different. And it can be different according to prior therapy, whether patients got immunotherapy as PD-1, PD-L1 inhibitor alone or combination strategy with CTLA-4, or the combination with chemotherapy. But the patterns of resistance can be very different and can be based on defects and antigen presentation. It can also be due to tumor microenvironment immunosuppressive effects, and there are also additional inhibitory checkpoints that can be involved. The definition in terms of when to call it primary or acquired resistance at this point has really been based on consensus guidelines by SITC, by Esmo, as well as our group Lung-MAP has developed clinical trials in this space. Specifically, through Lung-MAP, we've defined and incorporated the definition of acquired resistance as patients who have had prior exposure of 84 days or greater and then have had progression of their disease. Dr. Rohit Singh: I can see why it is so challenging to come up with a standard definition for immune checkpoint resistance and I think incorporating these definitions and predictive biomarkers for clinical trial design is going to be more important going forward. Your article talks about CONTACT-01 study, so can you please discuss the CONTACT-01 study and how the shifting treatment paradigm in the first-time study impacted it and at the same time also discuss the potential implication of the differential outcome observed between the men and women in the CONTACT-01 study. Dr. Ticiana Leal: CONTACT-01 was a much-awaited...

Dr. Shannon Westin and her guest, Dr. Chao Cao, discuss the paper "Prevalence and Cancer-Specific Patterns of Functional Disability Among US Cancer Survivors, 2017-2022" recently published in the JCO. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth with authors and manuscripts that have been published in the Journal of Clinical Oncology. I'm your host, Shannon Westin, gynecologic oncologist by trade and Social Media Editor for the JCO. And it is my pleasure to welcome Dr. Cao, a research fellow in medicine, Department of Medical Oncology, Dana Farber, Cancer Institute, Boston, Massachusetts. Welcome. Dr. Cao: Thanks for having me. Dr. Shannon Westin: Of course. And we're going to be discussing your very important work, “The Prevalence and Cancer Specific Patterns of Functional Disability Among US Cancer Survivors, 2017-2022,” which was published in the Journal of Clinical Oncology on April 4, 2024. And Dr. Cao has no conflicts of interest in regards to this podcast. So let's get right into it. I'd love to level set. Can you speak a little bit about the definition of cancer survivorship and the number of cancer survivors currently in the United States? Dr. Cao: I think this is an important question because everyone somewhat has confusion about the definition of cancer survivorship. So based on the definition by the National Cancer Institute, cancer survivorship refers to the phase of life following the diagnosed cancer. And nowadays, it's estimated about 80 million American individuals are living after being diagnosed with cancer. And this number is projected to rise to 26 million by 2040. Dr. Shannon Westin: Wow. So obviously, any research that we can do in this population is going to be so important as that number absolutely continues to grow. And before we get into the specifics of your work, I'd love for you to speak a little bit about the importance of functional disability, which is what we studied in this work and why it might be observed in cancer survivors. Dr. Cao: Yeah, sure. So, maintaining physical function is fundamental to perform life tasks and engage in fruitful jobs. In terms of cancer survivors, many cancer survivors experience side effects from cancer and its treatment. These side effects, include the pain, fatigue, and musculoskeletal dysfunction, which can induce physical limitation and eventually physical disability. And specifically, this is such a burden for the US, social, societal and economic burden. Here I have the specific number: so in 2019, an estimate of over 100,000 people living with and beyond cancer were unable to work and they received a Social Security Administration disability benefit with the resulting cost of US$1.8 billion in disability claims. Dr. Shannon Westin: Wow. We always think about the impact on the survivor, on their family, but I think it's also really important to look at those other objective data about the impact on society as a whole. Thank you, that was great detail. Do we know anything about who might be proportionately more affected by cancer induced physical impairments and disabilities? Dr. Cao: Actually, this is our key question for our manuscript, but before we developed our hypothesis, we also looked at the data from the general population. So we observed that visual minorities and underserved populations, such as people with lower socioeconomic status and living in the rural area, and also those with unhealthy types of behavior, for example, smoking, obesity, and physical inactivity, are more likely to have physical limitations and disabilities. And also the comorbidity in cancer survival, such as diabetes, cardiovascular disease, also increase the likelihood of physical disability. We also have cancer survivors, particularly for cancer patients who are currently receiving cancer treatment, for...

In this JCO Article Insights episode, Alexandra Rojek provides a summary on "Anti-CD19 Chimeric Antigen Receptor T-cell therapy for Richter’s Transformation: An International, Multicenter, Retrospective Study by Kittai, et al published in the Journal of Clinical Oncology March 29th, 2024. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Alexandra Rojek: Hello and welcome to JCO Article Insights. I'm your host, Alexandra Rojek, and today we will be discussing an original report published in the June 10th issue of JCO titled, “Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: An International, Multicenter, Retrospective Study,” by Kittai et al. This report addresses the real world efficacy of CAR T-cell therapy for patients with Richter transformation of CLL to large B cell lymphoma, which represents a high risk group of patients with an unmet need for novel and more effective therapeutic agents than are currently available. Richter's represents the transformation of chronic lymphocytic leukemia, or CLL, to an aggressive lymphoma, most often a large B cell lymphoma, most similar to diffuse large B cell lymphoma or DLBCL. Treatment for Richters is often modeled after treatment practices for DLBCL. However, there's no clear standard of care and outcomes for these patients lag behind those of large B cell lymphoma patients otherwise. An important advance in recent years in the DLBCL field is the approval of anti CD19 CAR T-cell therapy in the second and third line settings. However, patients with Richter transformation were largely excluded from these pivotal trials. This study in JCO thus set out to address what the real world outcomes were for patients with Richters who were treated with CAR T-cell therapy across 12 centers internationally. The study included 69 patients across these twelve sites, with a median age of 63 years at diagnosis of Richters and a median of six years after initial CLL diagnosis. Included patients received a median of four prior lines of therapy for either CLL or Richters, with a median of two prior lines of therapy for Richters, although two patients had not received any prior therapy for their Richter transformation. The most recent prior treatments included chemoimmunotherapy in 29% of patients, followed by BTK inhibitors in 19%, as well as combinations of BTK inhibitors and BCL2 inhibitors in 12%. 17% of patients had not received prior therapy for their CLL before their diagnosis with Richters, 58% of cases had known TP53 mutations at time of transformation, and 41% exhibited deletion 17p by FISH. Prior to receiving CAR T-cell therapy, 86% of patients required additional bridging therapy, most commonly with a BTK inhibitor or chemoimmunotherapy. A diverse set of commercial CAR T-cell products were represented in this study, with the majority of patients at 64% receiving axi-cel, 25% receiving tisa-cel, 10% receiving liso-cel, and one patient received brexu-cel in an investigational setting. Median time from apheresis to CAR T infusion was 34 days, and 59% of patients continued on a BTK inhibitor throughout CAR T-cell therapy. When we move on to look at responses, 66 out of 69 patients were available for response. Three patients died related to adverse events after infusion and before response assessment, with the best overall response of complete response or CR in 46% of patients and partial response or PR in 17% for an overall response rate of 63%. With a median follow up time of 24 months, the median PFS in the study was 4.7 months and the median OS was 8.5 months. For those who achieved a CR, the median duration of response was an impressive 27 months, and for those achieving PR, the median duration of response was only two months. The two year PFS rate was thus 28%, and the two year OS rate was 38%. Four patients who achieved a CR went on to receive an allogeneic stem cell transplant. Among those whose disease progressed, 8% had...

Dr. Shannon Westin and her guest, Dr. Bryan Schneider discuss the article “ECOG-ACRIN EAZ171: Prospective Validation Trial of Germline Predictors of Taxane-induced Peripheral Neuropathy in Black Women with Early Stage Breast Cancer” recently published in the JCO and presented at the 2024 ASCO Annual Meeting. 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, the podcast where we get in depth on manuscripts published in the Journal of Clinical Oncology. I am your host, Shannon Westin, GYN Oncology Extraordinaire and also the Social Media Editor of the Journal of Clinical Oncology. And it is my great pleasure to present some really incredible work today that is going to be a dual publication in the Journal Clinical Oncology and a presentation at the American Society of Clinical Oncology Annual Meeting on Monday, June 3. And this is the “ECOG-ACRIN EAZ171: Prospective Validation Trial of Germline Predictors of Taxane-induced Peripheral Neuropathy in Black Women with Early Stage Breast Cancer.” And I am joined today by the senior author on the presentation and the primary author on the manuscript, Dr. Bryan Schneider. He is the Vera Bradley Professor of Oncology, the Professor of Medicine and Medical Molecular Genetics at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center in Indianapolis. Welcome, Dr. Schneider. Dr. Bryan Schneider: Dr. Westin, thank you for having me on today. Shannon Westin: We're so excited and we're really excited to really summarize this incredible work that's being presented today. So, first, let's just levelset. Can you speak a little bit about peripheral neuropathy and the most common causes in patients with cancer? Dr. Bryan Schneider: Yeah, I mean, I think for those of us who treat patients using the taxanes, we recognize probably one of the most important and common side effects that we deal with is peripheral neuropathy, and one that can, I think, impact both quality of life, but also impacts the ability to maintain dose intensity. When we think about risk factors for neuropathy, historically, I think obesity has been reported as a potential risk factor, as has diabetes and other conditions which put people at risk for neuropathy. Shannon Westin: And prior to your work that you'll discuss with us today, what do we know about the incidence of peripheral neuropathy in patients that identify as black? Dr. Bryan Schneider: Yeah. So, interestingly, I think we've recognized that patients who self identify as black have disparate outcomes in terms of inferior survival and more aggressive subtypes of breast cancer, like triple negative breast cancer. But I think the idea of toxicity being a disparate factor as well is probably a more recent one. Interestingly, as we set out to identify biomarkers to predict outcomes in the large adjuvant trial E5103, we weren't really setting out to look at this by race. We were using at that time, genome-wide approaches to identify biomarkers for toxicity and also efficacy. But what was interesting as we did that one of the most important predictors, as we looked across a number of important toxicities, was ancestry. And really the science spoke to us, it was very clear that patients of African ancestry had higher rates of bev-induced hypertension, anthracycline-induced cardiomyopathies and also peripheral neuropathy. Shannon Westin: That's so interesting. We have so much overlap in gynecologic oncology and breast cancer. And I don't know that I've ever seen work like this. And now it's making me very intrigued and making me want to move forward to that. Can you talk a little bit more about this ECOG-ACRIN E5103, like briefly about the study and what it demonstrated specifically? Dr. Bryan Schneider: Yeah. So E5103 was an adjuvant breast cancer trial that really set out to look at the impact of bevacizumab in the curative setting....

In this JCO Article Insights episode, Alexandra Rojek provides a summary on "Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial" by Camus et al published February 16th, 2024 and the associated editorial written by Dr. Mehta-Shah and Dr. Horwitz. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Alexandra Rojek: Hello and welcome to JCO Article Insights. I'm your host, Alexandra Rojek, and today we will be discussing a clinical trial update published in the May 10th issue of JCO addressing the long term follow up of the addition of romidepsin to CHOP chemotherapy for previously untreated peripheral T-cell lymphoma, or PTCL. This report by Camus et al discusses a five-year follow up of the original Ro-CHOP trial, which did not meet its primary endpoint of progression free survival. The original Ro-CHOP study, conducted by the LYSA group, was published in 2021 in JCO and was conducted as a one-to-one randomized phase III study of Ro-CHOP versus CHOP for patients aged 18 to 80 years with PTCL. 98 international centers were included, and the study enrolled patients between 2013 and ‘17. Nodal follicular helper T-cell, or TFH lymphoma was defined in this study follow-up as a PTCL expressing at least two of five TFH markers according to the latest classifications. The study's primary endpoint was PFS with secondary endpoints of OS and duration of response, or DOR. Five year follow up was reached in December 2022. In the original study report, the addition of romidepsin to CHOP did result in a reduction of dose intensity of chemotherapy. However, in this updated follow up, there were no new safety signals reported. A total of 421 patients were enrolled in the trial with a median age of 65 years. Notably, those who were randomized to the Ro-CHOP arm had a higher proportion of IPI 4-5 scores at 33%, versus 24% of those who were assigned to CHOP alone despite randomization. Nearly half of patients carried a histologic diagnosis of angioimmunoblastic T-cell lymphoma. 30% were characterized as PTCL NOS, not otherwise specified, 10% ALK negative anaplastic large cell lymphoma, leaving 13% reported as other. Over 60% of patients had stage four disease at enrollment, with nearly half having more than two sites of extranodal involvement. Median follow up was six years with a median PFS of 12 months for Ro-CHOP and 10.2 months for CHOP, which did not reach statistical significance as reported in the original study publication. Estimated five year OS available as a part of this clinical trial update was 50% for Ro-CHOP and 43% for CHOP alone, and also did not reach significance. There was, however, a longer duration of response observed in the Ro-CHOP arm at 52 months versus 24 months for CHOP, which is a new finding in this extended follow up of the study. In an effort to better understand whether there are subgroups which may benefit from romidepsin despite the overall negative outcome of this study, the authors are able to provide new insights from this Ro-CHOP study in line with our current and updated understanding of PTCL. When the authors evaluated the study population for subgroups which may benefit from addition of romidepsin, TFH lymphomas, which included angioimmunoblastic, follicular, and NOS subtypes, were noted to have an improved response to the addition of this HDAC inhibitor. This subgroup, numbering 201 patients, experienced a mean PFS of over 19 months with Ro-CHOP versus over 10 months for those who received CHOP, and this difference achieved statistical significance. Similarly, there was a higher complete response rate and longer duration of response for those in the TFH subgroup who received romidepsin. The authors also make note that those patients in this subgroup with high IPI appeared to...

Dr. Shannon Westin and her guest, Dr. Patrick Stone, discuss the article, Methylphenidate Versus Placebo for Treating Fatigue in People with Advanced Cancer, a Randomized, Double-Blind, Multicenter Placebo-Controlled Trial, recently published in JCO. 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, the podcast where we go in depth on manuscripts and research published in the Journal of Clinical Oncology. I am your host, Shannon Westin, Social Media Editor for JCO and a Gynecologic Oncologist by trade. I am thrilled today to present Methylphenidate Versus Placebo for Treating Fatigue in People with Advanced Cancer, a Randomized, Double-Blind, Multicenter Placebo-Controlled Trial. This manuscript is a dual publication in the Journal of Clinical Oncology and presentation at the European Association of Palliative Care Congress here on May 17, 2024. And to review this incredible research with us will be Professor Patrick Stone, the Head of Department of Marie Curie Palliative Care Research Department, Division of Psychiatry at University College London. Welcome, Dr. Stone. Dr. Patrick Stone: Thank you very much. Thank you. Shannon Westin: Let's get right to it, we’ll level set. Can you speak a bit about the definition of cancer-related fatigue and how common it is in people with advanced cancer? Dr. Patrick Stone: Sure. I think fatigue is a difficult thing to nail down really and define it clearly, and there are lots of definitions out there. In many ways, the simplest definition is the EAPC, the European Association of Palliative Care's definition of just a subjective sensation of weakness, feeling tired, and exhaustion. The reality is that that symptom is very common in the general population. And so if you really want to get a handle on it, I think a good way to do it is to think about taking an operational definition and say, “Look, if fatigue is normally distributed approximately in the general population, then we should consider severe fatigue or pathological fatigue could be defined as fatigue that is worse than 95% of the general population. And if you think that definition, then prevalence of fatigue in patients with newly diagnosed breast or prostate cancer, for instance, is around 15%, so three times as common as the most severe fatigue in the general population. If you come to patients with newly diagnosed non-small cell lung cancer, it’s up to about 50%. And if you come to my area, which is palliative care and you go to a hospice and you ask people to complete a fatigue questionnaire, 78-80% of people complain of fatigue that is more severe than 95% of the general population. So that I think gives us a good handle on sort of the severity of this problem in cancer patients and how it progresses as disease progresses. Shannon Westin: I love this because I think we always struggle with exactly how to nail down the definition and exactly how to treat it. So I think that it’s a really nice transition to existing treatment options for this issue and exactly how they might work. Dr. Patrick Stone: The first thing to say is in medicine if you can find a cause then you give a treatment directed at the cause and obviously that applies to fatigue as well. So the first thing is to do a thorough assessment of your patient, and if you can find an easily remediable cause such as anemia, hypocalcemia, or hypomagnesemia, or maybe other things like depression, which might manifest as fatigue, then you should try and give a treatment directed at that cause. But, for many patients, there won't be a single clearly identifiable cause you can target. And then people use more broad spectrum approaches if you like. The most well-studied I think is exercise. And exercise, there have been lots of randomized controlled trials in different types of exercise and it’s a well attested treatment, which I think has good evidence of...

JCO Editor in Chief, Dr. Jonathan Friedberg interviews Dr. Pamela Kunz, Editor in Chief of the new premier open access journal, JCO Oncology Advances. Dr. Friedberg and Dr. Kunz discuss what is to come from the journal and the benefits of an open access journal. TRANSCRIPT Dr. Jonathan Friedberg: Hello and welcome to another episode of JCO After Hours. I'm your guest host, Jonathan Friedberg, Editor in Chief of JCO, and today we have a very special episode with Pamela Kunz, Associate Professor of Medicine in the Division of Oncology at Yale School of Medicine and Yale Cancer Center. As the new editor in chief of JCO Oncology Advances, she is with us today to share a new opportunity for authors to submit to ASCO’s new online open access journal. Pam, welcome. Dr. Pamela Kunz: Thank you. Dr. Jonathan Friedberg: I guess my first question to you is, why did you take this role of editor in chief? People have asked me the same question, and I'm still, I think, trying to figure out the answer. So how did you decide to do this? Dr. Pamela Kunz: That's a great question, and I might ask you the same thing. I think as I've gone on in my career, I really like saying I think about what I say yes and no to, and like saying yes to things that I think can make a difference and have real impact. And as a clinical trialist and someone who really hopes to advance the field scientifically, I think it was really exciting to think about helping to craft the future of the science of oncology and to also do it in a way, as we will later talk about open access, but do it in a way that really thinks about a broad audience, because open access really requires us to think about meeting the needs of our audience, as the articles will likely have broader reach. Dr. Jonathan Friedberg: So, I mean, I can say I'm very excited about this journal. We do have a number of outstanding papers that we're not able to accept at JCO and knowing that there'll be a good home for these papers is heartwarming for me. Can you tell me a little bit about your vision and goals for this journal? You're really starting with a blank palette. It must be exciting to try to craft what this is going to be about. Dr. Pamela Kunz: It is really exciting. It's a little scary, I'll be honest, to have a blank slate, but I'm appreciative of you and the other editors in chief and staff for helping to provide some guidance. I think that in the beginning, as you were speaking to, there's an opportunity for us to really keep some great science in the JCO family. And so at least early on, we're hoping to really attract and think about publishing some earlier phase trials that may not quite meet the bar of getting published in JCO. So, phase I, phase II trials, even secondary analyses that yield important data from some of the larger phase III trials. This will be an evolution, I think, also. I think that what we may look like this year may look a little bit different in future years, but at least initially, we'll be focusing on some of the earlier phase clinical trials. I'm now framing this around beyond the clinical trial of secondary analyses quality of life, PROs. One thing that's exciting, a new article type will be plain language summaries. So really interpreting the clinical trial for patients and the lay public, I think that's an initial way that we're going to be thinking about it. Dr. Jonathan Friedberg: And who do you see as the audience for this journal? Dr. Pamela Kunz: Well, the opportunity that we have with open access is that we really have a much broader audience than we will have had historically with some of the non-open access journals. And I think that means that we have an obligation to be thinking about who that audience is. So, it's a great question. I think our audience will certainly be some of our typical readers, really, the oncology scientific community, but it will likely also be other physicians, primary care physicians, community oncologists, global...

In this JCO Article Insights episode, Rohit Singh provides summary on two articles published in the April 10th issue of the Journal of Clinical Oncology. The first article, "Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)" describes a randomized, open-label, multicenter, phase III study evaluating the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy. The second is the accompanying Oncology Grand Rounds. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Rohit Singh: Hello and welcome to JCO Article Insights. I'm your host, Dr. Rohit Singh. Today I will provide a summary of a Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04), by Dr. Park and colleagues from Seoul, Korea. The purpose of this study was to evaluate the efficacy and safety of the ABCP regimen based on IMpower150 in patients with EGFR or ALK mutated non-small cell lung cancer who had progressed on prior targeted treatment. I will also discuss an Oncology Grand Round case titled "Management of Treatment Resistance in Patients with Advanced EGFR Lung Cancer: Personalization, Parsimony, and Partnership", by Dr. Vallillo and colleagues from Lahey Hospital Medical Center and Tufts University School of Medicine, Boston, Massachusetts. Oncology Grand Round cases help us to give a clinical context to the clinical trial. While TKIs are the established standard of care for non-small cell lung cancer harboring driver mutations, most patients will develop resistance to these treatments. Immune checkpoint inhibitors, with or without chemo, have shown clinical benefits of immune checkpoint monotherapy in patients with EGFR-mutated non-small cell lung cancer. Consequently, platinum-based chemo is the standard of care for patients with EGFR TKI failure. This was a phase III, multicenter, open-label, randomized trial conducted at 16 hospitals across the Republic of Korea. Patients diagnosed with stage four non-small cell lung cancer with sensitizing EGFR mutation or ALK translocation were included in the study. Patients were randomly assigned to the ABCP arm or chemo-only arm in a 2:1 ratio. Eligible patients were stratified on the mutation type (EGFR mutation vs. ALK translocation) and the presence of brain metastasis. No crossover to atezolizumab was permitted. The recruitment with T790M mutation was capped at 30%. Patients who responded continued to receive maintenance with atezolizumab until disease progression or unacceptable toxicities occurred. If a patient was identified to have an acquired T790M mutation after the failure of a first or second-generation EGFR TKI, the patient had to be treated with a third-generation EGFR TKI before enrollment. The primary endpoint was investigator-assessed objective response rate according to research criteria. The secondary endpoints included overall survival and progression-free survival at one and two years, and the duration of response, along with a safety analysis. Investigators also did an exploratory biomarker analysis based on PD-L1 expression and its correlation with the response. They also analyzed the distribution of tumor-infiltrating lymphocytes, and a cut-off of 20% inflamed score was used to compare the two arms. Overall, 228 patients were enrolled, 154 in the ABCP arm and 74 in the chemo-only arm. Most patients were female at 56.1% and never smokers at 62.7%. Brain metastasis was present in 42.7% of patients. Most patients had previously received EGFR TKI therapy, however, only 8% and 30% received third-generation TKI as first-line therapy in the ABCP arm and chemo-only arm, respectively. The majority of the patients were EGFR at 90%. The median duration of...

Dr. Shannon Westin and her guests, Dr. Emily S. Tonorezos and Dr. Michael Halpern, discuss their article, "Myths and Presumptions About Cancer Survivorship" recently published in the JCO. TRANSCRIPT The guests on this podcast episode have no disclosures to declare. Shannon Westin:Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we go in depth on manuscripts published in the Journal of Clinical Oncology. I am your host, Social Media Editor of the JCO, Shannon Westin, and also a GYN Oncologist by trade. I'm thrilled to bring a topic that is very close to my heart. We're going to be talking about a Comments and Controversies article published in the JCO on November 16, 2023, entitled "Myths and Presumptions about Cancer Survivorship." I know you all will find this topic as enthralling as I have, and the authors do not have any conflicts of interest. I'm joined by two of the authors on this important work. The first is Dr. Michael Halpern, he’s the Medical Officer in the Health Assessment Research Branch of the Health Care Delivery Research Program. Welcome, Dr. Halpern. Dr. Michael Halpern: Thank you for having us on. Shannon Westin: We're also accompanied by Dr. Emily Tonorezos, the Director of the Office of Cancer Survivorship, and both of them work in the Division of Cancer Control and Population Sciences at the National Cancer Institute, National Institutes of Health. Welcome. Dr. Emily Tonorezos: Thank you for having us. Shannon Westin: So, let's get right into it. I want to level set first. I would love for one or both of you to speak a little bit about the state of cancer survivorship currently. What's the prevalence of cancer survivors here in the US? Globally? What do we expect as time passes? Dr. Emily Tonorezos: Thank you for starting with this question. In the Office of Cancer Survivorship, we use a definition of cancer survivor that we got from the advocacy community many years ago. We use a definition that says “a person is a cancer survivor from the time of diagnosis through the balance of life.” That means in the United States, we estimate that we have a little over 18 million cancer survivors, and globally, it's a little more difficult to estimate those numbers. Not every country has a cancer registry to count the number of cases, but we think there are upwards of 53 million cancer survivors diagnosed within the last five years in the world. Shannon Westin: Wow. And so this is why it's so important, such a large number, and that's just an estimate. And we know this is only going to be growing. I personally learned so much from your manuscript, which is critically based on the understanding that our beliefs as practitioners truly impact the way we care for our cancer survivors. I admit, I definitely held or hold some of these beliefs, and I'm certainly grateful that you're providing that objective evidence to support or refute these claims. So, with that being said, let's tackle the first one that you all approached: Shared care results in the best outcomes for cancer survivors. I think first I'd love to hear about what your definition of shared care is. What does that really mean in the context of cancer survivorship? Dr. Michael Halpern: Shared care is a deliberate process to coordinate and integrate components of survivorship care between specialty, in this case, oncology providers, and primary care providers. And part of the issues with this belief about shared care being the best have to do with the broad practice experience of survivorship care. While the ideal definition is this integrated and coordinated care, shared care can range from one extreme to being essentially oncologist-led care - where the oncologist also sends information to the primary care providers; and to the other extreme - care led by primary care providers and an oncologist is available to answer questions as needed. So part of the issue with the available literature is that there is a...

In this JCO Article Insights episode, Alexandra Rojek provides a summary on two long term follow studies: "Long-Term Follow-Up of Rituximab Maintenance in Young Patients With Mantle-Cell Lymphoma Included in the LYMA Trial: A LYSA Study" by Sarkozy, et al published on December 18th, 2023 and "Long Term Follow Up of the RESORT Study (E4402): A Randomized Phase III Comparison of Two Different Rituximab Dosing Strategies for Low Tumor Burden Follicular Lymphoma," by Kahl, et al, published January 9, 2024. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Alexandra Rojek: Hello and welcome to JCO Article Insights. I'm your host, Alexandra Rojek, and today we will be discussing two clinical trial updates published in the March 1st issue of JCO, focusing on the long-term outcomes of rituximab therapy for patients with lymphoma. The first paper discusses the use of maintenance rituximab for mantle cell lymphoma patients in the LYMA trial, and the second paper addresses rituximab dosing strategies for low tumor burden follicular lymphoma in the RESORT study. The first article by Sarkozy et al. for the LYSA group is titled "Long-Term Follow-Up of Rituximab Maintenance in Young Patients with Mantle Cell Lymphoma Included in the LYMA Trial: A LYSA Study." The LYMA trial was designed to answer whether the addition of the CD20-targeting monoclonal antibody rituximab provided additional benefit for patients with mantle cell lymphoma who achieved a response to induction chemoimmunotherapy, followed by consolidative autologous stem cell transplant in randomized patients, maintenance rituximab for three years versus observation alone. The primary analysis of the LYMA trial was published in 2017 and showed that the primary endpoint of four-year event-free survival or EFS was met at 79% in the maintenance rituximab arm compared to 61% in the observation alone arm. Additionally, there was a four-year overall survival or OS benefit of 89% versus 80% in favor of maintenance rituximab. Thus, on the basis of the LYMA trial primary analysis, the use of maintenance rituximab after consolidative autologous stem cell transplantation has become the standard of care in the field for these patients. The long-term safety and efficacy data presented in this clinical trial update for the LYMA study continue to demonstrate ongoing EFS and OS benefit for patients randomized to maintenance rituximab. Patients were initially enrolled between 2008 and 2012, and 240 patients were randomized to either arm. EFS in this study was defined as absence of disease progression, relapse, or death, severe infection, or allergy to rituximab. The data cutoff for this updated analysis was April 2019, with a median follow-up from randomization of seven years for living patients with a note that this is prior to the COVID-19 pandemic. For those in the maintenance rituximab arm, the seven-year EFS was 76% compared to 46% for those under observation. For those on the rituximab arm, the majority of relapses occurred within three years of randomization and thus while on maintenance rituximab, which the authors suggest does not show an increase in incidence of relapse after the end of maintenance therapy. The seven-year overall survival was 83% for those on the rituximab arm compared to 72% for those on the observation, with a log-rank p-value of 0.08. There was no difference in causes of death between the treatment arms noted. Notably, the patients who received maintenance rituximab after induction and transplant experienced a shorter second OS after relapse therapy, with a median OS2 of 1.1 years compared to 4.6 years favoring those on the observation arm, without impact of the type of salvage therapy received. Although this study was conducted before BTK inhibitors were approved in France and thus used at a low rate for patients who relapsed after initial therapy. This suggests that those who relapse after maintenance rituximab were those with the...

Dr. Shannon Westin and her guests, Dr. Herbert Duvivier and Dr. Richard Schilsky, discuss the paper “Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study” published in the JCO. 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, the podcast where we get in-depth into articles published in the Journal of Clinical Oncology. I am your host, Shannon Westin, GYN Oncologist and Social Media Editor of the JCO. As always, it is my pleasure to serve and bring this information to you. Today, we will be discussing, “Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study.” And this was published in the JCO on August 10th, 2023. None of the authors have any conflicts of interest to disclose. Joining me today are two of the authors, Dr. Herbert Duvivier, the principal investigator of this arm of the TAPUR trial. Welcome. Dr. Herbert Duvivier: Thank you. Shannon Westin: And then, of course, many of you know Dr. Richard Schilsky, who is the former CMO and Executive Vice President of ASCO and a principal investigator on the TAPUR study. Dr. Richard Schilsky: Thank you, Shannon. Shannon Westin: So, let's get going. I think the first thing would be great is to level set and make sure everyone knows exactly what this TAPUR basket trial is, the Targeted Agent and Profiling Utilization Registry study. Can you guys give the audience a brief description of the objective of TAPUR and maybe how it came to fruition? Dr. Richard Schilsky: Sure. This is Richard Schilsky. Maybe I can start with that. The TAPUR study is a prospective, phase II, multi-basket, multi-center genomic-matching trial. Its primary objective is to identify signals of drug activity for targeted agents that are already marketed. But in the TAPUR study they are being used outside of their FDA-approved indication. The study, as you may know, was conceived in 2014, launched in 2016, and is still enrolling patients across the country. Really, the genesis of the study came from the fact that it began at the time where genomic profiling of patients with advanced cancer was becoming more commonplace. Genomic alterations that could be targeted by already marketed drugs were being identified. However, patients and doctors were having difficulty accessing these drugs because they were not used on label and were unlikely to be covered by insurance. And moreover, even if they could access the drugs, there was no organized mechanism to collect outcome data and report on the results of the patient experience receiving that treatment. So those factors led to the development of TAPUR, which attempts to solve both the drug access problem by having collaborating pharmaceutical companies donate their drugs to the trial so they’re available to patients at no cost, but also implements a structured data collection mechanism so all of the relevant clinical outcomes with the patients can be collected and ultimately reported. And that’s how TAPUR came about. Shannon Westin: Well, it was so necessary, and I think we do so much of our oncology treatments off-label, but as we get more and more expensive drugs when we move away from chemotherapies and more targeted immunotherapies, it’s very hard to get those drugs off label. So this was such a relevant and necessary trial that had to happen, and it's a great example of leadership that you had the vision to put this together through ASCO. I think the natural next question for me is having not put patients on the TAPUR study, how does a patient join this study? How do they get started? Walk us through that. Dr. Herbert Duvivier: At our institution, normally, all the physicians are aware of the TAPUR trial through internal conversations. When they have patients...

In this JCO Article Insights episode, Giselle de Souza Carvalho provides a summary on "Pathologic Exploration of the Axillary Soft Tissue Microenvironment and Its Impact on Axillary Management and Breast Cancer Outcomes" by Naoum, et al and "Optimization of Breast Cancer Regional Nodal Management" by Braunstein et al published in the January 10, 2024 issue in Journal of Clinical Oncology. The original report discusses how the examination of axillary soft tissue beyond lymph nodes is often omitted and it predicts breast cancer outcomes and need for nodal radiation. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Giselle Carvalho: Welcome to the JCO Article Insights episode for the February issue of the Journal of Clinical Oncology. This is Giselle Carvalho, your host, one of the ASCO editorial fellows at JCO this year. Today, I'll be providing a summary of an article focused on “The Association of Axillary Soft Tissue Involvement on Outcomes for Breast Cancer Patients.” It was published in November 2023 and was partially presented at the 64th Annual ASCO in October 2022. Although lymph node involvement in breast cancer patients is correlated with a worse prognosis, the impact of extracapsular involvement is still a matter of debate, and the implications of axillary soft tissue involvement are still not fully understood. There is some evidence indicating a decrease in disease-free survival for patients with less than four lymph nodes and with extracapsular extension, while other studies show that extracapsular involvement has no prognostic role in these patients and that the number of positive lymph nodes might matter more. Patients with node-positive disease may present with only lymph node involvement or lymph node involvement plus extracapsular extension and/or axillary soft tissue involvement. The axillary soft tissue involvement can result from either direct lymph node extension through the capsule or direct microscopic spread from the primary tumor. It is pathologically defined in this article as axillary lymphatic channel invasion, axillary soft tissue deposits, axillary blood vessel invasion, or any combination of these. This was a retrospective study of patients with invasive breast cancer who received treatment at Massachusetts General Hospital in Boston, Massachusetts, from 2000 to 2020. Lymph nodes and surrounding adipose tissue were submitted in their entirety for histopathologic evaluation using hematoxylin and eosin stain, and immunohistochemical stains could be added at the pathologist's discretion. Eligibility criteria included primary breast cancer and positive lymph nodes without prior or contralateral breast cancer. 2,162 patients were included. They were divided into four groups according to their axillary pathology: the first group was composed of patients with positive lymph nodes with no additional axillary involvement; the second group of patients with positive lymph nodes and extracapsular involvement; the third group of patients with positive lymph nodes and axillary soft tissue involvement but with no extracapsular extension; and the fourth group of patients with positive lymph node and both extracapsular extension and axillary soft tissue involvement. Primary endpoints were 10-year rates of local-regional failure, which was defined as recurrence in the breast or chest wall or ipsilateral axilla, axillary failure, and distant metastasis. Among 2,162 patients, 58% had lymph node involvement only, 25% had lymph nodes with extracapsular extension, 3.5% had lymph node involvement with axillary soft tissue involvement, and 14% had lymph node involvement with both extracapsular and axillary soft tissue involvement. 51% of cases of axillary soft tissue involvement were in the form of axillary lymphatic channel invasion. The median follow-up was 9.4 years, and 74% of the cohort had hormone receptor-positive breast cancer, 10% had triple-negative disease, and 16% had...

Dr. Shannon Westin and her guest, Dr. Reshma Jagsi, discuss the paper "Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA" recently published in the JCO. 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, the podcast where we get in depth with manuscripts that were published in the Journal of Clinical Oncology. I am your host, Shannon Westin, GYN Oncologist and Social Media Editor for the JCO. It is my pleasure to speak with Dr. Reshma Jagsi. Hello, Dr. Jagsi. Dr. Reshma Jagsi: Hello. Thanks for having me. Shannon Westin: I am so excited that you're here. Dr. Jagsi is the Lawrence W. Davis Professor and Chair of the Department of Radiation Oncology at Emory University School of Medicine, Winship Cancer Institute. She is going to be talking about her incredible work, "The Omission of Radiotherapy After Breast Conserving Surgery for Women with Breast Cancer with Low Clinical and Genomic Risk: Five-year Outcomes of IDEA," which was published in JCO in February 2024. All right, let's get right to it. First, I want to levelset. Can you run us through some brief facts and figures about breast cancer just to make sure that all the listeners are on the same page? Dr. Reshma Jagsi: Breast cancer is the most common cancer in the world. It’s 12.5% of all new annual cancer cases worldwide and is the most commonly diagnosed cancer among US women. About a third of all newly diagnosed cancers in women are breast cancer, and about 13% of US women develop invasive breast cancer over their lifetime. In 2023, there were nearly 300,000 new cases of invasive breast cancer. The median age of breast cancer diagnosis is 62, meaning an awful lot of people are getting diagnosed with breast cancer in the population that we specifically chose to study. Shannon Westin: Wow, you're really good at this. That's like the perfect transition to move to the next piece. So, first, I think I'd love to hear about the standard of care for the population that you were studying and how we got to this point. Dr. Reshma Jagsi: We offer women who are diagnosed with early-stage invasive breast cancer the option of breast conservation, and we encourage breast conservation because, of course, it is a better-tolerated surgery than mastectomy. Many women are eligible for breast-conserving therapy. And years ago, we as radiation oncologists encouraged our surgical colleagues to refer to breast-conserving therapy as lumpectomy plus radiation, just as one set. Because the studies that have been done in the 1970s and 1980s to establish that breast conversation was equally safe and effective in treating breast cancer relied on radiation therapy to minimize in-breast tumor recurrence rate, which one of those trials independently showed that there was no difference in survival. But the ones that compared lumpectomy surgery alone to lumpectomy followed by radiation therapy did show a pretty substantial improvement in local control with the addition of radiation treatment. And so radiation treatment became a part of a parcel of breast conservation in the early 1990s when consensus statements came out favoring breast conservation as a treatment approach. And so the net analysis has combined all of these studies together and showed that overall, without radiation treatment, a patient treatment with a lumpectomy had a 30% risk of in-breast tumor occurrence in those historical studies. And it was reduced by about two thirds to about 10% when that lumpectomy was followed by radiation in those historical randomized trials. But of course, we’ve made many advances in our understanding since that time, and so that’s what this study is seeking to build on. Shannon Westin: It makes sense. We all know that radiotherapy can lead to other issues, acute and chronic morbidities, as well...

Dr. Shannon Westin and her guests, Dr. Jeremy Davis and patient advocate Kathryn Carr, discuss the paper "Costs of Cancer Prevention: Physical and Psychosocial Sequelae of Risk-Reducing Total Gastrectomy" recently published and printed in the JCO. TRANSCRIPT Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth on manuscripts that are published in the Journal of Clinical Oncology. I am your host, Shannon Westin, a professor of GYN Oncology at MD Anderson, and the JCO social media editor. I am so thrilled to have wonderful authors here today who do not have any conflicts of interest. We are going to be discussing the “Costs of Cancer Prevention: Physical and Psychosocial Sequelae of Risk-Reducing Total Gastrectomy.” This was published in the Journal of Clinical Oncology online on October 30, 2023, and in print on February 1st, 2024. And I am excited. I am accompanied by the lead author, Dr. Jeremy Davis, who is an Associate Professor and Surgical Oncologist at the NIH, National Cancer Institute Intramural Research Program. Welcome, Dr. Davis. Dr. Jeremy Davis: Thank you. Shannon Westin: If it is okay with you, I'll call you Jeremy. Dr. Jeremy Davis: Yes, please. Shannon Westin: Fabulous. We also have patient advocate Kathryn Carr, who is a board member for No Stomach for Cancer. Welcome, Kathryn. Kathryn Carr: Thank you so much. Shannon Westin: So let's get right into it. I think this is really thought-provoking work. First, I'd love to level set. So this was work around hereditary diffuse gastric cancer syndrome. Can we get a little bit of information about what causes this and how common it is? Dr. Jeremy Davis: So, hereditary diffuse gastric cancer syndrome, also referred to as the diffuse gastric cancer and lobular breast cancer syndrome, is basically early-onset diffuse gastric cancer and in women, lobular type breast cancer attributed to germline mutations in the CDH1 gene. If we look at all cases of gastric cancer in the United States, only about 1-3% may be considered hereditary in nature. But when we do study hereditary causes of cancer, it is by far the most common one that we are aware of. Shannon Westin: What is the likelihood that someone who is a carrier of a germline CDH1 variant will develop gastric cancer? Dr. Jeremy Davis: That's a good question. Early on, when the syndrome was first described, the estimates of cancer risk were quite high, probably upwards of 70-80%. The good news is that more current estimates published in the last few years suggest that that risk in a lifetime is probably in the 25-40% range. It’s interesting, we do have our own data that are under review right now, where in some families where there’s no history of stomach cancer, that risk of stomach cancer in a lifetime getting a CDH1 mutation might be as low as 10%. So I think the takeaway is that there’s clearly a spectrum and that spectrum of risk is probably based on factors that we don’t quite yet understand. Shannon Westin: What are the options for management of this hereditary syndrome, really focusing on the gastric cancer syndrome portion today? How good does it do to reduce the risk? Dr. Jeremy Davis: The options are really two. One is probably the prevailing recommendation that most people would be aware of, is to prophylactically remove the stomach, and we choose to use the term most often ‘risk-reducing gastrectomy’, but to remove the entire stomach and really eliminate the risk of cancer from ever developing. The other option is enhanced surveillance, and people might think of this as akin to other high risk cancer syndromes. But for this we would do yearly or annual endoscopic surveillance. Many people think that that may not be the best option, but it is certainly an option. We discussed some of that in the paper about what are the risks and benefits of gastrectomy, and then what may be the benefit of enhanced surveillance for some...

In this JCO Article Insights episode, Subodh Selukar summarized findings from the original article published in the January 2024 JCO issue: “The Importance of Low and Moderate Grade Adverse Events on Patients’ Treatment Experience and Treatment Discontinuation” and accompanying editorial “Patient Experience, Adverse Event Reporting, and Clinical Trial Design”. The summary provides information regarding low and moderate grade adverse events and the patient experience in clinical trials. TRANSCRIPT Welcome to the JCO Article Insights episode for the January 2024 issue of Journal of Clinical Oncology. This is Subodh Selukar, your host, and today I will be providing a summary on 2 articles focused on low and moderate grade adverse events. The first article, titled “The Importance of Low and Moderate Grade Adverse Events on Patients’ Treatment Experience and Treatment Discontinuation” by Dr. O’Connell and colleagues, investigated low and moderate grade adverse events and the patient experience in clinical trials. Their article is accompanied by an editorial entitled “Patient Experience, Adverse Event Reporting, and Clinical Trial Design” by Dr. Neuman. In clinical trials, a standardized system for reporting adverse events is the Common Terminology Criteria for Adverse Events (or “CTCAE”) established by the NCI, the United States National Cancer Institute. The CTCAE categorizes adverse events at 5 severity grades across 26 system organ classes. However, some clinical trials may only report adverse events at grade 3 or higher, with one possible rationale being that low and moderate grades are unlikely to affect patient safety or key trial endpoints. In Dr. O’Connell’s article, the team investigated how the numbers of grade 1 and 2 adverse events related to patient self-reported side-effect burden and treatment discontinuation. To do this, they analyzed data from the Phase 3 trial E1912 conducted by ECOG-ACRIN comparing two treatments for chronic lymphocytic leukemia. They chose this trial as an example because the study data included all adverse event grades throughout the duration of treatment for each patient. The authors studied side-effect burden based on GP5, which is the fifth item in the FACT-G subscale in the Functional Assessment of Cancer Therapy. GP5 rates the patient’s agreement with the statement “I am bothered by side effects of treatment” in the past 7 days, and it has previously been connected with adverse event grade and treatment discontinuation. For treatment discontinuation, the authors focused on those discontinuations that were recorded as being due to “adverse events, side effects or complications.” They found that, for each adverse event grade, there were, on average, more adverse events in cycles that ended with a patient discontinuing treatment compared to other cycles. Next, they used Bayesian models to assess how the numbers of grade 1 and grade 2 adverse events in a treatment cycle were associated with the odds of higher side-effect bother and odds of treatment discontinuation, after adjusting for cycle number, treatment and occurrence of grade 3 or higher adverse events within the cycle. Baseline GP5 was also included in the models, and these models also accounted for the inclusion of multiple cycles for each patient. When adjusting for baseline GP5, treatment, cycle and presence of grade 3 or 4 adverse events, both the number of grade 1 and the number of grade 2 adverse events were each strongly associated with increasing side-effect bother. The adjusted odds of treatment discontinuation were also higher with more grade 2 adverse events. However, with the same adjustment variables, the odds of treatment discontinuation were actually lower with larger numbers of grade 1 adverse events. In their primary analysis, they focused on adverse events that were attributed to treatment, so they excluded non-treatment-related adverse events from the counts. Sensitivity analyses including these adverse...

Dr. Shannon Westin and her guest, Dr. Ash Alpert and Spencer Adams, discuss the paper "Debunking Sex and Disentangling Gender From Oncology" recently published in the JCO. TRANSCRIPT The guests on this podcast episode have no disclosures to declare. Shannon Westin: Hello and welcome to JCO After Hours, the podcast where we get in depth on manuscripts published in the Journal of Clinical Oncology. I'm your host, Shannon Westin, Social Media Editor and GYN oncologist by trade. I'm so excited to be discussing a very important manuscript. This is "Debunking Sex and Disentangling Gender from Oncology," which was published in the JCO Online on May 26, 2023. So I'm joined by two of the authors here today on the podcast. First is Dr. Ash Alpert. They are an instructor of medicine and hematology at Yale Cancer Center. Welcome. Dr. Ash Alpert: Thank you. Shannon Westin: And we also have Spencer Adams. They have a bachelor's in public health, are a certified health education specialist, and are currently pursuing a master's in public health at Western Michigan University. Welcome, Spencer. Spencer Adams: Thank you for having me. Shannon Westin: So let's get into it. I'm so excited. First off, I just want to say thank you because I learned a ton from this paper, and I'm hoping to be able to implement some of these changes that we're going to discuss over the next few minutes at my own institution. So I wanted to just make sure we kind of level set and everyone's on the same page. So let's start off by discussing ontological oppression. Can you explain to the listeners what this means and how it relates to sex and gender and oncology? Dr. Ash Alpert: Sure. So, ontological oppression is actually a concept from one of my colleagues at Yale, Robin Demroff, who's a philosopher. Ontology is a way of thinking about what exists and how we categorize what exists. And so ontological oppression is discrimination or stigma that happens because of the ways people imagine us fitting or not fitting into social categories. For example, if we think that people are women or men based on their sex assigned at birth, then it makes sense that we would think of transgender people and nonbinary people as abnormal, weird, or pathologic. In oncology, if we think of ovarian cancer as something that happens to women and a man with ovarian cancer comes into our clinic, we may be confused or uncomfortable. We may respond to those feelings by denying his identity, for example, thinking he's actually a woman or using the wrong pronouns or name for him or even potentially denying him care. And we have some data to suggest that clinicians respond to lack of knowledge about transgender people by treating them as abnormal, weird, or bad in some way. Spencer Adams: Yeah. And to add to that, when we consider how we classify people, first, there's a problem within that. There's an ethical problem within that, but it's an idea or a construct that society has created and wants people to fit into these nice little boxes just because it's easier to digest, or you make the person more palatable if they're able to do these things. And life is not like that. We have differences, and we have things that make people fit outside the box. And I believe that when we keep reminding people that a box exists or a social construct exists, you're stifling who they are, their personality, their guiding light. You're stifling a lot of things about that person and ignoring something that's incredibly important to them. Shannon Westin: I think that along those lines, kind of taking that to the next step, it would be really helpful to discuss a little bit more around this interaction between sex assigned at birth and gender and what assumptions are made. And I think you kind of started along this, like, how that impacts oncology care. But in your paper, you did, I think, a really great job of really laying out a lot of the problems that happen in this space, and I'd love to explore that...

Dr. Shannon Westin and her guests, Dr. Judy Garber and Dr. Geoffrey Oxnard, discuss the paper "Germline EGFR Mutations and Familial Lung Cancer" recently published in the JCO. TRANCRIPT The guest on this podcast episode has no disclosures to declare. Shannon Westin: Hello, and welcome to JCO After Hours, the podcast where we get in-depth on articles that are published in the Journal of Clinical Oncology. I am your host, Shannon Westin, Social Media Editor for the JCO and Gynecologic Oncologist by trade. And it is my great pleasure to speak today with you about an amazing manuscript entitled, “Germline EGFR Mutations and Familial Lung Cancer.” It was published in the JCO on August 14, 2023. The authors have no conflicts of interest, and they are Dr. Geoffrey Oxnard, he's a Thoracic Oncologist and Associate Professor, Hematology and Medical Oncology at Boston Medical Center. Welcome, Geoff. Dr. Geoffrey Oxnard: Hi, Shannon. Thanks. Shannon Westin: And Dr. Judy Garber, the chief of the Division of Cancer Genetics and prevention at the Dana-Farber Cancer institute in Boston. Welcome, Judy. Dr. Judy Garber: Thank you. Hi, Shannon. Hi, Geoff. Shannon Westin: So excited you both could be here. Let's get started. So first I just want to levelset for our audience. Can you speak just a little briefly about the incidence and mortality of lung cancer and how that's been changing over time? Dr. Geoffrey Oxnard: Sure. Lung cancer is common and it's deadly, more than 200,000 cases a year in the United States, more than 100,000 deaths a year in the United States. But I think importantly, it's evolving. Its biology is evolving as smoking incidence goes down. We've identified these genomic subtypes of lung cancer that are sort of increasingly apparent and important as we think about its treatment. Outcomes are changing with emerging therapies, presentation is changing with lung cancer screening and with a growing ability to now find cancers early and prevent them. And so it's in that setting of a very dynamic disease that we chose to study a really unique little slice of it, which is germline risk. Shannon Westin: So let's take that one step further because I think that's really interesting. You mentioned the genomic aberrations and kind of how you're using that to target. Can you expand upon that a little bit more for me? Dr. Geoffrey Oxnard: Lung cancer that I've long studied is different than breast cancer when Judy has long studied because we think about its somatic alterations, we've always thought about KRAS mutations, EGFR mutations, and smaller and smaller splice limit. ALK, RAS, RET HER2, etc. And so tumor testing in lung cancer has one of the first to be standard across on solid tumor oncology. And the germline genetics was kind of an afterthought and is the flip, I think, of how genetic testing evolved in the breast cancer space for example. Dr. Judy Garber: I might argue a little bit if breast cancer was earlier and it was subtyped some molecularly it doesn't have as many molecular subtypes yet perhaps as lung cancer. But we've all been studying the somatic space to look for targets for therapy. And the germline space, certainly in breast cancer, came much earlier. And everybody knows about BRCA1 and 2. Now, we hope everybody knows about Lynch Syndrome, but certainly not everybody's thinking about inherited lung cancer risk. Dr. Geoffrey Oxnard: Yeah, these have converged. I think 10 years ago when this kicked off, I felt like a super outlier for thinking about, wait a second, what about the genetics behind all this that is leading to this strange variable presentation of lung cancer? For example, we know that in Asian populations, one type of lung cancer, EGFR mutant lung cancer, is more common. There must be some geneticness that leads to that. What explains the sort of pattern of presentation of these genetic subtypes in the populations we see in the US, that’s pretty unclear? Dr. Judy Garber: So, I think, Shannon...