The Journal of Clinical Oncology (JCO) serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. Usually presented in conjunction with an original report and an editorial published on www.jco.org, the JCO podcasts enable readers to stay current on the latest research while placing the results into a clinically useful context.
JCO After Hours: A Discussion With Abby Rosenberg and Reshma Jagsi
Dr. Shannon Westin, Dr. Abby Rosenberg, and Dr. Reshma Jagsi discuss the timely issue of diversity, equity, and inclusion in the field of oncology.
SHANNON WESTIN: Hey, everyone and welcome to JCO After Hours, the podcast that gets a little bit more in-depth about some of the articles and amazing research that have been published in the Journal of Clinical Oncology. I'm so excited to be with you today. And more importantly, I'm very excited to talk about this amazing manuscript, which is called "Picture a Professional-- Rethinking Expectations of Medical Professionalism Through the Lens of Diversity, Equity, and Inclusion."
And this was a Comments and Controversies article that was just published in October of 2021. And I am beyond thrilled to be joined by Dr. Abby Rosenberg, who was the lead author on this manuscript. And she is currently an associate professor in the Division of Hematology-Oncology, as well as in the Division of Bioethics and Palliative Care at the University of Washington School of Medicine.
She has a number of different amazing accomplishments, including being the director of Palliative Care and Resilience Lab at the Seattle Children's Research Institute, the director of Pediatrics at the UW Cambia Palliative Care Center of Excellence, and the director of Survivorship and Outcomes Research in Pediatric Oncology at the University of Washington. In addition, she is our ASCO chair of our Ethics Committee. Welcome, Dr. Rosenberg. So excited to have you.
ABBY ROSENBERG: Thanks for having me. Happy to be here.
SHANNON WESTIN: And in addition to Dr. Rosenberg, we're also joined by one of her co-authors, Dr. Reshma Jagsi, who is the deputy chair of radiation oncology, the Newman Family Professor of Radiation Oncology, and the residency program director and the director of the Center for Bioethics and Social Sciences at the University of Michigan. You guys, we're going to spend this whole podcast just talking about how amazing the two of you are. Thank you so much for being here.
RESHMA JAGSI: Thanks for having me.
SHANNON WESTIN: So let's get into it. I'm really excited about this paper. I think it's super timely and certainly something that we've all been, I think, dealing with on a day-to-day basis and also reading about and really trying to get better at. So can you tell us a little bit-- and we'll start with you, Dr. Rosenberg-- about what first drew you to this work, how you got involved and, really, how you became passionate about it?
ABBY ROSENBERG: Yeah, happy to. I think just, as you said, Dr. Westin, there is this ubiquity in the experiences, in particular of women and folks of color in medicine, where we feel discriminated against, and we feel like we don't belong. And we know from some really great data from the National Academies of Sciences that 50% of women in med school, for example, experience discrimination before they graduate. And when we educate them about what microaggressive and sexist behaviors can actually look like, that number goes way up.
And most women, in particular, say that they're willing to, quote, "pay this price" for being in medicine because they believe in the work, and they believe in the mission. And for me, this was really personal. Because I was one of those people, too, until I got to the point in my career where I noticed how my mentees and people who reported to me were being held back. And that, to me, made me feel like there was something I really needed to do now as an advocate and mentor to try to change the system so that more women and people of color could be successful in our field.
SHANNON WESTIN: That's great. And then how did you get involved Dr. Jagsi? I'd love to know how the collaboration came about and also about your passion for this work.
RESHMA JAGSI: Thank you. Yes, so both Dr. Rosenberg and I have had the privilege of chairing ASCO's Ethics Committee. And I think, to both of us, this is a fundamental mat
JCO After Hours: A Discussion With Michael Gnant and Kathy Miller
Dr. Shannon Westin, Dr. Michael Gnant, and Dr. Kathy Miller discuss the results of the PALLAS trial.
JCO After Hours: A Discussion With Kirsten Beyer and Jennifer Griggs
Dr. Shannon Westin, Dr. Kirsten Beyer and Dr. Jennifer Griggs discuss how mortgage lending bias and residential segregation intersect with cancer disparities and survival outcomes.
SHANNON WESTIN: Hello, everyone. My name is Shannon Westin, and I'm an Associate Professor at the University of Texas MD Anderson Cancer Center in the Department of Gynecologic Oncology and Reproductive Medicine. And I currently serve as the Social Media Editor for the Journal of Clinical Oncology.
And we're starting a brand new podcast series to try to bring really exciting research that's being published in the JCO to you, and I'm so excited to kick off this series with a group of very accomplished women who are covering something that I don't think a lot of us don't know very much about. So I'm really excited to learn a ton over this next few minutes.
So it's my pleasure to introduce Dr. Kirsten Beyer, who is an Associate Professor in the Division of Epidemiology in the Institute for Health and Equity as well as the Director of the PhD program in Public and Community Health at the Medical College of Wisconsin.
We are also joined by Dr. Jennifer Griggs, who's a Professor the Department of Internal Medicine, Division of Hematology Oncology, as well as a member of the Institute of Health Care Policy and Innovation at the University of Michigan. She does predominantly practice taking care of women with breast cancer. Welcome, doctors.
JENNIFER GRIGGS: Thank you.
KIRSTEN BEYER: Thank you very much.
SHANNON WESTIN: So we're talking today about the manuscript "Mortgage Lending Bias and Breast Cancer Survival Among Older Women in the United States" that Dr. Beyer published just this month in the JCO. In addition, Dr. Griggs and her colleague Dr. Pleasant were invited to participate in an editorial called "Contemporary Residential Segregation and Cancer Disparities."
So let's get into to what was covered. So I think for me, the lowest hanging fruit here, Dr. Beyer, is understanding what exactly is redlining, because that was one of the critical exposure that you were assessing amongst these women with breast cancer.
KIRSTEN BEYER: Thank you, Dr. Westin. Yes, redlining-- I think most people think about redlining as being a historical practice, where mortgage lenders would essentially draw red lines around particular neighborhoods and then not lend mortgages in those areas, regardless of whether or not the applicant for that mortgage was otherwise qualified. So it's generally thought of as a historical practice.
But what we've done in this study is to look at some more contemporary data and create a new measure that we think represents contemporary redlining, maybe not in the legal sense in terms of housing discrimination. But this measure represents essentially the odds ratio of denial of a mortgage application for a property in a local neighborhood as compared to the metropolitan area as a whole. So we're really looking to see which areas of our US cities are systematically denied mortgage applications. By denying those mortgage applications, they are suffering from disinvestment, and I would argue structural racism is guiding a lot of that practice.
SHANNON WESTIN: So can you explore that a little bit more with us? And how do you find that type of data? Where do you get this information about these denied mortgages? How do you get into the different covariates like race, ethnicity, things like that?
KIRSTEN BEYER: Sure. So I think a little history lesson is important first. Between the historic practice of redlining and today, there have been a number of major laws that have been passed in the United States really to try to overcome housing discrimination. Some of the most important ones are-- in the Civil Rights Act of 1968, there was something called the Fair Housing Act, and that act prohibited discrimination in the sale, rental, and financing of housing based on race, religion, and national origin.
Is Dose-Adjusted EPOCH-R the Optimal Treatment for Children with Primary Mediastinal B-Cell Lymphoma?
This podcast will discuss data from a phase II trial evaluating the dose-adjusted EOPCH-R chemo-immunotherapy regimen for the treatment of primary mediastinal B-cell lymphoma in children.
LISA GIULINO-ROTH: This JCO podcast provides observations and commentary on the JCO article "Dose-Adjusted Rituximab Therapy in Children and Adolescents with Primary Mediastinal B-cell Lymphoma, a Multicenter Phase II Trial" by Burke et al. My name is Lisa Giulino-Roth, and I am a pediatric oncologist at Weill Cornell Medical College in New York. My oncology specialty is lymphoma in children, adolescents, and young adults. I have no relevant disclosures.
Primary mediastinal B-cell lymphoma, or PMBCL, is an aggressive non-Hodgkin lymphoma derived from thymic B-cells. While previously classified as a subtype of diffuse large B-cell lymphoma, PMBCL is now recognized as a distinct clinical and pathologic entity. Unlike diffuse large B-cell lymphoma, PMBCL has a peak incidence among adolescents and young adults and is more common in females.
PMBCL also shares many molecular characteristics with Hodgkin lymphoma, including alterations in JAK-STAT pathway signaling and amplification of the 9p24.1 locus, leading to upregulation of PD-L1. Adults with PMBCL have historically been treated on regimens designed for diffuse large B-cell lymphoma, which in the US was most commonly R-CHOP and radiation therapy. More recently, adult patients have been treated with a dose-adjusted EPOCH-R regimen, which is composed of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab.
This radiation-free approach is of interest, given this young and predominantly female population who are at risk for significant long-term toxicity from chest radiation. In a single center NCI-led study by Dunleavy and colleagues, dose-adjusted EPOCH-R was administered for six to eight cycles without radiation therapy and resulted in excellent outcomes with a five-year event free survival of 93% and overall survival of 97% among 51 adult patients.
Pediatric patients with PMBCL have historically been treated on regimens designed for mature B non-Hodgkin lymphoma, which in pediatrics is most commonly Burkitt lymphoma or diffuse large B-cell lymphoma. These dose intensive multi-agent regimens include doxorubicin, high dose methotrexate, and intrathecal chemotherapy without radiation.
Outcomes for children with PMBCL treated on these regimens are inferior to pediatric patients with diffuse large B-cell lymphoma treated on the same protocol. Children with PMBCL have a five-year event-free survival ranging from 65% to 75% in different international series. Given the excellent outcomes observed with dose-adjusted EPOCH-R in the adult NCI trial, an international phase II trial of this approach was conducted by two cooperative groups, The European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children's Oncology Group.
This single arm trial enrolled patients age 18 and under with primary mediastinal B-cell lymphoma. All patients were treated with six cycles of dose-adjusted EPOCH-R without radiation. The primary endpoint was event-free survival with events defined as any of the following-- viable cells in any residual mass after six cycles of treatment, relapse, progressive disease, secondary malignancy, or death from any cause. The four-year event-free survival from this trial would be compared with the event-free survival from historic controls, which was estimated at 67%.
A total of 46 pediatric patients were enrolled between 2012 and 2016. All patients received six cycles of dose-adjusted EPOCH-R without RT. At a median follow-up of 59 months, there were 14 events, including four patients with viable cells in the residual mass at the completion of therapy, eight progressions or relapses, and two secondary malignancies, including one case of Hodgkin lymphoma and one case of acute promyelocytic leuk
Steroid Dose and Taxanes
This podcast discusses the study, steroid dose reduction, practice experience, and guidance changes.
ROBIN ZON: This JCO podcast provides observations and commentary on the JCO article-- "Do Steroids Matter: A Retrospective Review of Pre-Medication for Taxane Chemotherapy and Hypersensitivity Reactions," by Lansinger et al.
My name is Dr. Robin Zon. And I am the quality oncology practice initiative lead physician for Michiana Hematology Oncology, an independent community oncology practice located in Mishawaka, Indiana. My oncologic specialty is general medical oncology. And I have a strong interest in breast cancer.
This article is based on the premise that there exists significant variation regarding the prescribing practices of steroids for pre-medication to minimize the known hypersensitivity reactions associated with the taxanes paclitaxel and docetaxel. In fact, the authors remind the reader that initial clinical development of paclitaxel was delayed due to the notable hypersensitivity rate of 25% to 30%, as patients did not receive pre-medication. Subsequent trials used a pre-medication strategy of dexamethasone, diphenhydramine, and H2 antagonist, with a reduction of the reaction occurrence to 2% to 3%. As a result of the improved reaction rates in clinical trials with the use of a pre-medication regimen, both paclitaxel and docetaxel, FDA approved package inserts recommend oral corticosteroid pre-medication, 20 milligrams, 12 and 6 hours prior to the taxane administration.
However, there has been no dose optimization to date. In fact, the authors note that lower dose regimens are routinely used in daily practice and may lead to increased risk of hypersensitivity reactions. Furthermore, steroids can cause multiple adverse effects if taken for extended periods of time, which can range from mild to moderate in their severity.
This study reviewed steroid prescribing patterns in patients receiving the first dose of paclitaxel or docetaxel at Stanford Cancer Institute between 2010 and 2020. A total of 3,181 patients met criteria for analysis, with an 8.3% rate of hypersensitivity reactions. And the adjusted multivariate analysis, the authors found no correlation between the hypersensitivity reaction rate or the severity among the variables evaluated, except for the gynecology/oncology clinic patients who had an increased risk for hypersensitivity reactions overall with a hazard ratio of 1.34 and high grade hypersensitivity reactions with a hazard ratio of 2.34, and female patients who had a higher rate of hypersensitivity reactions overall with a hazard ratio of 1.26, but not high grade hypersensitivity reactions.
The conclusion of the article is that neither dexamethasone dose nor route, IV or oral, correlated with subsequent hypersensitivity reactions. And that the recommended 40 milligrams dose of dexamethasone prior to taxane administration is no better than the 10 milligrams dose for protecting against hypersensitivity reactions. Therefore, the lower doses used in clinical practice is acceptable and even preferable to higher doses.
Although the study authors point out that the strength of the study is the large data set reviewed, they also point out that this study was a retrospective analysis completed on first dose dexamethasone use and not on subsequent taxane exposures Additionally, the authors also point out that since there was no external validity, the results may not be generalizable to other patient populations treated at other institutions. For the remainder of this podcast, the commentary represents my opinion only and may not represent the opinion of this journal or its editors.
First, I would like to commend the authors on this analysis, which addresses a very practical question-- do steroids matter. And is it possible to safely vary from the package insert? The work dedicated to collecting this data set does not go unnoticed.
As the authors acknowledge, the pres
Commentary on GROINSS VII
Improving care in vulvar cancer via the prospective Vulvar GROINSS VII study
This JCO Podcast provides observations and commentary on the JCO article “Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients with Micrometastases in the Sentinel Node: Results of GROINSS-V II” by Oonk et al. My name is David Gaffney, and I am a professor and Vice Chair of Radiation Oncology at the University of Utah. I am also Senior Director for Clinical Research at the Huntsman Cancer Institute in Salt Lake City, Utah. My oncologic specialty is radiation oncology. I have no relevant disclosures to this study.
The GROINS VII study is the successor trial of the GROINS V I trial. In the GROINSS-V I study, the authors demonstrated that omission of an inguinal femoral lymphadenectomy was safe in patients with a negative sentinel lymph node with an isolated GROIN recurrence rate of 2.3%. It also showed that with long term follow up a significant proportion of patients will recur. At 10 years local recurrence occurred in 39.5% of all patients. Although local recurrences are treated with curative intent, the disease-specific survival of these patients decreases significantly. It is important to ask if there is a dose response to radiotherapy in vulvar cancer? GOG 101 was published in 1998 and employed a split course of radiotherapy to a dose of 47.6 Gy with concurrent cisplatin and 5-FU. The complete response rate was 46.5%. The subsequent prospective phase II randomized trial, GOG 205, was published in 2012 and employed 10 Gy more of radiotherapy with weekly cisplatin to a total dose of 57.6 Gy. This study demonstrated a 78% pathologic complete response rate. Hence, by adding 10 Gy, the complete response rate increased by 30%, indicating a steep dose response. Also, by way of background, a retrospective study from MD Anderson by Stecklein et al. published in 2018 demonstrated a 3-year actuarial groin control rate of 83% with high dose conformal radiotherapy with a median dose of 66 Gy to grossly positive nodes. These data demonstrate that radiotherapy can sterilize gross disease in select circumstances.
The GROINSS-V II study was a phase II prospective study in a rare disease, and sought to answer whether radiotherapy to 50 Gy could be an effective and less morbid alternative to inguinofemoral lymphadenctomy Patients were accrued from 59 hospitals in 11 countries. Eligibility for this study were patients with tumors less than 4 cm, with negative groin nodes on preoperative CT, MRI, or ultrasound. The primary endpoint was a groin recurrence rate at 24 months. A combined technique was used to evaluate the sentinel lymph node of lymphoscintigram and blue dye. Bilateral sentinel lymph node procedures were required for midline lesions. The radiotherapy was 50 Gy in 25-28 fractions with the field size to extend to the bottom of the SI joints, including the distal external iliac lymph nodes. Greater than 1700 patients were registered. One hundred sixty patients were found to have micrometastases, that is disease less than 2 mm, whereas 162 patients were found to have macrometastases. The median size vulvar lesion for patients with negative sentinel lymph node was 18 mm, 23 mm for patients with micrometastases, and 25 mm for patients with macrometastases.
Results at 2 years demonstrated an isolated groin recurrence rate occurred in 1.6% of patients that were treated per protocol with micrometastases. Whereas patients with macrometastases had an isolated groin recurrence rate at 2 years of 12.2%. For patients with macrometastases treated with radiotherapy, the groin recurrence rate was 22%. Whereas groin failure was 6.9% for patients who had macrometastases treated with inguinal femoral lymphadenectomy and radiotherapy. For patients with macrometastases, no groin recurrences were observed in 7 patients treated with chemoradiotherapy. Among the 1213 patients with a negative sentinel l
Good Information, but
The information provided is important, but the presenters are stilted.
I really want to like this podcast, but...
unfortunately, although the content is excellent, the delivery is awful. Most of the time the presenters just read the text of the podcast - very fast, in a monotonous voice. While as a written piece it could perhaps work, it doesn't work as an audio. I end up pausing and rewinding, and eventually giving up on learning and remembering. An audio lecture needs to be delivered at a slower pace, with fewer lists and numbers...