TP53 mutations and the association with platinum resistance in high grade serous ovarian carcinoma.

OBJECTIVES: Alterations in the tumor suppressor TP53 gene are the most common mutations in high grade serous ovarian carcinoma. The impact of TP53 mutations on clinical outcomes and platinum resistance is controversial. We sought to evaluate the genomic profile of high grade serous ovarian carcinoma and explore the association of TP53 mutations with platinum resistance. METHODS: Next generation sequencing data was obtained from our institutional database for patients with high grade serous ovarian carcinoma undergoing primary treatment. Sequencing data, demographic, and clinical information was reviewed. The primary outcome analyzed was time to recurrence or refractory diagnosis. Associations between the primary outcome and different classification schemes for TP53 mutations (structural, functional, hot spot, pathogenicity scores, immunohistochemical staining patterns) were performed. RESULTS: 209 patients met inclusion criteria. TP53 mutations were the most common mutation. There were no differences in platinum response with TP53 hotspot mutations or high pathogenicity scores. Presence of TP53 gain-of-function mutations or measure of TP53 gain-of function activity were not associated with platinum resistance. Immunohistochemical staining patterns correlated with expected TP53 protein function and were not associated with platinum resistance. CONCLUSIONS: TP53 hotspot mutations or high pathogenicity scores were not associated with platinum resistance or refractory disease. Contrary to prior studies, TP53 gain-of-function mutations were not associated with platinum resistance. Estimation of TP53 gain-of-function effect using missense mutation phenotype scores was not associated with platinum resistance. The polymorphic nature of TP53 mutations may be too complex to demonstrate effect using simple models, or response to platinum therapy may be independent of initiating TP53 mutation.

"We had to put ourselves in their shoes": Experiences of Medical Students and ObGyn Residents with a Values Clarification Workshop on Abortion.

Purpose: Values clarification workshops on abortion have been shown to increase support for abortion among healthcare workers. However, few studies have examined the impact of values clarification workshops on abortion among medical trainees. This study aimed to understand medical student and obstetrics and gynecology (ObGyn) residents' experiences with a virtual values clarification workshop on abortion. Methods: Clerkship year medical students and ObGyn residents at four midwestern teaching hospitals were invited to be interviewed about their experiences in a virtual values clarification workshop on abortion from January 2021 through December 2021. A single interviewer conducted interviews via Zoom using a standardized interview guide. Participants were asked to provide feedback and discuss their experiences in the workshop. Four qualitatively trained evaluators coded the interview transcripts in NVivo, using an inductive approach to establish consensus codes then themes. Results: This study interviewed 37 trainees, including 24 medical students and 13 ObGyn residents, as well as five facilitators, between November 2021 and February 2022. Three themes emerged in both trainee groups. First, participants found the workshops helped trainees clarify and understand their own views on abortion through thought exploration, peer validation, and reflection on their views' potential societal impacts. Second, through the workshop, participants reflected on others' opinions on abortion and better understood the spectrum of beliefs their peers held. Finally, participants found the workshops helped them explore and develop their professional identity as physicians-in-training, through practicing communication skills and building trust and mutual respect among peers. Conclusions: Medical trainees found values clarification workshops on abortion to be valuable, helping them establish their own beliefs about abortion, contextualize these beliefs among their peers', and practice professionalism. These findings indicate that values clarification workshops can play a key role in helping medical trainees discuss abortion and prepare for their professional future.