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.

Gynecologic Oncology fellowship recruitment in the virtual era: An evaluation of program websites and survey of applicant preferences.

Objective: Virtual Gynecologic Oncology fellowship recruitment has altered how candidates and programs exchange information. This study analyzes programs' web-based content and the priorities of fellowship candidates. Methods: Web-based materials of Gynecologic Oncology fellowship programs participating in the 2022 match were reviewed. An anonymous survey was emailed to applicants. Questions assessed importance of web-based materials on a Likert scale. Respondents were asked to rank factors from most to least important in their decisions to interview and rank programs. Results: Of the 66 programs participating in the 2022 Gynecologic Oncology fellowship match, 62 (93.9%) had accessible websites. Over one-fourth (25.8%) of program websites did not list application requirements. Most (74.2%) websites contained requests for letters of recommendation, but fewer (48.4%) specified the preferred quantity or authorship. Residency in-service exam score requirement information was present on 61.3% of websites. Of 100 applicants invited to participate, 44 returned surveys (44% response rate). The median number of programs applied to was 60 (IQR 51-65). Web-based materials most important to candidates were application requirements and deadlines, letter of recommendation details, and in-service exam requirements. Interaction with faculty and program information received during interview days were among the most important factors in decisions to rank programs. Conclusions: Gynecologic Oncology fellowship applicants surveyed in this study applied to nearly all participating fellowships. The content of web-based materials varies across program websites, particularly for application requirements, which applicants indicated as the most important electronically available material. Programs should have clear application requirements and provide clinical details on their websites.

Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes.

High-grade serous ovarian cancer (HGSOC) metastasizes through transcoelomic spread, with both single cells and spheroids of tumor cells observed in patient ascites. These spheroids may form through single cells that detach and aggregate (Sph-SC) or through collective detachment (Sph-CD). We developed an in vitro model to generate and separate Sph-SC from Sph-CD to enable study of Sph-CD in disease progression. In vitro-generated Sph-CD and spheroids isolated from ascites were similar in size (mean diameter 51 vs 55 µm, p > 0.05) and incorporated multiple ECM proteins. Using the in vitro model, nascent protein labeling, and qRT-PCR, we determined that ECM was produced after detachment. As fibronectin plays a key role in many cell adhesion events, we confirmed that inhibiting RGD-based adhesion or fibronectin assembly reduced Sph-CD-mesothelial adhesion strength under shear stress. Our model will enable future studies to determine factors that favor formation of Sph-CD, as well as allow investigators to manipulate Sph-CD to better study their effects on HGSOC progression.

Mechanical and oral antibiotic bowel preparation in ovarian cancer debulking: Are we lowering or just trading surgical complications?

OBJECTIVES: To examine postoperative complications associated with preoperative mechanical and oral antibiotic bowel preparation (MOABP) for patients with ovarian cancer who underwent bowel resection at cytoreductive surgery (CRS). METHODS: This was a single-institution retrospective study of patients with ovarian cancer undergoing CRS from 01/2011-12/2020 using ICD-10 diagnoses and procedure codes. Patients were stratified by those who underwent bowel resection versus no resection. Bowel resection patients were further stratified by those who underwent MOABP versus no bowel preparation. Patient demographics, tumor data, and perioperative metrics were collected. Unadjusted and adjusted logistic regression evaluated odds of 30-day postoperative complications in patients with bowel resection versus no resection and those with MOABP versus no bowel preparation. RESULTS: Of 919 patients identified, 215 (23.3%) required bowel resection, which included 81 (37.7%) who received MOABP. Patient characteristics, co-morbidities, and cancer data were similar between MOABP versus no bowel preparation patients. MOABP patients underwent more interval CRS (34.6% versus 9.0%), more optimal surgical resections (96.3% versus 83.8%), fewer diverting ostomies (13.5% versus 33.5%), and shorter hospital stays (7.1 versus 9.4 days) than no bowel preparation patients. On adjusted analyses, MOABP patients experienced significantly lower odds of deep/organ-space surgical infections and 30-day readmissions but higher odds of unplanned intensive care unit (ICU) admissions and grade 3 or higher cardiac and gastrointestinal complications. CONCLUSIONS: Patients who underwent preoperative MOABP prior to ovarian cancer CRS with bowel resection had lower odds or deep/organ-space infections and readmissions, shorter hospital stays, fewer diverting ostomies, and more optimal resections. However, these patients also experienced higher odds of ICU admissions and grade 3 or higher cardiac and gastrointestinal complications. The positive and negative postoperative outcomes in this population should be considered in clinical practice.

Viscoelastic Testing in an Obstetric Population at High Risk of Hemorrhage.

INTRODUCTION: Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic test used in trauma for goal-directed transfusion. However, there are limited data on baseline ROTEM parameters in the U.S. obstetric population. Obtaining baseline parameters is a first step in implementing a goal-directed massive transfusion protocol in obstetric hemorrhage. OBJECTIVE: Our study aimed to establish pre- and postdelivery baseline parameters in a high-risk obstetric population and determine their association with postpartum hemorrhage (PPH). STUDY DESIGN: Prospective observational study of patients ≥34 weeks' gestation, at high risk of PPH, admitted for delivery. INTEM, EXTEM, FIBTEM, and APTEM assays were performed at the time of admission to labor and delivery and then 2 hours after delivery. Primary outcome was pre- and postdelivery ROTEM parameters among women without PPH. A sample size of 60 women was needed for >90% power to detect at least 50% correlation between pre- and postdelivery assuming a loss of 10% of participants to follow-up. RESULTS: Of 60 women in the study, 10 (17%) had PPH. Baseline characteristics were not different between those with or without PPH. Pre- and postdelivery ROTEM parameters were not significantly different except for APTEM. None of the patients who had PPH, compared with 4 (10%) of those who did not, had shortened clotting time and higher maximum clot firmness in postdelivery APTEM compared with EXTEM, a pattern suggestive of hyperfibrinolysis (p = 0.4). CONCLUSIONS: In this study, we describe baseline ROTEM parameters in women at high risk of PPH. The majority of patients did not have a ROTEM pattern that is suggestive of hyperfibrinolysis, for which tranexamic acid is thought to be beneficial. Based on our findings, previously established obstetric transfusion thresholds for goal-directed massive transfusion protocols are likely valid for the majority of the obstetric population regardless of the presence of comorbidities or pregnancy complications. KEY POINTS: · ROTEM parameters do not vary significantly before and after delivery.. · Most patients did not have a hyperfibrinolysis pattern, for which tranexamic acid is thought to be beneficial.. · Previous goal-directed obstetric transfusion thresholds are likely valid in most populations..

Differences in Health-Related Quality of Life and Health Behaviors Among Lesbian, Bisexual, and Heterosexual Women Surviving Cancer from the 2013 to 2018 National Health Interview Survey.

Purpose: Health-related quality of life (HRQoL) and health behaviors contribute to cancer morbidity and mortality, which are elevated in lesbian and bisexual women (LBW). The purpose of this study was to assess differences in HRQoL and health behaviors between heterosexual and lesbian women and heterosexual and bisexual women cancer survivors. Methods: We pooled 2013-2018 National Health Interview Survey data. HRQoL comprised physical, mental, financial, and social health domains. Health behaviors included tobacco and alcohol use, physical activity, and preventive health care. Weighted, multivariable logistic regression models estimated odds ratios (ORs) with 95% confidence intervals (CIs). Results: The sample included 10,830 heterosexual, 141 lesbian, and 95 bisexual cancer survivors. Lesbian women reported higher odds of fair/poor self-rated health (OR: 1.68, 95% CI 1.02-2.78), chronic obstructive pulmonary disease (OR: 1.98, 95% CI 1.09-3.56), and heart conditions (OR: 1.90, 95% CI 1.16-3.12) than heterosexual women. Bisexual women reported higher odds of severe psychological distress (OR: 3.03, 95% CI 1.36-6.76), heart conditions (OR: 1.98, 95% CI 1.12-3.53), and food insecurity (OR: 2.89, 95% CI 1.29-6.50) than heterosexual women. For health behaviors, lesbian women reported greater odds of current (OR: 2.34, 95% CI 1.26-4.34) and former tobacco use (OR: 1.89, 95% CI 1.21-2.96), and bisexual women had lower odds of a recent mammogram (OR: 0.42, 95% CI 0.23-0.78) than heterosexual women. Conclusions: LBW cancer survivors reported disparities in HRQoL and health behaviors. In cancer care settings, identification of LBW patients requiring physical and mental health promotion, financial services, and supported tobacco cessation may improve health and survival.

Positive sentinel lymph node in a patient with clinical stage I vaginal cancer.

•Sentinel lymph node mapping is feasible in patients with vaginal cancer.•Here we report a positive sentinel lymph node in a patient with clinically early-stage vaginal cancer.•Sentinel lymph node mapping and dissection may guide primary treatment decisions.

PARP Inhibitors in Gynecologic Cancers: What Is the Next Big Development?

PURPOSE OF REVIEW: Conventional and novel applications of Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) are reviewed in the context of recently published clinical trials and preclinical data supporting rapidly expanding uses of this class of chemotherapy. RECENT FINDINGS: PARPi block a pathway of DNA repair and target defects in homologous recombination repair (HRR), a pathway responsible for high-fidelity repair of double-strand breaks in DNA. BRCA1/2 proteins are essential to this pathway. Approximately 15-30% of women with ovarian cancer will have a germline or somatic BRCA mutation, and PARPi have shown promise in this population in a variety of settings. With growing understanding of the HRR pathway and its role in gynecologic malignancies, the potential applications of PARPi continue to expand. While the role of PARPi in gynecologic malignancies is most established in ovarian cancer, there are also promising applications in uterine and cervical cancer. We review current indications for PARPi use and promising applications of these medications in gynecologic malignancies.

Bariatric surgery after failed conservative management in a morbidly obese patient with endometrial cancer.

•Extreme obesity may preclude patients from primary surgical management of endometrial cancer.•Bariatric surgery is a safe and effective method of rapid weight loss in patients with extreme obesity.•Delayed hysterectomy, after weight loss from bariatric surgery, is an option in select patients with endometrial cancer.

Role of Olaparib as Maintenance Treatment for Ovarian Cancer: The Evidence to Date.

PARP inhibitors have shown significant promise in the treatment of ovarian cancer. Olaparib is a PARP inhibitor that has been approved for maintenance for BRCA-mutated ovarian cancer in the recurrent and front-line setting as well as for treatment of BRCA-mutated ovarian cancer in patients who have received multiple prior lines of chemotherapy. In this review, we focus on the use of olaparib in the maintenance setting including the evidence to date, ongoing research, and future directions.

Cutting costs and standardizing care: Once-per-cycle complete blood count monitoring may be safe for patients undergoing platinum-based chemotherapy.

AIM: The aim of this study was to evaluate whether frequency of complete blood count (CBC) testing during chemotherapy for gynecologic cancer impacts hospital admissions or rates of neutropenic fever. METHODS: A retrospective cohort study was performed at a single academic institution. Patients undergoing platinum-based chemotherapy for endometrial or ovarian cancer from January 2010 to December 2014 were identified from a clinical database. Patients receiving dose-dense chemotherapy or on a clinical trial were excluded. Electronic chart review collected demographic and clinical characteristics. The primary outcome was the rate of febrile neutropenia or hospital admission. RESULTS: A total of 174 patients were identified, 63 (36%) with endometrial and 111 (64%) with ovarian cancer. Fifty-four percent of patients received multiple CBC per cycle compared with 46% who only had one CBC per cycle. The majority of patients were treated with a platinum-based doublet (85%). Dose reductions, addition of granulocyte colony stimulating factor, and rates of grade 3 or 4 anemia and neutropenia were significantly associated with more frequent testing. There was no difference in rates of neutropenic fever (5.3 vs 3.8%, P = 0.45) or hospital admission (22.3 vs 21.3%, P = 0.86) for multiple versus single CBC monitoring. CONCLUSION: More frequent laboratory testing detected more cases of grade 3 or 4 hematopoietic toxicities and was associated with more interventions. There were no differences in number of hospitalizations or cases of neutropenic fever by frequency of laboratory testing, suggesting that it may be appropriate to decrease routine laboratory tests for select patients.

Death Notification: Someone Needs To Call the Family.

BACKGROUND: The death notification process can affect family grief and bereavement. It can also affect the well-being of involved physicians. There is no standardized process for making death notification phone calls. We assumed that residents are likely to be unprepared before and troubled after. OBJECTIVE: We investigated current death notification practices to develop an evidence-based template for standardizing this process. DESIGN: We used results of a literature review and open-ended interviews with faculty, residents, and widows to develop a survey regarding resident training and experience in death notification by phone. SETTING/SUBJECTS: We invited all internal medicine (IM) residents at our institution to complete the survey. MEASUREMENTS: Sixty-seven of 93 IM residents (72%) responded to the survey. Eighty-seven percent of responders reported involvement in a death that required notification by phone. RESULTS: Eighty percent of residents felt inadequately trained for this task. Over 25% reported that calls went poorly. Attendings were involved in 17% of cases. Primary care physicians were not involved. Nurses and chaplains were not involved. Respondents never delayed notification of death until family arrived at the hospital. There was no consistent approach to rehearsing or making the call, advising families about safe travel to the hospital, greeting families upon arrival, or following up with expressions of condolence. CONCLUSIONS: Poor communication skills during death notification may contribute to complicated grief for surviving relatives and stress among physicians. This study is the first to describe current practices of death notification by IM residents. More training is needed and could be combined with training in disclosure of medical error.