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Simple Summary: There is a crucial need to improve treatment regimens in patients with recurrent endometrial cancer. Although immunotherapy treatments have shown impressive benefit in microsatellite instability-high endometrial cancer, they have been less predictable in the majority of endometrial cancers, which are microsatellite stable. Our aim was to characterize clinical outcomes in patients with recurrent microsatellite stable endometrial cancer treated in early-phase immunotherapy clinical trials in order unravel treatment regimens that would improve response and survival. Our findings suggest that utilizing immunotherapy in combination with other non-immunotherapy agents resulted in greater duration of disease control and improved survival outcomes compared to immunotherapy only (monotherapy) or in combination with other immunotherapy agents. Future studies are needed to validate these findings. Recurrent microsatellite stable (MSS) endometrial cancer has poor response to conventional therapy and limited efficacy with immune checkpoint monotherapy. We conducted a retrospective study of recurrent MSS endometrial cancer patients enrolled in immunotherapy-based clinical trials at MD Anderson Cancer Center between 1 January 2010 and 31 December 2019. Patients were evaluated for radiologic response using RECIST 1.1 criteria, progression-free survival (PFS), and overall survival (OS). Thirty-five patients were treated with immune checkpoint inhibitors: 8 with monotherapy, 17 with immunotherapy (IO) in combination with another IO-only, and 10 with IO in combination with non-IO therapy. Among those treated with combination IO plus non-IO therapy, one had a partial response but 50% had clinical benefit. Patients who received combination IO plus non-IO therapy had improved PFS compared to those who received monotherapy (HR 0.56, 95% CI 0.33–0.97; p = 0.037) or combination IO-only therapy (HR 0.36, 95% CI 0.15–0.90; p = 0.028) and had improved OS when compared to monotherapy after adjusting for prior lines of therapy (HR 0.50, 95% CI 0.27–0.95; p = 0.036). The potential beneficial clinical outcomes of combination IO plus non-IO therapy in MSS endometrial cancer should be validated in a larger study. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) represent a promising novel class of cancer therapy, but immunemediated adverse events can complicate ICI treatment. Acute cholecystitis in patients receiving ICI therapy has not been characterized. We aimed to describe the clinical features of patients who developed ICI-related cholecystitis. Methods: We evaluated a case series of patients at a tertiary cancer center who received ICI therapy and developed cholecystitis, diagnosed by clinical presentation and diagnostic imaging, during 2010-2018. Patients with a history of chronic cholecystitis or other etiologies of acute cholecystitis, such as cholelithiasis, were excluded. A chi-square test was used to compare the frequency of cholecystitis between ICI regimens. Kaplan-Meier and log rank analyses were used to compare survival between subgroups. Results: Of the 4253 patients who received ICIs in the study period, 25 (0.6%) patients developed suspected ICI-related cholecystitis. Alternatively, of the 31,426 cancer-matched patients who received non-ICI therapy, 72 (0.2%) developed acalculous cholecystitis (P < 0.001). Among the 25 included patients, the median time from ICI initiation to cholecystitis was 6 months (range, 0.1-31 months). Fifteen (60%) patients received an inhibitor of programmed death protein 1 (anti--PD-1) or of its ligand (anti--PD-L1) as a single agent, and 10 (40%) patients received an inhibitor of cytotoxic T-lymphocyte associated protein 4 (anti--CTLA-4) therapy alone or combined with anti--PD-1/L1. Anti--CTLA-4 monotherapy was associated with a higher risk of cholecystitis (P = 0.006). ICI therapy was discontinued in 20 patients, in three (12%) as a result of acute cholecystitis. Two (8%) patients developed sepsis, and four (16%) had perforation of the gallbladder wall. Five (20%) patients underwent surgical cholecystectomy, and eight (32%) underwent percutaneous drainage. Five (20%) patients were treated with steroids; two of them required surgery. Ten (40%) patients were able to restart ICI therapy. Patients who received a combination of anti--CTLA-4 and anti--PD-1/L1 had more complications of cholecystitis than did patients who received either agent alone (P =0.03). Conclusions: ICI treatment can result in a clinical condition similar to typical acute cholecystitis in a minority of patients. ICI-related cholecystitis should be managed in a similar fashion to typical cholecystitis. The efficacy of steroids for the treatment of ICI-related cholecystitis is unclear. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate differences in morbidity, progression-flee interval, and survival in women with advanced epithelial ovarian cancer treated with initial chemotherapy versus initial surgery. Study design: All women with epithelial ovarian cancer who were treated surgically at our hospital between January 1, 1995, and January 1, 2003, were eligible; the cases of 200 patients met the criteria and underwent retrospective chart review. Results: Ninety-eight patients (49%) had initial chemotherapy, and 102 patients (51%) had initial surgery. Patients who received initial chemotherapy were more likely to have stage IV disease (initial chemotherapy, 27%, vs initial surgery, 8%; P = .042) and grade 3 disease (initial chemotherapy, 73%, vs initial surgery, 61%; P = .025). Optimal cytoreduction was achieved more often in patients who received initial chemotherapy (initial chemotherapy, 86%, vs initial surgery, 54%; P < .001). Only optimal cytoreduction (P = .022), and not treatment choice (P = .089), had an impact on median survival. Conclusion: Initial chemotherapy is a reasonable alternative to initial surgery for the treatment of selected patients with advanced epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Malignant large bowel obstruction (LBO) is a frequent complication affecting women with gynecologic cancers and is an indication for emergent surgery. However, the life expectancy and subsequent medical care utilization are unknown. We sought to estimate overall survival (OS) following colostomy and describe subsequent healthcare utilization among patients with advanced gynecologic malignancies. We conducted a retrospective analysis of patients with advanced gynecologic cancers who underwent colostomy with palliative intent due to LBO at our institution between March 2014 and January 2023. Summary statistics were used to describe the clinical and demographic characteristics of the study population. OS was estimated using the Kaplan-Meier method, and we defined healthcare utilization at the end-of-life using criteria published by the National Quality Forum. A total of 78 patients were included. The median age at the time of surgery was 61 (range: 34–83), and most patients had recurrent ovarian, fallopian tube, or primary peritoneal cancer (n = 51, 65.4%), followed by cervical cancer (n = 16, 20.5%), and uterine cancer (n = 10, 12.8%). The median Charlson comorbidity index was 3 and median postoperative length of stay was five days (range: 1–26). The median follow-up for all patients was 4.5 months (range: 0.07–46.2), and the median OS was 4.5 months (95% CI: 2.9–6.0), including 12 patients (15.4%) with <30-day OS and 21 (26.9%) with <60-day OS. In the last 30 days of life, 62.7% of patients were re-admitted to the hospital, 53.0% were seen in the emergency department, and 18.5% were admitted to an intensive care unit. A significant proportion of patients died within 60 days of surgery, and many had high healthcare utilization at the end of life. • Median overall survival for patients undergoing palliative colostomy for a large bowel obstruction was 4.5 months. • Fifteen percent of patients did not survive beyond post operative day 30. • Poor performance status and platinum resistance were associated with worse overall survival. • In the last 30 days of life, 63% were re-admitted to the hospital and 18% were admitted to an intensive care unit. [ABSTRACT FROM AUTHOR]

Simple Summary: Knowledge of ovarian cancer molecular characteristics is increasingly crucial to individualizing and optimizing treatment strategies for this heterogeneous disease. Molecular features such as germline or somatic mutations, homologous recombination deficiency (HRD) status, microsatellite instability, and tumor mutational burden are associated with increased susceptibility to poly-ADP ribose polymerase inhibitors (PARPi) or immunotherapy. Our aim was to characterize these molecular features among ovarian cancer patients and determine their association with survival. Two different HRD score thresholds were evaluated: one currently used in clinics (≥42) and another proposed as a new threshold (≥33). An HRD score ≥33 was associated with improved overall survival in ovarian cancer. As HRD assays are increasingly used for treatment planning, future studies should evaluate an HRD score threshold of ≥33 compared to the currently used threshold of ≥42 for PARPi use. New therapies, such as poly-ADP ribose polymerase inhibitors (PARPi), and immunotherapy treatments have generated great interest in enhancing individualized molecular profiling of epithelial ovarian cancer (EOC) to improve management of the disease. In EOC patients, putative biomarkers for homologous recombination deficiency (HRD), microsatellite instability (MSI), and tumor mutational burden (TMB) were characterized and correlated with survival outcomes. A series of 300 consecutive EOC patients were enrolled. Patients underwent neoadjuvant chemotherapy (n = 172) or primary cytoreductive surgery (n = 128). Molecular profiling and survival analyses were restricted to the primary cytoreductive surgery cohort due to tissue availability. All patients underwent germline testing for HRD- and MSI-related gene mutations. When sufficient tissue was available, screening for somatic BRCA1/2 mutations, BRCA1 promoter methylation, HRD score (a measure of genomic instability), MSI, and TMB testing were performed. HRD score ≥33 was associated with improved overall survival on multivariable analysis. In the era of biomarker-driven clinical care, HRD score ≥33 may be a useful adjunctive prognostic tool and should be evaluated in future studies to predict PARPi benefits. [ABSTRACT FROM AUTHOR]

Platinum-based therapy is the cornerstone of ovarian cancer treatment. Development of platinum hypersensitivity can limit therapeutic options. In this brief report, we present case of successful cisplatin administration following two unsuccessful carboplatin desensitization attempts, and without the need for pre-treatment steroids. Retrospective chart review was performed. One case of recurrent primary peritoneal carcinoma previously treated with a carboplatin-based regimen, developed a platinum hypersensitivity. Two attempts at carboplatin desensitization were unsuccessful. Cisplatin was substituted and the patient achieved a complete response to therapy without further hypersensitivity. Platinum-based therapies are vital to the treatment of primary peritoneal and ovarian carcinoma. Protocols that successfully incorporate platinum agents, despite a platinum hypersensitivity, are clinically relevant. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize variation in the gut microbiome of women with locally advanced cervical cancer and compare it to healthy controls. We characterized the 16S rDNA fecal microbiome in 42 cervical cancer patients and 46 healthy female controls. Shannon diversity index (SDI) was used to evaluate alpha (within sample) diversity. Beta (between sample) diversity was examined using principle coordinate analysis (PCoA) of unweighted Unifrac distances. Relative abundance of microbial taxa was compared between samples using Linear Discriminant Analysis Effect Size (LEfSe). Within cervical cancer patients, bacterial alpha diversity was positively correlated with age (p = 0.22) but exhibited an inverse relationship in control subjects (p < 0.01). Alpha diversity was significantly higher in cervical cancer patients as compared to controls (p < 0.05), though stratification by age suggested this relationship was restricted to older women (>50 years; p < 0.01). Beta diversity (unweighted Unifrac; p < 0.01) also significantly differed between cervical cancer patients and controls. Based on age- and race-adjusted LEfSe analysis, multiple taxa significantly differed between cervical cancer patients and controls. Prevotella, Porphyromonas , and Dialister were significantly enriched in cervical cancer patients, while Bacteroides, Alistipes and members of the Lachnospiracea family were significantly enriched in healthy subjects. Our study suggests differences in gut microbiota diversity and composition between cervical cancer patients and controls. Associations within the gut microbiome by age may reflect etiologic/clinical differences. These findings provide rationale for further study of the gut microbiome in cervical cancer. • Among cervical cancer patients, bacterial diversity was higher in older women as compared to younger women. • Compared to controls, women with cervical cancer have distinct differences in their gut microbiota diversity. • Compared to controls, women with cervical cancer have distinct differences in their gut microbiota composition. • Currently there is an important gap in studies investigating the gut microbiome and gynecologic cancers. [ABSTRACT FROM AUTHOR]

Objectives: Malignant large bowel obstructions are a frequent complication affecting women with gynecologic cancers and are an indication for possible emergent surgery. However, the life expectancy and subsequent medical care utilization following such a procedure when done for palliative intent are unknown. We sought to estimate overall survival (OS) following surgical formation of a colostomy due to large bowel obstruction with palliative intent and describe subsequent healthcare utilization among patients with recurrent gynecologic malignancies. Methods: We conducted a retrospective analysis of all gynecologic oncology patients with recurrent metastatic gynecologic cancers who underwent colostomy due to large bowel obstruction with a palliative intent at our institution between March 2014 and December 2020. Summary statistics were used to describe the clinical and demographic characteristics of the study population. OS was estimated using the Kaplan-Meier methods, and we defined healthcare utilization at the end of life using criteria published by the national quality forum. Results: A total of 51 women met the inclusion criteria. The median age at the time of surgery was 61 years (range: 34-82), and most patients had a recurrent ovarian, fallopian tube, or primary peritoneal cancer (n =22, 43%), followed by cervical cancer (n =9, 18%), and endometrial cancer (n =4, 8%). The median Charlson comorbidity index was 3, and 54% received chemotherapy in the 60 days prior to surgery. Median surgical time was 94 minutes, and median postoperative length of stay was five days (range: 1-26). The median follow-up for all subjects was 4.5 months (range: 0.2-46.2), and the median OS was 4.5 months (95% CI: 2.37 - 9.43). This includes nine patients (17%) with <30-day OS and 16 (31%) with <60-day OS. Forty- nine percent (n =25) of patients did not receive further chemotherapy after a colostomy. In the last 30 days of life, 67% of patients were re-admitted to the hospital, 58% were seen in the emergency department, and 15% were admitted to an intensive care unit. Conclusions: While palliative surgery with colostomy formation is often offered to gynecologic oncology patients with malignant large bowel obstructions, there are limited data to aid in the shared decision-making regarding palliative surgery at the end of life. In our study, a significant proportion of patients died within 60 days of surgery, and many had high healthcare utilization at the end of life. Additional analysis is planned to assess characteristics associated with shorter OS and increased healthcare utilization at the end of life. Further study is also needed to determine patient-reported outcomes related to palliative colostomy. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The objective of this pilot study was to determine if frailty predicts surgical complications among elderly women undergoing gynecologic oncology procedures. Methods: A cohort of gynecologic oncology patients age ≥65, undergoing surgery between March and December 2011 was identified. Frailty was evaluated using a validated assessment tool. The primary outcome measure was 30day postoperative complication rate. Results: Forty women were approached for study entry and 37 (92%) enrolled. The mean age was 73years (range 65–95). The majority of women had a malignancy and underwent a major abdominal surgical procedure. Twenty-one women (57%) were not frail, 10 (27%) were intermediately frail and 6 (16%) were frail. There was no difference in age or prevalence of medical comorbidities between groups. Frail women had a significantly higher BMI compared to intermediately frail and not frail women, (36.0, 31.5 and 26.1kg/m2, p =0.02). The rate of 30-day surgical complications increased with frailty score and was 24%, versus 67% for women who were not frail as compared to the frail (p =0.04). Conclusions: Pre-operative frailty assessment is well accepted by gynecologic oncology patients and feasible in a clinic setting. Frail women had a higher BMI, indicating that low body weight is not a marker for frailty, and had a significantly higher rate of 30-day postoperative complications in this pilot study. Initial findings support the concept of measuring frailty as a possible predictor for postoperative morbidity that will allow for improved patient counseling and decision making. [Copyright &y& Elsevier]