Trends in the use of neoadjuvant chemotherapy for low-grade serous ovarian cancer in the United States.

OBJECTIVE: To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery. METHODS: We identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004-December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control. RESULTS: We observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6-8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07-1.24), and stage IV disease (RR 2.66; 95% CI 2.31-3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65-0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08-1.42). CONCLUSION: NACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures.

Disease Distribution at Presentation Impacts Benefit of IP Chemotherapy Among Patients with Advanced-Stage Ovarian Cancer.

BACKGROUND: Ovarian cancer with miliary disease spread is an aggressive phenotype lacking targeted management strategies. We sought to determine whether adjuvant intravenous/intraperitoneal (IV/IP) chemotherapy is beneficial in this disease setting. METHODS: Patient/tumor characteristics and survival data of patients with stage IIIC epithelial ovarian cancer who underwent optimal primary debulking surgery from 01/2010 to 11/2014 were abstracted from records. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables. The Kaplan-Meier method was used to estimate survival curves, and outcomes were compared using log-rank tests. Factors significant on univariate analysis were combined into multivariate logistic regression survival models. RESULTS: Among 90 patients with miliary disease spread, 41 (46%) received IV/IP chemotherapy and 49 (54%) received IV chemotherapy. IV/IP chemotherapy, compared with IV chemotherapy, resulted in improved progression-free survival (PFS; 23.0 versus 12.0 months; p = 0.0002) and overall survival (OS; 52 versus 36 months; p = 0.002) in patients with miliary disease. Among 78 patients with nonmiliary disease spread, 23 (29%) underwent IV/IP chemotherapy and 55 (71%) underwent IV chemotherapy. There was no PFS or OS benefit associated with IV/IP chemotherapy over IV chemotherapy in these patients. On multivariate analysis, IV/IP chemotherapy was associated with improved PFS (HR, 0.28; 95% CI 0.15-0.53) and OS (HR, 0.33; 95% CI 0.18-0.61) in patients with miliary disease compared with those with nonmiliary disease (PFS [HR, 1.53; 95% CI 0.74-3.19]; OS [HR, 1.47; 95% CI 0.70-3.09]). CONCLUSIONS: Adjuvant IV/IP chemotherapy was associated with oncologic benefit in miliary disease spread. This survival benefit was not observed in nonmiliary disease.

Incidence of myelodysplastic syndrome and acute myeloid leukemia in patients receiving poly-ADP ribose polymerase inhibitors for the treatment of solid tumors: A meta-analysis of randomized trials.

BACKGROUND: Clinical trials demonstrated that PARPi (poly [adenosine diphosphate-ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML. METHODS: Medline, Embase, and Cochrane databases were searched (inception to January 6, 2020) and phase 2 and 3 clinical trials that randomized patients with solid tumors to a PARPi or control therapy were included. The PRISMA guidelines were used to extract data independently by multiple authors. We extracted person-time and number of cases of MDS/AML in the PARPi and control arms of each study and pooled results with a random-effects Poisson regression model. The pooled incidence rate ratio (IRR) for MDS/AML among patients randomized to PARPi therapy was compared to those randomized to a control. RESULTS: We identified 14 studies that included 5739 patients. Accounting for intra-study clustering, the risk of MDS/AML was similar in patients who were randomly assigned to receive PARPi compared to controls (IRR 1.32, 95% confidence interval [CI] 0.78-2.26). In the front-line setting, PARPi therapy was associated with developing MDS/AML (IRR 5.43, 95% CI 1.51-19.60). Among patients treated for recurrence, however, the risk of MDS/AML appeared to be similar among patients randomized to PARPi or control treatment. Among studies that included only patients with a BRCA mutation, the risk of MDS/AML was similar in both treatment groups (IRR 0.83, 95% CI 0.45-1.53), but PARPi therapy was associated with MDS/AML in studies with an unrestricted population (IRR 2.43, 95% CI 1.17-5.06). CONCLUSION: The pooled overall effect was not statistically significant. However, treatment with PARPi was associated with a statistically significant increase in the incidence of MDS/AML among patients receiving front-line cancer therapy and those with limited prior exposure to chemotherapy.

Palliative care referral patterns and measures of aggressive care at the end of life in patients with cervical cancer.

INTRODUCTION: Fifteen per cent of women with cervical cancer are diagnosed with advanced disease and carry a 5 year survival rate of only 17%. Cervical cancer may lead to particularly severe symptoms that interfere with quality of life, yet few studies have examined the rate of palliative care referral in this population. This study aims to examine the impact of palliative care referral on women who have died from cervical cancer in two tertiary care centers. METHODS: We conducted a retrospective review of cervical cancer decedents at two tertiary institutions from January 2000 to February 2017. We examined how aggressive measures of care at the end of life, metrics defined by the National Quality Forum, interacted with clinical variables to understand if end-of-life care was affected. Univariate and multivariate parametric and non-parametric testing was used, and linear regression models were generated to determine unadjusted and adjusted associations between aggressive measures of care at the end of life with receipt of palliative care as the main exposure. RESULTS: Of 153 cervical cancer decedents, 73 (47%) received a palliative care referral and the majority (57%) of referrals occurred during an inpatient admission. The median time from palliative care consultation to death was 2.3 months and 34% were referred to palliative care in the last 30 days of life. Palliative care referral was associated with fewer emergency department visits (OR 0.18, 95% CI 0.05 to 0.56), inpatient stays (OR 0.21, 95% CI 0.07 to 0.61), and intensive care unit admissions (OR 0.24, 95% CI 0.06 to 0.93) in the last 30 days of life. Palliative care did not affect chemotherapy or radiation administration within 14 days of death (p=0.36). Women evaluated by palliative care providers were less likely to die in the acute care setting (OR 0.19, 95% CI 0.07 to 0.51). DISCUSSION: In two tertiary care centers, less than half of cervical cancer decedents received palliative care consultations, and those referred to palliative care were often evaluated late in their disease course. Palliative care utilization was also associated with a lower incidence of poor-quality end-of-life care.

The Role of Minimally Invasive Surgery in the Care of Women with Ovarian Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To synthesize evidence from studies investigating survival outcomes for patients with ovarian cancer undergoing minimally invasive surgery (traditional or robotic laparoscopy) compared with those for patients with ovarian cancer undergoing laparotomy. DATA SOURCES: We searched Ovid MEDLINE and Embase (from inception to December 2019). METHODS OF STUDY SELECTION: Observational cohort studies and randomized controlled trials that compared risk of recurrence or death between women undergoing minimally invasive and open procedures for staging (10), interval cytoreduction (4), secondary cytoreduction (2), and evaluation of resectability (1) were included. TABULATION, INTEGRATION, AND RESULTS: Data on the number of participants, number of deaths and recurrences, and results of analyses of overall or progression-free survival were abstracted for all studies. A random-effects meta-analysis was used to pool the results of studies comparing minimally invasive staging and open staging. The surgical approach (minimally invasive versus open) was not significantly associated with hazard of death or recurrence (pooled hazard ratio 0.92; 95% confidence interval, 0.61-1.38) or all-cause mortality (pooled hazard ratio 0.96; 95% confidence interval, 0.49-1.89). One randomized trial demonstrated that diagnostic laparoscopy could triage patients to neoadjuvant chemotherapy and avoid suboptimal primary surgery, without affecting recurrence-free or overall survival. Most studies included in this review were observational and at high risk for bias, and few studies accounted for potential confounding. CONCLUSION: Although existing studies do not demonstrate deleterious survival effects associated with minimally invasive surgery for ovarian cancer, these data must be viewed with caution given the significant methodologic shortcomings in the existing literature.

Clinical trial participation and aggressive care at the end of life in patients with ovarian cancer.

OBJECTIVES: In non-gynecologic cancers, clinical trial participation has been associated with aggressive care at the end of life. The objective of this investigation was to examine how trial participation affects end of life outcomes in patients with ovarian cancer. METHODS: In a retrospective review of women diagnosed with ovarian cancer at our institution between January 2010 and December 2015, we collected variables identified by the National Quality Forum as measures of aggressive end of life care including chemotherapy in the last 14 days of life, intensive care unit (ICU) admission in the last 30 days of life, or death in the acute care setting. Trials investigating medications but not surgical interventions were included. The primary outcome of this study was the association between trial participation and the National Quality Forum measures of aggressive end of life care in ovarian cancer decedents. Data were analyzed with univariable and multivariable parametric and non-parametric testing, and time to event outcomes were analyzed using the Kaplan-Meier method and Cox's proportional hazard models. RESULTS: Among 391 women treated for ovarian cancer, 62 patients (16%) participated in a clinical trial. Patients enrolled in clinical trials were more likely to have chemotherapy administered within 14 days of death; however, no association was found with other metrics of aggressive care at the end of life including the initiation of a new chemotherapy regimen in the last 30 days of life, ICU admissions, and death in an acute care setting. Among patients with recurrent ovarian cancer, median overall survival for trial participants was 57 months compared with only 31 months in non-trial participants (p<0.001). CONCLUSIONS: In patients with ovarian cancer, clinical trial enrollment is associated with chemotherapy administration within 14 days of death, but not other measures of aggressive care at the end of life. Given the importance of clinical trial participation in improving care for women with ovarian cancer, this study suggests that concerns regarding aggressive care prior to death should not limit clinical trial participation.

A novel classification of residual disease after interval debulking surgery for advanced-stage ovarian cancer to better distinguish oncologic outcome.

BACKGROUND: Complete surgical resection affords the best prognosis at the time of interval debulking surgery. When complete surgical resection is unachievable, optimal residual disease is considered the next best alternative. Despite contradicting evidence on the survival benefit of interval debulking surgery if macroscopic residual disease remains, the current definition of "optimal" in patients undergoing interval debulking surgery is defined as largest diameter of disease measuring ≤1.0 cm, independent of the total volume of disease. OBJECTIVE: To examine the relationship between volume and anatomic distribution of residual disease and oncologic outcomes among patients with advanced-stage epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing neoadjuvant chemotherapy then interval debulking surgery. For patients who did not undergo a complete surgical resection, a surrogate for volume of residual disease was used to assess oncologic outcomes. STUDY DESIGN: Patient demographics, operative characteristics, anatomic site of residual disease, and outcome data were collected from medical records of patients with International Federation of Gynecology and Obstetrics stage IIIC and IV epithelial ovarian cancer undergoing interval debulking surgery from January 2010 to July 2015. Among patients who did not undergo complete surgical resection but had ≤1 cm of residual disease, the number of anatomic sites (single location vs multiple locations) with residual disease was used as a surrogate for volume of residual disease. The effect of residual disease volume on progression-free survival and overall survival was evaluated. RESULTS: Of 270 patients undergoing interval debulking surgery, 173 (64.1%) had complete surgical resection, 34 (12.6%) had ≤1 cm of residual disease in a single anatomic location, 47 (17.4%) had ≤1 cm of residual disease in multiple anatomic locations, and 16 (5.9%) were suboptimally debulked. Median progression-free survival for each group was 14, 12, 10, and 6 months, respectively (P<.001). Median overall survival for each group was: 58, 37, 26, and 33 months, respectively (P<.001). CONCLUSION: Following interval debulking surgery, patients with complete surgical resection have the best prognosis, followed by patients with ≤1 cm single-anatomic location disease. In contrast, despite being considered "optimally debulked," patients with ≤1 cm multiple-anatomic location disease have a survival similar to suboptimally debulked patients.

Tablet-Based Patient Education Regarding Human Papillomavirus Vaccination in Colposcopy Clinic.

OBJECTIVE: The aim of this study was to use an electronic tablet-based education module to increase patient knowledge about human papillomavirus (HPV). METHODS: Patients presenting to an academic colposcopy clinic were first queried as to whether they had been infected with HPV. A quality improvement project was then conducted using a 4-question pretest assessing baseline knowledge about HPV and cancer, followed by a tablet-based education module and a 5-question posttest. RESULTS: Between June 2017 and January 2018, 119 patients participated in the tablet education. At their initial visit, only 50 (42.0%) of patients were aware that they had an HPV infection; however, medical records revealed that 74 women (62.2%) were presenting with a documented HPV infection. After the tablet education, 95% of women identified cervical cancer as a problem that can be caused by HPV, as compared with 88.2% in the pretest (p = .046). Knowledge of head and neck cancer as a disease that can be caused by HPV increased from 10.9% to 80.7% (p < .001). More patients answered that they "definitely" or "probably" would consider the vaccine for a child in their family: 108 (95.6%) pretest vs. 112 (99.1%) posttest (p = .046). The activities were ranked as "extremely" or "very" helpful by 93.3% of patients. CONCLUSIONS: Patients presenting to colposcopy clinic are not well educated regarding the connection between an abnormal Pap test, HPV infection, and certain cancers. Tablet-based education improves patient knowledge of HPV-associated cancers in an outpatient clinic setting.

Durable response in a woman with recurrent low-grade endometrioid endometrial cancer and a germline BRCA2 mutation treated with a PARP inhibitor.

A 42-year-old woman with a germline BRCA2 mutation and recurrent low-grade endometrioid endometrial adenocarcinoma experienced clinical and radiographic response to the poly (ADP ribose) polymerase (PARP) inhibitor, olaparib. Molecular and treatment factors are discussed.

Moving beyond "complete surgical resection" and "optimal": Is low-volume residual disease another option for primary debulking surgery?

OBJECTIVES: To examine the relationship between volume of residual disease and oncologic outcomes among patients with advanced-stage epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing primary debulking surgery (PDS). For patients that did not undergo a complete surgical resection (CSR), a surrogate for volume of residual disease was used to assess oncologic outcomes. METHODS: Medical records of patients with FIGO stage IIIC and IV epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing PDS between January 2010 and November 2014 were reviewed. Patient demographics, operative characteristics, residual disease, anatomic site of residual disease and outcome data were collected. Among patients who did not undergo CSR, but had ≤1 cm of residual disease, the number of anatomic sites (single location vs. multiple locations) with residual disease was utilized as a surrogate for volume of residual disease. The effect of residual disease volume on progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Of 240 patients undergoing PDS, 94 (39.2%) had CSR, 41 (17.1%) had ≤1 cm of residual disease confined to a single anatomic location (≤1 cm-SL), 67 (27.9%) had ≤1 cm of residual disease in multiple anatomic locations (≤1 cm-ML) and 38 (15.8%) were sub-optimally (SO) debulked. Median PFS for CSR, ≤1 cm-SL, ≤1 cm-ML and SO-debulked were: 23, 19, 13 and 10 months, respectively (p < 0.001). Median OS for CSR, ≤1 cm-SL, ≤1 cm-ML and SO-debulked were: Not yet reached, 64, 50 and 49 months, respectively (p = 0.001). CONCLUSIONS: Following PDS, CSR and ≤ 1 cm-SL patients have the best prognosis. In contrast, despite being considered "optimally debulked", ≤1 cm-ML patients have survival similar to those SO-debulked.

The effect of adolescence and advanced maternal age on the incidence of complete and partial molar pregnancy.

OBJECTIVE: To compare the age-specific incidence of complete (CM) and partial molar (PM) pregnancy in a large tertiary care center in the United States. METHODS: Incidence rates of CM and PM per 10,000 live births were calculated using databases from Brigham and Women's Hospital, between 2000 and 2013. Age-specific rates were calculated for women younger than 20 years old (adolescents), 20-39 years old (average age), and 40 years and older (advanced maternal age). Pearson χ(2) test was used to evaluate potential differences among groups. Rate ratios (RR) and 95% confidence intervals (CI) were used to compare risk of molar pregnancy among average age women with that of adolescents and women of advanced age. Holm-Bonferonni adjustment was used to correct for multiple comparisons. RESULTS: Between 2000 and 2013, there were 255 molar pregnancies (140 CM and 115 PM) and 105,942 live births, corresponding to a molar pregnancy rate of 24 per 10,000 live births (95% CI 21-27). Rates of CM and PM were 13 (95% CI 11-16) and 11 (95% CI 9-14) per 10,000 live births respectively. The incidence of CM differed significantly among maternal age groups (p<0.001). Compared to average age women, adolescents were 7.0 times as likely to develop CM (95% CI 3.6-8.9, p<0.001), and women with advanced maternal age were nearly twice as likely (1.9, 95% CI 1.8-4.7, p=0.002). The rate of PM did not vary significantly among age groups (p=0.26). CONCLUSIONS: Adolescence and advanced maternal age were associated with increased risk of complete mole, but not partial mole.

Effect of race/ethnicity on risk of complete and partial molar pregnancy after adjustment for age.

OBJECTIVE: To quantify the effect of race/ethnicity on risk of complete and partial molar pregnancy. METHODS: We conducted a cross-sectional study including women who were followed for complete or partial mole and those who had a live singleton birth in a teaching hospital in the northeastern United States between 2000 and 2013. We calculated race/ethnicity-specific risk of complete and partial mole per 10,000 live births, and used logistic regression to estimate crude and age-adjusted relative risks (RR) of complete and partial mole. RESULTS: We identified 140 cases of complete mole, 115 cases of partial mole, and 105,942 live births. The risk of complete mole was 13 cases per 10,000 live births (95% confidence interval [CI] 11-16) and that of partial mole was 11 cases per 10,000 live births (95% CI 9-13). After age-adjustment, Asians were more likely to develop complete mole (RR 2.3 95% CI 1.4-3.8, p<0.001) but less likely to develop partial mole (RR 0.2; 95% CI 0.04-0.7, p=0.02) than whites. Blacks were significantly less likely than whites to develop partial mole (RR 0.4; 95% CI 0.2-0.8, p=0.01) but only marginally less likely to develop complete mole (RR 0.6; 95% CI 0.3-1.0, p=0.07). Hispanics were less likely than whites to develop complete mole (RR 0.4; 95% CI 0.2-0.7, p=0.002) and partial mole (RR 0.4; 95% CI 0.2-0.9, p=0.02). CONCLUSION: Race/ethnicity is a significant risk factor for both complete and partial molar pregnancy in the northeastern United States.

Effect of race/ethnicity on clinical presentation and risk of gestational trophoblastic neoplasia in patients with complete and partial molar pregnancy at a tertiary care referral center.

BACKGROUND: The reported incidence of molar pregnancy varies widely among different geographic locations. This variation has been attributed, at least in part, to racial/ethnic differences. While the incidence of molar pregnancies is decreasing, certain ethnic groups such as Hispanics, Asians, and American Indians continue to have an increased risk of developing gestational trophoblastic disease across the globe. OBJECTIVE: We sought to describe the potential effect of ethnicity/race on the presentation and clinical course of complete mole and partial mole. STUDY DESIGN: All patients followed up for complete mole and partial mole at a single institution referral center from 1994 through 2013 were identified. Variables including age, race, gravidity, parity, gestational age, presenting signs/symptoms, serum human chorionic gonadotropin values, and development of gestational trophoblastic neoplasia were extracted from medical records and patient surveys. Patients with complete mole and partial mole were categorized into race/ethnicity groups defined as white, black, Asian, or Hispanic. Due to low numbers of non-white patients with partial mole in each non-white category, patients with partial mole were grouped as white or non-white. Continuous variables were compared using the Kruskal-Wallis test and binary variables were compared using the Fisher exact test. RESULTS: A total of 167 complete mole patients with known race/ethnicity status were included (57.48% white, 14.97% Asian, 14.37% black, 13.17% Hispanic). Hispanics presented at younger age (median 24.5 years) compared to whites (median 32.0 years, P = .04) and Asians (median 31.0 years, P = .03). Blacks had higher gravidity than whites (P < .001) and Hispanics (P = .05). There was no significant difference in presenting symptoms, gestational age at diagnosis, and preevacuation serum human chorionic gonadotropin level by race/ethnicity. Hispanics were significantly less likely than whites to develop gestational trophoblastic neoplasia (absolute risk difference, 28.6%; 95% confidence interval, 8.1-39.2%; P = .02). A total of 144 patients with partial mole were analyzed. There were 108 white and 36 non-white patients. Median age was 31 years for white and 29 years for non-white patients (P = .006). Median gravidity was 2 for white and 3 for non-white patients (P < .001), and median parity was 0 for white patients and 1 for non-white patients (P = .003). There were no significant differences with respect to presenting signs and symptoms, gestational age, preevacuation human chorionic gonadotropin level, or risk of progression to gestational trophoblastic neoplasia. CONCLUSION: Hispanic patients with complete molar pregnancy had a significantly lower risk of developing gestational trophoblastic neoplasia than white patients. There were no significant differences among groups in terms of presenting symptoms, gestational age at diagnosis, or preevacuation human chorionic gonadotropin levels for either complete mole or partial mole patients.

Patterns of Care, Predictors, and Outcomes of Adjuvant Therapy for Early- and Advanced-Stage Uterine Clear Cell Carcinoma: A Population-Based Analysis.

OBJECTIVE: The aim of the study was to examine the patterns of care and the impact of chemotherapy and radiation on survival in women diagnosed with uterine clear cell carcinoma (UCCC). The primary outcomes of this analysis were receipt of treatment within 6 months of diagnosis and overall survival. METHODS AND MATERIALS: Women diagnosed with UCCC from 2003 to 2011 were identified through the National Cancer Data Base. Standard univariate and multivariable analyses with logistic regression were performed. Kaplan-Meier survival analysis was used to generate overall survival data. Factors predictive of outcome were evaluated using the log-rank test and Cox proportional hazards model. RESULTS: A total of 3212 patients were identified. Chemotherapy, radiation, and combination chemotherapy and radiation were administered in 23.3%, 19.7%, and 11.1% of women, respectively. After adjusting for age, race, socioeconomic status, facility type, stage, surgery, lymph node dissection, comorbidity index, period of diagnosis, and registry location, there was an association between combined chemotherapy and radiation (hazard ratio, 0.74; 95% confidence interval, 0.61-0.90) with improved survival. Adjuvant therapy was not associated with improved survival among patients with early-stage disease (stages I and II). Both chemotherapy and combined chemotherapy and radiation were associated with significantly improved survival among patients with advanced-stage disease (stages III and IV). CONCLUSIONS: In patients with early-stage UCCC, adjuvant therapy was not associated with significantly improved survival. Chemotherapy and combination of chemotherapy and radiation were associated with improved survival in patients with advanced-stage UCCC.

Uterine leiomyosarcoma: a review article.

Uterine leiomyosarcomas (LMSs) are rare aggressive tumors, with high recurrence rates, even when confined to the uterine corpus at the time of diagnosis. These tumors are large myometrial masses, which typically spread hematogenously. Patients present with vague symptoms similar to those of patients with leiomyomas. Most patients are diagnosed with LMS postoperatively. In the presence of metastatic disease, complete surgical cytoreduction should be attempted when feasible. Lymphadenectomy should be performed only in patients with nodes suspected of harboring metastatic disease and as part of a cytoreductive effort. There are conflicting data to support adjuvant chemotherapy or radiation therapy for early-stage disease. Patients with advanced-stage disease should receive gemcitabine and docetaxel adjuvant chemotherapy. Patients with recurrent disease are candidates for a wide variety of second-line treatments, of which many are investigational. Although prognosis remains dismal, ongoing studies are investigating the role of advanced imaging, multimodality treatment, prognostic nomograms, and unique biomedical pathways to increase understanding of LMS and improve therapeutic options for patients.

Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer.

Importance: Although the activity of pembrolizumab and lenvatinib (the only US Food and Drug Administration-approved immunotherapy for mismatch repair proficient endometrial cancer [MMRP EC]) is compelling, there are no biomarkers of response and most patients do not tolerate, do not respond to, or develop resistance to this regimen, highlighting the need for additional, potentially biomarker-driven therapeutic approaches for patients with recurrent MMRP EC. Objective: To assess the potential positive outcomes and safety of the combination of the polyadenosine diphosphate-ribose polymerase inhibitor talazoparib and the programmed cell death ligand 1 (PD-L1) inhibitor avelumab in recurrent MMRP EC. Design, Settings, and Participants: This investigator-initiated, open-label, single-arm, 2-stage, phase 2 study nonrandomized controlled trial patients at 4 institutions in the US. Key eligibility criteria included measurable disease, unlimited prior therapies, and all endometrial cancer histologies. Interventions: Talazoparib, 1 mg, orally, daily, and avelumab, 10 mg/kg, intravenously, every 2 weeks, were administered until disease progression or unacceptable toxic effects. Main Outcomes and Measures: Statistical considerations were developed for 2 coprimary objectives of objective response rate and rate of progression-free survival at 6 months, with a 2-stage design that allowed for early discontinuation for futility. Prespecified exploratory objectives included the association of immunogenomic features (determined by targeted-panel next-generation sequencing and immunohistochemistry) with activity. Results: Thirty-five female patients (mean [SD] age, 67.9 [8.41] years) received protocol therapy; 9 (25.7%) derived clinical benefit after meeting at least 1 of the 2 coprimary end points. Four patients (11.4%) exhibited confirmed objective response rates (4 partial responses), and 8 (22.9%) survived progression free at 6 months. The most common grade 3 and 4 treatment-related toxic effects were anemia (16 [46%]), thrombocytopenia (10 [29%]), and neutropenia (4 [11%]); no patient discontinued receipt of therapy because of toxic effects. Tumors with homologous recombination repair alterations were associated with clinical benefit from treatment with avelumab and talazoparib. Tumor mutational burden, tumor-infiltrating lymphocytes, and PD-L1 status were not associated with clinical benefit. Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that treatment with avelumab and talazoparib demonstrated a favorable toxic effect profile and met the predetermined criteria to be considered worthy of further evaluation in MMRP EC. Immunogenomic profiling provided insights that may inform ongoing and future studies of polyadenosine diphosphate-ribose polymerase and PD-L1 inhibitor combinations in endometrial cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02912572.

Association Between Overall Survival and the Tendency for Cancer Programs to Administer Neoadjuvant Chemotherapy for Patients With Advanced Ovarian Cancer.

IMPORTANCE: Randomized clinical trials have found that, in patients with advanced-stage epithelial ovarian cancer, neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes compared with primary cytoreductive surgery. Despite this, considerable controversy remains about the appropriate use of neoadjuvant chemotherapy, and the proportion of patients who receive this treatment varies considerably among cancer programs in the US. OBJECTIVE: To evaluate the association between high levels of neoadjuvant chemotherapy administration and overall survival in patients with advanced ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS: This difference-in-differences comparative effectiveness analysis leveraged differential adoption of neoadjuvant chemotherapy in Commission on Cancer-accredited cancer programs in the US and included women with a diagnosis of stage IIIC and IV epithelial ovarian cancer between January 2004 and December 2015 who were followed up through the end of 2018. The data were analyzed between September 2020 and January 2021. EXPOSURES: Treatment in a cancer program with high levels of neoadjuvant chemotherapy administration (more often than expected based on case mix) or in a program that continued to restrict its use after the 2010 publication of a clinical trial demonstrating the noninferiority of neoadjuvant chemotherapy compared with primary surgery for the treatment of patients with advanced ovarian cancer. MAIN OUTCOMES AND MEASURES: Case mix-standardized median overall survival time and 1-year all-cause mortality assessed with a flexible parametric survival model. RESULTS: We identified 19 562 patients (mean [SD] age, 63.9 [12.6] years; 3.2% Asian, 8.0% Black, 4.8% Hispanic, 82.5% White individuals) who were treated in 332 cancer programs that increased use of neoadjuvant chemotherapy from 21.7% in 2004 to 2009 to 42.2% in 2010 to 2015 and 19 737 patients (mean [SD] age, 63.5 [12.6] years; 3.1% Asian, 7.7% Black, 6.5% Hispanic, 81.8% White individuals) who were treated in 332 programs that marginally increased use of neoadjuvant chemotherapy (20.1% to 22.5%) over these periods. The standardized median overall survival times improved by similar magnitudes in programs with high (from 31.6 [IQR, 12.3-70.1] to 37.9 [IQR, 17.0-84.9] months; 6.3-month difference; 95% CI, 4.2-8.3) and low (from 31.4 [IQR, 12.1-67.2] to 36.8 [IQR, 15.0-80.3] months; 5.4-month difference, 95% CI, 3.5-7.3) use of neoadjuvant chemotherapy after 2010 (difference-in-differences, 0.9 months; 95% CI, -1.9 to 3.7). One-year mortality declined more in programs with high (from 25.6% to 19.3%; risk difference, -5.2%; 95% CI, -6.4 to -4.1) than with low (from 24.9% to 21.8%; risk difference, -3.2%, 95% CI, -4.3 to -2.0) use of neoadjuvant chemotherapy (difference-in-differences, -2.1%; 95% CI, -3.7 to -0.5). CONCLUSIONS AND RELEVANCE: In this comparative effectiveness research study, compared with cancer programs with low use of neoadjuvant chemotherapy, those with high use had similar improvements in median overall survival and larger declines in short-term mortality.

Impact of clinical characteristics on human chorionic gonadotropin regression after molar pregnancy.

OBJECTIVES: This study aimed to determine the effects of age, race/ethnicity, body mass index, and contraception on human chorionic gonadotropin (hCG) regression following the evacuation of a molar pregnancy. METHODS: This was a retrospective cohort study of 277 patients with molar pregnancies between January 1, 1994 and December 31, 2015. The rate of hCG regression was estimated using mixed-effects linear regression models on daily log-transformed serum hCG levels after evacuation. RESULTS: There were no differences in hCG half-lives among age (p=0.13) or race/ethnicity (p=0.16) groups. Women with obesity and hormonal contraceptive use demonstrated faster hCG regression than their counterparts (3.2 versus. 3.7 days, p=0.02 and 3.4 versus. 4.0 days, p=0.002, respectively). CONCLUSION: Age and race/ethnicity were not associated with hCG regression rates. Hormonal contraceptive use and obesity were associated with shorter hCG half-lives, but with unlikely clinical significance. It is important to understand whether the clinical characteristics of patients may influence the hCG regression curve, as it has been proposed as a way to predict the risk of gestational trophoblastic neoplasia.

Tubo-ovarian abscesses in postmenopausal women: Clinical presentation and outcomes.

OBJECTIVES: This study describes the presentation, clinical characteristics and outcomes of postmenopausal women diagnosed with tubo-ovarian abscesses (TOAs). STUDY DESIGN: All postmenopausal women aged over 50 years presenting to three academic institutions with TOAs between 2007 and 2017 were identified. Patient charts were retrospectively reviewed and clinical variables were extracted. Descriptive statistics were prepared and analyses were performed. MAIN OUTCOME MEASURES: The main outcome measures were complications and rate of malignancy. RESULTS: From 2007-2017, 61 postmenopausal women with TOAs were identified. Their median age was 62 years (range 50-87 years). Many of the women presenting with TOAs had co-morbidities; 34.4% had diverticulosis or diverticulitis and 9.8% had diabetes. Among the 61 women, 19 (31.1%) underwent interventional radiology (IR) drainage. Most postmenopausal women presenting with a TOA underwent surgical intervention (n = 47, 77.1%). Thirty-three (54.1%) women underwent early surgery (within 30 days), and 14 (22.9%) underwent late surgery (after 30 days). Overall, 14 (29.8%) women had either an intra-operative or a post-operative complication. Post-operative complications were more common among women who underwent late surgery than among those who underwent early surgery (35.7% vs 9.1%, P = 0.04). However, there was no difference in the readmission rate within 30 days of surgery (P = 1.0) or in the overall complication rate (P = 0.24) between surgery groups. Eight women (13.1%) had malignancy diagnosed either pre-operatively or at the time of their presentation with a TOA. CONCLUSIONS: Postmenopausal women presenting with TOAs often undergo surgical procedures that have a high rate of complications and may be associated with malignancy.

Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer.

PURPOSE: Despite the tissue-agnostic approval of pembrolizumab in mismatch repair deficient (MMRD) solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in mismatch repair-proficient (MMRP) and -deficient endometrial cancer (EC). METHODS: This phase II study evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: (1) MMRD/POLE (polymerase ε) cohort, as defined by immunohistochemical (IHC) loss of expression of one or more mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE; and (2) MMRP cohort with normal IHC expression of all MMR proteins. Coprimary end points were objective response (OR) and progression-free survival at 6 months (PFS6). Avelumab 10 mg/kg intravenously was administered every 2 weeks until progression or unacceptable toxicity. RESULTS: Thirty-three patients were enrolled. No patient with POLE-mutated tumor was enrolled in the MMRD cohort, and all MMRP tumors were not POLE-mutated. The MMRP cohort was closed at the first stage because of futility: Only one of 16 patients exhibited both OR and PFS6 responses. The MMRD cohort met the predefined primary end point of four ORs after accrual of only 17 patients; of 15 patients who initiated avelumab, four exhibited OR (one complete response, three partial responses; OR rate, 26.7%; 95% CI, 7.8% to 55.1%) and six (including all four ORs) PFS6 responses (PFS6, 40.0%; 95% CI, 16.3% to 66.7%), four of which are ongoing as of data cutoff date. Responses were observed in the absence of PD-L1 expression. IHC captured all cases of MMRD subsequently determined by polymerase chain reaction or genomically via targeted sequencing. CONCLUSION: Avelumab exhibited promising activity in MMRD EC regardless of PD-L1 status. IHC for MMR assessment is a useful tool for patient selection. The activity of avelumab in MMRP/non-POLE-mutated ECs was low.