Non-surgical management of recurrent Paget's disease of the vulva: A case report.

Paget's Disease of the Vulva is a relatively rare condition with a high rate of recurrence. Extensive work-up and treatment is warranted as lesions have the capacity to become invasive and can be associated with underlying malignancy. First line therapy includes surgical resection. For those that are not surgical candidates or who do not desire surgical intervention, non-surgical management options include topical therapy with imiquimod. Unfortunately, irritating side effects often results in poor treatment compliance and premature discontinuation limiting efficacy. Here we present a unique case of extensive, recurrent vulvar Paget's disease with excellent response to a combination therapy of imiquimod and Silver Sulfadiazine. To the best of our knowledge, this is the first documented case illustrating the utility of non-surgical management with combination therapy with topical imiquimod and Silver Sulfadiazine for treatment in patients who do not desire surgical intervention.

NCCN Guidelines® Insights: Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer, Version 3.2024.

The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.

Maintenance with mirvetuximab soravtansine plus bevacizumab vs bevacizumab in FRα-high platinum-sensitive ovarian cancer.

At first recurrence, platinum-sensitive ovarian cancer (PSOC) is frequently treated with platinum-based chemotherapy doublets plus bevacizumab, then single-agent bevacizumab. Most patients' disease progresses within a year after chemotherapy, emphasizing the need for novel strategies. Mirvetuximab soravtansine-gynx (MIRV), an antibody-drug conjugate, comprises a folate receptor alpha (FRα)-binding antibody and tubulin-targeting payload (maytansinoid DM4). In FRα-high PSOC, MIRV plus bevacizumab previously showed promising efficacy (objective response rate, 69% [95% CI: 41-89]; median progression-free survival, 13.3 months [95% CI: 8.3-18.3]; median duration of response, 12.9 months [95% CI: 6.5-15.7]) and safety. The Phase III randomized GLORIOSA trial will evaluate MIRV plus bevacizumab vs. bevacizumab alone as maintenance therapy in patients with FRα-high PSOC who did not have disease progression following second-line platinum-based doublet chemotherapy plus bevacizumab.Clinical Trial Registration: ClinicalTrials.gov ID: NCT05445778; GOG.org ID: GOG-3078; ENGOT.ESGO.org ID: ENGOT-ov76.

Most patients with ovarian cancer are initially treated with platinum-based chemotherapy. If the cancer reappears/recurs after more than 6 months following this therapy, it is called platinum-sensitive ovarian cancer (PSOC). Patients with PSOC usually receive additional platinum-based chemotherapy along with bevacizumab, a drug that reduces tumor growth by decreasing its blood supply. If patients improve or are stable on this therapy, they are usually kept on bevacizumab alone for 'maintenance therapy'. Unfortunately, this maintenance therapy does not work long-term in all patients, so better long-term treatments are needed. The GLORIOSA (NCT05445778) clinical trial will compare maintenance therapy with bevacizumab alone to maintenance therapy with bevacizumab plus a drug called mirvetuximab soravtansine-gynx (MIRV) to determine which therapy leads to better results in patients with PSOC. MIRV is made up of an antibody that binds to a specific protein (folate receptor alpha [FRα]) on cancer cells to directly deliver a cancer-killing drug. MIRV received US FDA approval to be used as a therapy for patients with ovarian cancer who are resistant to platinum-based chemotherapy and express high levels of FRα. The GLORIOSA trial will study maintenance therapy with MIRV plus bevacizumab in patients with PSOC who have not had cancer progression after second-line platinum-based chemotherapy plus bevacizumab, and whose cancer expresses high amounts of FRα. The main purpose of this trial is to determine if MIRV plus bevacizumab leads to better patient survival and decreases cancer growth and spread when compared with bevacizumab alone.

Associations between race and ethnicity and treatment setting among gynecologic cancer patients.

INTRODUCTION: Racial and ethnic disparities in gynecologic cancer care have been documented. Treatment at academic facilities is associated with improved survival, yet no study has examined independent associations between race and ethnicity with facility type among gynecologic cancer patients. MATERIALS & METHODS: We used the National Cancer Database and identified 484,455 gynecologic cancer (cervix, ovarian, uterine) patients diagnosed between 2004 and 2020. Facility type was dichotomized as academic vs. non-academic, and we used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between race and ethnicity and facility type. Secondarily, we examined joint effects of race and ethnicity and facility type on overall survival using Cox proportional hazards regression. RESULTS: We observed higher odds of treatment at academic (vs. non-academic) facilities among American Indian/Alaska Native (OR = 1.42, 95% CI = 1.28-1.57), Asian (OR = 1.64, 95% CI = 1.59-1.70), Black (OR = 1.69, 95% CI = 1.65-1.72), Hispanic (OR = 1.70, 95% CI = 1.66-1.75), Native Hawaiian/Pacific Islander (OR = 1.74, 95% CI = 1.57-1.93), and other race (OR = 1.29, 95% CI = 1.20-1.40) patients compared with White patients. In the joint effects survival analysis with White, academic facility-treated patients as the reference group, Asian, Hispanic, and other race patients treated at academic or non-academic facilities had improved overall survival. Conversely, Black patients treated at academic facilities [Hazard Ratio (HR) = 1.10, 95% CI = 1.07-1.12] or non-academic facilities (HR = 1.19, 95% CI = 1.16-1.21) had worse survival. DISCUSSION: Minoritized gynecologic cancer patients were more likely than White patients to receive treatment at academic facilities. Importantly, survival outcomes among patients receiving care at academic institutions differed by race, requiring research to investigate intra-facility survival disparities.

Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-oncology Research.

Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, in which immunotherapy is now incorporated as the standard of care up front for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor. Continued preclinical research and clinical trial development are crucial for our understanding of resistance mechanisms to immunotherapy and maximization of therapeutic efficacy. In this setting, syngeneic models are preferred over xenograft models as they allow for the evaluation of the tumor-immune interaction in an immunocompetent host, most closely mimicking the tumor-immune interaction in patients with cancer. Unfortunately, significant disparities exist about syngeneic models in gynecologic malignancy, in which queries from multiple large bioscience companies confirm no commercial availability of endometrial or cervical cancer syngeneic cell lines. Published data exist about the recent development of several endometrial and cervical cancer syngeneic cell lines, warranting further investigation. Closing the disparity gap for preclinical models in endometrial and cervical cancers will support physician scientists, basic and translational researchers, and clinical trialists who are dedicated to improving outcomes for our patients with advanced disease and poor prognosis.

RETRACTED: Cost-effectiveness of chemotherapy and dostarlimab for advanced or recurrent endometrial cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors have independently identified an error in the formula that was utilized to calculate the Quality Adjusted Life Years which invalidates the data and the conclusion of the paper. The authors have contacted the journal requesting to retract the article. Apologies are offered to the readers of the journal for any confusion or inconvenience that may have resulted from the publication of this article.

Does the choice of platinum doublet matter? A study to evaluate the impact of platinum doublet choice for treatment of platinum-sensitive ovarian cancer recurrence on the development of future PARP inhibitor and platinum resistance.

OBJECTIVES: The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the non­platinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. METHODS: Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. RESULTS: 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. CONCLUSIONS: Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival.

Racial and Ethnic Disparities in Clinical Trial Enrollment Among Women With Gynecologic Cancer.

Importance: Racial and ethnic disparities in clinical trial enrollment are unjust and hinder development of new cancer treatments. Objective: To examine the association of race and ethnicity with clinical trial enrollment among women with endometrial, ovarian, or cervical cancer. Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database, a hospital-based cancer registry, and the Surveillance, Epidemiology, and End Results Program (SEER), a population-based cancer registry. Population-based race and ethnicity-specific proportions for each cancer site were derived from SEER. Participants included women with an endometrial, ovarian, or cervical cancer diagnosed from 2004 to 2019. Analyses were performed from February 2 to June 14, 2023. Exposure: Race and ethnicity were categorized as American Indian/Alaska Native, Asian, Black, Hispanic (any race), Native Hawaiian/Pacific Islander, White, and other (not defined in the National Cancer Database). Main Outcomes and Measures: The primary outcomes were the odds of clinical trial enrollment and representation in clinical trials compared with the US population. Multivariable-adjusted logistic regression was used to estimate odds ratios (ORs) and 95% CIs for associations of race and ethnicity with clinical trial enrollment within the National Cancer Database sample. Participation-to-prevalence ratios (PPRs) according to diagnosis period (2004-2011 vs 2012-2019) were calculated by dividing the race and ethnicity-specific percentage of clinical trial participants in the study sample by the percentage of racial and ethnic groups in SEER. Results: Among 562 592 patients with gynecologic cancer (mean [SD] age at diagnosis, 62.9 [11.3] years), 1903 were American Indian/Alaska Native, 18 680 were Asian, 56 421 were Black, 38 145 were Hispanic, 1453 were Native Hawaiian/Pacific Islander, 442 869 were White, and 3121 were other race and ethnicity. Only 548 (<1%) were enrolled in clinical trials. Compared with White women, clinical trial enrollment was lower for Asian (OR, 0.44; 95% CI, 0.25-0.78), Black (OR, 0.70; 95% CI, 0.50-0.99), and Hispanic (OR, 0.53; 95% CI, 0.33-0.83) women. Compared with the US population, White women were adequately or overrepresented for all cancer types (PPRs ≥1.1), Black women were adequately or overrepresented for endometrial and cervical cancers (PPRs ≥1.1) but underrepresented for ovarian cancer (PPR ≤0.6), and Asian and Hispanic women were underrepresented among all 3 cancer types (PPRs ≤0.6). Conclusions and Relevance: In this cohort of patients with gynecologic cancer, clinical trial enrollment was lower among certain minoritized racial and ethnic groups. Continued efforts are needed to address disparate clinical trial enrollment among underrepresented groups.

The impact of antibiotic and proton pump inhibitor use at the time of adjuvant platinum-based chemotherapy on survival in patients with endometrial cancer.

OBJECTIVE: We sought to assess the impact of antibiotic (ABX) and proton-pump inhibitor (PPI) use on progression-free (PFS) and overall survival (OS) in patients treated with adjuvant platinum-based chemotherapy (PC) for endometrial cancer (EC). METHODS: A retrospective, single-institution cohort study of EC patients treated with ≥four cycles of adjuvant PC following surgical staging from 2014 to 2020. Demographics and clinicopathologic features, including ABX and PPI use, were compared using χ2 and Fisher's exact tests. Univariate and multivariable analyses were performed, and survival outcomes were compared using the log-rank test. RESULTS: Of 325 patients, 95 (29%) received ABX, and 80 (24.6%) received PPI. ABX were associated with decreased 3-year PFS (49.9% vs. 66%; p = 0.0237) but not 3-year OS (68.9% vs. 79.9%; p = 0.0649). ABX targeting gram-positive bacteria were associated with decreased 3-year PFS (21.2% vs. 66.0% vs. 55.4%; p = 0.0038) and 3-year OS (36.5% vs. 79.9% vs. 75.6%; p = 0.0014) compared to no ABX and other ABX, respectively. PPI use was associated with decreased 3-year PFS (46.9% vs. 66.0%; p = 0.0001) and 3-year OS (60.7% vs. 81.9%; p = 0.0041) compared to no PPI. On multivariable regression analysis controlling for confounders including stage, histology, grade, radiation, and co-morbidities, PPI use was independently associated with worse PFS (HR 1.96, 95% CI 1.25-3.08; p = 0.0041) and OS (HR 2.06, 95% CI 1.01-4.18, p = 0.04). CONCLUSION: In this retrospective cohort study, we demonstrate that PPI use is independently associated with worse PFS and OS in patients with EC treated with PC. ABX use was associated with worse PFS on univariate analysis only. There is an unmet need to understand how PPI, ABX, and, potentially, the microbiome impact the effectiveness of chemotherapy in EC patients.

Assessment of the feasibility of same-day discharge following minimally invasive hysterectomy in the elderly population.

Objective: To determine the safety and feasibility of same-day discharge (SDD) following minimally invasive hysterectomy (MIH) for elderly patients and to evaluate associations between age, frailty, and postoperative outcomes. Methods: Retrospective review was conducted of patients aged ≥ 70 who underwent MIH within a single gynecologic oncology institution from 2018 to 2020. Demographics, peri-operative factors, postoperative complications, and 30-day readmission rates were collected. Frailty was determined by an 11-point modified frailty index ≥ 2. Outcomes were compared between SDD and observation groups using Fisher's exact and Wilcoxon rank-sum tests. Results: Of 169 patients included in the analysis, 8.9% (n = 15) underwent SDD, and 91.1% (n = 154) were admitted for OBS following MIH. Demographics, peri-operative factors, and frailty rates (33% SDD vs 43.5% observation; p = 0.59) were similar between groups. 86.7% (n = 13) of SDD cases were completed before 12PM, and none were completed after 6PM. No SDD patients had early post-operative complications or hospital readmissions. Early postoperative complications were diagnosed in 9 (5.8%) patients admitted for OBS, and the 30-day hospital readmission rate for patients who underwent OBS was 8.4% (n = 13). While elderly patients who met objective frailty criteria (n = 72) did not have a higher likelihood of early post-operative complications (44.4% vs 55.6%; p = 0.909), they did have a higher likelihood of ED visit within 30 days of discharge (15.3 vs 3.1%; p = 0.009), and a trend was noted toward a higher rate of 30-day hospital readmission (12.5% vs 4.1%; p = 0.080). Conclusions: Elderly patients undergoing SDD following MIH did not have increased morbidity or mortality. Elderly patients who meet objective criteria for frailty, however, represent a more vulnerable population.

The right time for change: A report on the heterogeneity of IVB endometrial cancer and improved risk-stratification provided by new 2023 FIGO staging criteria.

OBJECTIVE: We sought to provide a contemporary report on stage IVB endometrial carcinoma (2009 FIGO criteria) and applied the 2023 FIGO staging criteria to this population. METHODS: Retrospective review of patients who underwent cytoreduction for stage IVB endometrial carcinoma (2009 FIGO criteria) from 2014 to 2020 was performed. Demographics, clinicopathologic factors, and outcomes were recorded. Disease burden and distribution were determined by imaging, operative notes, and pathology reports. Patients were re-staged according to 2023 FIGO staging criteria. Categorical variables were compared using χ2 or Fisher's exact test, and Kaplan-Meier curves compared survival outcomes using the log-rank test. RESULTS: Eighty-eight cases were included. Most patients (63.6%) were not suspected to have stage IVB (2009 FIGO criteria) disease prior to surgery. Seventy-two percent of patients underwent primary cytoreduction, and 12 (19%) were suboptimal. Median progression-free survival (PFS) was 12 months (95% CI 10-16 months), and median overall survival (OS) was 38 months (95% CI 19-61 months). Degree of cytoreduction (p = 0.0101) and pelvic-confined metastatic disease (p = 0.0149) were significant prognostic factors, while distant metastases were not associated with worse outcomes. For those patients who underwent primary cytoreduction, number (p = 0.0453) and diameter (p = 0.0192) of tumor deposits were associated with PFS. When 2023 FIGO staging criteria were applied, 58% of patients underwent change in stage, and 8% did not meet criteria for complete staging. PFS was significantly different based on 2023 FIGO staging (p = 0.0307); a trend in OS was also noted (p = 0.0550). CONCLUSION: Stage IVB endometrial carcinoma (2009 FIGO criteria) encompasses a diverse cohort of patients, where certain clinicopathologic features, tumor burden, and degree of cytoreduction are associated with outcomes. The 2023 FIGO staging criteria significantly improves our ability to risk-stratify patients.

Expression of microRNAs and their target genes in melanomas originating from gynecologic sites.

Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that MOGS would display unique miR and mRNA expression profiles. The miR and mRNA expression profile in RNA from formalin fixed, paraffin embedded vaginal melanomas (relative to vaginal mucosa) and vulvar melanomas (relative to cutaneous melanoma) were measured with the Nanostring Human miRNA assay and Tumor Signaling mRNA assay. Differential patterns of expression were identified for 21 miRs in vaginal and 47 miRs in vulvar melanoma (fold change >2, p<0.01). In vaginal melanoma, miR-145-5p (tumor suppressor targeting TLR4, NRAS) was downregulated and miR-106a-5p, miR-17-5p, miR-20b-5p (members of miR-17-92 cluster) were upregulated. In vulvar melanoma, known tumor suppressors miR-200b-3p and miR-200a-3p were downregulated, and miR-20a-5p and miR-19b-3p, from the miR-17-92 cluster, were upregulated. Pathway analysis showed an enrichment of "proteoglycans in cancer". Among differentially expressed mRNAs, topoisomerase IIα (TOP2A) was upregulated in both MOGS. Gene targets of dysregulated miRs were identified using publicly available databases and Pearson correlations. In vaginal melanoma, suppressor of cytokine signaling 3 (SOCS3) was downregulated, was a validated target of miR-19b-3p and miR-20a-5p and trended toward a significant inverse Pearson correlation with miR-19b-3p (p = 0.093). In vulvar melanoma, cyclin dependent kinase inhibitor 1A (CDKN1A) was downregulated, was the validated target of 22 upregulated miRs, and had a significant inverse Pearson correlation with miR-503-5p, miR-130a-3p, and miR-20a-5p (0.005 < p < 0.026). These findings support microRNAs as mediators of gene expression in MOGS.

Recurrence rate in early-stage epithelial ovarian cancer: Is there a role for upfront maintenance with PARP inhibitors in stages I and II?

Objective: To determine the recurrence rate and survival among early-stage epithelial ovarian cancer cases considering homologous recombination deficiency (HRD) status. Methods: Single institution retrospective study of stage I/II EOC patients from 2017 to 2020. HRD was defined as evidence of germline or somatic BRCA mutation, or loss of heterozygosity (LOH)/genomic instability (GIS) as determined by companion diagnostic tests. Kaplan-Meier analyses were performed. Results: 89 stage I/II cases were included. 4/89 (4.5%) had a germline BRCA1/2 mutation, 8 (9%) were germline negative but had a somatic BRCA mutation, and 8 (9%) were BRCA wild-type but had evidence of LOH/GIS on somatic testing; these 20/89 (22%) cases comprised the HRD group. The remaining tumors were confirmed homologous recombination proficient (HRP, 35/89, 39%) or homologous recombination unknown (HRU, 34/89, 38%). The overall recurrence rate was 33/89 (37%). There were more recurrences among HRD cases (14/20, 70%) compared to HRP/HRU cases (19/69, 27.5%, p = 0.0012). Median Recurrence-Free Survival (RFS) was 35 months for HRD cases and 225 months for HRP/HRU cases (p = 0.001). At 2 years, there were 60% HRD cases and 88% HRP/HRU cases recurrence-free. At 5 years there were 29% HRD and 69% HRP/HRU cases recurrence-free (p = 0.001). Conclusions: Despite a high rate of complete surgical staging and six cycles of adjuvant chemotherapy, recurrence rate was high in this early-stage cohort. Higher recurrence rates were seen in the HRD group, however these data are likely biased by the clinical practice of tumor testing primarily at the time of recurrence rather than the upfront setting. RFS was significantly lower for HRD cases.

Glassy cell carcinoma of the cervix: Findings from a combined National Cancer Database analysis and single institution review of treatment patterns and outcomes.

OBJECTIVES: To describe stage, treatment patterns, and survival for glassy cell carcinoma of the cervix (GCCC), a poorly understood rare tumor. METHODS: Clinical data and survival were compared between GCCC and more common histologic types using the National Cancer Database (NCDB) from 2004 to 2017. A retrospective review of GCCC cases at our institution from 2012 to 2020 was simultaneously performed with staging updated according to 2018 FIGO staging. Descriptive statistics and survival analyses were performed, and outcomes compared to historical references. RESULTS: 143/89,001 (0.16%) NCDB cervical cancer cases were GCCC. Compared to other histologies, GCCC cases were younger, with 74.8% diagnosed before age 50. Stage distribution was similar. Stage I cases were less commonly treated with surgery alone (19/69, 27%). 79.4% of locally advanced (stage II-IVA) cases were treated with definitive chemoradiation. GCCC demonstrated worse OS for early-stage and locally-advanced disease. No survival differences were observed for patients with stage IVB disease. Our institutional review identified 14 GCCC cases. Median age at diagnosis was 34 years. All nine early-stage cases underwent radical hysterectomy. Adjuvant radiation was given for cases meeting Sedlis criteria (4/9, 44%). All five advanced stage cases were stage IIIC and received definitive chemoradiation. Recurrence rate was 0% (0/9) for early-stage and 60% (3/5) for advanced-stage cases. 3-year PFS was 100% for early-stage and 40% for advanced-stage. 3-year OS was 100% for early-stage and 60% for advanced-stage GCCC. CONCLUSIONS: GCCC presents at earlier ages than other cervical cancer histologic types. Although NCDB showed worse OS, our more contemporary institutional review, which incorporates updated staging and newer treatment modalities found outcomes more similar to historical references of more common histologic subtypes.

Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series.

Effective second-line treatment options for patients with recurrent ovarian clear cell carcinoma (OCCC) are limited. This case series sought to report tumor characteristics and oncologic outcomes in a small group of patients treated with combination lenvatinib and pembrolizumab. A retrospective analysis of patients with ovarian clear cell carcinoma treated with combination lenvatinib and pembrolizumab at a single institution was performed. Patient and tumor characteristics were collected including demographics and germline/somatic testing. Clinical outcomes were also evaluated and reported. Three patients with recurrent OCCC were included in the study. The median age of patients was 48 years old. All patients had platinum-resistant disease and had received 1-3 prior lines of therapy. The overall response rate was 100% (3/3). Progression-free survival ranged from 10 months to not-yet-reached. One patient remains on treatment, while the other two died of disease with overall survival of 14 and 27 months. Combination lenvatinib-pembrolizumab demonstrated favorable clinical response in these patients with platinum-resistant, recurrent, ovarian clear cell carcinoma.

Epigenetic MMR defect identifies a risk group not accounted for through traditional risk stratification algorithms in endometrial cancer.

Purpose: We sought to evaluate the contribution of mismatch repair (MMR) status to traditional risk stratification algorithms used to predict nodal involvement and recurrence in a large single-institution cohort. Methods: Endometrioid endometrial cancer (EC) cases from 2014-2020 were evaluated. MMR immunohistochemistry (IHC) was performed universally. Uterine factors assessed in the Mayo criteria were used to retrospectively classify patients as low or high risk for lymphatic spread. Patients were classified according to risk for recurrence using GOG 99 and PORTEC criteria. Associations were evaluated using chi-square and t-tests and contributing factors assessed using logistic regression models. Results: 1,514 endometrioid EC were evaluated; 392 (25.9%) were MMR (MMR) deficient of which 80.4% of MMR defects were associated with epigenetic silencing of MLH1. Epigenetic MMR defects were significantly more likely to be high risk for lymph node (LN) metastasis based on Mayo criteria (74.9% vs 60.6%, p=<0.001) and with the presence of LN metastasis (20.3 vs 10.5%, p=0.003) compared to MMR proficient tumors. Tumors with epigenetic MMR defects were significantly more likely to be classified as high or high intermediate risk using GOG99 and PORTEC criteria. Furthermore, cases with epigenetic MMR defects classified as low or low intermediate risk were significantly more likely to recur (GOG99 p=0.013; PORTEC p=0.008) and independently associated with worse disease-free survival (DFS). MMR status was found to be independently associated with worse DFS (HR 1.90; 95% CI 1.34-2.70; p=0.003) but not overall survival. Conclusion: While MMR deficient EC has been associated with poor prognostic features in prior reports; we demonstrate that only epigenetic MMR defects have poorer outcomes. Epigenetic MMR defect were independently associated with lymph node metastasis after controlling for risk criteria. Epigenetic MMR deficiency was found to be an independent predictor of recurrence beyond the factors considered in traditional risk stratification algorithms. Traditional uterine-based risk stratification algorithms may not fully reflect the risk for recurrence in MMR deficient tumors. Consideration should be given to implementing MMR status and MLH1 hypermethylation alongside traditional risk stratification algorithms. Performing MMR IHC on preoperative pathologic specimens may aid in risk stratification and patient counseling.

Use of the Khorana score to predict venous thromboembolism in patients undergoing chemotherapy for uterine cancer.

Objective: Gynecologic cancers are associated with a high risk of venous thromboembolism (VTE). The Khorana score is a validated tool to assess risk of VTE in cancer patients. The purpose of this study is to determine if the Khorana score can be used as a risk stratification tool for VTE in patients with uterine cancer undergoing chemotherapy. Methods: A retrospective cohort study of patients with newly diagnosed uterine cancer receiving chemotherapy over a 4-year period was conducted. The patients were stratified based on their Khorana score as well as their chemotherapy sequence, neoadjuvant or definitive versus adjuvant. Results: A total of 276 patients were included: 40 received neoadjuvant or definitive, 236 adjuvant chemotherapy. Most patients had advanced stage disease (64.5%). 18 (6.5%) patients developed VTE within 180 days of initiating chemotherapy. High Khorana score was associated with a non-significant increase in VTE (K ≥ 2 OR 1.17, CI 0.40-3.39, K ≥ 3 OR 1.69, CI 0.61-4.69) but had poor predictive accuracy based on area under the curve (K ≥ 2 0.51, K ≥ 3 0.55). The VTE rate was higher in the neoadjuvant/definitive chemotherapy group to adjuvant (12.5% vs 5.5%, p = 0.11). While the former group had a higher average Khorana score (2.35 vs 1.93, p = 0.0048), this was not predictive of VTE. Conclusions: While validated in other cancer types, the Khorana score was found to be a poor predictor of VTE in patients with uterine cancer. The use of the Khorana score to guide routine thromboprophylaxis in these patients should be used with caution and further investigation is warranted.

Do Not Forget about Hormonal Therapy for Recurrent Endometrial Cancer: A Review of Options, Updates, and New Combinations.

Hormonal therapy has long been a treatment modality for recurrent endometrial cancer. It is appealing for patients with low-grade, slow-growing tumors or in patients for which other treatment types may be too toxic. Hormonal therapy is well tolerated and has response rates ranging from 9 to 33%. Hormonal treatment options take advantage of the estrogen-dependent molecular pathways in endometrial cancers. Current options for hormonal therapies include progesterone therapy (medroxyprogesterone acetate and megestrol acetate) as a single agent or in combination and agents that target the estrogen pathway. Aromatase inhibitors have had modest single-agent activity, but synergistic effects have been found when used in combination with targeted therapy including mTOR inhibitors and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Molecular profiling of endometrial cancers has begun to help individualize treatments. This review will report on existing data and ongoing trials investigating novel hormonal therapy agents.

Safety and feasibility of same-day discharge following minimally invasive hysterectomy in the morbidly obese patient population.

OBJECTIVES: To determine whether morbid obesity should serve as an independent factor in the decision for same day discharge following minimally invasive hysterectomy. METHODS: Retrospective review was performed of patients with BMI ≥ 40 who underwent minimally invasive hysterectomy within a single comprehensive cancer center between January 2018 - August 2020. Demographics, perioperative factors, post-operative monitoring, complications, and readmissions were compared between patients who underwent same day discharge and overnight observation using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: 374 patients with BMI ≥ 40 were included. Eighty-three (22.2%) patients underwent same day discharge, and 291 (77.8%) patients underwent overnight observation. Factors associated with increased likelihood of same day discharge included younger age (median age 53 vs 58; p = 0.001), lower BMI (median BMI 45 vs 47; p = 0.005), and fewer medical co-morbidities (Charlson Co-Morbidity Index 2 vs 3; p < 0.001). On multivariate regression analysis, frailty (OR 2.16 [1.14-4.11], p = 0.019) and surgical completion time after 12 PM (OR 3.67 [2.16-6.24], p < 0.001) were associated with increased risk of overnight observation. Few patients admitted for routine overnight observation required medical intervention (n = 14, 4.8%); most of these patients were frail (64.3%). The overall hospital readmission rate within 30 days of discharge was 3.2% (n = 12), with no patients discharged on the day of surgery being readmitted. CONCLUSIONS: Morbid obesity alone should not serve as a contraindication to same day discharge following minimally invasive hysterectomy. Admission for observation was associated with low rates of clinically meaningful intervention, and patients who underwent same day discharge were not at increased risk of adverse outcome.