Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer.

BACKGROUND: Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. METHODS: We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. RESULTS: A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). CONCLUSIONS: Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).

Characterization of mismatch-repair/microsatellite instability-discordant endometrial cancers.

BACKGROUND: Mismatch-repair (MMR)/microsatellite instability (MSI) status has therapeutic implications in endometrial cancer (EC). The authors evaluated the concordance of testing and factors contributing to MMR expression heterogeneity. METHODS: Six hundred sixty-six ECs were characterized using immunohistochemistry (IHC), MSI testing, and mut-L homolog 1 (MLH1) methylation. Select samples underwent whole-transcriptome analysis and next-generation sequencing. MMR expression of metastatic/recurrent sites was evaluated. RESULTS: MSI testing identified 27.3% of cases as MSI-high (n = 182), MMR IHC identified 25.1% cases as MMR-deficient (n = 167), and 3.8% of cases (n = 25) demonstrated discordant results. A review of IHC staining explained discordant results in 18 cases, revealing subclonal loss of MLH1/Pms 1 homolog 2 (PMS2) (n = 10) and heterogeneous MMR IHC (mut-S homolog 6 [MSH6], n = 7; MLH1/PMS2, n = 1). MSH6-associated Lynch syndrome was diagnosed in three of six cases with heterogeneous expression. Subclonal or heterogeneous cases had a 38.9% recurrence rate (compared with 16.7% in complete MMR-deficient cases and 9% in MMR-proficient cases) and had abnormal MMR IHC results in all metastatic recurrent sites (n = 7). Tumors with subclonal MLH1/PMS2 demonstrated 74 differentially expressed genes (determined using digital spatial transcriptomics) when stratified by MLH1 expression, including many associated with epithelial-mesenchymal transition. CONCLUSIONS: Subclonal/heterogeneous MMR IHC cases showed epigenetic loss in 66.7%, germline mutations in 16.7%, and somatic mutations in 16.7%. MMR IHC reported as intact/deficient missed 21% of cases of Lynch syndrome. EC with subclonal/heterogeneous MMR expression demonstrated a high recurrence rate, and metastatic/recurrent sites were MMR-deficient. Transcriptional analysis indicated an increased risk for migration/metastasis, suggesting that clonal MMR deficiency may be a driver for tumor aggressiveness. Reporting MMR IHC only as intact/deficient, without reporting subclonal and heterogeneous staining, misses opportunities for biomarker-directed therapy. PLAIN LANGUAGE SUMMARY: Endometrial cancer is the most common gynecologic cancer, and 20%-40% of tumors have a defect in DNA proofreading known as mismatch-repair (MMR) deficiency. These results can be used to guide therapy. Tests for this defect can yield differing results, revealing heterogeneous (mixed) proofreading capabilities. Tumors with discordant testing results and mixed MMR findings can have germline or somatic defects in MMR genes. Cells with deficient DNA proofreading in tumors with mixed MMR findings have DNA expression profiles linked to more aggressive characteristics and cancer spread. These MMR-deficient cells may drive tumor behavior and the risk of spreading cancer.

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.

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.

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

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.

Prevalence of type 2 diabetes diagnoses in the perioperative and survivorship periods following surgical management of endometrial cancer: An opportunity for screening and intervention?

OBJECTIVE: To determine the prevalence of Type 2 diabetes mellitus (T2DM) diagnoses during the peri-operative and survivorship periods in patients following surgical management of endometrial cancer (EC). METHODS: An IRB-approved, retrospective single-institution cohort study was performed in patients who underwent surgical management of EC from 2014 to 2020. The perioperative period was defined as the 30 days before and after surgery. T2DM diagnoses occurring during survivorship were recorded. T2DM diagnoses were defined by a HgbA1c ≥6.5% or a random blood glucose ≥200 mg/dL. Sequelae of peri-operative T2DM and predictors of future T2DM were examined utilizing univariate analysis. RESULTS: Of 519 patients meeting inclusion criteria, 37 (7.1%) were diagnosed with T2DM in the perioperative period. Patients diagnosed with T2DM in the perioperative period had significantly higher BMI (p = 0.006) compared to no T2DM, but there were no significant differences in age (p = 0.20), ethnicity/race (p > 0.05) or ECOG score (p = 0.19). The rates of intraoperative complications between groups did not significantly differ, except for vascular complications (p = 0.005), and the incidence of any postoperative complication was higher in the perioperative T2DM group (p = 0.01). With a median follow-up of 29 months [range 11.6-49.0 months], an additional 18.3% (n = 88) of the cohort met diagnostic criteria for T2DM. BMI (p < 0.001), perioperative glucose (p < 0.001), and HgbA1c (p = 0.002) demonstrate risk for a T2DM diagnosis during survivorship. CONCLUSION(S): In this retrospective cohort of EC patients, 25.4% were diagnosed with T2DM, with the majority diagnosed in the survivorship period. Surgical management and subsequent surveillance of EC presents an opportunity to diagnose at-risk patients with T2DM.

Mixed clear cell/endometrioid and clear cell/serous carcinoma of the uterus are clinicopathologically similar to pure clear cell carcinoma: An NRG Oncology/Gynecologic Oncology Group (GOG-210) study of 311 women.

OBJECTIVES: Clear cell carcinoma is a high-risk subtype of endometrial cancer. Some patients have a mixture of clear cell carcinoma with other histologic types (endometrioid or serous) or cannot be neatly assigned to one of these types. Protocol GOG-8032 within GOG-210 was designed to determine whether these tumors differ from pure clear cell carcinoma in stage at diagnosis, initial pattern of spread, or patient survival. METHODS: The term "mixed" was applied to tumors with multiple identifiable components, and "indeterminate" was applied to tumors with features intermediate between different histologic types. Three hundred eleven women with pure, mixed, or indeterminate clear cell carcinoma were identified in a larger cohort of patients undergoing hysterectomy for endometrial cancer in GOG-210. Histologic slides were centrally reviewed by expert pathologists. Baseline and follow-up data were analyzed. RESULTS: One hundred thirty-six patients had pure clear cell carcinoma and 175 had a mixed or indeterminate clear cell pattern. Baseline clinicopathologic characteristics were similar except for a small difference in age at presentation. Univariate survival analysis confirmed the significance of typical endometrial cancer prognostic factors. Patients in the mixed categories had disease-free and overall survival similar to pure clear cell carcinoma, but the indeterminate clear cell/endometrioid group had longer survival. CONCLUSION: In clear cell endometrial cancer, the presence of a definite admixed endometrioid or serous component did not correlate with a significant difference in prognosis. Patients whose tumors had indeterminate clear cell features had better prognosis. Some of these tumors may be endometrioid tumors mimicking clear cell carcinoma.

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.

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.

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.

TP53 mutation and abnormal p53 expression in endometrial cancer: Associations with race and outcomes.

OBJECTIVE: This multi-center cohort study assessed associations between race, TP53 mutations, p53 expression, and histology to investigate racial survival disparities in endometrial cancer (EC). METHODS: Black and White patients with advanced or recurrent EC with Next Generation Sequencing data in the Endometrial Cancer Molecularly Targeted Therapy Consortium database were identified. Clinicopathologic and treatment variables were summarized by race and compared. Overall survival (OS) and progression-free survival (PFS) among all patients were estimated by the Kaplan-Meier method. Cox proportional hazards models estimated the association between race, TP53 status, p53 expression, histology, and survival outcomes. RESULTS: Black patients were more likely than White patients to have TP53-mutated (N = 727, 71.7% vs 49.7%, p < 0.001) and p53-abnormal (N = 362, 71.1% vs 53.2%, p = 0.003) EC. Patients with TP53-mutated EC had worse PFS (HR 2.73 (95% CI 1.88-3.97)) and OS (HR 2.20 (95% CI 1.77-2.74)) compared to those with TP53-wildtype EC. Patients with p53-abnormal EC had worse PFS (HR 2.01 (95% CI 1.22-3.32)) and OS (HR 1.61 (95% CI 1.18-2.19)) compared to those with p53-wildtype EC. After adjusting for TP53 mutation and p53 expression, race was not associated with survival outcomes. The most frequent TP53 variants were at nucleotide positions R273 (n = 54), R248 (n = 38), and R175 (n = 23), rates of which did not differ by race. CONCLUSIONS: Black patients are more likely to have TP53-mutated and p53-abnormal EC, which are associated with worse survival outcomes than TP53- and p53-wildtype EC. The higher frequency of these subtypes among Black patients may contribute to survival disparities.

Postoperative venous thromboembolism risk stratification in patients with uterine cancer.

BACKGROUND: Uterine cancers are associated with a high risk for venous thromboembolisms. The American Society of Clinical Oncology practice guidelines recommend that all patients undergoing pelvic surgery for cancer should receive extended pharmacologic thromboprophylaxis with the duration being dependent on risk. However, risk stratification for patients with uterine cancer is not clearly defined. The Caprini score is the most widely used risk assessment model but it has been found to have limited use in the gynecologic oncology population. A modified Caprini score has been explored in other populations. The Khorana score is an additional risk assessment model that has not been studied in this context. OBJECTIVE: Our objective was to evaluate the ability of a modified Caprini model and the Khorana score to risk stratify patients with uterine cancer for postoperative venous thromboembolisms within 90 days of surgery. STUDY DESIGN: Following institutional review board approval, a retrospective cohort study was performed, and all patients with uterine cancer who underwent a hysterectomy over a 4-year period were included. The Caprini and Khorana scores were calculated for each patient. The Caprini score cutoff for highest risk was evaluated at ≥7, ≥8, and ≥9 (modified Caprini) and the Khorana score cutoff was evaluated at ≥2 and ≥3. To determine the prognostic use of each score and other clinico-pathologic criteria related to the development of a venous thromboembolism, univariate analyses were performed using independent t tests, chi-square tests, or Fisher's exact tests; a multivariate analysis was performed using logistic regression. RESULTS: A total of 954 patients were included. The rate of venous thromboembolism development was 1.7% (16/954). A minimally invasive surgical approach was used in 90.5% (863/954) of patients. The mean Caprini score for patients with a venous thromboembolism was 10.3 compared with 8.1 for patients without a venous thromboembolism (95% confidence interval, 1.17-3.33; P<.0001). The mean Khorana score for the venous thromboembolism group was 2.4 vs 1.9 for those without (95% confidence interval, 0.04-0.82; P=.03). Both the Caprini and Khorana scores were found to be associated with venous thromboembolisms, but only a Caprini score with a cutoff of ≥8 or ≥9 was statistically significant (risk ratio, 31.25; 95% confidence interval, 1.88-519.49; risk ratio, 4.59; 95% confidence interval, 1.49-14.13, respectively), with high accuracy based on the area under the curve (0.75 and 0.68, respectively). Of the minimally invasive subgroup, 11.7% (101/863) of patients had same-day discharge with no postoperative thromboprophylaxis; none of these patients developed venous thromboembolisms. Despite extended prophylaxis among the laparotomy patients (30 days), the rate of venous thromboembolisms was more than 3 times that of the minimally invasive group (5.49% vs 1.7%). Advanced tumor stage and leukocytosis were noted to be independent risk factors for venous thromboembolisms. CONCLUSION: Our study suggests that using a modified Caprini score could help to identify the highest-risk patients who would benefit from prolonged thromboprophylaxis, could reduce the incidence of postoperative venous thromboembolisms, and could minimize the cost and harm of overtreatment. These findings need to be validated in a prospective manner, and further research is needed to determine the optimal duration of therapy.

Less is more: clinical utility of postoperative laboratory testing following minimally invasive hysterectomy for endometrial cancer.

BACKGROUND: With the increasing rates of same-day discharge following minimally invasive surgery for endometrial cancer, the need for and value of routine postoperative testing is unclear. OBJECTIVE: This study aimed to determine whether routine postoperative laboratory testing following minimally invasive hysterectomy for endometrial cancer leads to clinically significant changes in postoperative care. STUDY DESIGN: This was a single-institution retrospective cohort study of patients undergoing minimally invasive hysterectomy for endometrial cancer by a gynecologic oncologist between June 2014 and June 2017. Patient demographics, preoperative comorbidities, operative and postoperative data, and pathologic findings were manually extracted from the patients' medical records. The financial burden of laboratory testing was computed using hospital-level cost data. RESULTS: Of the 649 women included in the analysis, most (91.4%) were White, with a mean age of 61 years, and mean body mass index of 38.0 kg/m2. The most common comorbidities were diabetes mellitus (31.9%, n=207), chronic pulmonary disease (7.9%, n=51), and congestive heart failure (3.2%, n=21). Median operative time was 151 minutes (range, 61-278), and median estimated blood loss was 100 mL (range, 10-1500). Most patients (68.6%, n=445) underwent lymphadenectomy. All patients had postoperative laboratory tests ordered: 100% complete blood count, 99.7% chemistry, 62.9% magnesium, 46.8% phosphate, 37.4% calcium, and 1.2% liver function tests. Twenty-six patients (4.0%) had a change in management owing to postoperative laboratory test results. Of these 26 women, 88% experienced a change in clinical status that would have otherwise prompted testing. Only 3 (0.5% of entire cohort) were asymptomatic: 1 received a blood transfusion for asymptomatic anemia, and the other 2, who did not carry a diagnosis of diabetes mellitus, had interventions for hyperglycemia. On univariable analysis, peripheral and cerebrovascular disease, diabetes mellitus with end-organ damage, and a Charlson Comorbidity Index of ≥3 were associated with increased odds of change in management; these were not significant on multivariable analysis. Routine postoperative laboratory evaluation in this cohort increased hospital costs by $292,000. CONCLUSION: Routine postoperative laboratory tests are unlikely to lead to significant changes in management for women undergoing minimally invasive hysterectomy for endometrial cancer, and may increase cost without providing a discernible clinical benefit. In the setting of strict postoperative guidelines, laboratory tests should be ordered when clinically indicated rather than as part of routine postoperative management for women undergoing minimally invasive hysterectomy for endometrial cancer.

Characterization of Patients with Frequent Utilization of the Obstetric Triage Unit: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to identify characteristics of patients with frequent obstetric triage visits ("superusers") compared to those with fewer visits and to evaluate the association of frequent obstetric triage visits with preterm birth and cesarean delivery. STUDY DESIGN: This retrospective cohort included patients presenting to the obstetric triage unit at a tertiary care center from March through April 2014. Superusers were defined as individuals having four or more triage visits. Participant characteristics, including demographic, clinical, visit acuity, and health care characteristics of superusers and nonsuperusers, were summarized and compared. In the subset of patients where data were available regarding prenatal care, prenatal visit patterns were analyzed and compared between the two groups. The outcomes of preterm birth and cesarean were compared between groups using modified Poisson regression to control for confounding. RESULTS: Of the 656 patients evaluated in the obstetric triage unit during the study period, 648 patients met the inclusion criteria. Factors associated with frequent triage use included race/ethnicity, multiparity, insurance status, high-risk pregnancy, and a prior preterm birth. Superusers were more likely to present at an earlier gestational age and had a higher proportion of visits for hypertensive disease. Patient acuity scores were not different between the groups. In the subset of patients receiving prenatal care at the institution, prenatal visit patterns were similar. The risk of preterm birth (adjusted risk ratio [aRR]: 1.06; 95% confidence interval [CI]: 0.66-1.70) did not differ between groups; however, the risk of a cesarean delivery was increased in superusers (aRR: 1.39; 95% CI: 1.01-1.92) when compared to nonsuperusers. CONCLUSION: Superusers, compared to nonsuperusers, have distinct clinical and demographic characteristics and are more likely to be seen in the triage unit at earlier gestational ages. Superusers tended to have a higher proportion of visits for hypertensive disease and had an increased risk of cesarean delivery. KEY POINTS: · Patients with frequent triage visits did not have an increased risk of preterm birth.. · Patients with frequent triage visits were more likely to undergo cesarean delivery.. · Acuity scales were similar for patients with frequent visits compared to those with few visits..

Racial Disparities in Surgical Outcomes Among Women with Endometrial Cancer.

PURPOSE: Endometrial cancer (EC) is the most common gynecological cancer among women in the United States. Despite well-documented racial/ethnic disparities in EC incidence and mortality rates, limited data exist regarding disparities in hysterectomy surgical outcomes. We evaluated associations of race/ethnicity with postoperative complications, serious adverse events (SAEs), and length of hospital stay among women undergoing EC-related hysterectomy. METHODS: Using National Surgical Quality Improvement Program (NSQIP) data, we identified women (≥18 years) undergoing hysterectomy to treat EC between 2014 and 2020. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of race/ethnicity (white, black, and Latina) with postoperative complications and SAEs. We used Poisson regression with robust standard errors to calculate incidence rate ratios (IRRs) and 95% CIs for the association of race/ethnicity with length of hospital stay. RESULTS: Of 22,778 women undergoing EC-related hysterectomy, 3.1% developed postoperative complications. Black (adjusted OR: 1.62; 95% CI 1.05-2.48) and Latina women (adjusted OR: 1.79; 95% CI 1.04-3.09) had higher postoperative complication risks than white women. The overall SAE incidence was 5.0%. Black women (adjusted OR: 1.55, 95% CI 1.13-2.15) had higher SAE risks than white women. Length of hospital stay was significantly longer for black women than white women (IRR: 1.18; 95% CI 1.07-1.30). CONCLUSIONS: We observed racial/ethnic disparities in EC-related hysterectomy surgical outcomes in a large, diverse sample of U.S. women between 2014 and 2020. Studies to elucidate the underlying mechanisms of these racial disparities, with a focus on social context remain necessary.

Hospital-based ovarian cancer patient traceback program results in minimal genetic testing uptake.

OBJECTIVE: To determine the feasibility of hospital-based genetic counseling and testing (GC/T) Traceback for Ovarian Cancer (OC) patients, as proposed by the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute. METHODS: Living patients with OC were sent a letter explaining the availability of guideline-supported GC/T for at least BRCA1/2 and surrogates of deceased patients were called on the telephone. Outcomes of contact attempts were systematically recorded and statistically described. RESULTS: 598 Traceback-eligible OC patients diagnosed from 2006 to 2016 were identified (163 presumed-living and 435 deceased). Two living patients called our office and scheduled an appointment for GC/T after receiving a letter. For surrogates of prior patients, successful contact occurred in 25% of call attempts. Fourteen individuals (2 living patients and 12 surrogates) underwent genetic counseling. Of those 14, 10 individuals consented to genetic testing and 5 followed through with sample collection. None of these individuals had pathogenic variants (PVs). When surrogate call notes were reviewed, 58% reflected positive responses to contact, however 42% were noted to have negative or indifferent responses, which were most common among spouses. Total time spent for hospital-based Traceback was 109 h. CONCLUSIONS: Overall, hospital-based Traceback via letter and telephone contact of surrogates is time-intensive and results in minimal uptake of GC/T. To practically execute this type of outreach program, health systems should consider collection of alternative contact information to allow for electronic communication of patient surrogates. Our study also underscores the importance of timely GC/T while patients are in active cancer care.

Racial and ethnic disparities in readmission risk following the surgical management of endometrial cancer.

OBJECTIVE: Most women diagnosed with endometrial cancer undergo primary surgical management with hysterectomy. Although racial disparities in readmission risk following hysterectomy for non-cancerous conditions have been reported, data among women with endometrial cancer are absent. This study evaluates racial differences in readmission risk among women undergoing endometrial cancer-related hysterectomy. METHODS: In the National Cancer Database, women who underwent surgical management for endometrial cancer from 2004 to 2018 were identified. Readmission and minimally invasive hysterectomy (MIH) proportions were plotted according to year of diagnosis and race/ethnicity. Multivariable logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between readmission risk and epidemiological, facility, tumor, and surgical characteristics. A base model was sequentially adjusted to incorporate significant covariates. RESULTS: There were 350,631 patients included in the study. The proportion of MIH increased among all race/ethnicities over the study period; however, MIH rates were lower among Black women. Readmission proportions were 2.7% among White, 4.2% among Black, 2.9% among Hispanic, 2.4% among Asian, 2.1% among American Indian/Alaska Native, and 3.1% among Native Hawaiian/Pacific Islander women. In the fully adjusted model incorporating surgical approach, Black women (OR: 1.20, 95% CI = 1.13, 1.28) and Native Hawaiian/Pacific Islander women (OR: 1.54, 95% CI = 1.09, 2.18) were more commonly readmitted compared to White women. CONCLUSIONS: In this study, Black and Native Hawaiian/Pacific Islander women with endometrial cancer had significantly higher readmission risk than White women. Optimizing perioperative care for minority women is an essential component of overcoming racially disparate endometrial cancer outcomes.

The contemporary presentation and diagnosis of endometrial cancer recurrence: When, where, and how?

OBJECTIVE: To examine patients with confirmed endometrial cancer recurrence; evaluate patterns, presentation, and mode of diagnosis. STUDY DESIGN: A retrospective review of women with endometrial cancer diagnosis between 2014 and 2020. Disease recurrences were evaluated. Medical records were reviewed focusing on presentation at time of recurrence. Relationships were assessed using χ2, Fisher's exact test, t-test, and Wilcoxon test. The Kaplan-Meier product limit was used to estimate survival. Multiple logistic regression analysis was used to assess the impact of covariates. RESULTS: Endometrial cancer recurrence was identified in 201 (11.7%) patients. Sixty percent (120/201) of patients presented with symptoms. Pain was the most common presenting symptom (23.4%, 47/201) and bleeding was reported in <14% (28/201). Patients with symptomatic presentation were less likely to be able to receive treatment for their recurrent disease (76.7% vs 91.3%, p = 0.005). Asymptomatic pelvic exam diagnosed recurrence in 13.4% (27/201) and was more common in patients initially diagnosed with early-stage disease (66.7% vs 34.5% p = 0.001) of endometrioid histology (66.7% vs 36.8%, p = 0.003) without prior adjuvant therapy (48.2% vs 17.9%, p = 0.001). More than1/3 of diagnoses were made by providers outside of the oncologic care team. CONCLUSION: The majority of women with recurrent endometrial cancer were symptomatic and pain is a common complaint associated with disease recurrence. Patients with symptomatic presentation of disease recurrence were less likely to receive treatment for recurrent disease but this did not result in an overall survival (OS) difference. Given the rising mortality rate of endometrial cancer further work is needed to develop multidisciplinary surveillance strategies that will enable meaningful treatment of disease recurrence.

Aberrant expression of TMEM205 signaling promotes platinum resistance in ovarian cancer: An implication for the antitumor potential of DAP compound.

INTRODUCTION: TMEM205 is a novel transmembrane protein associated with platinum resistance (PR) in epithelial ovarian carcinoma (OC), however, the specific mechanisms associated with this resistance remain to be elucidated. METHODS: TMEM205 expression was evaluated in platinum-sensitive (PS) versus platinum resistant (PR) ovarian cancer cell lines and patient serum/tissues. Exosomal efflux of platinum was evaluated with inductively coupled plasma mass spectrometry (ICP-MS) after pre-treatment with small molecule inhibitors (L-2663/L-2797) of TMEM205 prior to treatment with platinum. Cytotoxicity of combination treatment was confirmed in vitro and in an in vivo model. RESULTS: TMEM205 expression was 10-20 fold higher in PR compared to PS ovarian cancer cell lines, serum samples, and tissues. Co-localization with CD1B was confirmed by in-situ proximity ligation assay suggesting that TMEM205 may mediate PR via the exosomal pathway. Exosomal secretion was significantly increased 5-10 fold in PR cell lines after treatment with carboplatin compared to PS cell lines. Pre-treatment with L-2663 prior to carboplatin resulted in significantly increased intracellular concentration of fluorescently-labeled cisplatin and decreased exosomal efflux of platinum. Decreased cell survival and tumor growth in vitro and in vivo was observed when PR cells were treated with a combination of L-2663 with carboplatin compared to carboplatin alone. CONCLUSION: TMEM205 appears to be involved in the development of PR in ovarian cancer through the exosomal efflux of platinum agents. This study provides pre-clinical evidence that TMEM205 could serve as a possible biomarker for PR as well as a therapeutic target in combination with platinum agents.