Faculty Bibliography

OBJECTIVE:Despite the within-group heterogeneity, Asian American (AA) and Native Hawaiian and Pacific Islander (NH/PI) patients are often grouped together. We compared the patterns of guideline-concordant care for locally advanced cervical cancer for disaggregated AA and NH/PI patients. METHODS:Patients with stage II-IVA cervical cancer between 2004 and 2020 were identified from the National Cancer Database. AA patients were disaggregated as East Asian (EA), South Asian (SA), and Southeast Asian (SEA). NH/PI patients were classified as a distinct racial subgroup. The primary outcome was the proportion undergoing guideline-concordant care, defined by radiation therapy with concurrent chemotherapy, brachytherapy, and completion of treatment within eight weeks. RESULTS:Of 48,116 patients, 2107 (4%) were AA and 171 (<1%) were NH/PI. Of the AA patients, 36% were SEA, 31% were EA, 12% were SA, and 21% could not be further disaggregated due to missing or unknown data. NH/PI patients were more likely to be diagnosed at an early age (53% NH/PI vs. 30% AA, p < 0.001) and have higher rates of comorbidities (18% NH/PI vs. 14% AA, p < 0.001). Within the AA subgroups, only 82% of SEA patients received concurrent chemotherapy compared to 91% of SA patients (p = 0.026). SA patients had the longest median OS (158 months) within the AA subgroups compared to SEA patients (113 months, p < 0.001). CONCLUSION/CONCLUSIONS:Disparities exist in the receipt of standard of care treatment for cervical cancer by racial and ethnic subgroups. It is imperative to disaggregate race and ethnicity data to understand potential differences in care and tailor interventions to achieve health equity.

BACKGROUND:Participation in clinical trials may help mitigate disparate cancer outcomes. Thus, ensuring equitable access to clinical trials is a major priority for national cancer organizations. OBJECTIVE:This study aimed to examine clinical trial eligibility criteria that may adversely affect the enrollment of underrepresented groups and assess the availability of demographic information in published gynecologic oncology studies. STUDY DESIGN/METHODS:ClinicalTrials.gov was searched for gynecologic oncology studies conducted between 1997 and 2021. Each study's inclusion and exclusion criteria were reviewed to determine whether demographic factors were used for enrollment screening. For published studies, demographic variables that were reported were identified. The expected clinical trial enrollment based on disease incidence and mortality was compared with the observed trial enrollment based on race. RESULTS:There were 1597 gynecologic oncology studies: 883 (55%) from ovarian cancer studies, 336 (21%) from cervical cancer studies, 262 (17%) from uterine cancer studies, and 116 (7%) from multisite gynecologic oncology studies. Of the 581 published studies, 554 (95%) reported age, 363 (63%) reported race, and 171 (29%) reported ethnicities. Cervical cancer studies were most likely to report demographic information, including race (P=.026) and ethnicity (P<.001). During the study period, 189 studies (12%) excluded patients based on the language spoken. Industry-sponsored trials (odds ratio, 0.07; 95% confidence interval, 0.02-0.30) and organization-sponsored trials (odds ratio, 0.40; 95% confidence interval, 0.22-0.73) were less likely to exclude patients because of language than investigator-initiated trials. A minority of patients (37%) in cervical cancer trials were of White race, compared with 85% of patients in uterine cancer trials and 82% of patients in ovarian cancer trials. CONCLUSION/CONCLUSIONS:Over the last 3 decades, 1 in 10 gynecologic oncology trials excluded patients because of language. Race and ethnicity were reported in more than half of the available studies. Initiatives to increase transparency in recruiting underrepresented patients and reporting demographic data are urgently needed.

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.

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:To determine whether routine postoperative labs following minimally invasive hysterectomy for endometrial cancer leads to clinically significant changes in postoperative care. STUDY DESIGN/METHODS:This is a single-institution retrospective cohort study of patients undergoing minimally invasive hysterectomy for endometrial cancer by a gynecologic oncologist between June 2014-2017. 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, the majority (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 (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 minutes) and median estimated blood loss was 100 mL (range 10-1500 mL). Most patients (68.6%, n=445) underwent lymphadenectomy. All patients had post-operative labs 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 due to postoperative lab results. Of these 26 women, 88% experienced a change in clinical status that would have otherwise prompted testing. Only three (0.5% of entire cohort) were asymptomatic: one received a blood transfusion for asymptomatic anemia and the other two, who did not carry a diagnosis of diabetes, had interventions for hyperglycemia. On univariable analysis, peripheral and cerebrovascular disease, diabetes 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. CONCLUSIONS:Routine postoperative labs 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 discernable clinical benefit. In the setting of strict post-operative 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.

Objectives Endometrial cancer (EC) is a molecularly driven disease, and prognostic and treatment paradigms are transitioning to focus on molecular subtyping. Surgical staging and the role of lymphadenectomy has similarly evolved over time, however current lymph node (LND) algorithms do not account for molecular subtyping. The objective of this study was to evaluate the association of microsatellite instability (MSI) and lymph node metastases (LNM). Methods This was a retrospective cohort study of patients undergoing surgery for EC between 2010-2021. All EC patients at our institution undergo immunohistochemistry testing for mismatch repair (MMR) proteins and next generation sequencing per clinician discretion. Sarcomas were excluded. Mutations were classified as microsatellite instability high (MSI-H) or MMR proficient (MMRp). Results 367 patients were included. Of these, 273 were MMRp and 94 were MSI-H. An average of 6.1 LND were removed and there was no difference in the average LND removed between groups (p= 0.91). LNM were identified in 8% (n=31) of the entire cohort. There was a statistically significant difference in the average LNM between MMRp and MSI-H patients (p<0.0001), with 1% (n=2) of the MMRp cohort and 30% (n=28) of the MSI-H cohort having LNM. Within the MSI-H cohort, all LNM occurred within the MMR deficient, MLH1 hypermethylated subgroup - representing a LNM rate of 41%. Conclusions There is a significant association between MSI status and LNM. Molecular classification, which is obtainable from preoperative biopsy, may be used to guide intraoperative decision making and should be evaluated in the context of sentinel LND protocols

Objectives With the National Cancer Institute (NCI) call-toaction to increase racial/ethnic diversity in clinical trial enrollment, we sought to evaluate minority patient enrollment in gynecologic cancer clinical trials as compared with disease prevalence estimates by race/ethnicity. Methods Enrollment data from endometrial and ovarian therapeutic clinical trials from January 2018-May 2022 at a NCI-designated Comprehensive Cancer Center in New York City was analyzed. Minority enrollment in ovarian and endometrial cancer trials was compared to SEER estimates of disease prevalence using chi-square analysis. Population estimates of NYC demographics were obtained from the U. S. Census. Results Over the study period, 129 patients were enrolled in ovarian cancer trials and 52 patients in endometrial cancer trials. Regarding total enrollment, the proportion of clinical trial participants identifying as racial/ethnic minorities (34.1%) was significantly higher than the SEER disease estimate of ovarian cancer in minority patients (25.7%, p<0.05). Likewise, total enrollment of minority patients in endometrial cancer trials (61.5%) exceeded their disease prevalence estimate of 28.5% (p<0.05). However, enrollment of Asian patients in endometrial cancer trials (1.9%) remained under disease prevalence estimates (7.7%) despite the NCI call-to-action (table 2). Conclusions In a diverse city population, enrollment of minority patients exceeded disease prevalence estimates for most underrepresented racial/ethnic groups in gynecologic cancer, with the exception of Asian patients in endometrial cancer. Further efforts are needed to increase enrollment of Asian patients in endometrial cancer clinical trials so that novel therapies can be tested in all patients

Objectives Minority U.S. populations are underrepresented in oncologic clinical trials. In an urban NCI-designated Comprehensive Cancer Center, we evaluated enrollment in gynecologic cancer trials by race/ethnicity pre and post the June 2020 NCI call-to-action for increased diversity in clinical trials. Methods Enrollment data in 22 therapeutic clinical trials from January 2018-May 2022 was analyzed. Chi-square/Fisher's exact analysis compared proportions of accrued patients by race/ethnicity pre and post the NCI call-to-action. Results Over the study period 205 patients were enrolled in gynecologic cancer trials: 129 (62.9%) ovarian, 52 (25.4%) endometrial, 24 (11.7%) cervical. Overall racial/ethnic distribution of patients in clinical trials was: 112 (54.6%) non-Hispanic White, 33 (16.1%) Hispanic, 32 (15.6%) Black, 28 (13.7%) Asian. Although not statistically significant, accrual of underrepresented populations increased from pre call-to-action (45/108, 41.7%) to post (48/97, 49.5%). Significantly more Black patients were accrued post NCI call-to-action (8/108, 7.4% vs 24/97, 24.7%, p=0.001). However, significantly fewer Asian patients were accrued post NCI call-to-action (21/ 108, 19.4% vs 7/97, 7.2%, p=0.01). Conclusions Overall accrual of Black patients in gynecologic cancer clinical trials increased following the NCI call-to-action, but accrual of Asian patients decreased. Further efforts are needed to ensure all racial/ethnic groups are represented in clinical trials

OBJECTIVES/OBJECTIVE:The laparoscopic hysterectomy readmission score (LHRS) was created to identify patients for whom same day discharge (SDD) after minimally invasive hysterectomy (MIH) may not be advisable and includes diabetes, chronic obstructive pulmonary disease, disseminated cancer, chronic steroid use, bleeding disorder, length of surgery, and any postoperative complication prior to discharge. We evaluated the performance of the score at predicting readmission in a gynecologic oncology population, and additionally sought to determine if any factors known prior to surgery could replace those that are not known until the time of surgery (operative time and postoperative complication). METHODS:This was a single-institution retrospective cohort study of women undergoing robotic hysterectomy by a gynecologic oncologist in 2018. Associations between pre-operative, operative and post-operative factors and 30-day readmission, SDD and postoperative complications were assessed using logistic regression. RESULTS:The 30-day readmission rate among the 423 women in the cohort was 4.5% and 1.9% in those undergoing SDD. Readmission rates by LHRS were: score 1 (4.9%), score 2 (7.8%), score 3 (13.6%), score 4 (16.7%). Patients with a LHRS of ≥3 had higher odds of readmission compared to those with a lower score (OR 4.20, p = 0.02). Infectious morbidity accounted for the majority of postoperative complications, emergency room visits and readmissions. We did not identify preoperative factors to replace the intra- and post-operative factors used in the score. CONCLUSIONS:The readmission rate following MIH is low, and a LHRS of ≥3 is associated with increased risk of readmission. Our findings support the applicability of the LHRS to a gynecologic oncology population; addressing risk factors for postoperative infection or closer follow up for patients with a LHRS ≥3 could reduce postoperative readmissions.

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

Because of limits on specificity and purity to allow for in-depth protein profiling, a standardized method for exosome isolation has yet to be established. In this study, we describe a novel, in-house microfluidic-based device to isolate exosomes from culture media and patient samples. This technology overcomes contamination issues because sample separation is based on the expression of highly specific surface markers CD63 and EpCAM. Mass spectrometry revealed over 25 exosome proteins that are differentially expressed in high-grade serous ovarian cancer (HGSOC) cell lines compared with normal cells-ovarian surface epithelia cells and fallopian tube secretory epithelial cells (FTSEC). Top exosome proteins were identified on the basis of their fold change and statistical significance between groups. Ingenuity pathway analysis identified STAT3 and HGF as top regulator proteins. We further validated exosome proteins of interest (pSTAT3, HGF, and IL6) in HGSOC samples of origin-based cell lines (OVCAR-8, FTSEC) and in early-stage HGSOC patient serum exosome samples using LC/MS-MS and proximity extension assay. Our microfluidic device will allow us to make new discoveries for exosome-based biomarkers for the early detection of HGSOC and will contribute to the development of new targeted therapies based on signaling pathways that are unique to HGSOC, both of which could improve the outcome for women with HGSOC. SIGNIFICANCE: A unique platform utilizing a microfluidic device enables the discovery of new exosome-based biomarkers in ovarian cancer.