High visceral fat to subcutaneous fat ratios portend a poor prognosis in patients with advanced endometrial cancer.

OBJECTIVES: Visceral adiposity has been established as a predictor of outcomes in various cancers. We aimed to determine the association of radiographic measurements of visceral fat with clinical outcomes in patients with endometrial cancer. METHODS: A retrospective review of patients with stage III-IV endometrial cancer who underwent surgery between 2004 and 2014 was performed. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT;VAT+SAT) were assessed on preoperative computed tomography (CT) scans. Exploratory analysis was performed to establish the optimal cut-off values for VAT, SAT, and TAT to identify patients with poor prognostic body composition. Survival rates were analyzed using Kaplan-Meier analysis, log-rank tests, and cox-regression. RESULTS: Eighty-three patients were included. Forty-two (51%) patients had a low VAT/SAT ratio (<0.45) and 41 (49.4%) had a high VAT/SAT ratio (>0.45). There were no significant differences in demographics between the groups. The mean VAT, SAT, and TAT were 176.3 cm2, 379.3 cm2, and 555.3 cm2 respectively. Compared to patients with low VAT/SAT ratios, patients with high VAT/SAT ratios had a shorter recurrence-free survival (median 29.6 vs 32.3 months, P = 0.01) and shorter overall survival (median 56 vs 93.7 months, P = 0.03). CONCLUSIONS: Visceral fat measurements are predictive of outcomes in patients with advanced stage endometrial cancer. Specifically, VAT to SAT ratios are predictive of overall survival. Future studies should be pursued to identify potential therapeutic targets and biological mechanisms that underlie obesity's relationship with endometrial cancer.

Impact of employment and insurance status on distress in gynecologic oncology patients.

OBJECTIVES: To study associations among employment, insurance status, and distress in gynecologic oncology patients; and to evaluate the impact of being unemployed or having no/Medicaid insurance on different distress problem areas. METHODS: In this single institution, cross-sectional analysis of gynecologic oncology patients, we screened for distress and problem areas using the National Comprehensive Cancer Network distress thermometer and problem list at outpatient appointments between 6/2017-9/2017. Primary outcome was self-reported high distress (score ≥ 5). The distress problem list included 5 categories-practical, family, emotional, physical, and other. Employment status included employed, unemployed, homemaker, and retired. Logistic regression was used to predict high distress from employment and insurance statuses, adjusting for relevant covariates. RESULTS: Of 885 women, 101 (11.4%) were unemployed, and 53 (6.0%) uninsured or had Medicaid coverage. One in five patients (n = 191, 21.6%) indicated high distress. Unemployed patients were more likely than employed to endorse high distress [adjusted odds ratio (aOR) = 3.5, 95% confidence interval (CI) 2.2-5.7, p < 0.001]. Compared to employed patients, a greater proportion of unemployed patients endorsed distress related to practical (p < 0.05), emotional (p < 0.001), physical (p < 0.01), and other (p < 0.05) problems. Uninsured/Medicaid patients were more likely to endorse high distress (aOR = 2.8, 95% CI 1.5-5.1, p < 0.001) and report family (p < 0.001), emotional (p < 0.001), and other (p < 0.01) problems than patients who had Medicare/commercial insurance. CONCLUSIONS: Gynecologic oncology patients who are unemployed or have no/Medicaid insurance face high distress that appears to arise from issues beyond practical problems, including financial and/or insurance insecurities.

Text-message-based behavioral weight loss for endometrial cancer survivors with obesity: A randomized controlled trial.

OBJECTIVE: To evaluate the ability of a personalized text-message-based intervention to increase weight loss among endometrial cancer survivors with obesity. METHODS: In this randomized, controlled trial, endometrial cancer survivors with obesity (BMI ≥30 kg/m2) were randomized to a personalized SMS text-message-based weight loss intervention or enhanced usual care. Primary outcome was weight loss at 6 months; secondary outcomes were weight loss at 12 months and changes in psychosocial measures. We also compared clinical characteristics and weight change between trial participants and non-participants. RESULTS: Between May 18 and December 31, 2017, 80 endometrial cancer survivors with obesity consented to participate in the randomized trial. There were no differences in clinical characteristics between the two arms. Weight changes were similar in the two arms (P = 0.08). At 6 months, no differences in quality of life, physical activity, or body image were noted. Of 358 eligible patients, 80 became trial participants and 278, non-participants. Trial participants were younger (59.3 vs. 63.4 years, P < 0.001), more likely non-white (P = 0.02), on fewer medications (4 vs. 7, P < 0.001), and had a higher median BMI (38.7 vs. 37.6 kg/m2, P = 0.01) than non-participants. Weight change was similar between participants and non-participants (P = 0.85). At 6 months, similar percentages of participants and non-participants (47.7% vs. 44.4%) had gained weight, and similar percentages (9.2% vs. 11.2%) had lost at least 5% of their body weight. CONCLUSIONS: This text-message-based intervention did not increase weight loss among endometrial cancer survivors with obesity, nor did participation in the trial. Other weight management interventions should be promoted to increase weight loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03169023.

A deficit-accumulation frailty index predicts survival outcomes in patients with gynecologic malignancy.

OBJECTIVE: To determine the association between scores from a 25-item patient-reported Rockwood Accumulation of Deficits Frailty Index (DAFI) and survival outcomes in gynecologic cancer patients. METHODS: A frailty index was constructed from the SEER-MHOS database. The DAFI was applied to women age ≥ 65 diagnosed with all types of gynecologic cancers between 1998 and 2015. The impact of frailty status at cancer diagnosis on overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: In this cohort (n = 1336) the median age at diagnosis was 74 (range 65-97). Nine hundred sixty-two (72%) women were Caucasian and 132 (10%) were African-American. Overall, 651(49%) of patients were considered frail. On multivariate analysis, frail patients had a 48% increased risk for death (aHR 1.48; 95% CI 1.29-1.69; P < 0.0001). Each 10% increase in frailty index was associated with a 16% increased risk of death (aHR, 1.16; 95% CI, 1.11 to 1.21; P < 0.0001). In subgroup analyses of the varying cancer types, the association of frailty status with prognosis was fairly consistent (aHR 1.15-2.24). The DAFI was more prognostic in endometrial (aHR 1.76; 95% CI 1.41-2.18, P < 0.0001) and vaginal/vulvar (aHR 1.94; 95% CI 1.34-2.81, P = 0.0005) cancers as well as patients with loco-regional disease (aHR 1.94; 95% CI 1.62-2.33, P < 0.0001). CONCLUSIONS: Frailty appears to be a significant predictor of mortality in gynecologic cancer patients regardless of chronological age. This measure of functional age may be of particular utility in women with loco-regional disease only who otherwise would have a favorable prognosis.

A fellow-run clinic achieves similar patient outcomes as faculty clinics: A safe and feasible model for gynecologic oncology fellow education.

OBJECTIVES: Fellow involvement in patient care is important for education, but effect on patient care is unclear. Our aim was to compare patient outcomes in gynecologic oncology attending clinics versus a fellow training clinic at a large academic medical center. METHODS: A retrospective review of consecutive gynecologic oncology patients from six attending clinics and one faculty-supervised fellow clinic was used to analyze differences based on patient demographics, cancer characteristics, and practice patterns. Primary outcome was overall survival (OS); secondary outcomes included recurrence-free survival (RFS), postoperative complications and chemotherapy within the last 30 days of life. Survival analyses were performed using Kaplan-Meier curves with log-rank tests. RESULTS: Of 159 patients, 76 received care in the attending clinic and 83 in the fellow clinic. Patients in the fellow clinic were younger, less likely to be Caucasian, and more overweight, but cancer site and proportion of advanced stage disease were similar. Both clinics had similar rates of moderate to severe adverse events related to surgery (15% vs. 8%, p = .76), chemotherapy (21% vs. 23%, p = .40), and radiation (14% vs. 17%, p = .73). There was no difference in median RFS in the fellow compared to attending clinic (38 vs. 47 months, p = .78). OS on both univariate (49 months-fellow clinic, 60 months-attending clinic vs. p = .40) and multivariate analysis [hazard ratio 1.3 (0.57, 2.75), P = .58] was not significantly different between groups. CONCLUSIONS: A fellow-run gynecologic oncology clinic designed to provide learning opportunities does not compromise patient outcomes and is a safe and feasible option for fellow education.

Defining and mitigating the challenges of an older and obese population in minimally invasive gynecologic cancer surgery.

The incidence of endometrial cancer (EC) is steadily increasing due in large part to an aging world population and rise in rates of obesity. Patients with obesity and advancing age can be seen as vulnerable populations, as they are both often subject to physician bias regarding surgical choices and assumptions regarding long-term outcomes. As we operate on an older and/or obese patient population, it is increasingly important that we adopt peri-operative management strategies and surgical techniques to best serve this complex patient population. Careful orchestration pre-, intra- and postoperatively is key to successful outcomes in robotic and laparoscopic surgery. Here, we review existing literature regarding EC in women with older age and/or obesity, outline recommendations for peri-operative management and common intra-operative issues-specifically common anesthetic issues surrounding cardiovascular, respiratory and neuromuscular systems-that are of heightened importance in women with older age and/or obesity. The goal of this review is to help define and mitigate common complications for these vulnerable patients with an EC diagnosis who, in accordance with carefully assessed health risks, can and should be offered standard of care surgery and treatment.

Sparse feature selection for classification and prediction of metastasis in endometrial cancer.

BACKGROUND: Metastasis via pelvic and/or para-aortic lymph nodes is a major risk factor for endometrial cancer. Lymph-node resection ameliorates risk but is associated with significant co-morbidities. Incidence in patients with stage I disease is 4-22% but no mechanism exists to accurately predict it. Therefore, national guidelines for primary staging surgery include pelvic and para-aortic lymph node dissection for all patients whose tumor exceeds 2cm in diameter. We sought to identify a robust molecular signature that can accurately classify risk of lymph node metastasis in endometrial cancer patients. 86 tumors matched for age and race, and evenly distributed between lymph node-positive and lymph node-negative cases, were selected as a training cohort. Genomic micro-RNA expression was profiled for each sample to serve as the predictive feature matrix. An independent set of 28 tumor samples was collected and similarly characterized to serve as a test cohort. RESULTS: A feature selection algorithm was designed for applications where the number of samples is far smaller than the number of measured features per sample. A predictive miRNA expression signature was developed using this algorithm, which was then used to predict the metastatic status of the independent test cohort. A weighted classifier, using 18 micro-RNAs, achieved 100% accuracy on the training cohort. When applied to the testing cohort, the classifier correctly predicted 90% of node-positive cases, and 80% of node-negative cases (FDR = 6.25%). CONCLUSION: Results indicate that the evaluation of the quantitative sparse-feature classifier proposed here in clinical trials may lead to significant improvement in the prediction of lymphatic metastases in endometrial cancer patients.

Benefit of combination chemotherapy and radiation stratified by grade of stage IIIC endometrial cancer.

OBJECTIVE: The optimal strategy for adjuvant therapy in stage IIIC endometrial cancer has not been determined. Our aim was to evaluate survival benefit of different treatments and to investigate if benefit varied by histologic grade. METHODS: We identified 199 patients with stage IIIC endometrial cancer from 2000 to 2012 through the Siteman Cancer Center registry. All patients underwent surgical staging followed by no adjuvant therapy (NAT), radiation (RT), chemotherapy (CT) or chemoradiation (CRT). The association between adjuvant treatment and overall survival was explored using Kaplan-Meier plots and multivariable Cox regression analysis. Multivariable analysis was stratified by low- or high-grade to explore the interaction between grade and treatment. RESULTS: Most patients received CRT (50.3%) followed by CT (23.1%), RT (16.1%) and NAT (10.5%). Survival after CRT was superior to NAT (p<0.001), RT (p=0.010) and CT (p<0.001). After adjusting for covariates, treatment with RT, CT and CRT led to a 57% (p=0.024), 62% (p=0.003) and 83% (p<0.001) reduction in risk of death compared to NAT, respectively. With CRT as the reference, the adjusted hazard of death was higher with NAT (5.94, p<0.001), RT (2.56, p=0.009) and CT (2.24, p=0.004). Stratifying by grade, RT and CRT led to a 67% (p=0.039) and 85% (p<0.001) reduction in death, compared to NAT in low-grade patients. CT and CRT led to a 72% (p=0.003) and 83% (p<0.001) reduction in death, compared to NAT in high-grade patients. CONCLUSIONS: Our findings suggest that CRT should be the preferred adjuvant treatment strategy for patients with stage IIIC endometrial cancer.

A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcoma of the uterus, an NRG Oncology/Gynecologic Oncology Group study.

BACKGROUND: The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. METHODS: Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40mg/m2 as a 3hour IV infusion on day 1 of a 21daycycle. Treatment was continued until disease progression or unacceptable toxicity occurred. RESULTS: Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7mo and 7.7mo, respectively, with a median follow-up of 37mo. Six month PFS was 20.6%. Major grade≥3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. CONCLUSION: In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity.

Adult Comorbidity Evaluation 27 score as a predictor of survival in endometrial cancer patients.

BACKGROUND: The incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. Although a few cohort studies of <500 patients showed an association between comorbidity and survival in patients with endometrial cancer, the degree of association must be better described. The Adult Comorbidity Evaluation 27 is a validated comorbidity instrument that provides a score of 0-3 based on the number of and severity of medical comorbidities. OBJECTIVE: This study was performed to explore the association between medical comorbidities and survival of patients with endometrial cancer. STUDY DESIGN: Patients who were diagnosed with endometrial cancer from 2000-2012 were identified from the prospectively maintained Siteman Cancer Center tumor registry. Patients who underwent primary surgical treatment for endometrioid, serous, and clear cell endometrial carcinoma were included. Patients who primarily were treated with radiation, chemotherapy, or hormone therapy were excluded. Patients with uterine sarcomas or neuroendocrine tumors were excluded. Patients with missing Adult Comorbidity Evaluation 27 scores were also excluded from analysis. Information that included patient demographics, Adult Comorbidity Evaluation 27 score, tumor characteristics, adjuvant treatment, and survival data were extracted from the database. The association of Adult Comorbidity Evaluation 27 and overall and recurrence-free survival was explored in a multivariable Cox regression analysis after being controlled for variables that have been found to be associated significantly with survival in univariable analysis. RESULTS: A total of 2073 patients with a median age of 61 years (range, 20-94 years) at diagnosis were identified. The Adult Comorbidity Evaluation 27 score was 0, 1, 2, and 3 in 22%, 38%, 28%, and 12% of patients, respectively. Stage distribution was I (73%), II (5%), III (15%), and IV (7%), and grade distribution was 1 (52%), 2 (23%), and 3 (25%). Most patients had endometrioid histologic condition (87%) followed by serous (11%) and clear cell (3%) endometrial carcinoma. The median overall survival time for the entire cohort was 54 months (95% confidence interval, 3-154 months), and the median recurrence-free survival was 50 months (95% confidence interval, 2-154 months). On univariable analysis, age, race, marital status, stage, grade, histologic condition, and treatment type were associated significantly with overall survival and recurrence-free survival. After adjustment for these covariates, patients with an Adult Comorbidity Evaluation 27 score of 2 had a 52% higher risk of death (95% confidence interval, 1.16-2.00); patients with an Adult Comorbidity Evaluation 27 score of 3 had a 2.35-fold increased risk of death (95% confidence interval, 1.73-3.21) compared with patients with an Adult Comorbidity Evaluation 27 score of 0. Similarly, patients with an Adult Comorbidity Evaluation 27 score of 2 had a 38% higher risk of recurrence (95% confidence interval, 1.07-1.78); patients with Adult Comorbidity Evaluation 27 score of 3 had a 2.05-fold increased risk of recurrence (95% confidence interval, 1.53-2.75) compared with patients with an Adult Comorbidity Evaluation 27 score of 0. We found no interaction between Adult Comorbidity Evaluation 27 score and age, stage, or treatment type. CONCLUSION: Our findings demonstrate the importance of comorbidities in the estimation of the prognosis of patients with endometrial cancer, even after adjustment for age and known tumor-specific prognostic factors such as stage, grade, histologic condition, and adjuvant treatment.

A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.

PURPOSE: Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer. PATIENTS AND METHODS: Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤2 (≤1 if two prior cytotoxic regimens given). Cediranib 30mg orally daily for a 28daycycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]). RESULTS: Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD. CONCLUSION: Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity.

Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins.

Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The propensity for metastasis within the peritoneal cavity is a driving factor for the poor outcomes associated with this disease, but there is currently no effective therapy targeting metastasis. In this study, we investigate the contribution of stromal cells to ovarian cancer metastasis and identify normal stromal cell expression of the collagen receptor, discoidin domain receptor 2 (DDR2), that acts to facilitate ovarian cancer metastasis. In vivo, global genetic inactivation of Ddr2 impairs the ability of Ddr2-expressing syngeneic ovarian cancer cells to spread throughout the peritoneal cavity. Specifically, DDR2 expression in mesothelial cells lining the peritoneal cavity facilitates tumor cell attachment and clearance. Subsequently, omentum fibroblast expression of DDR2 promotes tumor cell invasion. Mechanistically, we find DDR2-expressing fibroblasts are more energetically active, such that DDR2 regulates glycolysis through AKT/SNAI1 leading to suppressed fructose-1,6-bisphosphatase and increased hexokinase activity, a key glycolytic enzyme. Upon inhibition of DDR2, we find decreased protein synthesis and secretion. Consequently, when DDR2 is inhibited, there is reduction in secreted extracellular matrix proteins important for metastasis. Specifically, we find that fibroblast DDR2 inhibition leads to decreased secretion of the collagen crosslinker, LOXL2. Adding back LOXL2 to DDR2 deficient fibroblasts rescues the ability of tumor cells to invade. Overall, our results suggest that stromal cell expression of DDR2 is an important mediator of ovarian cancer metastasis. IMPLICATIONS: DDR2 is highly expressed by stromal cells in ovarian cancer that can mediate metastasis and is a potential therapeutic target in ovarian cancer.

Genetic characterization of primary and metastatic high-grade serous ovarian cancer tumors reveals distinct features associated with survival.

High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS) < 3.5 years) and 16 were long-term (LT) survivors (OS > 5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene expression, immune cell infiltration, and gene fusion predictions between the primary and metastatic tumors and between ST and LT survivor cohorts. There were few differences in RNA expression between paired primary and metastatic tumors, but significant differences between the transcriptomes of LT and ST survivors in both their primary and metastatic tumors. These findings will improve the understanding of the genetic variation in HGSC that exist between patients with different prognoses and better inform treatments by identifying new targets for drug development.

RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer.

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status. CONCLUSIONS: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.

A phase II trial of radiation therapy and weekly cisplatin chemotherapy for the treatment of locally-advanced squamous cell carcinoma of the vulva: a gynecologic oncology group study.

OBJECTIVES: To determine the efficacy and toxicity of radiation therapy and concurrent weekly cisplatin chemotherapy in achieving a complete clinical and pathologic response when used for the primary treatment of locally-advanced vulvar carcinoma. METHODS: Patients with locally-advanced (T3 or T4 tumors not amenable to surgical resection via radical vulvectomy), previously untreated squamous cell carcinoma of the vulva were treated with radiation (1.8 Gy daily × 32 fractions=57.6 Gy) plus weekly cisplatin (40 mg/m(2)) followed by surgical resection of residual tumor (or biopsy to confirm complete clinical response). Management of the groin lymph nodes was standardized and was not a statistical endpoint. Primary endpoints were complete clinical and pathologic response rates of the primary vulvar tumor. RESULTS: A planned interim analysis indicated sufficient activity to reopen the study to a second stage of accrual. Among 58 evaluable patients, there were 40 (69%) who completed study treatment. Reasons for prematurely discontinuing treatment included: patient refusal (N=4), toxicity (N=9), death (N=2), other (N=3). There were 37 patients with a complete clinical response (37/58; 64%). Among these women there were 34 who underwent surgical biopsy and 29 (78%) who also had a complete pathological response. Common adverse effects included leukopenia, pain, radiation dermatitis, pain, or metabolic changes. CONCLUSIONS: This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with acceptable toxicity.

Impact of the COVID-19 pandemic on referral to and delivery of gynecologic oncology care.

OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on referral to and delivery of gynecologic oncology care at a National Cancer Institute-designated Comprehensive Cancer Center. METHODS: We conducted a retrospective cohort study of patients referred for evaluation by a gynecologic oncologist at Washington University in St. Louis from October 2019 - February 2020 (pre-COVID-19), and April - August 2020 (COVID-19). The primary outcome, time from referral to evaluation by a gynecologic oncologist, was compared between the two time periods. Secondary outcomes included time from initial evaluation to treatment and delays/interruptions in care due to the pandemic. Sub-group analyses were performed on patients with a cancer diagnosis to evaluate the impact of COVID-19 on treatment decision making. RESULTS: 884 patients were referred during the study period. Total referrals fell by 32% (526 to 358 patients, p < 0.001) and referrals for cancer fell by 18% (228 to 188 patients, p = 0.049). The pandemic did not impact time from referral to initial gynecologic oncology appointment overall (pre-COVID-19: 19.1 vs. COVID-19: 17.4 days, p = 0.315) or among patients with cancer (14.4 vs. 13.9 days, p = 0.662). Time from initial appointment to cancer treatment decreased by 9 days (34 days to 25 days, p = 0.001). CONCLUSION: Referrals to gynecologic oncology decreased significantly during the early months of COVID-19. Though time from referral to evaluation was not impacted by the pandemic, time to treatment initiation decreased despite institutional changes related to COVID-19.

Gynecologic oncology patient perspectives and knowledge on advance care planning: A quality improvement intervention.

Objectives: Assess and improve advance care planning (ACP) awareness and uptake among gynecologic oncology patients. Methods: Using a quality improvement Plan-Do-Check-Act framework, we completed a single institution needs assessment and intervention. The needs assessment was a 26-question survey assessing baseline ACP knowledge and preferences of gynecologic oncology patients. We used this survey to implement an outpatient intervention in which patients were offered ACP resources (pamphlet, discussion with their gynecologic oncologist, and/or social work referral). We conducted a post-intervention survey among patients who had and had not received ACP resource(s) to assess whether our intervention increased ACP knowledge, discussions, or uptake. Results: Among 106 patients surveyed in the needs assessment, 33 % had ACP documents, 26 % had discussed ACP with a physician, and 82 % thought discussing ACP was important. The majority preferred these conversations in the outpatient setting (52 %) with their gynecologic oncologist (80 %) instead of nurses or trainees. In the intervention, 526 patients were offered ACP resources. Compared to women who did not receive resources (n = 324), patients who received ACP resource(s) (n = 202) were more likely to have ACP discussions with their gynecologic oncologist (38 % vs 68 %, P = 0.001) and had greater proficiency regarding how to create ACP documents (median score 5/10 vs 8/10, P = 0.048), although they were no more likely to have ACP documented in their electronic medical record (27 % vs 9 %, p = 0.08). Conclusions: ACP uptake among gynecologic oncology patients is low, but ACP discussions with an oncologist during outpatient visits are important to patients and improve their knowledge regarding completing ACP documents.

Quantification of ovarian lesion and fallopian tube vasculature using optical-resolution photoacoustic microscopy.

The heterogeneity in the pathological and clinical manifestations of ovarian cancer is a major hurdle impeding early and accurate diagnosis. A host of imaging modalities, including Doppler ultrasound, MRI, and CT, have been investigated to improve the assessment of ovarian lesions. We hypothesized that pathologic conditions might affect the ovarian vasculature and that these changes might be detectable by optical-resolution photoacoustic microscopy (OR-PAM). In our previous work, we developed a benchtop OR-PAM and demonstrated it on a limited set of ovarian and fallopian tube specimens. In this study, we collected data from over 50 patients, supporting a more robust statistical analysis. We then developed an efficient custom analysis pipeline for characterizing the vascular features of the samples, including the mean vessel diameter, vascular density, global vascular directionality, local vascular definition, and local vascular tortuosity/branchedness. Phantom studies using carbon fibers showed that our algorithm was accurate within an acceptable error range. Between normal ovaries and normal fallopian tubes, we observed significant differences in five of six extracted vascular features. Further, we showed that distinct subsets of vascular features could distinguish normal ovaries from cystic, fibrous, and malignant ovarian lesions. In addition, a statistically significant difference was found in the mean vascular tortuosity/branchedness values of normal and abnormal tubes. The findings support the proposition that OR-PAM can help distinguish the severity of tubal and ovarian pathologies.

Community access to primary care is an important geographic disparity among ovarian cancer patients undergoing cytoreductive surgery.

Objective: Given the importance of understanding neighborhood context and geographic access to care on individual health outcomes, we sought to investigate the association of community primary care (PC) access on postoperative outcomes and survival in ovarian cancer patients. Methods: This was a retrospective cohort study of Stage III-IV ovarian cancer patients who underwent surgery at a single academic, tertiary care hospital between 2012 and 2015. PC access was determined using a Health Resources and Services Administration designation. Outcomes included 30-day surgical and medical complications, extended hospital stay, ICU admission, hospital readmission, progression-free and overall survival. Descriptive statistics and chi-squared analyses were used to analyze differences between patients from PC-shortage vs not PC-shortage areas. Results: Among 217 ovarian cancer patients, 54.4 % lived in PC-shortage areas. They were more likely to have Medicaid or no insurance and live in rural areas with higher poverty rates, significantly further from the treating cancer center and its affiliated hospital. Nevertheless, 49.2 % of patients from PC-shortage areas lived in urban communities. Residing in a PC-shortage area was not associated with increased surgical or medical complications, ICU admission, or hospital readmission, but was linked to more frequent prolonged hospitalization (26.3 % vs 14.1 %, p = 0.04). PC-shortage did not impact progression-free or overall survival. Conclusions: Patients from PC-shortage areas may require longer inpatient perioperative care in order to achieve the same 30-day postoperative outcomes as patients who live in non-PC shortage areas. Community access to PC is a critical factor to better understanding and reducing disparities among ovarian cancer patients.