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The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia.Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n = 126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors.The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR = 2.22, 95% CI 1.26-3.92), while later age at menarche was associated with decreased EC risk (HR = 0.14, 95% CI 0.04-0.46). In postmenopausal women, later age at menopause was associated with increased EC risk (HR = 2.82, 95% CI 1.24-6.43). Lifestyle and nutritional factors were not associated with risk of EC in this cohort.This study is one of the largest cohort studies exploring EC risk factors in Asian populations. Our study identified similarities in EC risk factors for European and Asian populations, which potentially suggests that strategies developed for EC prevention in Western populations can be potentially appropriate for the Singapore Chinese population due to risk factor similarities.

Evaluate the association between metformin and survival in women with Type 2 diabetes (T2DM) and breast, endometrial and ovarian cancer- 3 hormonally mediated cancers.We evaluated outcomes in a cohort of 6225 women with T2DM with a new diagnosis of ovarian, breast or endometrial cancer from 2010 to 2019. We classified glycemic medications at time of first cancer diagnosis into 3 tiers in accordance with ADA guidelines. Approaches compared: (i) metformin (tier 1) vs. no glycemic medication, (ii) metformin vs tier 2 medications (sulfonylureas, thiazolidinediones, SGLT2-inhibitors, DPP4-inhibitors, alpha glucosidase-inhibitors, GLP-1 agonists), (iii) metformin vs tier 3 medications (insulins, amylinomimetics), and (iv) tier 2 vs tier 3 medications. Analyses included Cox proportional-hazards models, Kaplan-Meier curves, and conditional logistic regression in a risk set-sampled nested case-control matched on T2DM duration- all modeling survival. Models were adjusted for demographics, cancer type, A1C, T2DM duration, and number of office visits and hospitalizations.Metformin was the most used medication (n = 3232) and consistently demonstrated survival benefit compared with tier 2 and 3 medications, across all methods. Tier 3-users demonstrated highest risk of death when compared to metformin rather than tier 2 [adjHR = 1.83 (95% CI: 1.58, 2.13) vs. adjHR = 1.32 (95% CI: 1.11, 1.57)], despite similar baseline profiles between tier 1 and 2 users.Metformin users experienced increased survival even after accounting for surrogates of diabetes progression. Benefit extended beyond that seen in tier 2-users. Our findings, consistent with prior studies, indicate metformin use improves survival in women with T2DM and hormonally mediated women's cancers.

There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy.Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes2 cm.Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes2 cm and by radiation dose (75% for55 Gy, 98% for 55 Gy in 25 fractions and 89% for55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%).This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.

Objectives A pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. Methods A retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). Results In total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), with a similar trend in the PORTEC-1 cohort. Extent of LVSI correlated with disease burden in LN metastases. Conclusion Our incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement. This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings.

Background Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives included evaluation of efficacy and safety. Methods In this open-label, single-institution, phase II trial, patients received everolimus 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days on a 28-day cycle. Treatment continued until disease progression or adverse event. Results Fifty patients were enrolled. Median age was 60.5 years (range 28–82). Forty-six (92%) subjects had measurable disease. Thirteen (26%) (24% adjusted) were progression-free at 6 months (95% CI 16.67–42.71%). One patient had a complete response, while six had a partial response and 35 had stable disease as their best response. Patients with both platinum-sensitive and -resistant disease demonstrated responses, as did some prior bevacizumab exposure. There were two grade 4 and 31 grade 3 toxicities noted in 25 distinct patients. The most common reported toxicities included oral mucositis, fatigue, diarrhea, hypertension, pain, nausea and anorexia. Thirty-eight (76%) patients came off study because of disease progression. Unique molecular profiles were identified in long-term responders. Conclusions Combining everolimus and bevacizumab does not distinctly improve response compared to bevacizumab alone, but further study of selected patients with alterations in the PI3K/mTOR pathway may document benefit.

Sentinel lymph node (SLN) mapping is a highly accurate surgical technique for detecting metastases in endometrial cancer. The objective of this study was to identify clinical factors associated with failed mapping.All patients with endometrial cancer undergoing minimally-invasive staging and planned SLN biopsy from 1/1/2017 to 12/31/2020 at a single institution were identified retrospectively. Demographic, clinicopathologic and treatment data were obtained. Data were compared using descriptive statistics. Univariate and multivariable logistic regression were performed to identify predictors of failed mapping.819 patients were identified with a mean age of 64.6 years (range 26-93) and mean BMI of 35.6 kg/mSLN mapping has a high success in patients undergoing minimally-invasive surgical staging for endometrial cancer. Increasing BMI, high risk histology, and lymph node metastases are risk factors for failed mapping.

Purpose The role of neoadjuvant chemoradiation therapy in locally advanced type II endometrial cancer is controversial. We thus aimed to present our experience with the hypothesis that neoadjuvant chemoradiation therapy is associated with similarly high rates of downstaging and locoregional control for type II endometrial cancer and type I endometrial cancer. Methods and Materials Thirty-four patients with type II endometrial cancer with clinical evidence of cervical ± parametrium involvement treated with neoadjuvant external beam radiation therapy (45-50.4 Gy in 25-28 fractions) and high-dose-rate brachytherapy with a median total dose of 20 Gy (range, 15-27.5) in 4 fractions (range, 3-5) and concurrent platinum chemotherapy ± adjuvant chemotherapy from 2008 to 2018 were retrospectively reviewed. Patients with type I pathologic diagnoses and those treated with definitive (rather than preoperative) intent were excluded. Results Pathologic characteristics were as follows: 38% were carcinosarcoma, 18% serous, and 24% clear cell. Ninety-four percent of patients were downstaged to an extrafascial hysterectomy, and 94% had negative surgical margins. The 2-year local control, regional control, distant control, disease-free survival, and overall survival were 87.8%, 81.3%, 76.3%, 52.5%, and 63.7%, respectively. There was 1 subacute grade 3 and 1 late grade 3 small bowel obstruction, directly attributable to radiation therapy. Conclusions Neoadjuvant chemoradiation therapy effectively downstages the majority of locally advanced type II endometrial cancers, thereby increasing the likelihood of achieving complete resection with negative margins.

Purpose Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus has been implicated as a causative factor for a subset of these patients. The purpose of this study was to evaluate whether p16-positivity (a human papillomavirus surrogate) predicts for better response rates in women who undergo surgery followed by adjuvant radiation therapy (RT). Methods and Materials We retrospectively analyzed data from women with VSCC who were treated with adjuvant RT. p16-Positivity was defined as diffuse strong immunoreactivity within the tumor. Time to event outcomes was performed with Kaplan-Meier and cumulative incidence methodologies. Results Thirty-nine women were identified. Ten had positive results for p16 (p16+), and 29 had negative results (p16−). The median follow-up was 25.7 months. The median age at diagnosis was 59 years for women with p16+ tumors and 74 years for women with p16− tumors (P = .022). The distribution of stage did not differ by p16 status. The indications for adjuvant RT were close/positive margins in 19 women, positive nodes in 9 women, and both in 11 women. There were 21 recurrences: 15 vulvar, 3 isolated nodal, 2 synchronous vulvar/nodal, and 1 distant metastasis. In-field relapse rates at 3 years were lower in p16+ patients (32.5%) than in p16− patients (59.1%, P = .072). This trend was also observed in progression-free survival (P = .062). A p16+ status and a lower International Federation of Gynecology and Obstetrics stage were associated with fewer in-field relapses and improved progression-free survival in multivariable analyses. The p16 status was not a predictor of overall survival. Conclusions p16-Positivity appears to be a prognostic factor for in-field relapse rates in patients with VSCC appropriately treated with adjuvant RT.

PURPOSE. Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC. METHODS AND MATERIALS. Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70–80 Gy. RESULTS. The median high-risk clinical target volume was 24.4 cm(3) (interquartile range [IQR], 14.1), with a median dose to 90% of 77.2 Gy (IQR, 2.8). After a median follow-up of 45 months (range, 11–78), the 4-year local-regional control, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p = 0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%. CONCLUSIONS. Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.

Purpose Vaginal brachytherapy (VBT) alone has been shown to be a viable adjuvant treatment strategy for most patients with Stage I endometrioid endometrial cancer. We sought to examine our institutional data following practice pattern changes resulting from the publications of GOG-99 and PORTEC-2. Methods and Materials We retrospectively analyzed women who underwent adjuvant VBT after surgical staging for Stage 1 endometrioid endometrial cancer at our institution from 2007 to 2014. Results We identified 297 women. Median time to last followup or death was 52.3 months (interquartile range: 32.3–72.3 months). By International Federation of Gynecology and Obstetrics 2009 staging, 162 patients (54.5%) had Stage IA and 128 (43.1%) had Stage IB disease. Ninety-nine (33.3%) patients had Grade 1, 153 (51.5%) had Grade 2, and 45 (15.2%) had Grade 3 disease. According to GOG-249 and PORTEC-2 criteria, 167 (56.2%) and 127 (42.7%) patients were with high–intermediate–risk disease. Two women had Stage IB Grade 3 disease. The most common high-dose-rate–VBT regimen was 2100 cGy/three fractions to a depth of 5 mm. Four (two acute and two late) (1.3%) Grade 3 genitourinary toxicities were reported: three episodes of vaginal dehiscence (after second course of VBT, 2 months after completion of VBT, and 1 year after completion of VBT) and one episode of radiation necrosis. Twenty-one (7%) women recurred: three recurred in the vagina, two recurred in the pelvic lymph nodes, and 16 recurred distantly. Conclusions Outcomes appear consistent with published randomized data in women with high–intermediate–risk endometrial cancer who are treated with brachytherapy alone. Recurrence and complication rates were minimal.

Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P

Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) arise from common progenitors. Tumor-derived factors redirect differentiation from immune-promoting DCs to tolerogenic MDSCs, an immunological hallmark of cancer. Indeed, in vitro differentiation of DCs from human primary monocytes results in the generation of MDSCs under tumor-associated conditions (PGE2 or tumor cell-conditioned media). Comparison of MDSC and DC DNA methylomes now reveals extensive demethylation with specific gains of DNA methylation and repression of immunogenic-associated genes occurring in MDSCs specifically, concomitant with increased DNA methyltransferase 3A (DNMT3A) levels. DNMT3A downregulation erases MDSC-specific hypermethylation, and it abolishes their immunosuppressive capacity. Primary MDSCs isolated from ovarian cancer patients display a similar hypermethylation signature in connection with PGE2-dependent DNMT3A overexpression. Our study links PGE2- and DNMT3A-dependent hypermethylation with immunosuppressive MDSC functions, providing a promising target for therapeutic intervention., This work was supported by grants SAF2014-55942-R and PI16/00132 from Instituto de Salud Carlos III, organisms ascribed to the Ministerio de Economía y Competitividad and cofunded by FEDER funds/European Regional Development Fund (ERDF) - a way to build Europe. The study was also supported by NCI/NIH/HHS (United States) grant P50 CA159981 (RPCI-UPCI Ovarian Cancer SPORE) (to N.O., R.P.E., and P.K.).

Objective Obesity has been strongly linked to endometrial cancer (EC) risk. A number of potential EC risk biomarkers have been proposed, including heightened pro-inflammatory cytokines and adipokines. To evaluate if bariatric surgery can serve as a means for altering levels of such EC risk biomarkers, we investigated changes in these biomarkers after weight loss. Methods Blood samples were collected pre-operatively and 6months post-operatively in 107 female bariatric surgery patients aged 18–72years. Wilcoxon signed-rank tests were used to compare biomarker levels (measured using xMAP immunoassays) pre- and post-surgery. Normative comparisons were implemented to contrast 6-month post-surgery biomarker levels to levels in a sample of 74 age-matched non-obese women. Linear regression was used to evaluate the relationship between biomarker expression at baseline and 6months post-surgery and the relationship between race and biomarker levels. Results On average, participants lost 30.15kg (SD: 12.26) after the bariatric intervention. Levels of C-peptide, insulin, CRP, leptin, IL-1Rα, and IL-6 significantly decreased, while levels of SHBG, IGFBP1, and adiponectin significantly increased with weight loss. Normative comparisons showed the levels of SHBG, C-peptide, insulin, IGFBP1, adiponectin, CRP, and TNFα after bariatric intervention approached the level of markers in comparison group. Multiple regression analyses revealed significant relationships between changes in BMI and changes in biomarker levels. The changes in IL-1Rα were significantly associated with race. Conclusions Our findings demonstrate that normalization of EC risk biomarkers can be achieved with bariatric surgery. Improved understanding of biological mechanisms associated with weight loss may inform preventive strategies for EC.

Objectives Ovarian cancer leads to abdominal carcinomatosis and late stage (III/IV) diagnosis in 75% of patients. Three randomized phase III trials have demonstrated that intraperitoneal (IP) chemotherapy improves outcomes in epithelial ovarian cancer. While IP treatment is validated by clinical trials, there is a poor understanding of the mechanism(s) leading to the survival advantage other than the increased concentration of cytotoxic drugs within the tumor microenvironment. A better understanding of this process through analysis of dynamic biomarkers should promote novel approaches that may enhance tumor clearance. We propose this pilot study to confirm the feasibility of collecting serial peritoneal samples from implanted catheters in women receiving IP chemotherapy. We believe these specimens may be used for multiplex analysis to reveal unique biomarker fluctuations when compared to peripheral blood. Methods From 13 women participating on GOG 252, 30 whole blood, 12 peritoneal fluid (PF), and 20 peritoneal wash (PW) with 30mL saline were obtained. Samples were requested prior to the first three chemotherapy cycles. Samples were assessed for volume, cell populations, protein, RNA, and miRNA content changes. Results Median volume for PF was 1.6mL and 3.1mL for PW. PW is a dilution of PF capable of capturing measurable biomarkers. Peritoneal aspirates contain a unique profile of biomarkers distinct from blood. miRNA undergo earlier alteration with chemotherapy than genes. Flow cytometry does not adequately capture biomarker fluctuations. Conclusions As a proof of principle study, this trial provides evidence that sampling the peritoneal cavity can be adapted for biomarker analysis.

Obesity is the main risk factor for endometrial cancer (EC), the most common gynecologic malignancy in the United States. A number of potential risk biomarkers have been associated with EC development, including altered proinflammatory cytokines, chemokines, and adipokines.The overarching aim of this research is to investigate racial differences in the expression of EC-associated biomarkers among bariatric surgery candidates.Tertiary academic medical center METHODS: Blood samples were collected from 175 women aged 18 to 72 (mean age: 42.93; standard deviation 11.66), before bariatric surgery. Levels of biomarkers associated with obesity and EC risk were measured using xMAP immunoassays. Wilcoxon rank sum and Fisher's exact tests were utilized to compare biomarker and demographic variables between African American and European American women. Linear regression models, adjusted for menopause status and diabetes, were utilized to identify factors associated with biomarker levels.When the biomarker levels were compared by race, insulin-like growth factor-binding protein 1 and adiponectin were significantly lower in African American women (P.05), whereas estradiol was significantly higher in African American women (P.05). Linear regression models found that race significantly predicted insulin-like growth factor binding protein 1, adiponectin, resistin, and interleukin-1 receptor alpha expression levels, menopause status and diabetes status were significantly associated with adiponectin and leptin levels, whereas body mass index was significantly associated with leptin, adiponectin, interleukin-1 receptor alpha, and interleukin-6 levels.As one of the first efforts to explore racial differences in EC-associated biomarkers in a cohort of women with severe obesity, this study found several significant differences that should be further explored in large-scale studies.

Objective To explore risk factors associated with sampling failure in women who underwent Pipelle biopsy. Methods A consecutive sample of 201 patient records was selected from women who underwent Pipelle biopsy procedures for suspected uterine pathology in a large healthcare system over a 6-month period (January 2013 through June 2013). Personal and medical data including age, BMI, gravidity and parity, and previous history of Pipelle biopsy were abstracted from medical records for each patient. Logistic regression analyses were used to determine factors associated with biopsy sampling failure. Results Pipelle biopsy sampling failed in 46 out 201 women (22.89%), where 8 (17.39%) were due to inability to access the endometrium, 37 (80.43%) were inadequate samples, and 1 (2.18%) was due to unknown reasons. Personal and medical factors found to be related to sampling failure included: postmenopausal bleeding as biopsy indication (OR 7.41, 95% CI 2.27–24.14); history of prior biopsy failure (OR 23.87, 95% CI 3.76–151.61); and provider type (physician vs. midlevel provider) (OR 9.152, 95% CI 2.49–33.69). Conclusion We identified several risk factors for biopsy failure that suggest the need for particular care with Pipelle sampling procedures among women with certain characteristics, including postmenopausal bleeding and a history of prior failed Pipelle biopsy. Our finding of a significantly higher risk of sampling failure based on personal and clinical data suggests that providers must take into account additional considerations to improve sampling success.

Purpose We evaluated the long-term outcome and toxicity of adjuvant intensity modulated radiation therapy (IMRT) for high-risk endometrial carcinoma via a retrospective institutional review of patients treated in this setting with extended follow-up. Methods and materials Patients with endometrial cancer who underwent comprehensive surgical staging followed by adjuvant IMRT with or without sequential chemotherapy between 1999 and 2010 were reviewed. Median doses delivered with IMRT and brachytherapy were 45 Gy in 25 fractions and 10 Gy in 2 fractions; 10.2% received extended field and 94.5% received vaginal brachytherapy. Kaplan-Meier estimates are provided for rates of locoregional (in-field) relapse, distant metastasis, and disease-free survival, and overall survival. Gastrointestinal (GI) and genitourinary (GU) toxicity reported were graded with the Common Terminology Criteria for Adverse Events, version 4.03. Results A total of 128 patients were identified. Median age at diagnosis was 64 years. Most patients (82.8%) had endometrioid adenocarcinoma followed by papillary serous (10.2%), clear cell (4.7%), and carcinosarcoma (2.3%). International Federation of Gynecology and Obstetrics staging distribution was as follows: IA, 13.3%; IB, 32.8%; II, 30.4%; IIIA, 5.5%; IIIC1, 9.4%; and IIIC2, 8.6%. Most (85.9%) underwent nodal dissections (28.1% pelvic only and 57.8% pelvic and para-aortic). Two patients (1.6%) experienced acute grade 3 GI toxicity; no other acute grade ≥3 GI/GU toxicities were noted. With a median follow-up of 57.0 months, 5-year locoregional relapse was 2.5%: vagina (n = 3), parametrium (n = 1), pelvic node (n = 1). Five-year estimates of distant metastasis, disease-free survival, and overall survival were 16.5%, 73.4%, and 77.4%, respectively. Five-year actuarial rates of late grade 3 GI and GU toxicities were 3.2% and 0.0%. The 5-year rate of symptomatic pelvic insufficiency fracture was 4.4%. Conclusions This study represents the largest cohort of endometrial cancer patients with extended follow-up receiving adjuvant IMRT. High rates of pelvic disease control and limited late toxicities demonstrate safety and efficacy of this approach in the setting of extended follow-up.

Institutions across the world have observed a decrease in the incidence of preterm births during the coronavirus disease 2019 pandemic. The reason for this reduction remains unknown.We sought to explore potential causes for the decrease in preterm births by exploring the following 3 hypotheses: (1) do women who are more likely to be able to work from home incur less physical/or emotional stress resulting in longer gestation? (2) Does the effect of the coronavirus disease 2019 pandemic on the incidence of preterm births vary by race? (3) Is this change provider driven?Using a retrospective cohort of all singleton deliveries at a single tertiary care center, we compared the deliveries for the period before the coronavirus disease 2019 pandemic (January 1, 2018-January 31, 2020) with those occurring during the pandemic (April 1, 2020-October 27, 2020). Comparisons between the period before and during the pandemic were made using Pearson chi-square or t tests as appropriate. The overall incidence of preterm birth, defined as delivery at37 weeks' gestation, was analyzed and then further classified into spontaneous or indicated preterm births. The population was then stratified by the following categories: (1) insurance type and neighborhood disadvantage; (2) race; and (3) provider type. The provider type was classified as delivery occurring within an outpatient care facility, a clinic that provides prenatal care to those eligible for medical assistance, or a nonoutpatient care facility.In a population of 17,687 pre-coronavirus disease 2019 deliveries, and 5396 deliveries occurring during the coronavirus disease 2019 pandemic, there was a significant decrease in the overall incidence of preterm births (11.1 vs 10.1%; P=.039). Both spontaneous and indicated preterm deliveries decreased across the entire population. When stratified, decreases in the incidence of spontaneous preterm birth before vs during the coronavirus disease 2019 pandemic were limited to deliveries to women from more advantaged neighborhoods (most advantaged, 4.4 vs 3.8%; least advantaged, 7.2 vs 7.4%), white mothers (white, 5.6 vs 4.7%; black, 6.6 vs 7.1%), and those receiving care from nonoutpatient care providers (nonoutpatient care providers, 5.5 vs 4.8%; outpatient care providers, 6.3 vs 6.7%).The incidence of preterm births has decreased during the coronavirus disease 2019 pandemic. Decreases in the rate of spontaneous preterm births were limited to deliveries to white women, living in more advantaged neighborhoods, and deliveries at nonoutpatient care facilities. The coronavirus disease 2019 response regulations may have benefited women with more indicators of advantage disproportionately more.

Objective We sought to compare symptoms identified as a priority by patients with recurrent ovarian cancer to symptoms most frequently documented by their clinicians, and examine the association between clinician documentation of symptoms and subsequent clinical intervention. Methods Single-institution, retrospective chart review of patients enrolled in WRITE Symptoms Study (GOG 259), a randomized controlled trial of internet-based recurrent ovarian cancer symptom management. As part of the trial, women completed the Symptom Representation Questionnaire for 28 symptoms and selected 3 priority symptoms (PS). We compared patient-reported PS to clinician documentation of symptoms and interventions over the time period corresponding to study enrollment. Results At least one PS was documented in 92% of patients. Of 150 PS reported by patients, 53% were never documented by clinicians; these symptoms tended to be less directly related to disease or treatment status. Symptoms not identified by patients as PS were frequently documented by clinicians; these symptoms tended to relate to physiologic effects of disease and treatment toxicity. 58% of patients had at least one PS intervention. PS intervened for were documented at 2.58 visits vs 0.50 visits for PS not receiving intervention ( p ≤0.0001). Conclusions Discordance was identified between symptoms reported by patients as important and symptoms documented by clinicians. Symptoms more frequently documented were also more frequently intervened for. Our study illustrates the need to improve identification of symptoms important to patients, and suggests that improving communication between patients and clinicians could increase intervention rates to enhance quality of life in women with recurrent ovarian cancer.

Objective The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian (OV), fallopian tube (FT) or peritoneal (PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL). Methods Patients received docetaxel 75mg/m 2 IV day (d) 1 and oxaliplatin escalating from 50mg/m 2 IP d2 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly. Results Thirteen patients were included. Median number of cycles was 6 (range 1–10). Ten patients had measureable disease. Best response was partial response (PR-2), stable disease (SD-7), and progressive disease (PD-1). Twenty-one Grades 3–4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75mg/m 2 IV and d2 oxaliplatin 50mg/m 2 IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50mg/m 2 , total unbound drug exposure (AUC) averaged 8 times larger and C max reached concentrations 50-fold greater in IP fluid compared to plasma. Conclusions Docetaxel 75mg/m 2 IV d1 and oxaliplatin 50mg/m 2 IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration.

Background Endometrial pathology risk has been linked to obesity; however, little is known of its prevalence in severely obese women not seeking care for endometrial pathology associated symptoms. This pilot study was designed to explore the frequency and risk factors associated with endometrial pathology in cancer-free, severely obese, bariatric surgery candidates using the Pipelle endometrial sampling technique (SureFlex Preferred Curette, Bioteque America, Inc, New Taipei City, Taiwan). Methods Twenty-nine severely obese bariatric surgery candidates with intact uteruses and no history of endometrial cancer or endometrial ablation were included in this subanalysis from a larger cohort of 47. Endometrial samples were obtained using a Pipelle endometrial suction curette at a single time point before surgery. Logistic regression was used to assess the relationship between body mass index and endometrial pathology when adjusting for age and race. Results Of the 29 successful biopsies, 8 (27.6%) were classified as abnormal endometrium: 1 was classified as complex atypical hyperplasia, 1 was classified as hyperplasia without atypia, 4 samples were identified with endometrial polyps, and 2 samples were identified with metaplasia. None presented with cancer. Increasing body mass index was significantly associated with higher risk of abnormal endometrium (OR = 1.19, 95% CI [1.03–1.36], P = .01). Conclusions The findings in this sample suggest that obesity may be associated with increased risk of having undiagnosed endometrial pathology. More thorough examination of relationships between levels of obesity and endometrial pathology are needed to better characterize high cancer risk groups who may benefit from introducing new screening measures.

Purpose To investigate the clinical feasibility and treatment outcomes of image-based high-dose-rate (HDR) brachytherapy using an intracavitary multichannel vaginal cylinder for the definitive treatment of vaginal cancers. Methods and Materials A total of 41 patients with vaginal cancer (24% primary vaginal and 76% recurrence from other gynecologic primaries) treated with definitive radiotherapy ± chemotherapy including image-based HDR brachytherapy with a multichannel vaginal cylinder were included in the study. Image-based brachytherapy was completed using either CT- (41%) or MR-based planning (59%) with each fraction. The high-risk clinical target volume was defined based on the pre- and postexternal beam radiotherapy gross tumor volume. Doses were converted to equivalent dose of 2 Gy per fraction. Endpoints examined were dose–volume parameters and early clinical outcomes. Results The median high-risk clinical target volume was 24.2 cc (interquartile range [IQR], 12.6), with a median dose to 90% ( D 90 ) of 77.1 Gy (IQR, 3.4). The median dose to 2 cc ( D 2 cc ) for the bladder, rectum, and sigmoid were 59.4 Gy (IQR, 5.6), 58.2 Gy (IQR, 4.1), and 52.3 Gy (IQR, 5.5), respectively. After a median followup of 16 months (range, 3–35), complete clinical response was documented in 98% of the patients. The 2-year local, regional, and distant control; and disease-free and overall survival were 93%, 100%, 81%, 78%, and 88%, respectively. The 2-year actuarial rate of late Grade 3 or higher toxicity was 4% overall with 0%, 0%, 0%, and 4% for vaginal, bladder, urethral, and gastrointestinal, respectively. Conclusions Image-based HDR brachytherapy using an intracavitary multichannel cylinder seems feasible in definitive vaginal cancer treatment. The described clinical implementation shows promising early clinical outcomes with high rates of local control and little toxicity, which should be validated with extended followup.

Purpose Positron emission tomography/computed tomography (PET/CT) is commonly used for nodal staging in locally advanced cervical cancer; however the false negative rate for para-aortic disease are 20% to 25% in PET-positive pelvic nodal disease. Unless surgically staged, pelvis-only treatment may undertreat para-aortic disease. We have treated patients with PET-positive nodes with extended field intensity modulated radiation therapy (IMRT) to address the para-aortic region prophylactically with concomitant boost to involved nodes. The purpose of this study was to assess regional control rates and recurrence patterns. Methods and Materials Sixty-one patients with cervical cancer (stage IBI-IVA) diagnosed from 2003 to 2012 with PET-avid pelvic nodes treated with extended field IMRT (45 Gy in 25 fractions with concomitant boost to involved nodes to a median of 55 Gy in 25 fractions) with concurrent cisplatin and brachytherapy were retrospectively analyzed. The nodal location was pelvis-only in 41 patients (67%) and pelvis + para-aortic in 20 patients (33%). There were a total of 179 nodes, with a median number of positive nodes of 2 (range, 1-16 nodes) per patient and a median nodal size of 1.8 cm (range, 0.7-4.5 cm). Response was assessed by PET/CT at 12 to 16 weeks. Results Complete clinical and imaging response at the first follow-up visit was seen in 77% of patients. At a mean follow-up time of 29 months (range, 3-116 months), 8 patients experienced recurrence. The sites of persistent/recurrent disease were as follows: cervix 10 (16.3%), regional nodes 3 (4.9%), and distant 14 (23%). The rate of para-aortic failure in patients with pelvic-only nodes was 2.5%. There were no significant differences in recurrence patterns by the number/location of nodes, largest node size, or maximum node standardized uptake value. The rate of late grade 3+ adverse events was 4%. Conclusions Extended field IMRT was well tolerated and resulted in low regional recurrence in node-positive cervical cancer. The dose of 55 Gy in 25 fractions was effective in eradicating disease in involved nodes, with acceptable late adverse events. Distant metastasis is the predominant mode of failure, and the OUTBACK trial may challenge the presented paradigms.

Purpose Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT). Methods and Materials Patients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1–2 cm of vagina. Equivalent 2 Gy doses (EQD 2 ) were calculated. Results Thirty-eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15-month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2–5 late toxicities were observed. Mean CTV D 90 EQD 2 for BT alone and combined therapy was 48.6 ± 5.6 and 72.4 ± 6.0 Gy, whereas mean GTV D 90 EQD 2 was 172.3 ± 59.6 and 138.0 ± 64.6 Gy. Conclusions Image-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery.

Purpose For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Materials and methods Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45–50.4Gy in 25–28 fractions) and image-based HDR brachytherapy (5–5.5Gy times 3–4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. Results All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0–153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. Conclusions Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5–5.5Gy times 3–4 fractions, for a cumulative EQD 2 of 60–70Gy, is well tolerated with high rates of clinical and pathological response.

Obesity increases risk for endometrial neoplasia, but neither the pathophysiology nor the effects of weight loss on the risk are well established. We attempted to characterize the molecular profile of the endometrium of asymptomatic women with morbid obesity before and following bariatric surgery-induced weight loss.59 asymptomatic, morbidly obese women underwent endometrial sampling before bariatric surgery; 46 (78%) of these returned one year later for re-biopsy (median weight loss of 41kg). Duplicate samples from these specimens were scored for expression of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), and Ki-67 by two independent, blinded pathologists using an H-score [staining intensity (0-3)×(percent of tissue involved)].The prevalence of hyperplasia pre-operatively was 7% overall and 10% among patients not on an anti-estrogen. ER H-scores were similar before and after surgery overall (median 190 and 196 respectively, p=0.82), but patients with hyperplasia had higher pre-operative H-scores (median 256, p0.001) and experienced greater H-score drops, than those without hyperplasia (-112 vs +50, p=0.028). In two patients with persistent hyperplasia at one year, ER H-scores fell to levels that were similar to those without pathology. One patient who developed hyperplasia during the study period had a rising ER H-score. Patients with hyperplasia had higher median PR H-scores pre-operatively (284 vs 188, p=0.01), which normalized through greater drops (75 vs 0, p=0.053). AR H-scores dropped significantly after surgery (13 vs 2, p=0.015), but were similar between patients with and without hyperplasia (p=0.33). Weight loss did not affect Ki-67 proliferation index.Asymptomatic morbidly obese patients have a high prevalence of occult hyperplasia, characterized by relatively high hormone receptor expression. These profiles appear to normalize with weight loss and in advance of pathologically identifiable changes. These data suggest a potential role for screening this population as well as the possibility that weight loss may be a valid treatment strategy for risk reduction.

Objective Obesity has been linked to a wide spectrum of malignancies, with the strongest association demonstrated for endometrial cancer. Although the mechanisms are not yet entirely clear, a number of risk biomarkers have been proposed, including altered adipokines. Systemic levels of these adipose derived molecules have also been linked in prior research to self-reported quality of life (QOL). The study objective was to examine the hypothesis that adipokine changes during intentional weight loss may be associated with changes in QOL. Methods Fifty-two female participants were selected from two behavioral weight loss trials (SMART and PREFER) on the basis of achieving successful weight loss at 6month assessment, availability of blood samples and completion of standard SF-36 QOL questionnaires. Levels of adiponectin, leptin, and resistin were measured using xMAP immunoassays. Changes in QOL were examined using linear regression models in relation to pre- and post-intervention changes in biomarker levels and BMI. Results Significant changes between pre- and post-intervention were observed for leptin. Controlling for baseline BMI, leptin was the only biomarker that predicted change in QOL (Physical Component Scale, PCS). Linear regression models demonstrated that leptin continued to be a significant predictor of change in PCS when other possible predictor variables were included in the model. Conclusions This study is among the first to demonstrate that changes in PCS may be regulated by levels of both metabolic variables and adipokines. An improved understanding of biological mechanisms associated with weight loss and the role of QOL may help guide preventive strategies for obesity-associated cancers.

Context Little research has focused on symptom management among women with ovarian cancer. Written Representational Intervention To Ease Symptoms (WRITE Symptoms) is an educational intervention delivered through asynchronous web-based message boards between a study participant and a nurse. Objectives We evaluated WRITE Symptoms for 1) feasibility of conducting the study via message boards, 2) system usability, 3) participant satisfaction, and 4) initial efficacy. Methods Participants were 65 women (mean age, 56.5; SD = 9.23) with recurrent ovarian cancer randomized using minimization with race/ethnicity (non-Hispanic white vs. minority) as the stratification factor. Measures were obtained at baseline and two and six weeks after intervention. Outcomes were feasibility of conducting the study, system usability, participant satisfaction, and efficacy (symptom severity, distress, consequences, and controllability). Results Fifty-six (87.5%) participants were retained, and the mean usability score (range 1–7) was 6.18 (SD = 1.29). All satisfaction items were scored at 5 (of 7) or higher. There were significant between-group effects at T2 for symptom distress, with those in the WRITE Symptoms group reporting lower distress than those in the control group [t(88.4) = −2.57; P = 0.012], with a similar trend for symptom severity [t(40.4) = −1.95; P = 0.058]. Repeated measures analysis also supported a group effect, with those in the WRITE Symptoms group reporting lower symptom distress than those in the control condition [F(1, 56.7) = 4.59; P = 0.037]. Conclusion Participants found the intervention and assessment system easy to use and had high levels of satisfaction. Initial efficacy was supported by decreases in symptom severity and distress.

Objectives To review nursing science history within the Gynecology Oncology Group (GOG); to discuss challenges of nursing science in the cooperative group (CG) using a current nurse-led protocol (GOG-0259) as an exemplar; and to propose recommendations to advance nursing science in the CG setting. Data Sources Indexed citations and personal experience. Conclusion Benefits of CG research include opportunities for inter-disciplinary collaboration and ability to rapidly accrue large national samples. Challenges include limited resources to support non-treatment trials, a burdensome protocol approval process, and lack of experience with nursing/quality-of-life intervention studies. Formal GOG structures need to evolve to encourage nurse scientists to become active members; promote collaboration between experienced GOG advanced practice nurses and nurse scientists to identify nursing research priorities; and consider new funding sources to support pilot intervention studies. Implications for Nursing Practice Understanding the CG research process is critical for nurse scientists. A multi-disciplinary team of CG leaders can help investigators navigate a complex research environment and increase awareness of the value of nursing research.

Objective Use of in vitro chemoresponse assays for informing effective treatment selection is a compelling clinical question and a topic of debate among oncologists. A prospective study was conducted evaluating the use of a chemoresponse assay in recurrent ovarian cancer patients. Methods Women with persistent or recurrent ovarian cancer were enrolled under an IRB-approved protocol, and fresh tissue samples were collected for chemoresponse testing. Patients were treated with one of 15 protocol-designated treatments empirically selected by the oncologist, blinded to the assay results. Each treatment was classified by the assay as: sensitive (S), intermediate (I), or resistant (R). Patients were prospectively monitored for progression-free survival (PFS) and overall survival (OS). Associations of assay response for the physician-selected treatment with PFS and OS were analyzed. Results A total of 262 evaluable patients were enrolled. Patients treated with an assay-sensitive regimen demonstrated significantly improved PFS and OS while there was no difference in clinical outcomes between I and R groups. Median PFS was 8.8months for S vs. 5.9months for I+R (hazard ratio [HR]=0.67, p=0.009). The association with assay response was consistent in both platinum-sensitive and platinum-resistant tumors (HR: 0.71 vs. 0.66) and was independent of other covariates in multivariate analysis (HR=0.66, p=0.020). A statistically significant14-month improvement in mean OS (37.5months for S vs. 23.9months for I+R, HR=0.61, p=0.010) was demonstrated. Conclusions This prospective study demonstrated improved PFS and OS for patients with either platinum-sensitive or platinum-resistant recurrent ovarian cancer treated with assay-sensitive agents.

The purpose of this study was to determine the patterns of failure in patients diagnosed with cervical cancer treated with definitive radiotherapy and who subsequently had complete metabolic response (CMR) seen on early post-therapy (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Additionally, we sought to determine what factors predict disease recurrence in this patient population.We reviewed the records of 155 patients diagnosed with cervical cancer from stages IB1 to IVA who were treated with definitive chemoradiation therapy between 2003 and 2011 and had a FDG-PET at 10-16 weeks following completion of therapy. One hundred and twelve (72.0%) had CMR on follow-up FDG-PET and comprised the patients in this study.The median age of patients with CMR was 51 years and the median tumor size 4.9 cm. Median follow up was 15 months. Of the 112 patients, 11 (9.8%) had a recurrence and six (5.4%) had isolated local recurrences, and five (4.5%) had distant recurrence. Median time to recurrence was 9 months. Three-year actuarial disease-free survival and overall survival rates were 78.9% and 88.0% respectively. On Cox regression multivariate analysis, tumor size was predictive of increased risk of local recurrence in these patients with CMR with p0.025. Age, stage, histology and nodal positivity were not significant for predicting local, distant or any recurrence.Patients treated with concurrent chemoradiation had a CMR which demonstrated good clinical outcomes in terms of local control. There were equal numbers of patients suffering local and distant recurrences. In patients with a CMR, only tumor size was an independent predictor for local recurrence.