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The treatment of cancer during pregnancy presents a unique challenge. Optimal treatments are often altered or even delayed to protect fetal growth and organogenesis. The landscape of cancer treatment has shifted dramatically over the past several years and treatment with checkpoint inhibitors, including anti-PD1 and anti-CTLA-4 agents has revolutionized treatment outcomes for patients across numerous tumor types. Until recently, little is known about the use of checkpoint inhibitor therapy during pregnancy; however, in animal studies, exposure to checkpoint inhibitors at the time of or after conception led to high incidences of spontaneous abortion, stillbirth, and premature delivery. In this report, we describe the successful pregnancy and clinical course of a patient diagnosed with metastatic melanoma who conceived twins while undergoing dual checkpoint blockade with ipilumumab and nivolumab. While there are case reports of patients receiving checkpoint inhibitors during pregnancy, our case is the first to describe a successful pregnancy that was conceived during treatment with combination anti-CTLA-4 and PD-1, with therapy continuing throughout pregnancy. This case adds to the growing evidence that favorable pregnancy outcomes may be possible while receiving checkpoint inhibition, which will hopefully allow for more optimal treatment of young pregnant patients with cancer.

CD8 + tumor-infiltrating lymphocytes (TILs) are not all specific for tumor antigens, but can include bystander TILs that are specific for cancer-irrelevant epitopes, and it is unknown whether the T-cell repertoire affects prognosis. To delineate the complexity of anti-tumor T-cell responses, we utilized a computational method for de novo assembly of sequences from CDR3 regions of 369 high-grade serous ovarian cancers from TCGA, and then applied deep TCR-sequencing for analyses of paired tumor and peripheral blood specimens from an independent cohort of 99 ovarian cancer patients. Strongly monoclonal T-cell repertoires were associated with favorable prognosis (PFS, HR = 0.65, 0.50-0.84, p = 0.003; OS, HR = 0.61, 0.44-0.83, p = 0.006) in TCGA cohort. In the validation cohort, we discovered that patients with low T-cell infiltration but low diversity or focused repertoires had clinical outcomes almost indistinguishable from highly-infiltrated tumors (median 21.0 months versus 15.9 months, log-rank p = 0.945). We also found that the degree of divergence of the peripheral repertoire from the TIL repertoire, and the presence of detectable spontaneous anti-tumor immune responses are important determinants of clinical outcome. We conclude that the prognostic significance of TILs in ovarian cancer is dictated by T-cell clonality, degree of overlap with peripheral repertoire, and the presence of detectable spontaneous anti-tumor immune response in the patients. These immunological phenotypes defined by the TCR repertoire may provide useful insights for identifying "TIL-low" ovarian cancer patients that may respond to immunotherapy., Competing Interests: CONFLICTS OF INTEREST HR has consultancy, patents & royalties, and equity ownership with Adaptive Biotechnologies. ROE has employment and equity ownership with Adaptive Biotechnologies. CDM holds restricted stock in OmniSeq. KO is a co-founder of Tactiva Therapeutics and receives research support from AstraZeneca and Tesaro. The other authors have declared that no conflict of interest exists.

Purpose: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated., Methods: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (n = 7,022). Using age- and stage-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors., Results: Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR = 1.37; 95% CI 1.10-1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR = 1.28; 95% CI 1.08-1.52, and HR = 1.26; 95% CI 1.04-1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS., Conclusions: Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients' survival.

Objectives: The purpose of this study was to evaluate the impact of a restrictive blood transfusion protocol in a postoperative gynecologic oncology population. The primary objective was the rate of blood transfusions after surgery before and after implementation of a restrictive transfusion protocol (from July 1 st 2011 to December 30 th 2016). Secondary outcomes were patient morbidity and included rates of surgical site infection, pneumonia, sepsis, unplanned intubation, prolonged ventilator use, renal insufficiency, acute renal failure, urinary tract infection, cerebral vascular accident, cardiac complications, venous thromboembolism, and death within 30 days of surgery, readmissions and length of stay., Methods: A restrictive blood transfusion protocol was implemented by the gynecologic oncology service at a National Comprehensive Cancer Network designated Comprehensive Cancer Center on January 1 st , 2014. The restrictive protocol required that no patient receive a blood transfusion for hemoglobin greater than 7.0 g/dL (or hematocrit greater than 21.0%) and that all red blood cells were administered in one unit increments followed by re-evaluation of blood parameters. Exceptions to this protocol were postoperative symptomatic anemia, intraoperative or day of surgery transfusion, active bleeding, postoperative severe sepsis, postoperative active coronary ischemia, and postoperative transfusion after 1.5 liter or greater blood loss., Results: 1482 patients were identified for this study (755 in the pre-protocol group and 727 in the post-protocol group). Patients treated under the restrictive protocol had decreased rates of red blood cell transfusion (11.0% vs 5.9% p<0.001), superficial surgical site infection (7.7% vs 4.1% p=0.005), deep surgical site infection (2.3% vs 0.7% p=0.02), and median length of stay (3.0 days vs 2.0 days p<0.001)., Conclusions: A restrictive blood transfusion protocol is associated with reductions in the rates of blood transfusions and postoperative morbidity with a 46.8% reduction in superficial surgical site infection and a 69.6% decrease in deep surgical site infection in the gynecologic oncology patient population.

Importance: Opioids are routinely prescribed for postoperative home pain management for most patients in the United States, with limited evidence of the amount needed to be dispensed. Opioid-based treatment often adversely affects recovery. Prescribed opioids increase the risk of chronic opioid use, abuse, and diversion and contribute to the current opioid epidemic., Objective: To evaluate whether after hospital discharge, postsurgical acute pain can be effectively managed with a markedly reduced number of opioid doses., Design, Setting, and Participants: In this case-control cohort study, an ultrarestrictive opioid prescription protocol (UROPP) was designed and implemented from June 26, 2017, through June 30, 2018, at a single tertiary-care comprehensive cancer center. All patients undergoing gynecologic oncology surgery were included. Patients undergoing ambulatory or minimally invasive surgery (laparoscopic or robotic approach) were not prescribed opioids at discharge unless they required more than 5 doses of oral or intravenous opioids while in the hospital. Patients who underwent a laparotomy were provided a 3-day opioid pain medication supply at discharge., Main Outcomes and Measures: Total number of opioid pain medications prescribed in the 60-day perioperative period, requests for opioid prescription refills, and postoperative pain scores and complications were evaluated. Factors associated with increased postoperative pain, preoperative and postoperative pain scores, inpatient status, prior opioid use, and all opioid prescriptions within the 60-day perioperative window were monitored among the case patients and compared with those from consecutive control patients treated at the center in the 12 months before the UROPP was implemented., Results: Patient demographics and procedure characteristics were not statistically different between the 2 cohorts of women (605 cases: mean [SD] age, 56.3 [14.5] years; 626 controls: mean [SD] age, 55.5 [13.9] years). The mean (SD) number of opioid tablets given at discharge after a laparotomy was 43.6 (17.0) before implementation of the UROPP and 12.1 (8.9) after implementation (P < .001). For patients who underwent laparoscopic or robotic surgery, the mean (SD) number of opioid tablets given at discharge was 38.4 (17.4) before implementation of the UROPP and 1.3 (3.7) after implementation (P < .001). After ambulatory surgery, the mean (SD) number of opioid tablets given at discharge was 13.9 (16.6) before implementation of the UROPP and 0.2 (2.1) after implementation (P < .001). The mean (SD) perioperative oral morphine equivalent dose was reduced to 64.3 (207.2) mg from 339.4 (674.4) mg the year prior for all opioid-naive patients (P < .001). The significant reduction in the number of dispensed opioids was not associated with an increase the number of refill requests (104 patients [16.6%] in the pre-UROPP group vs 100 patients [16.5%] in the post-UROPP group; P = .99), the mean (SD) postoperative visit pain scores (1.1 [2.2] for the post-UROPP group vs 1.4 [2.3] for pre-UROPP group; P = .06), or the number of complications (29 cases [4.8%] in the post-UROPP group vs 42 cases [6.7%] in the pre-UROPP group; P = .15)., Conclusions and Relevance: Implementation of a UROPP was associated with a significant decrease in the overall amount of opioids prescribed to patients after gynecologic and abdominal surgery at the time of discharge for all patients, and for the entire perioperative time for opioid-naive patients without changes in pain scores, complications, or medication refill requests.

Objective: We aimed to investigate the prognostic impact of duration of first-line chemotherapy administration in patients with epithelial ovarian cancer (EOC)., Methods: Chemotherapy records were abstracted from the electronic medical record. Patients with on-time completion (105 days) were compared to patients finishing early (<105 days), delays of 1-4 weeks, or >4 weeks. For 222 women with stage IIIC/IV, stage-stratified estimates of progression-free survival (PFS) and overall survival (OS) were compared. A delay sub-study was performed with outliers removed. Each week of delay was correlated with the change in PFS and OS to identify time points associated with change in outcome., Results: Most women had on-time completion of chemotherapy (23.6%) or a treatment delay of ≤4 weeks (21.8%); 21.6% of women experienced a delay longer than 4 weeks. R0 resection at initial debulking (OR = 1.99, 95%CI: 1.18-3.36, p = 0.010) and RECIST complete response (OR = 4.88, 95%CI: 2.47-10.63, p<0.001) were strongly associated with on-time completion. Patients with on-time completion and < 1 month delay had similar median survivals of 43.1 months (lower 95% CI bound 33.7 months) and 44.5 months (lower bound 37.0, p = 0.93). Women with >1 month delay had decreased median survival of 18.1 months (14.7-24.9 months), while women with short intervals survived 35.0 months (95%CI: 21.8-49.8 months). Short-term delays lead to progressively decreasing OS. This was significantly different from the on-schedule survival estimate after 6 weeks of delay., Conclusions: On-time completion of chemotherapy correlates with increased survival and higher complete response rates. Increasing delays in chemotherapy completion were associated with decreased survival., Competing Interests: The authors have declared that no competing interests exist.

Background: Although family history of testicular cancer is well-established as a risk factor for testicular cancer, it is unknown whether family history of ovarian cancer is associated with risk of testicular cancer., Materials and Methods: Using data from the Familial Ovarian Cancer Registry on 2636 families with multiple cases of ovarian cancer, we systematically compared relative frequencies of ovarian cancer among relatives of men with testicular and non-testicular cancers., Results: Thirty-one families with cases of both ovarian and testicular cancer were identified. We observed that, among men with cancer, those with testicular cancer were more likely to have a mother with ovarian cancer than those with non-testicular cancers (OR = 3.32, p = 0.004). Zero paternal grandmothers of men with testicular cancer had ovarian cancer., Conclusion: These observations provide compelling preliminary evidence for a familial association between ovarian and testicular cancers Future studies should be designed to further investigate this association and evaluate X-linkage., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry. The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and 13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square test X2 = 0.02, p = 0.89) and inconsistent with an autosomal dominant model (X2 = 20.4, p<0.001). Paternal grandmother cases had an earlier age-of-onset versus maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12-2.25) independent of BRCA1/2 status. Reinforcing the X-linked hypothesis, we observed an association between prostate cancer in men and ovarian cancer in his mother and daughters (odds ratio, OR = 2.34, p = 0.034). Unaffected mothers with affected daughters produced significantly more daughters than sons (ratio = 1.96, p<0.005). We performed exome sequencing in reported BRCA negative cases from the registry. Considering age-of-onset, one missense variant (rs176026 in MAGEC3) reached chromosome-wide significance (Hazard ratio HR = 2.85, 95%CI: 1.75-4.65) advancing the age of onset by 6.7 years. In addition to the well-known contribution of BRCA, we demonstrate that a genetic locus on the X-chromosome contributes to ovarian cancer risk. An X-linked pattern of inheritance has implications for genetic risk stratification. Women with an affected paternal grandmother and sisters of affected women are at increased risk for ovarian cancer. Further work is required to validate this variant and to characterize carrier families.

The purpose of this study is to determine the association between gynecologic oncology fellowship training factors, including fellowship length, and a career in academic medicine. A survey was sent to all 980 gynecologic oncologists identified via the SGO membership directory. The survey questions focused on demographics, fellowship training, practice- type, and research involvement. Demographics of the study population and survey responses were reported using frequencies and percentages. Chi-squared tests were used to test for associations between selected survey responses and length of fellowship. The authors received 410 (42 %) responses. Most respondents (60 %) graduated from a 3-year fellowship, while 27 and 13 % attended 2- and 4-year fellowships, respectively. Practice descriptions included academic/university (52 %), community/private practice (21 %), private practice with academic appointment (20 %), and other (7 %). A majority (64 %) reported current involvement in research as a principal investigator (PI); however, 54 % reported spending 10 % or less of their time in research-related activities. Approximately half reported that their fellowship research experience contributed to their current practice. Graduates of 3- and 4-year fellowships had similar rates of employment in academic/university settings (58 and 52 %, respectively). Graduates of 4-year fellowships were more likely to hold an advanced degree and 11 or more publications at completion of fellowship. A majority of graduates of a gynecologic oncology fellowship practice in an academic/university setting and are involved in research. Fellowship length does not correlate with a current academic medicine appointment. Graduates of 4-year fellowships are more likely to hold additional advanced degrees and more publications.

Objective: The aim of this study was to evaluate the ability of patients at risk of hereditary breast and ovarian cancer (HBOC) syndrome to select the extent of genetic testing personally preferred and the impact of demographic factors on the breadth of testing pursued., Methods: A single-institution cohort was enumerated consisting of patients referred for clinical genetic counseling secondary to risk of HBOC syndrome. This was a retrospective study of consecutive patients seen for genetic counseling; all patients completed an epidemiologic questionnaire and provided personal and family medical histories. Patients meeting guidelines for testing were offered testing at 3 levels: single gene/condition (Single), small panels with highly penetrant genes (Plus), and large panels with high and moderately penetrant genes (Next). Associations between personal or family-related factors and breadth of testing selected were investigated. Continuous and categorical variables were compared using Student t and χ tests, as appropriate. Joint classification tables were used to test for effect modification, and a log-binomial model was used to compute rate ratios (RR) with a threshold of P < 0.05 considered significant., Results: We identified 253 patients who underwent genetic counseling for HBOC syndrome. Most patients were personally affected by cancer (63.6%), reported at least some college (79.2%), met the National Comprehensive Cancer Network guidelines for BRCA testing (94.5%), and opted to undergo genetic testing (94.1%). Most (84.9%) patients opted for panel testing. An increased likelihood of choosing Next-level testing was found to be associated with patients having any college experience (RR, 1.53; 95% confidence interval, 1.02-2.30), as well as being unaffected by cancer (RR, 1.30; 95% confidence interval, 1.03-1.64)., Conclusions: Clinical genetic counseling is a highly specialized service, which should be provided to patients at risk of hereditary cancer syndromes. Although some epidemiologic factors can predict a patient's preference for testing breadth, patients were sufficiently able to self-identify the level of testing they were comfortable with after receiving genetic counseling. Most practitioners do not have the time or expertise to provide the degree of counseling needed to enable and empower patients to choose the level of testing they are comfortable with. When available, referral to genetic counselors remains an important component of comprehensive care for women with a personal or family history of cancer suggestive of hereditary risk.

Background: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited., Methods: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer., Results: Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival., Conclusions: In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients. Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes. Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced). Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival. Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470-3. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Objectives: To investigate the impact of ascites volume on ovarian cancer outcomes., Methods: Clinicopathologic features of a cohort of patients with ovarian cancer were obtained from a curated database at a single institution. Progression free survival (PFS) and overall survival (OS) were recorded. Ascites volume at primary surgery was dichotomized at 2000mL and comparisons for high and low volume ascites were made. Additionally, to elucidate interactions between ascites and ovarian tumor progression, we evaluated the effect of intraperitoneal administrations of murine cell-free ascites versus saline in a syngeneic mouse model of epithelial ovarian cancer., Results: Out of 685 patients identified, 58% had ascites present at the time of initial surgery. Considering the volume of ascites continuously, each liter of ascites was associated with shorter PFS (HR=1.12, 95% CI: 1.07-1.17) and OS (HR=1.12, 95%CI: 1.07-1.17). Patients with ascites greater than the median of 2000mL had significantly shorter PFS (14.5months vs. 22.7months; p<0.001) and OS (27.7months vs. 42.9months; p<0.001). After adjusting for stage, presence of ascites was inversely associated with ability to achieve optimal cytoreductive surgery. Consistent with these correlative results in patients, intraperitoneal administrations of murine cell-free ascites accelerated ovarian cancer progression in mice., Conclusions: The volume of ascites at initial diagnosis of ovarian cancer correlated with worse PFS and OS. The effect of large volume on prognosis is likely to be in part related to reduced likelihood for complete resection of tumor (R0). If these findings are confirmed in independent studies, consideration should be made to add the presence of large volume ascites at diagnosis to the staging criteria for ovarian cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Recreational physical inactivity has been gaining recognition as an independent epidemiological exposure of interest in relation to cancer endpoints due to evidence suggesting that it may associate with cancer independent of obesity. In the current analyses, we examined the associations of lifetime recreational physical inactivity with renal and bladder cancer risk., Methods: In this hospital-based case-control study, we identified N=160 renal cancer patients, N=208 bladder cancer patients, and N=766 age frequency-matched controls without cancer. Participants self-reporting never participating in any regular/weekly recreational physical activity throughout their lifetime were classified as physically inactive. Utilizing unconditional multivariable logistic regression analyses, we estimated odds ratios and 95% confidence intervals to represent the associations between lifetime physical inactivity and renal and bladder cancer risk., Results: In multivariable logistic regression models, we observed significant positive associations between lifetime recreational physical inactivity and renal cancer and bladder cancer risk: odds ratio=1.77 (95% CI: 1.10-2.85) and odds ratio=1.73 (95% CI: 1.13-2.63), respectively. Similar associations also persisted among individuals who were not obese for both renal and bladder cancer: odds ratio=1.75 (95% CI: 1.03-2.98) and odds ratio=1.70 (95% CI: 1.08-2.69), respectively., Conclusions: In this case-control study, we observed evidence of a positive association between renal and bladder cancer with lifetime recreational physical inactivity. These data add to the growing body of evidence suggesting that physical inactivity may be an important independent risk factor for cancer. However, additional studies using a larger sample and prospectively collected data are needed to substantiate the current findings., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records., Methods: Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N=436)., Results: Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (R0) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho>0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30months (log-rank p=0.002)., Conclusions: Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: NY-ESO-1 is a cancer testis antigen and a promising target for immunotherapy. The purpose of this study was to determine the expression frequency, immunogenicity, and clinical impact of NY-ESO-1 in ovarian cancer., Methods: Immunohistochemistry (IHC), reverse-transcription polymerase chain reaction (RT-PCR), and quantitative-PCR (qRT-PCR) were utilized in an ovarian cancer (including Fallopian tube and primary peritoneal cancers) patient cohort; humoral responses against NY-ESO-1 were determined by ELISA. Clinicopathologic outcomes including progression-free (PFS) and overall (OS) survival were evaluated based on NY-ESO-1 expression. Cohen's kappa (κ) tested agreement between expression tests., Results: NY-ESO-1 expression was detected by any method in 40.7% of 1002 patients' tumors (NY-ESO-1+) and baseline humoral response was identified in 19.0% of 689 tested patients. NY-ESO-1+ patients were older (p<0.001), higher stage (85% stage III/IV vs. 76.4%, p=0.015), less likely to have a complete response to initial therapy (53.9% vs. 68.9%, p=0.002), had more serous histotype (74.5% vs. 66.9%, p=0.011), and had more grade 3 tumors (83.7% vs. 70.8%, p<0.001). There was a trend towards shorter PFS (22.2 vs. 25.0months, p=0.07) and significantly shorter OS (42.9 vs. 50.0months, p=0.003) among NY-ESO-1+ patients. A subset analysis of NY-ESO-1+ patients that received immunotherapy demonstrated improved OS by >2years (52.6 vs. 27.2months, p<0.001)., Conclusions: This study is the first demonstration of an association between NY-ESO-1 expression and an aggressive cancer phenotype. The relatively high expression frequency of NY-ESO-1 in ovarian cancer patients coupled with the poor clinical outcomes in NY-ESO-1+ patients reveals an underappreciated need for targeted therapy against this antigen. In support, our study reveals that NY-ESO-1+ patients enrolled on immunotherapy trials targeting the antigen exhibited an improvement in OS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype., Methods: Using pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes., Results: History of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01-1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88-1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87-1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35-0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03-1.40, HR = 1.28; 95% CI = 1.05-1.55, and HR = 1.63; 95% CI = 1.20-2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53-0.94., Conclusions: Histories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients. Understanding mechanisms for these observations could provide insight regarding treatment.

Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing ( P < 3.5 × 10 -5 ), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Study Objective: To develop and validate a procedure-specific scoring algorithm to objectively measure robotic surgical skills during robot-assisted hysterectomy and to facilitate robotic surgery training and education., Design: (Canadian Task Force classification III)., Setting: A National Comprehensive Cancer Network-designated comprehensive cancer center., Patients: Deidentified videos for robot-assisted hysterectomies were evaluated., Interventions: Videos from 26 robotic hysterectomies performed by surgeons with varying degrees of experience using the scoring system were evaluated. In phase I, critical elements of a robotic hysterectomy were deconstructed into 6 key domains to assess technical skills for procedure completion. Anchor descriptions were developed for each domain to match a 5-point Likert scale. Delphi methodology was used for content validation. A panel of 5 expert robotic surgeons refined this scoring system. In phase II, video recordings of procedures performed by surgeons with varying degrees of experience (expert, advanced beginner, and novice) were evaluated by blinded expert reviewers using the scoring system. Descriptive statistics were used to summarize the scores for each domain. Intraclass correlation was used to determine the interrater reliability. A p value <.05 was considered significant., Measurements and Main Results: The average score for the 3 classes of surgeon was 75.6 for expert, 71.3 for advanced beginner, and 69.0 for novice (p = .006). There were significant differences in scores of most individual domains among the various classes of surgeons. Novice surgeons took significantly longer than expert surgeons to complete their half of a hysterectomy (22.2 vs 12.0 minutes; p = .001)., Conclusion: This pilot study demonstrates the feasibility of using a standardized rubric for clinical skills assessment in robotic hysterectomy. Blinded expert reviewers were able to differentiate between varying levels of surgical experience using this assessment tool., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: There is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case-control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer., Materials and Methods: Participants were identified for inclusion due to their participation in the Data Bank and BioRepository program at Roswell Park Cancer Institute in Buffalo, NY. Patients included 71 women with a primary diagnosis of EOC and 195 women with a diagnosis of benign ovarian conditions. Controls included 101 age- and race-matched women without a history of cancer. Nonfasting, pretreatment peripheral blood levels of CD3+CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analyses and expressed as a percentage of total CD3+ cells and as a percentage of total CD3+CD4+ cells., Results: Compared to healthy controls and women with benign ovarian conditions, patients with EOC had significantly higher frequency of Treg cells (P < 0.04). In multivariable logistic regression analyses using Treg frequency expressed as a percentage of CD+3 cells, we observed a significant positive association between Treg cell percentage and EOC risk, with each 1% increase associated with a 37% increased risk of EOC (odds ratio, 1.37; 95% confidence interval, 1.04-1.80). We observed a similar trend when Treg frequency was expressed as a percentage of CD3+CD+4 cells (odds ratio, 1.22; 95% confidence interval, 0.99-1.49)., Conclusions: The current study provides support that peripheral Treg cell frequency is elevated in patients with EOC in comparison to women with benign ovarian conditions and healthy controls.

Background: The time interval between diagnoses of breast cancer (BC) and endometrial cancer (EC) is not well established in women with metachronous primary tumors. We sought to examine this interval and identify associations with treatment-related and clinicopathologic factors., Methods: We identified 141 patients who developed both cancers during 1966 to 2013. Patients were divided into 2 groups: group 1, BC first, and group 2, EC first. Subanalysis performed of group 1 (59 patients) stratified around adjuvant tamoxifen use: pre-1990 BC diagnosis and post., Results: Fifty-nine and 82 patients were in groups 1 and 2, respectively. The mean time interval was comparable (76 vs 74 months, P = 0.861). Subanalysis divided group 1 into pre- (n = 27) and post- (n = 32) 1990 and resulted in different mean time intervals between diagnosis of metachronous cancers (106 vs 50 months, respectively [P = 0.042]). Median progression-free survival (PFS) and overall survival (OS) for EC were longer in the pre group (PFS, 51 vs 26 months [P = 0.169]; OS, 59 vs 27 months [P = 0.190]). Median PFS and OS for BC were also longer in this group (PFS, 147 vs 109 months [P = 0.005]; OS, 166 vs 114 months [P < 0.001])., Conclusions: Our data indicate the mean time interval between the diagnosis of EC and BC was approximately 6 years. Disease-specific EC survival was worse for patients with a previous diagnosis of BC. Stratification around implementation of tamoxifen use shows comparable grade and stage but different time interval and survival, suggesting resulting effects from adjuvant therapy for BC. These results are useful in counseling women at risk., Competing Interests: The authors declare no conflicts of interest.

Objective: In this study, we investigated whether physical inactivity was associated with risk of cervical cancer in women treated at an American cancer hospital., Methods: This case-control study included 128 patients with cervical cancer and 512 controls matched on age. Controls were women suspected of having but not ultimately diagnosed with a neoplasm. Physical inactivity was defined in accordance with the 2008 Physical Activity Guidelines for Americans. Thus, participants reporting, on average, no moderate or vigorous recreational physical activity were classified as inactive. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Compared with noncancer controls, those with cervical cancer had significantly increased odds of reporting abstinence from recreational physical activity (OR, 2.43; 95% CI, 1.56-3.80). No association was noted between occupational-related physical inactivity and cervical cancer (OR, 0.88; 95% CI, 0.58-1.36)., Conclusions: Our findings suggest that abstinence from regular recreational physical activity is associated with increased odds of cervical cancer. To our knowledge, this is the first US-based study examining these associations. Given the 2008 Physical Activity Guidelines for Americans, this study has identified yet another potential public health benefit to regular physical activity. Further investigation is needed using a larger sample and prospectively collected data to characterize dose of activity to mitigate risk and the optimal window of susceptibility.

Objectives: To characterize the association between major histocompatibility complex (MHC) types and spontaneous antibody development to the cancer testis (CT) antigen NY-ESO-1., Methods: Tumor expression of NY-ESO-1 and serum antibodies to NY-ESO-1 were characterized in addition to human leukocyte antigen (HLA) type for patients with epithelial ovarian cancer. HLA types were assigned to structure-based superfamilies and statistical associations were examined. HLA types were compared to existing reference libraries of HLA frequencies in a European-Caucasian American population., Results: Out of 126 patients identified, 81% were expression positive and 48% had spontaneous antibody responses to NY-ESO-1. There was an association between HLA-B superfamily and seropositivity among patients with tumors expressing NY-ESO-1 (p<0.001). The differences in HLA-B superfamily assignment were driven by HLA-B44. Among all patients, the B27 superfamily was over-represented compared with the general population (p<0.001)., Conclusions: HLA type appears to be associated with spontaneous anti-CT antigen antibodies, as well as with the overall risk of ovarian cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity and mortality., Methods: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing the associations of inactivity with mortality censored at 5 years., Results: In multivariate analysis, inactive women had significantly higher mortality risks, with (HR=1.34, 95% CI: 1.18-1.52) and without (HR=1.22, 95% CI: 1.12-1.33) further adjustment for residual disease, respectively., Conclusion: In this large pooled analysis, lack of recreational physical activity was associated with increased mortality among women with invasive EOC.

Introduction: Metabolomics is the emerging member of "omics" sciences advancing the understanding, diagnosis and treatment of many cancers, including ovarian cancer (OC)., Objectives: To systematically identify the metabolomic abnormalities in OC detection, and the dominant metabolic pathways associated with the observed alterations., Methods: An electronic literature search was performed, up to and including January 15th 2016, for studies evaluating the metabolomic profile of patients with OC compared to controls. QUADOMICS tool was used to assess the quality of the twenty-three studies included in this systematic review., Results: Biological samples utilized for metabolomic analysis include: serum/plasma (n = 13), urine (n = 4), cyst fluid (n = 3), tissue (n = 2) and ascitic fluid (n = 1). Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in OC. Increased levels of tricarboxylic acid cycle intermediates and altered metabolites of the glycolytic pathway pointed to perturbations in cellular respiration. Alterations in lipid metabolism included enhanced fatty acid oxidation, abnormal levels of glycerolipids, sphingolipids and free fatty acids with common elevations of palmitate, oleate, and myristate. Increased levels of glutamine, glycine, cysteine and threonine were commonly reported while enhanced degradations of tryptophan, histidine and phenylalanine were found. N-acetylaspartate, a brain amino acid, was found elevated in primary and metastatic OC tissue and ovarian cyst fluid. Further, elevated levels of ketone bodies including 3-hydroxybutyrate were commonly reported. Increased levels of nucleotide metabolites and tocopherols were consistent through out the studies., Conclusion: Metabolomics presents significant new opportunities for diagnostic biomarker development, elucidating previously unknown mechanisms of OC pathogenesis., Competing Interests: Conflict of Interest Onur Turkoglu, Amna Zeb, Stewart Graham, Thomas Szyperski, J Brian Szender, Kunle Odunsi and Ray Bahado-Singh declare that they have no conflict of interest.

To characterize the state of satisfaction with work-life balance (WLB) among gynecologic oncology fellows in training, risk factors for dissatisfaction, and the impact of dissatisfaction on career plans. A cross-sectional evaluation of gynecologic oncology fellows was performed using a web-based survey. Demographic data, fellowship characteristics, and career plans were surveyed. The primary outcomes were satisfaction with WLB and career choices. p < 0.05 was used as a test for significance. Regression analysis was used to estimate prevalence ratios (PRs) for various potential risk factors for dissatisfaction. Of 52.5% responding fellows, 22.2% were satisfied with WLB, but 83.3% would be physicians again and 80.3% would select gynecologic oncology again. Satisfaction with WLB was significantly associated with age (PR = 0.70, 95% CI: 0.54-0.91), working fewer than 80 h per week (PR = 4.35, 95% CI: 1.34-14.10), and fatigue (PR = 0.31, 95% CI: 0.12-0.75). Career and WLB satisfaction were not associated with gender, marital status, and whether or not the fellow is a parent. Those satisfied with WLB planned to work an average of 3.5 years longer than those who were not (p < 0.05). Gynecologic oncology fellows are not generally satisfied with their WLB, although this does not alter their overall career or specialty satisfaction. Satisfaction with WLB predicts a longer post-fellowship career. Further studies are needed to determine the workforce impact of this lack of perceived balance.

Objectives: While primary treatment for high-grade serous ovarian cancer tends to be uniform - maximal debulking and platinum/taxane adjuvant chemotherapy - there is little standardization of treatment in the recurrent setting beyond the exhaustive use of platinum therapies. Using secondary data from multiple centers participating in the Cancer Genome Atlas study (TCGA), we seek to characterize clinical features, timing and serial response data to provide empirical evidence for treatment expectations in the recurrent setting., Methods: We conducted a retrospective survival analysis of TCGA study primary and secondary patient chemotherapy regimens by characterizing the dynamics of 1119 lines of therapy comprising the treatment of 461 high-grade serous ovarian cancer patients. All patients with post-surgical drug therapy information from the TCGA database were included in this study., Results: A complete response to adjuvant therapy led to longer overall survival, but did not affect treatment free intervals (TFIs) after relapse of disease. A strong predictor of the TFI on the next treatment regimen was the previous TFI with a decaying effect. The number of previous treatments, of platinum treatments, and the length of time from surgery all have an exponentially decreasing effect on TFI. Re-treatment times appear to cluster at predictable times following surgery., Conclusions: While patients experience a consistent reduction in TFI with increasing re-treatment, the initial adjuvant interval is unrelated to later interval lengths. Platinum re-treatment remained an effective option in patients typically thought to be platinum resistant and the timing of monitoring visits may drive overall re-treatment patterns., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Prognostic risk factors influencing survival in patients with epithelial ovarian cancer (EOC) include tumor stage, grade, histologic subtype, debulking, and platinum status. Little is known about the impact of hormonal milieu and reproductive factors before cancer diagnosis on clinical outcome. We sought to evaluate whether oral contraceptive (OC) use carries any prognostic significance on overall survival (OS) in patients with EOC., Methods: Newly diagnosed patients with EOC, fallopian tube, and primary peritoneal cancers between 1982 and 1998 were prospectively evaluated with a comprehensive epidemiologic questionnaire. A retrospective chart review was performed to abstract clinicopathologic data, including OS. A Kaplan-Meier analysis was performed to compare survival across various exposures. A Cox regression model was used to compute adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs)., Results: We identified 387 newly diagnosed cancers with evaluable information in this cohort. Decreased risk of death was observed in women who reported prior use of OC (aHR, 0.79; 95% CI, 0.58-1.09), previous pregnancy (aHR, 0.77; 95% CI, 0.57-1.04), or a live birth (aHR, 0.81; 95% CI, 0.60-1.08) after adjusting for age at diagnosis, stage, and histologic subtype. Oral contraceptive use was associated with a crude reduced risk of death (HR, 0.55; 95% CI, 0.42-0.72), with reported median OS of 81 months in OC users versus 46 months in nonusers. Patients who reported a single live birth experienced the largest potential survival advantage (aHR, 0.61; 95% CI, 0.39-0.94). Oral contraceptive use and prior pregnancy were associated with improved survival across all strata., Conclusions: Oral contraceptive use may have lasting effects on epithelial ovarian tumor characteristics conferring favorable prognosis. Putative mechanisms that affect tumor biology include complex interactions between ovarian cells, host immune cells, and hormonal microenvironment during carcinogenesis. Future efforts should be directed to determine the role of reproductive factors in antitumor immunity.

Background: Use of analgesics has been associated with lower risk of ovarian cancer, but, to date, very few studies have explored the association between analgesics and ovarian cancer survival., Methods: We examined the relationship between self-reported prediagnostic use of aspirin, ibuprofen, and acetaminophen and overall survival (OS), progression-free survival (PFS), ascites at the time of primary treatment, and persistence of disease after primary treatment among 699 women diagnosed with epithelial ovarian carcinoma. The associations between use of these medications and OS and PFS were estimated using Cox proportional hazards models. We utilized unconditional logistic regression models to estimate associations between medication use and presence of ascites and persistence of disease., Results: Prediagnostic intake of aspirin, both low-dose and regular-dose, ibuprofen, and acetaminophen was not associated with any of the outcomes of interest., Conclusions: Our results indicate a lack of association between prediagnostic intake of selected analgesics and OS, PFS, presence of ascites at the time of primary treatment, and persistence of disease after primary treatment., Impact: Prediagnostic intake of analgesics may not be associated with ovarian cancer outcomes., (©2015 American Association for Cancer Research.)

Objectives: The National Surgical Quality Improvement Program is aimed at preventing perioperative complications. An online calculator was recently published, but the primary studies used limited gynecologic surgery data. The purpose of this study was to evaluate the performance of the National Surgical Quality Improvement Program Universal Surgical Risk Calculator (URC) on the patients of a gynecologic oncology service., Study Design: We reviewed 628 consecutive surgeries performed by our gynecologic oncology service between July 2012 and June 2013. Demographic data including diagnosis and cancer stage, if applicable, were collected. Charts were reviewed to determine complication rates. Specific complications were as follows: death, pneumonia, cardiac complications, surgical site infection (SSI) or urinary tract infection, renal failure, or venous thromboembolic event. Data were compared with modeled outcomes using Brier scores and receiver operating characteristic curves. Significance was declared based on P < 0.05., Results: The model accurately predicated death and venous thromboembolic event, with Brier scores of 0.004 and 0.003, respectively. Predicted risk was 50% greater than experienced for urinary tract infection; the experienced SSI and pneumonia rates were 43% and 36% greater than predicted. For any complication, the Brier score 0.023 indicates poor performance of the model., Conclusions: In this study of gynecologic surgeries, we could not verify the predictive value of the URC for cardiac complications, SSI, and pneumonia. One disadvantage of applying a URC to multiple subspecialties is that with some categories, complications are not accurately estimated. Our data demonstrate that some predicted risks reported by the calculator need to be interpreted with reservation.

Objectives: To evaluate the satisfaction with work-life balance (WLB) and career satisfaction of gynecologic oncologists., Methods: In August 2014, members of the Society of Gynecologic Oncology (SGO) were sent an anonymous, cross-sectional survey evaluating demographic variables, practice characteristics, career satisfaction, fatigue, and satisfaction with WLB. Fatigue was assessed using a visual-analog scale. Career satisfaction and WLB were assessed with a Likert scale. Inferential statistics were computed with type I error rates of 0.05., Results: Out of the 1002 gynecologic oncologists surveyed, 290 (28.9%) responded. Only 18.6% of respondents were satisfied with WLB and there were significant associations between gender (P = 0.0157), time spent in work related activities at home (P = 0.0024), on weekends (P = 0.0017), and in the hospital (P = 0.0001). More than 84% of physicians reported they would choose medicine as a career again and of those 90% would choose to be a gynecologic oncologist again. Fatigue was strongly associated with dissatisfaction with WLB in univariate and multivariate analysis (P < 0.0001)., Conclusions: Although gynecologic oncologists indicated they are satisfied with their careers, most are not satisfied with their WLB. Given the forecast shortage of gynecologic oncologists and projected increased cancer rates, understanding the factors associated with career satisfaction may assist the SGO in meeting future gynecologic cancer care needs.

Purpose of Investigation: Pain control and early ambulation are two important postoperative goals. Strategies that decrease morphine use while increasing ambulation have the potential to decrease postoperative complications. In this study the authors sought to determine the effect of an abdominopelvic binder on postoperative morphine use, pain, and ambulation in the first day after surgery., Materials and Methods: The authors randomly assigned 75 patients undergoing abdominal gynecologic surgery to either binder or not after surgery. Demographic data and surgical characteristics were collected. Outcome variables included morphine use, pain score, time to ambulation, and number of ambulations., Results: A group at high risk for decreased mobility was identified and the binder increased the number of ambulatory events by 300%, 260%, and 240% in patients with vertical incisions, age over 50 years, and complex surgeries, respectively. Morphine use and pain scores were not significantly different., Conclusion: The binder increased ambulations in the subset of patients at the highest risk for postoperative complications: elderly, cancer patients, and vertical incisions. Routine use of the binder may benefit particularly high-risk gynecologic surgical patients.