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The purpose of the present study is to describe a cohort who received contemporary primary treatment for stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC), including patient characteristics and determinants of relapse and disease-free survival.The study included 99 patients: 1) with pathologically confirmed stage II-IV LGSOC of the ovary or peritoneum, 2) who underwent primary treatment consisting of cytoreductive surgery and either a) platinum/taxane chemotherapy followed by aromatase inhibitor maintenance therapy or b) aromatase inhibitor monotherapy, and 3) for whom there was availability of clinical data. Descriptive statistics were used to characterize clinicodemographic features. Subgroups were compared for PFS and OS. Multivariable Cox regression analyses were performed.Median PFS for the entire cohort was 56.8 months (95% CI, 41.3-NE), and median OS was 130.7 months (95% CI, 115.0-146.4). Forty-nine of 99 (49.5%) patients have relapsed to date. For these 49 patients, median time from diagnosis to relapse was 29.6 months (95% CI, 24.6-33.1) (range, 5.4-69.1 months). Only 1/49 (2%) patients who relapsed did so5 years from diagnosis. Fifty (50.0%) patients have not experienced disease progression or relapse. Median follow-up time for these 50 patients is 86.2 months (range, 25.3-169.0). Thirty-three of the 50 (66.0%) have been followed for5 years from diagnosis. On regression analyses, factors associated with improved patient outcomes-either PFS, OS, or both-included no gross residual disease, normal serum CA 125 at diagnosis, primary peritoneal site, and presence of extensive psammomatous calcifications.This is the first report to describe the clinicopathologic features and outcomes of women with stage II-IV LGSOC who received contemporary primary therapy.

OBJECTIVES: To evaluate the factors associated with response to neoadjuvant chemotherapy (NACT) and the ability to undergo interval tumor reductive surgery (iTRS) in patients with advanced ovarian cancer. METHODS: We performed a retrospective review from April 2013 to March 2019 of patients with advanced stage ovarian cancer triaged to NACT based on our standard triage algorithm. Clinicopathologic and treatment data were analyzed for factors associated with response to NACT, outcomes at iTRS, and their impact on progression-free survival (PFS). RESULTS: 562 patients met inclusion criteria and triaged to NACT following laparoscopy (n=132) or without laparoscopy (n=430). 413 patients underwent iTRS (74%). Factors that correlated with a patient reaching iTRS included increasing age (p1cm, p

Although gynecologic cancers usually affect older women, a significant proportion of patients with rare ovarian tumors are of reproductive age. In a young patient who presents with a pelvic mass, a primary consideration should be the probability of a malignancy. If there is any suspicion of a cancer diagnosis, the patient should be referred to a gynecologic oncologist. Key factors in clinical management include assessment of preoperative studies (physical examination, tumor markers, and imaging) to determine the likelihood of a malignancy, appropriate preoperative counseling (including discussion of fertility preservation), choice of surgical approach (minimally invasive vs open), frozen section examination by a gynecologic pathologist, and intraoperative decision making. Fortunately, the clinical features of several rare ovarian tumors are compatible with fertility preservation. These characteristics include a high proportion of stage I disease and unilateral ovarian involvement for most rare histotypes. Once a final diagnosis of a rare ovarian tumor is determined, further clinical management may include the need for further studies, possible referral to a fertility expert, consideration of further surgery (if the initial surgery was incomplete), and recommendations for postoperative therapy. This article reviews the literature on fertility preservation in the context of the treatment of several rare ovarian tumor subtypes, including malignant germ cell tumors, sex cord-stromal tumors, borderline tumors, low grade serous carcinoma, clear cell carcinoma, mucinous carcinoma, and small cell carcinoma of the hypercalcemic type.

Low-grade serous carcinoma of the ovary/peritoneum (LGSC) is relatively chemoresistant in the adjuvant, neoadjuvant, and recurrent settings. We sought to expand our prior work and evaluate response rates of women with LGSC to neoadjuvant chemotherapy (NACT) compared to women with high-grade serous carcinoma of the ovary/peritoneum (HGSC).Thirty-six patients with LGSC who received NACT were matched to patients with HGSC. A single radiologist re-reviewed pre- and post-NACT imaging for response using RECIST 1.1. Pre- and post-NACT CA-125 values were compared using paired t-tests. Kaplan-Meier estimates of progression free survival (PFS) and overall survival (OS) were performed.All patients received neoadjuvant platinum-based regimens. LGSC patients received a median of 5 cycles (range 3-9), HGSC patients received a median of 4 cycles (range 3-9). Interval cytoreductive surgery was performed in 29/36 (81%) of LGSC and 32/36 (89%) HGSC patients. Complete cytoreduction was reported and achieved in 11/29 (38%) of LGSC patients and 24/32 (75%) of HGSC patients (p = 0.002). Median pre- and post-treatment CA-125 levels for LGSC patients were 295.5 U/mL and 144 U/mL (52% decrease) (p 0.001). The median pre- and post-treatment CA-125 levels for HGSC patients were 767.5 and 35.6 (96% decrease) (p 0.001). For LGSC patients, 4/36 (11%) had partial response (PR), 30/36 (83%) had stable disease (SD), and 2/36 (6%) had progressive disease (PD). In HGSC patients, 27/36 (75%) had PR, and 9/36 (25%) SD. Median PFS for LGSC patients was 18.5 months and median OS was 47.4 months.This study provides further evidence of relative chemoresistance of LGSC in patients treated with NACT.

Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes.The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed.Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0-176.6) versus 89.5 months (95% CI, 61.4-117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0-176.6) versus 78.0 months (95% CI, 57.6-98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9-166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS.Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.

5522 Background: Neoadjuvant chemotherapy has demonstrated limited activity in low-grade serous carcinomas (LGSOC) of the ovary, fallopian tube, and peritoneum, with objective response rate of 11% and complete gross resection (CGR) rate of 38% at the time of interval cytoreductive surgery (ICS). LGSOC has many similarities to hormone receptor positive (HR+) breast cancer, including clinical benefit from endocrine therapies in the recurrent and maintenance settings. Based on the activity of antiestrogen plus CDK4/6 inhibitor combination therapy in HR+ breast cancer, we conducted a phase II pilot study to assess the clinical benefit of neoadjuvant treatment with fulvestrant and abemaciclib for women with advanced LGSOC. Methods: Women with unresectable, untreated stage III or IV LGSOC of the ovary, fallopian tube or peritoneum were eligible. Patients received fulvestrant (500 mg IM on day 1 and 15 of the first 28-day cycle, followed by day 1 of subsequent cycles) and abemaciclib 150 mg orally BID. Pre/perimenopausal patients also received goserelin 10.8 mg subcutaneously every 12 weeks for ovarian suppression. Patients continued treatment until deemed resectable by the treating surgeon with imaging re-assessment every 8 weeks using RECIST 1.1. Following ICS, patients receive 4 cycles of adjuvant fulvestrant and abemaciclib and then transition to maintenance letrozole. Patients with progressive disease (PD) were removed from study and received standard of care chemotherapy. Primary endpoint is clinical benefit rate (CBR). Results: Fifteen patients were enrolled and evaluable. At data cutoff date (January 20, 2022), 7 of 15 patients (47%) had partial response (PR) (one patient with radiologic PR had a pathologic complete response at ICS), 5 of 15 (33%) had stable disease (SD), and 3 of 15 (20%) had progressive disease (PD), resulting in a CBR of 80%. Of the 7 patients with PR, 3 have had ICS with CGR, 3 have not yet had ICS, and 1 underwent resection of supraclavicular disease with small volume residual disease in the chest. Of the 5 patients with SD, one underwent ICS with CGR, and two have been on treatment for 8 and 16 weeks with reduction in measurable disease but not yet deemed to be candidates for surgery. Four of the 5 patients (80%) who had ICS, had CGR. Median time on study prior to surgery was 24 weeks. Adverse events (grade 3 or 4) possibly related to abemaciclib occurred in 2 patients (13.3%) and included acute kidney injury (6.7%) and neutropenia (6.7%). Conclusions: Neoadjuvant treatment with fulvestrant and abemaciclib was tolerable and demonstrated unprecedented response and CGR rates in this pilot study. These results compare favorably to published outcomes of neoadjuvant chemotherapy in LGSOC. Further studies are planned to explore this new treatment option in a larger study population. Clinical trial information: NCT03531645.

Objectives: The androgen receptor (AR) is more widely expressed than the estrogen or progesterone receptor in endometrial cancer (EC), including up to 90% of endometrioid type. Enzalutamide binds to the AR thereby nuclear translocation of receptors and blocking the association of the AR with DNA. We sought to evaluate the efficacy of paclitaxel, carboplatin and enzalutamide in a phase II study of advanced or recurrent endometrioid EC. Methods: Women with chemo-naive, advanced-stage or recurrent endometrioid EC with measurable disease and adequate end organ function were eligible. Documented AR expression was not required. A safety lead in of the triplet was performed to confirm dose. In phase II, patients received 28 days of enzalutamide (160mg daily) as a single agent before starting triplet therapy. Pre- and post-treatment biopsies were obtained during the single agent lead in for evaluation of molecular markers including AR receptor expression and activation, expression of AR-related genes/proteins, and DNA copy number alterations and mutations. Patients then received carboplatin (AUC 6 IV Q3wk), paclitaxel (175 mg/m2), and enzalutamide (160mg daily). Response per RECIST 1.1 was assessed every 3 cycles for a maximum of 9 cycles. Evaluable patients received at least 6 cycles of triplet therapy. Progression free survival (PFS) was calculated from date of treatment initiation to earliest date of progression, death, or last contact. This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Astellas Pharma Global Development, Inc. Results: A total 81 patients were screened with 49 patients treated to date (safety lead in n=7; phase II n=42). Median age was 64 years (range 41-81) and the majority of patients had grade 2 histology (53.1%) and recurrent disease (81.6%). There were no dose-limiting toxicities observed during the safety lead in. Patients received a median of 9 cycles of triplet therapy (range 0-9). 8 patients (16.3%) did not receive chemotherapy due to rapid progression during single agent enzalutamide (n=3), unrelated death (n=2), withdrawal (n=2), and unrelated stroke (n=1). PFS for the entire cohort was 11.47 months (95% CI 9.86 - 17.94; Figure 1a) and 6-month PFS probability was 0.77 (95% CI 0.61-0.87). Among 35 evaluable patients, confirmed objective response rate was 71% (95% CI 54–85%), 6 months PFS probability was 0.83 (95% CI 0.66-0.92) and median PFS was 14.42 months (95% CI 11.2-25.5; Figure 1B). The most common adverse events were as expected for chemotherapy alone, including neutropenia (20%), anemia (18%), fatigue (18%), neuropathy (10%), hyperglycemia (14%), nausea (8%), and thrombocytopenia (8%). Download : Download high-res image (41KB) Download : Download full-size image Conclusions: The combination of enzalutamide, carboplatin, and paclitaxel was tolerable and had promising clinical outcomes in chemo-naive advanced or recurrent endometrioid EC. Further analyses are ongoing regarding predictors of response and resistance to androgen-inhibitor therapy. Clinical Trials Registration: NCT02684227.

BackgroundRadiographic triage measures in patients with new advanced ovarian cancer have yielded inconsistent results.ObjectiveTo determine the correlation between surgeon radiology assessment and laparoscopic scoring by disease sites in patients with newly diagnosed advanced stage ovarian cancer.MethodsFourteen gynecologic oncology surgeons from a single institution performed a blinded review of pre-operative contrast-enhanced CT imaging from patients with advanced stage ovarian cancer. Each of the patients had also undergone laparoscopic scoring assessment, between April 2013 and December 2017, to determine primary resectability using the validated Fagotti scoring method, and assigned a predictive index value score. Surgeons were asked to provide expected predictive index value scores based on their blinded review of the antecedent CT imaging. Linear mixed models were conducted to calculate the correlation between radiologic and laparoscopic score for surgeons individually, and as a group. Once the model was fit, the inter-class correlation and 95% CI were calculated.ResultsRadiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Surgeon faculty rank included assistant professor (n=5), associate professor (p=4), and professor (n=5). The kappa inter-rater agreement was −0.017 (95% CI −0.023 to −0.005), indicating low inter-rater agreement between radiology review and actual laparoscopic score. The inter-class correlation in this model was 0.06 (0.02–0.21), indicating that surgeons do not score the same across all the images. When using a clinical cut-off point for the predictive index value of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI 0.49 to 0.73). Examination of disease site sub-scales showed that the probability of agreement was as follows: peritoneum 0.57 (95% CI 0.51 to 0.62), diaphragm 0.54 (95% CI 0.48 to 0.60), mesentery 0.51 (95% CI 0.45 to 0.57), omentum 0.61 (95% CI 0.55 to 0.67), bowel 0.54 (95% CI 0.44 to 0.64), stomach 0.71 (95% CI 0.65 to 0.76), and liver 0.36 (95% CI 0.31 to 0.42). The number of laparoscopic scoring cases, tumor reductive surgery cases, or faculty rank was not significantly associated with overall or sub-scale agreement.ConclusionsSurgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. Our study highlights the limited accuracy of surgeon radiographic assessment to determine resectability.

In January 2019, a group of basic, translational, and clinical investigators and patient advocates assembled in Miami, Florida, to discuss the current state of the science of low-grade serous carcinoma of the ovary or peritoneum-a rare ovarian cancer subtype that may arise de novo or following a diagnosis of serous borderline tumor. The purpose of the conference was to review current knowledge, discuss ongoing research by established researchers, and frame critical questions or issues for future directions. Following presentations and discussions, the primary objective was to initiate future collaborations, uniform database platforms, laboratory studies, and clinical trials to better understand this disease and to advance clinical care outside the boundaries of single academic institutions. This review summarizes the state of the science in five principal categories: epidemiology and patient outcomes, pathology, translational research, patient care and clinical trials, and patients' perspective.

ObjectiveEnhanced Recovery After Surgery (ERAS) protocols are designed to mitigate the physiologic stress response created by surgery, to decrease the time to resumption of daily activities, and to improve overall recovery. This study aims to investigate postoperative recovery outcomes following gynecologic surgery before and after implementation of an ERAS protocol.MethodsA retrospective chart review was performed of patients undergoing elective laparotomy at a major academic center following implementation of an ERAS protocol (11/4/2014–7/27/2016) with comparison to a historical cohort (6/23/2013–9/30/2014). The primary outcome was length of hospital stay. Secondary outcomes included surgical variables, time to recovery of baseline function, opioid usage, pain scores, and complication rates. Statistical analyses were performed using Wilcoxon rank sum, Fisher’s exact, and chi squared tests.ResultsOne hundred and thirty-three women on the ERAS protocol who underwent elective laparotomy were compared with 121 historical controls. There was no difference in length of stay between cohorts (median 4 days; P = 0.71). ERAS participants had lower intraoperative (45 vs 75 oral morphine equivalents; P < 0.0001) and postoperative (45 vs 154 oral morphine equivalents; P < 0.0001) opioid use. ERAS patients reported lower maximum pain scores in the post-anesthesia care unit (three vs six; P < 0.0001) and on postoperative day 1 (four vs six; P = 0.002). There was no statistically significant difference in complication or readmission rates.ConclusionsERAS protocol implementation was associated with decreased intraoperative and postoperative opioid use and improved pain scores without significant changes in length of stay or complication rates.

Traditionally, the management of epithelial ovarian cancer has been approached using a one-size-fits-all mentality. This strategy does not acknowledge the differences in epidemiology and clinical behavior of many of the histologic and molecular subgroups of ovarian cancer, specifically the rare histologies. While cytoreductive surgery followed by adjuvant platinum and taxane-based chemotherapy is the mainstay of primary treatment of epithelial ovarian cancer as a group, further investigation of novel therapeutics is critical for improving outcomes of these rare histologies. This article focuses on the management of non-high grade serous histologies of ovarian cancer.

5570 Background: To determine the correlation between surgeon radiology assessment and laparoscopic scoring in patients with newly diagnosed advanced stage ovarian cancer. Methods: Following IRB approval, 14 gynecologic oncologists from a single institution performed a blinded review of radiology imaging from 20 patients with advanced stage ovarian cancer. All patients previously underwent laparoscopic scoring assessment to determine primary resectability at tumor reductive surgery (TRS) using a validated scoring method from April 2013 to December 2017. The patients with predictive index value (PIV) scores < 8 were offered primary surgery and those with a score ≥8 received neoadjuvant chemotherapy (NACT). Surgeons viewed contrasted CT imaging reports and images from all patients in a blinded fashion and recorded PIV scores using the same validated scoring method. Linear mixed models were conducted to calculate the correlation between radiology and laparoscopic score for each surgeon and as a group. Once the model was fit, the inter-class correlation (ICC) and 95% confidence interval was calculated. Results: Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Most patients had stage IIIC disease (85%) and median laparoscopic score was 9 (range 0-14). Surgeon faculty rank included Assistant Professor (n = 5), Associate Professor (n = 4), and Professor (n = 5). Median surgeon experience during the study period with laparoscopic assessment was 13 cases (range 1-28) and TRS was 22.5 cases (range 2-48). The kappa inter-rater agreement was -0.017 (95% CI 0.023 to -0.005) indicating low inter-rater agreement between radiology review and actual laparoscopic score. The ICC in this model was 0.06 (0.02-0.21) indicating that surgeons do not score the same across all the images. When using a clinical cutoff of PIV of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI: 0.49-0.73). Number of laparoscopic cases, TRS cases, or faculty rank was not significantly associated with agreement. Conclusions: Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. 44% of patients in our study may have been inadequately triaged by radiology review alone, which may have led to suboptimal TRS. Our study highlights the utility of laparoscopic scoring assessment to determine resectability over radiology assessment alone in ovarian cancer.