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Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma.This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall survival.There were 737 patients included. Most patients had Stage IA disease (75%), 49% of which had no myometrial invasion. Only 164 (24%) tumors had lymphatic/vascular space invasion. Adjuvant treatment varied: 22% received no adjuvant therapy, 17% had chemotherapy alone, 19% had cuff brachytherapy, 35% had cuff brachytherapy with chemotherapy, and 6% underwent pelvic radiation. Adjuvant treatment was significantly associated with a decreased risk of recurrence (p = 0.04). Compared with no adjuvant therapy, patients who received brachytherapy or brachytherapy/chemotherapy had improved recurrence-free survival (HR 0.59, 95% CI 0.40-0.86; HR 0.65, 95% CI 0.49-0.88, respectively) and overall survival (HR 0.53, 95% CI 0.35-0.79; HR 0.49, 95% CI 0.35-0.69, respectively). Improved survival with brachytherapy and brachytherapy/chemotherapy persisted on multivariable analyses. Chemotherapy alone was also associated with improved overall survival compared with no adjuvant treatment (HR 0.55, 95% CI 0.37-0.81).Adjuvant therapy was associated with a decreased risk of recurrence relative to observation alone. Adjuvant cuff brachytherapy with and without chemotherapy was associated with improved survival outcomes in patients with early stage uterine serous carcinoma.

Sentinel lymph node (SLN) mapping has been adopted as an acceptable method of lymph node evaluation in the surgical staging for low-grade endometrial cancer. In this review, we analyze the literature on the utility of SLN mapping in high-grade endometrial cancer.SLN mapping in high-grade endometrial cancer demonstrates similar high detection rates and diagnostic accuracy as seen in low-grade endometrial cancers. However, obtaining sufficient operator experience (at least 30 cases) and following SLN mapping algorithm continues to be essential to preserving diagnostic accuracy. Although limited in retrospective study design and short-term follow-up, current studies have not demonstrated inferior survival outcomes of SLN mapping compared to traditional lymphadenectomy. SLN mapping is an acceptable and accurate method of lymph node evaluation in high-grade endometrial cancer. Future prospective studies are needed to evaluate long-term oncologic outcomes between SLN mapping and systematic lymphadenectomy in this patient population.

To assess the impact of frailty in patients with ovarian cancer on surgical procedures and outcomes.A retrospective review of patients with stage II-IV ovarian cancer from April 2013 to September 2017 was performed. Patients were triaged by laparoscopy to determine primary resectability. The adjusted modified frailty index score (amFI) was calculated and amFI ≥2 classified as high frailty. Clinical outcomes, progression free survival (PFS) and overall survival (OS) were estimated.592 patients met inclusion criteria; amFI of 0, 1 and ≥ 2 was noted in 57%, 29%, and 14%, respectively. Patients with high frailty were less likely to be offered laparoscopic assessment for primary surgery (49% v. 43% v. 28% for amFI = 0, 1, and ≥ 2, p = 0.004), and more likely to have a Fagotti score ≥ 8 (58%, 48%, and 34%, p = 0.04). Only 17% of the high frailty cohort had primary tumor reductive surgery compared to 26% and 34% in patients with amFI = 1 and amFI = 0 (p = 0.02). Furthermore, patients with higher amFI were less likely to undergo any tumor reductive surgery (85% v. 74% v. 59%, p0.001). Postoperative complications were more frequent in patients with higher amFI (44% v. 56% v. 64%, p = 0.01). Death within thirty days of treatment initiation was significantly higher in patients with high frailty (0.4% v. 2% v. 9%, p = 0.005). In multivariate analysis, high frailty was associated with worse PFS (p = 0.02) and OS (p0.05).Postoperative morbidity, PFS, and OS were worse in patients with high frailty scores. Quantification of frailty may be useful for clinical decision making in patients with newly diagnosed advanced ovarian cancer.

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Purpose:On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance.Patients and Methods:We performed a safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily and capivasertib orally twice daily on a 4-day on 3-day off schedule was evaluated. Two dose levels (DL) of capivasertib were planned: 400 mg (DL1) and 320 mg (DL-1). Patients underwent biopsies at baseline and 28 days.Results:A total of 38 patients were enrolled. Seven (18%) had germline BRCA1/2 mutations. The first 2 patients on DL1 experienced dose-limiting toxicities (DLT) of diarrhea and vomiting. No DLTs were observed on DL-1 (n = 6); therefore, DL1 was reexplored (n = 6) with no DLTs, confirming DL1 as RP2D. Most common treatment-related grade 3/4 adverse events were anemia (23.7%) and leukopenia (10.5%). Of 32 evaluable subjects, 6 (19%) had partial response (PR); PR rate was 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlations between response and immune activity, cell-cycle alterations, and DNA damage response. Therapy resistance was associated with receptor tyrosine kinase and RAS-MAPK pathway activity, metabolism, and epigenetics.Conclusions:The combination of olaparib and capivasertib is associated to no serious adverse events and demonstrates durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. Importantly, tumor samples acquired pre- and on-therapy can help predict patient benefit.

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Purpose:Treatment for patients with recurrent endometrioid endometrial cancer (EEC) are limited as paclitaxel is the only second-line chemotherapy with a response rate >13%. Targeting PIK3/mTOR in combination with hormonal therapy has shown promise. The addition of metformin may enhance this response. We conducted a phase II study evaluating everolimus, letrozole, and metformin in advanced/recurrent EEC.Patients and Methods:A Simon two-stage design was employed. Women with ≤2 prior chemotherapy regimens for recurrence were eligible. Pretreatment biopsy was required, followed by everolimus 10 mg orally, letrozole 2.5 mg orally, and metformin 500 mg orally twice a day on a 4-week cycle. The primary endpoint was clinical benefit (CB), defined as complete response (CR), partial response (PR), or stable disease (SD) confirmed at 16 weeks. Patients were treated until progression or toxicity.Results:Sixty-two patients were enrolled. Median age was 62 years (40–77) with 401 cycles completed, median of 6 cycles (1–31). Fifty-four patients were evaluable for response with a CB rate of 50% (27/54). Best overall response (OR) was PR 28% (15/54) and SD 22% (12/54). Thirteen patients received >12 cycles. Median follow-up was 17.9 months (2–47). Median progression-free survival was 5.7 [95% confidence interval (CI), 3.0–8.1] and OS was 19.6 months (95% CI, 14.2–26.3). Positive progesterone receptor expression was associated with CB (89.5% vs. 27.3%, P = 0.001).Conclusions:Everolimus, letrozole, and metformin resulted in 50% CB and 28% OR in women with recurrent EEC. Progesterone receptor–positive tumors may have better response; validation studies are needed.See related commentary by Madariaga et al., p. 523

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The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Endometrial cancer is the second most common gynecologic cancer worldwide and the most common gynecologic cancer in the United States, with an increasing incidence in high-income countries. Although the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer is a surgical staging system, contemporary published evidence-based data and expert opinions recommend MRI for treatment planning as it provides critical diagnostic information on tumor size and depth, extent of myometrial and cervical invasion, extrauterine extent, and lymph node status, all of which are essential in choosing the most appropriate therapy. Multiparametric MRI using a combination of T2-weighted sequences, diffusion-weighted imaging, and multiphase contrast-enhanced imaging is the mainstay for imaging assessment of endometrial cancer. Identification of important prognostic factors at MRI improves both treatment selection and posttreatment follow-up. MRI also plays a crucial role for fertility-preserving strategies and in patients who are not surgical candidates by helping guide therapy and identify procedural complications. This review is a product of the Society of Abdominal Radiology Uterine and Ovarian Cancer Disease-Focused Panel and reflects a multidisciplinary international collaborative effort to summarize updated information highlighting the role of MRI for endometrial cancer depiction and delineation, treatment planning, and follow-up. The article includes information regarding dedicated MRI protocols, tips for MRI reporting, imaging pitfalls, and strategies for image quality optimization. The roles of MRI-guided radiation therapy, hybrid PET/MRI, and advanced MRI techniques that are applicable to endometrial cancer imaging are also discussed.

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

Background We implemented a systematic multidisciplinary process to engage new outpatients with cancer in selecting and preparing a medical decision-maker. Measures Templated advance care planning notes and medical power of attorney documents were used in the electronic health record by the third office visit. Intervention Patients were coached to meet with social work from a “culture of yes,” viewed a video about the importance of selecting a prepared medical a decision-maker in English or in Spanish, and referenced cards containing simple explanations of advance directives when responding to advance directive questions. Outcomes A total of 351 patients were evaluated. By visit 3, there was no increase in documented social work advance care planning notes in intervention or scanned medical power of attorney documents in the electronic health record. Conclusions/Lessons Learned This systematic multidisciplinary approach did not engage new outpatients with cancer in preparing a medical decision-maker. More active physician involvement and varied ways of engagement are needed.

In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. Despite these advances, the incidence of endometrial cancer as well as the deaths attributable to the disease have continued to rise; from 1987 to 2014 there has been a 75% increase in cases and almost 300% increase in endometrial cancer deaths. Fortunately, since then, there has been progress in the treatment of patients with endometrial cancer with increased utilization of molecular pathology, greater understanding of genetic predisposition, enhanced methods for lymph node assessment, a broader understanding of the efficacy of radiation and chemotherapy, and a more efficient approach to survivorship and surveillance. The purpose of this document is to present a comprehensive review of this progress.The authors reviewed the available evidence, contributed to the development of this manuscript, provided critical review of the guidelines, and finalized the manuscript recommendations. The review was also presented to and approved by the Society of Gynecologic Oncology (SGO) Clinical Practice Committee, SGO Publications Committee, and the SGO board members prior to submission for publication. The recommendations for this manuscript were developed by a panel of gynecologic oncologists who were members of the SGO Clinical Practice and Education Committees. Panelists reviewed and considered evidence from current uterine cancer literature. The terminology used in these guidelines was adopted from the ASCCP management guidelines [1] using a two-part rating system to grade the strength of recommendation and quality of evidence (Table 1). The rating for each recommendation is given in parentheses.

In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. This manuscript, Part II in a two-part series, includes specific recommendations on treatment of recurrent disease, post treatment surveillance and survivorship, considerations for younger women, and special situations. Part I covered histopathology and molecular pathology, risk factors, presentation and diagnostic approach, surgical approach and adjuvant therapy.

BackgroundIn the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node algorithm without complete lymphadenectomy can be used without jeopardizing oncologic outcome, prospective data are lacking.Primary ObjectivesTo assess the 36 month incidence of pelvic/non-vaginal recurrence in women with pathologically confirmed stage I intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes.Study HypothesisWe hypothesize that patients with stage I, intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes will demonstrate a pelvic/non-vaginal recurrence rate comparable to historical estimate of stage I, intermediate-risk endometrioid endometrial carcinoma patients (estimated 2.5%).Trial DesignThis prospective multicenter single-arm observational study will follow women with stage I, intermediate risk endometrioid endometrial adenocarcinoma who have undergone successful hysterectomy, bilateral salpingo-oophorectomy, and bilateral sentinel lymph node biopsies, for recurrence. All patients will undergo lymphatic mapping using indocynanine green and will either receive no adjuvant treatment or vaginal brachytherapy only. Patients will be followed for 36 months.Major Inclusion/Exclusion CriteriaPatients will be enrolled in the study cohort if all the following criteria are met: (i) at time of surgery: hysterectomy with bilateral adnexectomy, and successful bilateral pelvic sentinel lymph node mapping; (ii) on final pathology: pathologic stage I, intermediate-risk endometrioid endometrial carcinoma (grade 1 or grade 2 with ≥50% myometrial invasion, or grade 3 with Primary EndpointIncidence of pelvic/non-vaginal recurrence at 36 months.Sample Size182 patients for study cohortEstimated Dates for Completing Accrual and Presenting ResultsAccrual will be completed in 2023 with results reported in 2026.Trial RegistrationNCT04291612

Purpose: Treatment for patients with recurrent endometrioid endometrial cancer (EEC) are limited as paclitaxel is the only second-line chemotherapy with a response rate >13%. Targeting PIK3/mTOR in combination with hormonal therapy has shown promise. The addition of metformin may enhance this response. We conducted a phase II study evaluating everolimus, letrozole, and metformin in advanced/recurrent EEC. Patients and Methods: A Simon two-stage design was employed. Women with ≤2 prior chemotherapy regimens for recurrence were eligible. Pretreatment biopsy was required, followed by everolimus 10 mg orally, letrozole 2.5 mg orally, and metformin 500 mg orally twice a day on a 4-week cycle. The primary endpoint was clinical benefit (CB), defined as complete response (CR), partial response (PR), or stable disease (SD) confirmed at 16 weeks. Patients were treated until progression or toxicity. Results: Sixty-two patients were enrolled. Median age was 62 years (40–77) with 401 cycles completed, median of 6 cycles (1–31). Fifty-four patients were evaluable for response with a CB rate of 50% (27/54). Best overall response (OR) was PR 28% (15/54) and SD 22% (12/54). Thirteen patients received >12 cycles. Median follow-up was 17.9 months (2–47). Median progression-free survival was 5.7 [95% confidence interval (CI), 3.0–8.1] and OS was 19.6 months (95% CI, 14.2–26.3). Positive progesterone receptor expression was associated with CB (89.5% vs. 27.3%, P = 0.001). Conclusions: Everolimus, letrozole, and metformin resulted in 50% CB and 28% OR in women with recurrent EEC. Progesterone receptor–positive tumors may have better response; validation studies are needed. See related commentary by Madariaga et al., p. 523

IntroductionThe purpose of this study was to compare operative times, surgical outcomes, resource utilization, and hospital charges before and after the implementation of a sentinel lymph node (SLN) mapping algorithm in endometrial cancer.MethodsAll patients with clinical stage I endometrial cancer were identified pre- (2012) and post- (2017) implementation of the SLN algorithm. Clinical data were summarized and compared between groups. Total hospital charges incurred on the day of surgery were extracted from the hospital financial system for each patient and all charges were adjusted to 2017 US dollars.ResultsA total of 203 patients were included: 71 patients in 2012 and 130 patients in 2017. There was no difference in median age, body mass index, or stage. In 2012, 35/71 patients (49.3%) underwent a lymphadenectomy. In 2017, SLN mapping was attempted in 120/130 patients (92.3%) and at least one SLN was identified in 110/120 (91.7%). Median estimated blood loss was similar between groups (100 mL vs 75 mL, p=0.081). There was a significant decrease in both median operative time (210 vs 171 min, p=0.007) and utilization of intraoperative frozen section (63.4% vs 14.6%, pDiscussionImplementation of an SLN mapping algorithm for high- and low-risk endometrial cancer resulted in a decrease in both operative time and intraoperative frozen section utilization with no change in surgical morbidity. While hospital charges did not significantly change, further studies are warranted to assess the true cost of SLN mapping.

Objective We reviewed our institutional data to evaluate toxicity and efficacy outcomes of pembrolizumab/lenvatinib in recurrent endometrial cancer in a “real-world” clinical setting and to compare the impact of reduced lenvatinib starting dose on outcomes. Methods Retrospectively, we reviewed toxicity, treatment responses, and survival outcomes of patients with recurrent endometrial cancer who received ≥1 cycle of pembrolizumab/lenvatinib. We compared subgroups based on lenvatinib starting dose (recommended [20 mg] vs reduced [ Results We analyzed 70 patients (recommended dose cohort, n = 16; reduced dose cohort, n = 54). The most common starting dose was 14 mg daily. Compared to the reduced dose cohort, the recommended dose cohort had a significantly higher mean number of lenvatinib dose reductions due to side effects (1.1 vs. 0.4; p = 0.003) and significantly shorter median time to treatment toxicity (1.3 vs. 3.7 days; p = 0.0001). Response rates did not differ significantly between the recommended and reduced dose cohorts (28.6% vs. 38.3%, respectively; p = 0.752). Two patients, both in the reduced dose cohort, had complete responses. Patients with carcinosarcoma histology had response and clinical benefit rates of 25% (3 of 12) and 58.3% (7 of 12), respectively. There were no differences between the 2 dose cohorts with respect to progression-free (p = 0.245) or overall survival (p = 0.858). Conclusion In clinical practice, a lower starting dose of lenvatinib (14 mg daily) in combination with pembrolizumab was safe and efficacious in recurrent endometrial cancer. The combination produced responses in endometrial carcinosarcomas. Larger studies are required to validate these findings.

OBJECTIVE: To identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer. METHODS: We retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT+RT. Survival rates were calculated using the Kaplan-Meier method. RESULTS: The 5-year disease-specific survival (DSS) rate for all patients was 65%. Adjuvant CT+RT conferred higher rates of 5-year DSS as compared to CT alone in patients with grade 3 endometrioid and non-endometrioid tumors (61% vs. 27%, P = 0.04 and 67% vs. 38%, P = 0.02, respectively). Among patients with non-endometrioid tumors, treatment with concurrent chemoradiotherapy followed by additional sequential chemotherapy had higher 5-year DSS rates than with concurrent chemoradiotherapy alone (74% vs. 50%, P = 0.02). The 3-year pelvic recurrence rate was 5% with RT±CT and 35% with CT alone (P < 0.001) for all patients. No paraaortic nodal failures were observed following extended-field RT, but 14% of patients who received pelvic-only RT or CT alone developed recurrences in the paraaortic nodes (P < 0.001). CONCLUSIONS: Combined-modality therapy including adjuvant external beam pelvic radiotherapy yields excellent outcomes for patients with all subtypes of node-positive endometrial cancer. The most pronounced DSS advantage from adjuvant chemoradiotherapy was evident in women with non-endometrioid endometrial cancer.

Background The identification of extrauterine disease is critical to the management of patients with high-risk endometrial cancer. The purpose of the current study was to determine the accuracy of preoperative positron emission tomography (PET)/computed tomography (CT) in the detection of extrauterine disease. Methods Women with high-risk endometrial cancer were enrolled prospectively and underwent preoperative PET/CT followed by surgery, including sentinel lymph node biopsy and lymphadenectomy. Primary tumor factors on PET/CT were correlated with lymph node pathology. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the detection of lymphadenopathy and peritoneal disease by PET/CT. Results A total of 112 patients were enrolled and underwent PET/CT between April 2013 and May 2016, 108 of whom were evaluable. On PET/CT, 21 patients (19.4%) were found to have extrauterine disease, 18 (17%) had positive lymph nodes, and 8 (7%) had peritoneal disease. A total of 108 patients underwent surgery, 103 of whom (95%) underwent lymphadenectomy. The sensitivity of PET/CT to detect positive lymph nodes was 45.8%, with a specificity of 91.1%, positive predictive value of 61.1%, and negative predictive value of 84.7%. The false-negative rate was 54.2%. There was no difference in primary tumor characteristics on imaging noted between patients with positive and negative lymph nodes. The sensitivity of PET/CT to detect peritoneal disease was 37.5%, with a specificity of 97.8%, positive predictive value of 75%, and negative predictive value of 90.0%. The false-negative rate was 62.5%. Conclusions Preoperative PET/CT did not reliably predict the presence of extrauterine disease in women with high-risk endometrial cancer. Given the high false-negative rates, PET/CT should not be used in the preoperative treatment planning of these patients.

BACKGROUND. Hypomagnesemia is a known side effect of several antineoplastic agents, but its impact on outcomes of patients with cancer is not well understood. We examined whether magnesium abnormalities affect survival in patients with ovarian cancer who receive chemotherapy containing carboplatin. MATERIALS AND METHODS. We included patients with advanced ovarian cancer who had undergone surgery and chemotherapy between January 1, 2004, and December 31, 2014, at our institution. Inclusion criteria were age 18 years or older, pathology of high‐grade serous carcinoma, first treatment (surgery or chemotherapy) within 60 days of diagnosis, and chemotherapy containing carboplatin. The final cohort consisted of 229 patients. Vital signs and laboratory tests were recorded at baseline and during the treatment course. The associations between magnesium abnormalities (and other clinical characteristics) and survival were analyzed. RESULTS. The median patient age was 64 years. Higher baseline heart rate (beats per minute; hazard ratio [HR] = 1.02, p = .002) and greater frequency of hypomagnesemia during the treatment course (HR = 1.05, p = .002) were significantly associated with shorter survival independent of completeness of tumor reduction (HR = 1.60, p = .02), and International Federation of Gynecology and Obstetrics stage (HR = 1.63, p = .01). CONCLUSION. Baseline heart rate and the frequency of hypomagnesemia episodes during treatment are prognostic of survival for patients with advanced ovarian cancer receiving carboplatin‐containing chemotherapy and tumor reductive surgery. Future research is needed for strategies to detect and prevent hypomagnesemia in this patient population. IMPLICATIONS FOR PRACTICE. Despite standard laboratory tests and intravenous magnesium replacement prior to each cycle of chemotherapy, hypomagnesemia remains a common side effect of platinum‐based chemotherapy. This study revealed that frequent occurrence of hypomagnesemia during the course of treatment including carboplatin‐containing chemotherapy and tumor reductive surgery was strongly predictive of shorter survival in patients with advanced ovarian cancer. Strategies to effectively mitigate hypomagnesemia, such as more frequent detection, dietary recommendations, and timely replacement, should be considered in the overall cancer treatment plan for these patients.

Purpose/objective(s) Long-term adverse effects of uterine cancer patients are not well reported. In this single-institution, cross-sectional study we compared pelvic floor dysfunction (PFD) in uterine cancer survivors across different treatment modalities. Materials/methods Patients with uterine cancer treated from 2006-2018 were eligible. Three cohorts with no recurrence of cancer were identified through the institutional tumor registry, including patients who: underwent hysterectomy/bilateral salpingo-oophorectomy (BSO) alone; hysterectomy/BSO and adjuvant brachytherapy; or, hysterectomy/BSO and adjuvant external beam radiation therapy (EBRT). A non-cancer cohort who had a hysterectomy/BSO for benign indications was also identified. To compare PFD, we utilized the Pelvic Floor Distress Inventory (PFDI-20), a validated 20-item measure to assess lower urinary distress (UDI-6), colorectal distress (CRAD-8), and pelvic organ prolapse dysfunction (POPDI-6). The three subscale scores ranged from 0-100, with an overall summary score ranging from 0-300. Treatment, BMI, comorbidities, and number of vaginal births were obtained from medical records. A generalized linear model with γ-distribution and subsequent multivariable model was used to assess treatment modalities and covariate effects on PFDI-20 results. Results A total of 302 patients completed the PFDI-20 (hysterectomy/BSO alone, n = 64; brachytherapy, n = 77; EBRT, n = 96; benign hysterectomy/BSO, n = 65). Median time from surgery to completion of survey was 6.7 years. Median age was 65.9 years (range 34-92), median BMI at surgery 30.9 (range 18.1-68), median current BMI 29.9 (range 16.8-64.3), and median number of vaginal births 1.28 (range 0-10). Most uterine cancers were endometroid (73%, n = 173); 45% (n = 105) were treated with concurrent chemotherapy. Any PFD symptoms were reported in 76% of patients with a median total PFDI-20 score of 38.7. Overall, lower urinary tract symptoms were the most predominant (median 20.1), followed by colorectal-anal distress (median 11.8), then uterovaginal prolapse (median 6.8). The EBRT cohort had the highest median PFDI-20 score (48.9), followed by the benign hysterectomy group (median 43.5), surgery only group (median 34.6), and brachytherapy group (median 27.5). Among the treatment groups, the EBRT cohort had a statistically significant increase in PFD (P = 0.011). Number of vaginal births was associated with significantly worsened overall pelvic floor dysfunction (P = 0.015). Upon multivariable analysis which included treatment cohort, BMI at surgery, current age, number of vaginal births, and Charlson Comorbidity Index, only number of vaginal births remained significant (P = 0.003). Conclusion This study highlighted the effect of treatment modality on pelvic floor dysfunction in uterine cancer survivors and underscores the impact of EBRT on late pelvic floor symptoms and need to screen survivors for symptoms to improve long-term quality of life.

Background: Despite high rates of remission after frontline management, most patients with advanced stage ovarian cancer recur. Second look laparoscopy (SLL) can provide more sensitive detection of minimal residual disease (MRD) allowing for more individualized prognostication and possible therapeutic intervention. It may also assess tumor biology and microenvironment associated with undetectable chemoresistant MRD phase of ovarian cancer. The objective of this study was to determine SLL feasibility, and clinicopathologic and molecular characteristics of MRD after frontline therapy in ovarian cancer. Methods: SLL was offered to patients with stage III-IV high grade epithelial ovarian cancer who achieved complete response after frontline surgery and 6 cycles of carboplatin and paclitaxel chemotherapy. Patients were offered standard of care or investigational management options based on homologous recombination deficiency (HRD) and MRD status at SLL. Preliminary translational studies included RNAseq for comparison of serial, matched tumor from primary or interval TRS and SLL derived MRD+ biopsies at the time of SLL. In addition, Nanostring analyses of SLL surgical biopsies both with and without residual tumor were performed. Molecular profiling employed hierarchical clustering, principle component analysis, non-parametric testing, and pathway analyses. Results: Between 4/2017- 7/2021, 39 patients underwent SLL. The majority had stage III disease (74%), high grade serous histology (90%) and underwent neoadjuvant chemotherapy with interval tumor reductive surgery (TRS; 54%). MRD was present in 49% (n=19) of patients and was more frequent among neoadjuvant chemotherapy recipients (73% vs 26%, P=0.015) and patients with homologous recombination proficient tumors (81% vs 25%, P=0.01). Most patients without MRD were dispositioned to observation; 4 patients with HRD received a PARP inhibitor per standard of care. All other patients with MRD received bevacizumab as part of a clinical trial, except for one patient who received a PARP inhibitor. Median follow-up was 6.74 months (range 0.66 - 28.62). Presence of MRD was associated with worse PFS (HR 3.7, 95% CI 1.3- 10.9; 5.5 vs 24.6 months; P= 0.02). Based on transcriptional signature, MRD are immunologically distinct from untreated tumors or those collected at interval TRS (after 3 cycles of chemo) but also displayed heterogeneity with two distinct subclusters. Conclusions: SLL to assess for MRD has potential to further individualize post-frontline therapy, and identify patients at high risk for progression for early intervention clinical trials. Transcriptional profiling suggests that MRD phase of ovarian cancer is characterized by a distinct, heterogeneous, and evolving tumor and immune microenvironment. Citation Format: Roni Nitecki, Minghao Dang, Sanghoon Lee, Bryan Fellman, J Alejandro Rauh-hain, Jolyn Taylor, Lois Ramondetta, Michaela Grinsfelder, Lauren Cobb, David M. Boruta, Pamela T. Soliman, Aaron Shafer, Nicole D. Fleming, Shannon N. Westin, Anil K. Sood, Chris Tanguma, Pedro T. Ramrez, Karen H. Lu, Linghua Wang, Amir A. Jazaeri. Initial clinicopathologic and molecular characterization of minimal residual disease detected by second look laparoscopy after completion of frontline surgery and chemotherapy in patients with advanced stage ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4135.

6574 Background: Advanced care planning (ACP) involves sharing of knowledge related to prognosis, treatment options, and patient values/goals, among the patient, their caregivers, and the clinical care team. These goals of care (GOC) discussions are critical at different time points during the care of a cancer patient, but are not performed or documented consistently in most oncology practices. The American Society of Clinical Oncology recommends that documentation of advance directive discussions, a component of ACP, take place by the third office visit for patients with newly diagnosed invasive cancer. We implemented a quality improvement initiative to improve ACP discussion and documentation in our large gynecologic oncology practice. Methods: As part of an institution-wide effort called “Mind the Gap: bridging the gap between patients’ perception of their oncologic situation and the reality thereof”, we identified 3 critical timepoints for which a GOC discussion and ACP documentation was recommended in the outpatient setting. These time points included: (1) by the 3rd visit for new patients with an invasive cancer, (2) preoperative (within 30 days of surgery), and (3) at time of treatment/chemotherapy change. Providers were educated on the key components of ACP documentation including surrogate decision maker and goals of cancer treatment. Standard templates were used to document these discussions for easy identification in the electronic health record. Metrics for each faculty team were shared monthly with the entire department. The department goal was to reach a cumulative goal > 60% completion for all patients in each of the 3 clinical time points within 6 months. Results: The proposed plan and education on ACP standard documentation was presented to 22 gynecologic oncologists during a faculty retreat in 10/2020. Baseline data from 8/2020 was shared revealing that ACP documentation was completed in 24% of new patients, 1% of preoperative, and 19% at treatment change. At the 6-month assessment (5/2021), ACP documentation was completed in 83.6% of new patients, 79.8% of preoperative, and 63% of patients at the time of treatment change. At one year (10/2021), ACP documentation was completed on 88.6% of new patients, 70.3% of preoperative, and 59% of patients at the time of treatment change. There was variability among providers in documentation of ACP for new patients (range 50-100%), preoperative (range 0-100%) and treatment change (range 12.5-100%). Conclusions: Through a departmental initiative, we were able to successfully encourage more frequent goals of care discussions and their standardized documentation, which was maintained at 1 year. We are currently evaluating the impact of this program on end-of-life quality metrics including chemotherapy within 14 days, ICU stay within 30 days and multiple hospital admissions within 30 days of end of life.

The success of targeted and immune therapies in other malignancies has led to an exponential increase in the number of active and pending clinical trials using these therapeutic approaches in patients with gynecologic cancers. These novel investigational agents are associated with unique and potentially life-threatening toxicities and many require special multidisciplinary logistical considerations. The objective of this review is to describe a practical approach for the safe implementation of targeted and immune therapies in academic gynecologic oncology practices based on our experience at M.D. Anderson Cancer Center.

BackgroundCombining poly (ADP-ribose) polymerase (PARP) with phosphatidylinositol-3-kinase (PI3K) pathway inhibitors is supported by strong preclinical rationale. We sought to assess safety and determine a recommended phase 2 dose (RP2D) for PARP inhibitor olaparib combined with the AKT inhibitor, capivasertib, and evaluate molecular markers of response and resistance.MethodsAs part of a larger phase 1b trial, we performed a safety lead in of olaparib and capivasertib followed by expansion (n=24) in endometrial, triple negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300mg orally twice daily and capivasertib orally twice daily on a four day on three day off schedule was evaluated. Two dose levels (DL) were planned: capivasertib 400mg (DL1); capivasertib 320mg (DL-1). Patients underwent biopsies at baseline and after 28 days.Findings38 patients were enrolled. 7 (18%) patients had known germlineBRCA1/2mutations. The first two patients on DL1 experienced dose limiting toxicities (DLTs) of diarrhea and vomiting in absence of maximum supportive care. No DLTs were observed on DL-1 (n=6), therefore, DL1 was re-explored (n=6) with no DLTs, confirming this as RP2D. Most common treatment-related grade 3 or 4 adverse events were anemia (23.7%) and leukopenia (10.5%).Of 32 subjects evaluable for response, 6 (19%) had partial response (PR) with a PR rate of 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlation between response and immune activity, as well as alterations in cell cycle and DNA damage response genes. Therapy resistance was associated with receptor tyrosine kinase (RTK) and RAS-MAPK pathway activity, as well as metabolism and epigenetics.InterpretationThe combination of olaparib and capivasertib is well tolerated and demonstrates evidence of durable activity in women’s cancers, with particularly promising response in endometrial cancer. Importantly, tumor samples acquired pre and on-therapy can help predict patient benefit.FundingAstraZeneca, MDACC Moonshots Program, MDACC Support Grant CA016672 NCI SPOREs in Ovarian (CA217685) and Uterine (CA098258) Cancer and a kind gift from the Miriam and Sheldon Medical Research Foundation. AZD5363 was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

OBJECTIVES: To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC). METHODS: A multi-institutional retrospective study of patients with SLN ITCs (

Objective A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). Data Sources We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. Study Eligibility Criteria We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. Methods We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Results We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44–82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4–43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%–95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%–73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%–34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%–96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%–16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%–99%; I2=0%). Conclusion Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.

Objectives: Surgeons have significant choices when selecting specific disposable operating room (OR) equipment and supplies, while most are unaware of the costs associated with these choices. We used a cost transparency tool to demonstrate an impact on discretionary OR spending for disposable supplies. Methods: Patients undergoing laparoscopic hysterectomy or debulking within a gynecologic oncology department were included in this prospective, single-institution study. The operating room staff as well as the surgeons were informed of the cost of disposable equipment including the lowest-cost alternatives for commonly used supplies. Intraoperative supply cost feedback for all included procedures were provided to all surgeons in the department via a custom dashboard and monthly email reports with itemized costs. The results for all surgeons were transparent to all other surgeons in the department and the lowest cost surgeons were highlighted monthly. The primary outcome was percentage change in the cost of disposable supplies in the intervention year (11/1/2018-10/31/2019) as compared to baseline (11/1/2017-10/31/2018). Major postoperative complications including return to OR, wound dehiscence and wound infection were also collected. Results: A total of 21 surgeons performed 539 laparoscopic hysterectomies and a total of 18 surgeons performed 119 debulkings between 11/1/2017-10/31/2019. For laparoscopic hysterectomy, there was an overall average cost increase of 4.6% between the baseline year and the intervention year. Five (28%) of 18 surgeons with surgeries in both years demonstrated average decreases in costs by more than 5%. For debulking, there was an overall average cost decrease of 12.9% from baseline to the intervention year. Eight (53%) of the 15 surgeons with surgeries in both years demonstrated decreased costs by more than 5%. Complication rates did not change significantly over the study period (p=0.83). Conclusions: Transparency in the cost of disposable OR equipment and supplies may result in significant decrease in OR spending without affecting major postoperative complications.

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.

Objectives: We aimed to assess the impact of frailty in ovarian cancer patients on surgical procedures and outcomes. Methods: A retrospective review of a prospectively collected database from April 2013 to September 2017 was performed. Patients with advanced disease were triaged by laparoscopy to determine primary resectability. The modified frailty index score (mFI) was calculated based on the sum of 10 items: chronic obstructive pulmonary disease or recent pneumonia, congestive heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease (CVA), CVA with neurologic deficit, and Eastern Cooperative Oncology Group (ECOG) status 3 or 4, with each item receiving a score of 1 if present. Patients with an mFI ≥2 were classified as high frailty. Clinical outcomes were assessed and compared by mFI using t-test or Fisher's exact test. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: A total of 591 patients met inclusion criteria. A total of 57% of patients had an mFI of 0, 29% mFI of 1, and 14% mFI ≥2. There was no difference in stage by mFI (p=0.984). Patients with high frailty were less likely to be offered a laparoscopic surgery to determine primary resectability than those with an mFI of 1 or 0 (27.63% vs 42.77% vs 48.58%, respectively, p=0.004). If laparoscopy was performed, the modified Fagotti score was more likely to be ≥8 in patients with a higher frailty score (58%, 48%, and 34% for a score of ≥2, 1, and 0, respectively, p=0.038), leading to only 17% of the high frailty cohort proceeding with primary debulking surgery, compared to 26% and 34% in patients with mFI = 1 and mFI = 0 (p=0.015). Furthermore, patients with a higher frailty score were less likely to undergo any tumor reductive surgery (TRS), whether primary or interval (59% vs 74% vs 85% for a score of ≥2, 1, and 0, respectively, p Conclusions: Frailty is associated with bulkier disease, decreased surgical intervention, and worse clinical outcomes.

Objectives: To compare clinical and pathologic characteristics of women with surgical stage I endometrial cancer by location of first recurrence; to describe characteristics of isolated vaginal recurrence. Methods: All women with surgical stage I endometrial carcinoma treated at two major cancer centers from 2009-2017 were identified. Surveillance was done at standard intervals and consisted of symptom assessment and pelvic exam. Imaging was ordered as clinically indicated. Appropriate statistical analyses were used to compare isolated with extra-vaginal recurrences. Vaginal recurrence in the presence of other sites of disease were included in the extra-vaginal recurrence group. Results: 2817 women were analyzed. Median age at diagnosis was 61 years (range 26-92 yrs). At a median follow-up of 36 months (range, 0-139 mos). 280 (10%) recurred: 61 (2%) isolated vaginal, 219 (8%) extra-vaginal (which included 18 cases with a vaginal component). Of the 61 isolated vaginal recurrences, 42 (69%) were located at the cuff, 19 (31%) along the vaginal canal (Figure 1). All isolated recurrences were clinically detected on exam, except for 1 (2%) detected by imaging; endometrioid histology and Grade II were the most common findings (85% and 44%, respectively).Median time to recurrence after initial diagnosis for isolated vaginal recurrence was 11 months (range, 1-68 mos); for extra-vaginal recurrence, 20 months (range, 1-98 mos) (p Download : Download high-res image (134KB) Download : Download full-size image Conclusions: Isolated vaginal recurrences in stage I endometrial cancer are detected earlier than non-vaginal recurrences, likely due to frequency of clinical exams after initial staging surgery. Surgical approach does not seem to impact overall or isolated recurrence. Adjuvant IVRT alone after primary surgery carries a 2% risk of isolated cuff recurrence.

Objectives: Pembrolizumab/lenvatinib demonstrated impressive response rates in advanced/recurrent endometrial cancer (EC) in a recent phase II clinical trial, leading to its accelerated FDA approval. However, tolerability of the recommended 20 mg starting dose of lenvatinib may pose clinical challenges. To comprehend how this regimen translates into daily clinical practice, we evaluated our preliminary data regarding toxicity and efficacy of pembrolizumab/lenvatinib in the treatment of advanced/recurrent EC at the University of Texas MD Anderson Cancer Center. Methods: In this single-institution, retrospective cohort study, we evaluated recurrent/advanced EC patients who received ≥1 cycle of pembrolizumab/lenvatinib treatment. Toxicity was evaluated through rates of hospitalization and treatment interruptions or discontinuations, as well as number of dose reductions. Clinical efficacy was evaluated by best radiologic response to treatment. Clinical benefit was defined as having stable disease or partial/complete response. Results: From October 2019 to July 2020, 83 EC patients were identified but 16 were excluded for unconfirmed administration of pembrolizumab/lenvatinib or lack of toxicity or response data. Thus, 67 EC patients were included in the analysis with a median follow-up of 5 months (range 1 - 11). The median age and number of prior lines of therapy were 67 (range 31–77) and 2 (range 1–9), respectively. The majority had an ECOG performance status of 0 to 1 (91%). The predominant histologic subtype was endometrioid and serous (n=19 each) followed by carcinosarcoma (n=13), mixed (n=8), clear cell (n=4), and other (n=4). The most common starting dose of lenvatinib was 14 mg (n=43; 64.2%), followed by 20 mg (n=15; 22.4%). Treatment-related hospitalizations occurred in 26.9% of patients but did not differ between lenvatinib dosage groups (p=0.37). Compared to those with a lower starting dosage level, patients started on 20 mg doses had significantly higher treatment discontinuations (100% vs 69.2%, p=0.01) and numbers of lenvatinib dose reductions (1.0 vs 0.38, p=0.004), with a trend of higher treatment interruptions (93.3% vs 73.1%, p=0.09). Among the 56 patients with evaluable radiologic response, there were 21 (37.5%) patients with either a partial (n=18) or complete response (n=3), while 18 patients (32.1%) had stable disease. Of the patients with complete response, all patients had a starting lenvatinib dose of 14 mg. Based on a starting lenvatinib dose of 20 mg vs Conclusions: In treatment of recurrent/advanced EC, lower starting dosage of lenvatinib was associated with fewer treatment interruptions/discontinuations and dose de-escalations compared to the FDA recommended 20 mg dosage level while maintaining equivalent response and clinical benefit rates. Furthermore, patients with carcinosarcoma histology also appeared to benefit from pembrolizumab/lenvatinib. While larger studies are needed to validate these safety and efficacy findings, our preliminary data supports starting a lower dosage of lenvatinib in clinical practice.

Uterine serous cancer (USC) is an aggressive subtype of endometrial cancer, with poor survival and high recurrence rates. The development of novel and effective therapies specific to USC would aid in its management. However, few studies have focused solely on this rare subtype. The current study demonstrated that the orally bioavailable, investigational new drug and novel imipridone ONC206 suppressed USC cell proliferation and induced apoptosis both in vitro and in vivo. Disruption of the DRD2-mediated p38MAPK/ERK/PGC-1&alpha, network by ONC206 led to metabolic reprogramming and suppression of both glycolysis and oxidative phosphorylation. ONC206 also synergized with paclitaxel in reducing USC cell viability. In addition, DRD2 overexpression correlated with poor overall survival in patients. This study provides the first evidence that ONC206 induced metabolic reprogramming in USC cells and is a promising therapeutic agent for USC treatment. These findings support further development of ONC206 as a promising therapeutic agent and improves survival rates in patients with USC.

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.

The COVID-19 pandemic has challenged our abilities to provide timely surgical care for patients, including women with gynecologic cancer In March 2020, the American College of Surgeons, The US Surgeon General, and many medical and surgical academic societies recommended postponing elective surgical interventions Recognizing that the pandemic may occur in waves, special considerations should be made for appropriate indications for surgical intervention in the setting of strained resources and personnel to meet surgical demand and prioritize excellent patient care The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to hesitate, and reintegrate surgery Regarding prioritization, patients should be counseled on risks of surgical delay versus in-hospital or community-acquired COVID-19 exposure in the perioperative setting Patients should be informed that surgical prioritization is based on (1) local projected resources, (2) disease prevalence, (3) patient and tumor characteristics, and (4) expected outcomes from delays Several prioritization algorithms have been developed that take into account disease characteristics, patient comorbidities, available personal protective equipment, length of hospital stay, local COVID-10 prevalence, and more Most oncological procedures have been classified as semiurgent, with a high priority tier 3 designation (second to emergent cases and trauma) Published literature demonstrates that most women with newly diagnosed gynecologic cancer are unlikely to be impacted by a few weeks surgical delay Those with malignancies with a propensity for metastasis or advanced stage ovarian and uterine malignancies that require interval cytoreduction should be prioritized when possible For mitigation of complications before, during, and after surgery, patients should be educated on recommendations for social distancing, hand hygiene, and personal protective equipment such as face masks Providers should abide by similar recommendations and use eye protection in the ambulatory and inpatient settings N95 respirators or powered air-purifying respirators are recommended in the care of suspected or known COVID-19 patients Clinical screening should be done at multiple points, COVID-19 testing should be done preoperatively, and a positive test result should delay surgery until asymptomatic formore than 14 days Safety protocols are critical during procedural intubation and extubation, as this is themost hazardous aspect of surgery in a COVID-19-positive/unknown patient Open surgery should not be considered safer than minimally invasive surgery Practitioners for whom the risk of severe disease and death is highest should avoid participating in the surgical care of known COVID-19-positive patients, if possible Telemedicine should be incorporated to limit provider and patient exposure in the postoperative setting Virtual platforms have also demonstrated efficacy in virtual rounding as well as patient care settings to involve family members in treatment planning and discussions around diagnosis Platforms emphasizing enhanced recovery time and same-day discharge should be prioritized, and measures should be taken to reduce delirium risk given lack of patient visitors Reintegration efforts should focus on systematically prioritizing the nonurgent cases that were initially delayed Surgical restrictions are likely to continue for some time, and institutional and departmental leadership will be paramount to optimize surgical manpower, support operative personnel, and use hospital resources equitably and responsibly

Background Obesity is a well-known risk factor for endometrial cancer, but the mechanisms of obesity-related carcinogenesis are not well defined, particularly for premenopausal women. With the continuing obesity epidemic, increases in the incidence of endometrial cancer and a younger age of diagnosis are often attributed to a hyperestrogenic state created by hormone production in adipose tissue, but significant knowledge gaps remain. The balance of estrogen-responsive signals has not been defined in the endometrium of premenopausal women with obesity, where obesity may not create hyperestrogenism in the context of ovaries being the primary source of estrogen production. Obesity is associated with a state of low-grade, chronic inflammation that can promote tumorigenesis, and it is also known that hormonal changes alter the immune microenvironment of the endometrium. However, limited research has been conducted on endometrial immune-response changes in women who have an increased risk for cancer due to obesity. Objective Endometrial estrogen-regulated biomarkers, previously shown to be dysregulated in endometrial cancer, were evaluated in a cohort of premenopausal women to determine if obesity is associated with differences in the biomarker expression levels, which might reflect an altered risk of developing cancer. The expression of a multiplexed panel of immune-related genes was also evaluated for expression differences related to obesity. Study Design Premenopausal women with a body mass index of ≥30 kg/m2 (n=97) or a body mass index of ≤25 kg/m2 (n=33) were prospectively enrolled in this cross-sectional study, which included the assessment of serum metabolic markers and a timed endometrial biopsy for pathologic evaluation, hormone-regulated biomarker analysis, and immune response gene expression analysis. Medical and gynecologic histories were obtained. Endometrial gene expression markers were also compared across the body mass index groups in a previous cohort of premenopausal women with an inherited cancer risk (Lynch syndrome). Results In addition to known systemic metabolic differences, histologically normal endometria from women with obesity showed a decrease in gene expression of progesterone receptor (P=.0027) and the estrogen-induced genes retinaldehyde dehydrogenase 2 (P=.008), insulin-like growth factor 1 (P=.016), and survivin (P=.042) when compared with women without obesity. The endometrial biomarkers insulin-like growth factor 1, survivin, and progesterone receptor remained statistically significant in multivariate linear regression models. In contrast, women with obesity and Lynch syndrome had an increased expression of insulin-like growth factor 1 (P=.017). There were no differences in endometrial proliferation, and limited endometrial immune differences were observed. Conclusion When comparing premenopausal women with and without obesity in the absence of endometrial pathology or an inherited cancer risk, the expression of the endometrial biomarkers does not reflect a local hyperestrogenic environment, but it instead reflects a decreased cancer risk profile that may be indicative of a compensated state. In describing premenopausal endometrial cancer risk, it may be insufficient to attribute a high-risk state to obesity alone; further studies are warranted to evaluate individualized biomarker profiles for differences in the hormone-responsive signals or immune response. In patients with Lynch syndrome, the endometrial biomarker profile suggests that obesity further increases the risk of developing cancer.

IntroductionThe surgical approach for interval debulking surgery after neoadjuvant chemotherapy has been extrapolated from primary tumor reductive surgery for high-grade ovarian cancer. The study objective was to compare pathologic distribution of malignancy at interval debulking surgery versus primary tumor reductive surgery.MethodsPatients with a diagnosis of high-grade serous or mixed, non-mucinous, epithelial ovarian, fallopian tube or primary peritoneal cancer who underwent neoadjuvant chemotherapy or primary tumor reductive surgery and had at least 6 months of follow-up were identified through tumor registry at a single institution from January 1995 to April 2016. Pathologic involvement of organs was categorized as macroscopic, microscopic, or no tumor. Statistical analyses included Mann-Whitney and Fisher’s exact tests.ResultsOf 918 patients identified, 366 (39.9%) patients underwent interval debulking surgery and 552 (60.1%) patients underwent primary tumor reductive surgery. Median age was 62.3 years (range 25.3–92.5). The majority of patients in the interval debulking surgery group were unstaged (261, 71.5%). In the patients who had a primary tumor reductive surgery, 406 (74.6%) had stage III disease. In both groups, the majority of patients had serous histology: 325 (90%) and 435 (78.8%) in the interval debulking and primary tumor reductive surgery groups, respectively. There was a statistically significant difference between disease distribution on the uterus between the groups; 31.4% of the patients undergoing interval debulking surgery had no evidence of uterine disease compared with 22.1% of primary tumor reductive surgery specimens (pConclusionIn patients undergoing interval debulking surgery, there was less macroscopic involvement of tumor in the uterus, adnexa and bowel compared with patients undergoing primary cytoreductive surgery.

// Shin Nishio 1, 2 , Koji Matsuo 3, 4 , Koji Yonemoto 5 , Mototsugu Shimokawa 6 , Masayuki Hosaka 1 , Michiko Kodama 1 , Takahito M. Miyake 1 , Kimio Ushijima 2 , Toshiharu Kamura 2 , Shannon N. Westin 1 , Pamela T. Soliman 1 and Robert L. Coleman 1 1 Department of Gynecologic Oncology and Reproductive Medicine, University of Texas, MD Anderson Cancer Center, Houston, TX, USA 2 Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan 3 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA 4 Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA 5 Biostatistics Center, Kurume University, Kurume, Fukuoka, Japan 6 Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan Correspondence to: Shin Nishio, email: shinshin@med.kurume-u.ac.jp Keywords: stage IVB; cervical cancer; prognostic factor; African-American; para-aortic chain Received: March 19, 2018 Accepted: July 27, 2018 Published: August 17, 2018 ABSTRACT Background: Patients presenting with stage IVB cervical cancer pose a significant clinical challenge. While previous studies described several poor prognostic factors, they were limited by small sample sizes. The aim of this study was to identify clinicopathological prognostic factors in a large sample of patients with stage IVB cervical cancer at a single institution. Methods: Patients with primary stage IVB cervical cancer diagnosed between 1992 and 2011 were extracted from a search of the MD Anderson Cancer Center registry. Clinicopathological data retrieved from their medical records included demographics (age and race), tumor characteristics (primary lesion size, grade, and histology), TNM classification, and metastatic site (nodal/organ). Treatment approach (radiation, chemotherapy, or both) and intent (palliation or curative) were recorded. Survival rates were evaluated using the Kaplan-Meier method. Cox proportional hazards regression was used to model the association between key variables and overall survival (OS). Results: Two hundred sixty-six patients with stage IVB cervical cancer were identified. Their median OS was 12.7 months. The hazard ratio for African-Americans vs. patients with other ethnicities was 1.76 (95% confidence interval [CI], 1.18–2.54, P= 0.0063), and that for patients with para-aortic nodes alone vs. more extensive metastases was 0.37 (95% CI, 0.26–0.51, P< 0.0001). Other clinicopathological factors were not significantly associated with survival. Conclusions: African-American race was an independent adverse prognostic factor in this cohort. On the other hand, nodal disease in the para-aortic chain alone predicted a favorable prognosis.