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Objective: To summarize comparative studies describing clinical outcomes of robotic-assisted surgeries compared with traditional laparoscopic or laparotomy techniques for the treatment of endometrial cancer.Data Sources: Using search words "robotic hysterectomy" and "endometrial cancer," 22 citations were identified from Medline and PubMed (2005 to February 2010).Methods Of Study Selection: We selected English language studies reporting at least 25 robotic cases compared with laparoscopic or laparotomy cases that also addressed surgical technique, complications, and perioperative outcomes. Patients underwent total hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy.Tabulation, Integration, and Results: Eight eligible comparative studies were identified that included 1,591 patients (robotic=589, laparoscopic=396, and laparotomy=606). Pooled means of the resected aortic lymph nodes for robotic hysterectomy and laparoscopy were 10.3 and 7.8 (P=.15), and robotic hysterectomy and laparotomy were 9.4 and 5.7 (P=.28). Pooled means of pelvic lymph nodes for robotic and laparoscopic hysterectomy were 18.5 and 17.8 (P=.95) and 18.0 compared with 14.5 (P=.11) for robotic hysterectomy compared with laparotomy. Estimated blood loss was reduced in robotic hysterectomy compared with laparotomy (P<.005) and laparoscopy (P=.001). Length of stay was shorter for both robotic and laparoscopic cases compared with laparotomy (P<.01). Operative time for robotic hysterectomy was similar to laparoscopic cases but was greater than laparotomy (P<.005). Conversion to laparotomy for laparoscopic hysterectomy was 9.9% compared with 4.9% for robotic cases (P=.06). Vascular, bowel, and bladder injuries; cuff dehiscence; and thromboembolic complications were similar for each surgical method. Transfusions for robotic hysterectomy compared with laparotomy was 1.7% and 7.2% (P=.06) and robotic hysterectomy compared were laparoscopy was 2.6% and 5.0% (P=.22).Conclusion: Perioperative clinical outcomes for robotic and laparoscopic hysterectomy appear similar with the exception of less blood loss for robotic cases and longer operative times for robotic and laparoscopy cases. [ABSTRACT FROM AUTHOR]

Objective: To compare clinical outcomes of patients with early-stage, high-intermediate risk (HIR) endometrial cancer (EC) and isolated tumor cells (ITC) lymph node metastases treated with chemotherapy/radiotherapy (CRT) vs. external beam radiotherapy (EBRT)/vaginal brachytherapy (VBT)., Methods: We retrospectively identified all patients with early-stage HIR endometrioid EC and ITC treated with CRT or EBRT from our institutional database (January-2015 to December-2023). All patients underwent sentinel lymph node (SLN) assessments per NCCN guidelines. Progression-free survival (PFS) and cancer specific survival (CSS) were analyzed using Kaplan-Meier method. We utilized a GOG-99 scoring system in the HIR-ITC cohort to assess risk factors for recurrence., Results: 48 patients were identified, 32(67 %) treated with CRT, 15(31 %) with EBRT and 1(2 %) with VBT alone. Median follow-up was 63.2 and 28 months in CRT vs EBRT/VBT, respectively ( p  = 0.001). In CRT cohort, 4(12.5 %) recurred; two patients with isolated lung metastasis were salvaged and two with multiple sites of metastasis died with disease. No patient in EBRT/VBT cohort (n = 16) recurred. Estimated PFS were 84.4 % and 100 % for CRT and EBRT/VBT, respectively ( p  = 0.392), and CSS were 93.7 % vs. 100 %, respectively ( p  = 0.457). Using HIR scoring per GOG-99, 21(66 %) patients in CRT cohort had three or more HIR risk factors and 4(19 %) recurred despite adjuvant therapy., Conclusion: In this retrospective study, there was no significant difference in survival for patients with HIR endometrial cancer and ITC SLNs treated with either EBRT/VBT or CRT. Patients with three or more HIR risk factors remain at risk for recurrence despite CRT. Further prospective studies should assess recurrence risk factors in HIR EC with ITC, likely incorporating standard histopathology and molecular profiles to tailor adjuvant CRT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Background/objectives: Patients with recurrent or metastatic endometrial cancer (EC) have poor prognoses with limited therapeutic options following immunotherapy or immunochemotherapy treatments. Inhibitors of KRAS mutations (KRAS-mut) have shown efficacy in early solid tumor studies, but data in EC are lacking. This study describes the frequency of KRAS-mut relative to other oncogenic alterations in EC to identify genomic characteristics of KRAS-mut tumors that could lead to novel therapeutic options., Methods: A molecular database of 7870 ECs was queried for presence of oncogenic mutations and immunotherapy biomarkers. Comparisons were performed using Fisher-Exact/ChiSquare (p-values) and adjusted for multiple tests by Benjamini-Hochberg (q) and pairwise nonparametric analysis using Wilcoxon Method., Results: KRAS-mut is a relatively frequent genotype in EC, detected in 16% of cases. Codon 12 was most frequently mutated, with G12D (31%) and G12V (27%) the most common subtypes. Biomarkers of immunotherapy response co-occur with KRAS-mut. Microsatellite instability-high and tumor mutational burden-high status were observed in 34.1% and 36.5% in KRAS-mut compared to 19.8% and 16.9% in KRAS-WT, respectively (p < 0.05). PD-L1 >1% was detected in 8.4% vs 6.4% of KRAS-mut vs KRAS-WT (p < 0.05). BRCA1/2 mutations were detected with similar low frequency (5.9% vs 4.9%) among KRAS-mut and KRAS-WT ECs (p > 0.05). KRAS-mut was inversely associated with Her-2 overexpression (1.8% KRAS-mut vs 13% KRAS-WT. (p < 0.001)., Conclusions: KRAS-mut represents a genotypically distinct group of ECs. Overlap exists with genomic predictors (TMB-high, MSI-high) of immunotherapy response, suggesting a possible biomarker-driven combination option with immunotherapy. Clinical trials to evaluate these strategies should be developed., Competing Interests: Declaration of competing interest RWH has Speaking Honoraria with AstraZeneca, Eisai, Merck, Natera, and Tesaro/GSK; and Consulting or Advisory Roles with Caris, Genelux, Natera, ImmunoGen, and GSK. PHT has done advisory boards or consulting work with Iovance, Astra Zeneca, Glaxo Smith Kline, Clovis Oncology, Zentalis, Novocure, Seagen, Abbvie, R Pharm, Aadi Pharmaceuticals, Caris, Merck, Imunon, Verastem; and has institutional grant funding from Merck and Glaxo Smith Kline. TJH has done advisory boards or consulting work with Aadi, Astra Zeneca, AbbVie (Immunogen), Caris, Clovis, Corcept, Eisai, Genmab, GSK, GOG Foundation, Merck, Pfizer (Seagen), Roche (Genentech). There are no conflicts to report for other co-authors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects. Radical vulvectomy post-radiation for persistent disease is often compromised with poor wound healing. We describe clinical outcomes for patients who received neoadjuvant chemotherapy plus bevacizumab followed by radical vulvectomy for locally advanced vulvar cancer., Methods: We performed retrospective analyses of all patients at our institution who underwent radical vulvectomy from January 2015 to November 2023. Of 113 patients, 13 patients underwent neoadjuvant chemotherapy. Demographics and clinicopathologic data were extracted, and descriptive statistical analyses were performed. Cases with neoadjuvant chemotherapy plus bevacizumab were further evaluated for response, adverse effects, and survival., Results: Neoadjuvant chemotherapy was administered to 13 patients with stage II-IV disease that involved the urethra, vagina, or anus. Lesion sizes ranged from 4 to 20 cm (median 7 cm). Patients received 2-6 cycles of carboplatin or cisplatin, paclitaxel, and bevacizumab. Nine (69.2%) patients had partial pathologic responses, and four patients had complete responses. All patients had negative surgical margins. Ten (76.9%) patients had radiographic evidence of inguinal lymph node metastasis prior to neoadjuvant chemotherapy, and four had residual nodal disease. Only one patient developed a superficial groin seroma. Three patients developed recurrence, two locally and one distant, and there was one death. The median follow-up was 23 months (range 6-84 months)., Conclusions: Neoadjuvant chemotherapy using combination platinum/paclitaxel/bevacizumab was efficacious for locally advanced vulvar cancer, resulting in complete resections, negative margins, and excellent wound healing. A multi-institutional phase II trial is warranted to validate these findings., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This phase 1b study (ClinicalTrials.gov identifier NCT03695380) evaluated regimens combining PARP and MEK inhibition, with or without PD-L1 inhibition, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer (PSROC)., Methods: Patients with PSROC who had received one or two prior treatment lines were treated with 28-day cycles of cobimetinib 60 mg daily (days 1-21) plus niraparib 200 mg daily (days 1-28) with or without atezolizumab 840 mg (days 1 and 15). Stage 1 assessed safety before expansion to stage 2, which randomized patients who had BRCA wild-type PSROC to receive either doublet or triplet therapy, stratified by genome-wide loss of heterozygosity status (<16% vs. ≥16%; FoundationOne CDx assay) and platinum-free interval (≥6 to <12 vs. ≥12 months). Coprimary end points were safety and the investigator-determined objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Potential associations between genetic parameters and efficacy were explored, and biomarker profiles of super-responders (complete response or those with progression-free survival [PFS] >15 months) and progressors (disease progression as the best response) were characterized., Results: The ORR in patients who had BRCA wild-type PSROC was 35% (95% confidence interval, 20%-53%) with the doublet regimen (n = 37) and 27% (95% confidence interval, 14%-44%) with the triplet regimen (n = 37), and the median PFS was 6.0 and 7.4 months, respectively. Post-hoc analyses indicated more favorable ORR and PFS in the homologous recombination-deficiency-signature (HRDsig)-positive subgroup than in the HRDsig-negative subgroup. Tolerability was consistent with the known profiles of individual agents. NF1 and MKNK1 mutations were associated with sustained benefit from the doublet and triplet regimens, respectively., Conclusions: Chemotherapy-free doublet and triplet therapy demonstrated encouraging activity, including among patients who had BRCA wild-type, HRDsig-positive or HRDsig-negative PSROC harboring NF1 or MKNK1 mutations., (© 2024 F. Hoffmann‐La Roche. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: Among uterine malignancies, endometrial cancer (EC) is the most common cancer of the female reproductive tract. Traditionally, risk stratification in EC is determined by standard clinicopathological risk factors. Although circulating tumor DNA (ctDNA) has emerged as a prognostic biomarker in various malignancies, its clinical validity in EC remains to be established., Methods: In this analysis of real-world data, 267 plasma samples from 101 patients with stage I EC were analyzed using a tumor-informed ctDNA assay (Signatera™ bespoke mPCR-NGS). Patients were followed post-surgically and monitored with ctDNA testing for a median of 6.8 months (range: 0.37-19.1)., Results: Patients who tested ctDNA-positive at both their first time point and longitudinally experienced inferior recurrence-free survival (RFS) (HR = 6.2; p = 0.0006 and HR = 15.5; p < 0.0001, respectively), and showed a recurrence rate of 58% and 52%, vs. 6% and 0%, respectively for the ctDNA-negative patients. Most ctDNA-positive patients had high-risk histologies or sarcoma, versus low-risk and high-intermediate risk (H-IR) EC. Furthermore, patients with high-risk histologies who were ctDNA-positive showed shorter RFS compared to those who tested negative (HR = 9.5; p = 0.007), and those who tested positive in the low/H-IR cohort (HR = 0.25; p = 0.04). Post-surgically, detectable ctDNA was highly prognostic of clinical outcome and remained the only significant risk factor for recurrence when adjusted for clinicopathological risk factors, such as histologic risk group, mismatch repair (MMR), and p53 status., Conclusion: Incorporating ctDNA monitoring along with traditional known risk factors may aid in identifying patients with stage I EC who are at highest risk of recurrence, and possibly aid in treatment stratification., Competing Interests: Declaration of Competing Interest COIs for A.P: Stock ownership: Natera. COIs for R.H: Speaker's Bureau: Natera, Inc., Bard Davol, AstraZeneca, GSK, Merck, Eisai; Consultant: Genelux. C.B·S, E.K., S.RH., T.F., P.D., M.M., A.E., and M.C.L. are employees of Natera, Inc. and have stock/option to hold stock in the company. T.B. and B.N. are former employees of Natera, Inc. Additional COIs for M.C.L: Grants/Contracts: Funding to Institution (Mayo) from: Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; Travel Support Reimbursement from AstraZeneca, Genomic Health, Ionis; Ad hoc advisory board meetings. All funds to Mayo Clinic. No personal compensation from: AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax. All other authors have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Infusion-related hypersensitivity reactions with paclitaxel are common despite the use of dexamethasone and diphenhydramine premedications. Paclitaxel titration protocols that may reduce reactions are empirically derived from clinical observations, and there are no phase III trials that confirm superiority of any management recommendations. The purpose of this study was to compare the frequency and severity of hypersensitivity reactions associated with a recently initiated standardized paclitaxel titration protocol verses standard-of-care (SOC) infusion protocols., Materials and Methods: This was a retrospective review of hypersensitivity reactions in patients receiving paclitaxel infusions at five ambulatory infusion centers using a standardized titration protocol (February 2021 to April 2021) versus SOC paclitaxel (November 2018 to December 2019). Patients were age 18 years or older and presented for their first or second infusions. The primary study measure was the rate of hypersensitivity reactions. Secondary evaluations included the timing of the reaction after the start of the infusion, use of premedications, and severity of reactions., Results: A total of 451 patients were included in this study. Eighty-four (18.6%) patients were identified in the titration protocol group and 367 (81.4%) patients in the SOC group. Hypersensitivity reactions occurred in 4.8% of the titration group and 18.3% of the SOC group (odds ratio [OR], 0.224; 95% CI, 0.09 to 0.74; P = .002). Grade 3 or greater infusion reactions were 0% in the titration group versus 18% in the SOC group (OR, 0.28; P < .008). Reactions occurred later with the titration protocol, compared with the SOC paclitaxel infusion. Finally, no differences were observed in the use of appropriate premedications., Conclusion: A standardized paclitaxel titration protocol was associated with a significant reduction in the rate of infusion-related hypersensitivity reactions in patients receiving their first and second infusions. A prospective randomized trial is needed to validate these observations.

High-grade serous ovarian cancer (HGSOC) is a particularly lethal malignancy that is prognostically influenced by the immune profile of the tumor microenvironment (TME). TME immune profiles have been sub-categorized according to features associated with both survival outcomes as well as response to systemic therapies. Five suggested immune phenotypes have been described and correlated with overall survival outcomes. Phenotypes associated with shorter overall survival rates appear to have prominent immunosuppressive features within their TME. The opportunity to triage patients according to their prognostic TME profile might allow selection of individual patients with poor prognostic features who could most benefit from innovative immunomodulatory treatment strategies. Two potential strategies to indirectly manipulate the TME (and oncologic outcomes) are alteration of the gut microbiome composition and alteration of TME metabolism through dietary interventions. Experimental dietary modifications in humans designed for influencing cancer outcomes are only beginning to be studied in a prospective fashion. Herein we summarize prognostic TME features in HGSOC and potential opportunities for immunomodulation via dietary and gut microbial interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study assessed the efficacy, safety, and health-related quality of life (HRQoL) of the treatment regimen of dostarlimab, a programmed death-1 inhibitor, combined with niraparib, a poly (ADP-ribose) polymerase inhibitor, in patients with BRCA wild type (BRCAwt) recurrent platinum-resistant ovarian cancer (PROC) who had previously received bevacizumab treatment., Methods: This Phase II, open-label, single-arm, multicenter study, conducted in the USA, enrolled patients with recurrent PROC to receive niraparib and dostarlimab until disease progression or unacceptable toxicity (up to 3 years). A preplanned interim futility analysis was performed after the first 41 patients had undergone ≥1 radiographic evaluation (approximately 9 weeks from the first treatment)., Results: The prespecified interim futility criterion was met and the study was therefore terminated. For the 41 patients assessed, the objective response rate (ORR) was 7.3% (95% confidence interval: 1.5-19.9); no patients achieved a complete response, 3 patients (7.3%) achieved a partial response (duration of response; 3.0, 3.8, and 9.2 months, respectively), and 9 patients (22.0%) had stable disease. In total, 39 patients (95.1%) experienced a treatment-related adverse event, but no new safety issues were observed. HRQoL, assessed using FOSI, or Functional Assessment of Cancer Therapy - Ovarian Symptom Index scores, worsened over time compared with baseline scores., Conclusions: The study was terminated due to the observed ORR at the interim futility analysis. This highlights a need for effective therapies in treating patients with recurrent BRCAwt PROC., Competing Interests: Declaration of Competing Interest LMR reports personal fees from GSK/TESARO for consultancy unrelated to this study; research grant (to institution): Seagen, Genmab, Merck, Akeso, Mersana, Incyte, GOG Foundation, Genentech; consulting fees: Agenus, Akeso, AstraZeneca, Clovis Oncology, Eisai, Elevar, EMD Serono/Merck, Genmab, Seagen, GOG Foundation, Hengrui, ImmunoGen, Iovance, Merck, Mersana, Myriad, Novocure, Pfizer, Regeneron, Roche/Genentech, GSK/Tesaro, Zentalis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Eisai, Myriad, Roche/Genentech, GSK/Tesaro. DMO reports grant funding (to the institution) from AbbVie; personal fees for an advisory board from AbbVie; support for manuscript preparation from GSK/TESARO. BJM reports consulting/advisory role and honoraria for AbbVie, ChemoCare, ChemoID, Eisai, Geistlich Pharma, Incyte, Mateon Therapeutics, Merck, Myriad Pharmaceuticals, Perthera, Precision Oncology, Samumed, Takeda, and VBL Therapeutics; consulting/advisory role, honoraria, and research funding (to the institution) from Advaxis, Amgen, Immunogen, NuCana BioMed and Pfizer; consulting/advisory role, speakers bureau, honoraria, and research funding (to the institution) from AstraZeneca, Roche/Genentech and TESARO; consulting/advisory role, speakers bureau and honoraria from Clovis Oncology; speakers bureau, honoraria and research funding (to the institution) from Janssen; consulting/advisory role for Cerulean Pharma, OncoMed, and OncoSec; a leadership role for US Oncology; honoraria from Agenus, Conjupro Biotherapeutics, Genmab, Immunomedics, OncoQuest, and PumaBiotechnology; research funding (to the institution) from Array BioPharma, Lilly, Morphotek, Novartis, and Regeneron. RLC reports consulting, grant and honoraria/reimbursement from AstraZeneca, Clovis Oncology, Janssen, Merck, and Roche/Genentech; consulting and honoraria/reimbursement from Arrivive, Eisai, Novocure, Oncomed/Mateo, and TESARO/GSK; consulting and grant from AbbVie, grant from Genmab. SG reports a consulting/advisory role for AstraZeneca, Immunogen, Rigel, and Sermonix Pharmaceuticals; research funding (to the institution) from AbbVie, AstraZeneca, Genentech/Roche, Iovance Biotherapeutics, Pfizer, PharmaMar, and GSK/TESARO; hold patents, royalties or other intellectual property with Sermonix Pharmaceuticals. SA reports research funding from AstraZeneca. LRD reports consulting/advisory role for Genentech/Roche, Merck, Inovio Pharmaceuticals, CUE Biopharma; institutional research funding from GSK, Millennium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, GSK/TESARO, Cerulean Pharma, Aduro Biotech, Advaxis, Syndax, Pfizer, Merck, Genentech/Roche, Cerulean Pharma, Morab, Morphotek, Syndax, Ludwig Institute for Cancer Research, Leap Therapeutics. HD reports a consulting/advisory role for Eisai and Merck. RWH reports speaker's bureau from AstraZeneca, Clovis, and GSK. MH reports advisory board participation for Clovis Oncology, Janssen, Immunogen, Eisai, Seagen, and Tesaro; grant funding from Merck. HSC has nothing to disclose. NGC reports participation in advisory boards from AstraZeneca, GSK, Toray, Tarveda Therapeutics, Aadi. ACE is an employee and stockholder in Natera Inc. REO is funded in part by the NIH/NCI Cancer Center Support Grant P30 CA008748, reports personal fees for advisory boards from TESARO/GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, R-Pharm, Miltenyi, 2seventybio and Immunogen; reports personal fees from MJH Life Sciences, Onclive/PER and Curio; and reports non-compensated membership of steering committees for the PRIMA and DUO-O studies. SW reports a consulting/advisory role for Regeneron. AT, AS, LMN, AB and VS are employees of and hold stocks/shares in GSK. PAK reports personal fees from GSK/TESARO for consultancy unrelated to this study and personal fees for advisory board participation from AstraZeneca, Merck, and Pfizer., (Copyright © 2023. Published by Elsevier Inc.)

Background: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer., Primary Objective: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer., Study Hypothesis: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab., Trial Design: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab., Major Inclusion/exclusion Criteria: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy., Primary Endpoint: The primary endpoint is PFS in the intention-to-treat population., Sample Size: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events., Estimated Dates for Completing Accrual and Presenting Results: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025., Trial Registration: NCT05281471., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Malignant peritoneal cytology in endometrial cancer (EC) is not considered an independent adverse prognostic factor for uterine-confined disease and is not a determinant factor in the International Federation of Gynecology and Obstetrics (FIGO) staging system. NCCN Guidelines still recommend obtaining cytologies. The aim of this study was to determine the prevalence of peritoneal cytologic contamination following robotic hysterectomy for EC., Methods: Peritoneal cytology from the pelvis and diaphragm were obtained at the initiation of surgery, and from the pelvis only at the completion of robotic hysterectomy with sentinel lymph node mapping (SLNM). Cytology specimens were evaluated for the presence of malignant cells. Pre- and post-hysterectomy cytology results were compared, and pelvic contamination was defined as conversion from negative to positive cytology following surgery., Results: 244 patients underwent robotic hysterectomy with SLNM for EC. Pelvic contamination was identified in 32 (13.1%) cases. In multivariate analysis, pelvic contamination was associated with >50% myometrial invasion, tumor size >2 cm, lymphovascular space invasion (LVSI), and lymph node metastasis. There was no association with FIGO stage or histology subtypes., Conclusions: Malignant peritoneal contamination occurred during robotic surgery for EC. Large lesions (>2 cm), deep invasion (>50%), LVSI, and lymph node metastasis were each independently associated with peritoneal contamination. Whether or not peritoneal contamination increases risk for disease recurrence should be studied in larger series, including an evaluation of patterns of recurrence and the potential impact of adjuvant therapies. Until the clinical impact of peritoneal contamination during hysterectomy for EC is better understood, methods to reduce peritoneal contamination are warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest associated with this research project., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need., Objective: To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC., Design, Setting, and Participants: This open-label, nonrandomized multisite phase 2 VIRO-15 clinical trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022., Interventions: Olvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab., Main Outcomes and Measures: Primary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS)., Results: Twenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths., Conclusions and Relevance: In this phase 2 nonrandomized clinical trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3 trial., Trial Registration: ClinicalTrials.gov Identifier: NCT02759588.

Objective: ARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma who responded to their latest line of platinum therapy. Rucaparib improved progression-free survival across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib., Methods: Patients were randomized 2:1 to receive rucaparib 600 mg twice daily or placebo. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were evaluated for association with exceptional benefit (progression-free survival ≥2 years) versus progression on first scan (short-term subgroup) and other efficacy outcomes., Results: Rucaparib treatment was significantly associated with exceptional benefit compared with placebo: 79/375 (21.1%) vs 4/189 (2.1%), respectively (p < 0.0001). Exceptional benefit was more frequent among patients with favorable baseline clinical characteristics and with carcinomas harboring molecular evidence of homologous recombination deficiency (HRD). A comparison between patients who derived exceptional benefit from rucaparib and those in the short-term subgroup revealed both clinical markers (no measurable disease at baseline, complete response to latest platinum, longer penultimate platinum-free interval) and molecular markers (BRCA1, BRCA2, RAD51C, and RAD51D alterations and genome-wide loss of heterozygosity) significantly associated with exceptional benefit., Conclusions: Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favorable clinical characteristics or molecular features associated with HRD. Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of patients with recurrent high-grade ovarian carcinoma., Competing Interests: Declaration of Competing Interest DMO reports personal fees from consulting and/or advisory board participation from Clovis Oncology, AbbVie, Agenus, Ambry, Amgen, Arquer Diagnostics, AstraZeneca, Celsion Corp, Corcept Therapeutics, Eisai, Elevar, Genelux, Genentech/Roche, GOG Foundation, Immunogen, Inxmed, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Merck, Mersana, Myriad Genetics, Novartis, Novocure, Regeneron, Roche Diagnostics MSA, Rubis, SeaGen, SDP Oncology (BBI), Takeda, and Tesaro/GlaxoSmithKline, Toray; research funding (all funding to institution) from Clovis Oncology, AbbVie, Agenus, Ajinomoto, Amgen, Array Biopharma, AstraZeneca, Bristol Myers Squibb, Cerulean Pharma, Eisai, EMD Serono, Ergomed, Genentech/Roche, GenMab, GOG Foundation, Immunogen, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Ludwig Institute for Cancer Research, Merck, National Cancer Institute, New Mexico Cancer Care Alliance, Novocure, PRA International, Regeneron, SeaGen, Serono, Stemcentrx, Tesaro/GlaxoSmithKline, Tracon Pharmaceuticals, VentiRx, and Yale University; and has given a presentation on ovarian cancer at the National Comprehensive Cancer Network. AMO reports grants to his institution from AstraZeneca; has served on steering committees for Clovis Oncology, AstraZeneca (uncompensated), and Tesaro (uncompensated); has served in an advisory role for AstraZeneca and GlaxoSmithKline (uncompensated); and has acted as a principal investigator on investigator-initiated trials with agents from Clovis Oncology, AstraZeneca, and GlaxoSmithKline. DL reports institutional research funding from Clovis Oncology, AstraZeneca, Corcept Therapeutics, GlaxoSmithKline, Genmab, ImmunoGen, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, and Seagen; consulting fees from Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and PharmaMar; payment or honoraria for lectures from Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and Seagen; support for attending meetings and/or travel from AstraZeneca, PharmaMar, and Roche; participation on a data safety monitoring board or advisory board for Clovis Oncology, Agenus, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche; and serves on the board of directors for GCIG and as chair of GCA for ENGOT. CA has served on a steering committee for AbbVie and Genentech; has served as a principle investigator for studies by Clovis Oncology, AbbVie, AstraZeneca, and Genentech; served on advisory boards for AbbVie, AstraZeneca/Merck, Blueprint Medicine, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech; and serves on the board of directors (unpaid) for GOG Foundation and NRG Oncology. AO reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology, AstraZeneca Farmaceutica Spain, AstraZeneca, Corcept Therapeutics, Deciphera Pharmaceutical, Eisai Europe Limited, EMD Serono, F. Hoffmann-La Roche, GlaxoSmithKline, Got It Consulting, Immunogen, KL Logistics, Medison Pharma, Merck Sharp & Dohme de España, Mersana Therapeutics, Novocure GmbH, PharmaMar, prIME Oncology, Roche Farma, Shattuck Labs, Sutro Biopharma, Tesaro Bio GmbH, Tesaro Bio Spain, and Tesaro; and support for attending meetings and/or travel from AstraZeneca, Roche, and PharmaMar. AD has served in a consulting or advisory role for Precision Oncology Australia, Shire Pharmaceuticals, and Specialised Therapeutics Australia; and sits on the scientific advisory board for A2A Pharmaceuticals. NC reports institutional research funding from Clovis Oncology; serving in a consulting or advisory role for Clovis Oncology, AstraZeneca, BIOCAD, Eisai, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, Mersana, Novartis, Nuvation Bio, Oncxerna, Pfizer, PharmaMar, Roche, and Tesaro; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and Novartis; and support for attending meetings and/or travel from AstraZeneca. JIW has received research support from AstraZeneca. ARC reports consulting fees for advisory boards for AstraZeneca; payment or honoraria for speakers bureaus for Clovis Oncology and Merck Sharp & Dohme; support for attending meetings and/or travel from Tesaro; and institutional research funding from Clovis Oncology and AstraZeneca. GS reports royalties or licenses from Merck Sharp & Dohme Italia; consulting fees from Tesaro Bio Italy and Johnson & Johnson; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology Italy. AL has served on advisory boards for Clovis Oncology, Ability Pharmaceuticals, AstraZeneca, BIOCAD, GamaMabs, Genmab/Seattle Genetics, GlaxoSmithKline, Gritstone, Merck Serono, Merck Sharp & Dohme, and Tesaro; steering committee for Merck Sharp & Dohme; reports institutional support for clinical trials or academic research from Clovis Oncology, Ability Pharmaceuticals, Agenus, AstraZeneca, Incyte, Inivata, Iovance, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, and Tesaro; and reports boarding and travel expenses for congress activities from Clovis Oncology, AstraZeneca, and Roche. RWH reports consulting fees from Clovis Oncology, AstraZeneca, and GlaxoSmithKline; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology, AstraZeneca, and GlaxoSmithKline. MAG has served on speakers' bureaus for Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and PharmaMar; and reports support for attending meetings and/or travel from GlaxoSmithKline. PCF reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Merck Sharp & Dohme; support for attending meetings and/or travel from Merck Sharp & Dohme and Pfizer. JCG reports consulting fees from AstraZeneca, Bristol Myers Squibb, Eisai, and Merck Sharp & Dohme; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Bristol Myers Squibb, Ipsen, and Merck Sharp & Dohme Australia; support for attending meetings and/or travel from AstraZeneca; participation on a data safety monitoring board or advisory board for Bristol Myers Squibb and Janssen; and stock or stock options for ICON Cancer Care, Australia. EMS reports institutional research funding from Clovis Oncology. LM, SG, KL, and TK are employees of Clovis Oncology and may own stock or have stock options in that company. JAL has received lecture fees from Clovis Oncology, AstraZeneca, GlaxoSmithKline, and Pfizer; served on advisory boards for Clovis Oncology, Amgen, Artios Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, Merck/Merck Sharp & Dohme, Nuvation, Pfizer, Regeneron, VBL Therapeutics, and Tesaro/GlaxoSmithKline; and received research grants from AstraZeneca and Merck/Merck Sharp & Dohme. RLC reports grants or contracts from Clovis Oncology, AstraZeneca, Gateway Foundation, Genelux, Genmab, Janssen, Merck, and Roche/Genentech; consulting fees from Clovis Oncology, Agenus, Alkermes, AstraZeneca, Deciphera, Genelux, Genmab, GlaxoSmithKline, Immunogen, Janssen, OncoQuest, OncXerna, Onxeo, Regeneron, and Roche/Genentech., (Copyright © 2022. Published by Elsevier Inc.)

Objective: The aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG)., Methods: A systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion., Results: Fourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%-97.9%) and 76.5% (95% CI=68.1%-84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%-15.2%) in patients with grade 1-2 endometrial cancer and 11.8% (95% CI=8.1%-16.1%) in patients with grade 1-3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%-100%) in studies that included grade 1-2 endometrial cancer and 99.2% (95% CI=97.9%-99.9%) in studies that also included grade 3., Conclusion: SLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediate-risk endometrial cancer., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The gold standard therapeutic approach is a combination of surgery plus chemotherapy. Unfortunately, 80% of patients with EOC suffer recurrence within 2-years and the overall response rate for platinum-resistant epithelial ovarian cancer to cytotoxic chemotherapy or poly-(adenosine diphosphate)-ribose polymerase (PARP) inhibitor is modest. New therapies are needed to improve overall survival. The role of immunotherapy has been established in endometrial and cervical cancers, however its effective use in EOC has been limited due to the intrinsic genomics and micro-immune environment associated with EOC. Studies evaluating immunotherapy, largely immune checkpoint inhibitors (ICI), have shown limited activity, yet some patients benefit greatly. Thus, significant efforts must be devoted to finding new strategies for the use of immunotherapy/immunomodulatory drugs (IMiDs). Immunotherapy has a well-tolerated safety profile; however, cost-effectiveness can be an obstacle. The aim of this article is to review the most recent research into the use of IMiDs in patients with platinum-resistant epithelial ovarian cancer., Competing Interests: Dr Nathalie D McKenzie reports advisory board and/or speaker fees from GSK, Merck, Clovis, and AstraZeneca, outside the submitted work. Prof. Dr. Robert W Holloway reports personal fees from Eisai, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Awada et al.)

Purpose: Minimally invasive radical hysterectomy has been associated with increased recurrence of disease and worse survival compared with open radical hysterectomy for early-stage cervical cancer. We evaluated patterns of recurrence and histopathologic risk factors in patients who underwent robotic radical hysterectomy (RRH)., Methods: Patients who underwent RRH (4/2007-12/2018) were evaluated for specific locations of recurrent disease, disease-free survival, overall survival (OS), and histopathologic risk factors for recurrence. Inclusion criteria were follow-up ≥ 1 year, histology with adenocarcinoma, adenosquamous, or squamous carcinoma and clinical stage IA2 to IB ≤ 4-cm tumor size cervical cancers (FIGO-2018)., Results: A total of 140 patients underwent RRH and 112 met criteria. Median tumor size was 2.1 cm [interquartile range (IQR): 1.1-3.3]. Median follow-up was 61 months (IQR: 36-102). Fifty (45%) patients underwent adjuvant radiation ± cisplatin with either Sedlis' or Peters' risk factors. There were 11 (9.8%) recurrences with median disease-free survival of 12 (IQR 8.5) months. All patients with recurrence had measured tumor size ≥ 2 cm (median tumor size 3-cm (IQR: 2.6-4.0). Tumor size > 2 cm was associated with Sedlis' intermediate-risk factors (p < 0.05) and Peters' high-risk factors (p < 0.05). Forty patients underwent preoperative conization, and two (5%) with deep positive margins in lesions > 2 cm recurred. Five (4.5%) of patients had carcinomatosis representing 45% of all recurrences. Carcinomatosis was associated with reduced OS compared with other recurrence patterns (22 months vs. 7.8 years, p < 0.05)., Conclusions: Carcinomatosis was observed in early-stage cervical cancers treated with RRH and was associated with reduced OS. All recurrences were associated with lesions ≥ 2 cm, and no recurrences were identified with negative conization margins., (© 2021. Society of Surgical Oncology.)

Intravenous leiomyomatosis (IVL) is an uncommon variant of leiomyoma characterized by intravascular proliferation of a histologically benign smooth muscle tumor extending beyond the uterus into the distant great vessels. Leiomyomatosis may reach the inferior vena cava, right atrium, and pulmonary arteries. Owing to its rare occurrence, intracardiac leiomyomatosis has been reported as isolated case reports and small case series. Early diagnosis and prompt surgical intervention are vital to prevent cardiac symptoms, pulmonary embolism, and sudden death. Complete tumor resection is essential for a favorable outcome, usually assisted with multimodal surgical imaging and multidisciplinary surgical planning. Herein, we report the case of a 50-year-old female that presented with a three-month history of abdominal pain and lower extremity edema with evidence of IVL extending to the inferior vena cava and right atrium. The patient was managed with a single-stage surgery involving cardiopulmonary bypass and excision of the right atrial and inferior vena cava tumors, as well as modified radical total abdominal hysterectomy and bilateral salpingo-oophorectomy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

CDK12 biallelic inactivation is associated with a distinct genomic signature of focal tandem duplications (FTDs). Gene fusions resulting from FTDs increase neoantigen load, raising interest in CDK12 as a biomarker of response to immune checkpoint inhibitors. Despite evidence of FTDs in multiple CDK12-altered cancer types, notably prostate and ovarian, report of fusion-associated neoantigen load is limited to prostate cancer. Molecular profiles were retrospectively reviewed for CDK12-biallelic (CDK12-biLOF) and -monoallelic loss-of-function (CDK12-monoLOF) in a primary cohort of >9000 tumors, representing 39 cancer types, and immune epitopes were predicted from fusions detected by whole transcriptome sequencing. CDK12-biLOF was identified for 0.3% tumors overall, most frequently in prostate cancer (4.7%). CDK12-biLOF tumors had higher mean fusion rates and fusion-associated neoantigen load than CDK12-monoLOF and CDK12-WT tumors (P < 0.01). However, concurrent mismatch repair deficiency/microsatellite instability with CDK12-biLOF associated with low fusion rates. Among CDK12-biLOF tumors, fusion-associated neoantigen load was highest in prostate and ovarian cancers, which correlated with distinct immune profiles. In a validation cohort, CDK12-biLOF tumors (0.4%) exhibited high mean fusion rates, particularly for prostate and ovarian tumors. Low fusion rates in other CDK12-biLOF tumor types warrant further investigation and highlight the value of quantitative biomarkers. Fusion rate and fusion-associated neoantigen load are linked to CDK12-biLOF in select cancers and may help to identify responders of immune checkpoint inhibitor therapy., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: Our objective was to assess safety and adverse events associated with intraperitoneal Olvi-Vec virotherapy in patients with platinum-resistant or refractory ovarian cancer (PRROC). Secondary objectives included objective response rate (ORR) per RECIST 1.1 and progression-free survival (PFS)., Methods: Olvi-Vec is a modified vaccinia virus that causes oncolysis and immune activation. An open-label phase 1b trial using a 3 + 3 dose escalation was conducted. Intraperitoneal Olvi-Vec was given as monotherapy in two consecutive daily doses. Translational analyses included anti-virus antibody levels, viral shedding, circulating tumor cells (CTCs) and T cells., Results: Twelve patients (median age: 69 years, range: 45-77) with median 5 prior therapies (range: 2-10) and 2 prior platinum lines (range: 1-5) were enrolled. There were three dose level cohorts: 3 × 10 9 (n = 6), 1 × 10 10 (n = 5), and 2.5 × 10 10 (n = 1) plaque forming units (PFU)/day on two consecutive days. Treatment-related adverse events (TRAEs) included G1/G2 nausea (n = 6), fever (n = 6), abdominal distention (n = 5), and abdominal pain (n = 4). There were no Grade 4 TRAEs, no dose relationship to TRAEs, and no deaths attributed to Olvi-Vec. The ORR was 9% (1/11). Stable disease (SD) was 64% (7/11), and SD ≥15 weeks was 46% (5/11). Median PFS was 15.7 weeks (95%CI: 5.7-34.5), including extended PFS in four patients (23.2, 34.5, 59.4+ and 70.8 weeks). Three patients had extended overall survival (deceased 33.6 months, and alive with disease at 54 and 59 months). CTCs diminished in 6/8 (75%) baseline-positive patients. Immune activation was demonstrated from virus-enhanced tumor infiltration of CD8+ T-cells and activation of tumor-specific T-cells in peripheral blood., Conclusions: Oncolytic viral therapy with intraperitoneal Olvi-Vec showed promising safety, clinical activities, and immune activation in patients with PRROC, warranting further clinical investigation., Competing Interests: Declaration of Competing Interest Dr. Robert W. Holloway serves as Chair, Clinical Advisory Board on Gynecologic Cancers to Genelux. None of the other authors have any potential financial or commercial conflict of interest associated with this research manuscript., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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/m 2 (range, 19.4-43.7 kg/m 2 ). The pooled detection rates were 91% per patient (95% confidence interval, 85%-95%; I 2 =59%) and 64% bilaterally (95% confidence interval, 53%-73%; I 2 =69%). The overall node positivity rate was 26% (95% confidence interval, 19%-34%; I 2 =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%; I 2 =0%), a false negative rate of 8% (95% confidence interval, 4%-16%; I 2 =0%), and a negative predictive value of 97% (95% confidence interval, 95%-99%; I 2 =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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The efficacy and safety of rucaparib maintenance treatment in ARIEL3 were evaluated in subgroups based on best response to most recent platinum-based chemotherapy and baseline disease., Methods: Patients were randomized 2:1 to receive either oral rucaparib at a dosage of 600 mg twice daily or placebo. Investigator-assessed PFS was assessed in prespecified, nested cohorts: BRCA-mutated, homologous recombination deficient (HRD; BRCA mutated or wild-type BRCA/high loss of heterozygosity), and the intent-to-treat (ITT) population., Results: Median PFS for patients in the ITT population with a complete response to most recent platinum-based chemotherapy was 11.1 months in the rucaparib arm (126 patients) versus 5.6 months in the placebo arm (64 patients) (HR, 0.33 [95% CI, 0.23-0.48]), and in patients with a partial response (249 vs. 125), it was 9.0 versus 5.3 months (HR, 0.38 [0.30-0.49]). In subgroups of the ITT population based on baseline disease, median PFS was 8.2 versus 5.3 months (HR, 0.40 [0.28-0.57]) in patients with measurable disease (141 rucaparib vs. 66 placebo), 10.4 versus 4.5 months (HR, 0.31 [0.20-0.48]) in those with nonmeasurable but evaluable disease (104 vs. 56), and 14.1 versus 7.3 months (HR, 0.35 [0.24-0.51]) in those with no residual disease (130 vs. 67). Across subgroups, significantly longer median PFS was observed with rucaparib versus placebo in the BRCA-mutated and HRD cohorts. Objective responses were reported in patients with measurable disease and in patients with nonmeasurable but evaluable baseline disease. Safety was consistent across subgroups., Conclusion: Rucaparib maintenance treatment provided clinically meaningful efficacy benefits across subgroups based on response to last platinum-based chemotherapy or baseline disease., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Approach to the management of early stage cervical cancers with tumor size >2 cm in women who desire fertility preservation has been fraught with controversy. Fertility sparing surgery for FIGO 2018 stage IB cancers has been validated most for tumors ≤2 cm. In this review, our objective was to evaluate the oncologic and obstetric outcomes for women that underwent neoadjuvant chemotherapy (NACT) before fertility sparing surgery for tumors 2-4 cm., Methods: We performed a systematic literature review and searched PubMed, Google Scholar, Cochrane Reviews and UpToDate (from January 2000 to February 2021) using the terms: cervical cancer, fertility preservation, trachelectomy, radical trachelectomy, neoadjuvant chemotherapy, cervical cancer treatment, stage IB1 or IB2 cervical cancer, and cervical cancer size 2-4 cm. We included manuscripts with information on patients with tumor sizes 2-4 cm, lymph node status, follow-up, obstetric and oncologic outcome. We excluded review articles or articles without all pertinent patient information., Results: Eighteen articles were identified including 249 patients. For final analysis, 114 met inclusion criteria. All included patients had FIGO 2018 stage IB2 cervical cancer, underwent neoadjuvant chemotherapy and subsequent fertility sparing surgery. Vaginal radical trachelectomy, cold knife conization, abdominal radical trachelectomy, laparoscopic radical trachelectomy, simple vaginal trachelectomy, and cone laser were performed in 46 (40.4%), 26 (22.8%), 14 (12.3%), 13 (11.4%), 8 (7%), and 7 (6.1%) women, respectively. The most common regimen of chemotherapy was platinum-based therapy with cisplatin. The follow-up time reported in all studies ranged from 1 to 225 months. Of 64 attempted pregnancies, there were 49 (76.6%) viable deliveries which included 6 preterm births (9.4%). The recurrence rate was 6.1% and two patients (1.8%) died of disease., Conclusion: Fertility sparing surgery following NACT is an option for women with cervical cancers that are 2-4 cm that wish to preserve fertility without sacrificing oncologic or obstetric outcomes. Confirmation of these findings are anticipated from an ongoing international phase II clinical trial [1]., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest associated with this review article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: In ARIEL3 (NCT01968213), the poly(adenosine diphosphate-ribose) polymerase inhibitor rucaparib significantly improved progression-free survival versus placebo regardless of biomarker status when used as maintenance treatment for recurrent ovarian cancer. The aim of the current analyses was to evaluate the efficacy and safety of rucaparib in subgroups based on progression-free interval following penultimate platinum, number of prior chemotherapies, and prior use of bevacizumab., Methods: Patients were randomized 2:1 to rucaparib 600 mg twice daily or placebo. Within subgroups, progression-free survival was assessed in prespecified, nested cohorts: BRCA -mutant, homologous recombination deficient ( BRCA -mutant or wild-type BRCA /high genomic loss of heterozygosity), and the intent-to-treat population., Results: In the intent-to-treat population, median investigator-assessed progression-free survival was 8.2 months with rucaparib versus 4.1 months with placebo (n=151 vs n=76; HR 0.33, 95% CI 0.24 to 0.46, p<0.0001) for patients with progression-free interval 6 to ≤12 months, and 13.6 versus 5.6 months (n=224 vs n=113; HR 0.39, 95% CI 0.30 to 0.52, p<0.0001) for those with progression-free interval >12 months. Median progression-free survival was 10.4 versus 5.4 months (n=231 vs n=124; HR 0.42, 95% CI 0.32 to 0.54, p<0.0001) for patients who had received two prior chemotherapies, and 11.1 versus 5.3 months (n=144 vs n=65; HR 0.28, 95% CI 0.19 to 0.41, p<0.0001) for those who had received ≥3 prior chemotherapies. Median progression-free survival was 10.3 versus 5.4 months (n=83 vs n=43; HR 0.42, 95% CI 0.26 to 0.68, p=0.0004) for patients who had received prior bevacizumab, and 10.9 versus 5.4 months (n=292 vs n=146; HR 0.35, 95% CI 0.28 to 0.45, p<0.0001) for those who had not. Across subgroups, median progression-free survival was also significantly longer with rucaparib versus placebo in the BRCA -mutant and homologous recombination deficient cohorts. Safety was consistent across subgroups., Conclusions: Rucaparib maintenance treatment significantly improved progression-free survival versus placebo irrespective of progression-free interval following penultimate platinum, number of lines of prior chemotherapy, and previous use of bevacizumab., Competing Interests: Competing interests: ARC has served on advisory boards for AstraZeneca, Eisai, and Tesaro/GlaxoSmithKline; has received research funding from Clovis Oncology and AstraZeneca; and has received travel and accommodation support for congress attendance from Clovis Oncology, AstraZeneca, and Roche. DL has served in a consulting or advisory role for Clovis Oncology, AstraZeneca, ImmunoGen, Merck, PharmaMar, Roche, Takeda, and Tesaro/GlaxoSmithKline, Genmab; has received institutional research support from Merck, PharmaMar and Tesaro/GlaxoSmithKline; and received support for travel or accommodation from AstraZeneca, PharmaMar, Roche, and Tesaro/GlaxoSmithKline. AMO has served on steering committees for Clovis Oncology, AstraZeneca, and Tesaro (uncompensated). CA has served on a steering committee for AbbVie and Genentech; served on advisory boards for Clovis Oncology, AbbVie, Eisai/Merck, ImmunoGen, Mersana Therapeutics, Roche, and Tesaro; and received research grants from Clovis Oncology, AbbVie, AstraZeneca, and Genentech. AO has served on advisory boards for Clovis Oncology, AstraZeneca, Genmab/Seattle Genetics, ImmunoGen, PharmaMar, Roche, and Tesaro; has received support for travel or accommodation from Clovis Oncology, AstraZeneca, PharmaMar, and Roche; and reports institutional research grant support from Clovis Oncology, AbbVie Deutschland, Ability Pharmaceuticals, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics, Eisai, ImmunoGen, Merck/Merck Sharp & Dohme, Millennium Pharmaceuticals, PharmaMar, Roche, and Tesaro. AD has served in a consulting or advisory role for Precision Oncology Australia, Shire Pharmaceuticals, and Specialised Therapeutics Australia. NC has served in a consulting or advisory role for Clovis Oncology, Advaxis, AstraZeneca, BIOCAD, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, PharmaMar, Roche, Takeda, and Tesaro. JIW has received research support from AbbVie and AstraZeneca and served on advisory boards for AstraZeneca. GS has served in a consulting or advisory role for Clovis Oncology, AstraZeneca, PharmaMar, Roche, and Tesaro. AL has served on advisory boards for Clovis Oncology, Ability Pharmaceuticals, AstraZeneca, BIOCAD, GamaMabs, Genmab/Seattle Genetics, Gritstone, GlaxoSmithKline, Merck Serono, Merck Sharp & Dohme, and Tesaro; steering committee for Merck Sharp & Dohme; reports institutional support for clinical trials or academic research from Clovis Oncology, Ability Pharmaceuticals, Agenus, AstraZeneca, Incyte, Inivata, Iovance, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, and Tesaro; and reports boarding and travel expenses for congress activities from Clovis Oncology, AstraZeneca, and Roche. RWH has served on speakers bureaus for Clovis Oncology, AstraZeneca, and Tesaro, and on advisory boards for Clovis Oncology and AstraZeneca. MAG has served on speakers’ bureaus for Clovis Oncology, AstraZeneca, PharmaMar, and Roche. PCF has served on advisory boards for Clovis Oncology and AstraZeneca and received honoraria from AstraZeneca. JCG has received honoraria from AstraZeneca and Bristol-Myers Squibb; served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, and Tesaro; served on speakers’ bureaus for AstraZeneca, Ipsen, and Merck Sharp & Dohme; and received support for travel and/or accommodation from Astellas and AstraZeneca. DMO has served on advisory boards for Clovis Oncology, AbbVie, AstraZeneca, Eisai, Genentech/Roche, Genelux, Iovance Biotherapeutics, Janssen, Novocure, Regeneron, and Tesaro; has served on steering committees for Clovis Oncology, Agenus, Amgen, and Novocure; has served as a consultant for AbbVie, Ambry, AstraZeneca, Genentech/Roche, Gynecologic Oncology Group Foundation, and Tesaro; has given a presentation on ovarian cancer at the National Comprehensive Cancer Network; and his institution has received research support from Clovis Oncology, AbbVie, Agenus, Ajinomoto, Amgen, Array BioPharma, AstraZeneca, Bristol-Myers Squibb, Cerulean Pharma, Eisai, EMD Serono, ERGOMED Clinical Research, Genentech, Gynecologic Oncology Group, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, Janssen Research and Development, Ludwig Institute for Cancer Research, New Mexico Cancer Care Alliance, Novocure, PRA International, Regeneron Pharmaceuticals, Serono, Stemcentrx, Tesaro, TRACON Pharmaceuticals, VentiRx, and Yale University. DKA has served as a scientific advisor for Morphotek and received research funding from Clovis Oncology, Advaxis, AstraZeneca, Pfizer, Syndax, and Tesaro. SB has served on advisory boards and received honoraria from Clovis Oncology, AstraZeneca, Genmab, GlaxoSmithKline, Immunogen, Merck Sereno, Merck Sharp & Dohme, Mersana, Pfizer, Roche, Seattle Genetics, and Tesaro; received honoraria for lectures from AstraZeneca/Merck Sharp & Dohme, GlaxoSmithKline, Pfizer, Roche, and Tesaro; received support for travel or accommodation from NuCana and Tesaro; and reports institutional funding from AstraZeneca, GlaxoSmithKline, and Tesaro. JG-D has received research funding from AstraZeneca, Pierre Fabre, and Pfizer; received personal fees from Clovis Oncology, Astellas, Pierre Fabre, and Pfizer; and received nonfinancial support from Astellas, Pierre Fabre, and Pfizer. TC and SG are employees of Clovis Oncology and may own stock or have stock options in that company. RLC reports grants from Clovis Oncology, AstraZeneca, Gateway Foundation, Janssen, Judy Reis/Albert Pisani, MD, Ovarian Cancer Research Fund, Merck, National Institutes of Health, Roche/Genentech, and V-Foundation; has served as an advisor to Clovis Oncology, Agenus, AstraZeneca, GamaMabs, Genmab, Janssen, OncoQuest, Pfizer (Medivation), Regeneron, Roche/Genentech, and Tesaro; and has an endowment as the Ann Rife Cox Chair in Gynecology. JAL has received lecture fees from Clovis Oncology, AstraZeneca, and Pfizer; served on advisory boards for Clovis Oncology, Artios Pharma, AstraZeneca, Cristal Therapeutics, Merck/Merck Sharp & Dohme, Pfizer, Regeneron, Roche, Seattle Genetics, and Tesaro; and received research grants from AstraZeneca and Merck/Merck Sharp & Dohme., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Although histiocytic lesions of the fallopian tube are relatively rare compared to their epithelial counterparts, there exists a spectrum of histiocytic lesions involving the fallopian tube that are described under different terminologies dependent on the involved compartment of the fallopian tube. A common histologic denominator of all the hitherto reported tubal histiocytic lesions is the presence of sheets and clusters of histiocytes without any supportive connective tissue. The current study describes three cases of a heretofore-undescribed papillary histiocytic lesion in the lumen of the fallopian tube. All 3 lesions were characterized by avascular, hyaline collagenous papillary cores surrounded by a monotonous population of epithelioid cells, morphologically resembling mesothelial cell hyperplasia, but displaying a histiocytic immunophenotype with diffuse immunopositivity for CD68. Since the papillary cores did not harbor any vasculature, the term intratubal pseudopapillary histiocytic hyperplasia was proposed for this histiocytic proliferation which expands the spectrum of histiocytic lesions of the fallopian tube. Although probably of no clinical significance, practicing pathologists should be aware of this peculiar histiocytic lesion of the fallopian tube to avoid misdiagnosis and unnecessary immunohistochemical testing., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Up to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target of rapamycin (mTOR) pathway activity and a metabolic shift to glycolysis. Although inhibitors targeting the HER2 receptor have been successful in treating HER2-positive breast cancer, anti-HER2 therapy is associated with a high risk of recurrence and drug resistance due to stimulation of the PI3K-Akt-mTOR signaling pathway and glycolysis. Combination therapies against HER2 with inhibition of mTOR improve clinical outcomes compared to HER2 inhibition alone. Here, we review the role of the HER2 receptor, mTOR pathway, and glycolysis in HER2-positive breast cancer, along with signaling mechanisms and the efficacy of treatment strategies of HER2-positive breast cancer.

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 (<200 cells and < 0.2 mm) was performed. Only patients with otherwise stage I/II EC, endometrioid histology, and no evidence of micro-or macrometastases were included. Univariate and multivariable Cox proportional hazard models were used to evaluate associations between treatment, tumor characteristics, and RFS., Results: 175 patients were included. Median follow up time was 31 months. 39% stage IB and 12% stage II disease. 76 (43%) received no adjuvant therapy or vaginal brachytherapy only (NAT/VBT), 21 (12%) had external beam radiation (EBRT), and 78 (45%) received chemotherapy +/- radiation. Patients who received chemotherapy more often had tumors with deep myoinvasion, lymphovascular space invasion (LVSI), and higher grade. Nine (5.1%) patients recurred; 5 distant, 3 retroperitoneal, and 1 vaginal. Extra-vaginal recurrences were similar in patients with or without chemotherapy (5.2% vs 3.8%, p = 0.68). After controlling for stage, LVSI and grade, chemotherapy and EBRT were not associated with RFS (HR = 0.63, 95%CI 0.11-3.52, and HR = 0.90, 95%CI 0.22-3.61, respectively). Type of lymph node dissection and ITC detection method were not associated with RFS., Conclusions: Risk of retroperitoneal and/or distant recurrence is low (4.6%) for patients with stage I/II endometrioid EC and ITCs in SLNs regardless of treatment. Our preliminary data suggests that adjuvant therapy may not be significantly associated with RFS. However, longer follow-up time and a larger sample size are needed before definitive recommendations regarding adjuvant therapy for patients with EC and only ITCs in SLN can be made., Competing Interests: Declaration of Competing Interest Dr. Leitao reports personal fees from JnJ/Ethicon, outside the submitted work; and Dr. Leitao is an ad hoc speaker for Intuitive Surgical, Inc. Dr. Abu-Rustum reports grants from GRAIL, grants from Stryker, outside the submitted work. Dr. Backes reports grants and personal fees from Eisai, grants and personal fees from Merck, grants from Immunogen, grants and personal fees from Clovis, personal fees from Agenus, personal fees from AstraZeneca, personal fees from Genentech, personal fees from GlaxoSmithKline, all outside the submitted work. None of the other authors have a significant conflict of interest related to the current study. Some of the investigators (Felix, Abu-Rustum, Leitao) receive grants for other projects that fund part of their time., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The tumor microenvironment (TME) is now being widely accepted as the key contributor to a range of processes involved in cancer progression from tumor growth to metastasis and chemoresistance. The extracellular matrix (ECM) and the proteases that mediate the remodeling of the ECM form an integral part of the TME. Plasmin is a broad-spectrum, highly potent, serine protease whose activation from its precursor plasminogen is tightly regulated by the activators (uPA, uPAR, and tPA), the inhibitors (PAI-1, PAI-2), and plasminogen receptors. Collectively, this system is called the plasminogen activation system. The expression of the components of the plasminogen activation system by malignant cells and the surrounding stromal cells modulates the TME resulting in sustained cancer progression signals. In this review, we provide a detailed discussion of the roles of plasminogen activation system in tumor growth, invasion, metastasis, and chemoresistance with specific emphasis on their role in the TME. We particularly review the recent highlights of the plasminogen receptor S100A10 (p11), which is a pivotal component of the plasminogen activation system.

Investigation of the gynecologic tract microbial milieu has revealed potential new biomarkers. Simultaneously, immunotherapeutics are establishing their place in the treatment of gynecologic malignancies. The interplay between the microbiome, the tumor micro-environment and response to therapy is a burgeoning area of interest. There is evidence to support that microbes, through their genetic make-up, gene products, and metabolites affect human physiology, metabolism, immunity, disease susceptibility, response to pharmacotherapy, and the severity of disease-related side effects. Specifically, the richness and diversity of the gut microbiome appears to affect carcinogenesis, response to immunotherapy, and modulate severity of immune-mediated adverse effects. These effects have best been described in other tumor types and these have shown compelling results. This review summarizes the current understanding and scope of the interplay between the human microbiome, host factors, cancer, and response to treatments. These findings support further exploring whether these associations exist for gynecologic malignancies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

S100A10 (p11) is a plasminogen receptor that regulates cellular plasmin generation by cancer cells. In the current study, we used the MMTV-PyMT mouse breast cancer model, patient tumor microarray, and immunohistochemical (IHC) analysis to investigate the role of p11 in oncogenesis. The genetic deletion of p11 resulted in significantly decreased tumor onset, growth rate, and spontaneous pulmonary metastatic burden in the PyMT/p11-KO (knock-out) mice. This phenotype was accompanied by substantial reduction in Ki67 positivity, macrophage infiltration, decreased vascular density in the primary tumors, and decrease in invasive carcinoma and pulmonary metastasis. Surprisingly, IHC analysis of wild-type MMTV-PyMT mice failed to detect p11 expression in the tumors or metastatic tumor cells and loss of p11 did not decrease plasmin generation in the PyMT tumors and cells. Furthermore, tumor cells expressing p11 displayed dramatically reduced lung metastasis when injected into p11-depleted mice, further strengthening the stromal role of p11 in tumor growth and metastasis. Transcriptome analysis of the PyMT tumors from p11-KO mice showed marked reduction in genes such as Areg , Muc1 , and S100a8 involved in breast cancer development, progression, and inflammation. The PyMT/p11-KO tumors displayed a remarkable increase in inflammatory cytokines such as interleukin ( Il)-6 , Il-10 , and interferon ( Ifn )- γ . Gene expression profiling and IHC of primary breast cancer samples showed that p11 mRNA and protein levels were significantly higher in tumor tissues compared to normal mammary tissue. P11 mRNA expression was significantly associated with poor patient prognosis and significantly elevated in high grade, triple negative (TN) tumors, and tumors with high proliferative index. This is the first study examining the crucial role of p11 in breast tumor development and metastasis, thus emphasizing its potential as a diagnostic and prognostic biomarker in breast cancer.

Objective: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes., Methods: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method., Results: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11)., Conclusions: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in a post hoc exploratory analysis of the phase III ARIEL3 study of rucaparib maintenance treatment versus placebo., Patients and Methods: Patients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned to rucaparib (600 mg twice per day) or placebo. QA-PFS was calculated as progression-free survival function × the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function. Q-TWiST analyses were performed defining TOX as the mean duration in which a patient experienced grade ≥ 3 treatment-emergent adverse events (TEAEs) or the mean duration in which a patient experienced grade ≥ 2 TEAEs of nausea, vomiting, fatigue, and asthenia. Q-TWiST was calculated as μTOX × TOX + TWiST, with μTOX calculated using EQ-5D-3L data., Results: The visit cutoff was Apr 15, 2017. Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo; difference, 6.28 months [95% CI, 4.85 to 7.47 months]); BRCA -mutant cohort (130 rucaparib v 66 placebo; 9.37 months [95% CI, 6.65 to 11.85 months]); homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo; 7.93 months [95% CI, 5.93 to 9.53 months]); and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo; 2.71 months [95% CI, 0.31 to 4.44 months]). With TOX defined using grade ≥ 3 TEAEs, the difference in mean Q-TWiST (rucaparib v placebo) was 6.88 months (95% CI, 5.71 to 8.23 months), 9.73 months (95% CI, 7.10 to 11.94 months), 8.11 months (95% CI, 6.36 to 9.49 months), and 3.35 months (95% CI, 1.66 to 5.40 months) in the ITT population, BRCA -mutant cohort, HRD cohort, and BRCA wild-type/LOH low patient subgroup, respectively. Q-TWiST with TOX defined using select grade ≥ 2 TEAEs also consistently favored rucaparib., Conclusion: The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib versus placebo in all predefined cohorts.

Background: In the phase 3 trial ARIEL3, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib provided clinical benefit versus placebo for patients with recurrent, platinum-sensitive ovarian cancer. Here, we evaluate the impact of age on the clinical utility of rucaparib in ARIEL3., Methods: Patients with platinum-sensitive, recurrent ovarian carcinoma with ≥2 prior platinum-based chemotherapies who responded to their last platinum-based therapy were enrolled in ARIEL3 and randomized 2:1 to rucaparib 600 mg twice daily or placebo. Exploratory, post hoc analyses of progression-free survival (PFS), patient-centered outcomes (quality-adjusted PFS [QA-PFS] and quality-adjusted time without symptoms or toxicity [Q-TWiST]), and safety were conducted in three age subgroups (<65 years, 65-74 years, and ≥75 years)., Results: Investigator-assessed PFS was significantly longer with rucaparib than placebo in patients aged <65 years (rucaparib n = 237 vs placebo n = 117; median, 11.1 vs 5.4 months; hazard ratio [HR]: 0.33 [95% confidence interval (95% CI) 0.25-0.43]; P < 0.0001) and 65-74 years (n = 113 vs n = 64; median, 8.3 vs 5.3 months; HR 0.43 [95% CI 0.29-0.63]; P < 0.0001) and numerically longer in patients aged ≥75 years (n = 25 vs n = 8; median, 9.2 vs 5.5 months; HR 0.47 [95% CI 0.16-1.35]; P = 0.1593). QA-PFS and Q-TWiST were significantly longer with rucaparib than placebo across all age subgroups. Safety of rucaparib was generally similar across the age subgroups., Conclusions: Efficacy, patient-centered outcomes, and safety of rucaparib were similar between age subgroups, indicating that all eligible women with recurrent ovarian cancer should be offered this therapeutic option, irrespective of age. https://clinicaltrials.gov/ct2/show/NCT01968213., Competing Interests: Declaration of competing interest Nicoletta Colombo: Served in a consulting or advisory role for Clovis Oncology, AstraZeneca, BIOCAD, Pfizer, PharmaMar, Roche, and Tesaro. Amit M. Oza: Served on advisory boards for Clovis Oncology, Amgen, AstraZeneca, GlaxoSmithKline, and Immunovaccine. Domenica Lorusso: Served in a consulting or advisory role for Clovis Oncology, AstraZeneca, ImmunoGen, Merck, PharmaMar, Roche, Takeda, and Tesaro and received support for travel or accommodation from PharmaMar and Roche. Carol Aghajanian: Served on a steering committee for Clovis Oncology, AbbVie, Genentech, and Mateon Therapeutics; served on advisory boards for Clovis Oncology, Cerulean Pharma, Eisai/Merck, ImmunoGen, and Tesaro; received research grants from Clovis Oncology, AbbVie, AstraZeneca, and Genentech; and received honoraria from Clovis Oncology, Cerulean Pharma, Eisai/Merck, ImmunoGen, Mateon Therapeutics, and Tesaro. Ana Oaknin: Served on advisory boards for Clovis Oncology, AstraZeneca, ImmunoGen, Genmab/Seattle Genetics, PharmaMar, Roche, and Tesaro; received support for travel or accommodation from Clovis Oncology, AstraZeneca, PharmaMar, and Roche; and received research grants from Clovis Oncology, AbbVie Deutschland, Ability Pharmaceuticals, Advaxis, Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, Bristol-Myers Squibb, Eisai, F. Hoffmann-La Roche, ImmunoGen, Merck Sharp & Dohme de España SA, Millennium Pharmaceuticals, PharmaMar, Regeneron Pharmaceuticals, and Tesaro. Andrew Dean: Served in a consulting or advisory role for Precision Oncology Australia, Shire Pharmaceuticals, and Specialised Therapeutics Australia. Johanne I. Weberpals: Received research support from AbbVie and AstraZeneca and served on advisory boards for AstraZeneca. Andrew R. Clamp: Served on advisory boards for AstraZeneca; received research funding from Clovis Oncology and AstraZeneca; and received support for travel and accommodation for congress attendance from Clovis Oncology, AstraZeneca, and Roche. Giovanni Scambia: Served in a consulting or advisory role for Clovis Oncology, AstraZeneca, PharmaMar, Roche, and Tesaro. Alexandra Leary: Served on advisory boards for Clovis Oncology, AstraZeneca, BIOCAD, GamaMabs, Genmab/Seattle Genetics, Merck Sharp & Dohme, Pfizer, PharmaMar, and Tesaro; received support for travel and accommodation from Clovis Oncology, AstraZeneca, Roche, and Tesaro; and reports institutional research grant support from Clovis Oncology, AstraZeneca, GamaMabs, Inivata, Merck Sharp & Dohme, Merus, Sanofi, and Tesaro. Robert W. Holloway: Served on speakers bureaus for Clovis Oncology, AstraZeneca, and Tesaro. Margarita Amenedo Gancedo: Served on advisory boards for Clovis Oncology and on speakers bureaus for AstraZeneca, PharmaMar, and Roche. Peter C. Fong: Served on advisory boards for Clovis Oncology and AstraZeneca and received honoraria from AstraZeneca. Jeffrey C. Goh: Served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb and Tesaro; served on speakers bureaus for Ipsen and Merck Sharp & Dohme; and received support for travel or accommodation from Astellas, AstraZeneca, and Bristol-Myers Squibb. David M. O'Malley: Served on advisory boards for Clovis Oncology, AbbVie, AstraZeneca, Eisai, Genentech/Roche, Genelux, Iovance Biotherapeutics, Janssen, Novocure, Regeneron, and Tesaro; has served on steering committees for Clovis Oncology, Agenus, Amgen, and Novocure; has served as a consultant for AbbVie, Ambry, AstraZeneca, Genentech/Roche, Gynecologic Oncology Group Foundation, and Tesaro; has given a presentation on ovarian cancer at the National Comprehensive Cancer Network; and his institution has received research support from Clovis Oncology, AbbVie, Agenus, Amgen, Ajinomoto, Array BioPharma, AstraZeneca, Bristol-Myers Squibb, Cerulean Pharma, Eisai, EMD Serono, ERGOMED Clinical Research, Genentech, Gynecologic Oncology Group, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, Janssen Research and Development, Ludwig Institute for Cancer Research, New Mexico Cancer Care Alliance, Novocure, PRA International, Regeneron Pharmaceuticals, Serono, Stemcentrx, Tesaro, TRACON Pharmaceuticals, VentiRx, and Yale University. Deborah K. Armstrong: Served as a scientific advisor for Morphotek and received research funding from Clovis Oncology, Advaxis, AstraZeneca, Pfizer, Syndax, and Tesaro. Susana Banerjee: Served on advisory boards and received honoraria from Clovis Oncology, AstraZeneca, PharmaMar, Seattle Genetics, and Tesaro; received honoraria from Merck Serono and Roche; and received support for travel or accommodation from NuCana and Tesaro. Jesus García-Donas: Received research funding from AstraZeneca, Pierre Fabre, and Pfizer; received personal fees from Clovis Oncology, Astellas, Pierre Fabre, and Pfizer; and received nonfinancial support from Astellas, Pierre Fabre, and Pfizer. Elizabeth M. Swisher: Has nothing to disclose. Juliette Meunier: Employee of Modus Outcomes, which was contracted by Clovis Oncology to conduct these analyses. Terri Cameron, Lara Maloney, Sandra Goble, and Josh Bedel: Employees of Clovis Oncology and may own stock or have stock options in that company. Jonathan A. Ledermann: Received lecture fees from Clovis Oncology, AstraZeneca, Merck/Merck Sharp & Dohme, Pfizer, and Tesaro; served on advisory boards for Clovis Oncology, Artios Pharma, AstraZeneca, Cristal Therapeutics, Merck/Merck Sharp & Dohme, Pfizer, Regeneron, Roche, Seattle Genetics, and Tesaro; and received research grants from AstraZeneca and Merck/Merck Sharp & Dohme. Robert L. Coleman: Reports grants from Clovis Oncology, AstraZeneca, Gateway Foundation, Janssen, Judy Reis/Albert Pisani, MD, Ovarian Cancer Research Fund, Merck, National Institutes of Health, Roche/Genentech, and V-Foundation; has served as an advisor to Clovis Oncology, Agenus, AstraZeneca, GamaMabs, Genmab, Janssen, OncoQuest, Pfizer (Medivation), Regeneron, Roche/Genentech, and Tesaro; and has an endowment as the Ann Rife Cox Chair in Gynecology., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Recurrent ovarian cancer frequently involves the spleen. Our aims were to describe the technique of robotic-assisted laparoscopic splenectomy and to evaluate outcomes including progression-free and overall survival in patients who underwent this procedure for recurrent ovarian cancer., Methods: Chart reviews were performed on all consecutive patients who underwent robotic splenectomy (April 2012 to May 2019) for recurrent ovarian cancer. Patients had ≤3 sites of disease and no ascites. Extent of disease was confirmed by positron emission tomography-computed tomography (PET-CT) pre-operatively and platinum-doublet chemotherapy was initiated post-operatively. Peri- and post-operative outcomes, progression-free survival, and overall survival were assessed. Two video links are included to demonstrate variations in technique and anatomy., Results: A total of 10 patients were included. The median age was 63.5 years (range 46-74) and median body mass index was 30 kg/m 2 (range 21.5-40.1). Disease was limited to the spleen in seven patients and three had evidence of up to two other sites of disease on imaging. The median robotic splenectomy operative time was 159 min (range 112-214) that included laparoscopic lysis of adhesions prior to robotic port placement in seven cases, and excision of diaphragm or omental implants in three cases. There were no transfusions, laparotomy conversions, return to the operating room, abscesses, or pancreatic pseudocysts. The median length of stay was 2 days (range 1-4). The median time to resumption of chemotherapy was 40 days (range 25-78). After a median follow-up of 51 months (range 12-98), five patients had recurrence (two deaths, three alive with disease), with a median time to recurrence of 14 months (range 12-15). The median progression-free survival was 15 months (range 12-98) and the median overall survival was 51 months (range 12-98) post-splenectomy., Conclusions: Robotic splenectomy was feasible, achieving complete cytoreduction of splenic recurrent ovarian cancer, short hospital length-of-stay, and acceptable morbidity., Competing Interests: Competing interests: RWH received compensation for advanced training programs from Intuitive Surgical, Inc (Sunnyvale, CA) and speaking honoraria from Bard-Davol (Warwick, RI) during the time these surgeries occurred., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Dysregulation of DNA methylation is an established feature of breast cancers. DNA demethylating therapies like decitabine are proposed for the treatment of triple-negative breast cancers (TNBC) and indicators of response need to be identified. For this purpose, we characterized the effects of decitabine in a panel of 10 breast cancer cell lines and observed a range of sensitivity to decitabine that was not subtype specific. Knockdown of potential key effectors demonstrated the requirement of deoxycytidine kinase (DCK) for decitabine response in breast cancer cells. In treatment-naïve breast tumors, DCK was higher in TNBCs, and DCK levels were sustained or increased post chemotherapy treatment. This suggests that limited DCK levels will not be a barrier to response in patients with TNBC treated with decitabine as a second-line treatment or in a clinical trial. Methylome analysis revealed that genome-wide, region-specific, tumor suppressor gene-specific methylation, and decitabine-induced demethylation did not predict response to decitabine. Gene set enrichment analysis of transcriptome data demonstrated that decitabine induced genes within apoptosis, cell cycle, stress, and immune pathways. Induced genes included those characterized by the viral mimicry response; however, knockdown of key effectors of the pathway did not affect decitabine sensitivity suggesting that breast cancer growth suppression by decitabine is independent of viral mimicry. Finally, taxol-resistant breast cancer cells expressing high levels of multidrug resistance transporter ABCB1 remained sensitive to decitabine, suggesting that the drug could be used as second-line treatment for chemoresistant patients., (©2020 American Association for Cancer Research.)

Background: In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival versus placebo. Here, we report prespecified, investigator-assessed, exploratory post-progression endpoints and updated safety data., Methods: In this ongoing (enrolment complete) randomised, placebo-controlled, phase 3 trial, patients aged 18 years or older who had platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least two previous platinum-based chemotherapy regimens and responded to their last platinum-based regimen were randomly assigned (2:1) to oral rucaparib (600 mg twice daily) or placebo in 28-day cycles using a computer-generated sequence (block size of six with stratification based on homologous recombination repair gene mutation status, progression-free interval following penultimate platinum-based regimen, and best response to most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary endpoint of investigator-assessed progression-free survival has been previously reported. Prespecified, exploratory outcomes of chemotherapy-free interval (CFI), time to start of first subsequent therapy (TFST), time to disease progression on subsequent therapy or death (PFS2), and time to start of second subsequent therapy (TSST) and updated safety were analysed (visit cutoff Dec 31, 2017). Efficacy analyses were done in all patients randomised to three nested cohorts: patients with BRCA mutations, patients with homologous recombination deficiencies, and the intention-to-treat population. Safety analyses included all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT01968213., Findings: Between April 7, 2014, and July 19, 2016, 564 patients were enrolled and randomly assigned to rucaparib (n=375) or placebo (n=189). Median follow-up was 28·1 months (IQR 22·0-33·6). In the intention-to-treat population, median CFI was 14·3 months (95% CI 13·0-17·4) in the rucaparib group versus 8·8 months (8·0-10·3) in the placebo group (hazard ratio [HR] 0·43 [95% CI 0·35-0·53]; p<0·0001), median TFST was 12·4 months (11·1-15·2) versus 7·2 months (6·4-8·6; HR 0·43 [0·35-0·52]; p<0·0001), median PFS2 was 21·0 months (18·9-23·6) versus 16·5 months (15·2-18·4; HR 0·66 [0·53-0·82]; p=0·0002), and median TSST was 22·4 months (19·1-24·5) versus 17·3 months (14·9-19·4; HR 0·68 [0·54-0·85]; p=0·0007). CFI, TFST, PFS2, and TSST were also significantly longer with rucaparib than placebo in the BRCA-mutant and homologous recombination-deficient cohorts. The most frequent treatment-emergent adverse event of grade 3 or higher was anaemia or decreased haemoglobin (80 [22%] patients in the rucaparib group vs one [1%] patient in the placebo group). Serious treatment-emergent adverse events were reported in 83 (22%) patients in the rucaparib group and 20 (11%) patients in the placebo group. Two treatment-related deaths have been previously reported in this trial; there were no new treatment-related deaths., Interpretation: In these exploratory analyses over a median follow-up of more than 2 years, rucaparib maintenance treatment led to a clinically meaningful delay in starting subsequent therapy and provided lasting clinical benefits versus placebo in all three analysis cohorts. Updated safety data were consistent with previous reports., Funding: Clovis Oncology., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions., Methods: Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017., Results: Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group ( P = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group ( P = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group ( P = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18)., Conclusion: In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.

Purpose: To establish the bilateral pelvic concordance rate of the sentinel lymph node (SLN) and determine the likelihood of lymph node metastasis in cases of mapping failure., Methods: A database analysis was performed on 414 patients with clinical stage I endometrial cancer who underwent SLN mapping followed by robotic hysterectomy and completion pelvic (n=414, 100%) and aortic (n=186, 44.9%) lymphadenectomy from March 2011 to August 2016. Stage, histology, SLN sites, and surgico-pathologic findings were analyzed. The bilateral concordance rate of SLN location, successful unilateral and bilateral mapping rates, false negative rate, and non-SLN metastasis associated with mapping failure were calculated., Results: Histologies included 354 (85.5%) endometrioid, 39 (9.4%) serous, 16 (3.9%) carcinosarcoma, 4 (1.0%) clear cell, and 1 (0.2%) undifferentiated. Final stages included 262 (63.3%) IA, 36 (8.7%) IB, 15 (3.6%) II, 6 (1.4%) IIIA, 68 (16.4%) IIIC1, and 27 (6.5%) IIIC2. Bilateral SLN mapping was successful in 355 (85.7%) patients, and 266 (74.9%) demonstrated mapping to the symmetrical lymphatic group contralaterally. The mapping failure rate was 13.5% (56/414) unilaterally and 0.7% (3/414) bilaterally. SLN locations were external iliac (69.1%), obturator (25.1%), internal iliac (2.2%), common iliac (1.9%), pre-sacral (0.9%), aortic (0.4%), parametrial (0.3%), and para-rectal (0.1%). Lymph node metastases were identified in 95 (22.9%) pelvic and 27 (6.5%) aortic nodes. 10 (16.9%) cases with mapping failure had lymph node metastasis on completion lymphadenectomy, similar to the proportion of SLNs with metastases (p=0.35). However, macro-metastases were more common in mapping failure completion lymphadenectomies than in the positive SLNs (80% vs 22.3%, p<0.001)., Conclusion: The contralateral SLN location concordance rate was 75%. Most SLNs were along the medial external iliac or obturator locations. The rate of positive lymph nodes associated with SLN mapping failure was 16.9%, similar to the overall node-positive rate. The detection of pelvic node metastasis with SLN mapping failure was largely populated with macro-metastases and confirms the necessity of completion lymphadenectomy with mapping failure., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine which non-narcotic analgesic, acetaminophen (Ofirmev®) or ketorolac (Toradol®), provides better post-operative pain control when combined with an opioid patient-controlled analgesia (PCA) pump. Secondary objectives include comparisons of the rates of ileus, post-operative bleeding, transfusions, and length-of-hospitalization (LOH)., Methods: A prospective, randomized trial of acetaminophen (A) 1-g intravenous (IV) every 6-h or ketorolac (K) 15-mg IV every 6-h from post-operative day 1-3 in addition to an opioid PCA for patients undergoing benign or malignant gynecologic laparotomy procedures was performed. Abstracted data included pain levels via visual analogue pain scales (VAS), amount of narcotic used, hepatic enzyme levels, hemoglobin, urine output, blood transfusions, time to return of flatus and LOH., Results: One-hundred patients were accrued and underwent 55 benign gynecologic laparotomies and 45 cancer-related laparotomies. VAS pain levels (3.3 K, 3.5 A) and morphine PCA use (79.1 oral morphine equivalents [OME] K vs. 84.5 A) were not different, however dilaudid PCA usage was less by K patients (84.4 OME K and 136.8 OME A, p < 0.001). There was a significant hemoglobin change between the two groups (2.6 g K vs. 2 g A, p = 0.015), however blood transfusions were equal (28% K, 22% A, p > 0.05). Return of flatus was 2.7-days for K vs. 3.4-days for A (p = 0.011) and LOH was not different (4.4-days K vs. 5.1-days A, p = 0.094)., Conclusions: Both intravenous ketorolac and acetaminophen provide similar post-operative analgesia through VAS pain scales and total usage of morphine via PCA pumps. Use of ketorolac with dilaudid PCA was associated with less dependence on dilaudid and a quicker return of bowel function than acetaminophen, however length of stay and transfusion rates were not different., (Copyright © 2019 Elsevier Inc. All rights reserved.)