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Objective: To examine the risk of sentinel lymph node (SLN) metastases in apparent uterine-confined endometrial cancer (EC) using molecular classification with clinicopathologic features and assess oncologic outcomes by molecular subtypes with micro- or macro-metastases in SLN., Methods: Patients undergoing surgical staging for presumed uterine-confined EC of any histology, with successful bilateral SLN mapping were included. Primary tumors were assigned molecular subtypes using a published algorithm. SLN pathology was categorized as negative, isolated tumor cells (ITCs), or micro- or macro-metastases., Results: Overall, 756 patients were included; 80 (10 %) had micro- or macro-metastases and 51 (7 %) had ITCs. On multivariate multinomial logistic regression, risk of micro- or macro-metastases versus negative SLN was higher for ECs with copy number-high (CN-H)/TP53abn (OR 3.1; 95 % CI 1.3-7), lymphovascular space invasion ([LVSI]; OR 8.0; 95 % CI 4-16), and deep myoinvasion (≥50 %; OR 3.33; 95 % CI 1.9-6.04). Three-year PFS rates by subtype for 68 patients with macro-metastases were 38 % (95 % CI 10-67 %) CN-low/no specific molecular subtype (CN-L/NSMP), 66 % (95 % CI 44-82 %) microsatellite instability-high (MSI-H), and 23 % (95 % CI 10-40 %) CN-H/TP53abn (p = 0.006). Three-year OS rates were 55 % (95 % CI 20-80 %) CN-L/NSMP, 83 % (95 % CI 61-93 %) MSI-H, and 55 % (95 % CI 34-71 %) CN-H/TP53abn (p = 0.048)., Conclusions: Integrating molecular subtype with uterine risk factors (LVSI and myoinvasion) further stratifies risk of occult SLN metastases in patients undergoing surgical staging for early-stage EC. No molecular subgroup had exceedingly low SLN metastases detected, supporting continued universal SLN assessment. Patients with macro-metastases and CN-L/NSMP or CN-H/TP53abn EC had worse outcomes than those with MSI-H EC., Competing Interests: Declaration of competing interest Dr. Weigelt reports funding by REPARE Therapeutics, and employment of an immediate family member at AstraZeneca, outside the submitted work. Dr. Momeni-Boroujeni reports consulting work at Scorpion Therapeutics. Dr. Leitao reports personal fees from Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. Dr. Abu-Rustum reports research funding paid to the institution from GRAIL. The other authors do not have potential conflicts of interest to declare. Funding Research reported in this publication was supported in part by a Cancer Center Support Grant of the NIH/NCI (Grant No. P30CA008748). B. Weigelt is funded in part by Cycle for Survival and Breast Cancer Research Foundation grants. C. Dagher was supported in part by the Bobst Foundation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We compared grading systems and examined associations with tumor stroma and survival in patients with cervical squamous cell carcinoma. Available tumor slides were collected from 10 international institutions. Broders tumor grade, Jesinghaus grade (informed by the pattern of tumor invasion), Silva pattern, and tumor stroma were retrospectively analyzed; associations with overall survival (OS), progression-free survival (PFS), and presence of lymph node metastases were examined. Binary grading systems incorporating tumor stromal changes into Broders and Jesinghaus grading systems were developed. Of 670 cases, 586 were reviewed for original Broders tumor grade, 587 for consensus Broders grade, 587 for Jesinghaus grade, 584 for Silva pattern, and 556 for tumor stroma. Reproducibility among grading systems was poor (κ = 0.365, original Broders/consensus Broders; κ = 0.215, consensus Broders/Jesinghaus). Median follow-up was 5.7 years (range, 0-27.8). PFS rates were 93%, 79%, and 71%, and OS rates were 98%, 86%, and 79% at 1, 5, and 10 years, respectively. On univariable analysis, original Broders ( P < 0.001), consensus Broders ( P < 0.034), and Jesinghaus ( P < 0.013) grades were significant for OS; original Broders grade was significant for PFS ( P = 0.038). Predictive accuracy for OS and PFS were 0.559 and 0.542 (original Broders), 0.542 and 0.525 (consensus Broders), 0.554 and 0.541 (Jesinghaus grade), and 0.512 and 0.515 (Silva pattern), respectively. Broders and Jesinghaus binary tumor grades were significant on univariable analysis for OS and PFS, and predictive value was improved. Jesinghaus tumor grade ( P < 0.001) and both binary systems (Broders, P = 0.007; Jesinghaus, P < 0.001) were associated with the presence of lymph node metastases. Histologic grade has poor reproducibility and limited predictive accuracy for squamous cell carcinoma. The proposed binary grading system offers improved predictive accuracy for survival and the presence of lymph none metastases., Competing Interests: N.A.R. reports research funding paid to the institution from GRAIL. A.I. reports consulting fees from Mylan. The remaining authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

Objectives: Mesonephric (MA) and mesonephric-like (MLA) adenocarcinomas are rare cancers, and data on clinical behavior and response to therapy are limited. We sought to report molecular features, treatment, and outcomes of MA/MLA from a single institution., Methods: Patients with MA (cervix) or MLA (uterus, ovary, other) treated at Memorial Sloan Kettering Cancer Center (MSK) from 1/2008-12/2021 underwent pathologic re-review. For patients with initial treatment at MSK, progression-free survival (PFS1) was calculated as time from initial surgery to progression or death; second PFS (PFS2) was calculated as time from start of treatment for recurrence to subsequent progression or death. Overall survival (OS) was calculated for all patients. Images were retrospectively reviewed to determine treatment response. Somatic genetic alterations were assessed by clinical tumor-normal sequencing (MSK-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT])., Results: Of 81 patients with confirmed gynecologic MA/MLA, 36 received initial treatment at MSK. Sites of origin included cervix (n = 9, 11%), uterus (n = 42, 52%), ovary (n = 28, 35%), and other (n = 2, 2%). Of the 36 patients who received initial treatment at MSK, 20 (56%) recurred; median PFS1 was 33 months (95% CI: 17-not evaluable), median PFS2 was 8.3 months (95% CI: 6.9-14), and median OS was 87 months (95% CI: 58.2-not evaluable). Twenty-six of the 36 patients underwent MSK-IMPACT testing, and 25 (96%) harbored MAPK pathway alterations., Conclusion: Most patients diagnosed with early-stage disease ultimately recurred. Somatic MAPK signaling pathway mutations appear to be highly prevalent in MA/MLA, and therapeutics that target this pathway are worthy of further study., Competing Interests: Declaration of competing interest B. Weigelt reports research funding by Repare Therapeutics, outside the current work. N. R. Abu-Rustum reports grant funding from GRAIL paid to the institution. A. Iasonos reports consulting fees from Mylan. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). D. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. R.N. Grisham reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. The other authors do not have potential conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the impact of short-term postoperative complications on oncologic outcomes for patients with epithelial ovarian cancer undergoing primary cytoreductive surgery (PCS) or interval cytoreductive surgery (ICS) with intestinal resection., Methods: A retrospective chart review was performed for patients with ovarian cancer who underwent PCS or ICS with at least one intestinal resection at our institution from 1/1/2015 to 12/31/2020. Progression-free survival (PFS) and overall survival (OS) were analyzed for the PCS and ICS cohorts separately. Short-term complications within 30 days of surgery (surgical secondary events [SSEs]) were graded by a validated institutional SSE system., Results: Among 437 patients who underwent intestinal resections during PCS (n = 289) or ICS (n = 148), 183 (42%) had one, 180 (41%) had two, and 74 (17%) had three intestinal resections. Six (1.4%) of 437 patients experienced an anastomotic leak postoperatively. There were no perioperative deaths. There was no difference in PFS and OS for patients who underwent PCS with any SSE vs. no SSE within 30 days of surgery (HR, 1.05; 95% CI: 0.76-1.47; p = 0.75 and HR, 0.79; 95% CI: 0.49-1.26; p = 0.32, respectively). There was no difference in PFS and OS for patients who underwent ICS with any SSE vs. no SSE within 30 days of surgery (HR, 1.43; 95% CI: 0.99-2.07; p = 0.055 and HR. 1.18; 95% CI: 0.72-1.93; p = 0.52, respectively., Conclusion: Short-term postoperative morbidity for patients who underwent intestinal surgery during primary surgical management for advanced ovarian cancer did not impact oncologic outcomes., Competing Interests: Declaration of Competing Interest Outside the submitted work, N.R. Abu-Rustum reports research grants from GRAIL, Inc. paid to the institution; MSK also has equity in GRAIL, Inc. A. Iasonos reports consulting fees from Mylan. M.M. Leitao is an ad-hoc speaker for Intuitive Surgical, Inc., has served on advisory boards for JnJ/Ethicon and Immunogen, and reports consulting fees from Medtronic. D.S. Chi reports fees from AstraZeneca, UptoDate, and Biom'Up, has stock in Doximity, and has served on advisory boards for Apyx Medical Corp, Biom'Up, and Verthemia. The remaining authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

BACKGROUND. Imaging reports that consistently document all disease sites with a potential to increase surgical complexity or morbidity can facilitate ovarian cancer treatment planning. OBJECTIVE. The aims of this study were to compare simple structured reports and synoptic reports from pretreatment CT examinations in patients with advanced ovarian cancer in terms of completeness of documenting involvement of clinically relevant anatomic sites as well as to evaluate physician satisfaction with synoptic reports. METHODS. This retrospective study included 205 patients (median age, 65 years) who underwent contrast-enhanced abdominopelvic CT before primary treatment of advanced ovarian cancer from June 1, 2018, to January 31, 2022. A total of 128 reports generated on or before March 31, 2020, used a simple structured report (free text organized into sections); 77 reports generated on or after April 1, 2020, used a synoptic report (a list of 45 anatomic sites relevant to ovarian cancer management, each of which was classified in terms of disease absence versus presence). Reports were reviewed for completeness of documentation of involvement of the 45 sites. For patients who underwent neoadjuvant chemotherapy based on diagnostic laparoscopy findings or underwent primary debulking surgery with suboptimal resection, the EMR was reviewed to identify surgically established sites of disease that were unresectable or challenging to resect. Gynecologic oncology surgeons were electronically surveyed. RESULTS. The mean report turnaround time was 29.8 minutes for simple structured reports versus 54.5 minutes for synoptic reports ( p < .001). A mean of 17.6 of 45 sites (range, four to 43 sites) were mentioned by simple structured reports versus 44.5 of 45 sites (range, 39-45) for synoptic reports ( p < .001). Forty-three patients had surgically established unresectable or challenging-to-resect disease; involvement of anatomic site(s) with such disease was mentioned in 37% (11/30) of simple structured reports versus 100% (13/13) of synoptic reports ( p < .001). All eight surveyed gynecologic oncology surgeons completed the survey. CONCLUSION. A synoptic report improved completeness of pretreatment CT reports in patients with advanced ovarian cancer, including for established sites of unresectable or challenging-to-resect disease. CLINICAL IMPACT. The findings indicate the role of disease-specific synoptic reports in facilitating referrer communication and potentially guiding clinical decision-making.

Objective: To assess the clinicopathologic, molecular profiles, and survival outcomes of patients with endometrial carcinomas (ECs) harboring telomerase reverse transcriptase (TERT) hotspot mutations or gene amplification., Methods: ECs harboring somatic TERT promoter hotspot mutations or gene amplification (TERT-altered) were identified from 1944 ECs that underwent clinical tumor-normal sequencing from 08/2016-12/2021. Clinicopathologic variables, somatic mutation profiles, and survival outcomes of TERT-alt and TERT-wild-type EC were assessed., Results: We identified 66 TERT-altered ECs (43 TERT-mutated and 23 TERT-amplified), representing 3% of the unselected ECs across histologic subtypes. Most TERT-altered ECs were of copy number (CN)-high/TP53abn molecular subtype (n = 40, 60%), followed by microsatellite-unstable (MSI-H) or CN-low/no specific molecular profile (NSMP)(n = 13, 20% each). TERT-amplified and TERT-mutated ECs were molecularly distinct, with TERT-amplified ECs being more genomically instable and more frequently harboring TP53 and PPP2R1A alterations (q < 0.1). Compared to TERT-wild-type ECs, TERT-altered ECs were more commonly of CN-H/TP53abn molecular subtype (31% vs 57%, p = 0.001), serous histology (10% vs 26%, p = 0.004), and were significantly enriched for TP53, CDKN2A/B, and DROSHA somatic genetic alterations (q < 0.1). Median progression-free survival was 18.7 months (95% CI 11.8-not estimable [NE]) for patients with TERT-altered EC and 80.9 months (65.8-NE) for patients with TERT-wild-type EC (HR 0.33, 95% CI 0.21-0.51, p < 0.001). Similarly, median overall survival was 46.7 months (95% CI 30-NE) for TERT-altered EC patients and not reached for TERT-wild-type EC patients (HR 0.24, 95% CI 0.13-0.44, p < 0.001)., Conclusion: TERT-altered ECs, although rare, are enriched for CN-high/TP53abn tumors, TP53, CDKN2A/B and DROSHA somatic mutations, and independently predict worse survival outcomes., Competing Interests: Declaration of Competing Interest N.R. Abu-Rustum reports Stryker/ Novadaq and GRAIL grants paid to the institution, outside the current study. B. Weigelt reports a research grant from REPARE Therapeutics paid to the institution, outside the submitted work. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We aimed to determine the frequency of human papillomavirus-independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics. Among 670 patients with surgically treated SCCs in an established multi-institutional cohort, 447 had available tissue. Tissue microarrays were constructed and studied by in situ hybridization (ISH) for high-risk and low-risk human papillomavirus (HPV) mRNA and immunohistochemistry for p16 and p53. Tumors were HPVI if negative by HPV ISH and they failed to show diffuse p16 positivity by immunohistochemistry, and human papillomavirus-associated (HPVA) if positive by HPV ISH. Ten HPVI SCCs and 435 HPVA SCCs were identified; 2 cases were equivocal and excluded from analysis. The overall rate of HPVI SCC was low (2%) but was higher among older patients (7% in patients above 60 y of age and 17% in patients above 70 y of age). Compared with HPVA, patients with HPVI SCC were significantly older (median age, 72 vs. 49, P <0.001) and diagnosed at a higher stage (40% vs. 18% with stage III/IV disease, P =0.055). p53 expression was varied; 2 cases (20%) had null expression and 8 (80%) had wild-type expression. HPVI SCCs were heterogenous, with keratinizing, nonkeratinizing, and warty morphologies observed. Several cases had a precursor lesion reminiscent of differentiated vulvar intraepithelial neoplasia, with prominent basal atypia and hypereosinophilia or a basaloid-like morphology. Two patients (20%) had distant recurrences within 12 months, and 3 (30%) died of disease during follow-up. HPVI SCCs are rare tumors that are more common among older patients with higher stage disease and have important clinical and histologic differences from HPVA SCCs., Competing Interests: Conflicts of Interest and Source of Funding: Funded in part by the National Institutes of Health (NIH)/National Cancer Institute (NCI) Cancer Center Support Grant P30 CA008748. Outside the submitted work, N.R.A.-R. reports research funding paid to the institution from GRAIL. A.I. reports consulting fees from Mylan. For the remaining authors none were declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We evaluated clinicopathologic parameters of patients with cervical squamous cell carcinoma (SCC) who were treated with initial surgical management and assessed their relation to survival outcomes. Specifically, we evaluated the relation between extent of lymphovascular invasion (LVI) and survival outcomes., Methods: All available tumor slides from patients with initially surgically treated cervical SCC were collected from 10 institutions and retrospectively analyzed. Standard clinicopathological parameters, tumor stroma, and extent of LVI were assessed (focal: <5 spaces, extensive: ≥5 spaces). PFS and OS were evaluated using Kaplan-Meier methodology. Univariable and multivariable Cox proportional hazards models were created to determine prognostic survival-related risk factors., Results: A total of 670 tumor samples were included in the analysis. Median age at diagnosis was 47 years (IQR: 38-60), 457 patients (72%) had a 2018 International Federation of Gynecology and Obstetrics (FIGO) stage I tumor, and 155 tumors (28%) were flat and/or ulcerated. There were 303 nonkeratinizing tumors (51%), 237 keratinizing tumors (40%), and 356 histologic grade 2 tumors (61%). Quantifiable LVI was present in 321 cases (51%; 23% focal and 33% extensive). On multivariable analysis for PFS, extensive and focal LVI had worse outcomes compared to negative LVI (HR: 2.38 [95% CI: 1.26-4.47] and HR: 1.54 [95% CI: 0.76-3.11], respectively; P = 0.02). The difference did not reach statistical significance for OS., Conclusion: Presence of LVI is a prognostic marker for patients with cervical SCC. Quantification (extensive vs. focal vs. negative) of LVI may be an important biomarker for oncologic outcome., Competing Interests: Declaration of Competing Interest Outside the submitted work, N.R. Abu-Rustum reports research funding paid to the institution from GRAIL. A. Iasonos reports consulting fees from Mylan. All other authors have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl)., Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event., Results: AUC statistics (range, 0.52-0.64) showed log(CrCl Jelliffe ) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl <60 mL/min. Positive predictive values for adverse events ranged from 1.8%-15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively., Conclusion: The formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl <60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl <60 mL/min as an exclusion criterion from clinical trials., Competing Interests: Declaration of Competing Interest Dr. O'Cearbhaill reports support for this study from NCI/NIH P30 CA008748 and grants to Institution from Bayer/Celgene/Juno, Tesaro/GSK, Merck, Ludwig Cancer Institute, AbbVie/Stemkens, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, Marker Therapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Genentech, Kite Pharma, Acrivon and Gynecologic Oncology Foundation. Outside of the submitted work, Dr. O'Cearbhaill reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences and Curio. Dr. O'Cearbhaill reports receiving support to attend meetings and/or travel from Hitech Health, Gathering Around Cancer, Ireland, GOG Foundation and SGO. Dr. O'Cearbhaill participated on Data Safety Monitoring Board or Advisory Board for each of the following: AstraZeneca (DUO-0), GSK (moonstone, Prima), Acrivon, Carina Biotech, Link therapeutics, Tesaro/GSK, Regeneron, Seattle Genetics/Seagen, Immunogen, Bayer, R-Pharm, 2seventybio, Miltenyi and Fresenius Kabi. Dr. O'Cearbhaill also served as Vice-chair for the CPC, SGO as well a Chair, Developmental Therapeutics Committee for NRG Oncology. Dr. Aghajanian received research grants from AbbVie, Clovis, Genentech and Astra Zeneca and served on advisory boards for AbbVie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics and Roche/Genentech and received consulting fees for serving. Dr. Aghajanian served on the Blueprint Medicine Advisory Board (uncompensated). Dr. Aghajanian also serves on the GOG Foundation, Board of Directors (travel cost reimbursement for attending meetings) as well as the NRG Oncology Board of Directors (unpaid). Dr. Floor Backes wishes to report research grants from Immunogen, Clovis, Merck, Eisai, Natera and Beigene. Dr. Backes reports receiving consulting fees received from Eisai, Merck, Agenus, AstraZeneca, GlaxoSmithKline; Myriad, Clovis Oncology and Immunogen. Dr. Backes received honoraria for serving on advisory boards from Medlearning Group, CEC Oncology, OncLive, i3Health, and Medscape. Dr. Backes serves as Co-Chair of the NRG Oncology Developmental Therapeutics. Dr. Backes is a member of the Uterine Corpus Committee as well as a NCCN Ovary member and serves as an SGO Board Member. Dr. Michael Bookman reports payment to his Institution from Immunogen Data Monitoring Committee (unrelated to this project). Dr. David Cohn reports receiving honoraria from UpToDate as an Author as well as receiving payment for his role with Elsevier, Gynecologic Oncology as an Editor-in-Chief. Dr. Michael Friedlander reports that personally receiving consulting fees from AstraZeneca, Novartis, GSK and Incyclix (Nil). Dr. Friedlander also reports receiving honoraria from AstraZeneca and GSK and also received travel funding from AstraZeneca. Dr. Friedlander reports participating on Data Safety Monitoring Board/Advisory Board for AGITG IDSMB and ENDO-3. Dr. Friedlander reports that his Institution received grants from AstraZeneca, Beigene and Novartis. Dr. David Gershenson reports support from NRG Oncology with regard to this Study. Dr. Gershenson also acknowledges grants to his Institution from Novartis, GOG Foundation, and the NCI. Dr. Gershenson personally received royalties from Elsevier and UpToDate and consulting fees from Genentech (uncompensated) and Verastem. Dr. Gershenson received honoraria from University of Washington OB/GYN Grand Rounds and Yale University OB/GYN Grand Rounds and participating in a data safety monitoring/advisory board for Onconova, Aadi and Springworks. Dr. Gershenson also served on the International Consortium for Low-Grade Serous Ovarian Cancer and NCCN Ovarian Cancer Panel (uncompensated). Dr. Gershenson also wishes to disclose having stock in managed accounts for Bristol Myers Squibb, Johnson & Johnson and Procter & Gamble. Dr. Michael Goodheart reports receiving consulting fees from GlasoSmithKlein GSK/Tesaro, Merck, AstraZeneca, Clovis Oncology, SeaGen and Eisai. Dr. Angeles Alvarez Secord reports clinical trial grants received from the following: AbbVie, Aravive, AstraZeneca, BoehringerIngelheim, Clovis, Eisai, Ellipses, I-MAB Biopharma, Immunogen, Merck, Oncoquest/Canaria Bio, Seagen Inc., TapImmune, Tesaro/GSK, VBL Therapeutics. Dr. Secord also wishes to report receiving clinical trial grant/translational research grant from Roche/Genentech as well as Consulting fee from Myriad. Dr. Secord also received support for attending meetings/travel from GSK, GOG Foundation and NRG. Dr. Secord also served on the Clinical Trial Steering Committees for Aravive, Genentech/Roche, VBL Therapeutics and Oncoquest/Canaria Bio without compensation. Dr. Secord personally received compensation from GOG Foundation and NRG Oncology paid compensation to Institution. Dr. Secord also served in Leadership roles for Society of Gynecologic Oncology and American Association of Obstetrics and Gynecology Foundation (uncompensated). Dr. Judith Smith received honoraria for Speaking at the HOPA Annual Meeting 2016 – Harmonization of Carboplatin Dosing, Dr. Smith serves as Chair on the NRG Oncology Pharmacy Subcommittee. Dr. Tewari also reports receiving honoraria from Eisai, AstraZeneca, Clovis, GSK/Tesaro, Merck and Seagen/Genmab. Dr. Krishnansu Tewari reports receiving consulting fees from Regeneron, Eisai, AstraZeneca, Clovis, GSK/Tesaro, Merck, Seagen/Genmab. Dr. Andrea Wahner Hendrickson reports receiving Clinical Trial support from Prolynx and Site PI Clinical Trial Support from both Amgen and TORL Biotherapeutics. Dr. Wahner Hendrickson reports serving on Oxcia Advisory Board (uncompensated). Dr. Wahner Hendrickson reports serving on an Advisory Board for the Mayo Clinic Data Safety Monitoring Board (uncompensated). Dr. Wahner Hendrickson also served on the NCCN Ovarian Cancer Committee (uncompensated). Dr. Robert Wenham reports personal and institutional grants received from Merck and Ovation Diagnostics. Dr. Wenham reports receiving consulting fees from Merck, Legend Biotech, Genentech, Ovation Diagnostics, GSK/Tesaro, Clovis, AstraZeneca, AbbVie, Legend Biotech, Regeneron, Seagen, Sonic Biotherapeutics, Shattuck Labs, Novacure, Eisai and Immunogen. Dr. Wenham also reports receiving Institutional Clinical Trial Fees from AbbVie, AstraZeneca, Regeneron and Eisai. Dr. Wenham reports serving on Advisory Board for Seagen and GSK/Tesaro. Dr. Wenham would like to disclose personally owning stock in Ovation Diagnostics. Dr. Peter Argenta, Dr. Heidi Gray, Dr. Roger Lee, Dr. Stuart Lichtman, Dr. Austin Miller, Dr. David Mutch, Dr. Aaron Praiss, Dr. Paul Sabbatini and Dr. Linda Van Le have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess postoperative complications after secondary cytoreductive surgery (SCS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), we conducted an exploratory analysis of patients with platinum-sensitive recurrent ovarian cancer enrolled in a randomized phase II trial., Methods: Complications occurring within 30 days of surgery were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0; only hemoglobin and platelet levels were assessed. Patients were grouped by CTCAE grade ≥ 3 and < 3 complications., Results: Among 83 eligible patients, 33 (40%) had grade ≥ 3 complications and 50 (60%) had grade < 3 complications; anemia and abdominal infections were the most common. There were no perioperative mortalities. Time to initiation of postoperative chemotherapy for patients with grade ≥ 3 and grade < 3 events was 34 days (range, 18-60) and 31 days (range, 21-43), respectively (P = .017). Median progression-free survival (PFS) did not significantly differ between patients with grade ≥ 3 and grade < 3 complications (11.2 months [95% CI: 9.3-14.4] vs 14.9 months [95% CI: 11.3-16.5], respectively; P = .186), nor did median overall survival (OS) (46.9 months [95% CI: 34-NE] vs 68.2 months [95% CI: 52.1-NE], respectively; P = .053)., Conclusion: Postoperative complications following SCS with or without HIPEC were associated with slight delays in chemotherapy initiation but did not significantly impact oncologic outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials., Methods: The National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens., Results: A total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%-81.7% for patients meeting GOG-249 inclusion criteria, 40.2%-81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%-75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology., Conclusions: Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results., Competing Interests: Declaration of Competing Interest Dr. Wright received research support from Merck and honoraria from UpToDate., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: Our objective is to provide a history, rationale, and review of the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of ovarian cancer., Recent Findings: In the last decade, there has been an increase in the literature regarding HIPEC in the treatment of ovarian cancer. The rationale for HIPEC extends from earlier trials demonstrating improved survival using intraperitoneal chemotherapy. HIPEC provides a one-time opportunity for intraperitoneal chemotherapy at the time of cytoreduction and with the addition of hyperthermia. Cisplatin HIPEC has been demonstrated to have a survival benefit when used in the interval cytoreductive setting. In terms of safety, nephroprotection remains a key concern when administering HIPEC. Sodium thiosulfate provides nephroprotection and should be considered when performing HIPEC. Various institutions have created multidisciplinary protocols for administering HIPEC, which include operating room staff, nursing, anesthesia, pharmacy, and surgical teams., Summary: HIPEC has a role in the treatment paradigm of ovarian cancer. Currently, HIPEC is approved in the interval cytoreductive surgery setting. Further trials are needed to understand the appropriate timing, chemotherapeutic agents, and protocolization of HIPEC., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center., Methods: Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis., Results: A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab., Conclusions: GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype., Competing Interests: Declaration of Competing Interest Outside the submitted work, B. Weigelt reports ad hoc membership in the scientific advisory board of Repare Therapeutics, outside the scope of the study. C. Friedman reports participation in the scientific advisory boards for Merck (LYNK-002) and Genentech (MyPathway) without compensation, consulting for Seagen and Bristol Myers Squibb, and institutional research funds from Genentech/Roche, Bristol Myers Squibb, Merck, AstraZeneca, and Daiichi. E. Jewell reports personal fee from Covidien/Medtronic. K. Cadoo reports grant funding from the Irish Cancer Society, MSD, and Immunogen; consulting fees from Nextcure, MJH Life Sciences, and GSK; payments/honoraria from GSK, AstraZeneca, and MSD; financial support to attend meetings from Roche, Pfizer, and MSD; advisory board participation at MSD, AstraZeneca, GSK, and Eisai; a voluntary advisory role at the National Cancer Control Programme Ireland; and a voluntary board member at ARC Cancer Support Centers. N. Abu-Rustum reports grant funding from GRAIL paid to the institution. S. issa Bhaloo reports stock or stock options in BioNTech, Moderna, Inc., Inovio, Relief Therapeutics Holding SA, Cansino Biologics, Inc., and Pfizer, Inc. M. Leitao reports personal fees from Medtronic, Intuitive Surgical, Inc., and JnJ/Ethicon. C. Aghajanian has received research grants from Abbvie, Clovis, Genentech, and Astra Zeneca and served on advisory boards for Abbvie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech. R. O'Cearbhaill reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences and Curio. C. Kyi reports grant funding from Conquer Cancer Foundation; grant funding paid to the institution from Merus, Gritstone, and BMS; and consulting fees from Scenic Immunology B.V. and OncLive. D. Zamarin is an inventor on a patent related to the use of oncolytic Newcastle Disease Virus for cancer therapy, and reports grant funding paid to the institution from AstraZeneca, Roche, Plexxikon, and Synthekine; consulting fees from Memgen, Celldex, Agenus, Astellas, AstraZeneca, Crown Biosciences, Roche, GSK, Hookpia, ImmunOS, Kalvir, Synlogic Therapeutics, Synthekine, Takeda, Targovax, Tessa Therapeutics, and Xencor; stock options in Accurius Therapeutics, Immunos Therapeutics and Calidi Biotherapeutics; and a Merck licensed patent (with personal payments and payments to the institution). All other authors have no potential conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Total vaginal hysterectomy (TVH) has been proposed as an alternative to laparoscopic (TLH) and abdominal hysterectomy (TAH), particularly for women with medical comorbidities. We examined the use and long-term outcomes of vaginal hysterectomy for women with early-stage endometrial cancer., Methods: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women with stage I-II endometrial cancer treated with primary hysterectomy from 2000 to 2015. Multivariable regression models were developed to examine clinical, demographic, and pathologic factors associated with performance of TVH. The association between route of hysterectomy and cancer-specific and overall survival was examined using multivariable Cox proportional hazards models., Results: A total of 19,212 patients including 837 (4.6%) who underwent TVH were identified. Performance of TVH declined from 4.5% in 2000 to 2.2% in 2015 (P < 0.0001). Compared to patients 65-69 years of age, patients 75-79 years old (aRR = 1.46; 95% CI, 1.19-1.79) and those >80 years old (aRR = 1.60; 95% CI, 1.30-1.97) were more likely to undergo TVH. Women with high grade tumors were less likely to undergo TVH. Five-year overall and cancer specific survivals were similar for TAH, TLH, and TVH. In multivariable models, there was no association between TVH and either cancer-specific survival (HR = 0.89; 95% CI, 0.65-1.22) compared to laparoscopic hysterectomy., Conclusion: Use of TVH for stage I and II endometrial cancer has decreased in the U.S. Chronologic age is the greatest predictor of performance of TVH. Performance of TVH does not negatively impact survival for women with early-stage endometrial cancer., Competing Interests: Declaration of Competing Interest Dr. Wright has served as a consultant for and Clovis Oncology, received royalties from UpToDate, and received research funding from Merck. Dr. Hou has served as a consultant for Foundation Medicine and Natera., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: We used a novel machine learning algorithm to develop a precision prognostication system for endometrial cancer., Methods: The Ensemble Algorithm for Clustering Cancer Data (EACCD) unsupervised machine learning algorithm was applied to women with endometrioid endometrial cancer in the Surveillance, Epidemiology, and End Results database from 2004 to 2015. The prognostic system was created based on TNM stage, grade, and age. The concordance (C-index) was used to cut dendrograms and create prognostic groups. Kaplan-Meier cancer-specific survival was employed to visualize the survival function of EACCD-based prognostic groups and AJCC groups., Results: A total of 46,773 women were identified. Using the machine learning algorithm with TNM stage, grade, and three age groups, eleven prognostic groups were generated with a C-index of 0.8380. The five-year survival rates for the eleven groups ranged from 37.9-99.8%. To simplify the classification system further, using visual inspection of the data we created a modified EACCD grouping, and combined the top six survival groups into three new prognostic groups. The new five-year survival rates for these eight modified prognostic groups included: 99.1% for group 1, 96.5% for group 2, 92.2% for group 3, 84.8% for group 4, 72.7% for group 5, 61.1% for group 6, 52.6% for group 7, and 37.9% for group 8. The C-index for the modified eight prognostic groups was 0.8313., Conclusion: This novel machine learning algorithm demonstrates improved prognostic prediction for patients with endometrial cancer. Using machine learning for endometrial cancer allows for the integration of multiple factors to develop a precision prognostication system., Competing Interests: Declaration of Competing Interest Dr. Wright has served as a consultant for Clovis Oncology and received research funding from Merck. Dr. Hur has served as a consultant for Kite Pharmaceuticals and has equity in Cambridge Biomedical Economic Consulting Group. No other authors have any conflicts of interest or disclosures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To examine the risk of nodal metastases in a contemporary cohort of women based on pathologic risk factors including histology, depth of invasion, tumor grade, and lymphovascular space invasion., Methods: Women with endometrial cancer who underwent hysterectomy from 2004 to 2016 who were registered in the National Cancer Database were analyzed. Patients were stratified by T stage: T1A (<50% myometrial invasion), T1B (>50% myometrial invasion) and T2 (cervical involvement). Lymph node metastases were assessed in relation to tumor T stage and grade, and further stratified by lymphovascular space invasion., Results: We identified 161,960 patients. The rate of nodal metastases within the endometrioid histology cohort was 2.2% for T1A cancers, 12.8% for T1B cancers and 19.9% for T2 cancers. For stage TIA cancers, the percent of patients with positive nodes increased from 1.1% for grade 1 cancers, to 2.9% for grade 2 cancers to 4.8% for grade 3 cancers. The corresponding rates of nodal metastases for stage T1B cancers were 8.6%, 13.7%, and 16.9%, respectively. For T1A cancers without lymphovascular space invasion, nodal metastases ranged from 0.6% in those with grade 1 cancers to 3.0% for grade 3 cancers. The corresponding risk of nodal disease ranged from 11.8% to 13.9% for T1A cancers with lymphovascular space invasion., Conclusions: There was a sequential increase in the risk of lymph node metastases based on depth of uterine invasion, tumor grade, and the presence of lymphovascular space invasion. The overall rate of nodal metastasis is lower than reported in the original GOG 33., Competing Interests: Declaration of competing interest Dr. Wright has served as a consultant for Tesaro and Clovis Oncology and received research funding from Merck. Dr. Neugut has served as a consultant to Pfizer, Teva, Otsuka, Hospira, and United Biosource Corporation. He is on the scientific advisory board of EHE, Intl. Dr. Hur has served as a consultant for Kite Pharmaceuticals and has equity in Cambridge Biomedical Economic Consulting Group. No other authors have any conflicts of interest or disclosures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Same-day discharge is becoming increasingly common for women who undergo minimally invasive hysterectomy. For women with endometrial cancer, there are limited data to describe the safety of same-day discharge., Objective: To examine trends and outcomes of same-day discharge for women with endometrial cancer who underwent minimally invasive hysterectomy., Study Design: The National Surgical Quality Improvement Program database was used to identify patients who underwent minimally invasive hysterectomy based for endometrial cancer from 2011 to 2016. The cohort was limited to women discharged on the day of surgery/postoperative day 0 or postoperative day 1. Multivariable models were used to examine clinical, demographic, and procedural characteristics associated with discharge on postoperative day 0. Multivariable models also were developed to examine the association between same-day discharge and readmission., Results: A total of 17,935 patients who underwent minimally invasive hysterectomy were identified. Of those discharged within 1 day, 1828 (12.4%) were discharged on postoperative day 0 and 12,892 (87.6%) were discharged on postoperative day 1 or after. The rate of same-day discharge rose from 5.6% in 2011 to 16.3% in 2016 (P<.001). In a multivariable model, more recent year of surgery was associated with same-day discharge whereas older age (≥70 years old), chronic obstructive pulmonary disease, and hypertension were associated with a decreased likelihood of same-day discharge. Similarly, obese women were 15% less likely to have a same-day discharge than normal-weight women (risk ratio, 0.85; 95% confidence interval, 0.75-0.97). Hispanic women (risk ratio, 1.61; 95% confidence interval, 1.35-1.92 compared with white women) and those who underwent lymphadenectomy (risk ratio, 1.17; 95% confidence interval, 1.07-1.29) were more likely to have a same-day discharge. The readmission rate was 2.3% in those women discharged on the day of surgery compared with 3.1% in women discharged on postoperative day 1 (P=.051). In a multivariable model, there was no association between same-day discharge and readmission (risk ratio, 0.99; 95% confidence interval, 0.71-1.38). Among women discharged on the day of surgery, a longer operative time and the occurrence of a perioperative complication were associated with readmission., Conclusion: Same-day discharge for minimally invasive hysterectomy for endometrial cancer is increasing. In selected patients, there is no increased risk of readmission with same day discharge., (Copyright © 2019 Elsevier Inc. All rights reserved.)