Search

Competing Interests: Competing interests: None declared.

Objectives: To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC)., Methods: We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000-12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation., Results: Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33-91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1-234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94)., Conclusions: Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated., Competing Interests: Declaration of competing interest 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. Dr. Eriksson reports speaker fees from Intuitive Surgical and AstraZeneca. Dr. Makker reports unpaid consulting/advisory roles with the following: Duality, Novartis, Morphosys, AstraZeneca, Eisai, Clovis Oncology, Karyopharm Therapeutics, GlaxoSmithKline, Merck, ArQule, Cullinan, Faeth Therapeutics, Jazz, Immunocore, Iteos Therapeutics, Ideaya, Kartos Therapeutics, Lilly, Moreo, Prelude, Takeda, and Zymeworks; research funding from the following: Merck (Inst), Eisai (Inst), AstraZeneca (Inst), Clovis Oncology (Inst), Bayer (Inst), Takeda (Inst), Duality (Inst), Zymeworks (Inst), Karyopharm Therapeutics (Inst), Faeth Therapeutics (Inst), Bristol-Myers Squibb (Inst), Lilly (Inst), and Cullinan (Inst); travel, accommodations, and expenses from the following: Eisai, Merck, AstraZeneca; and a relationship with IBM. Dr. du Bois reports honoraria/expenses from Amgen, AstraZeneca, BIOCAD, Clovis, GSK/Tesaro, Roche, and Zodiac; and consulting/advisory board role for Amgen, AstraZeneca, BIOCAD, Clovis, Genmab/Seattle Genetics, GSK/Tesaro, MSD, Roche, Pfizer. The other authors do not have potential conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sentinel lymph node biopsy (SLN) is increasingly used for surgical staging of endometrial carcinoma., Objective: To estimate the effect and cost-effectiveness of the implementation of an SLN algorithm for surgical staging in patients with intermediate- and high-risk endometrial carcinoma compared with lymphadenectomy., Methods: We performed a model-based, cost-effectiveness analysis using primary data from a tertiary referral hospital that included 829 patients with endometrial carcinoma undergoing surgical staging. We quantified the health and economic outcomes from two time periods, before and after implementation of the SLN algorithm by robotic surgery. Costs were measured directly from the hospital's financial department, while long-term health outcomes were estimated using self-reported lymphedema and health-related quality-of-life among survivors. Sensitivity analyses were conducted to evaluate uncertainty., Results: We projected that the SLN implementation period, predominately reflecting use of robotic SLN, simultaneously improved health outcomes (0.08 incremental quality-adjusted life-years) and lowered costs (US$1051) compared with the prior period involving robotic or open lymphadenectomy. SLN remained more beneficial and less costly across key sensitivity analyses-namely, varying the cost of the robotic platform, surgical equipment, number of yearly robotic procedures, percentage of robotic procedures versus percentage of laparotomies, length of stay, and lymphedema development. After 1000 simulations of the model, SLN implementation provided greater health benefits for lower costs (ie, cost saving) in 89% of simulations., Conclusion: Implementation of an SLN algorithm in the staging of intermediate- and high-risk endometrial carcinoma improved health outcomes for lower costs compared with lymphadenectomy. Cost-effectiveness could further improve by continuing to increase the proportion of robotic procedures., Competing Interests: Competing interests: AGE reports receiving speaking fees from Intuitive and GSK., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: To assess clinicopathologic features and survival outcomes of patients with endometrial carcinoma involving adnexal, full-thickness serosal, or combined involvement., Methods: This international, multi-institutional, retrospective study examined patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIIA endometrial cancer and tumors involving the uterine serosa and/or adnexa, who were surgically staged between 2000 and 2019. Patients with sarcoma histology, concurrent endometrial/ovarian malignancy, neoadjuvant treatment, positive lymph nodes, or peritoneal disease were excluded., Results: Of 185 patients identified, 139 had tumors with adnexal-only, 40 with serosal-only, and six with combined adnexal/serosal involvement. Median age at diagnosis was 60 years (range 23-89). Among tumors of endometrioid histology, 12 (48%) with serosal-only and 17 (19%) with adnexal-only involvement were FIGO grade 3 (p=0.007). Twenty-three tumors with serosal-only (64%) and 50 with adnexal-only (37%) involvement had lymphovascular invasion (p=0.004). Non-endometrioid histology was present in five tumors (83%) with combined adnexal/serosal, 15 (38%) with serosal-only, and 50 (36%) with adnexal-only involvement.Median follow-up was 77 months (range 0.6-254). Five-year progression-free survival and overall survival rates for all patients with stage IIIA disease were 73.8% (SE 3.5%) and 81.0% (SE 3.1%), respectively. For patients with adnexal-only, serosal-only, and combined adnexal/serosal involvement, 5-year progression-free survival rates were 80% (SE 3.8%), 61% (SE 8.3%), and 33% (SE 19.2%), respectively (p<0.01); 5-year overall survival rates were 85% (SE 3.3%), 70% (SE 7.8%), and 60% (SE 21.9%), respectively (p=0.09). On univariate analysis, tumors having serosal involvement with/without adnexal involvement, non-endometrioid histology, and lymphovascular invasion were significantly associated with progression. On multivariate analysis, tumors having serosal involvement with/without adnexal involvement remained significantly associated with recurrence (adjusted HR=2.2, 95% CI 1.2 to 4.3; p=0.01)., Conclusions: Patients with 2009 FIGO stage IIIA endometrial cancer have distinct survival outcomes depending upon adnexal and/or serosal involvement. Progression-free survival was worse for patients with serosal involvement after adjusting for histology, adjuvant treatment, and lymphovascular space invasion., Competing Interests: Competing interests: ML reports personal fees from Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. NRA-R reports research funding paid to the institution from GRAIL. AGE reports speaker fees from Intuitive Surgical and AstraZeneca. DZ reports institutional research support from AstraZeneca, Merck, Plexxikon, Synthekine, and Genentech; consulting fees from AstraZeneca, Synthekine, Astellas, Tessa Therapeutics, Memgen, Celldex, Crown Biosciences, Hookipa Biotech, Kalivir, Xencor, and GSK; royalties from Merck; and stock options from Accurius Therapeutics, ImmunOS Therapeutics, and Calidi Biotherapeutics, all outside the submitted work. The other authors do not have potential conflicts of interest to declare., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The objective of the present study was to characterize the molecular features of endometrial carcinomas with ambiguous histology. Eighteen carcinomas that could not be conclusively typed based on morphology and immunohistochemistry underwent analysis of mismatch repair (MMR) status, microsatellite status, and whole-exome sequencing. None of the tumors had pathogenic POLE mutation. Twelve tumors (67%) were microsatellite stable, and 6 (33%) had microsatellite instability. Fourteen tumors (78%) harbored TP53 mutations, and 2 (11%) had mutations in MMR genes. Eleven carcinomas (61%) were classified as copy number high and 7 (39%) as MSI-hypermutated, the latter including 3 tumors with TP53 mutation who concomitantly had MSI or mutation in a MMR gene. Other mutations that were found in > 1 tumor affected MUC16 (7 tumors), PIK3CA (6 tumors), PPP2R1A (6 tumors), ARID1A (5 tumors), PTEN (5 tumors), FAT1 (4 tumors), FAT4 (3 tumors), BRCA2 (2 tumors), ERBB2 (2 tumors), FBXW7 (2 tumors), MET (2 tumors), MTOR (2 tumors), JAK1 (2 tumors), and CSMD3 (2 tumors). At the last follow-up (median = 68.6 months), 8 patients had no evidence of disease, 1 patient was alive with disease, 8 patients were dead of disease, and 1 patient died of other cause. In conclusion, based on this series, the molecular landscape of endometrial carcinomas with ambiguous histology is dominated by TP53 mutations and the absence of POLE mutations, with heterogeneous molecular profile with respect to other genes. A high proportion of these tumors is clinically aggressive., (© 2024. The Author(s).)

Carcinosarcoma (CS) is an uncommon and clinically aggressive malignancy. The objective of the present study was to characterize the molecular features of CS at various anatomic locations, including serous effusions. Specimens (n = 32) consisted of 25 biopsies/surgical resection specimens and 7 serous effusions (6 peritoneal, 1 pleural) from 25 patients. Fresh-frozen cell pellets and surgical specimens underwent targeted next-generation sequencing covering 50 unique genes. A total of 31 mutations were found in 25 of the 32 tumors studied, of which 1 had 3 mutations, 4 had 2 different mutations, and 20 had a single mutation. The most common mutations were in TP53 (n = 25 in 24 tumors; 1 tumor with 2 different mutations), with less common mutations found in RB1 (n = 2), MET (n = 1), KRAS (n = 1), PTEN (n = 1), and KIT (n = 1). Patient-matched specimens harbored the same TP53 mutation. Tumors with no detected mutations were more common in serous effusion specimens (3/7; 43%) compared with surgical specimens (4/25; 16%). In conclusion, the molecular landscape of CS is dominated by TP53 mutations, reinforcing the observation that the majority of these tumors develop from high-grade serous carcinoma. Whether CS cells in serous effusions differ from their counterparts in solid lesions remains uncertain., (© 2024. The Author(s).)

Competing Interests: Competing interests: CF has reported being on the advisory board for Roche, Tesaro, GSK, MSD/AZ, and Clovis; AT has reported grants for travelling from MSD; AS has reported grants for travelling from Medical University of Vienna; RA has reported grants for travelling from GSK, Roche, MSD and Novocure; CC has reported advisory boards for GSK, MSD and Eisai; AGZE, FP, PM, OFC, MJH and FM have reported no conflicts of interest.

Purpose of Review: To review evidence around the value and challenges of surgery for recurrent epithelial ovarian cancer (ROC). Both cytoreductive and palliative aspects will be addressed RECENT FINDINGS: Prospective and retrospective evidence demonstrates a significantly longer remission derived from the combination of surgical and systemic modalities as opposed to systemic treatment alone in carefully selected ROC-patients who have relapsed more than 6 months from the end of their 1st line platinum-based chemotherapy. Nevertheless, this benefit appears to be limited when total macroscopic tumor clearance is not achieved. Selection algorithms to identify optimal surgical candidates are of paramount importance to prevent surgical morbidity without the equivalent oncological benefit. In the palliative setting, the risks and benefits of salvage surgery need to be counterbalanced with the advances of conservative techniques for optimal care. Well-defined selection algorithms to identify those who will benefit from surgery in the relapsed setting appear to be the key to oncologic and surgical success., (© 2023. The Author(s).)

Objective: The primary objective was to reveal the impact of social media ambassadors and the collaboration between the European Society of Gynaecological Oncology (ESGO) and the OncoAlert Network on Twitter during the ESGO 2022 Congress by comparing it with the ESGO 2021 Congress. We also aimed to share our experience on how to organize a social media ambassador program and evaluate the potential benefits for the society and the ambassadors., Methods: We defined the impact as promoting the congress, sharing the knowledge, change in follower count, and change in tweet, retweet, and reply counts. We used the Academic Track Twitter Application Programming Interface to retrieve data from ESGO 2021 and ESGO 2022. We used the keywords of ESGO2021 and ESGO2022 to retrieve data for each of the conferences. The time range in our study captured interactions from before, during, and after conferences. We collected the ambassadors', ESGO's, and the European Network of Young Gynae Oncologists' (ENYGO's) follower data on Twitter from November 2021 to November 2022 for comparative analysis., Results: There was a 7.23-fold increase in the use of the official congress hashtag in 2022 compared with 2021. Compared with #ESGO2021 data, the main interventions of the Social Media Ambassadors and OncoAlert partnership determined 7.79-, 17.36-, 5.50-, 10.58-, and 8.50-fold increases with #ESGO2022 data in the mentions, mentions in retweet, tweet, retweet, and replies, respectively. Similarly, all other most commonly used hashtags in the top 10 list indicated a range from 2.56- to 7.00-fold increase. Compared to the ESGO 2021 congress month, ESGO and the majority (83.3%, n=5) of ambassadors gained more followers during ESGO 2022 congress month., Conclusions: An official social media ambassadors program and collaboration with influential accounts in the field of interest are beneficial for congress-related engagement on a social media platform (Twitter). Individuals participating in the program can also benefit from gaining higher visibility among specific audience., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There is a paucity of international data regarding self-reported lower extremity lymphedema and quality of life after surgery for gynecological cancer. Validated questionnaires are emerging, but translated versions are lacking. Cross-cultural adaptation is important to reduce the risk of introducing bias into a study., Objective: To translate and culturally adapt the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire for a Norwegian population., Methods: Permission to use the original English versions of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire for translation was obtained. The questionnaires were translated using a procedure based on standard guidelines, including forward translation by native speakers of the target language, synthesis, back translation, and review. Seventeen patients from the Norwegian Radium Hospital gynecological cancer outpatient clinic, all expected to have stable disease, were invited for questionnaire test-retest by completing the same questionnaires twice at 3-4-week intervals. Internal consistency was assessed by calculating Cronbach's alpha. Test-retest reliability was assessed using an intra-class correlation coefficient., Results: Twelve patients completed the questionnaires twice. Cronbach's alpha was 0.75 for the Gynecologic Cancer Lymphedema Questionnaire and 0.89 for the Lower Extremity Lymphedema Screening Questionnaire. The intra-class correlation coefficient was 0.86 for the Gynecologic Cancer Lymphedema Questionnaire and 0.91 for the Lower Extremity Lymphedema Screening Questionnaire., Conclusions: Translation and cross-cultural adaptation of these internationally validated patient-reported outcomes questionnaires for survivors of lower extremity lymphedema in gynecological cancer was feasible. The Norwegian translation of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire showed acceptable internal consistency and the test-retest reliability was excellent., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objectives: Twitter is the most frequently used social media platform by healthcare practitioners, at medical conferences. This study aimed to analyze Twitter conversations during the virtual International Gynecological Cancer Society 2020 conference to understand the interactions between Twitter users related to the conference., Methods: Tweets using the hashtag '#IGCS2020' were searched using the Twitter Search Application Programming Interface (API) during the period 10-13 September 2020. NodeXL Pro was used to retrieve data. The Clauset-Newman-Moore cluster algorithm clustered users into different groups or 'clusters' based on how users interacted., Results: There were 2009 registrants for the virtual IGCS 2020 conference. The total number of users within the network was 168, and there were 880 edges connecting users. Five types of edges were identified as follows: 'replies to' (n=18), 'mentions' (n=221), 'mentions in retweets' (n=375), retweets (n=198), and tweets (n=68). The most influential account was that of the IGCS account itself (@IGCSociety). The overall network shape resembled a community where distinct groups formed within the network. Our current analyses demonstrated that less than 10% of the total members interacted on Twitter., Conclusion: This study identified the most influential Twitter users within the '#IGCS2020' community. he results also confirmed the community network shape of the #IGCS2020 hashtag and found that the most frequent co-related words were 'ovarian' and 'cancer' (n=39)., Competing Interests: Competing interests: AGE is a Member of the Education Council of IGCS and social media editor of the International Journal of Gynecological Cancer., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology., Material and Methods: The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts., Results: The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology., Conclusions: As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients., Competing Interests: Declaration of Competing Interest There are no conflicts of interest reported., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Optimizing and ensuring the quality of surgical care is essential to improve the management and outcome of patients with cervical cancer.To develop a list of quality indicators for surgical treatment of cervical cancer that can be used to audit and improve clinical practice., Methods: Quality indicators were developed using a four-step evaluation process that included a systematic literature search to identify potential quality indicators, in-person meetings of an ad hoc group of international experts, an internal validation process, and external review by a large panel of European clinicians and patient representatives., Results: Fifteen structural, process, and outcome indicators were selected. Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are also detailed to define how the indicator will be measured in practice. Each indicator has a target which gives practitioners and health administrators a quantitative basis for improving care and organizational processes., Discussion: Implementation of institutional quality assurance programs can improve quality of care, even in high-volume centers. This set of quality indicators from the European Society of Gynaecological Cancer may be a major instrument to improve the quality of surgical treatment of cervical cancer., Competing Interests: Competing interests: DC has reported advisory roles for AstraZeneca, Roche, and Sotio; FR has reported activities for Roche, AstraZeneca, and Tesaro; IV has reported advisory boards for Advaxis, Inc, Eisai Inc, MSD Belgium, Roche NV, Genmab, F Hoffmann-La Roche Ltd, PharmaMar, Millenium Pharmaceuticals, Clovis Oncology Inc, AstraZeneca NV, Tesaro, Oncoinvent AS, Immunogen Inc, Sotio, contracted research (via KU Leuven) with Oncoinvent AS, Genmab, research grants from Amgen, Roche, Stichting tegen Kanker, accommodations and/or travel expenses from Takeda Oncology, PharmaMar, Genmab, Roche, AstraZeneca and Tesaro; DF, CF, CK, FL, PM, RN, FP, JP, DQ, AR, KT, CT, PW, and AGZE have reported no conflicts of interest., (© IGCS and ESGO 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objectives: To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases., Methods: Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts., Results: 214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70-3.04) and 0.44 (95% CI: 0.19-1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02-9.57) and 0.69 (95% CI: 0.24-1.95), respectively., Conclusion: OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival., Primary Objective: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy., Study Hypothesis: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes., Trial Design: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden., Major Inclusion/exclusion Criteria: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years., Primary Endpoint: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer., Sample Size: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1-β) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients., Estimated Dates for Completing Accrual and Presenting Results: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter., Trial Registration: The trial is registered at ClinicalTrials.gov (NCT03719547)., Competing Interests: Competing interests: HF, RK, and JP are proctors for Intuitive Surgical Inc., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Radical hysterectomy and complete pelvic lymphadenectomies are the most commonly performed procedures for women with early-stage cervical cancer. Sentinel lymph node (SLN) mapping could be an alternative to routine pelvic lymphadenectomy, aiming to diagnose accurately nodal extension and decrease lymphatic morbidity., Primary Objective: To compare 3-year disease-free survival and health-related quality of life after SLN biopsy or SLN biopsy + pelvic lymphadenectomy in early cervical cancer., Study Hypothesis: We hypothesize that disease-free survival is non-inferior and health-related quality of life superior after SLN biopsy compared with SLN biopsy + pelvic lymphadenectomy., Trial Design: International, randomized, multicenter, single-blind trial. The study will be run by teams trained to carry out SLN biopsy, belonging to clinical research cooperative groups or recognized as experts in this field. Patients with an optimal mapping (Memorial Sloan Kettering Cancer Center [MSKCC] criteria) and a negative frozen section will be randomized 1:1 to SLN biopsy only or SLN biopsy + pelvic lymphadenectomy., Inclusion, Exclusion Criteria: Patients with early stages (Ia1 with lymphovascular invasion to IIa1) of disease. Histological types are limited to squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma., Primary Endpoint: Main endpoint will be co-primary endpoint, associating 3-year disease-free survival and quality of life (QLQ-C30 and QLQ-CX24)., Sample Size: 950 patients need to be randomized.Estimated dates for completing accrual and presenting results: study started on Q2 2018, last accrual is scheduled for Q2 2021, and last follow-up in Q2 2026., Trial Registration: ClinicalTrials.gov identifier: NCT03386734., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The objective of this study was to assess and compare the sentinel lymph node (SLN) detection rate with indocyanine green (ICG) and near-infrared fluorescence imaging versus blue dye using the robotic platform in patients with uterine cancer., Methods: We identified all patients with uterine cancer undergoing SLN mapping using ICG or blue dye on the robotic platform from January 2011 to December 2013. Our institutional SLN algorithm and pathologic processing protocol were adhered to uniformly. We compared detection rates of SLNs stratified by dye used. Appropriate statistical tests were used., Results: A total of 472 patients were identified. ICG was used in 312 patients (66%) and blue dye in 160 patients (34%). Successful mapping was achieved in 425 (90%) of 472 patients. Mapping was bilateral in 352 patients (75%) and unilateral in 73 patients (15%); 47 patients (10%) did not map. Successful mapping was achieved in 295 (95%) of 312 patients using ICG compared with 130 (81%) of 160 patients using blue dye (P < 0.001). Mapping was bilateral in 266 (85%) of 312 patients in the ICG group compared with 86 (54%) of 160 in the blue dye group (P < 0.001). Additional lymph node dissection beyond removal of the SLNs was performed in 122 patients (39%) mapped with ICG compared with 98 patients (61%) mapped with blue dye (P < 0.001)., Conclusions: The SLN detection rate was superior when mapping with ICG rather than blue dye. Bilateral mapping was significantly improved, resulting in a lower rate of additional lymphadenectomy.

Purpose: The aim of this study was to determine the impact of obesity on the rate of successful sentinel lymph node (SLN) mapping in patients with uterine cancer undergoing robotic surgery, and compare SLN detection rates using indocyanine green (ICG) versus blue dye., Methods: We reviewed robotic cases undergoing SLN mapping with a cervical injection from January 2011 to December 2013 using either blue dye or ICG with near-infrared (NIR) fluorescence imaging. Data were stratified by body mass index (BMI) and the dye used. Appropriate statistical tests were applied., Results: Overall, 472 cases were identified. Bilateral mapping was successful in 352 cases (75 %), and unilateral mapping was successful in 73 cases (15 %). Bilateral mapping was achieved in 266 (85 %) of 312 ICG cases compared with 86 (54 %) of 160 blue-dye cases (p < 0.001). Cases with successful bilateral mapping had a median BMI of 29.8 kg/m(2) (range 16.3-65.3 kg/m(2)); cases with no mapping had a median BMI of 34.7 kg/m(2) (range 21.4-60.4 kg/m(2)) (p = 0.001). With increasing BMI, there was a significant decrease in successful bilateral mapping rates for both the ICG (p < 0.001) and blue-dye groups (p = 0.041); however, the use of ICG resulted in better bilateral (p = 0.002) and overall (p = 0.011) mapping rates compared with the use of blue dye in all BMI groups., Conclusions: ICG results in a higher overall and bilateral SLN detection than blue dye in women with uterine cancer. Successful mapping decreases with increasing BMI irrespective of the dye used; however, it is significantly improved with the use of ICG and NIR fluorescence imaging compared with blue dye.

Background: Minimally invasive surgery (MIS) is associated with decreased complication rates, length of hospital stay, and cost compared with laparotomy. Robotic-assisted surgery-a method of laparoscopy-addresses many of the limitations of standard laparoscopic instrumentation, thus leading to increased rates of MIS. We sought to assess the impact of robotics on the rates and costs of surgical approaches in morbidly obese patients with uterine cancer., Methods: Patients who underwent primary surgery at our institution for uterine cancer from 1993 to 2012 with a BMI ≥40 mg/m(2) were identified. Surgical approaches were categorized as laparotomy (planned or converted), laparoscopic, robotic, or vaginal. We identified two time periods based on the evolving use of MIS at our institution: laparoscopic (1993-2007) and robotic (2008-2012). Direct costs were analyzed for cases performed from 2009 to 2012., Results: We identified 426 eligible cases; 299 performed via laparotomy, 125 via MIS, and 2 via a vaginal approach. The rates of MIS for the laparoscopic and robotic time periods were 6 % and 57 %, respectively. The rate of MIS was 78 % in this morbidly obese cohort in 2012; 69 % were completed robotically. The median length of hospital stay was 5 days (range 2-37) for laparotomy cases and 1 day (range 0-7) for MIS cases (P < 0.001). The complication rate was 36 and 15 %, respectively (P < 0.001). The rate of wound-related complications was 27 and 6 %, respectively (P < 0.001). Laparotomy was associated with the highest cost., Conclusions: The robotic platform provides significant health and cost benefits by increasing MIS rates in this patient population.

Purpose: The aim of this study was to characterize treatment patterns and oncologic outcomes in patients with low-volume lymph node metastasis (isolated tumor cells [ITCs] and micrometastasis [MM]) discovered during sentinel lymph node (SLN) mapping for endometrial carcinoma., Methods: We identified endometrial cancer cases treated surgically from September 2005 to April 2013 in which SLN mapping was performed. MM was defined as tumor within a lymph node measuring >0.2 mm but <2.0 mm, and ITCs were those measuring ≤0.2 mm., Results: Overall, 844 patients, with a median age of 61 years (range 30-90), met the inclusion criteria. Histology was as follows: endometrioid, 724 (85.8 %) patients; serous, 104 (12.3 %) patients; and clear cell, 16 (1.9 %) patients. The median number of lymph nodes resected was six (range 0-60), and the median number of SLNs was two (range 0-15). Overall, 753 (89.2 %) patients were node-negative, 23 (2.7 %) had ITCs only, 21 (2.5 %) had MM only, and 47 (5.6 %) had macrometastasis. Adjuvant chemotherapy was administered to 106 (14 %) of 753 node-negative patients, 19 (83 %) of 23 patients with ITCs, 17 (81 %) of 21 patients with MM, and 42 (89 %) of 47 with macrometastasis. Median follow-up was 26 months (range 0-108). Three-year recurrence-free survival was as follows: node-negative patients, 90 % (±1.5); ITCs only, 86 % (±9.4); MM only, 86 % (±9.7); and macrometastasis, 71 % (±7.2) [p < 0.001]., Conclusions: Patients with ITCs and MM frequently received adjuvant chemotherapy and had improved oncologic outcomes in comparison to those with macrometastasis to the lymph nodes. Further prospective study is needed to determine optimal post-resection management in patients with ITCs or MM alone.

Objective: The aim of this study was to evaluate the use of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) before and after results from a randomized trial were published and showed non-inferiority between NACT and PDS in the management of advanced-stage ovarian carcinoma., Methods: We evaluated consecutive patients with advanced-stage ovarian cancer treated at our institution from 1/1/08-5/1/13, which encompassed 32 months before and 32 months after the randomized trial results were published. We included all newly diagnosed patients with high-grade histology and stage III/IV disease. Associations between the use of NACT and clinical variables over time were evaluated., Results: Our study included 586 patients. Median age was 62 years (range, 30-90); 406 patients (69%) had stage III disease, and 570 (97%) had disease of serous histology. Twenty-six percent (154/586) were treated with NACT and 74% (432/586) with PDS. NACT use increased significantly from 22% (56/256) before 2010 (at which point the results of the randomized trial were published) to 30% (98/330) after 2010 (p=0.037). Although patients who underwent PDS were more likely to experience grade 3/4 surgical complications than those who underwent NACT, those selected for PDS had a median OS of 71.7 months (CI, 59.8-not reached) compared with 42.9 months (CI 37.1-56.3) for those selected for NACT., Conclusions: In this single-institution analysis, the best survival outcomes were observed in patients who were deemed eligible for PDS followed by platinum-based chemotherapy. Selection criteria for NACT require further definition and should take institutional surgical strategy into account., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To assess clinicopathologic outcomes between two nodal assessment approaches in patients with endometrioid endometrial carcinoma and limited myoinvasion., Methods: Patients with endometrial cancer at two institutions were reviewed. At one institution, a complete pelvic and para-aortic lymphadenectomy to the renal veins was performed in select cases deemed at risk for nodal metastasis due to grade 3 cancer and/or primary tumor diameter>2cm (LND cohort). This is a historic approach at this institution. At the other institution, a sentinel lymph node mapping algorithm was used per institutional protocol (SLN cohort). Low risk was defined as endometrioid adenocarcinoma with myometrial invasion <50%. Macrometastasis, micrometastasis, and isolated tumor cells were all considered node-positive., Results: Of 1135 cases identified, 642 (57%) were managed with an SLN approach and 493 (43%) with an LND approach. Pelvic nodes (PLNs) were removed in 93% and 58% of patients, respectively (P<0.001); para-aortic nodes (PANs) were removed in 14.5% and 50% of patients, respectively (P<0.001). Median number of PLNs removed was 6 and 34, respectively; median number of PANs removed was 5 and 16, respectively (both P<0.001). Metastasis to PLNs was detected in 5.1% and 2.6% of patients, respectively (P=0.03), and to PANs in 0.8% and 1.0%, respectively (P=0.75). The 3-year disease-free survival rates were 94.9% (95% CI, 92.4-97.5) and 96.8% (95% CI, 95.2-98.5), respectively., Conclusions: Our findings support the use of either strategy for endometrial cancer staging, with no apparent detriment in adhering to the SLN algorithm. The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy is yet to be determined., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The study objective was to investigate and validate plasma growth differentiation factor-15 (GDF-15) as a predictor of lymph node metastasis and a poor prognosis in primary endometrial cancer., Experimental Design: Plasma samples from 510 women treated for endometrial cancer in a primary investigation cohort (n = 44) and a secondary validation cohort (n = 466) were analyzed for GDF-15. Plasma from healthy premenopausal (n = 20) and postmenopausal (n = 20) women, women with borderline (n = 43), benign (n = 144), and malignant ovarian tumors (n = 125) were used for comparison., Results: Median plasma GDF-15 concentration for the endometrial cancer group was elevated (1,077 ng/L) as compared with pre- and postmenopausal controls (590 and 684 ng/L) and women with benign (591 ng/L) or borderline ovarian tumors (718 ng/L; all P < 0.001), but similar to the ovarian cancer group. In the large validation cohort of endometrial carcinomas, high plasma GDF-15 was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease, nonendometrioid histology, high grade, older age, postmenopausal status, and lymph node metastases (all P ≤ 0.001). High GDF-15 was also an independent predictor of poor disease-specific and recurrence-free survival., Conclusions: Based on findings indicated in a primary investigation set and confirmed in the large secondary validation set, we report for the first time plasma GDF-15 as a biomarker for endometrial cancer phenotype, including presence of lymph node metastasis and reduced survival. Its applicability as a predictor of metastatic nodes and in monitoring treatment of endometrial cancer needs to be further studied.

Objective: To investigate the prenatal appearance of the holoprosencephaly spectrum., Methods: A database of 1750 fetuses with congenital anomalies identified by ultrasound was prospectively collected from 1987 to 2000. Among them, 30 cases (1.7%) with holoprosencephaly were prenatally identified and described., Results: The prevalence of holoprosencephaly in the Health Region of the National Center for Fetal Medicine in Norway was 1.26 : 10 000; the sex distribution (male : female) was 1.4 : 1. Holoprosencephaly was found in one dichorionic twin pregnancy and one pair of conjoined twins. Among the 30 cases of holoprosencephaly, 18 were alobar, five were semilobar, two were lobar, two were lobar variants, and three were anencephalic. The facial features varied considerably. Sixty-seven per cent (20/30) had associated structural anomalies that were not related to the cerebral and facial holoprosencephaly condition. Thirty-seven per cent (11/30) had detectable chromosome aberrations and 23% (7/30) had nonchromosomal syndromal origin. The size or shape of the head was abnormal in 83% (25/30) of holoprosencephaly cases., Conclusion: This study indicates that holoprosencephaly represents a heterogeneous entity with different etiologies and clinical appearances. The fact that holoprosencephaly features are found associated with particular conditions such as fronto-nasal dysplasia (2/30; 6.7%), agnathia-otocephaly (3/30; 10%), and anencephaly (3/30; 10%), suggests that these may be underreported conditions in other large holoprosencephaly series.