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To compare the performance of transvaginal and transabdominal ultrasound with that of the first-line staging method (contrast-enhanced computed tomography (CT)) and a novel technique, whole-body magnetic resonance imaging with diffusion-weighted sequence (WB-DWI/MRI), in the assessment of peritoneal involvement (carcinomatosis), lymph-node staging and prediction of non-resectability in patients with suspected ovarian cancer.Between March 2016 and October 2017, all consecutive patients with suspicion of ovarian cancer and surgery planned at a gynecological oncology center underwent preoperative staging and prediction of non-resectability with ultrasound, CT and WB-DWI/MRI. The evaluation followed a single, predefined protocol, assessing peritoneal spread at 19 sites and lymph-node metastasis at eight sites. The prediction of non-resectability was based on abdominal markers. Findings were compared to the reference standard (surgical findings and outcome and histopathological evaluation).Sixty-seven patients with confirmed ovarian cancer were analyzed. Among them, 51 (76%) had advanced-stage and 16 (24%) had early-stage ovarian cancer. Diagnostic laparoscopy only was performed in 16% (11/67) of the cases and laparotomy in 84% (56/67), with no residual disease at the end of surgery in 68% (38/56), residual disease ≤ 1 cm in 16% (9/56) and residual disease 1 cm in 16% (9/56). Ultrasound and WB-DWI/MRI performed better than did CT in the assessment of overall peritoneal carcinomatosis (area under the receiver-operating-characteristics curve (AUC), 0.87, 0.86 and 0.77, respectively). Ultrasound was not inferior to CT (P = 0.002). For assessment of retroperitoneal lymph-node staging (AUC, 0.72-0.76) and prediction of non-resectability in the abdomen (AUC, 0.74-0.80), all three methods performed similarly. In general, ultrasound had higher or identical specificity to WB-DWI/MRI and CT at each of the 19 peritoneal sites evaluated, but lower or equal sensitivity in the abdomen. Compared with WB-DWI/MRI and CT, transvaginal ultrasound had higher accuracy (94% vs 91% and 85%, respectively) and sensitivity (94% vs 91% and 89%, respectively) in the detection of carcinomatosis in the pelvis. Better accuracy and sensitivity of ultrasound (93% and 100%) than WB-DWI/MRI (83% and 75%) and CT (84% and 88%) in the evaluation of deep rectosigmoid wall infiltration, in particular, supports the potential role of ultrasound in planning rectosigmoid resection. In contrast, for the bowel serosal and mesenterial assessment, abdominal ultrasound had the lowest accuracy (70%, 78% and 79%, respectively) and sensitivity (42%, 65% and 65%, respectively).This is the first prospective study to document that, in experienced hands, ultrasound may be an alternative to WB-DWI/MRI and CT in ovarian cancer staging, including peritoneal and lymph-node evaluation and prediction of non-resectability based on abdominal markers of non-resectability. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL ( P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Purpose Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. Methods Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. Results Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. Conclusion The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.

BackgroundThe Global Gynaecological Oncology Surgical Outcomes Collaborative (GO SOAR) aims to develop a network of gynecological oncology surgeons, surgical departments, and other interested parties that will have the long-term ability to collaborate on outcome studies. The protocol for the first collaborative study is presented here.Primary ObjectiveTo evaluate international variation in 30-day post-operative morbidity and mortality following gynecological oncology surgery between very high/high and medium/low human development index country settings.HypothesisThere is no variation in post-operative morbidity and mortality following gynecological oncology surgery between very high/high and medium/low human development index country settings.Study DesignInternational, multicenter, prospective cohort study. Patient data will be collected over a consecutive 30-day period through gynecological oncology multidisciplinary teams/tumor boards and clinics across different human development index country groups. All data are collected on a customized, secure, password protected, central REDCap database.Major Inclusion/Exclusion CriteriaInclusion criteria include women aged ≥18 years undergoing elective/emergency, curative/palliative surgery for primary/recurrent tubo-ovarian/peritoneal, endometrial, cervical, vulval, vaginal, gestational trophoblastic malignancies. Surgical modality may be open, minimal access (laparoscopic/robotic), or vaginal.Primary Endpoint30-day post-operative morbidity and mortality defined as per Clavien-Dindo classification system.Sample Size1100 (550/arm).Estimated Dates for Completing Accrual and Presenting ResultsIt is estimated recruitment will be completed by 2022 and results published by 2023.Trial RegistrationClinicalTrials.gov registry: NCT04579861 (https://clinicaltrials.gov/ct2/show/NCT04579861).

Background The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. Patients and methods We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA–IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. Results The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799–1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458–1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690–1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. Conclusion We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. Clinical trials identifier NCT04037124 .

Background Models predicting recurrence risk (RR) of cervical cancer are used to tailor adjuvant treatment after radical surgery. The goal of our study was to compare available prognostic factors and to develop a prognostic model that would be easy to standardise and use in routine clinical practice. Methods All consecutive patients with early-stage cervical cancer treated by primary surgery in a single referral centre (01/2007–12/2016) were eligible if assessed by standardised protocols for pre-operative imaging and pathology. Fifteen prognostic markers were evaluated in 379 patients, out of which 320 lymph node (LN)-negative. Results The best predictive model for the whole cohort entailed a combination of tumour-free distance (TFD) ≤ 3.5 mm and LN positivity, which separated two subgroups with a substantially distinct RR 36% and 6.5%, respectively. In LN-negative patients, a combination of TFD ≤ 3.5 mm and adenosquamous tumour type separated a group of nine patients with RR 33% from the rest of the group with 6% RR. Conclusions A newly identified prognostic marker, TFD, surpassed all traditional tumour-related markers in the RR assessment. Predictive models combining TFD, which can be easily accessed on pre-operative imaging, with LN status or tumour type can be used in daily practice and can help to identify patients with the highest RR.

BackgroundVaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients’ risk of recurrence based on molecular tumor characteristics.Primary objectivesTo compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapyStudy hypothesisAdjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs.Trial designA multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm).Major inclusion/exclusion criteriaWomen aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1).EndpointsThe primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs.Sample size500 eligible and evaluable patients.Estimated dates for completing accrual and presenting resultsEstimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023.Trial registrationThe trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

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

BackgroundQuality of surgical care as a crucial component of a comprehensive multi-disciplinary management improves outcomes in patients with endometrial carcinoma, notably helping to avoid suboptimal surgical treatment. Quality indicators (QIs) enable healthcare professionals to measure their clinical management with regard to ideal standards of care.ObjectiveIn order to complete its set of QIs for the surgical management of gynecological cancers, the European Society of Gynaecological Oncology (ESGO) initiated the development of QIs for the surgical treatment of endometrial carcinoma.MethodsQIs were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for the identification of potential QIs and documentation of the scientific evidence, two consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians and patient representatives. QIs were defined using a structured format comprising metrics specifications, and targets. A scoring system was then developed to ensure applicability and feasibility of a future ESGO accreditation process based on these QIs for endometrial carcinoma surgery and support any institutional or governmental quality assurance programs.ResultsTwenty-nine structural, process and outcome indicators were defined. QIs 1–5 are general indicators related to center case load, training, experience of the surgeon, structured multi-disciplinarity of the team and active participation in clinical research. QIs 6 and 7 are related to the adequate pre-operative investigations. QIs 8-22 are related to peri-operative standards of care. QI 23 is related to molecular markers for endometrial carcinoma diagnosis and as determinants for treatment decisions. QI 24 addresses the compliance of management of patients after primary surgical treatment with the standards of care. QIs 25–29 highlight the need for a systematic assessment of surgical morbidity and oncologic outcome as well as standardized and comprehensive documentation of surgical and pathological elements. Each QI was associated with a score. An assessment form including a scoring system was built as basis for ESGO accreditation of centers for endometrial cancer surgery.

Introduction/Background* The Global Gynaecological Oncology Surgical Outcomes Collaborative aims to develop a network of gynaecological oncology surgeons, surgical departments and other interested parties that will have the long-term ability to collaborate on outcome studies. Presented is the protocol for the first collaborative study. Our primary objective is to evaluate international variation in thirty day post-operative morbidity and mortality following gynaecological oncology surgery between very high/high and medium/low human development index country settings. Methodology Design International, multi-centre, prospective, observational, cohort-study. Two study-arms: very high/high and medium/low human development index (HDI) country settings. ClinicalTrials.gov registry: NCT04579861. Inclusion criteria Women aged ≥18 years undergoing elective/emergency, curative/palliative surgery for primary/recurrent tubo-ovarian/peritoneal, endometrial, cervical, vulval, vaginal, gestational trophoblastic malignancies. Surgical modality may be open, minimal access (laparoscopic/robotic), or vaginal. Exclusion criteria Non-gynaecological disease as the primary malignancy, diagnostic procedures, or any procedure not requiring a skin incision under general/regional anaesthesia. Recruitment Patient data will be collected over a consecutive thirty day period through Gynaecological Oncology multidisciplinary teams and clinics across different HDI country groups. All data is collected on a customised, secure, password protected, central REDCap database. Primary outcome Thirty day post-operative morbidity and mortality defined as per Clavien Dindo classification system. Secondary outcomes Intra-operative morbidity/mortality; rate of tumour clearance; international prospective surgical outcomes database; comparison of current practice against selected tumour specific audit standards derived from the European Society of Gynaecological Oncology guidelines. Sample size 1100 (550/arm) inflated by 20% to account for missing data and loss to follow up, at 90% power, α=0.05, will be able to determine a 10% point difference in thirty day post-operative morbidity and mortality following Gynaecological Oncology surgery between high/high and medium/low HDI country settings Result(s)* GO SOAR1 is open to recruitment internationally. Conclusion* The GO SOAR Collaborative aims to improve surgical outcomes through collaborative research. It will provide risk adjusted patient level outcome data collected via a centralised database to advise HDI country group specific policy formation.

Introduction/Background* SENTIX is a prospective cohort multicentric international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. SLN frozen section (FS) and pathological ultrastaging were mandatory by the protocol. Samples from SLN were reviewed centrally for pathological assessment quality control. Only sites experienced in SLN biopsy technique could join the trial. Methodology In total, 47 sites from 18 countries participated in the trial. Patients with FIGO 2009 stages T1A1/LVSI+ – T1B1 ( Result(s)* Altogether 733 patients were registered until Sentix enrolment closure in October 2020, 83 patients were excluded (table 1) and 650 patients was analysed. Patients` characteristics are shown in table 1. Bilateral SLN detection rate reached 95%. FS detected macrometastases (MAC) in 44 cases and micrometastasis (MIC) in 4 cases. SLN ultrastaging found additional 9 cases with MAC, 26 with micrometastases (MIC) and all 19 cases with isolated tumor cells (ITC). Sensitivity of FS was 83.0% for the detection of MAC, 57.8% for pN1 status (MAC or MIC) and 47.1% for any type of SLN involvement (MAC, MIC, ITC). Table 2. Conclusion* High bilateral detection rate of 95% was achieved in Sentix sites experienced in the SLN biopsy technique. Intraoperative pathological assessment of SLN failed to detect majority of MIC (86.7%), all cases with ITC and 42.2% with pN1 (MIC or MAC).

Introduction/Background* Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. In studies, LLL is often assessed by calculation of limb volumes based on five circumference measurements. However, the lack of standardisation of this method hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective SENTIX trial that have implications for the standardisation of LLL assessment. Methodology In the prospective international multicentre trial SENTIX (ENGOT-cx2/CEEGOG CX-01), a group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery. Result(s)* Patient LVC substantially fluctuated in both positive and negative directions (figure 1), which were comparable in frequency up to 14% +/- LVC increments. Thirty-eight patients experienced persistent LVC increase and >10% classified as LLL, for whom median time to onset was nine months (95% CI: 7.0-11.0). Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits (figure 2). No significant correlation between LVC >10% and a patient-reported swelling was observed. Conclusion* Our study showed that lower-limb volumes after surgical treatment of cervical cancer significantly fluctuate in positive and negative directions. A diagnostic threshold for LLL should be increased to >15% LVC. Transient oedema occurs frequently, and its distinction from persistent LLL requires repeated measurements. One-third of new LLL cases were diagnosed in the second year of follow-up, highlighting the importance of a sufficient follow-up period duration. Finally, patient-reported limb swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment.

Introduction/Background* Pembrolizumab, an anti-PD-1 antibody, has demonstrated activity in patients with previously treated mismatch repair (MMR) deficient (dMMR; 57.1% objective response rate [ORR] as monotherapy and 63.6% ORR as combination therapy with lenvatinib) and MMR proficient (pMMR; 36.2% ORR as combination therapy with lenvatinib) endometrial cancer. ENGOT-en11/GOG-3053/KEYNOTE-B21 (NCT04634877) is a phase 3, randomized, double-blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with endometrial cancer. Methodology Eligible patients are ≥18 years old with newly diagnosed, high-risk (stage I/II non-endometrioid or with p53 abnormality and any histology, stage III/IVA), previously untreated endometrial cancer following surgery with curative intent with no evidence of disease post-operatively. Approximately 990 patients are randomized to receive pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for 6 cycles plus chemotherapy (carboplatin area under the curve [AUC] 5/6 plus paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2/2.7 plus paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2. Radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin-EBRT vs EBRT vs no EBRT), histology (endometrioid vs non-endometrioid), and International Federation of Gynecology and Obstetrics surgical stage (I/II vs III/IVA). Dual primary endpoints are disease-free survival (DFS; per investigator assessment) and overall survival (OS). Secondary endpoints include DFS (per blinded independent central review), DFS (per investigator assessment) and OS by biomarker status (PD-L1 and tumor mutational burden), safety (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0), and quality of life (per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] and Endometrial Cancer Module [EORTC QLQ-EN24]). Enrolment began December 2020 and is ongoing at 221 sites in 28 countries. Result(s)* N/A Conclusion* N/A

Introduction/Background* According to current guidelines fertility-sparing treatment (FST) in cervical cancer patients should follow the same principles as in patients without fertility preservation. The literature from the last years, however, show a trend towards less-radical procedures. Although oncological outcomes are reported to be equal or better than in non-FST, published groups are small, mostly single institutional, inclusion criteria vary, and treatment is not uniform. The aim of this study was to collect retrospective data from multiple institutions across several countries on oncological and reproductive outcomes after FST. Methodology Included were cervical cancer patients between 18–40 years with stages ≥ IA1+LVSI, who underwent any type of FST and completed follow-up of at least 6 months. Patients were eligible irrespective of neoadjuvant chemotherapy, histotype or tumour grade. Result(s)* Altogether 733 patients from 44 centers in 13 countries were eligible for analyses. Median follow-up of the whole cohort was 6 years (1.2–14.5). More than half of the cases had stage IB1 (54.2%; 397/733). Mean age of patients was 32 years and two thirds were nulliparous (484/733). Most common surgical procedure was conization (48%). Repeated cervical surgery was performed in 161 patients (21.9%), most frequently re-conization (57.8%). Less than half of the patients (49.2%; 361/733) attempted to conceive after treatment. Out of them, 138 (38.2%) got pregnant and 100 (27.7%) successfully delivered. Pre-cancer recurrence was diagnosed in 22 (3%) patients, 51 (7%) patients had cancer recurrence and 19 (2.6%) died of disease. Three times higher risk of recurrence was observed in tumours ≥ 2 cm in comparison to smaller tumours (19.4% vs. 5.7%; p Conclusion* Data from the real life practice showed that FST in cervical cancer patients is safe in patients with HPV related tumours smaller than 2 cm. In such tumours conization represents sufficient procedure with satisfactory pregnancy outcomes. Surprisingly less than half of patients attempt to conceive after treatment.

Introduction/Background* Metastatic involvement of lymph nodes (LNs) represents one of the most important prognostic parameter in cervical cancer patients. According to the stage it shortens the 5years survival rate by 25-60 %. Moreover, even in low risk group without any risk factor, a part of radicaly treated patiens suffer from relapse of the disease. Presence of HPV DNA in LNs had been therefore studied as a potential marker of unrecognized metastatic involvement. Methodology Detected were 13 genotypes of high-risk HPV in the lymphatic tissue harwested from patiens who underwent radical hysterectomy with sentinel node biopsy and pelvic lymphadnectomy or paraaortic LN staging. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Only patients with HPV positive tumours who finished their treatment were included and followed. Result(s)* Out of 119 patients who were included in the study, 93 had available data from their follow-up; 68 underwent radical surgery and 25 were treated by primary definitive radiotherapy. All 19 patients with metastaticaly involved LNs also had HPV in LNs. Another 23 patients had HPV in uninvolved LNs. After a mean follow up of 147 months 19 patients (5 early and 14 localy advanced stages) recurred and died. The majority of them (13/19) had HPV DNA in their LNs, but only 7 had metastases in the LNs at the same time. Only 6 patients (6.5%) without HPV DNA in LNs recurred – 2 early and 4 localy advanced stages. Negative predictive value for recurrence in cases with HPV negative LNs reached 87.8% in the whole cohort and 95% in early stages. Conclusion* Our pilot study shows that the presence of HPV DNA in LNs is a promising marker of occult metastatic involvement. Its prognostic value should be confirmed in a prospective trial.

Introduction/Background* The aim of the study was to evaluate diagnostic accuracy of ultrasound in preoperative assessment of pelvic lymph nodes (LNs) in cervical cancer patients. Methodology Patients were retrospectively included if they met following inclusion criteria: 1) histologically verified cervical cancer; 2) preoperative ultrasound examination performed by one of three experienced sonographers (transvaginal or transrectal and transabdominal approach); 3) surgical lymph node staging (sentinel lymph node biopsy, SLNB and/or systematic pelvic lymphadenectomy, PLND or pelvic lymph node debulking). The final pathological examination served as the reference standard. Lymph nodes with macrometastases (the largest diameter > 2 mm) were considered positive, while LNs with isolated tumour cells (ITC) and micrometastases (MIC) were considered negative. Result(s)* 394 patients meeting the inclusion criteria between 2009 a 2019 were enrolled into the study. The characteristics of study population are shown in table 1. Squamous cell carcinomas were most common (298/394) and the majority of cases was represented by early stage cancers (274/394), specifically IB1 FIGO 2009 (236/394). Macrometastes in pelvic LNs were pathologically confirmed in 53 patients (13.5%) and micrometastases solely in 23 patients (5.8%). Ultrasound failed to detect pelvic lymph node macrometastases in 15 patients (3.8%) and median largest diameter of these unidentified metastases was 6 mm (range 3 – 11 mm). There were 27 false positive ultrasound findings (6.9%). Ultrasound reached sensitivity 71.7%, specificity 92.1%, PPV 58.5%, NPV 95.4% and overall accuracy 89.3%. Conclusion* Transvaginal/transrectal ultrasound is a reliable method for preoperative assessment of pelvic LNs in cervical cancer patients. It showed similar accuracy in detection of nodal macrometastases as reported for other imaging modalities. Similarly to all imaging methods, it had low sensitivity in detection of small volume macrometastases and micrometastases. Key words: cervical cancer, lymph nodes, ultrasound, diagnostic accuracy Klikněte nebo klepněte sem a zadejte text.

Introduction/Background* The impact of lymph node (LN) micrometastases (MIC) in cervical cancer patients remains a controversial topic given their low incidence and good prognosis of patients managed by primary surgery. We aim to evaluate the prognostic significance of MIC and isolated tumour cells (ITC) in a large cohort of patients from the SCCAN retrospetive study (Surveillance in Cervical CANcer). SCCAN study analysed data from more than 4300 patients with early stage cervical cancer treated by primary surgery at 20 large tertiary institutions from Europe, North America, South America and Australia. Methodology In this SCCAN sub-study, we included patients with early stage cervical cancer (T1a1 LVSI+ – T2b) treated between 2007 and 2016 with at least 1-year follow-up data availability, who underwent primary surgery including sentinel lymph node (SLN) biopsy and in whom SLNs were processed by pathological ultrastaging protocol. Result(s)* Out of 969 included patients with at least 1 SLN detected, 174 (18%) had positive LN (table 1). Maximal tumour diameter >2cm, positive LVSI, grade ≥ 2, uncommon histological type (neuroendocrine, sarcoma, etc.) and macrometstasis (MAC) or MIC in LN were factors associated with significantly decreased five-years disease free survival (DFS) (table 2). MAC, MIC or ITC was the largest LN metastasis in 84 (9%), 59 (6%) and 31 (3%) cases respectively. Adjuvant (chemo)radiation was administred in 89%, 85% and 58% of patients with MAC, MIC and ITC. DFS reached 75%, 73% and 83% in patients with MAC, MIC and ITC compared with 90% in the N0 patients. Patients with MAC and MIC had significantly decreased DFS than those with N0 disease (HR=2.36 and 2.55). Conclusion* Early-stage cervical cancer patients with MIC in pelvic LN have significantly decreased DFS. Their management should follow the same principles as in patients with MAC.

Introduction/Background* There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from those infiltrated by cancer or lymphoma. Methodology The Vulvar International Tumor Analysis (VITA) collaborative group was established involving gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The steering committee for the study held special meeting to discuss the problems of standardization and to formulate terms and procedures to derive morphologic end-points by B-mode imaging and end-point of vascularity and blood flow by color Doppler imaging. The recommendations of the steering committee were distributed to each participating center and subsequently refined. The following consensus is going to be tested in international multicentric interobserver and diagnostic accuracy studies. Result(s)* We present a consensus of international multidisciplinary VITA group on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature is not limited to inguinal lymph nodes as part of vulvar cancer staging; it can be used for the assessment of peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes. Conclusion* VITA terms and definitions were developed as a basis for international standardization of lymph node assessment by ultrasound and lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes.

Introduction/Background* The international Charite MAYO Conference aims at promoting international dialogue on diagnostics, management, scientific breakthroughs and state-of-the-art surgical procedures in gynecology and gynecological oncology. Live surgeries are a fundamental tool of interdisciplinary and international exchange of experts in their respective fields. There is a controversy about the usefulness, risks and safety of live-surgical broadcasts. The aim of the current study is to analyse perioperative risks and oncological outcomes in patients who underwent live-surgery during the Charite MAYO Conferences. Methodology Live-surgeries were performed by the core Charite team consisting of gynecologic oncologic surgeons, partly in collaboration with visiting gynecologic oncological surgeons. We performed a retrospective analysis of all live-surgeries performed during seven Charite MAYO Conferences from 2010 to 2019 held in Berlin, Germany. Result(s)* In total, 69 patients underwent live-surgeries. 13 patients received urogynecological procedures, 21 patients underwent surgery on the breast and 35 patients underwent surgery due to gynecological cancer such as ovarian, uterine, vulvar or cervical cancer. Perioperative complications were classified according to the Clavien-Dindo classification. The rate of perioperative complications, macroscopic tumor resection and oncological outcomes were within the range published in the literature. Conclusion* Based on our analysis live-surgeries were safe to perform in terms of multidisciplinary approach, perioperative complications and oncological outcome. With this, we established specific recommendations for performing live-surgeries.

Introduction/Background* European Society of Gynaecological Oncology (ESGO) and partners are committed to improving the quality of training for gynecological oncology fellows. The aim of this survey was to take a real-life picture of the type and level of the training in cervical cancer surgery, and to investigate whether LACC-trial changes may have affected quality of training in radical hysterectomy for gynecologic oncology fellows. Methodology In June 2020, a 47-question electronic survey was shared with European Network of Young Gynaecologic Oncologists (ENYGO) members. Specialist in Obstetrics and Gynecology and Gynecologic Oncology Fellows, who started the training between 01/01/2017 and 01/01/2020 or started before 01/01/2017 but finished their training at least 6 months after LACC trial publication, were included. Result(s)* 81 respondents were included in the present study. The median time from the start of fellowship to the date of completion of survey was 28.0 months (range, 6-48). Fifty-six (69.1%) respondents were still fellows-in-training. Six out of 56 (10.7%) and 14/25 (56.0%) of respondents who were still in training and completed the fellowship respectively, performed ≥10 radical hysterectomies during their training. Fellows trained in an ESGO-accredited center had higher chance to be exposed to sentinel lymph node biopsy (p=0.027). There was no difference in the mean number of radical hysterectomies performed by fellows before and after LACC-trial publication (8±12.0 versus 7±8.4, respectively) (p=0.463). A significant reduction in number of minimally-invasive radical hysterectomies was evident when comparing the period before and after LACC-trial (38.5% versus 13.8%, respectively; p Conclusion* Exposure to radical surgery for cervical cancer is relatively low amongst gynecologic oncology fellows. Centralization of cervical cancer cases to high-volume centers provides an increase in fellows’ exposure to radical procedures. LACC-trial publication did not reduce the possibility for a fellow to perform radical hysterectomies, but it may have affected the opportunity of performing minimally-invasive radical hysterectomy.

Introduction/Background* Up to 26% of early-stage cervical cancer patients relapse after primary surgical treatment. However, little is known about the factors affecting prognosis following disease recurrence. Hence, the aim of this study was to evaluate post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors. Methodology Data from 528 early-stage cervical cancer patients who relapsed after primary surgical treatment performed between 2007 and 2016 were obtained from the SCCAN study (Surveillance in Cervical CANcer). Parameters related both to primary disease and recurrence diagnosis were combined to develop a multivariable Cox proportional hazards model predicting PR-DSS. Result(s)* Five-year PR-DSS reached 39.1% (95% confidence interval: 22.7% – 44.5%) with median disease-free survival between primary surgery and recurrence diagnosis (DFI1) of 1.5 years and median survival after recurrence of 2.5 years. Six variables significant in multivariable analysis were included in the PR-DSS prognostic model; two related to the primary disease characteristics: maximal diameter of the tumour and lymphovascular space invasion; and four related to the recurrence diagnosis: DFI1, age, presence of symptoms, and recurrence localization (table 1). C-statistics of the final model after 10-fold internal validation equalled 0.701 (95% CI: 0.675 – 0.727). Five risk groups significantly differing in prognosis were identified, with 5-year DSS after recurrence of 85.6%, 62.0%, 46.7, 19.7%, and 0% in the highest risk group (figure 1). Conclusion* We have developed the first robust model of disease-specific survival after recurrence stratifying relapsing cervical cancer patients according to their risk profile using six traditional prognostic markers. The strongest factor related to the length of post-recurrence survival was the largest size of the primary tumour, followed by the presence of symptoms at the time of diagnosis, which remained significant even after correction for lead-time bias.

Epithelial ovarian carcinoma (EOC) is a relatively rare malignancy but is the fifth-leading cause of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant disease to the peritoneum. At odds with other neoplasms, EOC is virtually insensitive to immune checkpoint inhibitors, correlating with a tumor microenvironment that exhibits poor infiltration by immune cells and active immunosuppression. Here, we comparatively summarize the humoral and cellular features of primary and metastatic EOC, comparatively analyze their impact on disease outcome, and propose measures to alter them in support of treatment sensitivity and superior patient survival. ispartof: JOURNAL FOR IMMUNOTHERAPY OF CANCER vol:9 issue:10 ispartof: location:England status: published

Introduction/Background* Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust and comprehensive model allowing for individualised surveillance strategy based on risk profile of early-stage cervical cancer patients that were referred for surgical treatment with curative intent. Methodology The data of 4,343 cervical cancer patients with pathologically confirmed early-stage cervical cancer treated between 2007 and 2016 were obtained from SCANN consortium centres of excellence (Surveillance in Cervical CANcer). Only patients with complete key predictor variables and a minimum of one-year follow-up data availability were included. Based on the prognostic markers, a multivariable Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. A risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated by conditional survival analysis. Result(s)* Five variables significant in multivariable analysis of recurrence risk were included in the prognostic model: maximal pathologic tumour diameter, tumour histotype, tumour grade, the number of positive pelvic lymph nodes, and lymphovascular space invasion (table 1). The model was ten-fold internally cross-validated with the average AUC of 0.732. Five risk groups significantly differing in prognosis were identified: with five-year DFS of 97.5%, 94.7%, 85.2%, and 63.3% in consecutive increasing risk groups, while two-year DFS in the highest risk group equalled 15.4%. Based on ARRM, the annual recurrence risk in the lowest risk group was below 1% in the first year of follow-up and declined below 1% at years three, four, and >5 in the three medium-risk groups (figure 1). The proportion of pelvic recurrences declined in groups with the growing risk. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two, and 78% by year five. Conclusion* ARRM represents a powerful tool for tailoring the surveillance strategy in early-stage cervical cancer patients based on the patient´s risk status and respective annual recurrence risk. It can easily be utilised in routine clinical settings internationally.

Introduction/Background* The SENTIX is a prospective cohort international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. The primary end point is a recurrence rate at 24 months´ follow-up after the surgery. Either magnetic resonance imaging (MRI) or expert ultrasound (EUS) was mandatory as a preoperative staging method. The aim of this study is to report the accuracy of preoperative local staging. Methodology Forty-seven sites from 18 countries participated in the study. Patients with stages T1a1/LVSI+ – T1b1 (FIGO 2009), common histological types and no suspicious lymph nodes on imaging were eligible. Patients were excluded from further study if SLN were not detected on both sides and if SLN was positive on frozen section histological evaluation. Compared were results from preoperative imaging with final pathology reports. Result(s)* From May 2016 to October 2020, 733 registered patients underwent surgery, 132 were excluded intraoperatively, data from 708 were analysed in this study. Patients’ characteristics are in table 1. Out of 90 patients clinically staged as 1A tumours, 42 (46.7%) were upstaged to IB1 (86% ≤ 2 cm, 14% 2-4cm, 0% > 4cm); 76.3% had conisation as diagnostic procedure. Fourteen out of 547 preoperatively IB1 tumours (2.6%) were upstaged to IB2 > 4cm. Analogously 33 patients (6%) with IB tumours were downstaged to IA. Preoperatively unrecognized parametrial involvement was found by pathology only in 22 out of 637 patients (3.5%). EUS and MRI were used equally in the study (53.5% vs 56.1%), both were comparable in the accuracy of tumour size measurement (2 cm size categories shift in stage IB) (p=1.000) and in the failure to detect parametrial involvement (2.9% vs 4.0%) (p=0.535). Chart 1. Conclusion* Clinical staging with EUS and MRI failed to detect positive parametria only in 3.5% of patients in the Sentix trial. Upstaging from IA tumours was frequent, mostly after previous conization. Only 2.6% of patients were upstaged to IB2 tumours >4 cm (IB3 FIGO 2018). Both EUS and MRI were equally reliable in tumour size and parametrial involvement assessment.

Introduction/Background* High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 years. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab may be enhanced by concurrent chemoradiotherapy (CCRT). After the KEYNOTE-158 study, in which pembrolizumab showed durable antitumor activity, pembrolizumab monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/GOG 3047/KEYNOTE-A18 (NCT04221945) is a phase 3, randomized, placebo-controlled study evaluating pembrolizumab with CCRT for the treatment of high-risk, locally advanced cervical cancer. Methodology Approximately 980 patients with high-risk (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) + CCRT followed by 15 cycles of pembrolizumab 400 mg Q6W or 5 cycles of placebo Q3W + CCRT followed by 15 cycles of placebo Q6W. CCRT includes 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT followed by brachytherapy. Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the patient has received 20 cycles of pembrolizumab (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 years) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator and overall survival (OS). Secondary endpoints include PFS by blinded independent central review, PFS at 2 years, OS at 3 years, complete response at 12 weeks, objective response rate, PFS and OS by PD-L1 status, quality of life, and safety. Enrolment began May 2020 and is planned for 193 sites in 30 countries. Klikněte nebo klepněte sem a zadejte text.

Introduction/Background* Lower-limb lymphedema (LLL) is a well-recognized adverse outcome of the surgical management of cervical cancer. Recently, sentinel lymph node (SLN) biopsy has emerged as an alternative procedure to systematic pelvic lymphadenectomy (PLND) aiming to decrease the risk of complications, especially LLL development. Our study represents the first prospective analysis of LLL incidence in cervical cancer patients after a uterine procedure with SLN biopsy, without systematic PLND. Methodology In a prospective international multicenter trial SENTIX, the group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy was prospectively evaluated using both objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. The characteristics of the patients are summarized in table 1. Result(s)* The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI >40%). The median interval to LLL onset was nine months (figure 1). A transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. Conclusion* Contrary to the expectations, the replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed. Trial registration ClinicalTrials.gov: NCT02494063 Funding This work was supported by Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1) and by a grant from the Czech Health Research Council (NV19-03-00023). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Conflicts of Interest The authors declare no conflict of interest.

Background Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. However, the lack of standardisation of volumetric LLL assessment hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective trial that have implications for LLL assessment standardisation. Methods In the prospective international multicentre trial SENTIX, a group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral sentinel lymph node biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery. Results Patient LVC substantially fluctuated in both positive and negative directions, which were comparable in frequency up to ±14% change. Thirty-eight patients experienced persistent LVC increase >10% classified as LLL, with nine months median time to onset. Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits. No significant correlation between LVC >10% and a patient-reported swelling was observed. Conclusions Given that we observed comparable fluctuations of the the lower-limb volumes after surgical treatment of cervical cancer in both positive and negative direction up to ±14%, the diagnostic threshold for LLL diagnosis based on LVC should be increased to >15% LVC. The distinction of transient oedema from persistent LLL requires repeated measurements. Also, as one-third of LLL cases are diagnosed >1-year post-surgery, a sufficient follow-up duration needs to be ensured. Patient-reported swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment. Trial registration: ClinicalTrials.gov : NCT02494063

BackgroundThe management of patients with intraoperative detection of lymph node involvement remains controversial. The most significant aspect is the decision regarding the completion of the cervical procedure, such as hysterectomy, radical hysterectomy, or a fertility sparing procedure.Primary objectiveThe primary objective of the ABandoning RAd hyst in cerviX cancer (ABRAX) trial is to determine whether the completion of the cervical procedure (ie, radical hysterectomy) improves oncological outcome in patients with intraoperatively detected lymph node involvement before they are referred for definitive chemoradiation.Study hypothesisWe hypothesize that, in patients with intraoperative lymph node involvement, completion of radical hysterectomy or other cervical procedure does not improve the oncological outcome of definitive chemoradiation.Trial designThe ABRAX trial is a multicenter, retrospective, cohort study. Patients with negative lymph nodes in clinical staging, in whom lymph node involvement is detected intraoperatively, are included. Completion or abandonment of the planned cervical procedure stratifies the cohort into two subgroups in which oncological outcome and morbidity will be compared.Major Inclusion/Exclusion criteriaPatients with early stage (pT1a–pT2b) cervical cancer, who did not have positive lymph nodes on preoperative imaging, who were scheduled for primary surgical treatment, and in whom metastatic involvement of pelvic lymph node was found during surgery either as a grossly (macroscopically) involved or on intraoperative pathology assessment will be enrolled. Patients can be included irrespective of surgical approach (minimal invasive surgery or laparotomy) and type of cervical procedure performed (hysterectomy, radical hysterectomy, or a fertility sparing procedure).Primary endpointThe primary endpoint of this retrospective study is a progression free survival in two subgroups with abandoned or completed cervical procedure followed by definitive chemoradiation in both groups.Sample sizeThe assumed sample size is 718 patients (in total for both groups).Estimated dates for completing accrual and presenting resultsEstimated end of data collection: December 2019; estimated date of presenting results: Q2/3 2020.Trial registrationClinicaltrials.gov: NCT04037124.

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement. ispartof: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER vol:31 issue:7 pages:961-982 ispartof: location:England status: published

There are multiple classifications in imaging and surgery of endometriosis and in this article, we offer a review of the main evaluation systems. The International Deep Endometriosis Analysis group consensus is the leading document for ultrasound assessment, while magnetic resonance imaging is guided by the European Society for Urogenital Radiology recommendations on technical protocol. In surgery, the revised American Society for Reproductive Medicine classification is the oldest system, ideally combined with newer classifications, such as Enzian or Endometriosis Fertility Index. Recently, The World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project introduced detailed proforma for clinical and intraoperative findings. There is still no universal consensus, so the initial emphasis should be on the uniform reporting of the disease extent until research clarifies more the correlations between extent, symptoms and progression in order to develop a reliable staging system.Impact Statement

Objective DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. Methods In this open-label, parallel-group, phase 2 trial ( ClinicalTrials.gov number NCT02107950 ), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3–6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). Results Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42–1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20–0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. Conclusions DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

IntroductionSentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance.MethodsA Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability.ResultsSeventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; PConclusionSpecific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

Summary Background Few effective second-line treatments exist for women with recurrent or metastatic cervical cancer. Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue factor-directed antibody–drug conjugate, in this patient population. Methods This multicentre, open-label, single-arm, phase 2 study was done across 35 academic centres, hospitals, and community practices in Europe and the USA. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1); and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 2·0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously once every 3 weeks until disease progression (determined by the independent review committee) or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST (version 1.1), as assessed by the independent review committee. Activity and safety analyses were done in patients who received at least one dose of the drug. This study is ongoing with recruitment completed and is registered with ClinicalTrials.gov, NCT03438396. Findings 102 patients were enrolled between June 12, 2018, and April 11, 2019; 101 patients received at least one dose of tisotumab vedotin. Median follow-up at the time of analysis was 10·0 months (IQR 6·1–13·0). The confirmed objective response rate was 24% (95% CI 16–33), with seven (7%) complete responses and 17 (17%) partial responses. The most common treatment-related adverse events included alopecia (38 [38%] of 101 patients), epistaxis (30 [30%]), nausea (27 [27%]), conjunctivitis (26 [26%]), fatigue (26 [26%]), and dry eye (23 [23%]). Grade 3 or worse treatment-related adverse events were reported in 28 (28%) patients and included neutropenia (three [3%] patients), fatigue (two [2%]), ulcerative keratitis (two [2%]), and peripheral neuropathies (two [2%] each with sensory, motor, sensorimotor, and neuropathy peripheral). Serious treatment-related adverse events occurred in 13 (13%) patients, the most common of which included peripheral sensorimotor neuropathy (two [2%] patients) and pyrexia (two [2%]). One death due to septic shock was considered by the investigator to be related to therapy. Three deaths unrelated to treatment were reported, including one case of ileus and two unknown causes. Interpretation Tisotumab vedotin showed clinically meaningful and durable antitumour activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer. Funding Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups.

BackgroundPlatinum-resistant ovarian cancer patients have a poor prognosis and few treatment options are available. Preclinical and clinical data demonstrated that the combination of poly-ADP ribose polymerase inhibitors with immune checkpoint inhibitors could have a synergistic antitumor activity in this setting of patients.Primary ObjectiveThe primary objective is to assess the efficacy of niraparib plus dostarlimab compared with chemotherapy in recurrent ovarian cancer patients not suitable for platinum treatment.Study HypothesisThis trial will assess the hypothesis that niraparib plus dostarlimab therapy is effective to increase overall survival, progression-free survival, and time to first subsequent therapy respect to chemotherapy alone, with an acceptable toxicity profile.Trial DesignThis is a phase III, multicenter trial, where recurrent ovarian cancer patients not eligible for platinum re-treatment will be randomized 1:1 to receive niraparib plus dostarlimab vs physician’s choice chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent. The study will be performed according to European Network for Gynaecological Oncological Trial groups (ENGOT) model B and patients will be recruited from 40 sites across MITO, CEEGOG, GINECO, HeCOG, MANGO, and NOGGO groups.Major Inclusion/Exclusion criteriaEligible patients must have recurrent epithelial ovarian cancer not eligible for platinum retreatment. Patients who received previous treatment with poly-ADP ribose polymerase inhibitors and/or immune checkpoint inhibitors will be eligible. No more than two prior lines of treatment are allowed.Primary EndpointThe primary endpoint is overall survival defined as the time from the randomization to the date of death by any cause.Sample Size427 patients will be randomized.Estimated Dates for Completing Accrual and Presenting ResultsJune 2024Trial Registration NumberNCT04679064.

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of ovarian tumors, including imaging techniques, biomarkers and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.

We thank Isabelle Thomassin-Nagarra et al for their interest in the ESGO/ISUOG/IOTA/ESGE consensus statement on the pre-operative diagnosis of ovarian tumors. This statement is based on a careful review of the relevant literature and available evidence as well as on structured discussions between

IntroductionComprehensive updated information on cervical cancer surgical treatment in Europe is scarce.ObjectiveTo evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database.MethodsThe SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified.ResultsThe mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) ConclusionsIn this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Objectives: The Phase III SOLO2 trial (NCT01874353) showed the significant benefit of maintenance olaparib for patients (pts) with platinum-sensitive relapsed ovarian cancer (PSROC) and a BRCA mutation (BRCAm), compared with placebo (median progression-free survival [PFS] 19.1 vs 5.5 months [m], respectively); however, no pts had a confirmed somatic (s) BRCAm and data prospectively evaluating efficacy of olaparib in this pt group were limited. ORZORA (NCT02476968), an open-label, single-arm, multicenter trial, was conducted to assess efficacy and safety of maintenance olaparib in PSROC pts with a BRCAm (s or germline [g]) who were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. Methods: Pts underwent prospective central screening for tumor BRCAm status (myChoice CDx, Myriad Genetic Laboratories, Inc.), then s or g BRCAm status was determined by central g testing (BRACAnalysis CDx, Myriad Genetic Laboratories, Inc.). Pts received maintenance olaparib (400 mg bid; capsules) until disease progression. Co-primary endpoints were investigator-assessed PFS (RECIST v1.1) in BRCAm and s cohorts, conducted at 60% maturity. Secondary endpoints included time to second progression or death (PFS2), health-related quality of life (HRQoL; FACT-O trial outcome index) and tolerability. An additional exploratory cohort comprised pts with predefined homologous recombination repair gene mutations (HRRm) excluding BRCAm (FoundationOne CDx, Foundation Medicine, Inc.). Results: A total of 181 pts were enrolled in ORZORA (BRCAm n=145 [s n=55; g n=87; n=3 s vs g status unknown]; HRRm n=33; unassigned n=3). Pt characteristics were similar between s and g cohorts: ≥3 prior lines of chemotherapy (38% vs 48%, respectively); partial response to prior platinum (45% vs 49%); tumor BRCA1-mutated (65% vs 64%). At the data cut-off (April 17, 2020), median follow-up for PFS was 22.3 months. Median PFS was similar in the BRCAm, s and g cohorts, and exploratory HRRm cohort (Figure). Median PFS2 for BRCAm pts was 30.9 m (95% confidence interval [CI] 24.7–40.0; s 24.7 [21.8–36.1]; g 32.5 [25.3–not calculable]). HRQoL was comparable in BRCAm and s cohorts (best overall change from baseline: improved 22 vs 21%; no change 69 vs 68%; worsened 11 vs 12%, respectively). Most common adverse events (AE; n=177 treated pts) were nausea (54% pts), fatigue (43%), anemia (42%) and vomiting (28%). A total of 25% and 35% pts experienced serious and grade ≥3 (anemia 16% pts) AEs, respectively. 5% had an AE leading to treatment discontinuation. A total of 2 new primary malignancies, two acute myeloid leukemia and no myelodysplastic syndrome cases occurred. Download : Download high-res image (102KB) Download : Download full-size image Conclusions: PFS in pts with PSROC who received maintenance olaparib was similar irrespective of s or g BRCAm status. Activity of maintenance olaparib was also shown in pts with a non-BRCA HRRm. PFS, HRQoL and tolerability were consistent with previous olaparib studies in this population. Results highlight that PSROC pts beyond those with a gBRCAm can benefit from maintenance olaparib.

In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Background High-risk locally advanced cervical cancer (CC) has a poor prognosis, and >50% of patients recur in 2 years. Concurrent chemoradiotherapy (CRT) may enhance the immunostimulatory activity of the PD-1 inhibitor pembrolizumab. After KEYNOTE-158, in which pembrolizumab demonstrated durable antitumor activity, pembrolizumab monotherapy was approved for patients with PD-L1–positive recurrent or metastatic CC who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase 3, randomized, placebo-controlled study evaluating pembrolizumab with concurrent CRT in locally advanced CC. Trial design Approximately 980 patients with high-risk, locally advanced, histologically confirmed CC who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive 5 cycles of pembrolizumab 200 mg Q3W + CRT (5 cycles [with optional 6th cycle] of cisplatin 40 mg/m2 Q1W + external beam radiotherapy [EBRT] followed by brachytherapy) followed by 15 cycles of pembrolizumab 400 mg Q6W or 5 cycles of placebo Q3W + CRT followed by 15 cycles of placebo Q6W. Randomization is stratified by planned EBRT type, cancer stage at screening, and planned total radiotherapy dose. Treatment will continue until patient receives ≤20 cycles of pembrolizumab (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 years) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are PFS per RECIST v1.1 by blinded independent central review and OS. Secondary endpoints include PFS at 2 years, OS at 3 years, complete response at 12 weeks, ORR, PFS and OS in PD-L1–positive patients, and safety. Enrollment is ongoing.

Background Tumor Treating Fields (TTFields) are a non-invasive, antimitotic cancer therapy. The Phase 2 INNOVATE study demonstrated safety of TTFields/weekly paclitaxel in 31 PROC (platinum-resistant ovarian cancer) patients (Vergote Gyn Onc 2018); efficacy: median PFS 8.9 months, 25% partial response,71% clinical benefit and 61% 1-year survival rate. This phase 3 ENGOT-ov50/GOG-329/INNOVATE-3 study [NCT03940196] investigates TTFields plus weekly paclitaxel in PROC patients. Study Design Patients (N=540) will have PROC (RECIST V1.1) within 6 months of last platinum therapy with maximum of 2–5 prior lines of systemic therapy, ECOG 0–1 and no peripheral neuropathy >grade1. Patients with primary refractory disease will be excluded. Patients will be randomized 1:1 to weekly paclitaxel alone or weekly paclitaxel (starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle ) plus TTFields (200 kHz for 18 hours/day and continued if no progression in the abdominal or pelvic regions (‘in-field region’) per RECIST V1.1. Clinical follow-up will be performed q4w, with radiological follow-up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Secondary endpoints: PFS, objective response rate, AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n=540) will detect an increase in median OS from 12 to 16 months (HR 0.75). Data Monitoring Committee (DMC) meeting (March 2020) concluded that data to-date showed no safety issues and recommended trial continuation.

OBJECTIVE: Voiding dysfunctions represent a leading morbidity after radical hysterectomy performed in patients with early-stage cervical cancer. The aim of this study was to perform ad hoc analysis of factors influencing voiding recovery in SENTIX (SENTinel lymph node biopsy in cervIX cancer) trial. METHODS: The SENTIX trial (47 sites, 18 countries) is a prospective study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer. Overall, the data of 300 patients were analysed. Voiding recovery was defined as the number of days from surgery to bladder catheter/epicystostomy removal or to post-voiding urine residuum ≤50 mL. RESULTS: The median voiding recovery time was three days (5th-95th percentile: 0-21): 235 (78.3%) patients recovered in 30 days. In the multivariate analysis, only previous pregnancy (p = 0.033) and type of parametrectomy (p < 0.001) significantly influenced voiding recovery >7 days post-surgery. Type-B parametrectomy was associated with a higher risk of delayed voiding recovery than type-C1 (OR = 4.69; p = 0.023 vs. OR = 3.62; p = 0.052, respectively), followed by type-C2 (OR = 5.84; p = 0.011). Both previous pregnancy and type C2 parametrectomy independently prolonged time to voiding recovery by two days. CONCLUSIONS: Time to voiding recovery is significantly related to previous pregnancy and type of parametrectomy but it is not influenced by surgical approach (open vs minimally invasive), age, or BMI. Type B parametrectomy, without direct visualisation of nerves, was associated with longer recovery than nerve-sparing type C1. Importantly, voiding dysfunctions after radical surgery are temporary, and the majority of the patients recover in less than 30 days, including patients after C2 parametrectomy.

Purpose. We aimed to compare the learning curves of an ultrasound trainee (obstetrics and gynecology resident) and a radiology trainee when assessing pelvic endometriosis. Methods. Consecutive patients with suspected endometriosis were prospectively enrolled in a tertiary center. They underwent an ultrasound and magnetic resonance imaging preoperatively, which was reported according to the International Deep Endometriosis Analysis (IDEA) group consensus. Trainees reported on deep endometriosis (DE), endometriomas, frozen pelvis, and adenomyosis. Using the Kappa agreement, their findings were compared against laparoscopy/histology and expert findings. The learning curve was considered positive when performance improved over time and indeterminate in all other cases. Results. Reports from thirty-five women were divided chronologically into 3 equal blocks to assess the learning curve. For ultrasound, trainee versus expert showed a positive learning curve in overall pelvic DE assessment. There was an excellent agreement for adenomyosis (Kappa=1.00, p=0.09), frozen pelvis (Kappa=0.90, p=0.01), bowel (Kappa=1.00, p=0.01), and bladder DE assessment (Kappa=1.00, p=0.01). Endometrioma and uterosacral ligament assessment showed an indeterminate curve. For radiology, trainee versus expert showed a positive curve when detecting adenomyosis (Kappa=0.42, p=0.09) and bladder DE (Kappa=1.00, p=0.01). The assessment of endometriomas, frozen pelvis, overall pelvic DE, bowel, and uterosacral ligament DE showed indeterminate curve. Agreement between trainees and laparoscopy/histology showed a positive curve for bladder (both) and frozen pelvis (ultrasound only). Conclusion. A positive learning curve can be seen in some areas of pelvic endometriosis mapping after as little as 35 cases, but a bigger caseload is required to demonstrate the curve in full. The ultrasound trainee had positive learning curves in more anatomical locations (bladder, adenomyosis, overall bowel DE, frozen pelvis) than the radiology trainee (bladder, adenomyosis), which could be down to individual factors, differences in training, or the imaging method itself.

PURPOSE Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician’s choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.