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Background: In breast cancer patients, neoadjuvant chemotherapy (NAC) allows to obtain pathological complete response (pCR). In case of initially involved node before NAC, pCR after NAC could make it possible to avoid axillary surgery. The aim of our study was to address parameters to build a tool able to accurately select patients at a high probability of axillary pCR after NAC. Method: GANEA 3 was a French prospective multi institutional cohorts of breast cancer patients with a proven axillary involved node treated with NAC (NCT03630913). Initially involved node was clipped before treatment. Each patient received, before and after NAC, a bilateral mammography, a Magnetic Resonance Imaging (MRI), an axillary sonography. After NAC breast, conservative or radical, and axillary surgery, were performed. Breast surgery allowed to measure breast tumor residual and to perform a Sataloff classification. Targeted axillary detection (TAD) was defined as the combination of the resection of the clipped node and SLN dissection. Axillary clipped node, sentinel lymph node (SLN) and axillary lymph node dissection (ALND) were always performed. ALND allowed to assess the false negative rate (FNR) of axillary clipped node and SLN dissection. A total of 500 included patients is planned to close this still ongoing trial. Results : From January 2019 to March 2022, 405 patients were included from 18 institutions. We present here the results of the 260 first patients, who experienced a complete treatment with NAC courses and post NAC breast and axillary surgery. Among these patients, SBR grade was III in 52%, OR and PR were positive in 59% and 46% respectively, HER2 was overexpressed in 40%, 26% were triple negative and pCR was present in 28%. FNR of the SLN detection was 21.1%, 9% for the clipped node alone and 6% for the TAD. Histopronostic grading, progesteron receptors, HER2 expression, MRI results and Sataloff grading of breast residual tumor were indepently linked with global pCR (breast and axilla) in multivariate analysis. The Area Under the Curve (AUC) model was 0.91 with 82% correctly patients classified. The false negative rate of no pCR classified patients was 14%. Conclusion : Intermediate results of Ganea 3 trial showed that operable breast cancer patients with an initially involved axillary node treated with NAC, showed that TAD allows to reduce the FNR of axillary surgery. Patients with histopronostic grade 3, negative progesteron receptors, HER2 overexpression, a normal MRI after NAC and a breast Sataloff A, have a low risk of axillary tumour residual burden and could be safely spare from any axillary surgery. Large prospective trials are needed to confirm the safety of this surgical de-escalation. Citation Format: Céline Renaudeau, Pierre Gimbergues, Eugénie Guillot, Marie-Pierre Chauvet, Marian Gutowski, Eva Jouve, Philippe Rauch, Monique Cohen, Christelle Faure, Marie-Martine Padeano, Vivien Ceccato, Catherine Uzan, Anne-Sophie Bats, Hélène Charitansky, Pierre-François Dupré, Augustin Reynard, Séverine Alran, Cécile Bendavid-Athias, Loïc Campion, Isabelle Doutriaux, Jean-Marc Classe. Axillary surgery de-escalation after neoadjuvant chemotherapy in breast cancer patients with initially involved node: the GANEA 3 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-09-01.

ObjectiveChemotherapy for high-grade serous ovarian cancers in platinum-sensitive relapse includes carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin. According toin vitrodata,BRCAmutated patients are sensitive to replicative stress agents butBRCAstatus is not yet used for the choice of chemotherapy at relapse. Our aim was to assess these doublets according toBRCAstatus in first platinum-sensitive relapse.MethodsThe ESME ovarian cancer database comprises a multicenter retrospective cohort of patients with ovarian cancer treated in French cancer centers between January 2011 and December 2017. Patients with high-grade serous ovarian cancers at first platinum-sensitive relapse who received one of these doublets were included. The objective was to compare progression-free survival of each chemotherapy doublet according toBRCAstatus.ResultsAmong the 10 263 patients in the database, 1539 patients had a first platinum-sensitive relapse: 825BRCAwild type patients (53.6%) and 304BRCAmutated patients (19.8%) (7 patients had a homologous recombination mutation andBRCAstatus was unkown for 403 patients). Median progression-free survival was longer inBRCAmutated patients than inBRCAwild type patients when receiving carboplatin/pegylated liposomal doxorubicin without maintenance treatment (15.8 vs 11.8 months; pBRCAwild type patients without maintenance, better progression-free survival occurred with carboplatin/paclitaxel (median progression-free survival 14.3 months) than with carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin (9.8 and 11.8 months, respectively; p=0.017). InBRCAmutated patients without maintenance, there was no difference between the three doublets (median progression-free survival of 14.6, 12.0, and 15.8 months with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin, respectively; p=0.40).ConclusionWhile treatment with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin shows comparable efficacy inBRCAmutated patients, treatment with carboplatin/paclitaxel appears to be more effective than carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin inBRCAwild type patients with high-grade serous ovarian cancers at first platinum-sensitive relapse.

Introduction: Few data have been reported regarding endocrine therapy (ET) in patients with small pT1a-b ER-postive breast cancer (BC). Thus, we conducted a study to detect possible survival improvements due to ET in such patients. Methods: Our retrospective observational study included 5545 patients with pT1a-b ERpositive BC treated in 15 French centres, excluding patients with HER2-positive status, neoadjuvant chemotherapy, ER-negative status, unknown pN status or in situ BC. We estimated disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) via univariate analysis and multivariate Cox regression. Results: Most patients (80.3%: 4453) received ET and-when compared to those without ET -experienced increases of 2.5% and 3.3% in DFS and 1.9% and 4.3% in RFS after 5 and 7 years of follow-up, respectively, with little difference in OS. In Cox regression analysis, no ET was significantly associated with decreased DFS (hazard ratio, HR = 1.275, p = 0.047, 95% CI[1.003-1.620]) but not OS or RFS in all patients, while in 2363 patients with pT1ab ER-positive grade 2-3 BC, no ET was significantly associated with decreased DFS (HR = 1.502, p = 0.049, 95% CI[1.001-2.252]), but not OS (HR = 1.361, p = 0.272). ET omission was not significantly associated with decreased survival in 3047 patients with pT1a-b ER-positive grade 1 BC. Conclusion: Our results indicate that while ET provided a beneficial impact on survival to patients with pT1a-bN0 ER-positive BC-and especially in those with grade 2-3 tumours-no such impact was observed in grade 1 tumours. Consequently, ET should be discussed with these patients, particularly in those with pT1a grade 1 tumours. 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BackgroundIn patients treated for advanced ovarian cancer not suitable for complete primary surgery, interval surgery after three courses of neoadjuvant chemotherapy has been considered standard management since the EORTC randomized trial published in 2010. An alternative approach with delayed surgery after six courses of neoadjuvant chemotherapy was reported in retrospective series.Primary ObjectivesTo assess the efficacy on progression free survival of interval cytoreduction surgery after three cycles of neoadjuvant chemotherapy compared with delayed surgery after six cycles of neoadjuvant chemotherapy.Study HypothesisIn women with ovarian cancer not suitable for primary surgical cytoreduction, surgery after six cycles of neoadjuvant chemotherapy will prove better disease-free survival than cytoreductive surgery after only three cycles.Trial DesignCHRONO is a multicenter, randomized phase III trial. After three courses of neoadjuvant chemotherapy, eligible patients will be randomized (1:1) to either completion surgery followed by an additional five cycles of chemotherapy (control arm) or an additional three cycles of neoadjuvant chemotherapy followed by completion surgery and then two additional cycles of chemotherapy (experimental arm). Patients in both groups will receive eight total cycles of chemotherapy.Major Inclusion/Exclusion CriteriaThe main inclusion criteria are histologically confirmed epithelial high-grade serous or endometrioid ovarian cancer, documented FIGO stage IIIB–IVA unsuitable for complete primary surgery but considered resectable after three courses of neoadjuvant chemotherapy. The main exclusion criteria are mucinous, clear cell, carcinosarcoma, or low-grade serous histologies.Primary EndpointThe primary endpoint is progression-free survival.Sample Size210 eligible patientsEstimated Dates for Completing Accrual and Presenting ResultsThe estimated date for completing accrual will be Q2 2023. The estimated date for presentation of the first results is Q3 2028.Trial Registration NumberNCT03579394.

ObjectivesThis retrospective study aimed to assess the efficiency of consolidation chemotherapy after 6 cycles of neoadjuvant chemotherapy and delayed complete surgery on overall survival and progression-free survival among patients with advanced epithelial ovarian cancer.MethodsThis was a retrospective consecutive study with a propensity score to ensure balance for the baseline characteristics between the study groups. All patients treated for advanced ovarian cancer with 6 cycles of neoadjuvant chemotherapy followed by delayed complete surgery, without post-operative chemotherapy (group 1), or with post-operative chemotherapy (group 2), were included. We evaluated survival and the quality of cytoreductive surgery using the propensity score.ResultsFrom 2000 to 2017, 42 patients were included in group 1, and 59 in group 2. The median follow-up was 78 months (confidence interval (CI) 95% (60.1;not computable)). Neither progression-free survival nor overall survival were different between the two groups. The median progression-free survival was 10.2 months (CI 95% (8.8–17.0)) for group 1 and 10.4 months (CI 95% (7.9–12.8)) for group 2 (p=0.57). Five-year overall survival was 21.0% (CI 95% (10.4–42.3)) for group 1 and 26.1% (CI 95% (16.0–42.5)) for group 2 (p=0.73).ConclusionsAdding cycles of consolidation chemotherapy after delayed surgery following 6 cycles of neoadjuvant chemotherapy did not demonstrate any survival improvement in patients treated for advanced ovarian cancer not amenable to primary or interval surgery.

Simple Summary Since 2000, scientific literature has recommended the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of ovarian cancer relapse. This treatment, combining heavy abdominal surgery and intraperitoneal heated chemotherapy is associated with a risk of post-operative death and severe morbidity. Previous systematic reviews of the scientific literature concluded that HIPEC was effective for improving patient survival following a first relapse of ovarian cancer. This current systematic review, emphasizing the level of evidence of the published series, using the Oxford levels of evidence grading system, has made it possible to analyze the weaknesses of this scientific literature. This literature is characterized by biases—such as patient inclusion, and weak methods—such as retrospective patient collection, a small number of included patients, and no statistical hypothesis. As a results, HIPEC must remain an experimental procedure in ovarian cancer relapse, patients until there are positive results from ongoing clinical trials. Abstract Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used in the treatment of a first ovarian cancer relapse. Methods: This systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, aimed to assess the quality of scientific proof of the survival benefits of HIPEC, using Medline and Google Scholar. Qualitative analysis using the Oxford CEBM Levels of Evidence 2011 grading is reported. Results: Of 469 articles identified, 23 were included; 15 based on series of patients treated with HIPEC without a control group, and 8 case control series of patients treated with or without HIPEC. The series without a control group showed median overall survival (OS) ranged from 23.5 to 63 months, highlighting a broad standard deviation. Considering the case control series, OS was significantly better in the HIPEC group in 5 studies, and similar in 1. The current review showed considerable heterogeneity and biases, with an Oxford Level of Evidence grading of 4 for 22 selected series and 2 for one. Conclusions: There is no strong evidence to suggest efficacy of HIPEC in improving survival of patients treated for a first relapse of ovarian cancer due to the low quality of the data.

International audience; Background: In spite of the frequency and clinical impact of BRCA1/2 alterations in high-grade epithelial ovarian cancer (HGEOC), real-world information based on robust data warehouse has been scarce to date. Methods: Consecutive patients with BRCA-mutated HGEOC treated between 2011 and 2016 within French comprehensive cancer centers from the Unicancer network were extracted from the ESME database. The main objective of the study was the assessment of clinicopathological and treatments parameters. Results: Out of the 8021 patients included in the ESME database, 266 patients matching the selection criteria were included. BRCA1 mutation was found in 191 (71.8%) patients, while 75 (28.2%) had a BRCA2 mutation only; 95.5% of patients received a cytoreductive surgery. All patients received a taxane/platinum-based chemotherapy (median = six cycles). Complete and partial response were obtained in 53.3% and 20.4% of the cases, respectively. Maintenance therapy was administered in 55.3% of the cases, bevacizumab being the most common agent. After a median follow up of 51.7 months, a median progression-free survival of 28.6 months (95% confidence interval (CI) [26.5; 32.7]) and an estimated 5-year median overall survival of 69.2% (95% CI [61.6; 70.3]) were reported. Notably, BRCA1- and BRCA2-mutated cases exhibited a trend towards different median progression-free survivals, with 28.0 (95% CI [24.4; 32.3]) and 33.3 months (95% CI [26.7; 46.1]), respectively (p-value = 0.053). Furthermore, five-year OS for BRCA1-mutated patients was 64.5% (95% CI [59.7; 69.2]), while it was 82.5% (95% CI [76.6; 88.5]) for BRCA2-mutated ones (p-value = 0.029). Conclusions: This study reports the largest French multicenter cohort of BRCA-mutated HGEOCs based on robust data from the ESME, exhibiting relevant real-world data regarding this specific population.

Background There is a trend towards de-escalation in early breast cancer axillary surgery. In the American College of Surgeons Oncology Group (ACOSOG) Z-0011 trial, observation was shown to be non-inferior in terms of overall survival to complementary axillary lymph node dissection (cALND) in patients with up to two sentinel lymph node (SLN) metastases. The study included patients with T1-T2 invasive breast cancer, clinically node negative, undergoing breast-conserving surgery with SLN biopsy, followed by systemic therapy and radiotherapy. The aim of our study was to evaluate the impact of applying these ACOSOG Z-0011 inclusion criteria in routine practice. Patients and methods This retrospective observational study was conducted in a French comprehensive cancer center where patients treated for breast cancer with primary surgery were prospectively included between 2010 and 2016. Patients meeting ACOSOG Z-0011 inclusion criteria were analyzed. Results Among the 1900 included patients, 1497 (79 %) met the ACOSOG Z-0011 criteria before surgery. Of these, 390 (20 %) had one or two metastatic SLN and could have avoided cALND. Out of these patients, 319 (81 %) presented cT1 tumors. During the study period, cALND was performed in 320 (82 %) patients and was free of metastases in 80 % of cases, having an impact on eligibility for adjuvant chemotherapy in only 3 (0.8 %) patients. Conclusions In situations of primary breast cancer surgery, use of ACOSOG Z-0011 criteria could reduce the rate of cALND by 20 %. Further studies are needed to help select patients for whom abstention from any axillary surgery would be reasonable.

BackgroundAlmost half of the patient with initially metastatic axillary node, treated with neoadjuvantchemotherapy (NAC) for a large operable breast cancer, has no axillary lymph node involvementat the time of surgery after NAC. Sentinel lymph node detection (SLND), performed after NAC,has a high false negative rate (FNR) when compared to FNR after primary surgery. GANEA 3 isa French prospective multi institutional ongoing trial, aimed at assessing the impact of targeting,before NAC, the initially positive node and removing it after NAC. The main objective of GANEA3 trial is the accuracy of this initially positive node to predict pathological status of the otheraxillary nodes after NAC. A total of 385 patients are required.ObjectiveThe current abstract assessed preliminary results of the detection rate of the clipped node and thedifferent methods to find it during axillary surgery based on the first 41 patients.Patients and MethodThis study is part of GANEA 3 Trial validated by scientific national board (clinicialtrials.gov:NCT03630913).Inclusion criteria: TNM stage T1-T3 N1 infiltrating breast carcinoma, indication of NAC, andsigned consent form,Exclusion criteria: more than 5 suspicious axillary nodes, inflammatory cancer, local relapse,mental disorder, pregnancy or no contraceptive method, contra-indication to NAC, NACinterrupted due to progressive disease.Design: Patients treated for an early breast cancer with NAC, axillary sonography with fine needlecytology before NAC to select patients with a proven lymph node involvement. Initially positive node identification warranted, for example with a clip. After NAC patients underwent the removalof the clipped node, a SLN detection with the combined method (patent blue and technetium) andan axillary lymph node dissection (ALND). In order to find the clipped node, during surgery thesurgeon attempted to find it with palpation and sonography. Each surgical specimen was then x-rayed before pathological examination.Studied parameters were clipped node and SLND detection rate, and the methods used to find theclipped node.ResultsFrom January 2019, to November 2019, 41 patients were enrolled, from 13 institutions, withinitially positive axillary node clipped, NAC courses and surgery after NAC.Median age was 53 (31-75), pathological subtype infiltrative ductal carcinoma (n=40) andinfiltrative lobular carcinoma (n=1), a median of 7 courses of NAC (1-16).SLN detection rate was 90% (37/41). A median number of 2 sentinel nodes were removed (1-7).The clipped node was removed in 100% of cases. The clipped node was identified by thesurgeon palpation (n=11), an axillary wire (n=13), per operative axillary sonography (n=4),surgical specimen radiography (n=11), the pathologist (n=2).The clipped node was part of SLN in 29 cases (70%). It was part of axillary lymphadenectomyspecimen in 6 cases (14.5%) and was find alone as an isolated node in 6 cases (14.5%).ConclusionThe clipped node was always found after NAC. It was mostly always part of SLN or ALNDspecimens. Further studies are needed in order to help the surgeon to remove only the clippednode. Citation Format: Celine Renaudeau, Roman Rouzier, Pierre Gimbergues, Marian Gutowski, Eva Jouve, Philippe Rauch, Charles Coutant, Christelle Faure, Catherine Uzan, Pierre-François Dupré, Vivien Ceccato, Charlotte N'go, Augustin Reynard, Isabelle Doutriaux, Loic Campion, Jean-Marc Classe. Axillary surgery after neoadjuvant chemotherapy in patients treated for an operable breast cancer with a proven initially positive axillary node: Preliminary results of identification and removal of the initially positive axillary node [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-43.

International audience; Objective. Interval debulking surgery is recommended after 3–4 cycles (standard IDS) of neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer (EOC) not able to received upfront complete debulking surgery. However, real world practices frequently report performing IDS after ≥5 NAC cycles (delayed IDS). The aim of this work was to evaluate the impact on survival of the number of NACT cycles before IDS.Methods. We identified from a French national database, women with newly diagnosed EOC who underwent IDS from January 2011 to December 2016. Progression free survival (PFS) and overall survival (OS) were compared using Cox model with adjustments for confounding factors provided by two propensity score methods: inverse probability of treatment weighting (IPTW) and matched-pair analysis.Results. 928 patients treated by IDS for which our propensity score could be applied were identified. After a median follow-up of 49.0 months (95% CI [46.0;52.9]); from the IPTW analysis, median PFS was 17.6 months and 11.5 months (HR = 1.42; CI 95% [1.22–1.67]; p < 0.0001); median OS was 51.2 months and 44.3 months (HR = 1.29; CI 95% [1.06–1.56]; p = 0.0095) for the standard and delayed IDS groups. From the matched-pair analysis (comparing 352 patients for each group), standard IDS was associated with better PFS (HR = 0,77; CI 95% [0.65–0.90]; p = 0.018) but not significantly associated with better OS (HR = 0,84; CI 95% [0.68–1,03]; p = 0.0947).Conclusions. Carrying IDS after ≥5 NACT cycles seems to have a negative effect on patients survival. The goal of IDS surgery is complete resection and should not be performed after >3–4 NACT cycles.

Resume Introduction Le traitement dans le cancer de l’ovaire localement avance est une chirurgie optimale suivie d’une chimiotherapie. Les patientes avec une dissemination tumorale importante, un OMS superieur a deux et un âge superieur a 75 ans sont de mauvaises candidates pour une chirurgie premiere agressive. La chirurgie d’intervalle, apres une chimiotherapie neo adjuvante, a pour but d’obtenir davantage de chirurgies completes, d’augmenter la survie et de diminuer la morbidite liee a la chirurgie. Le critere principal de jugement etait la survie sans progression. Les criteres secondaires de jugement etaient la survie globale et la morbi-mortalite post-chirurgie. Methode Il s’agit d’une etude retrospective effectuee dans deux centres de reference francais entre janvier 2000 et decembre 2015. Les patientes qui ne pouvaient pas beneficier d’une chirurgie initiale complete etaient operees apres trois cures de chimiotherapie au centre Francois Baclesse et apres au moins cinq cures au centre Rene Gauducheau. Resultats La population analysee comportait 104 patientes, 43 (41,0 %) patientes traitees au centre Rene Gauducheau (groupe 1) et 61 (59,0 %) patientes traitees au centre Francois Baclesse (groupe 2). La survie sans progression et globale etait similaire entre les deux groupes. Elles etaient respectivement de 15,9 mois et 34 mois dans le groupe 1 vs 15,4 mois et 37,6 mois dans le groupe 2 (p = 0,72 ; p = 0,65). La duree d’hospitalisation moyenne et la morbidite postoperatoire etait similaire dans les deux groupes. Conclusion Pour des patientes fragiles, afin de limiter une chirurgie invasive, faire plus de cinq cures de chimiotherapie peut etre une option raisonnable.

Based on recently published data, these recommendations present some evolutions in the surgical management of high grade epithelial ovarian cancers. In apparently early stages (FIGO I and II), surgical staging must be undertaken to confirm the absence of both peritoneal lesions and lymph node involvement (that might change stage and management). Neoadjuvant chemotherapy is not indicated, surgical exploration should be performed upfront, by laparotomy, to reduce the risk of rupture of the primary tumor. In advanced stages, the first step is to evaluate the feasibility of primary surgery with complete tumor cytoreduction. If it appears unfeasible, 3 or 4 cycles of neoadjuvant chemotherapy are administered before interval surgey. Whether it is implemented in the primary or interval setting, surgery must be performed by experimented teams, in an approved facility, having developed a rehabilitation program. Lymph node dissection is not mandatory if no adenopathies have been identified by imaging and by peroperative palpation. At first relapse, the surgical decision must be made by a multidisciplinary team, using scores predictive of complete cytoreduction (AGO or iMODEL criteria). Similarly as in first line, the objective is to achieve resection without any residual disease. Surveillance after first-line treatment must be adapted, according to the probability of another complete cytoreduction in case of late relapse, especially in patients who benefited from primary complete surgery and maintained good performance status.

Since the LACC study in 2018, the use of the uterine manipulator (UM) has been questioned in Oncological surgery. Nowadays, there are few data on UM use in patients eligible for minimally invasive surgery for endometrial cancer. Our objective was to evaluate the practices and modalities of UM use by French onco-gynecologic surgeons in the management of endometrial cancer.We surveyed the practices of 3 French medical societies-affiliated onco-gynecological surgeons with a web questionnaire composed of 16 questions.A total of 165 responses were collected. In the case of minimally invasive hysterectomy for endometrial cancer, the routine use of UM was 42.7%. Of the 40.9% of surgeons who never used UM, 83.6% justified it with the risk of tumor spillage. When UM was used, surgeons mentioned reducing operating time and reducing complications in 67.0% and 59.8% of cases respectively as its main advantages. UM was set up without laparoscopic control in 54.6% of cases. In 47.4% of cases, the medical student was in charge of UM instrumentation. Tubal obliteration at the beginning of the procedure was performed systematically in 35.4% of cases. For 63.5% of UM users, the adjuvant treatment could be modified in case of uterine perforation.This survey confirms the heterogeneity of practices regarding the use of UM in endometrial cancer surgery. Prospective data on the benefit (reduction of surgical complications)/risk (impact on survival) balance are needed to recommend or not the use of this device.

The objective of this review is to evaluate the optimal positioning of cytoreduction surgery and perioperative medical treatments in the initial management and relapse of advanced-stage epithelial ovarian carcinoma. In the initial management, primary surgery should be proposed if the absence of tumor residue is feasible with reasonable surgery (extensive surgical resections to be considered and their complications, but also the general condition of the patient). Guidelines recommend 3 to 4 cycles of neoadjuvant chemotherapy before interval surgery for patients not eligible for primary surgery. Late interval surgery (i.e. after≥5-6 cycles of chemotherapy) is not a standard of care and should only be proposed in case of poor tumor response after 3-4 cycles and when complete interval surgery seems feasible. At first tumor recurrence in platinum-sensitive patients, a primary cytoreduction surgery can be considered if complete surgery can be managed. Predictive scores (AGO score; i-model score) can be used to select eligible patients. Given the lack of strong evidence, performing cytoreduction surgery at first recurrence in platinum-resistant patients or in the event of subsequent recurrence cannot be recommended. Nevertheless, obtaining a complete surgery in these clinical situations seems to provide a benefit in terms of overall survival and its application should be based on the expertise of specialized teams.

International audience

Prognostic significance of endometrioid epithelial ovarian cancer (EOC) is controversial. We compared clinical, pathological, and biological features of patients with endometrioid and serous EOC, and assessed the independent effect of histology on outcomes.We conducted a multicenter retrospective analysis of patients with EOC selected from the French Epidemiological Strategy and Medical Economics OC database between 2011 and 2016. Our main objective was to compare overall survival (OS) in endometrioid and serous tumors of all grades. Our second objectives were progression-free survival (PFS) and prognostic features.Out of 10,263 patients included, 3180 cases with a confirmed diagnosis of serous (N = 2854) or endometrioid (N = 326) EOC were selected. Patients with endometrioid histology were younger, more often diagnosed at an early stage, with lower-grade tumors, more frequently dMMR/MSI-high, and presented more personal/familial histories of Lynch syndrome-associated cancers. BRCA1/2 mutations were more frequently identified in the serous population. Endometrioid patients were less likely to receive chemotherapy, with less bevacizumab. After median follow-up of 51.7 months (95CI[50.1-53.6]), five-year OS rate was 81% (95CI[74-85]) in the endometrioid subgroup vs. 55% (95CI[53-57] in the serous subset (p0.001, log-rank test). In multivariate analyses including [age, ECOG-PS, FIGO, grade, and histology], the endometrioid subtype was independently associated with better OS (HR = 0.38, 95CI[0.20-0.70], p= 0.002) and PFS (HR = 0.53, 95CI[0.37-0.75], p0.001).Clinicopathological features at diagnosis are not the same for endometrioid and serous EOC. Endometrioid histology is an independent prognosis factor in EOC. These observations suggest the endometrioid population requires dedicated clinical trials and management.

Cancers 13(7), 1565 (2021). doi:10.3390/cancers13071565 special issue: "Special Issue "Clinical Trials in Breast Cancer" / Special Issue Editor: Prof. Dr. Gilles Freyer, Guest Editor", Published by MDPI, Basel

ObjectiveThe aim of this study was to explore the feasibility and safety of the laparoscopic approach after neoadjuvant chemotherapy among selected chemosensitive patients with advanced ovarian cancer.MethodsThe CILOVE study was a phase II prospective non-randomized multicenter study. It aimed to enroll 47 women with unresectable disease at the time of initial diagnosis (International Federation of Gynecology and Obstetrics (FIGO) stage IV and/or diffuse extensive carcinomatosis for advanced FIGO stage IIIC or patients unfit to withstand radical primary surgery), in response to chemotherapy and fit to undergo laparoscopy.ResultsAmong the 48 patients enrolled in the trial, 44 (92%) patients underwent exploratory staging laparoscopy and, as a result, 41 patients were eligible for cytoreductive surgery. Among them, 32 were intended to be managed by laparoscopy and nine patients were managed by laparotomy. The conversion rate to laparotomy was 9.4% (3/32) and the reasons were multiple surgical adhesions (n=1), miliary carcinomatosis and adhesion to the intraperitoneal mesh (n=1), and poor laparoscopic evaluation of transverse colon involvement (n=1). All except one patient had optimal cytoreduction (97% complete cytoreduction, 3% incomplete cytoreduction (residual tumor ConclusionsInterval ovarian cytoreduction by a laparoscopic approach is safe and feasible for patients with a favorable response to chemotherapy. With the widespread use of neoadjuvant chemotherapy in the management of advanced ovarian cancer, a minimally invasive approach may be a potential option.

PURPOSE: National guidelines define adequate axillary lymph node dissections as those yielding ≥ 10 lymph nodes (LNs). We aimed to identify the optimal LN yield among node-positive patients. METHODS: Using the National Cancer Data Base (2010–2015), we categorized node-positive patients as follows: (1) neoadjuvant chemotherapy (NAC, cN1–3 or ypN1mi-3) or (2) upfront surgery (pN1–3). A restricted cubic splines model was used to estimate LN retrieval thresholds associated with change in overall survival (OS). RESULTS: 129,685 patients were identified: 21.2% NAC, 78.8% upfront surgery. Low, moderate, and high retrieval thresholds were estimated to be 1–6, 7–21, and > 21 LNs (upfront surgery), and 1–7, 8–22, and > 22 LNs (NAC). In an adjusted model, high versus low LN yield was associated with greater receipt of adjuvant chemotherapy (upfront surgery OR 1.96, p < 0.001) and greater use of adjuvant radiation (upfront surgery OR 1.08, p = 0.02; NAC OR 1.23, p = 0.002). After adjustment, high versus low LN retrieval was associated with improved OS (upfront surgery HR 0.86, p < 0.001; NAC HR 0.77, p < 0.001). Worse OS was associated with retrieving fewer LNs, likely as a result of an under-staged axilla and missed opportunity for adjuvant therapy, while better OS was independently associated with retrieval of up to approximately 20 LNs, after which survival did not improve. CONCLUSION: In node-positive breast cancer, the number of nodes retrieved is significantly associated with an increased positive nodal count and greater use of adjuvant therapy. Removal of approximately 20 LNs may improve survival by both more accurate nodal staging and increased adjuvant therapy use.

Introduction/Background Clinical trials in Epithelial Ovarian Cancer (EOC) frequently examine treatment at a particular phase of the patient’s disease trajectory. Few major studies have examined the management of patients from diagnosis to death. This international network was developed to compare treatment sequencing and outcomes from six centres across Europe and South Korea. Methodology This retrospective cohort study used longitudinal data collected from electronic medical records from 6 European and South Korean treatment centres. A standard protocol & common data model was developed to capture consistent data for patients diagnosed between January 2012 and December 2018, with a minimum of 12 months follow-up. Full treatment data was collected and categorized in programmes of care based on exemplar patient narratives. An extensive data harmonization process was implemented to ensure different country and site medical records were interpreted in a common manner. Overall survival (OS) and time to next treatment (TTNT) were estimated using Kaplan Meier methodology and outcomes stratified by categories of interest. Each site analysed their own EMR data and shared aggregated results for comparison. Results Table 1 demonstrates patient characteristics from six sites. In total the overall study cohort includes 2889 patients. Median age for each centre ranged from 53 to 67 years. The majority of patients were FIGO stage III (range 31% to 66%) and high-grade serous morphology (52% to 69.9%) Additional data on treatment pathways and outcomes for each centre will be presented. Conclusion Preliminary analysis from this network suggests a consistent profile of adults treated for EOC across most contributing treatment centres in Europe, but with some substantial differences compared to patients treated at centres in South Korea and Romania. The establishment of a common data model between sites across five different countries allows for detailed exploration of the factors influencing differences in patient management and treatment outcomes in ovarian cancer patients. Disclosures Sue Cheeseman: I receive consultancy fees from IQVIA Bethany Levick: I am an employee of IQVIA Eunji Nam: I have no conflict of interest to disclose Dongkyu Kim: I have no conflict of interest to disclose Roman Rouzier: I have no conflict of interest to disclose Claire Bonneau: I have no conflict of interest to disclose Paul Kubelac: served on a speaker’s bureau for Roche, Bristol-Myers Squibb, AstraZeneca, Novartis. Patriciu Achimas-Cadariu: I have no conflict of interest to disclose Jean-Marc Classe: I have no conflict of interest to disclose Francois Bocquet: I have no conflict of interest to disclose Sven Becker: I have no conflict of interest to disclose Mariana Guergova-Kuras: I am an employee of IQVIA Geoff Hall: I receive grant support and consultancy fees from IQVIA

Background: The selection of women with hormone receptor-positive (HR+) early breast cancer (EBC) at high risk of relapse after five years (yrs.) of adjuvant aromatase inhibitors (AIs) is crucial, as the benefit of extending AIs is counterbalanced by toxicity. We developed a clinicopathological tool to estimate the residual risk of relapse after five years of adjuvant AIs. Methods: The Institut de Canc&eacute, rologie de l&rsquo, Ouest (ICO) database was used to determine a prognostic score of post-five-year AI relapse. Cox regression models estimated our score&rsquo, s prognostic performance. Results: In total, 1105 women were included. Median follow-up was 44 months (IQR = 21&ndash, 70) post-AI treatment. From the Cox models, we designed a dichotomous prognostic score including the number of macrometastases, age (&gt, 70 yrs. vs. &le, 70 yrs.), tumor size (&ge, T2 vs. not), and mitotic activity (&ge, 2 vs. not). Overall, 77.5% of patients were classified as being at low risk and 22.5% at high risk of late recurrence. Low-risk patients had a five- to ten-year local or distant recurrence risk of 7.6% (95% CI, 5.4% to 10.6%) as compared with 26.9% (95% CI, 19.9% to 35.7%) for the high-risk roup. Conclusion: In this study, we developed a simple tool to identify women at high risk of relapse despite completing five years of AIs.

International audience; Objectives: In 2016, the European Society of Gynecology Oncology (ESGO) published indicators defining the quality of surgical management of advanced ovarian cancer. The objective of the study was to assess the quality of ovarian cancer patient management in regional centers authorized for gynecological cancer, based on the ESGO list of quality indicators. Methods: A multicenter retrospective observational cohort study was conducted from January 1 to June 30, 2016. The following quality indicators 1 "rate of complete surgical resection", 4 "center participating in clinical trials in gynecologic oncology", 5 "treatment planned and reviewed at a multidisciplinary team meeting", 6 "required preoperative workup", 8 "minimum required elements in operative reports" and 9 "minimum required elements in pathology reports" were selected. Results: 91 patients were evaluated in 16 centers. The required preoperative workup was incomplete in 25% of cases. Treatment was not planned at a multidisciplinary team meeting for 24%. An evaluation score of peritoneal involvement was included in 40% of the operative reports and the quality of surgical resection was reported in 72%. Primary surgery was most often performed in a peripheral hospital (48%), interval surgery in a private center (37%), and closure surgery in a regional cancer center (43%). No institution respected the six quality indicators evaluated. One regional cancer center respected five items and two private centers did not respect any. Conclusion: Whilst the ESGO quality indicators provide objective, validated and evaluable support which centers can use to improve quality of care, we observed heterogeneous practices amongst the centers evaluated.

BACKGROUND: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. METHODS: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. FINDINGS: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. INTERPRETATION: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.

International audience; PréambuleLa pandémie de COVID 19 impacte l’activité de chirurgie oncologique, directement et indirectement. Les patients atteints de cancer sont plus à risque d’infection du fait de l’immunosuppression secondaire au cancer et aux traitements (chimiothérapie, chirurgie). En cas d’infection COVID 19, les patients atteints de cancer ont plus de risque d’évolution péjorative que les patients indemnes de cancer [1]. Il faut donc à tout prix éviter l’infection COVID 19 pour les patients atteints de cancer.

International audience; Ovarian cancers express highly immunogenic tissue-specific antigens. The resulting immune infiltration is a major prognostic factor. There is therefore a strong biological rationale for the development of immunotherapy in ovarian cancer. However, based on Phase I and II clinical trials data, the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors (ICPIs) remains limited in monotherapy in heavily pre-treated patients. Currently, the identification of predictive biomarkers of response and resistance is one of the major areas of research. Identifying effective combination of anti-PD-1 or anti-PD-L1 with other anticancer agents is another clinical need. Several combinations were evaluated. The association of ICPIs with chemotherapy (anthracyclines or carboplatin+paclitaxel) is disappointing (JAVELIN studies). The association with PARP inhibitors, anti-angiogenic agents and CTLA-4 inhibitors seems promising. Other immune therapies such as cell therapies (adoptive transfer of intra-tumor lymphocytes, CAR T cells or vaccines from dendritic cells) could be the future of immunotherapy in ovarian cancer but only early phase studies clinical data is available at this time.

objective: to analyze the evolution of surgical techniques and strategies, and to determine their influence on the survival of patients with stage III or IV epithelial ovarian cancer (EOC). Methods: a retrospective data analysis was performed in two French tertiary cancer institutes. The analysis included clinical information, cytoreductive outcome (complete, optimal and suboptimal), definitive pathology, Overall Survival (OS), and Progression-Free Survival (PFS). Three surgical strategies were compared: Primary Cytoreductive Surgery (PCS), Interval Cytoreductive Surgery (ICS) after three cycles of Neo-Adjuvant Chemotherapy (NAC), and Final Cytoreductive Surgery (FCS) after at least six cycles of NAC. We analyzed four distinct time intervals: prior to 2000, between 2000 and 2004, between 2005 and 2009, and after 2009. Results: data from 1474 patients managed for International Federation of Gynecology and Obstetrics (FIGO) stages III (80%) or IV (20%) EOC were analyzed. Throughout the four time intervals, the rate of patients who were treated only medically increased significantly (10.1% vs. 22.6% p &lt, 0.001). NAC treatment increased from 20.1% to 52.2% (p &lt, 0.001). Complete resection rate increased from 37% to 66.2% (p &lt, 0.001). Of our study population, 1260 patients (85.5%) underwent surgery. OS was longer in cases of complete cytoreduction (Hazard Ratio (HR) = 2.123 CI 95% [1.816&ndash, 2.481] p &lt, 0.001) but the surgical strategy itself did not affect median OS. OS was 44.9 months, 50.3 months, and 42 months for PCS, ICS, and FCS, respectively (p = 0.410). After adjusting for surgical strategies (PCS, ICS, and FCS), all patients with complete cytoreduction presented similar OS with no significant difference. However, PFS was three months shorter when FCS was compared to PCS (p &lt, 0.001). Conclusion: In our 30 years&rsquo, experience of EOC management, complete resection rate was the only independent factor that significantly improved OS and PFS, regardless of the surgical strategy.

GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients. Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone. From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3–17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed. In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.

Resume Introduction L’obesite peut complexifier la prise en charge en cancerologie. L’objectif de cette etude etait l’evaluation des prises en charge des patientes obeses morbides traitees pour cancer de l’endometre et de la concordance vis-a-vis des recommandations ESMO. Materiel et methode Une etude retrospective incluant les patientes d’IMC = a 40 kg/m2 operees pour cancer de l’endometre au centre hospitalo-universitaire et a l’institut cancerologique de l’ouest de Nantes entre 2010 et 2017 a ete menee. Les donnees sociodemographiques carcinologiques et operatoires ont ete recueillies. Resultats Vingt patientes d’âge median de 65,5 ans (28–86) et d’IMC median de 47 kg/m2 (40–60) ont ete incluses. Il s’agissait d’un type I histologique dans 90 % des cas et d’un stade FIGO I dans 75 % des cas. Toutes ont beneficie d’une biopsie preoperatoire et 70 % des patientes ont beneficie d’une IRM preoperatoire (14/20). La chirurgie a ete realisee par laparotomie dans 40 % des cas, par cœlioscopie dans 50 % des cas et par voie vaginale dans 10 % des cas. La cœlioscopie a ete convertie en laparotomie dans 40 % des cas (4/10). La stadification chirurgicale realisee etait discordante des recommandations dans 40 % des cas. Deux patientes sur 14 n’ont pas beneficie de radiotherapie adjuvante du fait de retard de cicatrisation. Discussion Le cancer de l’endometre chez les patientes en obesite morbide est pourvoyeur de sous traitement par une evaluation preoperatoire non optimale et une stadification chirurgicale incomplete pour un plus d’un tiers des patientes.