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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.

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.

The panel of therapeutic options available for medical treatment of relapsed ovarian cancer increased over the last years. In late, platinum-sensitive relapse, standard treatment remains platinum-based polychemotherapy. The choice between bevacizumab added to chemotherapy followed by maintenance and inhibitors of poly-(ADP-riboses) polymerases (PARPi) after response to platinum-based therapy should be discussed, taking into account prior treatment, contraindications, and disease characteristics (biology, symptoms…). The addition of bevacizumab at first platinum-sensitive relapse can be considered if it has not been administered in first line, and it is optional (rechallenge) if previously administered (but without Marketing Authorization in this setting). PARPi are indicated for maintenance therapy after response to platinum-based chemotherapy (whatever the treatment line), regardless of BRCA mutational status, in case of no prior administration. Early relapses are associated with poor prognosis and therapeutic options are more limited. They are treated by monochemotherapy without platinum agents, associated with bevacizumab if not administered previously. Beyond first early relapse, there is no standard and inclusion in a clinical trial should be proposed if possible. Several clinical studies assessing associations of immunotherapy and chemotherapy and/or antiangiogenic drugs and/or targeted therapies (such as PARPi) are ongoing in early or late relapse.

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.

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.

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.

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.

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.

Aim To assess the value of post-mastectomy radiation therapy (PMRT) to breast cancer (BC) patients with no or minimal lymph node (LN) involvement. Materials and methods We retrospectively analysed a French multi-centric cohort of 4283 patients treated by mastectomy and axillary dissection, with or without PMRT, between 1980 and 2013. Practices were analysed for three treatment periods (1980–1999, 2000–2005 and 2006–2013). The impact of PMRT on loco-regional recurrence (LRR), disease-free survival (DFS), BC-specific survival and overall survival was assessed in pN0-1mi patients using multivariate analyses (logistic regression and Cox model). It was subsequently assessed based on the number of clinicopathological recurrence-risk factors, generating a prognostic index (French-PMRT index), to isolate a pN0-1mi patients subgroup that might derive a benefit from PMRT. We tested the accuracy of the Cambridge-PMRT (c-PMRT) index to discriminate between patients with significantly different outcomes and the value of PMRT in each c-PMRT prognostic group. Results More than half of the pN0-1mi patients of our cohort underwent PMRT, which almost significantly improved LRR-free survival and DFS. Matching pN0-1mi patients based on the number of clinicopathologic recurrence-risk factors identified a higher risk subpopulation (≥3 recurrence-risk factors), but PMRT did not improve patient outcomes. Although the c-PMRT index had the potential to predict patient outcomes, its use did not help in making the decision of whether or not to use PMRT. Conclusion We failed to isolate a subgroup of early BC patients without LN involvement suitable for PMRT, despite studying a large cohort.

Introduction The aim of this study was to examine changes in therapeutic practices for early breast cancer T0-2 N0 managed by upfront surgery and SLNB. Population Between 1999 and 2012, 15.508 patients were treated. Four periods were determined: 1999–2003, 2004–2006, 2007–2009 and > 2009. Five tumor subtypes were defined according to hormonal receptors (HR) and Her2: Luminal A (HR + Her2- Grade 1–2), Her2 (Her2+ HR-), Triple-negative (HR- Her2-), Luminal B Her2- (HR + Her2- Grade 3), Luminal B Her2+ (HR + HER2+). Methods Rates of axillary lymph node dissection (ALND), adjuvant chemotherapy ± trastuzumab, endocrine treatment, mastectomy and post mastectomy radiotherapy (PMRT) were analyzed according to treatment periods with univariate and multivariate analysis. Overall and disease-free survivals were analyzed according to treatment periods adjusted for HR and then for tumor subtypes. Results Rates of ALND, adjuvant chemotherapy and endocrine treatment varied significantly according to treatment periods, for HR positive and negative tumors. ALND rate decreased for all tumor subtypes with a decrease of adjuvant chemotherapy rate for Luminal A tumors and an increase for Luminal B Her2+ and Her2-tumors. Endocrine treatment rate decreased for Luminal A and increased for Luminal B Her2+ tumors. In multivariate analysis, these modifications with time remained significant. Mastectomy and PMRT rates increased. In multivariate analysis, overall and disease-free survivals increased during successive periods. Conclusion A global therapeutic de-escalation in ALND and adjuvant systemic treatment, combined with an actual escalation in some specific subsets was demonstrated, but without negative impact on survival.

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.

Treatment in locally advanced ovarian cancer is optimal surgery followed by chemotherapy. Patients with significant tumor spread, OMS2, age75 years old are poor candidates for aggressive primary surgery. Interval surgery, after neo-adjuvant chemotherapy, aims to achieve more complete surgery, increase survival, and reduce surgical morbidity. The primary endpoint was progression-free survival. Secondary outcomes were overall survival and postoperative morbidity and mortality.This is a retrospective study conducted in 2 French referral centers between January 2000 and December 2015. Patients who could not benefit from a complete initial surgery were operated after 3 cures of chemotherapy at the François Baclesse center and after least 5 cures at the center René Gauducheau.The population analyzed included 104 patients, 43 (41.0%) patients treated at the René Gauducheau center (group 1) and 61 (59.0%) patients treated at the François Baclesse center (group 2). Progression-free and overall survival were similar between the 2 groups, they were, respectively, 15.9 months and 34 months in group 1 vs. 15.4 months and 37.6 months in group 2 (P=0.72; P=0.65). Mean hospital stay and postoperative morbidity were similar in both groups.For weak patients, to limit invasive surgery, doing more than 5 courses of chemotherapy may be a reasonable option.

Objectives: To analyze axillary lymph node involvement (ALNI) rate and survival for mucinous (MC) and tubular (TC) breast carcinomas considered being of very good prognosis and for which an axillary surgical exploration could be questioned. Methods: Our multicentric cohort consisted of 21,135 patients with clinically node-negative invasive breast cancer, without neoadjuvant therapy, between 1999 and 2013 in 10 French centers. ALNI rate and survival were analyzed according to patient and tumor characteristics. Results: Our cohort consisted of 672 TC and 245 MC. Patients were older and tumor size greater for MC and pathologic factors were more pejorative. The rate of mastectomies and adjuvant chemotherapy was higher in the MC group. Axillary lymph node status was determined by SLNB alone in 71.2% of patients. ALNI rates were 17.9% and 18% for TC and MC, respectively. ALNI rate was lesser for MC (OR 0.503, p = 0.024) and greater in case of lympho-vascular invasion (OR 5.0, p < 0.0001) and for tumors >10 mm (OR 2.17, p = 0.042). Median follow-up was 58 months. The 5- and 7-year overall survival rates were 97.1% and 95% for TC, respectively; 92.3% and 91.2% for MC ( p = 0.043); 5- and 7-year disease-free survival rates were 97.9% and 97.2% versus 95.2 and 93.6% ( p = 0.041). Lympho-vascular invasion was the only predictive factor for overall survival (hazard ratio [HR] = 2.70)’ grade 2 (HR = 10) and HR-negative (HR = 4.9) were the two predictive factors for disease-free survival. Conclusion: This study confirms the need for an axillary exploration for these tumors even for a tumor size

This systematic review and meta-analysis pools data from studies in the neoadjuvant setting on axillary pathologic complete response rates for different breast cancer subtypes in patients with initial clinically node-positive disease.Importance An overview of rates of axillary pathologic complete response (pCR) for all breast cancer subtypes, both for patients with and without pathologically proven clinically node-positive disease, is lacking. Objective To provide pooled data of all studies in the neoadjuvant setting on axillary pCR rates for different breast cancer subtypes in patients with initially clinically node-positive disease. Data Sources The electronic databases Embase and PubMed were used to conduct a systematic literature search on July 16, 2020. The references of the included studies were manually checked to identify other eligible studies. Study Selection Studies in the neoadjuvant therapy setting were identified regarding axillary pCR for different breast cancer subtypes in patients with initially clinically node-positive disease (ie, defined as node-positive before the initiation of neoadjuvant systemic therapy). Data Extraction and Synthesis Two reviewers independently selected eligible studies according to the inclusion criteria and extracted all data. All discrepant results were resolved during a consensus meeting. To identify the different subtypes, the subtype definitions as reported by the included articles were used. The random-effects model was used to calculate the overall pooled estimate of axillary pCR for each breast cancer subtype. Main Outcomes and Measures The main outcome of this study was the rate of axillary pCR and residual axillary lymph node disease after neoadjuvant systemic therapy for different breast cancer subtypes, differentiating studies with and without patients with pathologically proven clinically node-positive disease. Results This pooled analysis included 33 unique studies with 57 531 unique patients and showed the following axillary pCR rates for each of the 7 reported subtypes in decreasing order: 60% for hormone receptor (HR)-negative/ERBB2 (formerly HER2)-positive, 59% for ERBB2-positive (HR-negative or HR-positive), 48% for triple-negative, 45% for HR-positive/ERBB2-positive, 35% for luminal B, 18% for HR-positive/ERBB2-negative, and 13% for luminal A breast cancer. No major differences were found in the axillary pCR rates per subtype by analyzing separately the studies of patients with and without pathologically proven clinically node-positive disease before neoadjuvant systemic therapy. Conclusions and Relevance The HR-negative/ERBB2-positive subtype was associated with the highest axillary pCR rate. These data may help estimate axillary treatment response in the neoadjuvant setting and thus select patients for more or less invasive axillary procedures.Question What are the rates of axillary pathologic complete response (pCR) for different breast cancer subtypes in patients with initially clinically node-positive breast cancer? Findings This systematic review and meta-analysis, including 33 unique studies with 57 531 unique patients, showed that the hormone receptor (HR)-negative/ERBB2-positive subtype was associated with the highest axillary pCR rate (60%). The remaining subtypes were associated with the following axillary pCR rates in decreasing order: 59% for ERBB2-positive, 48% for triple-negative, 45% for HR-positive/ERBB2-positive, 35% for luminal B, 18% for HR-positive/ERBB2-negative, and 13% for luminal A breast cancer. Meaning These data can help estimate axillary treatment response in the neoadjuvant setting and thus select patients for more or less invasive axillary procedures.

International audience; BACKGROUND:Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points.METHODS:Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes.RESULTS:Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p

International audience; PURPOSE: From the MINDACT trial, Cardoso et al. did not demonstrate a significant efficacy for adjuvant chemotherapy (CT) for women with early-stage breast cancer presenting high clinical and low genomic risks. Our objective was to assess the usefulness of the 70-gene signature in this population by using an alternative endpoint: the number of Quality-Adjusted Life-Years (QALYs), i.e., a synthetic measure of quantity and quality of life. METHODS: Based on the results of the MINDACT trial, we simulated a randomized clinical trial consisting of 1497 women with early-stage breast cancer presenting high clinical and low genomic risks. The individual preferences for the different health states and corresponding decrements were obtained from the literature. RESULTS: The gain in terms of 5-year disease-free survival was 2.8% (95% CI from -\,0.1 to 5.7%, from 90.4% for women without CT to 93.3% for women with CT). In contrast, due to the associated side effects, CT significantly reduced the number of QALYs by 62~days (95% CI from 55 to 70 days, from 4.13~years for women without CT to 3.96~years for women with CT). CONCLUSION: Our results support the conclusions published by Cardoso et al. by providing additional evidence that the 70-gene signature can be used to avoid overtreatment by CT for women with high clinical risk but low genomic risk.

International audience; BACKGROUND:Invasive lobular carcinomas (ILCs) represent approximately 10% of all breast cancers. Despite this high frequency, benefit of adjuvant chemotherapy (CT) is still unclear.METHODS:Our objective was to investigate the impact of CT on survival in ILC. Patients were retrospectively identified from a cohort of 23,319 patients who underwent primary surgery in 15 French centers between 1990 and 2014. Only ILC, hormone-positive, human epidermal growth factor 2 (HER2)-negative patients who received adjuvant endocrine therapy (ET) were included. End-points were disease-free survival (DFS) and overall survival (OS). A propensity score for receiving CT, aiming to compensate for baseline characteristics, was used.RESULTS:Of a total of 2318 patients with ILC, 1485 patients (64%) received ET alone and 823 (36%) received ET + CT. We observed a beneficial effect of addition of CT to ET on DFS and OS in multivariate Cox model (HR = 0.61, 95% confidence interval, CI [0.41-0.90]; p = 0.01 and 0.52, 95% CI [0.31-0.87]; p = 0.01, respectively). This effect was even more pronounced when propensity score matching was used. Regarding subgroup analysis, low-risk patients without CT did not have significant differences in DFS or OS compared to low-risk patients with CT.CONCLUSION:ILC patients could derive significant DFS and OS benefits from CT, especially for high-risk patients.

Morbid obesity may lead to difficulties for management of endometrial cancer. The aim of this study was the assessment of management of endometrial cancer for morbidly obese women and the implementation of recommendations.this is retrospective study including women with BMI =40kg/mTwenty patients met the inclusion criteria with a median age of 65.5 (28-86) and a median BMI of 47kg/mAlthough good prognosis, the endometrial cancer of morbidly obese women seem to be under treat. These patients do not seem benefited an optimal pre-operative assessment. The surgery is mainly realized by laparotomy with a not complete surgical stadification for one more than a third of the patients.

Sentinel lymph node biopsy (SLNB) remains under discussion for large size tumors. The aim of this work has been to study the false negative rate (FNR) of SLNB for large tumors and predictive factors of false negative (FN).A study of a multicentric cohort, involved patients presenting N0 breast cancer with a SLNB eventually completed by complementary axillary lymph node dissection (cALND). The main criteria were the FNR and the predictive factors of FN.12.415 patients were included: 748 with tumors ≥30 mm, 1101 with tumors20 and 30 mm and 10.566 with tumors ≤20 mm, with a cALND respectively for 501 patients (67%), 523 (62.1%) and 2775 (26.3%). The FNR were respectively: 3.05% (IC95%: 1.3-4.8) for tumors ≥30 mm*, 3.5% (1.8-5.2) for tumors20 and 30 mm*, 1.8% (1-2.4) for tumors ≤20 mm (p 0.05) (*Not significant). At multivariate analysis, SN number harvested ≤2 (OR:2.0, p = 0.023) and tumor size20 and 30 mm (OR:2.07, p = 0.017) were significant predictive factors of FN, without significant value for tumor size ≥30 mm (OR:1.83, p = 0.073).The FNR of SLNB was not higher amongst large size tumors compared to tumors of a smaller size. These results support the validation of SNLB for tumors up to 50 mm.

Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or1 cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation.A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade.A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07-0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors.Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.

The aim of this study was to assess the impact of the preservation of the intercostobrachial nerve on the quality of life of patients operated for breast cancer.This study was ancillary to cost comparison study of axillary sentinel lymph node detection and axillary lymphadenectomy in early breast cancer. It was a prospective multicenter, observational, non-randomized study. The quality of life was assessed using two questionnaires: QLQ-C30 and specific module QLQ-BR23 Surveys have been performed before initiation of surgery, one week, and 1 month, 8 months and 12 months after discharge from hospitalization for the first surgical procedure.Five hundred and seventy-eight patients with preservation of intercostobrachial nerve without axillary lymph node dissection (C- P+), 85 without preservation of nerve and axillary lymph node dissection (C+P-) and 57 with preservation of nerve and axillary lymph node dissection (C+P+) have been included in the study. The changing arm symptoms score was significantly different during follow-up between the three groups (P0.001). This difference between the two groups C- P+ and C+P+ was significant clinically at one week [16.9, IC95%: 11.9 to 22 (P0.01)], and persisted for up to 12 months [9.9, IC95%: 3.2 à16.6 (P=0.022)]. There was no difference between the group C+P- and C+P+. Results for physical functioning score were similar.Preservation of the intercostobral nerve is not associated with better quality of life. Only axillary lymph node dissection has an impact on quality of life.

To define the prognostic value of isolated tumor cells (ITC), micrometastases (pN1mi) and macrometastases in early stage breast cancer (ESBC). We conducted a retrospective multicenter cohort study at 13 French sites. All the eligible patients who underwent SLNB from January 1999 to December 2008 were identified, and appropriate data were extracted from medical records and analyzed. Among 8001 patients, including 70% node-negative (n = 5588), 4% ITC (n = 305), 10% pN1mi (n = 794) and 16% macrometastases (n = 1314) with a median follow-up of 61.3 months, overall survival (OS) and recurrence-free survival (RFS) rates at 84 months were not statistically different in ITC or pN1mi compared to tumor-free nodes. Axillary recurrence (AR) was significantly more frequent in ITC (1.7%) and pN1mi (1.5%) compared to negative nodes (0.6%). Survival and AR rates of single macrometastases were not different from those of ITC or pN1mi. In case of 2 macrometastases or more, survival rates decreased and recurrence rates increased significantly. Micrometastases and ITC do not have a negative prognostic value. Single macrometastases might have an intermediate prognostic value while 2 macrometastases or more are associated with poorer prognosis.

Paraoxonase 1 (PON1) and serum amyloid A (SAA) are carried by HDL. In case of inflammation, SAA and PON1 tend to change in opposite direction. In this study we determined if inflammation leads to altered PON1 activity using three different substrate hydrolysis rates, paraoxonase (PON), arylesterase (ARE) and lactonase (LAC) in breast cancer recurrence.49 patients with a recurrence of breast cancer were analyzed for SAA, CRP, lipids, oxidized LDL, PON, ARE and LAC. Distribution of PON1 activities across the quartiles of CRP and SAA were compared by the Kruskal Wallis test. Non-parametric estimates of the survivor function were computed with Kaplan-Meier method. The association of SAA and ARE with short term death was assessed by logistic regression models.HDL and ARE decrease significantly across the quartiles of CRP. No significant differences were observed across SAA quartiles. The survival time was significantly related to the level of SAA (log rank: p0.001) as well as the level of ARE (log rank: p=0.039). SAA and ARE were independently related to survival time below one year.PON1 does not seem to be directly affected by SAA, for any of the tested substrates, PON, ARE and LAC. The combined measurement of SAA and ARE could be a useful tool in this clinical situation, since they are independently related to short term death.

Whereas tumor infiltration by T effectors is generally associated with a more favorable prognosis, the accumulation of CD4+ regulatory T cells (Treg) within tumors is instead often associated with poor disease outcome. Because approaches to improve antitumor immunity aim, on one hand, at expanding tumor antigen-specific T cells and, on the other, at eliminating or inactivating Treg, an outstanding question is whether, and to what extent, tumor antigen-specific CD4+ T effectors present at tumor sites overlap with tumor-associated Treg. Here, we used MHC class II/peptide tetramers incorporating an immunodominant peptide from the human tumor-specific antigen NY-ESO-1 to assess antigen-specific CD4+ T cells among conventional CD4+ T effectors and Treg at sites of ovarian cancer. We found that, in patients who spontaneously respond to the antigen, the frequency of NY-ESO-1 tetramer+ cells detected ex vivo was highly enriched in tumors as compared with the periphery. At tumor sites, NY-ESO-1 tetramer+ cells were detected concomitantly with high proportions of Treg but were distinct from the latter and displayed characteristics of TH1 effectors. Thus, even in the presence of high proportions of Treg, tumor antigen-specific CD4+ T cells can accumulate in ovarian tumors and maintain an effector phenotype. Cancer Immunol Res; 1(5); 303–8. ©2013 AACR.

Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications.We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected.5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p 0.01). A young age ≤40 years (p 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or ≤35 years (p 0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age ≤35 (p 0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p 0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p 0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p 0.01).Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.

ObjectivesTo evaluate the outcome of maximal cytoreductive surgery in patients with stage IIIC to stage IV ovarian, tubal, and peritoneal cancer regarding overall survival (OS) and disease-free survival (DFS).Materials and MethodsFive hundred twenty-seven patients with stage IIIC (peritoneal) and stage IV (pleural) ovarian, fallopian tube, and peritoneal carcinoma underwent surgery between January 2003 and December 2007 in 7 gynecologic oncology centers in France. Patients undergoing primary and interval debulking surgery were included, whichever the number of chemotherapy cycles. The extent of disease, type of surgical procedure, and amount of residual disease were recorded. A multivariate analysis of the outcome was performed, taking into account the stage, grade, and timing of surgery.ResultsMedian DFS was 17.9 months, but median OS was not reached at the time of analysis. Complete cytoreductive surgery, without evident residual tumor at the end of the procedure, was obtained in 71% of all patients (primary surgery, 33%). After neoadjuvant therapy, the rate of complete debulking surgery was higher (74%) compared to primary cytoreductive surgery (65%). Twenty-three percent of patients needed “ultra radical surgery” to achieve this goal. The most significant predictive factor for DFS and OS was complete cytoreductive surgery compared to any amount, even minimal (1–10 mm), of residual disease. In the group of patients with complete cytoreductive surgery, the patients undergoing surgery before chemotherapy showed better DFS than those having first chemotherapy.ConclusionThe findings confirm that complete cytoreduction is the criterion standard of surgery in the management of advanced ovarian, peritoneal, and fallopian tube cancer, whatever the timing of surgery. With experienced teams, surgery was completed, without evident residual tumor in 71% of the cases.

International audience; PURPOSE: The risk of non sentinel node (NSN) involvement varies in function of the characteristics of sentinel nodes (SN) and primary tumor. Our aim was to determine and validate a statistical tool (a nomogram) able to predict the risk of NSN involvement in case of SN micro or sub-micrometastasis of breast cancer. We have compared this monogram with other models described in the literature. METHODS: We have collected data on 905 patients, then 484 other patients, to build and validate the nomogram and compare it with other published scores and nomograms. RESULTS: Multivariate analysis conducted on the data of the first cohort allowed us to define a nomogram based on 5 criteria: the method of SN detection (immunohistochemistry or by standard coloration with HES); the ratio of positive SN out of total removed SN; the pathologic size of the tumor; the histological type; and the presence (or not) of lympho-vascular invasion. The nomogram developed here is the only one dedicated to micrometastasis and developed on the basis of two large cohorts. The results of this statistical tool in the calculation of the risk of NSN involvement is similar to those of the MSKCC (the similarly more effective nomogram according to the literature), with a lower rate of false negatives. CONCLUSION: this nomogram is dedicated specifically to cases of SN involvement by metastasis lower or equal to 2 mm. It could be used in clinical practice in the way to omit ALND when the risk of NSN involvement is low.

To determine overall survival of patients treated for a first relapse of FIGO stage III ovarian cancer, outside of randomized trial, with a long term follow-up and to identify prognostic factors.A consecutive series of 108 patients treated for a first relapse of a FIGO stage III ovarian cancer was retrospectively included from December 1999 to November 2004. Each patient was treated with platinum-based chemotherapy in case of late (6 months) relapse and with salvage chemotherapy without platinum in case of6 months relapse. For statistical analysis the studied parameters were age, histological subtype, the completeness of initial surgery, disease-free period, localization of the relapse, clinical response to second-line chemotherapy, the completeness of secondary cytoreductive surgery (SCS) when it was performed.Median follow-up from the first relapse was 40 months. From the 108 patients, 35 underwent SCS. Median overall survival from the first relapse was 13 months in case of no SCS or non-optimal SCS and 35 months for patient with an optimal SCS (p = 0.006). In a multivariate analysis age, disease-free period, the clinical presentation of the relapse, completeness of SCS and response to second line chemotherapy appeared to be independent prognostic factors.Prognostic factors of ovarian cancer relapse are directly or indirectly linked with the feasibility of a complete SCS. Thus in the case of an ovarian cancer relapse, the feasibility of SCS must be considered in order to give the patient the best chance to experience its complete removal.

Purpose: Hyperthermic intraperitoneal chemotherapy is continuously under evaluation in ovarian cancer. The purpose of the present study was to evaluate the effect of chemotherapy, drug concentration and temperature. Materials and Methods: A human ovarian carcinoma cell line was used. The effect of hyperthermia combined with chemotherapy was analyzed. Results: When hyperthermia was combined with chemotherapy, the 50% lethal dose (LD50) decreased with the duration of exposure. The effect of temperature was similar between 39 and 43°C for a 30-min exposure. For a 60- to 90-min exposure, the LD50 was equivalent between 38 and 43°C. Beyond 40°C, an increase in platinum salt concentration was necessary to obtain similar results according to the duration of exposure. Conclusions: The cytotoxic effect of the combination seemed to be potentiated and limited at 40°C.

Presented at the 16th International Meeting of the European Society for Gynaecological Oncology (ESGO 16) Belgrade, Serbia, October 11–14, 2009.; International audience; INTRODUCTION: The aim of the present study was to prospectively evaluate morbidity of intra-peritoneal hyperthermic chemotherapy (HIPEC) using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma and, secondly, to study peritoneal recurrence. METHODS: Between 2004 and 2007, 31 patients from 18 to 65 years with FIGO stage IIIC epithelial ovarian carcinoma were treated by surgery and a total of 6 cycles of platinum based chemotherapy. Those patients were eligible for consolidation therapy. We performed a second look laparotomy operation with intra-peritoneal hyperthermic chemotherapy. We used Oxaliplatin 460 mg/m(2) with 2 l/m(2) of dextrose in an open medial laparotomy for a total of 30 min at a temperature of 42-44 degrees C. RESULTS: The grade 3 morbidity rate was 29% (95 CI: 14-45%). Nine patients experienced a total of 13 exploratory laparotomies for intra-abdominal bleeding after HIPEC. Two-year disease free and overall survival were 27% and 67% respectively. As a result of this high level of morbidity the trial was closed. CONCLUSION: Using intra-peritoneal Oxaliplatin associated with hyperthermia as consolidation therapy for advanced ovarian cancer results in a high risk of grade 3 morbidities with only a small benefit on survival

PurposeTo determine the detection rate, the false-negative rate, and the accuracy of sentinel lymph node (SLN) detection after neoadjuvant chemotherapy (NAC) for advanced breast cancer.Patients and MethodsA prospective multicentric study was initiated to evaluate the results of SLN biopsy with the combined method after NAC for advanced large operable breast cancer.ResultsFrom September 2003 to March 2007, 195 patients enrolled from 12 institutions were found suitable for evaluation. The detection rate was 90% (176 of 195 patients), and the false-negative rate was 11.5% (six of 52 patients). Patients without axillary palpable nodes (N0) before NAC had a better detection rate compared with patients with axillary suspicious nodes (N1, 94.6% v 81.5%; P = .008). The false-negative rate was not correlated with clinical nodal status before NAC (9.4% v 15%; P = .66).ConclusionThis study confirms the feasibility of SLN biopsy after NAC in the case of large operable breast cancer. The detection rate, false-negative rate, and accuracy do not differ from those obtained in the case of early breast cancer without NAC, thus demonstrating the feasibility of SLN biopsy after NAC.

Purpose To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). Patients and Methods All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time. Results Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test). Conclusion Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.

Axillary lymph node dissection in patients with ductal carcinoma in situ (DCIS) of the breast is not warranted because DCIS has no metastatic potential. However, the risk of microinvasive carcinoma (MIC) exists in large DCIS treated by mastectomy. The aim of this series is to evaluate the incidence of lymph node metastases in DCIS and DCIS-MIC. We analyzed retrospectively patients treated in six French cancer centers for pure DCIS or DCIS-MIC. Surgical procedures were lumpectomy or mastectomy associated with an axillary sentinel node (SN) procedure. We included 161 patients suffering from pure DCIS (116/161, 72%) or DCIS-MIC (45/161, 28%). Mean age was 56 years (32-78). We observed underestimation between core biopsy and histological result in 43/142 cases (30%). These data show an association between lesion size, solid subtype, high-grade DCIS, and underestimation. Forty-eight breast conservative procedures were performed and 113 mastectomies (70%). SN procedure was performed using blue dye, technetium, or both. In our series, we selected patients with a high risk of occult invasive carcinoma: high grade (55%), mean size (27 mm), and mastectomy (112). Six SN were found positive (3.7%). In the five patients treated with complete axillary dissection, the SN was the only positive node. SN in DCIS is an interesting procedure but not necessary for all patients. We need to focus on the subgroup with or a high risk of occult MIC: extensive calcifications or palpable mass, DCIS diagnosed by core biopsy and underestimation, multifocality, high grade, large tumor size, MIC, and mastectomy.

Lobular neoplasia (LN) is a risk factor for bilateral breast cancer without consensus as to its appropriate management. The authors report on a retrospective multi-institutional study concerning 52 patients in whom a diagnosis of LN was made after core needle biopsy (CNB) and who subsequently underwent surgical excision. The excision specimens revealed seven cases of invasive carcinoma and three cases of ductal carcinoma in situ, indicating an underestimation of lesions at CNB in 19% of cases, and in particular in those patients with pleomorphic LN, and when clinical, radiological masses were detected. This lesion is increasingly being diagnosed by CNB due to widespread screening. Follow-up surgical excision should be performed in order to examine the whole lesion in the case of masses or when the histologic specimen reveals a pleomorphic subtype. In other cases, annual mammographic surveillance should be undertaken due to the persistent long-term risk of developing bilateral breast cancer.

Chest wall reconstruction after radiation damage is a challenge in oncologic and plastic surgery. The defect can be reconstructed with laparoscopically harvested omental flap and meshed skin grafts. Our aim was to evaluate the use of vacuum-assisted closure (V.A.C.) in combination with laparoscopically harvested omental flap and meshed skin graft for treating these complex wounds.Between October 2003 and December 2004, 11 patients underwent a chest wall reconstruction with laparoscopic omentoplasty and V.A.C. treatment of severe chest wall radionecrosis after breast cancer treatment (n = 10) or for locally advanced breast cancer treated first by irradiation (n = 1).Laparoscopic harvesting was uneventful in 10 cases. One patient had a laparoscopic transverse colic resection because of a middle colic artery injury. Mean time of the laparoscopic procedure was 53 minutes (range: 35-120). Wound surface area averaged 360 cm (range: 80-750). The mean duration of V.A.C. treatment was 9.3 days (range: 6-16). Nine patients showed primary wound healing without adverse events. Complications occurred in 3 patients. One developed a pulmonary infection and died after healing during the postoperative course. One presented a partial flap loss, leading to delayed healing after 45 days. One patient with severe radiation damage and a complete brachial plexus paralysis required a shoulder amputation after an extensive necrosis. All but 1 patient are alive and resumed their normal daily activities.Combination of laparoscopic omentoplasty and V.A.C. can successfully be used for reconstruction of complex chest wall radiation damage.

International audience; Introduction: The direct relationship between surgical radicality to compensate biologic behavior and improvement of patient outcome at the time of primary or interval cytoreduction remains unclear.Objective: The aim of this study was to evaluate the impact of disease extension and surgical complexity on survival after complete macroscopic resection for stage IIIC-IV ovarian cancer.Materials and methods: Medical records from seven referral centers in France were reviewed to identify all patients who had complete cytoreductive surgery for stage IIIC-IV epithelial ovarian, fallopian, or primary peritoneal cancer. All patients had at least six cycles of carboplatin and paclitaxel combination therapy.Results: From the 374 consecutive patients with complete cytoreduction who were included in this study, stage, grade, upper abdominal disease, surgical complexity, and carcinomatosis extent were significantly associated with disease-free survival (DFS) at univariate analysis. Stage IV and the need for ultra-radical procedures were significantly associated with lower overall survival (OS). On multivariate analysis, radical surgery, including more than two visceral resections, was significantly associated with decreased DFS and OS.Conclusions: Patients who need complex surgical procedures involving two or more visceral resections in order to achieve successful complete cytoreduction have worse outcome than patients with less extensive procedures. The negative impact of surgical complexity was not significant in patients who underwent upfront procedures. Tumor volume and extension were associated with decreased DFS in patients undergoing a primary surgical approach. This adds to the evidence that, even though complete cytoreduction is currently the objective of surgery, tumor load remains an independent poor prognostic factor and probably reflects a more aggressive behavior.

The rate of axillary recurrence (AR) after sentinel lymph node biopsy is usually low but few studies investigated its impact on survival. Our aim was to determine the rate and predictive factors of AR in a large cohort of breast cancer patients and its impact on survival.From 1999 to 2013, 14,095 patients who underwent surgery for clinically N0 previously untreated breast cancer and had sentinel lymph node biopsy were analysed. A simplified score predictive of AR was established.Median follow-up was 55.2 months. AR was observed in 0.51% of cases, with a median time to onset of 43.4 months. In multivariate analysis, the occurrence of AR was significantly correlated with grade 2 or 3 disease, absence of radiotherapy and tumour subtype (hormonal receptor [HR]- / human estrogen receptor [HER]+). AR rates were 1% for triple-negative tumours, 2.8% for HER2-positive tumours, 0.4% for luminal A tumours, 0.9% for HER2-negative luminal B tumours, and 0.5% for HER2-positive luminal B tumours. A simplified score predictive of the occurrence of AR was established. Patients could be divided into three different score groups (p0.0001). In multivariate analysis, overall survival was significantly lower in cases of AR (p0.0001), age50, lymphovascular invasion, grade 3 disease, sentinel node (SN) macrometastases, tumour size20 mm, absence of chemotherapy and triple-negative phenotype. Survival in patients with AR was significantly lower in case of early-onset (2 years) AR (p = 0.017).Isolated AR is more common in Her2-positive/HR-negative triple-negative tumours with a more severe prognosis in triple-negative and Her2-positive/HR-negative tumours, and represents an independent adverse factor justifying an indication for systemic treatment for AR treatment. However, the benefit of any systemic treatment remains to be proven.

Background After axillary lymphadenectomy for breast cancer, a suction drain is routinely inserted into the axilla to prevent seroma formation. This drain is an obstacle to reducing hospital stay after breast-conserving surgery. This was a prospective randomized clinical trial to assess the safety and results of axillary padding without the use of a drain. Methods Between May 2001 and August 2003, 100 women were randomly allocated axillary padding without a drain or with the use of an axillary suction drain. Prospective assessments were made of morbidity, pain, shoulder mobility, quality of life and medical costs including length of hospital stay. Results Using axillary padding significantly reduced the mean (s.d.) length of hospital stay (1·8(1) versus 4·5(2) days, P < 0·001). Postoperative complications, pain, shoulder mobility and quality of life were similar in the two groups. There was no difference in the duration of the two procedures. Conclusion Axillary padding after axillary lymphadenectomy was feasible and safe, without a drain, and shortened hospital stay.

PurposeTo determine the rate of nonsentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) and predictive factors of this involvement following detection of micrometastasis in sentinel nodes (SN).MethodsWe analyzed 700 observations of SN micrometastases with additional ALND with the characteristics of the patients, tumors, and SN.ResultsInvolvement of SN was diagnosed 388 times by serial sections (55.4%) with standard hemoxylin and eosin staining (HES) and 312 times solely on immunohistochemical analysis (IHC; 44.6%). The accurate size of the micrometastases was indicated in 488 cases: 301 larger than 0.2 mm (61.7%) and 187 ≤ 0.2 mm (38.3%). Ninety-four patients (13.4%) presented an NSN involvement with only one NSN involved in 62 cases (66%). Predictive factors of NSN involvement were in univariate analysis (pT stage [P < .000], menopausal status [P = .048], T stage [P = .006], grade [P = .013], lymphovascular invasion [LVI; P = .013], histologic tumor type [P = .017], and method of micrometastasis detection, by HES or IHC [P = .015]) and in multivariate analysis (pT stage ≤ or > 20 mm [odds ratio, 2.54], micrometastases detected by HES or IHC [odds ratio,1.734], presence or absence of LVI [odds ratio, 1.706]). Micrometastasis size ≤ or greater than 0.2 mm was not predictive.ConclusionThis study confirms the value of serial sections and the vital role played by IHC in screening for small micrometastases. Omission of additional ALND may be envisaged with minimal risk for pT1a and pT1b tumors, and pT1a-b-c tumors corresponding to tubular, colloidal, or medullar cancers.

Objective. Hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated for patients with minimal residual or no residual disease after primary surgery and chemotherapy for stage III ovarian carcinoma. The use of operative laparoscopy to perform peritonectomy and HIPEC is reported. Methods. Five adult pigs were used. The placement of trocars in the four quadrants was planned in order to complete a total peritonectomy and then to place the HIPEC drains. The umbilical trocar was then replaced manually by the surgeon through a Lapdisc® to manipulate the bowel loops. The abdominal cavity was filled with heated saline (43°C), and the pumps were activated for 30 min. Results. The procedure was successfully completed with an adequate intraabdominal temperature and distribution. Conclusion. These preliminary data suggest the technical feasibility of the laparoscopic approach for HIPEC, in an animal model without carcinomatosis. Our ongoing research is designed to gather pharmacokinetic data in an experimental controlled randomized fashion to compare a laparoscopic to a laparotomy approach on the same model.

Aim This study aimed to evaluate patient information provided, the management of post-operative symptoms and post-operative care, and patient satisfaction with ambulatory breast surgery over a 1-year period. Methods From January to December 2000, all breast cancer patients undergoing conservative breast surgery were offered surgery as an outpatient procedure at the Ambulatory Surgery Unit. Results Two hundred and thirty six patients underwent outpatient surgery. None were readmitted during the first night or the first week. Two hundred and nineteen patients completed a questionnaire. One hundred and sixty nine patients (group 1) underwent wide local excision (WLE) and 50 (group 2), WLE and axillary lymphadenectomy. Patients in group 2 experienced more pain at discharge from the hospital ( p ≤0.01) and during the first week after discharge ( p ≤0.00001) than patients in group 1. The mean overall satisfaction score was 8.97 on a scale of 1–10. Post-operative information provided by the surgeon before discharge from the hospital was rated 8.90 on a scale of 1–10 while information provided by the nurse was rated 9.33 ( p Conclusion Ambulatory surgery for breast cancer patients is safe and popular with patients, however, post-operative pain presents problem.

Many components of mitogenic signalling pathways have been identified over the past 15 years, including the large family of protein kinases. Dysregulation of these biological processes may play an important role in the growth and survival of cancer cells. The 20 members of the fibroblast growth factor (FGF) family transduce a variety of biological signals via distinct transmembrane tyrosine kinase receptors (FGFR1 – FGFR4) encoded by four closely related genes (Powers et al, 2000). Mature FGFR proteins, which act as membrane-spanning tyrosine kinase receptors, have an extracellular ligand-binding domain, a transmembrane domain and a split intracellular tyrosine kinase domain (Green et al, 1996). Fibroblast growth factor -mediated signals have mitogenic, angiogenic and hormone regulatory effects and play key roles in a wide variety of crucial biological activities requiring cell growth, differentiation, migration and chemotaxis. Molecular anomalies of FGFR genes (inappropriate expression, single nucleotide polymorphism (SNP), splice variations, genomic alterations) have been described in several types of human cancer (bladder, cervical, colorectal carcinomas and multiple myeloma) and in skeletal deformities (achondroplasia, Crouzon syndrome and thanatophoric dysplasia type II) (Muenke and Schell, 1995; Avet-Loiseau et al, 1998; Cappellen et al, 1999; Vajo et al, 2000. Bange et al, (2002) recently studied the role of an SNP responsible for a missense mutation (G388R) in the transmembrane domain of FGFR4, in the progression and prognosis of nodepositive breast cancer. This G → A transition changes the sense of codon 388 from Gly (GGG) to Arg (AGG). The authors concluded that the G388R mutation in heterozygous or homozygous state was significantly over-represented in node-positive breast cancer patients with early relapse, but has no role in tumour formation, making this SNP a prognostic marker. On a worldwide basis, they found that allele distribution in normal controls and breast cancer patients did not differ significantly, showing an estimated 45.4% for the Gly/Gly allele, 45.7% for the Gly/Arg allele, and 8.9% for the Arg/Arg allele (Bange et al, 2002). No relationship has been found between this SNP and the prognosis for node-negative breast cancer. Our aim was to confirm the findings of Bange et al on a larger cohort, using an improved PCR – RFLP analysis and a reinforced and more adapted statistical analysis for investigating the possible association between G388R mutation and early cancer progression. Screening was conducted in a cohort of node-positive breast cancer patients who received different adjuvant therapies (endocrine (n=67), or chemotherapeutic (n=72)) and in a cohort of node-negative breast cancer patients (n=95). These cohorts were followed up, respectively, for median periods of 89 and 87 months. PCR – RFLP analysis was modified to make molecular screening more convenient and less time-consuming. Curves for disease-free survival (DFS) were plotted according to the Kaplan – Meier method, and the log-rank test was used for comparisons between groups, as in the study of Bange et al, (Kaplan and Meier, 1958; Cox and Oakes, 1984). Statistical analysis was reinforced by using three other nonparametric linear rank tests (Breslow, Peto – Prentice and Tarone – Ware) (Breslow, 1970; Peto and Peto, 1972; Tarone and Ware, 1977; Prentice, 1978).