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Intravenous administration of monoclonal antibodies leads to low concentrations in the central nervous system, which is a serious concern in neuro-oncology, especially in leptomeningeal carcinomatosis of HER2-overexpressing breast cancer. Case reports of intrathecal (IT) administrations of trastuzumab have shown promising results in these patients but dosing regimens are empirical in absence of pharmacokinetic study. With a population pharmacokinetic approach, we described the fate of trastuzumab after IT administration in 21 women included in a phase I-II clinical trial. Trastuzumab was administered by IT route every week for 8 weeks and both cerebrospinal fluid (CSF) and serum were sampled to measure trough concentrations. Some patients showed noticeable CSF concentration fluctuations predicted using a target-mediated drug disposition. This target was latent and produced with a delayed feedback. Apparent volumes of distribution were close to physiological volumes (V1 = 3.25 L, V2 = 0.644 L, for serum and CSF, respectively). Estimated (constant) transfer from serum to CSF was very slow (k12 = 0.264 mg.d-1 ) while estimated half-life of transfer from CSF to serum was rapid (2.2 days). From the individual parameters of patients, a single IT administration of 150 mg of trastuzumab corresponded to median mean residence times (MRT) of 3.8 days and 15.6 days in CSF and serum, respectively. Survival without neurological relapse was not related to trastuzumab exposure. This study confirms that transfer of trastuzumab from serum to CSF is very limited and that this monoclonal antibody, when administered by IT route, is rapidly transferred to the serum.

BackgroundEarly luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients.MethodsOur study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients. We created a cohort of T1N0 luminal BC patients (tumors between 0.5–2 cm without lymph node metastasis) with metastatic recurrence (“cases”) and corresponding “controls” (without relapse) matched 1:1 on main prognostic factors: age, grade, and proliferation. We deciphered different characteristics of cancer cells and their tumor micro-environment (TME) by deep analyses using immunohistochemistry. We performed in vitro functional assays and highlighted a new mechanism of cooperation between cancer cells and one particular subset of cancer-associated fibroblasts (CAF).ResultsWe found that specific TME features are indicative of relapse in early luminal BC. Indeed, quantitative histological analyses reveal that “cases” are characterized by significant accumulation of a particular CAF subset (CAF-S1) and decrease in CD4+T lymphocytes, without any other association with immune cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, thereby demonstrating their clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic activity is mediated by the CDH11/osteoblast cadherin, consistent with bones being a major site of metastases in luminal BC patients.ConclusionsThis study shows that distant recurrence in T1N0 BC is strongly associated with the presence of CAF-S1 fibroblasts. Moreover, we identify CDH11 as a key player in CAF-S1-mediated pro-metastatic activity. This is independent of tumor cells and represents a new prognostic factor. These results could assist clinicians in identifying luminal BC patients with high risk of relapse. Targeted therapies against CAF-S1 using anti-FAP antibody or CDH11-targeting compounds might help in preventing relapse for such patients with activated stroma.

Purpose: Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemoradiation or to predict relapse during the follow-up period. Experimental Design: We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV E7 gene as a marker for residual disease compared to HPV integration site and PIK3CA mutations. Finally, the prognostic impact of circulating HPV E7 gene was assessed with its prediction value of relapse. Results: HPV E7 gene was the most sensitive tumor marker, superior to both HPV integration sites and PIK3CA mutations in serum. Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (P = 0.02) and para-aortic lymph node involvement (P = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R = 0.39, P < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (P < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2–15) from HPV ctDNA detection. Conclusions: HPV ctDNA detection is a useful marker to predict relapse in cervical cancer. See related commentary by Wentzensen and Clarke, p. 5733

Objectives Vulvar cancer is a gynecological cancer for which posttreatment morbidity must be known to propose the appropriate medical strategy. The objectives of this article were to review and to summarize the available studies evaluating the impact of vulvar surgery on the quality of sex life. Materials and methods We searched MEDLINE abstracts (source PubMed) and included all studies published between 1990 and 2020 that evaluated the impact of vulvar surgery on the patients' sex life. Articles were selected in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. We evaluated the quality of the studies using the "study quality assessment tools" established by the National Heart Lung and Blood Institute and the health-related quality-of-life score. Summary statistics were used to report the results of the studies selected. Results A total of 41 articles were screened, and 15 studies were included in this review. Two questionnaires, that is, European Organization for Research and Treatment of Cancer QLC C30 and Female Sexual Function Index, were used in 60% of the studies. The quality of the studies was heterogeneous. None of them had a high level of evidence. Eleven of the 16 studies reported an impairment of quality of sex life, mainly related to the size of the initial lesion and the type of surgery performed. Preoperative sexual status, that is, active sex life, age, and morbidity seemed to be important factors. Conclusions None of the studies had a high level of evidence, and their methodological quality was heterogeneous. More powerful studies using validated questionnaires are necessary. Because this is essential surgery, patients should be informed that if it impacts their sexual life, management strategies will be part of their postoperative care.

Objective The objective of our study was to analyze quality of life (QOL) in an e-cohort of patients treated for breast cancer (BC) by endocrine therapy (ET), by means of validated quality of life questionnaires. Study design and setting A retrospective, observational, e-cohort study was conducted (Seintinelles platform). Female patients treated for nonmetastatic and nonrecurrent BC, treated in France after 2005, filled in online questionnaires concerning: QOL (QLQ-C30 and QLQ-BR23), tolerability of treatment and demographic characteristics. A multivariate analysis including variables significant on univariate analysis (P Results We included 1,198 patients, 1140 of whom declared that they were taking ET (37.7% tamoxifen, 17.1% aromatase inhibitor (AI), 5.6% LHRH-agonist and 39.6% sequential tamoxifen and AI). Different tolerability profiles were observed when comparing the tamoxifen and AI groups. Treatment adherence was similar in the 2 groups. QOL varied slightly according to the type of ET. On multivariate analysis, ET had no impact on QOL. However, individual patient characteristics (socioeconomic, education and age) were significantly associated with QOL Conclusion Using a real-life study questionnaire on a large e-cohort, individual patient characteristics were strongly associated with deterioration of QOL. The use of e-cohorts must be encouraged to modulate the conclusions of randomized trials.

Over the past century, epidemiologic changes and implementation of screening may have had an impact on tumor doubling time in breast cancer. Our study was designed to evaluate changes in tumor doubling time in breast cancer over the past 80 years. A systematic review of published literature and meta‐regression analysis was performed. An online electronic database search was undertaken using the PubMed platform from inception until June 2020. All studies that measured tumor doubling time in breast cancer were included. A total of 151 publications were retrieved. Among them, 16 full‐text articles were included in the qualitative analysis. An exponential growth model was used for quantitative characterization of tumor growth rate. Tumor doubling time has remained stable over the past 80 years. Recent studies have not only identified “fast growing tumor” (grade 3, human epidermal growth factor receptor 2‐positive, triple‐negative, or tumor with an elevated Ki‐67) but also “inactive breast cancer” feeding the ongoing debate of overdiagnosis due to screening programs. The stability of tumor doubling time over the past 80 years, despite increasing and changing risk factors, supports the validity for our screening guidelines. Prospective studies based on more precise measurement of tumor size and adjustment for tumor characteristics are necessary to more clearly characterize the prognostic and predictive impact of tumor doubling time in breast cancer., The stability of tumor doubling time over the past 80 years, despite increasing and changing risk factors, supports the validity of our screening guidelines. Recent studies have not only identified “fast growing tumor” but also “inactive breast cancer” feeding the ongoing debate of overdiagnosis due to screening programs.

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

High-grade serous ovarian cancer is one of the deadliest gynecological malignancies and remains a clinical challenge. There is a critical need to effectively define patient stratification in a clinical setting. In this study, we address this question and determine the optimal number of molecular subgroups for ovarian cancer patients. By studying several independent patient cohorts, we observed that classifying high-grade serous ovarian tumors into four molecular subgroups using a transcriptomic-based approach did not reproducibly predict patient survival. In contrast, classifying these tumors into only two molecular subgroups, fibrosis and non-fibrosis, could reliably inform on patient survival. In addition, we found complementarity between transcriptomic data and the genomic signature for homologous recombination deficiency (HRD) that helped in defining prognosis of ovarian cancer patients. We also established that the transcriptomic and genomic signatures underlined independent biological processes and defined four different risk populations. Thus, combining genomic and transcriptomic information appears as the most appropriate stratification method to reliably subgroup high-grade serous ovarian cancer patients. This method can easily be transferred into the clinical setting.

Ovarian cancer is mostly diagnosed at advanced stage. Better survival is achieved through complete debulking surgery and chemotherapy. Historically, neoadjuvant chemotherapy (NAC) has been introduced for unresectable disease to decrease tumor load and perform a unique complete surgery. Four randomized control trials have compared primary debulking surgery to NAC, but there is still controversy about the use of neoadjuvant chemotherapy and questions about its modalities. Areas covered: We made a review of knowledge on benefits of NAC compared to primary debulking chemotherapy, in terms of survival and morbidity, methods of administration, new drugs in early and late phase trials, the selection of patients. Similar survival was observed after NAC and interval debulking surgery or primary debulking surgery. Morbidity of surgery was decreased after interval debulking compared primary debulking surgery. Conventional drugs are carboplatin and paclitaxel. Safety of bevacizumab was evaluated in phase 2 trials associated with conventional drugs. Immunotherapy trials are enrolling patients in phase 1 study. Expert commentary: NAC followed by debulking surgery is the best treatment for patients with advanced ovarian cancer.

Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence, and prognosis remain controversial in the literature. The 2012 WHO classification of breast cancer categorizes neuroendocrine carcinomas into three morphologically distinct subtypes: well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. We aimed to gain insight into the clinical, morphologic, phenotypic, and molecular features of 47 neuroendocrine breast carcinomas. Targeted next-generation sequencing by an AmpliSeq 22 cancer gene hotspot panel and the Prosigna assay were performed on 42/47 and 35/47 cases, respectively. Average age at diagnosis was 69 years. All tumors were estrogen receptor-positive and the large majority expressed progesterone receptor (89%), GATA3 (98%), FOXA1 (96%), and CK8/18 (98%). There was an almost equal distribution of luminal A (52%) and B (48%) carcinomas. Almost half of the cohort (49%) displayed a high risk of recurrence score with the Prosigna test. Patients with a neuroendocrine carcinoma had a shorter disease-free survival compared with those affected by carcinomas of no special type matched for age, size, grade, and estrogen receptor status. No significant differences were observed in terms of overall survival. Stratification of neuroendocrine carcinomas using the 2012 WHO criteria did not reveal statistically significant differences among the distinct categories (well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and invasive breast carcinomas with neuroendocrine differentiation), in terms of either progression-free or overall survival. Our targeted sequencing analysis found three cases (7%) harboring a PIK3CA mutation, and in three other cases (7%) TP53 mutations were detected. This study showed that neuroendocrine breast carcinoma is a distinct subtype of luminal carcinoma with a low rate of PIK3CA mutations and with an aggressive clinical behavior. An accurate identification of neuroendocrine differentiation may be useful to better tailor patient adjuvant therapy within luminal carcinomas.Modern Pathology advance online publication, 8 September 2017; doi:10.1038/modpathol.2017.107.

Although fibroblast heterogeneity is recognized in primary tumors, both its characterization in and its impact on metastases remain unknown. Here, combining flow cytometry, immunohistochemistry and RNA-sequencing on breast cancer samples, we identify four Cancer-Associated Fibroblast (CAF) subpopulations in metastatic lymph nodes (LN). Two myofibroblastic subsets, CAF-S1 and CAF-S4, accumulate in LN and correlate with cancer cell invasion. By developing functional assays on primary cultures, we demonstrate that these subsets promote metastasis through distinct functions. While CAF-S1 stimulate cancer cell migration and initiate an epithelial-to-mesenchymal transition through CXCL12 and TGFβ pathways, highly contractile CAF-S4 induce cancer cell invasion in 3-dimensions via NOTCH signaling. Patients with high levels of CAFs, particularly CAF-S4, in LN at diagnosis are prone to develop late distant metastases. Our findings suggest that CAF subset accumulation in LN is a prognostic marker, suggesting that CAF subsets could be examined in axillary LN at diagnosis., Cancer associated fibroblasts are known to promote the progression of cancer. Here, the authors show that two particular subsets of cancer associated fibroblasts induce metastasis but work via distinct mechanisms including, chemokine signalling and Notch signalling.

A subset of cancer-associated fibroblasts (FAP+/CAF-S1) mediates immunosuppression in breast cancers, but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 19,000 single CAF-S1 fibroblasts from breast cancer. We validate the five most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extracellular matrix proteins and TGFβ signaling, respectively, are indicative of primary resistance to immunotherapies. Cluster 0/ecm-myCAF upregulates PD-1 and CTLA4 protein levels in regulatory T lymphocytes (Tregs), which, in turn, increases CAF-S1 cluster 3/TGFβ-myCAF cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance. Significance: Our work provides a significant advance in characterizing and understanding FAP+ CAF in cancer. We reached a high resolution at single-cell level, which enabled us to identify specific clusters associated with immunosuppression and immunotherapy resistance. Identification of cluster-specific signatures paves the way for therapeutic options in combination with immunotherapies. This article is highlighted in the In This Issue feature, p. 1241

Centrosome amplification has been described as a common feature of human cancers and it is known to promote tumorigenesis when induced in animals. However, little is known about the real status of centrosome numbers in human cancers and whether numerical alterations are solely associated with poor prognosis. To address this question, we have analyzed a large cohort of human epithelial ovarian cancers (EOCs) from 100 patients using state-of-the-art microscopy to determine the Centrosome-Nucleus Index (CNI) of each tumor. We found that EOCs are highly heterogeneous, with infrequent but strong centrosome amplifications leading to higher CNI than in healthy tissues. Strikingly, while a correlation between CNI and genomic alterations, such as aneuploidy or chromosome rearrangements could not be established, we found that high CNI correlates with increased patient survival and sensitivity to chemotherapy. Using ovarian cancer cellular models to manipulate centrosome numbers and Patient-Derived Xenografts (PDXs), we found that higher CNIs can positively impact the response to chemotherapy and inhibit cell dissemination. Our findings highlight a novel paradigm linking centrosome amplification to the inhibition of tumor progression.

Background Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC. Methods We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR. Results HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013). Conclusion This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse., Highlights • HPV ctDNA can be detected before CRT in patients with LACC (69%). • HPV-ctDNA detection was associated with tumor stage and lymph node status. • A lower detection rate of HPV ctDNA was observed for HPV18 genotype. • Residual ctDNA levels after CRT and during follow-up had a prognostic impact.

Background: Recent molecular biology technologies reveals insight into tumor heterogeneity but quantification and impact on reproducibility of tests is not well known. The objective of this study was to assess the extent to which tumor heterogeneity may affect the prognosis of patients assessed by Prosigna™ (PAM50) gene signature assay compared to test reproducibility. Methods: Reproducibility was measured by testing replicate tissue sections from 186 FFPE breast tumor blocks across 2 sites (Institut Curie, Centre Jean Perrin) following independent pathology review at each site. Consecutive slides came from blocks of patients included in the Decision Impact prospective study which examined whether the Prosigna™ test influences adjuvant treatment decision (Clinical trial information: NCT02395575). To evaluate heterogeneity and its impact in terms of outcome, we selected among T1N0 patients treated in Institut Curie between 2003 and 2008, 32 patients who did recur and 28 matched control group who did not (2 'controls' recurred during the study). Analyses were performed on two parts of each tumor. NanoString's Prosigna™ outputs (risk of recurrence (ROR) score, 10 year probability of distant recurrence, risk category, and intrinsic subtype (Luminal A/B, HER2-enriched, Basal-like)) were measured and compared to evaluate heterogeneity (defined as difference in terms of subtype and/or risk category between the two parts) and reproducibility. Correlation between heterogeneity and outcome was performed. Impact was assessed by tumor board analysis. Results: Pearson correlation coefficients for ROR score and probability of distant recurrence predicted were .95 and .97, respectively in the reproducibility study and .82 and .86, in the tumor heterogeneity study. The measured standard deviation (SD) was 5.4 and 8.1 ROR units corresponding to 1.6% and 2.8% in terms of risk of distant metastasis free survival within the reproducibility study and the tumor heterogeneity study, respectively. Kappa coefficients for intrinsic subtype and risk category agreement were 0.88 and 0.87 in the reproducibility study, and 0.67 and 0.58 in the tumor heterogeneity study. Tumor board analysis of discordant cases showed that the impact, in terms of decision of chemotherapy administration, concerns 3% of patients because of reproducibility and 8% because of tumor heterogeneity, comparing favorably with the discordance between Prosigna™ and immunohistochemistry (27%). Probability of distant recurrence was higher in the cases (15%) compared to control (9%) (p=.001) in the tumor heterogeneity study confirming the performance of the Prosigna™ test. Conclusion: We validated in the prospective Decision Impact study the analytical performance of NanoString's Prosigna™ assay across multiple clinical testing laboratories. We showed in these two studies that tumor heterogeneity has more impact than reproducibility performance. The clinical impact on the decision making based on tumor heterogeneity is however limited, since it does not correlate to outcomes, whereas the Prosigna™ ROR score has been shown to correlate very well to outcomes. Citation Format: Rouzier R, Bonneau C, Cayre A, Hequet D, Gentien D, Bonhomme A, Mouret-Reynier M-A, Dubot C, Cottu P, Roulot A, Morel P, Salomon A, Callens C, Guinebretiere J-M, Penault-Llorca F. Evaluation of intra-tumor heterogeneity, test reproducibility and their impact in breast cancer samples assessed by Prosigna™: Results from a decision impact prospective study and a matched case-control study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-04.

Summary Background and aim Persistent postsurgical pain (PPP) has been reported by patients following various surgeries. Body contouring procedures are being performed more frequently, but no data are available regarding the effects of these procedures. Long-term disability occurring after performing "functional" procedures on healthy subjects is a particular concern. The aim of this study was to describe the risk factors, prevalence, characteristics, and effects of persistent pain after body contouring procedures. Methods Patients who underwent body contouring surgery (e.g., abdominoplasty, lower body lift, medial thigh lift, brachioplasty, and abdominal liposuction) between January 1 2009 and December 31 2013 were included in this retrospective, monocentric cohort study. Pain evaluation was performed using a visual analog pain scale (VAS) and the Douleur Neuropathique 4 (DN4) questionnaire. Major risk factors previously identified in the literature were evaluated. Results The study included 199 patients. Pain was reported by 42 patients (21%). Seventy-one percent ( n = 30) of these 42 patients presented with neuropathic pain. Risk factors that were significantly associated with PPP were acute postoperative pain ( p = 0.0003), medical history of bariatric surgery ( p = 0.002), longer period of hospitalization ( p = 0.04), depressive status during the operative period ( p = 0.03), substantial stress before surgery ( p = 0.03), and major complications after surgery ( p = 0.03). Conclusion Persistent chronic pain is frequent after body contouring procedures. Preemptive approaches and early postoperative diagnosis are important measures that can be used to limit the effects of this complication on the patient's quality of life.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The most common subtype of EOC is high-grade serous (HGSOC), which responds at least initially to chemotherapy but has a worse overall prognosis. Genomic, transcriptomic, and proteogenomic profiling of HGSOC suggested a whole spectrum of molecular diversity, including homologous recombination pathway deficiencies (HRD). The centrosome is the main microtubule (MT)-organizing center of animal cells. It facilitates the accuracy of chromosome segregation during mitosis and influences cell polarity and migration. The presence of more than two centrosomes in a cell, centrosome amplification, has long been associated with tumorigenesis. However, little is known about the real status of centrosome numbers in human cancers and whether numerical alterations are solely associated with poor prognosis. We screened 100 samples of primary EOCs including 88 HGSOC, using immunofluorescence and state-of-the-art microscopy, to determine the centrosome-nucleus index (CNI). We integrated these data with genomic alterations, HRD status, and patient outcome. We found that EOCs are highly heterogeneous, with infrequent but strong centrosome amplifications leading to higher CNI than in healthy tissues. Strikingly, while a correlation between CNI and genomic alterations, such as aneuploidy or chromosome rearrangements, could not be established, we found that high CNI correlates with increased patient survival and sensitivity to chemotherapy, independently of HRD status. Using ovarian cancer cellular models to manipulate centrosome numbers and patient-derived xenografts (PDXs), we found that higher CNIs can positively impact the response to chemotherapy and inhibit peritoneal cell dissemination. Citation Format: Jean-Philippe Morretton, Aurelie Herbette, Camille Cosson, Bassirou Mboup, Aurelien Latouche, Pierre Gestraud, Tatiana Popova, Marc-Henri Stern, Fariba Nemati, Didier Decaudin, Guillaume Bataillon, Veronique Becette, Didier Meseure, Andre Nicolas, Odette Mariani, Claire Bonneau, Jorge Barbazan, Anne Vincent-Salomon, Fatima Mechta-Grigoriou, Sergio Roman-Roman, Roman Rouzier, Xavier Sastre-Garau, Oumou Goundiam, Renata Basto. Centrosome amplification favors survival and impairs ovarian cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A43.

Purpose Leptomeningeal carcinomatosis (MC) is commonly associated with HER2-positive breast cancer (HER2-BC), with a poor prognosis and no standardised treatment. We conducted a phase I dose-escalation study of intrathecal (IT) administration of trastuzumab in HER2-BC patients with MC to determine the maximum tolerated dose (MTD), which was based on both the achievement of a trastuzumab intra-cerebrospinal fluid concentration close to a conventional therapeutic plasma concentration (30 mg/L) and/or dose-limiting toxicity (DLT). Methods The protocol planned IT administration of trastuzumab (30 mg, 60 mg, 100 mg or 150 mg dose levels) once a week, over the course of at least 4 weeks. Sixteen patients with MC from HER2-BC received IT trastuzumab. Intra-cerebrospinal fluid samples were obtained before each injection for pharmacokinetics. Results We did not observe DLT of IT trastuzumab. Eleven patients had no toxicity attributed to IT trastuzumab. For 60 mg or higher dose levels, minor toxicities attributed to IT trastuzumab included headache (2 patients), nausea (2 patients), vomiting (1 patient), cervical pain (1 patient) and peripheral neuropathy (1 patient). Two patients experienced immediate toxicity including headache or vomiting. The mean residual intra-cerebrospinal fluid concentration of trastuzumab was 27.9 mg/L for the 150 mg dose level. Three patients achieved a clinical response, seven patients had stable disease and four patients had progressive disease. Conclusions The MTD and recommended phase II weekly dose of IT trastuzumab in patients with HER2-BC and MC is 150 mg. A phase II trial using this dose regimen in MC from HER2-BC is ongoing. Registration identification ClinicalTrials.gov Identifier: NCT01373710 ( https://clinicaltrials.gov/ct2/show/NCT01373710?term=trastuzumab+intrathecal&rank=1 ).

BACKGROUND/AIM We aimed to evaluate the impact of bevacizumab on the lymphocele rate in patients after complete cytoreductive surgery for advanced ovarian cancer. PATIENTS AND METHODS This retrospective study included patients with advanced ovarian cancer who had undergone complete cytoreductive surgery with pelvic and para-aortic lymphadenectomy at the Gustave Roussy Institute from 2005 to 2014. The introduction of bevacizumab was discussed in a multidisciplinary meeting. RESULTS During the study period, 247 patients were included; 24.6% of patients (61 patients) received adjuvant bevacizumab. The rate of symptomatic lymphocele was 34% (84 patients). In the lymphocele group, patients tended to receive adjuvant bevacizumab more often than did the control group (32% and 21%, respectively, p=0.05). In multivariate analysis, bevacizumab was not significantly associated with the risk of symptomatic lymphocele (hazard ratio(HR)=1.62, 95% confidence interval(CI)=0.87-3.01, p=0.12). CONCLUSION Adjuvant bevacizumab has no impact on the formation or duration of symptomatic lymphocele in patients after complete cytoreductive surgery for advanced ovarian cancer.

BACKGROUND: The benefit of chemotherapy for patients with estrogen receptor(ER)+ HER2- breast cancers is an ongoing question. The evaluation of the tumor's proliferation by Ki67 may guide the indication but no consensual predictive cut-off has been set yet. MATERIALS AND METHODS: This study included women with a first ER+HER2- invasive breast cancer treated by primary surgery between 2003 and 2008. Data was collected prospectively. Ki67 cut-off was sequentially set each 1% from 5% to 30%. For each threshold, the interaction between Ki67 and adjuvant chemotherapy was integrated in a multivariate Cox model to determine when it became statistically significant in predicting distant-disease free survival (DDFS). Using different Ki67 cut-offs, we also compared DDFS of patients who had or not an indication of chemotherapy, depending on whether they actually received it or not. RESULTS: Among the 3221 breast cancers, median Ki67 was 10%, with a mean of 15% (S.D = 14). Ki67 was an independent prognosis factor whether the cut-off was set to 14% or to 20% (p CONCLUSION: In ER+ HER2- breast cancers, a Ki67 level of expression >= 20% was predictive of benefit from adjuvant chemotherapy. A threshold at 14% was not as discriminant. Based on this large cohort study, we recommend the use of a cut-off at 20% to decide whether patientes with ER positive tumors should receive chemotherapy or not/. Citation Format: Rouzier R, Rossi L, Lerebours F, Savignoni A, Falcou M-C, Bonneau C, Pierga J-Y, Guinebretière J-M. Ki67 cut-off point to predict the benefit of adjuvant chemotherapy in ER+ HER2- breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-63.

Comment inBreast cancer: Fibroblast subtypes alter the microenvironment. [Nat Rev Clin Oncol. 2018]; International audience; Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, we characterize four CAF subsets in breast cancer with distinct properties and levels of activation. Two myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. These data are consistent with FOXP3+ T lymphocyte accumulation in CAF-S1-enriched TNBC and show how a CAF subset contributes to immunosuppression.

To describe the characteristics of patients with colorectal endometriosis and extraserosal pelvic fascia (EPF) involvement and to assess the effect of EPF resection.Prospective cohort study (Canadian Task Force classification II-2).University hospital.Two hundred twenty-seven patients who underwent segmental colorectal resection to treat symptomatic deep infiltrating endometriosis between 2001 and 2011, with or without EPF resection.Segmental colorectal resection with or without EPF resection.One hundred twelve patients (49.4%) required EPF resection. In these patients the total American Society for Reproductive Medicine endometriosis scores were higher (p = .004), there were more associated resected lesions of deep infiltrating endometriosis (p.001), and the operative time was longer (p.001). They were more likely to require blood transfusion (p = .003) and to experience intraoperative complications (p = .01) and postoperative voiding dysfunction (p = .04).EPF infiltration reflects disease severity in patients with colorectal endometriosis. Its removal affects intraoperative morbidity and leads to a higher rate of voiding dysfunction.

Resume L’objectif de ce travail est de decrire l’apport respectif de l’echographie pelvienne et de l’IRM pour differencier tumeurs myometriales benignes et malignes. Cliniquement, les sarcomes sont souvent decouverts devant des symptomes non specifiques comme des metrorragies post-menopausiques ou une augmentation rapide du volume uterin. En echographie, des criteres simples comme le caractere unique d’une lesion, une origine non myometriale, un endometre anormal doivent faire remettre en cause le diagnostic de leiomyome. Par ailleurs, une hypervascularisation tumorale et une distribution vasculaire irreguliere sont souvent decrites dans la pathologie maligne. En IRM, les sarcomes se presentent sous la forme de masses souvent uniques, de signal T2 intermediaire, heterogene, sieges de frequents remaniements hemorragiques intratumoraux. Parfois la presentation est celle d’un epaississement endometrial majeur. Leur rehaussement est heterogene apres injection. L’utilite de l’etude dynamique apres injection n’a pas ete prouvee. Les sarcomes sont toujours en hypersignal en diffusion, avec un ADC significativement plus bas que dans les lesions benignes. Un ADC

Background To predict the individual benefit of adjuvant chemotherapy (CT) is challenging especially in estrogen receptor tumors HER2 negative tumors. Existing tools are based on data from randomized trials or on genomic tests with benefit calculated for outmoded CT. The aim of this study was to develop an exportable model to predict from real life data the invidual benefit of adjuvant anthracyclines/taxanes based CT. Patients and methods Women with estrogen receptor-positive HER2-negative tumors without metastasis at the time of the diagnosis treated at the Institut Curie - Centre René Huguenin (St Cloud, France) between 2000 and 2008 were included. Clinical characteristics, pathological data and information concerning the treatments and outcomes had been prospectively registered. We divided the study population into 2 groups: patients who did not receive adjuvant CT and patients who did. Multivariate survival analysis and prediction were performed according to the Cox model (proportional hazard model). Non-informative variables in the Cox model were excluded from the final model. The individual benefit of CT was calculated by comparing predicted distant disease-free survival without chemotherapy (using a model constructed in patients treated without adjuvant CT) and modeled distant disease-free survival with CT. Benefit of chemotherapy was validated by cross validation and compared to Adjuvant online predictions. Results Data from 3385 women were available: 2137 treated without adjuvant chemotherapy and 1248 with. The models to predict survival without and with CT were based on tumor size, number of metastatic nodes, grade and KI67 (all patients had ER-positive-HER2 negative tumors). The discrimination and the calibration of the models were excellent: C-index were 0.81 and 0.76 for patients treated without and with CT. In this population, the mean 10-year benefit provided by CT was 6.2% (median: 1.5%, min: -4%, max: 35%). The accuracy of the model was internally validated and over-performed predictions of adjuvant online because Ki67 and HER2 status are included in our model (p Conclusion We constructed a tool to evaluate the benefit of adjuvant anthracycline / taxane at an individual level. This tool is based on a model that outperform currently availble methods. Citation Format: Rouzier R, Stevens D, Bonneau C, Falcou M-C, Hequet D, Pierga J-Y, Lerebours F. Development of individual adjuvant chemotherapy benefit estimating program for breast cancer patients management. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-07-05.

Objective To evaluate ultrasonography and magnetic resonance imaging (MRI) performance in differentiating benign leiomyomas from malignant mesenchymal or mixed tumors (MMT) and smooth muscle tumors of uncertain malignant potential of the uterus (STUMP). Design Retrospective cohort study. Setting University hospital, France. Population One hundred and eight women who underwent imaging before surgery for uterine mesenchymal tumor (85 with benign leiomyomas and 23 with MMT/STUMP). Methods The ultrasonography reports were reviewed. Conventional, perfusion and diffusion MRI were blindly analyzed. Recursive partitioning analysis (RPA) was performed to construct diagnostic flowcharts. Main outcome measures Accuracy of a diagnostic flowchart. Results At ultrasonography, single tumor, non-myometrial origin, absence of acoustic shadowing, thickened endometrium and ascites were associated with MMT/STUMP (p = 0.001, p

International audience; Objectives: To validate a model predicting the risk of threatened preterm delivery and to establish the optimal threshold for this risk scoring system. Materials and methods: Two cohorts were studied: one of singleton pregnancies without preterm premature rupture of membranes (PPROM) and no cervical cerclage (cohort 1) and one of twin pregnancies without PPROM and no cervical cerclage (cohort 2). Patients were included from January 1st 2013 until December 31st 2013 by the Regional Perinatal Network of Ile de France with patients transferred because of threatened preterm delivery at 22 to 32 weeks of gestation. The individual probability of delivery within 48 hours of admission was calculated using the nomogram for every patient. Discrimination and calibration of the nomogram as well as the optimal threshold were determined using R studio. Results: The nomogram accurately predicted obstetric outcome. Discrimination and calibration were excellent, with an area under the curve (AUC) of 0.88 (95% CI 0.86-0.90) for cohort 1 and 0.73 (95% CI 0.66-0.80) for cohort 2. The optimal threshold would be 15% for cohort 1 and 10% for cohort 2. Using these thresholds, the performance characteristics of the nomogram were: sensitivity 80% (cohort 1) and 69% (cohort 2), negative predictive value 94.8% (cohort 1) and 91.3% (cohort 2). Use of the nomogram would avoid 253 unnecessary transfers in cohort 1. Conclusions: The nomogram was efficient and clinically relevant in our high risk population. A threshold set at 15% would help minimize the risk of preterm deliveries in singleton pregnancies and should reduce unnecessary, costly and stressful in utero transfer.

International audience; Aim: To assess the decrease in the number of bowel resections (BR) necessary to achieve complete cytoreduction (CC-0) in advanced epithelial ovarian cancer (EOC) permitted by neoadjuvant chemotherapy (NAC). Patients and Methods: Patients were selected from a population of advanced EOC cases diagnosed between 2002 and 2009 at the Curie Institute: 97 patients with Federation International of Gynecology and Obstetrics IIIc and IV with unresectable disease treated with NAC followed by interval debulking surgery were included. We proceeded to a systematic blinded review of all the surgical reports pre-and post-NAC by two different surgeons to assess the surgical procedures required to obtain CC-0. Results: Before NAC, at least 84 patients (87%) would have required BR to obtain a CC-0 resection. At interval debulking surgery, 47 (49%) still required a BR, which corresponds to a decrease of 38% (p

Lymph node status is a major prognostic element in endometrial cancer and affects the choice of adjuvant therapy. The sentinel lymph node (SLN) procedure is proposed as an alternative to lymphadenectomy. This review aims to assess its feasibility. To this end, 19 studies have been analysed. It appears that double detection (colorimetric and isotopic) is better than single detection, independent of injection site. Hysteroscopic injection is technically more difficult, yet can be done near the tumoral lesion. The cervical site does not accurately reflect the lymphatic drainage of the uterine body but is easier to access. SLN detection rate is notably identical between these two injections sites. Lomboaortic detection rate is lower for cervical injections than for endometrial ones. The myometrial site is also difficult to access (intraoperatively), due to same limitations as the hysteroscopic route, and can be deceiving (insufficient detection rate and high false-negative rate). The SLN allows for ultrastadification (micrometastases and isolated tumoral cells) with the development of new pathological techniques (serial sections and immunohistochemistry). Data on SLN in endometrial cancer is very heterogeneous in terms of methodology and populations studied. Despite being well-known, the SLN procedure in endometrial cancer remains in its feasibility stage. Its place in therapeutic strategies needs to be further explored and its potential benefit remains to be confirmed.

International audience; Background: The aim of this study is to evaluate a new tumour marker, HE4, and to compare it with CA125 in predicting optimal cytoreduction and response to chemotherapy. Thirty patients with advanced epithelial ovarian cancer and multiple sera harvested during neoadjuvant chemotherapy (NAC) were included. Results: Based on ROC curves analysis, CA125 ≤ 75 UI/ml and HE4 ≤ 252 pmol/L after the 3rd cycles of NAC, with a sensitivity of 93.7 % and a specificity of 92.3 % (PPV = 93.7 % and NPV = 92.3 %), offered the best combination for predicting optimal cytoreduction. In addition, the HE4 value of 115 pmol/L is the best cut-off level for identifying platinum-sensitive patients. Conclusions: The introduction of HE4 as a new tool for predicting platinum-sensitivity and interval optimal cytoreduction is promising.

International audience; Breast cancer involves various types of tumors. The objective of this review was to provide a summary of the main methods currently available in clinical practice to characterize breast cancers at a molecular level and to discuss their prognostic and predictive values. Hormonal receptors expression and the HER2 status are prognostic markers and can also predict the response to targeted therapies. Their analysis through immunohistochemistry is systematical. Ki67 is an effective prognostic marker, but its reliability is debated because of its low reproducibility between laboratories and between pathologists. Commercial genomic signatures are all considered valid prognostic tools and may guide physicians to make therapeutic choices. These signatures are costly and should therefore be restricted to situations in which the use of chemotherapy remains equivocal.

Objective To show an external validation of the Endometriosis Fertility Index (EFI) and to observe cumulated pregnancy rates after infertility management combining surgery and assisted reproductive technologies (ART). Design Observational study from January 2004 to December 2012. Setting Tertiary-care university hospital and ART center. Patient(s) Four hundred twelve infertile and endometriotic patients after laparoscopic surgery. Intervention(s) Surgical diagnosis and treatment followed by spontaneous fertility or ART management. Main Outcome Measure(s) Spontaneous pregnancy rates and cumulative (spontaneous and ART) pregnancy rates according to the EFI. Result(s) A significant relationship between EFI and spontaneous pregnancy rates was observed at 12 months ( P =.001). The least function score and complete removal of endometriotic lesions and pelvic adhesions were significantly associated with spontaneous pregnancy ( P =.006). Cumulative pregnancy rate at 18 months was 78.8%. ART benefits for pregnancy rates were higher for patients with poor EFI. Conclusion(s) External validation of the EFI in a French population was demonstrated. Combining surgery for endometriosis and ART led to a 78.8% pregnancy rate at 18 months after surgery.

International audience; Aims: In patients with breast cancer, the association between the number of sentinel lymph node (SLN) removed and survival is poorly known. Our objective was to evaluate this association on disease-specific survival (DSS). Methods: Data of 144 517 patients with invasive T1-3M0 breast carcinoma and initial treatment with SLN biopsy were extracted from the SEER database. Univariate and multivariate analyses were performed. Results: The number of SLNs harvested and the completion of axillary lymph node dissection (ALND) were not associated with DSS improvement for patients without metastatic nodes. After adjustment, patients with three SLNs had a better DSS than did other groups (HR of 0.73 CI 95% [0.60e0.88], p 1/4 0.001). This result was mainly driven by the group of patients with one metastatic LN. When patients had two or more metastatic LNs, there was no difference in DSS according to the number of SLNs or to completion of ALND. Conclusions: The number of SLN harvested was associated with DSS. According to DSS, the optimal number of SLNs harvested was three in this large series, thereby calling into question the understaging or undertreatment of SLN biopsy in which only one or two SLNs are harvested but also the therapeutic effect of completion ALND.

Aim The objective of this study was to determine the effects of axillary lymph node dissection (ALND) versus sentinel lymph node biopsy alone (SLNB) on the survival of patients with 3 or more metastatic lymph nodes (MLN) in invasive breast cancer. Methods Data of 9521 patients with invasive T1-2M0 breast carcinoma and initial treatment with SLNB completed or not by ALND and 3 or more MLN were extracted from the SEER database. Univariate and multivariate analyses were performed. Results Overall, 9521 patients were included in the study. SLNB-alone compared with ALND did not result in different overall survival (OS) or specific survival (SS) for patients with 3 or more MLN (p = 0.46 and 0.58, respectively). In subgroup analyses, OS was comparable between SLNB-alone and ALND when patients had only 3 or more than 3 MLN. When patients had 3 MLN, the 5-year SS was significantly better for patients with ALND compared with SLNB-alone: 91.5% and 85.1%, respectively (p = 0.02). The Hazard Ratio (HR) for OS comparing SLNB-alone with ALND adjusting for age, adjuvant radiotherapy, tumor size, estrogen receptor status, grade and tumor type resulted in an HR of 1.05 (95% CI, 0.72–1.54, p = 0.77). Conclusion In conclusion, patients with a T1–T2 invasive breast cancer and at least 3 MLN do not benefit from ALND after SLNB for specific and overall survival, thus limiting ALND to a staging procedure. A subgroup of patients with 3 MLN had a better SS with ALND, possibly due to an under-staging of the SLNB-alone group.

Objective DNA repair mechanisms, environment-mediated drug resistance and cancer initiating cells (CIC) are three major research concepts that can explain the chemoresistance of epithelial ovarian cancer (EOC). The objective was to test if changes in the expression of potential markers associated with drug resistance before and after chemotherapy would correlate with platinum resistance, defined as a recurrence within the first year after chemotherapy cessation, and with survival, in advanced EOC. Methods We included 32 patients with stage IIIC–IV EOC who underwent laparoscopy to evaluate the extent of carcinomatosis, neoadjuvant chemotherapy (carboplatin/taxol) and interval surgery. Biopsies taken during the initial laparoscopies and interval surgeries were evaluated using immunohistochemistry for the expression of 7 proteins: CD117, CD44 and ALDH1 to evaluate CIC; IL-6, IL-8 and BMP2 to evaluate environment-mediated drug resistance; and ERCC1 to evaluate DNA repair. Expression measurements were correlated with platin resistance and survival. The markers' relevance was confirmed in vitro using chemoresistance tests and flow cytometric measurements of the proportion of CD44+ cells. Results 17 patients were chemoresistant and 15 patients were chemosensitive. We observed increases in CD44, IL-6 and ERCC1 expression and stable ALDH1, CD117, IL-8, and BMP2 expression. Reduced expression of cancer initiating cell markers and increased expression of environment-mediated drug resistance markers were associated with poor prognosis. We also demonstrated that CD44+ cells had survival advantages in vitro . Conclusions Changes in CD44 and IL-8 expression on tumor cells appeared to correlate with overall survival and should be further tested as predictors of chemoresistance using larger cohort.

Objective To compare the efficacy and the safety of flexible ureterorenoscopy (f-URS) in the treatment of kidney stones according to the body mass index (BMI), which seems to be less influenced by weight compared with shock wave lithotripsy and percutaneous nephrolithotomy. Methods We conducted a retrospective monocentric study in patients with a known BMI who underwent an f-URS for kidney stones between 2006 and 2008. Success rates in the obese patients (OP) group (BMI ≥30 kg/m 2 ) were compared with success rates in the normal weight patients (NWP) control group (BMI 2 ). Patients with a BMI ≥40 kg/m 2 were defined as morbidly obese patients (MOP), a subgroup of the OP group. The success was defined as a stone-free status (no or ≤2 mm residual stone) at the time of control, 3 months after the procedure assessed by kidneys-ureters-bladder radiography coupled with ultrasound (only in NWP with radiopaque stones), or computed tomography-scan. Results A total of 327 procedures were performed, including 97 f-URS in 87 OP (including 14 procedures in 13 MOP) and 230 procedures for 188 NWP. The overall success rate was 67.4% and 68% in the NWP and OP, respectively; P = .91 (71.4% in the MOP subgroup). Success rates decreased with an increasing stone size without any differences between the groups. Regardless of location and stone size ( 20 mm), there was no statistical difference in the success rate. Postoperative morbidity was similar in both groups and occurred in 2.44% of cases. Conclusion f-URS for kidney stones resulted in similar outcomes in NWP and OP, and even MOP, regardless of stone size and location and with equivalent morbidity.

International audience; Objective. To evaluate the different kinetic parameters of serum CA125 during neoadjuvant chemotherapy (NAC) to predict optimal interval debulking surgery (IDS). Methods. The present retrospective multicenter study included patients with advanced ovarian cancer treated with neoadjuvant platinum-based chemotherapy followed by IDS between 2002 and 2009. Demographic data, CA125 levels, radiographic data, chemotherapy and surgical-pathologic information were obtained. Univariate and multivariate analyses were performed to evaluate variables associated with complete IDS. ROC analysis was used to determine potential cut-off values to predict the likelihood of complete cytoreduction via IDS. Results. One hundred and forty-eight patients met the study criteria. Ninety-three patients (62.8%) had optimal cytoreduction with no residual macroscopic disease (CC-0) after IDS. In multivariate analyses, the CA125 level after the 3rd NAC was an independent predictor for optimal cytoreduction (odds ratio: 0.98 [0.97-0.99], p = 0.04). The area under the ROC curve was 0.73. A threshold of 75 UI/ml displayed the most predictive power. The odds ratio to predict complete cytoreduction was 3.29 [1.56-7.10] (p = 0.0008). Conclusion. Our data indicate that for advanced ovarian cancer, a CA125 level less than 75 UI/ml after the 3rd NAC was an independent predictor factor for complete IDS.

To retrospectively evaluate the ability of magnetic resonance imaging (MRI) to differentiate malignant from benign myometrial tumours. Fifty-one women underwent MRI before surgery for evaluation of a solitary myometrial tumour. At histopathology, there were 25 uncertain or malignant mesenchymal tumours and 26 benign leiomyomas. Conventional morphological MRI criteria were recorded in addition to b 1,000 signal intensity and apparent diffusion coefficient (ADC). Odds ratios (OR) were calculated for each criterion. A multivariate analysis was performed to construct an interpretation model. The significant criteria for prediction of malignancy were high b 1,000 signal intensity (OR = +∞), intermediate T2-weighted signal intensity (OR = +∞), mean ADC (OR = 25.1), patient age (OR = 20.1), intra-tumoral haemorrhage (OR = 21.35), endometrial thickening (OR = 11), T2-weighted signal heterogeneity (OR = 10.2), menopausal status (OR = 9.7), heterogeneous enhancement (OR = 8) and non-myometrial origin on MRI (OR = 4.9). In the recursive partitioning model, using b 1,000 signal intensity, T2 signal intensity, mean ADC, and patient age, the model correctly classified benign and malignant tumours in 47 of the 51 cases (92.4 %). We have developed an interpretation model usable in routine practice for myometrial tumours discovered at MRI including T2 signal, b 1,000 signal and ADC measurement. • MRI is widely used to differentiate benign from malignant myometrial tumours. • By combining T2-weighted, b 1,000 and ADC features, MRI is 92.4 % accurate. • DWI may limit misdiagnoses of uterine sarcoma as benign leiomyoma. • Patient age is important when considering a solitary myometrial tumour.

e16568 Background: Bowel involvement in ovarian cancer is responsible of an increased surgical effort. However, it have been demonstrated that complete cytoreduction (CC-0) remains the only signifi...

e16536 Background: Platinum-based chemotherapy agents are major drugs in ovarian cancer. The platinum-sensitivity of disease is defined by treatment-free interval (recurrence-free interval>12 month...