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PubMed | Clinique Mutualiste de Bellevue, Institute Paoli Calmettes, Institute Bergonie, Institute National du Cancer and 14 more.
Type: | Journal: Nature communications | Year: 2016

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism.


PubMed | Breast Pathology Unit, Institute Regional Du Cancer Of Montpellier Icm, Institute Of Cancerologie Of Louest, Center Leon Berard and Institute Claudius Regaud
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2016

Few data are currently available regarding the efficacy and safety of T-DM1 in breast cancer (BC) patients with unselected brain metastases (BM), since most clinical trials have excluded BM patients or have only included highly selected patients. HER2+BC patients with BM treated with T-DM1 in 5 French centers were included in this retrospective study. Clinical management was performed according to the product guidelines. Efficacy was evaluated recording tumor response rates, progression-free (PFS) and overall survival, treatment compliance, and safety. Thirty nine patients received T-DM1, among whom 82% presented with concomitant extra-cerebral disease. Median number of previous metastatic chemotherapy and HER2-directed targeted therapy regimens was 2 (range 0-8) and 1 (0-7), respectively. Thirty six patients had received BM loco-regional treatment (72% whole-brain radiation therapy). After a median follow-up of 8.1months (1.4-39.6), 24 patients had progressed (first site of progression: brain 14; meningeal 2; outside of the central nervous system 5; both intra- and extra-cerebral 3), 12 patients had died (disease progression), and 27 patients were still alive. Median number of T-DM1 cycles was 8 (1-43). There were 17 partial responses (44%) and 6 patients achieved disease stabilization (59% clinical benefit rate). Median PFS was 6.1months (95%CI 5.2-18.3), with one- and two-year PFS rates of 33 and 17%, respectively. Treatment was well tolerated, without unexpected toxicities, treatment delay, or dose reduction. In this retrospective study, T-DM1 appeared to be an effective and well-tolerated therapeutic option in unselected HER2+BC patients with BM. These findings require a prospective validation.


Satge D.,Institut Universitaire de France | Sauleau E.-A.,University of Strasbourg | Jacot W.,Institute Regional Du Cancer Of Montpellier Icm | Raffi F.,Tulle hospital | And 2 more authors.
BMC Cancer | Year: 2014

Background: Breast cancer has been poorly studied in women with intellectual disability (ID), which makes designing a policy for screening the nearly 70 million women with ID in the world difficult. As no data is available in the literature, we evaluated breast cancer at diagnosis in women with ID.Methods: Women with ID were searched retrospectively among all women treated for invasive breast cancer in a single hospital over 18 years. Age at diagnosis was compared among the whole group of women. Tumor size, lymph node involvement, SBR grade, TNM classification, and AJCC stage were compared to controls matched for age and period of diagnosis using conditional logistic regression.Results: Among 484 women with invasive breast cancer, 11 had ID. The mean age at diagnosis was 55.6 years in women with ID and 62.4 years in the other women. The mean tumor size in women with ID was 3.53 cm, compared to 1.80 cm in 44 random controls from among the 473 women without ID. Lymph node involvement was observed in 9 of the 11 women with ID compared to 12 of the controls (OR = 11.53, p = 0.002), and metastases were found in 3 of the 11 women with ID compared to 1 of the 44 controls (OR = 12.00, p = 0.031). The AJCC stage was higher in women with ID compared to controls (OR = 3.19, p = 0.010).Conclusions: Women with ID presented at an earlier age with tumors of a higher AJCC stage than controls despite no significant differences in tumor grade and histological type. Thus, delayed diagnosis may be responsible for the differences between disabled and non-disabled women. © 2014 Satgé et al.; licensee BioMed Central Ltd.


Samalin E.,Institute Regional Du Cancer Of Montpellier Icm | Ychou M.,Institute Regional Du Cancer Of Montpellier Icm
World Journal of Clinical Oncology | Year: 2016

Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patienttailored therapeutic interventions. © The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.


PubMed | Institute Regional Du Cancer Of Montpellier Icm and Montpellier University
Type: Journal Article | Journal: Bulletin du cancer | Year: 2016

Metastatic process is described as a dissemination of neoplastic cells in a distant secondary site, in which cells proliferate to develop a mass of cells partially differentiated. The vast majority of death in solid cancers is the consequence of metastasis development which lead to vital organ dysfunction. In the present review, either recent discoveries or controversial subjects associated with metastasis process will be discussed. Indeed epithelia-mesenchymal transition (EMT), circulating tumor cells, tumor dormancy, colonization in distant organ and cancer stem cells are tackled.


PubMed | Institute Regional Du Cancer Of Montpellier Icm
Type: Journal Article | Journal: Journal of robotic surgery | Year: 2016

Rectal cancer continues to be a surgical challenge. As more technology is developed, the surgeon must both incorporate this new technology into his practice and, at the same time, keep improving oncologic surgery and overall outcomes. We describe a standardized approach and fully robotic proctectomy, using four arms and one single docking (SI system). Patient cart and ports placement, as well as arms position to avoid collision, are key points to perform the entire procedure with one single docking. Although the place of robotic surgery might still need to be defined, standardizing the procedures is a step towards its evaluation. We propose with this report a solution to perform a single docking four arms robotic proctectomy.


PubMed | Institute Regional Du Cancer Of Montpellier Icm
Type: Journal Article | Journal: World journal of clinical oncology | Year: 2016

Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions.


Robotic total mesorectal excision (R-TME), a novel way for minimally invasive treatment of rectal cancer, was shown in previous studies to be safe and effective. However, comparison with laparoscopic total mesorectal excision (L-TME) has drawn contradictory disputes, especially concerning operative high-risk patients. The aim of this study was to compare R-TME and L-TME on the rectal technical approach.Between October 2009 and March 2013, a total of 120 consecutive rectal carcinomas, operated for sphincter-saving procedure, were enrolled. The patient population included the last 60 laparoscopic procedures and the first 60 robotic surgeries (six hybrid approaches, then 54 full robotic surgeries). There were no exclusions.Patients baseline characteristics were similar in both the R-TME and L-TME groups. Outcomes were equivalent for blood loss (200vs. 100mL), postoperative hospital stay (12 vs. 11days), conversion rate (3.2 vs. 4.8%), lymph nodes yield (15 vs. 19), no positive distal margin (0%), positive radial margin (6.4 vs. 9.3%), diverting ileostomy (73 vs. 58%) and severe morbidity (28vs. 20%). Significant differences were found for median operative time (274 vs. 228min; p=0.003) and proctectomy performed via transanal approach (1.7vs. 16.7%; p=0.004). The R-TME operative time curve stabilized to 245min after the first 25 procedures.For rectal cancer, R-TME may be as feasible and safe as L-TME in terms of technique. In our practice and for difficult cases, R-TME allows complete rectal dissection by an abdominal approach, while L-TME requires a transanal approach.


PubMed | Montpellier University, Center Leon Berard, University of Rouen, Nestlé and 4 more.
Type: Clinical Trial, Phase III | Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | Year: 2016

Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities.The primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-2 (TGF-2) in the prevention of grade 3-4 non-hematological toxicities induced by chemotherapy in patients with GI cancer.We designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect() (CP) or a control isocaloric diet (without TGF-2 or glutamine).Between November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3-4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3-4 hematological toxicities or reasons for treatment interruption.This randomized study does not support the hypothesis that oral glutamine and TGF-2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm.


PubMed | Institute Regional Du Cancer Of Montpellier Icm, Service de radiotherapie and Institute Of Cancerologie Of La Loire Icl
Type: | Journal: Radiation oncology (London, England) | Year: 2016

To verify the accuracy of volumetric arc therapy (VMAT) using the RapidArc device when switching patients from one single linear accelerator (linac) to a paired energy and mechanics twin linac without reoptimization of the original treatment plan.Four centers using 8 linacs were involved in this study. Seventy-four patients previously treated with the 6MV photon RapidArc technique were selected for analysis, using 242 measurements. In each institution, all patients were planned on linac A, and their plans were verified both on linac A and on the twin linac B. Verifications were done using the amorphous silicium electronic portal imager (EPID) of the linacs and were analyzed with the EpiQa software (Epidos, Bratislavia, Slovakia). The gamma index formalism was used for validation with a double threshold of 3 % and 3 mm with a measurement resolution of 0.39 mm/pixel, and a smoothed resolution of approximately 2.5 mm.The number of points passing the gamma criteria between the measured and computed doses was 94.79 2.57 % for linac A and 94.61 2.46 % for linac B. Concerning the smoothed measurement analysis, 98.67 1.26 % and 98.59 1.20 % points passing the threshold were obtained for linacs A and B, respectively. The difference between the 2 dose matrices acquired on the EPID was very small, with 99.92 0.06 % of the points passing the criteria.For linacs sharing the same mechanical and energy parameters, this study tends to indicate that patients may be safely switched from treatment with one linac to treatment with its twin linac using the same VMAT plan.

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