Val dAurelle Cancer Institute

Montpellier, France

Val dAurelle Cancer Institute

Montpellier, France
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Braccini A.-L.,Val dAurelle Cancer Institute | David A.,Val dAurelle Cancer Institute | Simon T.,Val dAurelle Cancer Institute | Gilles R.,Val dAurelle Cancer Institute | And 2 more authors.
BMC Cancer | Year: 2013

Background: Several prognostic indexes (PI) have been developed in the brain metastases (BM) setting to help physicians tailor treatment options and stratify patients enrolled in clinical studies. The aim of our study was to compare the clinical relevance of the major PI for breast cancer BM.Methods: Clinical and biological data of 250 breast cancer patients diagnosed with BM at two institutions between 1995 and 2010 were retrospectively reviewed. The prognostic value and accuracy of recursive partitioning analysis (RPA), graded prognostic assessment (GPA), basic score for BM (BS-BM), breast RPA, breast GPA, Le Scodan's Score and a clinico-biological score developed in a phase I study (P1PS) were assessed using Cox regression models. PI comparison was performed using Harrell's concordance index.Results: After a median follow-up of 4.5 years, median overall survival (OS) from BM diagnosis was 8.9 months (CI 95%, 6.9-10.3 months). All PI were significantly associated with OS. Harrell's concordance indexes C favored BS-BM and RPA. In multivariate analysis, the RPA, Le Scodan's score and GPA were found to be the best independent predictors of OS. In multivariate analysis restricted to the 159 patients with known LDH and proteinemia, RPA 2 and 3, Le Scodan's Score 3 and P1PS 2/3 were associated with worse survival. RPA was the most accurate score to identify patients with long (superior to 12 months) and short (inferior to 3 months) life expectancy.Conclusions: RPA seems to be the most useful score and performs better than new PI for breast cancer BM. © 2013 Braccini et al; licensee BioMed Central Ltd.

Braccini A.L.,Val dAurelle Cancer Institute | Azria D.,Val dAurelle Cancer Institute | Thezenas S.,Val dAurelle Cancer Institute | Romieu G.,Val dAurelle Cancer Institute | And 2 more authors.
Breast | Year: 2013

Introduction: Brain metastases (BM) from breast cancer are associated with poor prognosis. This study was made to determine the prognostic influence of breast cancer biological subtypes, and to define the best therapeutic options in this setting, with a special focus on the HER2-positive population. Patients and methods: Breast cancer patients with known hormone receptors (HR) and HER2 status presenting with BM treated between 1995 and 2010 in our two institutions were considered for this retrospective study. Results: 250 patients were included. The study population consisted of 25.6% patients categorized as triple-negative (HR-/HER2-), 30.8% as HR+/HER2- and 43.6% as HER2+ breast cancer. Median overall survival (OS) was 8.9 months (95% CI, 6.9-10.3 months). Cerebral progression remained the most frequent cause of death (57.1%). On multivariate analysis, HER2 positivity and the RPA score were the two most important prognostic factors. Local treatment (surgery or stereotactic radiotherapy) and chemotherapy were significantly associated with an increased survival. On multivariate analysis of the RPA1-2 population, local treatment and chemotherapy were independent prognostic factors in addition to biological subtypes, RPA class, liver metastases and clinical signs of intra-cranial hypertension. Anti-HER2 therapies administered after BM diagnosis significantly and independently increased OS. Median OS in patients receiving both trastuzumab and lapatinib after BM diagnosis was significantly better than that the one of patients receiving only one of the 2 targeted therapies (25.7 vs. 9.6 months, p<0.001). Conclusions: Biological subtypes are independent prognostic determinants. Chemotherapy and targeted therapies positively affect the prognosis after first BM. © 2013 Elsevier Ltd.

PubMed | Val dAurelle Cancer Institute, Italian National Cancer Institute, Dana-Farber Cancer Institute, Rigshospitalet and 7 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2015

We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial.The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or letrozole) included 4922 women, of whom 4091 had central pathology review. Histotype groups were defined as: mucinous (N = 100), tubular/cribriform (N = 83), ductal (N = 3257), and other (N = 651). Of 183 women with either mucinous or tubular/cribriform tumors, 96 were randomly assigned to letrozole and 87 to tamoxifen. Outcomes assessed were disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Median follow-up in the analytic cohort was 8.1 years.Women with tubular/cribriform breast cancer had the best outcomes for all end points compared with the other three histotypes, and had less breast cancer recurrence (97.5% 5-year BCFI) than those with mucinous (93.5%), ductal (88.9%), or other (89.9%) histotypes. Patients with mucinous or tubular/cribriform carcinoma had better DRFI (5-year rates 97.8% and 98.8%, respectively) than those with ductal (90.9%) or other (92.1%) carcinomas. Within the subgroup of women with special histotypes, we observed a nonsignificant increase in the hazard of breast cancer recurrence with letrozole [hazard (letrozole versus tamoxifen): 3.31, 95% confidence interval 0.94-11.7; P = 0.06].Women with mucinous or tubular/cribriform breast cancer have better outcomes than those with other histotypes, although the observation is based on a limited number of events. In postmenopausal women with these histotypes, the magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with mucinous or tubular/cribriform disease.NCT00004205.

MacHon C.,Lapeyronie Hospital | Thezenas S.,Val dAurelle Cancer Institute | Dupuy A.-M.,Lapeyronie Hospital | Assenat E.,Val dAurelle Cancer Institute | And 4 more authors.
Supportive Care in Cancer | Year: 2012

Purpose Inflammatory, angiogenic and oxidative stress markers have been explored in head and neck squamous cell carcinoma (HNSCC) patients before and during radiochemotherapy. Furthermore, the effects of an oral supplementation containing amino acids, ω-3 fatty acids, ribonucleic acids, vitamins, and antioxidants on biological markers and acute toxicities were investigated. Methods Thirty-one patients with non-metastatic stage III or IV HNSCC treated with concomitant radiochemotherapy were recruited. A nutritional support (Oral Impact®) was given during 5 days before each cycle of chemotherapy. Biological samples were collected at baseline, after 5 days of oral supplementation and before the last cycle of chemotherapy. Acute phase proteins levels, proteomic cytokines determination and urinary isoprostanes levels were used as inflammatory and oxidative stress biomarkers. Toxicities were followed up during radiochemotherapy. Results At baseline, median levels of inflammatory (CRP 9.8 mg/l [0.8-130.1], IL-6 4.2 pg/ml [0.7-126.5]), proangiogenic (VEGF 229.5 pg/ml [13.1-595.9]) and prooxidative stress (urinary isoprostanes 118 pmol/mmol creatinine [51-299]) markers were increased. Decrease in CRP (p=0.002) and α-1 acid glycoprotein (p=0.020) levels were observed after 5 days of oral supplementation. During radiochemotherapy, no significant variation of inflammatory markers was reported, and a low incidence of severe acute mucositis was noted. Conclusions Stage III or IV HNSCC patients are characterised by a pro-inflammatory, pro-angiogenic and pro-oxidative status. Nutritional support could improve this inflammatory state and could prevent severe acute mucositis. © Springer-Verlag 2012.

Ho-Pun-Cheung A.,Val dAurelle Cancer Institute | Ho-Pun-Cheung A.,French Institute of Health and Medical Research | Assenat E.,Val dAurelle Cancer Institute | Bascoul-Mollevi C.,Val dAurelle Cancer Institute | And 11 more authors.
International Journal of Cancer | Year: 2011

Aberrant activation of the HER signaling pathways plays a critical role in the invasive and metastatic potential of tumors. The aim of this study was to address whether, in rectal cancer, alterations of these pathways could have a value as prognostic factors to be used to identify patients who are at risk of distant metastases. Therefore, the mRNA expression of the four members of the HER family as well as the frequency of PTEN allelic loss and KRAS/BRAF mutations were determined in pretreatment biopsies from a series of 100 locally advanced rectal cancers and then their ability to predict distant metastases was evaluated. Over-expression of EGFR (p = 0.021), HER2 (p = 0.011) and HER3 (p = 0.020) was significantly associated with worse metastasis-free survival in univariate analysis. In multivariate analysis, both over-expression of EGFR (p = 0.028) and HER3 (p = 0.011) remained independent prognostic factors for distant metastasis. In conclusion, quantification of EGFR and HER3 mRNA expression in pretreatment biopsies may be useful to identify patients who are at risk of developing metastases. © 2010 UICC.

Assenat E.,CRLC Val dAurelle | Thezenas S.,Val dAurelle Cancer Institute | Flori N.,CRLC Val dAurelle | Pere-Charlier N.,Val dAurelle Cancer Institute | And 4 more authors.
Journal of Pain and Symptom Management | Year: 2011

Context: Few studies have evaluated outcomes of combined chemoradiotherapy for Stage III-IV head and neck squamous cell carcinoma in terms of the use of nutritional support by means of percutaneous endoscopic gastrostomy (PEG). Objectives: To compare nutritional status and treatment interruption because of acute toxicity in patients with advanced head and neck tumors who were treated by combined chemoradiotherapy and received or did not receive prophylactic PEG tubes. Methods: This was a retrospective study that evaluated data obtained from a cancer center in Montpellier, France. A total of 139 consecutive patients treated for Stage III-IV head and neck squamous cell carcinoma from January 1, 1998 to June 30, 2003 were evaluated in terms of nutritional status before and after therapy, treatment interruption because of toxicity, and duration of hospitalization. Results: Seventy-eight of the 139 patients (58%) did not receive prophylactic PEG feeding, and 61 patients (44%) received PEG feeding. Pretreatment nutritional status was worse in the PEG group. Compared with the initial nutritional status, nutritional status at the end of treatment was unchanged in the PEG group and much worse in the group that did not receive the PEG (P < 0.05). Cumulative incidence of treatment interruption because of toxicity was significantly lower in the PEG group than in the no-PEG group (100 and 236 days of interruption, respectively, P = 0.03) and hospitalization was significantly shorter (P = 0.003). Conclusion: Prophylactic PEG sustains nutritional status and reduces the cumulative incidence of treatment interruption caused by toxicity and duration of hospitalization. A randomized study is warranted to validate these results. © 2011 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All Rights reserved.

Boissiere-Michot F.,Val dAurelle Cancer Institute | Lopez-Crapez E.,Val dAurelle Cancer Institute | Frugier H.,Val dAurelle Cancer Institute | Berthe M.-L.,Arnaud Of Villeneuve Hospital | And 5 more authors.
Modern Pathology | Year: 2012

KRAS status assessment is mandatory in patients with metastatic colorectal cancer before therapy with anti-epidermal growth factor receptor monoclonal antibodies, as KRAS mutations are associated with resistance to this treatment. However, KRAS genotyping may be very challenging in case of poor tumor cellularity, particularly when major tumor regression is achieved in locally advanced rectal adenocarcinomas after radiochemotherapy. We aimed at identifying the most reliable strategy to detect KRAS mutations in such samples. DNA was extracted from 31 surgical specimens with major tumor regression, following manual dissection, and from paired pre-treatment biopsies and analyzed by high-resolution melting. DNA samples displaying altered melting curve shapes were then sequenced. Samples with unmodified melting curves or wild-type sequence were further investigated by using an allele-specific PCR assay (TheraScreen) and laser microdissection (followed by high-resolution melting and sequencing analyses). In the 31 post-radiochemotherapy surgical specimens, seven KRAS mutations were identified by high-resolution melting analysis/sequencing. One additional mutation was detected by the TheraScreen assay and two mutations, including the one identified by the TheraScreen assay, were detected following laser microdissection. Altogether, 9/31 surgical specimens (29%) presented KRAS mutations. In the manually dissected pre-treatment biopsies, 12 mutations (39%) were identified by high-resolution melting analysis and sequencing. No additional mutations were found by using the TheraScreen assay or laser microdissection. These results indicate that, in the case of post-radiochemotherapy surgical specimens of colorectal cancer with low tumor cellularity, pre-treatment biopsies might represent the most cost-effective option for reliable KRAS genotyping. The use of more sensitive assays, such as allele-specific PCR or laser microdissection, can be envisaged but with higher costs and longer delays. © 2012 USCAP, Inc. All rights reserved.

Lemanski C.,Val dAurelle Cancer Institute | Azria D.,Val dAurelle Cancer Institute | Azria D.,French Institute of Health and Medical Research | Gourgon-Bourgade S.,Val dAurelle Cancer Institute | And 7 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment. Methods and Materials: We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival. Results: The median follow-up was 30 months (range, 12-49 months), and median age was 72 years (range, 66-80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy. Conclusion: Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment. © 2010 Elsevier Inc. All rights reserved.

PubMed | Hospital Angeles Lomas and Val dAurelle Cancer Institute
Type: Comparative Study | Journal: Cirugia y cirujanos | Year: 2014

Laparoscopic surgery for colorectal cancer is currently accepted and widespread worldwide. However, according tol the surgical experience on this approach, surgical and short-term oncologic results may vary. Studies comparing laparoscopic vs. open surgery in our population are scarce.To determine the superiority of the laparoscopic vs. open technique for colorectal cancer surgery.This retrospective and comparative study collected data from patients operated on for colorectal cancer between 1999 and 2011 at the Angeles Lomas Hospital, Mexico.A total of 82 patients were included in this study; 47 were operated through an open approach and 35 laparoscopically. Mean operative time was significantly lower in the open approach group (p= 0.008). There were no significant difference between both techniques for intraoperative bleeding (p= 0.3980), number of lymph nodes (p= 0.27), time to initiate oral feeding (p= 0.31), hospital stay (p= 0.12), and postoperative pain (p= 0.19). Procedure-related complications rate and type were not significantly different in both groups (p= 0.44). Patients operated laparoscopically required significantly less analgesic drugs (p= 0.04) and less need for epidural postoperative analgesia (p= 0.01).Laparoscopic approach is as safe as the traditional open approach for colorectal cancer. Early oncological and surgical results confirm its suitability according to this indication.

PubMed | Val daurelle Cancer Institute
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

13556 Background: Oral fluoropyrimidines, notably capecitabine, are increasingly replacing IV 5-FU/LV as the backbone of therapy for metastatic colorectal cancer. The bi-weekly combination of capecitabine/irinotecan warrants further examination.We conducted an open-label phase I trial, in metastatic cancer patients treated for solid tumors, to determine the recommended dose of capecitabine administered orally bid from day 1 to 8 in combination with a bi-weekly fixed-dose of IV irinotecan 180 mg/mA total of 17 patients were enrolled, with a median age of 60 (range 52-73) years. All patients had an ECOG performance status of either 0 (59%), 1 (35%), or 2 (6%). Primary tumor types were: pancreatic adenocarcinoma (n=6), endocrine tumors (n=5), cholangiocarcinoma (n=2), esophageal adenocarcinoma (n=1), anal carcinoma (n=1), and adenocarcinomas with unknown primary site (n=2). Patients received a total of 122 (range 3-12) cycles at 4 dose levels (3 patients at DL1, 4 at DL2, 6 at DL3, and 4 at DL4). Four patients experienced dose-limiting toxicity: 2 (12%) patients developed grade 4 neutropenia (at DL 1 and 4) and 2 others (12%) developed grade 4 febrile neutropenia (at DL 3 and 4). No toxicity-related deaths occurred. The maximal tolerated dose (MTD) was DL4, and the recommended dose regimen was bi-weekly irinotecan 180 mg/mThis bi-weekly combination of capecitabine/irinotecan (XELIRI) is feasible and could be tested in patients with metastatic colorectal cancer in combination with a targeted therapy. This phase I trial will be continued into a second stage to define the MTD of capecitabine in bi-weekly combination with a fixed dose of irinotecan and oxaliplatin (XELIRINOX). No significant financial relationships to disclose.

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