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Culine S.,Henri Mondor Hospital | Culine S.,Saint Louis Hospital | Chambrier C.,Clinical Nutrition Intensive Care Unit | Tadmouri A.,ClinSearch | And 7 more authors.
Supportive Care in Cancer | Year: 2014

Purpose: Malnutrition is a predictor of poor outcomes in patients with cancer. Little is known about the benefit of nutritional support in these patients. The purpose of this study was to assess the impact of home parenteral nutrition (HPN) on quality of life (Qol) in cancer patients. Methods: We performed an observational prospective study to determine the impact of HPN on Qol in a population of patients with heterogeneous cancer. Physicians, patients and family members had to complete a questionnaire before HPN administration and 28 days after the course of HPN. Qol was evaluated using the self-administered questionnaire FACT-G. Results: We included 767 patients with cancer of whom 437 ended the study. Mean patient age was 63±11.4 years and 60.5 % were men. Primary gastrointestinal cancer was reported in 50 % of patients and 65.3 % were presenting metastases. Malnutrition was reported in 98.3 %. After 28 days of HPN intake, significant improvement was observed in the Qol (49.95±5.82 vs. 48.35±5.01 at baseline, p<0.0001). The mean weight, serum albumin and the nutrition risk index had also improved significantly. Most patients (78 %) had perceived a positive impact of the HPN. A significant improvement in patient's well-being was perceived also by family members and physicians. Conclusions: Our data suggest that preventing and correcting malnutrition using HPN in patients with cancer might have a significant benefit on their well-being. Randomized controlled studies are required to confirm this finding. © 2014 Springer-Verlag.


Jacot W.,Institute Regional Du Cancer Of Montpellier Icm Val Daurelle
Future Oncology | Year: 2014

The 2013 San Antonio Breast Cancer Symposium, held under the auspices of the San Antonio Cancer Therapy & Research Center, the AACR, and Baylor College of Medicine, took place in San Antonio (TX, USA) on 10-14 December 2013. This international Symposium was attended by more than 7000 academic and private physicians and researchers from more than 90 countries, involved in all the fields of breast cancer (BC) research and treatment, including basic, translational and clinical research. Topics of discussion covered all aspects of BC research, from basic science to clinical practice, from prevention to targeted therapies. This report will focus on some of the most important results that were presented during the meeting. © 2014 Future Medicine Ltd.


Anota A.,Quality of Life in Oncology National Platform | Anota A.,Besancon University Hospital Center | Barbieri A.,Institute Regional Du Cancer Of Montpellier Icm Val Daurelle | Barbieri A.,Montpellier University | And 6 more authors.
Health and Quality of Life Outcomes | Year: 2014

Background: Health-Related Quality of Life (HRQoL) is an important endpoint in oncology clinical trials aiming to investigate the clinical benefit of new therapeutic strategies for the patient. However, the longitudinal analysis of HRQoL remains complex and unstandardized. There is clearly a need to propose accessible statistical methods and meaningful results for clinicians. The objective of this study was to compare three strategies for longitudinal analyses of HRQoL data in oncology clinical trials through a simulation study. Methods: The methods proposed were: the score and mixed model (SM); a survival analysis approach based on the time to HRQoL score deterioration (TTD); and the longitudinal partial credit model (LPCM). Simulations compared the methods in terms of type I error and statistical power of the test of an interaction effect between treatment arm and time. Several simulation scenarios were explored based on the EORTC HRQoL questionnaires and varying the number of patients (100, 200 or 300), items (1, 2 or 4) and response categories per item (4 or 7). Five or 10 measurement times were considered, with correlations ranging from low to high between each measure. The impact of informative missing data on these methods was also studied to reflect the reality of most clinical trials. Results: With complete data, the type I error rate was close to the expected value (5%) for all methods, while the SM method was the most powerful method, followed by LPCM. The power of TTD is low for single-item dimensions, because only four possible values exist for the score. When the number of items increases, the power of the SM approach remained stable, those of the TTD method increases while the power of LPCM remained stable. With 10 measurement times, the LPCM was less efficient. With informative missing data, the statistical power of SM and TTD tended to decrease, while that of LPCM tended to increase. Conclusions: To conclude, the SM model was the most powerful model, irrespective of the scenario considered, and the presence or not of missing data. The TTD method should be avoided for single-item dimensions of the EORTC questionnaire. While the LPCM model was more adapted to this kind of data, it was less efficient than the SM model. These results warrant validation through comparisons on real data. © Anota et al.


Boissiere-Michot F.,Institute Regional Du Cancer Of Montpellier Icm Val Daurelle | Lazennec G.,French National Center for Scientific Research | Frugierz H.,Institute Regional Du Cancer Of Montpellier Icm Val Daurelle | Jarlier M.,Institute Regional Du Cancer Of Montpellier Icm Val Daurelle | And 8 more authors.
OncoImmunology | Year: 2014

Sporadic or hereditary colorectal cancer (CRC) with microsatellite instability (MSI) is frequently characterized by inflammatory lymphocytic infiltration and tends to be associated with a better outcome than microsatellite stable (MSS) CRC , probably reflecting a more effective immune response. We investigated inflammatory mechanisms in 48 MSI CRC s and 62 MSS CRC s by analyzing: (1) the expression of 48 cytokines using Bio-Plex multiplex cytokine assays, and (2) the in situ immune response by immunohistochemical analysis with antibodies against CD3 (T lymphocytes), CD8 (cytotoxic T lymphocytes), CD45RO (memory T lymphocytes), T-bet (Th1 CD4 cells), and FoxP3 (regulatory T cells). MSI CRC exhibited significantly higher expression of CCL 5 (RANTES), CXCL 8 (IL-8), CXCL 9 (MIG), IL -1ß, CXCL 10 (IP-10), IL -16, CXCL 1 (GROα), and IL -1ra, and lower expression of MIF, compared with MSS CRC . Immunohistochemistry combined with image analysis indicated that the density of CD3+, CD8+, CD45RO+, and T-bet+ T lymphocytes was higher in MSI CRC than in MSS CRC , whereas the number of regulatory T cells (FoxP3+) was not statistically different between the groups. These results indicate that MSI CRC is associated with a specific cytokine expression profile that includes CCL 5, CXCL 10, and CXCL 9, which are involved in the T helper type 1 (Th1) response and in the recruitment of memory CD45RO+ T cells. Our findings highlight the major role of adaptive immunity in MSI CRC and provide a possible explanation for the more favorable prognosis of this CRC subtype. © 2014 Landes Bioscience.


PubMed | Aarhus University Hospital, Copenhagen University and Institute Regional Du Cancer Of Montpellier Icm Val Daurelle
Type: | Journal: Nature communications | Year: 2016

We currently have limited knowledge of the involvement of long non-coding RNAs (lncRNAs) in normal cellular processes and pathologies. Here, we identify and characterize SNHG5 as a stable cytoplasmic lncRNA with up-regulated expression in colorectal cancer. Depletion of SNHG5 induces cell cycle arrest and apoptosis in vitro and limits tumour outgrowth in vivo, whereas SNHG5 overexpression counteracts oxaliplatin-induced apoptosis. Using an unbiased approach, we identify 121 transcript sites interacting with SNHG5 in the cytoplasm. Importantly, knockdown of key SNHG5 target transcripts, including SPATS2, induces apoptosis and thus mimics the effect seen following SNHG5 depletion. Mechanistically, we suggest that SNHG5 stabilizes the target transcripts by blocking their degradation by STAU1. Accordingly, depletion of STAU1 rescues the apoptosis induced after SNHG5 knockdown. Hence, we characterize SNHG5 as a lncRNA promoting tumour cell survival in colorectal cancer and delineate a novel mechanism in which a cytoplasmic lncRNA functions through blocking the action of STAU1.


PubMed | French Institute of Health and Medical Research, University of Lorraine, Gui Of Chauliac Hospital and Institute Regional Du Cancer Of Montpellier Icm Val Daurelle
Type: | Journal: Journal of neuro-oncology | Year: 2016

Primary central nervous system tumors (PCNST) are rare tumors responsible for high mortality and morbidity. Their epidemiology is poorly known, and clinical data are scarcely analyzed at a national level. In this study, we aimed at providing descriptive epidemiological data and incidence rates for all histological subtypes of PCNST according to the WHO classification. We conducted a nationwide population-based study of all newly diagnosed and histologically confirmed PCNST in France, between 2006 and 2011. A total of 57,816 patients were included: male 46.4%, median age at diagnosis 56 years old (range 0-99). For all newly diagnosed PCNST with histological confirmation the crude incidence rate was 15.5/10


PubMed | Montpellier RIO Imaging Facility, Institute Regional Du Cancer Of Montpellier Icm Val Daurelle, French Institute of Health and Medical Research, Montpellier University and Functional Proteomics Platform
Type: | Journal: Nature communications | Year: 2016

ERBB2 overexpression in human breast cancer leads to invasive carcinoma but the mechanism is not clearly understood. Here we report that TOM1L1 is co-amplified with ERBB2 and defines a subgroup of HER2(+)/ER(+) tumours with early metastatic relapse. TOM1L1 encodes a GAT domain-containing trafficking protein and is a SRC substrate that negatively regulates tyrosine kinase signalling. We demonstrate that TOM1L1 upregulation enhances the invasiveness of ERBB2-transformed cells. This pro-tumoural function does not involve SRC, but implicates membrane-bound membrane-type 1 MMP (MT1-MMP)-dependent activation of invadopodia, membrane protrusions specialized in extracellular matrix degradation. Mechanistically, ERBB2 elicits the indirect phosphorylation of TOM1L1 on Ser321. The phosphorylation event promotes GAT-dependent association of TOM1L1 with the sorting protein TOLLIP and trafficking of the metalloprotease MT1-MMP from endocytic compartments to invadopodia for tumour cell invasion. Collectively, these results show that TOM1L1 is an important element of an ERBB2-driven proteolytic invasive programme and that TOM1L1 amplification potentially enhances the metastatic progression of ERBB2-positive breast cancers.


PubMed | Limoges University Hospital Center, Institute Of Recherche En Cancerologie Of Montpellier, Toulouse University Hospital Center, Montpellier University Hospital Center and 3 more.
Type: Clinical Trial, Phase I | Journal: Oncotarget | Year: 2015

To improve treatment efficacy, we decided to simultaneously target HER1 and HER2 with trastuzumab and cetuximab. Following promising preclinical results, we conducted a phase 1-2 trial in advanced pancreatic cancer patients after first-line gemcitabine-based chemotherapy failure. In this single-arm, non-randomized, multicenter trial, patients received weekly cetuximab (400mg/m, then 250mg/m). They were sequentially included in two trastuzumab dose levels: 3.0 or 4.0mg/kg, then 1.5 or 2.0mg/kg/weekly. Endpoints were the objective response rate, safety, progression-free (PFS) and overall survival (OS). During phase 1 (n=10 patients), toxicities were evenly distributed except for skin toxicities that frequently caused compliance issues. The higher dose level was defined as the trastuzumab recommended dose. During phase 2 (n=39 patients), toxicities were mainly cutaneous reactions and asthenia. No objective response was observed. Nine patients were stabilized but arrested treatment due to toxicity. Median PFS was 1.8 months (95%CI: 1.7-2.0 months) and median OS was 4.6 months (95%CI: 2.7-6.6 months). Both were positively correlated with skin toxicity severity (P=0.027 and P=0.001, respectively). Conventional phase 1 dose-escalation schedules are unsuitable for targeted therapies because most cutaneous toxicities are not considered dose-limiting toxicities. The compliance issues caused by skin toxicities were particularly detrimental because of the toxicity-response correlation.


PubMed | Institute Regional Du Cancer Of Montpellier Icm Val Daurelle
Type: Journal Article | Journal: Clinical & experimental metastasis | Year: 2015

Colorectal (CRC) and gastroesophageal (GEC) cancers unusually spread to the bone. However, bone metastases (BM) are responsible for skeletal-related events (SREs) associated with an altered quality of life. Aiming to describe the characteristics and prognostic influence of BM from gastro-intestinal cancers, we performed a retrospective analysis of prospectively collected data in patients treated in our institution (1996-2006). 189 patients (5.5 %) developed BM: 79 with GEC and 110 with CRC. 57 patients had bone-exclusive metastases. In univariate analyses, the median time to BM occurrence was correlated with the primary tumour (PT) localisation, surgery, histology and TNM staging. However, in multivariate analyses, the occurrence delay was significantly shorter only for patients with GEC (HR 2.1), N1-2 status (HR 1.9), M1 status (HR 2.4), and epidermoid carcinoma (HR 6.0). Pain was the most frequent clinical sign leading to BM diagnosis (77.2 %). SRE occurred in 55 % of patients. Median overall survivals (OSs) of patients with CRC and GEC were 9.4 months [95 % confidence interval (95 % CI) 6.4-11.1] and 3.4 months (95 % CI 2.5-9.0), respectively. In univariate analyses, OS was correlated with PT surgery and NM staging, and the number of BM. In multivariate analyses, only the PT surgery and the number of BM remained correlated with OS. Our results suggest that there may be a subset of patients associated with a quicker development of BM. Given their higher risk of SRE, they could benefit from an early screening, calling for further prospective studies encompassing patients with and without BM.


PubMed | Institute Regional Du Cancer Of Montpellier Icm Val Daurelle
Type: Congresses | Journal: Future oncology (London, England) | Year: 2014

The 2013 San Antonio Breast Cancer Symposium, held under the auspices of the San Antonio Cancer Therapy & Research Center, the AACR, and Baylor College of Medicine, took place in San Antonio (TX, USA) on 10-14 December 2013. This international Symposium was attended by more than 7000 academic and private physicians and researchers from more than 90 countries, involved in all the fields of breast cancer (BC) research and treatment, including basic, translational and clinical research. Topics of discussion covered all aspects of BC research, from basic science to clinical practice, from prevention to targeted therapies. This report will focus on some of the most important results that were presented during the meeting.

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