Pivot X.,University Hospital njoz |
Romieu G.,Center Val dAurelle |
Debled M.,Institute Bergonie |
Pierga J.-Y.,University Pierre and Marie Curie |
And 16 more authors.
The Lancet Oncology | Year: 2013
Background: Since 2005, 12 months of adjuvant trastuzumab has been the standard treatment for patients with HER2-positive early-stage breast cancer. However, the optimum duration of treatment has been debated. We did a non-inferiority trial of a shorter exposure of 6 months versus the standard 12 months of trastuzumab for patients with early breast cancer. Methods: We did an open-label, randomised, phase 3 trial in 156 centres in France. Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy, had breast-axillary surgery, and had received up to 6 months of trastuzumab (administered by intravenous infusions over 30-90 min every 3 weeks; initial loading dose 8 mg/kg; 6 mg/kg thereafter) before randomisation were eligible. Patients were randomly assigned via central randomisation procedure with web-based software to continue trastuzumab for another 6 months (12 months total duration; control group) or to discontinue trastuzumab at 6 months (6 months total duration; experimental group). Randomisation was stratified by concomitant or sequential administration of trastuzumab with chemotherapy, oestrogen-receptor status, and centre using a minimisation algorithm. The primary endpoint was disease-free survival, with a prespecified non-inferiority margin of 1·15. Analyses were done in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00381901. Findings: 1691 patients were randomly assigned to receive 12 months of trastuzumab and 1693 to receive 6 months of trastuzumab; 1690 patients in each group were included in the intention-to-treat analyses. After a median follow-up of 42·5 months (IQR 30·1-51·6), 175 disease-free survival events were noted in the 12-month group and 219 in the 6-month group. 2-year disease-free survival was 93·8% (95% CI 92·6-94·9) in the 12-month group and 91·1% (89·7-92·4) in the 6-month group (hazard ratio 1·28, 95% CI 1·05-1·56; p=0·29). 119 (93%) of the 128 cardiac events (clinical or based on assessment of left ventricular ejection fraction) occurred while patients were receiving trastuzumab. Significantly more patients in the 12-month group experienced a cardiac event than did those in the 6-month group (96 [5·7%] of 1690 patients vs 32 [1·9%] of 1690 patients, p<0·0001). Interpretation: After 3·5 years follow-up, we failed to show that 6 months of treatment with trastuzumab was non-inferior to 12 months of trastuzumab. Despite the higher rates of cardiac events, 12 months of adjuvant trastuzmab should remain the standard of care. Funding: French National Cancer Institute. © 2013 Elsevier Ltd.
Pivot X.,University Hospital njoz |
Suter T.,University of Bern |
Nabholtz J.M.,Center jean Perrin |
Pierga J.Y.,Institute CurieParis |
And 7 more authors.
European Journal of Cancer | Year: 2015
Abstract Background: This article reports, the cardiac toxicity according to 6- versus 12-month durations of adjuvant trastuzumab in PHARE randomised trial (NCT00381901). Patients and methods: Cardiac follow-up and Left Ventricular Ejection Fraction (LVEF) assessment by echocardiography or multigated acquisition scan were performed every 3 months while patients received trastuzumab and after completion of treatment over the first 2 years and every 6 months afterwards. The primary cardiac end-point was Cardiac Heart Failure (CHF) defined as New York Heart Association (NYHA) class III or IV. The secondary cardiac end-points were: cardiac events, cardiac dysfunctions defined by NYHA class I and II; LVEF decreases, cardiac recoveries. The cardiac subcommittee reviewed cardiac events and assessed if patients had favourable outcomes or not on the basis of trends from LVEF measurements. Results: Among 3380 patients the cardiac dysfunction assessment included 14,055 and 13,218 LVEF measurements in the 12- and 6-month arms. The overall incidences of CHF were 0.65% (11/1690) and 0.53% (9/1690) in the 12 and 6 month arms, respectively (p > 0.05). Cardiac dysfunction occurred in 5.9% (100/1690) and 3.4% (58/1690) of patients in the 12 and 6 month arms, respectively (p = 0.001). Recoveries were observed for the majority patients and 0.79% (27/3380) of patients experienced an unfavourable cardiac outcome. Conclusion PHARE confirm that the incidence of cardiac end-points remains low and mostly reversible after trastuzumab. Identification at baseline of cardiac risk categories of patients should be of interest to provide an optimal adaptation of adjuvant modalities and a shorter duration might be an option. © 2015 Elsevier Ltd.
PubMed | National Polytechnic Institute of Toulouse, University of Paris 13, University of Burgundy, French National Cancer Institute and 2 more.
Type: | Journal: Critical reviews in oncology/hematology | Year: 2016
Prevention is a priority in the fight against cancers, especially nutritional prevention. To update the levels of evidence of relationships between 10 nutritional factors and cancer risk, the scientific literature published from 2006 to 2014 was reviewed by an expert group.Data from 133 meta-analyses, pooled analyses or intervention trials were examined. Nearly 150 relationships between nutritional factors and cancer at various sites were evaluated.According to the evidence graded as convincing or probable, these factors were divided in two groups. Factors which increase the risk of cancer are alcoholic beverages, overweight and obesity, red meat and processed meat, salt and salted foods and beta-carotene supplements. Factors which decrease the risk of cancer are physical activity, fruits and vegetables, dietary fiber, dairy products and breastfeeding.Three main nutritional objectives should be attained to improve cancer prevention: to reduce alcoholic beverages consumption, to have a balanced and diversified diet and to be physically active.
Mensink G.B.M.,Robert Koch Institute |
Fletcher R.,Kellogg Europe |
Gurinovic M.,University of Belgrade |
Huybrechts I.,Ghent University |
And 8 more authors.
British Journal of Nutrition | Year: 2013
Achieving an understanding of the extent of micronutrient adequacy across Europe is a major challenge. The main objective of the present study was to collect and evaluate the prevalence of low micronutrient intakes of different European countries by comparing recent nationally representative dietary survey data from Belgium, Denmark, France, Germany, The Netherlands, Poland, Spain and the United Kingdom. Dietary intake information was evaluated for intakes of Ca, Cu, I, Fe, Mg, K, Se, Zn and the vitamins A, B1, B2, B6, B12, C, D, E and folate. The mean and 5th percentile of the intake distributions were estimated for these countries, for a number of defined sex and age groups. The percentages of those with intakes below the lower reference nutrient intake and the estimated average requirement were calculated. Reference intakes were derived from the UK and Nordic Nutrition Recommendations. The impact of dietary supplement intake as well as inclusion of apparently low energy reporters on the estimates was evaluated. Except for vitamin D, the present study suggests that the current intakes of vitamins from foods lead to low risk of low intakes in all age and sex groups. For current minerals, the study suggests that the risk of low intakes is likely to appear more often in specific age groups. In spite of the limitations of the data, the present study provides valuable new information about micronutrient intakes across Europe and the likelihood of inadequacy country by country. © 2012 The Authors.
Kramar A.,Methdology and Biostatistics Unit |
Bachelot T.,Center Leon Berard |
Madrange N.,Institute Bergonie |
Pierga J.-Y.,University Pierre and Marie Curie |
And 7 more authors.
Annals of Oncology | Year: 2014
Background: At 42.5 months of median follow-up, PHARE failed to show that 6 was non-inferior to 12 months of adjuvant trastuzumab. From the results of PHARE, questions remain regarding whether the magnitude of benefit derived from 1 year is sufficient to justify its systematic use for different patient subgroups. Methods: Treatment effects were evaluated according to various tumour characteristics, and the multivariate Cox proportional hazards regression models were carried out on metastases-free survival (MFS) in the 12 months control arm. A prognostic score was defined providing the identification of patient categories with similar risks. The 6-month arm was used as a validation set in order to test for heterogeneity. This study is registered at clinicaltrials.gov, number NCT00381901. Results: A total of 261 metastatic events were observed and four prognostic groups were defined: very low, low, intermediate and high risk in the 12-month arm. The corresponding 3-year MFS rates were 98.3%, 95.8%, 90.4% and 78.4% in the four prognostic groups, respectively. In the 6-month arm, the 3-year MFS rates were 98.3%, 94.2%, 85.7% and 74.8% in the four prognostic groups, respectively. Conclusion: In the very low-risk group, the potential absolute benefit of standard duration of trastuzumab was small enough to indicate that optimal standard treatment might be clinically questionable. On the other hand, the 3-year metastasis occurrence rates strongly support the need for a search of a more efficient treatment in the low-, intermediate- and high-risk groups. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Latino-Martel P.,University of Paris 13 |
Cottet V.,University of Burgundy |
Druesne-Pecollo N.,University of Paris 13 |
Pierre F.H.F.,National Polytechnic Institute of Toulouse |
And 7 more authors.
Critical Reviews in Oncology/Hematology | Year: 2016
Purpose: Prevention is a priority in the fight against cancers, especially nutritional prevention. To update the levels of evidence of relationships between 10 nutritional factors and cancer risk, the scientific literature published from 2006 to 2014 was reviewed by an expert group. Methods: Data from 133 meta-analyses, pooled analyses or intervention trials were examined. Nearly 150 relationships between nutritional factors and cancer at various sites were evaluated. Results: According to the evidence graded as convincing or probable, these factors were divided in two groups. Factors which increase the risk of cancer are alcoholic beverages, overweight and obesity, red meat and processed meat, salt and salted foods and beta-carotene supplements. Factors which decrease the risk of cancer are physical activity, fruits and vegetables, dietary fiber, dairy products and breastfeeding. Conclusion: Three main nutritional objectives should be attained to improve cancer prevention: to reduce alcoholic beverages consumption, to have a balanced and diversified diet and to be physically active. © 2016 The Authors Published by Elsevier Ireland Ltd.
Hofman V.,University of Nice Sophia Antipolis |
Hofman V.,Pasteur Hospital |
Ilie M.,University of Nice Sophia Antipolis |
Ilie M.,Pasteur Hospital |
And 18 more authors.
Biopreservation and Biobanking | Year: 2013
The number of biobanks, in particular hospital-integrated tumor biobanks (HITB), is increasing all around the world. This is the consequence of an increase in the need for human biological resources for scientific projects and more specifically, for translational and clinical research. The robustness and reproducibility of the results obtained depend greatly on the quality of the biospecimens and the associated clinical data. They also depend on the number of patients studied and on the expertise of the biobank that supplied the biospecimens. The quality of a research biobank is undoubtedly reflected in the number and overall quality of the research projects conducted with biospecimens provided by the biobank. Since the quality of a research project can be measured from the impact factor of resulting publications, this also provides some indication of the quality of a research biobank. It is necessary for the biobank community to define "surrogate" quality indicators, and to establish systems of evaluation in relation to current and future resource requirements. These indicators will help in the realistic assessment of biobanks by institutions and funding bodies, and they will help biobanks demonstrate their value, raise their quality standards, and compete for funding. Given that biobanks are expensive structures to maintain, funding issues are particularly important, especially in the current economic climate. Use of performance indicators may also contribute to the development of a biobank impact factor or "bioresource research impact factor" (BRIF). Here we review four major categories of indicators that appear to be useful for the evaluation of a(m) HITB (quality, activity, scientific productivity, and "visibility"). In addition, we propose a scoring system to measure the chosen indicators. © Mary Ann Liebert, Inc.
Leuraud K.,French Institute for Public Health Surveillance |
Jezewski-Serra D.,French Institute for Public Health Surveillance |
Viguier J.,French National Cancer Institute |
Salines E.,French Institute for Public Health Surveillance
Cancer Epidemiology | Year: 2013
Background: The French national screening programme for colorectal cancer (CRC) was rolled out nationwide from 2008. It targets men and women aged 50-74 who are invited every 2 years to perform a guaiac faecal occult blood test, followed, if positive, by a colonoscopy. This paper presents the evaluation of the programme for the 46 French districts that conducted a comprehensive screening campaign during 2008-2009, targeting 9.7 million people. Methods: National database gathering information on people who were screened was used to estimate indicators reflecting the programme performance. Results: Participation was 34.3%, with nearly three million people being tested. The percentage of positive tests was 2.8%. Completion of colonoscopies following a positive test was 88%. For men, 36.8% of the results of colonic explorations were normal, 40.1% were adenomas, and 9.0% were CRC, based on the most pejorative lesion. For women, corresponding figures were 55.9%, 25.7% and 5.8%. A CRC was detected for 7.5% of people who had a colonic exploration. The advanced adenoma detection rate among those screened was 4.9‰ and the CRC detection rate was 1.9‰. The description of CRC could only be made for 21 districts, for which 1441 invasive colonic adenocarcinomas were diagnosed; of these, 43% were stage I, 23% stage II, 25% stage III and 9% stage IV. Conclusion: This first evaluation since the programme was rolled out provides an inventory of CRC screening in France and points out some improvements expected, especially in terms of participation which is below the European recommendations. Future evaluations will analyse trends in these indicators. © 2013 Elsevier Ltd.