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Villejuif, France

Farah J.,Institute for Radiological Protection and Nuclear Safety | Bonfrate A.,Institute for Radiological Protection and Nuclear Safety | De Marzi L.,Institut Universitaire de France | De Oliveira A.,Institut Universitaire de France | And 5 more authors.
Physica Medica | Year: 2015

Purpose: This study focuses on the configuration and validation of an analytical model predicting leakage neutron doses in proton therapy. Methods: Using Monte Carlo (MC) calculations, a facility-specific analytical model was built to reproduce out-of-field neutron doses while separately accounting for the contribution of intra-nuclear cascade, evaporation, epithermal and thermal neutrons. This model was first trained to reproduce in-water neutron absorbed doses and in-air neutron ambient dose equivalents, H*(10), calculated using MCNPX. Its capacity in predicting out-of-field doses at any position not involved in the training phase was also checked. The model was next expanded to enable a full 3D mapping of H*(10) inside the treatment room, tested in a clinically relevant configuration and finally consolidated with experimental measurements. Results: Following the literature approach, the work first proved that it is possible to build a facility-specific analytical model that efficiently reproduces in-water neutron doses and in-air H*(10) values with a maximum difference less than 25%. In addition, the analytical model succeeded in predicting out-of-field neutron doses in the lateral and vertical direction. Testing the analytical model in clinical configurations proved the need to separate the contribution of internal and external neutrons. The impact of modulation width on stray neutrons was found to be easily adjustable while beam collimation remains a challenging issue. Finally, the model performance agreed with experimental measurements with satisfactory results considering measurement and simulation uncertainties. Conclusion: Analytical models represent a promising solution that substitutes for time-consuming MC calculations when assessing doses to healthy organs. © 2015 Associazione Italiana di Fisica Medica.

Lemiale V.,Saint Louis University Hospital | Mokart D.,IPC | Resche-Rigon M.,APHP | Pene F.,APHP | And 42 more authors.
JAMA - Journal of the American Medical Association | Year: 2015

IMPORTANCE: Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear. OBJECTIVE: To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015. INTERVENTIONS: Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183). MAINOUTCOMESAND MEASURES: The primaryoutcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay. RESULTS: At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, -3.2 [95% CI, -12.1 to 5.6]; P =.47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, -6.6 [95% CI, -16.6 to 3.4]; P =.20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. CONCLUSIONS AND RELEVANCE: Among immunocompromised patients admittedto the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited. Copyright 2015 American Medical Association. All rights reserved.

The AcSé crizotinib project is the first clinical trial of the AcSé program (for “secure access to innovative targeted therapies”) developed by the French National Cancer Institute. This trial aims to offer cancer patients, for whom validated therapies have failed, access to this targeted therapy, based on a molecular abnormality of their tumour. © 2014, Springer-Verlag France.

Samson E.,Institute for Radiological Protection and Nuclear Safety | Telle-Lamberton M.,Institute for Radiological Protection and Nuclear Safety | Caer-Lorho S.,Institute for Radiological Protection and Nuclear Safety | Bard D.,EHESP School of Public Health | And 7 more authors.
International Archives of Occupational and Environmental Health | Year: 2011

Purpose: The aim of this paper is to study the effect of external photon radiation on the mortality of two populations of French nuclear workers: workers exposed only to external photon radiation and workers potentially exposed also to internal contamination or to neutrons. Method: External photon radiation has been measured through individual dosimeters. Potential exposure to internal contamination or to neutrons has been assessed by experts on the basis of quantitative measurements or of worksite and type of activity. The mortality observed in each population was compared with that expected from national mortality statistics, by computing standardized mortality ratios. Dose-effect relationships were analyzed through trend tests and log-linear Poisson regressions. Results: 14,796 workers were exposed only to external photon radiation; 14,408 workers were also potentially exposed to internal radiation or to neutrons. Between 1968 and 1994, the number of deaths is respectively, 645 and 1,197. The mean external photon dose was respectively, 3.7 and 12.9 mSv. Similar Healthy Worker Effects were observed in the two populations (SMR = 0.59). SMR of 2.41 90% CI [1.39-3.90] was observed for malignant melanoma among workers of the second population. Significant dose-effect relationships were observed: among workers exposed only to external photon radiation for leukemia except CLL and in the other population, for cancers and other diseases related to tobacco or alcohol consumption. Conclusions: Results differed between the two populations. The increase in leukemia risk with dose in the first population will have to be confirmed with extended follow-up. In the other population, results may have been confounded by alpha-emitters inhalation, tobacco, or alcohol consumption. © 2011 Springer-Verlag.

Adenis A.,Center Oscar Lambret | Blay J.-Y.,Center Leon Berard | Bui-Nguyen B.,Institute Bergonie | Bouche O.,Reims University Hospital Center | And 18 more authors.
Annals of Oncology | Year: 2014

Background: Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. Patients and methods: Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1: 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. Results: Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09-0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). Conclusions: Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit-risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

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