Assessment of a clay barrier resaturation in isothermal conditions

Many projects of underground repositories for high level radioactive wastes involve an engineered clay barrier, placed between the waste canister and the surrounding rock. By hydrating progressively, the barrier swells, seals the gaps and provides a good global watertightness. In a high level radioactive waste repository, the maximum admissible temperature for the barrier governs the space between canisters and consequently the cost of the civil engineering works. Thus a precise assessment of this criterion is compulsory. Even though the barrier behaviour depends on the thermal-hydro-mechanical interactions with the canister and the host rock, the study is only focused on the hydraulic behaviour of the barrier without phase change in a first step.A chamber containing one high level radioactive waste canister is simulated for the East of France repository site. A 2D-plane computation is done with the CASTEM2000 code. A cylindrical geometry, composed of a barrier layer surrounded by a site layer, is represented. Two kinds of clay are studied for the barrier.The clay foreseen for the french repository sites is the FoCa clay. But in order to compare our results with those of other european countries, we studied the spanish La Serrata clay too for the barrier. The East of France site is made of a clay, different from the barrier one. To understand the influence of the boundary conditions on the barrier resaturation time, two sorts of boundary conditions are considered for the external site limit: an imposed water pressure or no water flow. On the internal barrier limit, we enforce a water flow equal to zero. Initially, the site is saturated whereas the barrier is partially unsaturated. Neglecting the initial ventilation phase in the repository site, we suppose that the barrier is in thermal equilibrium with the surrounding site. Their average temperature is 50°C.The models implemented in the CASTEM-2000 code are based on the mixed-hybrid finite element formulation. The numerical model used for this computation supposes that air remains at a constant pressure and water only exists in a liquid state. This paper is devoted to the analysis of the barrier resaturation by the site water. A parametric study on the barrier material and the boundary conditions is realised. The results are the water pressure and the saturation versus time and along a radius

Evaluation of the influence of various parameters on a clay barrier resaturation in isothermal conditions

Many projects of high level waste repositories in geological media involve an engineered clay barrier, placed between the waste and the surrounding host rock. By hydrating progressively on contact with the interstitial water, the barrier swells, seals the gaps, and then provides a global mechanical stability of the waste - clay barrier - host rock system. In a high-level radioactive waste repository, the thermal waste creates a thermal field in the vicinity of the waste. The maximum admissible temperature for the barrier (beyond which physical, mechanical or chemical properties break down) dictates the distance between the canister cells and consequently the size of the repository. Thus a precise assessment of this criterion is a matter of great importance.The study is focused on the hydraulic behaviour of the barrier. A storage cell containing one high level radioactive waste canister is simulated for the East of France repository site. A cylindrical geometry, composed of a barrier layer surrounded by a site layer, is computed with the code CASTEM2000.Initially, the site is saturated whereas the barrier is partially unsaturated. Neglecting the initial ventilation phase in the repository site, we suppose that the barrier is in thermal equilibrium with the surrounding site. Their average temperature is 50$^o$C.The models implemented in the CASTEM code are based on the mixed-hybrid finite element formulation. The numerical model used for this computation supposes that air remains at a constant pressure and water only exists in a liquid state. This paper is devoted to the analysis of the barrier resaturation by the site water. The parametric study concerns the influence on the resaturation time of the clay material, the boundary conditions on the external site limit, the air pressure and the taking into account of the gravity. The results are the pressure and the saturation versus time

Nutritional advice in older patients at risk of malnutrition during treatment for chemotherapy: a two-year randomized controlled trial.

We tested the effect of dietary advice dedicated to increase intake in older patients at risk for malnutrition during chemotherapy, versus usual care, on one-year mortality.We conducted a multicentre, open-label interventional, stratified (centre), parallel randomised controlled trial, with a 1∶1 ratio, with two-year follow-up. Patients were aged 70 years or older treated with chemotherapy for solid tumour and at risk of malnutrition (MNA, Mini Nutritional Assessment 17-23.5). Intervention consisted of diet counselling with the aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d, by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Interviews were performed 6 times during the chemotherapy sessions for 3 to 6 months. The primary endpoint was 1-year mortality and secondary endpoints were 2-year mortality, toxicities and chemotherapy outcomes.Between April 2007 and March 2010 we randomised 341 patients and 336 were analysed: mean (standard deviation) age of 78.0 y (4·9), 51.2% male, mean MNA 20.2 (2.1). Distribution of cancer types was similar in the two groups; the most frequent were colon (22.4%), lymphoma (14.9%), lung (10.4%), and pancreas (17.0%). Both groups increased their dietary intake, but to a larger extent with intervention (p<0.01). At the second visit, the energy target was achieved in 57 (40.4%) patients and the protein target in 66 (46.8%) with the intervention compared respectively to 13 (13.5%) and 20 (20.8%) in the controls. Death occurred during the first year in 143 patients (42.56%), without difference according to the intervention (p = 0.79). No difference in nutritional status changes was found. Response to chemotherapy was also similar between the groups.Early dietary counselling was efficient in increasing intake but had no beneficial effect on mortality or secondary outcomes. Cancer cachexia antianabolism may explain this lack of effect.ClinicalTrials.gov NCT00459589

Two-year mortality according to groups UC and UC+NI. N = 336.

<p>Comparisons were performed with Cox model adjusted on recruiting centres.</p

Main baseline characteristics of participants in the trial.

<p>ECOG PS: Eastern Cooperative Oncology Group performance status.</p><p>Main baseline characteristics of participants in the trial.</p

Two-year mortality and other outcomes.

<p>Two-year mortality and other outcomes.</p

Flowchart of participant progression through a randomized controlled trial of nutritional intervention in older patients at risk of malnutrition.

<p>Flowchart of participant progression through a randomized controlled trial of nutritional intervention in older patients at risk of malnutrition.</p

Dietary intake the day before each cycle during the chemotherapy period.

<p>Data are presented as mean and 95% CI, or proportion. Total dietary intake was analyzed with mixed models: increase of total intake at the second visit in both groups (UC+NI, P<0.0001; **UC, P = 0.02), with higher increased in UC+NI compared to UC, P<0.01.</p

Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort

IF 6.029International audienceBackgroundDiagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC.Patients and methodsAll patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded.Results253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0–1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20–100). Median overall survival was 15.6 (13.6–17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE > 2 upper limit of normal [ULN]; HR = 3.2), CgA > 2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72).ConclusionsWe report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial

International audienceImportance Early results at 3 years from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial showed survival benefits with adjuvant treatment with modified FOLFIRINOX vs gemcitabine in patients with resected pancreatic ductal adenocarcinoma; mature data are now available. Objective To report 5-year outcomes and explore prognostic factors for overall survival. Design, Setting, and Participants This open-label, phase 3 randomized clinical trial was conducted at 77 hospitals in France and Canada and included patients aged 18 to 79 years with histologically confirmed pancreatic ductal adenocarcinoma who had undergone complete macroscopic (R0/R1) resection within 3 to 12 weeks before randomization. Patients were included from April 16, 2012, through October 3, 2016. The cutoff date for this analysis was June 28, 2021. Interventions A total of 493 patients were randomized (1:1) to receive treatment with modified FOLFIRINOX (oxaliplatin, 85 mg/m 2 of body surface area; irinotecan, 150-180 mg/m 2 ; leucovorin, 400 mg/m 2 ; and fluorouracil, 2400 mg/m 2 , every 2 weeks) or gemcitabine (1000 mg/m 2 , days 1, 8, and 15, every 4 weeks) as adjuvant therapy for 24 weeks. Main Outcomes and Measures Primary end point was disease-free survival. Secondary end points included overall survival, metastasis-free survival, and cancer-specific survival. Prognostic factors for overall survival were determined. Results Of the 493 patients, 216 (43.8%) were women, and the mean (SD) age was 62.0 (8.9) years. At a median of 69.7 months’ follow-up, 367 disease-free survival events were observed. In patients receiving chemotherapy with modified FOLFIRINOX vs gemcitabine, median disease-free survival was 21.4 months (95% CI, 17.5-26.7) vs 12.8 months (95% CI, 11.6-15.2) (hazard ratio [HR], 0.66; 95% CI, 0.54-0.82; P &amp;lt; .001) and 5-year disease-free survival was 26.1% vs 19.0%; median overall survival was 53.5 months (95% CI, 43.5-58.4) vs 35.5 months (95% CI, 30.1-40.3) (HR, 0.68; 95% CI, 0.54-0.85; P = .001), and 5-year overall survival was 43.2% vs 31.4%; median metastasis-free survival was 29.4 months (95% CI, 21.4-40.1) vs 17.7 months (95% CI, 14.0-21.2) (HR, 0.64; 95% CI, 0.52-0.80; P &amp;lt; .001); and median cancer-specific survival was 54.7 months (95% CI, 45.8-68.4) vs 36.3 months (95% CI, 30.5–43.9) (HR, 0.65; 95% CI, 0.51-0.82; P &amp;lt; .001). Multivariable analysis identified modified FOLFIRINOX, age, tumor grade, tumor staging, and larger-volume center as significant favorable prognostic factors for overall survival. Shorter relapse delay was an adverse prognostic factor. Conclusions and Relevance The final 5-year results from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial indicate that adjuvant treatment with modified FOLFIRINOX yields significantly longer survival than gemcitabine in patients with resected pancreatic ductal adenocarcinoma. Trial Registration EudraCT: 2011-002026-52; ClinicalTrials.gov Identifier: NCT01526135EudraCT: 2011-002026-52; ClinicalTrials.gov Identifier: NCT01526135