Combination, Modulation and Interplay of Modern Radiotherapy with the Tumor Microenvironment and Targeted Therapies in Pancreatic Cancer: Which Candidates to Boost Radiotherapy?

Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC's tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions

Assessment of Executive Functions in Children and Adolescents with acquired brain injury (ABI) using a novel complex multi-tasking computerized task – the Jansari assessment of Executive Functions for Children (JEF-C©)

Objectives: The Jansari assessment of Executive Functions for Children (JEF-C©) is a new non-immersive computerized assessment of executive functions. The objectives of the study were to test the feasibility and validity of JEF-C© in children and adolescents with acquired brain injury (ABI). Methods: Twenty-nine patients with ABI aged 10-18 years and 30 age-and gender-matched controls were tested. Participants performed JEF-C©, Wechsler Abbreviated Scale of Intelligence (WASI) and the Behavioral Assessment of the Dysexecutive Syndrome for Children (BADS-C), while parents completed the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire. Results: JEF-C© task proved feasible in patients with ABI. The internal consistency was medium (Cronbach's alpha =0.62 and significant inter-correlations between individual JEF-C© constructs). Patients performed significantly worse than controls on most of the JEF-C© subscales and total score, with 41.4 % of participants with ABI classified as having severe executive dysfunction. No significant correlations were found between JEF-C© total score, the BRIEF indices and the BADS-C. Significant correlations were found between JEF-C© and demographic characteristics of the sample and intellectual ability, but not with severity/medical variables. Conclusion: JEF-C© is a playful complex task that appears to be a sensitive and ecologically valid assessment tool, especially for relatively high-functioning individuals

Réactivité de nanoparticules de palladium supportées en hydrogénation : rôle de la densité surfacique de particule

SSCI-VIDE+CARE+CDSNational audienceNon

Reactivity of palladium nanoparticles supported in hydrogenation: role of the particle surface density

SSCI-VIDE+CARE+CDSInternational audienceNon

Hydrogenation of unsaturated hydrocarbons by (very) small Pd alumina supported particles : factors governing catalytic activity

SSCI-VIDE+CARE+CDSInternational audienceNon

Hydrogenation of unsaturated hydrocarbons by (very) small Pd alumina supported particles : factors governing catalytic activity

SSCI-VIDE+CARE+CDSInternational audienceNon

Study of hydrogen surface mobility and hydrogenation reactions over alumina-supported palladium catalysts

EAU+CDSAlumina-supported Pd catalysts with different particle surface densities have been prepared using incipient wetness impregnation of aqueous solution of a palladium nitrite complex. Buta-1,3-diene and orthoxylene hydrogenation reactions were performed both in a batch and a fixed bed reactor. Hydrogen surface mobility was studied using H-2-D-2 isotopic exchange. The influence of (i) the particle surface density and (ii) the surface area of the support on the catalytic properties are discussed. The turnover frequency (TOF) of the but-1,3-diene hydrogenation was highly sensitive to the surface density of Pd particles (D-sp). Moreover, for a given surface density, TOF also depend on the nature of the alumina support. For a given support, modifications of the electronic properties of palladium can explain the increase of the reaction rate with D-sp while changes in the kinetics of hydrogen surface diffusion are proposed to explain the support effect. (C) 2008 Elsevier B.V. All rights reserved

Meta-Analysis on Induction Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma.

Concurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta-analysis investigates the value of adding ICT to CCRT in LA-NPC. Two reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment-naive adult patients with histologically proven nonmetastatic LA-NPC. Eight RCTs with in total 2,384 randomized patients, of whom 69% had N2-N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%-100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) -0.001-0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, -0.243; 95% CI, -0.403 to -0.083; p = .003). Grade 3-4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511-0.905; p = .001) and progression-free survival (HR, 0.657; 95% CI, 0.568-0.760; p < .001). Although ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA-NPC, but further study on optimal patient selection for this treatment is warranted. Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta-analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA-NPC is associated with a significant clinical improvement in both overall survival and progression-free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA-NPC