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The incidence of hypersensitivity reactions (HSRs) to PEG-asparaginase (PEG-ASNase) was evaluated in 6136 children with ALL enrolled in the AIEOP-BFM ALL 2009 study. Patients with B-cell precursor-acute lymphoblastic leukemia (BCP-ALL) were stratified as standard-risk/medium-risk (MR)/high-risk (HR) and those with T-ALL as non-High/HR. PEG-ASNase was administered intravenously at 2500 IU/sqm/dose. All patients received 2 PEG-ASNase doses in induction; thereafter non-HR versus HR patients received 1 versus 6 PEG-ASNase doses, respectively. After the single regular dose of PEG-ASNase at the beginning of delayed intensification, BCP-ALL-MR patients were randomized to receive 9 additional PEG-ASNase doses every 2 weeks (experimental arm [EA]) versus none (standard arm [SA]); HR patients were randomized to receive, in consolidation, 4 weekly PEG-ASNase doses (EA) versus none (SA). The HSR cumulative incidence (CI) was estimated adjusting for competing risks. An HSR occurred in 472 of 6136 (7.7%) patients. T-non- HR/BCP-Standard-Risk, BCP-MR-SA, BCP-MR-EA, HR-SA and HR-EA patients had 1-year-CI-HSR (±SE) rates of 5.2% (0.5), 5.2% (0.5), 4.0% (0.8), 20.2% (1.2), and 6.4% (1.3), respectively. The randomized intensification of PEG-ASNase did not significantly impact on HSR incidence in BCP-MR patients (1-y-CI-HSR 3.8% [0.8] versus 3.2% [0.6] in MR-EA versus MR-SA; P = 0.55), while impacted significantly in HR patients (1-y-CI-HSR 6.4% [1.3] versus 17.9% [1.8] in HR-EA and HR-SA, respectively; P < 0.001). The CI-HSR was comparable among non-HR groups and was not increased by a substantial intensification of PEG-ASNase in the BCP-MR-EA group whilst it was markedly higher in HR-SA than in HR-EA patients, suggesting that, in such a chemotherapy context, a continuous exposure to PEG-ASNase reduces the risk of developing an HSR.

The water-cooled lithium-lead (WCLL) test blanket module (TBM) of ITER and the respective breeding blanket (BB) of DEMO need to be efficiently characterized from the point of view of hydrogen isotopes inventory. An in situ detection is required to guarantee tritium self-sufficiency and to control the radiological hazards toward the external environment. In this context, a reliable hydrogen isotopes permeation sensor is essential both for tritium management at the several steps of the reactor fuel cycle and for monitoring the tritium processing systems, e.g., the tritium extraction system (TES). Hence, the hydrogen isotopes permeation sensors were characterized by protium experiments in a 1:1 scale experimental facility named TRIEX-II, located in ENEA C. R. Brasimone, Italy. The results obtained were used for preliminary validation of the novel hydrogen isotopes transport (HIT) code. Moreover, in order to test the sensor in different operative conditions, a new experimental device named Hyper-Quarch II (Hydrogen Permeation Quartz Chamber) is under development and will be installed in ENEA C. R. Brasimone, on the basis of the experience gained in the past experimental campaigns. This device, characterized by an upgraded quartz chamber and new instrumentation equipment, will be used to test and qualify an advanced hydrogen permeation sensor at a laboratory-scale in both dynamic and equilibrium modes: protium or deuterium will be used instead of tritium to simulate the operative conditions of ITER and DEMO reactors.

Background and purpose: Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment. Methods: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75mg/m2 i.v. every 3weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6months after the enrollment. PFS, overall survival at 9months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints. Results: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients. Conclusion: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time. Trial registration: This study is registered with ClinicalTrials.gov, number NCT01989884.

The International Energy Agency (IEA) has been promoting the IEA Environment, Safety and Economic Aspects of Fusion Power program for many years. Among the tasks of this program, one task in particular deals with radioactive waste management in order to analyze the issue of the final destination of fusion activated and tritiated materials after their use in a fusion power reactor. A collaborative study on these aspects has been carried out in recent years. An optimized waste management strategy is proposed, with the goals of avoiding underground disposal as much as possible, maximizing recycling of activated materials within the nuclear industry, and/or clearance and release to commercial markets if materials contain only slight traces of radioactivity. Some technological problems and recent research advances in this field are summarized.

Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose VitC modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell-dependent manner. VitC not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of VitC and ICT can be curative in models of mismatch repair-deficient tumors with high mutational burden. This work provides a rationale for clinical trials combining ICT with high doses of VitC.

Some technological problems of radioactive fusion materials management are being addressed in the paper. These problems are being studied in the frame of the International Energy Agency (IEA) collaborative study on fusion radioactive waste. These studies address the management procedures for radioactive materials following the changeout of replaceable components and decommissioning of fusion facilities. Key issues include clearance levels, hands-on and remote recycling procedures, fusion permanent waste hazard assessment, and detritiation of activated materials.

The efficacy of therapeutic regimens incorporating weekly or every-3-weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose-dense-equi (every other day to the conventional cumulative dose), or dose-dense-high (total dose 1.5 times higher), with or without bevacizumab. Treatment efficacy was evaluated analyzing tumor growth in different time-windows in two patient-derived ovarian cancer xenografts with different sensitivity to cisplatin. Tumor progression, metastasis and survival were studied in ovarian cancer models growing orthotopically and disseminating in the mouse peritoneal cavity. Short-term effects on cell cycle, tumor cell proliferation/apoptosis and vasculature were evaluated by flow cytometry and immunohistochemistry. PTX dose-dense (with/without DDP) was superior to the conventional scheme in a dose-dependent manner; the high efficacy was confirmed by the lower ratio of tumor to normal cells. All schemes benefited from bevacizumab, which reduced tumor vessels. However, DDP/PTX dose-dense-high (only chemotherapy) was at least as active as DDP/PTX conventional plus bevacizumab. DDP/PTX dose-dense-high plus bevacizumab was the most effective in delaying tumor progression, though it did not prolong mouse survival and the continuous treatment with bevacizumab was associated with a malignant disease. These findings indicate that the effect of bevacizumab in combination with chemotherapy may depend on the schedule-dose of the treatment and help to explain the unclear benefits after bevacizumab.

Some results of the collaborative studies organized by the International Energy Agency (IEA) in the area of technological problems of the fusion radioactive materials management following the withdrawing of replaceable components from the fusion facilities and de-commissioning of these facilities are addressed in this paper. Key issues include clearance conditions, hands-on and remote recycling procedures, radioactive fusion material hazard assessment, and detritiation of activated materials. To broaden the options for fusion development, researchers examined five potentially alternative high-Z materials: zirconium, niobium, molybdenum, hafnium, and tantalum from four standpoints: neutron-induced activation, sputter erosion/redeposition, plasma transient response and recycling possibility