Formation of nanosized hills on Ti3SiC2 oxide layer irradiated with swift heavy ions

International audienceThe Ti3SiC2 refractory compound that combines properties of both metals and ceramics is a fuel cladding candidate under investigation for Gas-cooled Fast Reactor. Its behavior under swift heavy ion irradiation (Xe ions, 92 MeV, 1019 m−2) was investigated. Significant and unexpected surface changes have been highlighted: hills have been observed by AFM on the surface of Ti3SiC2. Such a topographic modification has never been observed in other materials irradiated in similar conditions. The characterization of these hills by both XPS and X-TEM has highlighted that the surface modifications do not appear in Ti3SiC2 but in the amorphous oxide layer located on the sample surface before irradiation. Moreover, the thickness of this oxide layer grew under irradiation dose. The comparison with previous irradiations has led to the conclusion that this surface modification stems from electronic interactions in this amorphous layer, and that there is a threshold in the electronic stopping power to overcome to form hills

Damages induced by heavy ions in titanium silicon carbide: effects of nuclear and electronic interactions at room temperature

International audienceThanks to their refractoriness, carbides are sensed as fuel coating for the IVth generation of reactors. Among those studied, the Ti3SiC2 ternary compound can be distinguished for its noteworthy mechanical properties: the nanolamellar structure imparts to this material some softness as well as better toughness than other classical carbides such as SiC or TiC. However, under irradiation, its behaviour is still unknown. In order to understand this behaviour, specimens were irradiated with heavy ions of different energies, then characterised. The choice of energies used allowed separation of the effects of nuclear interactions from those of electronic ones

Cost effectivenes of erlotinib versus chemotherapy for first-line treatment of non small cell lung cancer (NSCLC) in fit elderly patients participating in a prospective phase 2 study (GFPC 0504)

BACKGROUND: The median age of newly diagnosed patients with non-small cell lung cancer (NSCLC) is 67 years, and one-third of patients are older than 75 years. Elderly patients are more vulnerable to the adverse effects of chemotherapy, and targeted therapy might thus be a relevant alternative. The objective of this study was to assess the cost-effectiveness of erlotinib followed by chemotherapy after progression, compared to the reverse strategy, in fit elderly patients with advanced NSCLC participating in a prospective randomized phase 2 trial (GFPC0504). METHODS: Outcomes (PFS and overall survival) and costs (limited to direct medical costs, from the third-party payer perspective) were prospectively collected until second progression. Costs after progression and health utilities (based on disease states and grade 3–4 toxicities) were derived from the literature. RESULTS: Median overall survival, QALY and total costs for the erlotinib-first strategy were respectively 7.1 months, 0.51 and 27 734 €, compared to 9.4 months, 0.52 and 31 688 € for the chemotherapy-first strategy. The Monte Carlo simulation demonstrates that the two strategies do not differ statistically. CONCLUSION: In terms of cost effectiveness, in fit elderly patients with NSCLC, erlotinib followed by chemotherapy compares well with the reverse strategy

Creation of multiple nanodots by single ions

In the challenging search for tools that are able to modify surfaces on the nanometer scale, heavy ions with energies of several 10 MeV are becoming more and more attractive. In contrast to slow ions where nuclear stopping is important and the energy is dissipated into a large volume in the crystal, in the high energy regime the stopping is due to electronic excitations only. Because of the extremely local (< 1 nm) energy deposition with densities of up to 10E19 W/cm^2, nanoscaled hillocks can be created under normal incidence. Usually, each nanodot is due to the impact of a single ion and the dots are randomly distributed. We demonstrate that multiple periodically spaced dots separated by a few 10 nanometers can be created by a single ion if the sample is irradiated under grazing angles of incidence. By varying this angle the number of dots can be controlled.Comment: 12 pages, 6 figure

Routine molecular profiling of cancer: results of a one-year nationwide program of the French Cooperative Thoracic Intergroup (IFCT) for advanced non-small cell lung cancer (NSCLC) patients.

International audienceBackground: The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute. Methods This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582. Findings 18 679 molecular analyses of 17 664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18–98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7–16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17 706 analyses for which data were available, HER2 mutations in 98 (1%) of 11 723, KRAS mutations in 4894 (29%) of 17 001, BRAF mutations in 262 (2%) of 13 906, and PIK3CA mutations in 252 (2%) of 10 678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8–25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7–38·2] for presence of a genetic alteration vs 33% [29·5–35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0–18·8] vs 9% [6·7–11·9]; p&lt;0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2–10·7] vs 7·1 months [6·1–7·9]; p&lt;0·0001) and overall survival (16·5 months [15·0–18·3] vs 11·8 months [10·1–13·5]; p&lt;0·0001) compared with absence of a genetic alteration. Interpretation Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit

COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non–Small-Cell Lung Cancer

Durvalumab; Non-Small-Cell Lung CancerDurvalumab; Cáncer de pulmón de células no pequeñasDurvalumab; Càncer de pulmó de cèl·lules no petitesPURPOSE Durvalumab significantly improves overall survival for patients with unresectable stage III non–small-cell lung cancer and no progression after concurrent chemoradiotherapy (cCRT). Building upon that standard of care, COAST is a phase II study of durvalumab alone or combined with the anti-CD73 monoclonal antibody oleclumab or anti-NKG2A monoclonal antibody monalizumab as consolidation therapy in this setting. METHODS Patients with unresectable stage III non–small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and no progression after cCRT were randomly assigned 1:1:1, ≤ 42 days post-cCRT, to durvalumab alone or combined with oleclumab or monalizumab for up to 12 months, stratified by histology. The primary end point was investigator-assessed confirmed objective response rate (ORR; RECIST v1.1). RESULTS Between January 2019 and July 2020, 189 patients were randomly assigned. At this interim analysis (data cutoff, May 17, 2021), median follow-up was 11.5 months (range, 0.4-23.4 months; all patients). Confirmed ORR was numerically higher with durvalumab plus oleclumab (30.0%; 95% CI, 18.8 to 43.2) and durvalumab plus monalizumab (35.5%; 95% CI, 23.7 to 48.7) versus durvalumab (17.9%; 95% CI, 9.6 to 29.2). Progression-free survival (PFS) was prolonged with both combinations versus durvalumab (plus oleclumab: hazard ratio, 0.44; 95% CI, 0.26 to 0.75; and plus monalizumab: hazard ratio, 0.42; 95% CI, 0.24 to 0.72), with higher 12-month PFS rates (plus oleclumab: 62.6% [95% CI, 48.1 to 74.2] and plus monalizumab: 72.7% [95% CI, 58.8 to 82.6] v durvalumab alone: 33.9% [95% CI, 21.2 to 47.1]). All-cause grade ≥ 3 treatment-emergent adverse events occurred in 40.7%, 27.9%, and 39.4% with durvalumab plus oleclumab, durvalumab plus monalizumab, and durvalumab, respectively. CONCLUSION Both combinations increased ORR and prolonged PFS versus durvalumab alone. Safety was similar across arms with no new or significant safety signals identified with either combination. These data support their further evaluation in a phase III trial

Examining Different Regimes of Ionization-Induced Damage in GaN Through Atomistic Simulations

Peer reviewe

Electron and electron-ion sequential irradiation of borosilicate glasses: Impact of the pre-existing defects

A three-oxide sodium borosilicate glass was irradiated with 2.3 MeV electrons up to 0.15 GGy and 4.6 GGy, and subsequently with 96 MeV Xe ions. The irradiated samples were characterised using Raman spectroscopy, ToF-SIMS, microhardness and surface profilometry. Electron irradiation of the pristine glasses resulted in different structural modifications at the sample surface and in the bulk of the glass, whereas, ion irradiation of either the pristine or bulk of the electron pre-irradiated glasses induced same structural, physical and mechanical property changes. Furthermore, sample surfaces showed a different behaviour than that of the bulk upon subsequent ion irradiation. These results show that the radiation sensitivity of surfaces can significantly vary depending on the type of the irradiation. Therefore, detailed studies aimed at understanding the response of the surfaces to mono and electron-ion double-beam irradiations should be undertaken to address the long-term evolution of the nuclear waste glass matrix surfaces

Swift heavy ion-irradiated multi-phase calcium borosilicates: implications to molybdenum incorporation, microstructure, and network topology

Abstract: A series of calcium borosilicate glasses with varying [B2O3], [MoO3], and [CaO] were prepared and subjected to 92 MeV Xe ions used to simulate the damage from long-term α-decay in nuclear waste glasses. Modifications to the solubility of molybdenum, the microstructure of separated phases, and the Si–O–B network topology were investigated following five irradiation experiments that achieved doses between 5 × 1012 and 1.8 × 1014 Xe ions/cm2 in order to test the hypotheses of whether irradiation would induce, propagate, or anneal phase separation. Using electron microscopy, EDS analysis, Raman spectroscopy, and XRD, irradiation was observed to increase the integration of MoO42− by increasing the structural disorder within and between heterogeneous amorphous phases. This occurred through Si/B-O-Si/B bond breakage and reformation of boroxyl and 3/4-membered SiO4 rings. De-mixing of the Si–O–B network concurrently enabled cross directional Ca and Mo diffusion along defect created pathways, which were prevalent along the interface between phases. The initiation and extent of these changes was dependent primarily on the [SiO2]/[B2O3] ratio, with [MoO3] having a secondary effect on influencing the defect population with increasing dose. Microstructurally, these changes to bonding caused a reduction in heterogeneities between amorphous phases by reducing the size and increasing the spatial distribution of immiscible droplets. This general increase in structural disorder prevented crystallization in most cases, but where precipitation was initiated by radiation, it was re-amorphized with increasing dose. These outcomes suggest that internal radiation can alter phase separation tie lines, and can therefore be used as a tool to design certain structural environments for long-term encapsulation of radioisotopes