Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients

Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab.Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line.Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6 months) and atezolizumab plus bev-acizumab first-line (15.7 months; p = 0.12; hazard ratio [HR] = 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who under-went trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8 months, p < 0.01; HR = 0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0 months) and those who under-went TACE (15.9 months) had a significative longer OS than patients treated with sorafenib (14.2 months; respectively, p = 0.01; HR = 0.45, and p < 0.05; HR = 0.46).Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy

Les suicides et tentatives de suicide en Polynésie française (étude épidémiologique (1988/1999))

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Contact fatigue behavior of a-Al2O3-Ti(C,N) CVD coated WC-Co under dry and wet conditions

The response to cycling contact fatigue load of a WC-6%Co carbide coated with a Ti(C,N)/a-Al2O3 CVD multilayer was investigated in dry and wet conditions. Imprints in dry conditions were characterized by small thin cracks forming a circumference at the maximum radii of the imprint. The damaged coating was totally present in the final imprint of the dry test. Wet indentations showcase an area in the imprint where the a-Al2O3 layer has been removed throughout a ring but was kept at the center of the indentation, suggesting that the coating damage under cycling contact load in wet conditions is dominated by a-Al2O3 degradation, associated with a fretting effect or tangential loads accelerating the fatigue-corrosion of the alumina layer.Peer ReviewedPostprint (author's final draft

Agricultural exposure and risk of soft tissue sarcomas and gastrointestinal stromal sarcoma in the AGRIculture and CANcer (AGRICAN) cohort

BACKGROUND: Sarcomas are a heterogeneous group of tumors whose incidence is nearly 5 per 100 000 inhabitants in Europe. Their causes are poorly understood, although occupational exposures (especially farming and pesticides) are suspected. METHODS: The AGRICAN cohort is a prospective study of 181,842 individuals enrolled in 2005-2007 who completed an enrolment questionnaire with data on lifelong agricultural exposure. Associations between agricultural exposure and sarcoma overall, GIST (gastro-intestinal stromal tumors) and myomatous and fibrous sarcoma together, were analyzed with a Cox model. RESULTS: Until 2015, 188 incident cases of sarcoma were identified. Increased risks were observed (1) among cattle farmers working < 10 years (HR(<10years) =2.45, 95%CI 1.36-4.43) and breeding ≥ 50 livestock (HR(≥50 animals) =3.84, 95%CI 1.60-9.22), especially if involved in animal care and building disinfection, (2) in greenhouse production (HR=1.82, 95%CI 1.01-3.30), and (3) in field-grown vegetable production (HR=1.49, 95%CI 0.96-2.32). Concerning histological subtypes, GIST were positively associated with pesticide use in vineyards (HR=2.24, 95%CI 0.95-5.30). For myomatous and fibrous sarcoma, the only increase was seen in field-grown vegetable production (HR=2.37, 95%CI 1.16-4.85). CONCLUSION: In AGRICAN, the risk of sarcomas was increased in several farming activities with differences according to histological subtype

α-FAtE: A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

: Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first-line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real-world AB-treated HCC patients were analyzed in uni- and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α-FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni- and multivariate analyses for OS of a comparable lenvatinib-treated HCC population. Finally, comparison between treatments was performed in patients with low and high α-FAtE scores and predictivity estimated by interaction analysis. Time-to-progression (TTP) was a secondary endpoint. OS of AB-treated HCC patients was statistically longer in those with α-fetoprotein &lt;400 ng/mL (HR 0.62, p = .0407), alkaline phosphatase (ALP) &lt;125 IU/L (HR 0.52, p = .0189) and eosinophil count ≥70/μL (HR 0.46, p = .0013). The α-FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p &lt; .02). Patients with high score had longer OS (HR 0.44, p = .0009) and TTP (HR 0.34, p &lt; .0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p = .0043) and inferior in low score ones (HR 1.75, p = .0227). At interaction test, low α-FAtE score resulted as negative predictive factor of response to AB (p = .0004). In conclusion, α-FAtE is a novel prognostic and predictive score of response to first-line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB