The lancet oncology
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The lancet oncology · Oct 2015
Risk of death among children of atomic bomb survivors after 62 years of follow-up: a cohort study.
No clear epidemiological hereditary effects of radiation exposure in human beings have been reported. However, no previous studies have investigated mortality into middle age in a population whose parents were exposed to substantial amounts of radiation before conception. We assessed mortality in children of the atomic bomb survivors after 62 years of follow-up. ⋯ Late effects of ionising radiation exposure include increased mortality risks, and models of the transgenerational effects of radiation exposure predict more genetic disease in the children of people exposed to radiation. However, children of people exposed to the atomic bombs in Hiroshima and Nagasaki had no indications of deleterious health effects after 62 years. Epidemiological studies complemented by sensitive molecular techniques are needed to understand the overall effects of preconception exposure to ionising radiation on human beings.
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The lancet oncology · Oct 2015
Randomized Controlled Trial Multicenter Study Comparative StudyComparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial.
In the COMBI-v trial, patients with previously untreated BRAF Val600Glu or Val600Lys mutant unresectable or metastatic melanoma who were treated with the combination of dabrafenib and trametinib had significantly longer overall and progression-free survival than those treated with vemurafenib alone. Here, we present the effects of treatments on health-related quality of life (HRQoL), an exploratory endpoint in the COMBI-v study. ⋯ From the patient's perspective, which integrates not only survival advantage but also disease-associated and adverse-event-associated symptoms, treatment with the combination of a BRAF inhibitor plus a MEK inhibitor (dabrafenib plus trametinib) adds a clear benefit over monotherapy with the BRAF inhibitor vemurafenib and supports the combination therapy as standard of care in this population.
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The lancet oncology · Oct 2015
ReviewRadiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy.
Checkpoint blockade immunotherapy has received mainstream attention as a result of striking and durable clinical responses in some patients with metastatic disease and a reasonable response rate in many tumour types. The activity of checkpoint blockade immunotherapy is not restricted to melanoma or lung cancer, and additional indications are expected in the future, with responses already reported in renal cancer, bladder cancer, and Hodgkin's lymphoma among many others. Additionally, the interactions between radiation and the immune system have been investigated, with several studies describing the synergistic effects on local and distant tumour control when radiation therapy is combined with immunotherapy. ⋯ Herein, we discuss the biological and mechanistic rationale behind combining radiation with checkpoint blockade immunotherapy, with a focus on the preclinical data supporting this potentially synergistic combination. We explore potential hypotheses and important considerations for clinical trial designs. Finally, we reintroduce the notion of radiosensitising immunotherapy, akin to radiosensitising chemotherapy, as a potential definitive therapeutic modality.
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The lancet oncology · Oct 2015
Randomized Controlled Trial Multicenter Study Comparative StudyFOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study.
In the TRIBE study, FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab significantly improved progression-free survival of patients with metastatic colorectal cancer compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. In this updated analysis, we aimed to provide mature results for overall survival-a secondary endpoint-and report treatment efficacy in RAS and BRAF molecular subgroups. ⋯ FOLFOXIRI plus bevacizumab is a feasible treatment option for those patients who meet the inclusion criteria of the present study, irrespective of baseline clinical characteristics and RAS or BRAF mutational status.