The lancet oncology
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Hair loss can be a psychologically devastating adverse effect of chemotherapy, but satisfactory management strategies for chemotherapy-induced alopecia remain elusive. In this Review we focus on the complex pathobiology of this side-effect. ⋯ Additionally, the degree of hair-follicle stem-cell damage determines whether chemotherapy-induced alopecia is reversible. We highlight the need for carefully designed preclinical research models to generate novel, clinically relevant pointers to how this condition may be overcome.
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The lancet oncology · Feb 2013
Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation.
Clear-cell renal-cell carcinomas display divergent clinical behaviours. However, the molecular genetic events driving these behaviours are unknown. We discovered that BAP1 is mutated in about 15% of clear-cell renal-cell carcinoma, and that BAP1 and PBRM1 mutations are largely mutually exclusive. The aim of this study was to investigate the clinicopathological significance of these molecular subtypes and to determine whether patients with BAP1-mutant and PBRM1-mutant tumours had different overall survival. ⋯ Cancer Prevention and Research Institution of Texas and National Cancer Institute.
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Patients with metastatic melanoma had few treatment options until 2011, when two drugs-ipilimumab and vemurafenib-were approved following advances in the understanding of melanoma biology and tumour immunology. Almost 50% of melanomas harbour mutations in BRAF, mainly at codon 600, which result in constitutive activation of the MAPK pathway. The selective inhibitors of mutant BRAF Val600, vemurafenib and dabrafenib, showed major tumour responses, resulting in improved progression-free and overall survival in patients with metastatic disease, compared with chemotherapy. ⋯ Multiple resistance mechanisms have been identified, including those that lead to reactivation of the MAPK pathway and other pathways, such as the PI3K-AKT-mTOR and VEGF pathways. Some patients with BRAF Val600 mutant melanoma seem to also benefit from immunotherapies such as high-dose interleukin 2 and ipilimumab, which, by contrast with BRAF inhibitors, can produce durable complete responses. We review the available data to best guide initial treatment choice and the sequence of treatments for patients with BRAF Val600 mutant melanoma.
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The lancet oncology · Feb 2013
Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study.
Low-grade serous carcinoma of the ovary is chemoresistant but mutations in the MAPK pathway could be targeted to control tumour growth. We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer. ⋯ National Cancer Institute.
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The lancet oncology · Feb 2013
Radiotherapy capacity in European countries: an analysis of the Directory of Radiotherapy Centres (DIRAC) database.
Radiotherapy is used for cure or palliation in around half of patients with cancer. We analysed data on radiotherapy equipment in 33 European countries registered in the Directory of Radiotherapy Centres (DIRAC) database, managed by the International Atomic Energy Agency. As of July, 2012, Europe had 1286 active radiotherapy centres. ⋯ Most western and southern European countries have several small centres with one or two machines, with few larger centres. The fragmentation in radiotherapy services that prevails in many European countries might affect the economic burden of radiotherapy and its quality. Eastern and southeastern European countries need to expand and modernise their radiotherapy equipment.