The lancet oncology
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The lancet oncology · Apr 2015
ReviewTransformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin.
Lung cancer is the most common cause of cancer deaths worldwide. The two broad histological subtypes of lung cancer are small-cell lung cancer (SCLC), which is the cause of 15% of cases, and non-small-cell lung cancer (NSCLC), which accounts for 85% of cases and includes adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma. Although NSCLC and SCLC are commonly thought to be different diseases owing to their distinct biology and genomic abnormalities, the idea that these malignant disorders might share common cells of origin has been gaining support. ⋯ Additionally, other case reports have described the coexistence of NSCLC and SCLC, further challenging the commonly accepted view of their distinct lineages. Here, we summarise the published clinical observations and biology underlying tumours with combined SCLC and NSCLC histology and cancers that transform from adenocarcinoma to SCLC. We also discuss pre-clinical studies pointing to common potential cells of origin, and speculate how the distinct paths of differentiation are determined by the genomics of each disease.
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The lancet oncology · Apr 2015
Randomized Controlled Trial Multicenter StudyNivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.
Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of chemotherapy (ICC) as a second-line or later-line treatment in patients with advanced melanoma. ⋯ Bristol-Myers Squibb.
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Nomograms are widely used as prognostic devices in oncology and medicine. With the ability to generate an individual probability of a clinical event by integrating diverse prognostic and determinant variables, nomograms meet our desire for biologically and clinically integrated models and fulfill our drive towards personalised medicine. Rapid computation through user-friendly digital interfaces, together with increased accuracy, and more easily understood prognoses compared with conventional staging, allow for seamless incorporation of nomogram-derived prognosis to aid clinical decision making. ⋯ However, the statistical foundations of nomogram construction, their precise interpretation, and evidence supporting their use are generally misunderstood. This issue is leading to an under-appreciation of the inherent uncertainties regarding nomogram use. We provide a systematic, practical approach to evaluating and comprehending nomogram-derived prognoses, with particular emphasis on clarifying common misconceptions and highlighting limitations.
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The lancet oncology · Apr 2015
Randomized Controlled TrialDocetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial.
Patients with metastatic castration-resistant prostate cancer have few treatment options. We investigated the safety and efficacy of lenalidomide, an immunomodulatory agent with anti-angiogenic properties, in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. ⋯ Celgene Corporation.
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The lancet oncology · Apr 2015
Randomized Controlled TrialVorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.
Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival. ⋯ Merck & Co.