Memorial Sloan Kettering Cancer Center

About: Memorial Sloan Kettering Cancer Center is a healthcare organization based out in New York, New York, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 30293 authors who have published 65381 publications receiving 4462534 citations. The organization is also known as: MSKCC & New York Cancer Hospital.

Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study

Abstract: Summary Background In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF V600 mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAF V600E and BRAF V600K mutation subgroups. Methods Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF V600 mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m 2 of body surface area intravenously every 3 weeks). Coprimary endpoints were overall survival and progression-free survival, analysed in the intention-to-treat population (n=675), with data censored at crossover. A sensitivity analysis was done. This trial is registered with ClinicalTrials.gov, NCT01006980. Findings 675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4, 2010, and Dec 16, 2010. 337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine. Median follow-up was 12·5 months (IQR 7·7–16·0) on vemurafenib and 9·5 months (3·1–14·7) on dacarbazine. 83 (25%) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib. Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group (13·6 months [95% CI 12·0–15·2] vs 9·7 months [7·9–12·8]; hazard ratio [HR] 0·70 [95% CI 0·57–0·87]; p=0·0008), as was median progression-free survival (6·9 months [95% CI 6·1–7·0] vs 1·6 months [1·6–2·1]; HR 0·38 [95% CI 0·32–0·46]; p BRAF V600E disease, median overall survival in the vemurafenib group was 13·3 months (95% CI 11·9–14·9) compared with 10·0 months (8·0–14·0) in the dacarbazine group (HR 0·75 [95% CI 0·60–0·93]; p=0·0085); median progression-free survival was 6·9 months (95% CI 6·2–7·0) and 1·6 months (1·6–2·1), respectively (HR 0·39 [95% CI 0·33–0·47]; p BRAF V600K disease, median overall survival in the vemurafenib group was 14·5 months (95% CI 11·2–not estimable) compared with 7·6 months (6·1–16·6) in the dacarbazine group (HR 0·43 [95% CI 0·21–0·90]; p=0·024); median progression-free survival was 5·9 months (95% CI 4·4–9·0) and 1·7 months (1·4–2·9), respectively (HR 0·30 [95% CI 0·16–0·56]; p Interpretation Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF V600E mutation and in patients with the less common BRAF V600K mutation. Funding F Hoffmann-La Roche-Genentech.

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

Abstract: Background The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. ...

Regulation of ceramide production and apoptosis

Abstract: Ceramide is a sphingosine-based lipid signaling molecule that regulates cellular differentiation, proliferation, and apoptosis. The emerging picture suggests that coupling of ceramide to specific signaling cascades is both stimulus and cell-type specific. Ceramide action is determined within the context of other stimuli and by the subcellular topology of its production. Here, we discuss the pathways of ceramide generation and the interaction of ceramide with caspases and other apoptotic signaling cascades.

American Association of Physicists in Medicine Radiation Therapy Committee Task Group 53: Quality assurance for clinical radiotherapy treatment planning

Abstract: In recent years, the sophistication and complexity of clinical treatment planning and treatment planning systems has increased significantly, particularly including three-dimensional (3D) treatment planning systems, and the use of conformal treatment planning and delivery techniques. This has led to the need for a comprehensive set of quality assurance (QA) guidelines that can be applied to clinical treatment planning. This document is the report of Task Group 53 of the Radiation Therapy Committee of the American Association of Physicists in Medicine. The purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a comprehensive but viable program of quality assurance for modern radiotherapy treatment planning. The scope of the QA needs for treatment planning is quite broad, encompassing image-based definition of patient anatomy, 3D beam descriptions for complex beams including multileaf collimator apertures, 3D dose calculation algorithms, and complex plan evaluation tools including dose volume histograms. The Task Group recommends an organizational framework for the task of creating a QA program which is individualized to the needs of each institution and addresses the issues of acceptance testing, commissioning the planning system and planning process, routine quality assurance, and ongoing QA of the planning process. This report, while not prescribing specific QA tests, provides the framework and guidance to allow radiation oncology physicists to design comprehensive and practical treatment planning QA programs for their clinics.