Long-Term Survivorship of Esophageal Cancer Patients Treated with Radical Intent

To investigate the recent trends in definitive management of esophageal cancer, the records of 138 consecutive patients treated with radical intent in a single institution between 1995 and 2003 were reviewed and analyzed. The median follow-up period was 5.7 years (range 1.1 to 10.4 years). Seventy-seven patients were treated with radiation therapy (RT) only and 61 with combined regimens (CRT), in which RT was combined with either radical surgery or chemotherapy, or both. The overall survival of the entire cohort was 32% over two years and 20% over five years. The survivorship in the RT group was 17% over two years and 5% over five years. In the CRT group, 51% and 35% survived over two and five years, respectively. From all the potential prognostic factors examined by univariate and multivariate analyses, only male sex and use of CRT were strongly associated with better survivorship. There was no significant difference in the outcomes among the different regimens of CRT. Survivorship was not affected by the location or histology of the tumour, clinical stage, dose of RT or use of endoluminal brachytherapy in addition to external beam RT. There was a greater tendency to use RT only more often in older patients, but patient age did not affect survivorship. The proportion of patients treated with CRT did not change significantly over the last versus the first four years of the observed period. Combined regimens are undoubtedly superior to RT as a single modality. The long-term survivorship of patients in a subgroup of our patients treated with combined modality protocols compared favourably with the previously reported results in the literature and specifically in prospective randomized trials. However, the optimal combined modality regimen is yet to be defined

Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial

Abstract Metformin may exert anticancer effects through indirect (mediated by metabolic changes) or direct mechanisms. The goal was to examine metformin impact on metabolic factors in non-diabetic subjects and determine whether this impact varies by baseline BMI, insulin, and rs11212617 SNP in CCTG MA.32, a double-blind placebo-controlled randomized adjuvant breast cancer (BC) trial. 3649 subjects with T1-3, N0-3, M0 BC were randomized; pretreatment and 6-month on-treatment fasting plasma was centrally assayed for insulin, leptin, highly sensitive C-reactive protein (hsCRP). Glucose was measured locally and homeostasis model assessment (HOMA) calculated. Genomic DNA was analyzed for the rs11212617 SNP. Absolute and relative change of metabolic factors (metformin versus placebo) were compared using Wilcoxon rank and t-tests. Regression models were adjusted for baseline differences and assessed interactions with baseline BMI, insulin, and the SNP. Mean age was 52 years. The majority had T2/3, node positive, hormone receptor positive, HER2 negative BC treated with (neo)adjuvant chemotherapy and hormone therapy. Median baseline body mass index (BMI) was 27.4 kg/m2 (metformin) and 27.3 kg/m2 (placebo). Median weight change was −1.4 kg (metformin) vs +0.5 kg (placebo). Significant improvements were seen in all metabolic factors, with 6 month standardized ratios (metformin/placebo) of 0.85 (insulin), 0.83 (HOMA), 0.80 (leptin), and 0.84 (hsCRP), with no qualitative interactions with baseline BMI or insulin. Changes did not differ by rs11212617 allele. Metformin (vs placebo) led to significant improvements in weight and metabolic factors; these changes did not differ by rs11212617 allele status