Background: Significantly longer OS has been reported in advanced NSCLC pts. who gained weight or maintained (skeletal muscle mass) SMI during treatment with platinum containing chemotherapy. None of these studies evaluated the relationship between OS and both weight and SMI. Sex specific distributions are described for cachexia and muscle wasting. Methods: The objective of this retrospective study was to evaluate the relationships between OS and both weight gain and SMI maintenance during front line chemotherapy in advanced NSCLC pts. Weight and SMI measurements(cm²/m²) were done at baseline and at 6, 12, & 24 weeks. OS was estimated using the Kaplan-Meier method. The associations of weight and SMI with overall survival were assessed using Kaplan-Meier, log-rank test and proportional hazards regression. Results with p < 0.05 were reported as significant. Results: Characteristics for the 88 patients were: median age – 64 years, women – 57%, caucasian – 68%, black – 25%, and adenocarcinoma histology – 63%. Weight gain (i.e., > 0%) and > 5% weight gain were observed in 50% and 11.3% of the patients, respectively. For all 88 patients the hazard ratio(HR) for OS in patients with > 0% vs < 0% weight change was 0.544 (p = 0.0164), and the HR for OS for weight > 5% vs < 5% was 0.469 (p = 0.099). The HR for OS in men for > 0% vs < 0% weight gain was 0.421(p = 0.031), and HR for OS > 5% vs < 5% weight gain was 0.421 (p = 0.031). The same analyses in women showed no significant differences. Increases in SMI > 0% and > 5% SMI were found in 48% and 35% of patients, respectively. Maintenance of SMI defined as > - 1.3% was observed in 25% of pts. The HR for OS in men with SMI maintenance versus loss was 0.230 (p = 0.031), and the HR for OS in men with SMI increase > 5% vs < 5% was 0.219 (p = 0.0267). Neither SMI gain nor maintenance were significantly related to OS in the entire patient group or in women. Conclusions: In patients treated with first line platinum doublet, as a group there were no significant relationships between weight changes or SMI changes and OS. The observation that either weight gain or SMI maintenance was associated with longer OS in men only is based on data from a small number of patients. However, if larger studies show similar results, these findings could have implications for clinical and translational research in cachexia.