O3-2-1 - Loss of muscle mass associated with the long term use of mTOR inhibitors

Abstract

Background: The loss of muscle mass is known as sarcopenia and has recently been known to be a predictor of poor prognosis and treatment toxicities in a variety of cancers. Some molecular targeted drugs are known to alter the muscle composition of the body. The effect of mTOR inhibitors on muscle composition is not known yet. Because mTOR pathway plays a key role in muscle metabolism, we studied the effect of long term use of mTOR inhibitors in the muscle mass of cancer patients. Methods: We retrospectively retrieved the CT scans at the level of the third lumber vertebra taken at baseline and after at least 6 months of any mTOR inhibitor use and performed body composition analysis using the software sliceOmatic ver5.0. The difference in body composition parameters was evaluated for significance. Time to treatment failure (TTF) was also compared between the sarcopenic and non-sarcopenic patients at baseline arms. Results: Of the 75 patients studied, 20 matched the entry criteria (16 male, median age 65.5 years, median BMI 20.7 kg/m2). The median duration of drug use was 11.9 months (range: 6.0-44.1 months). The number of sarcopenic patients at baseline was 12 (60%) which rose to 15 (75%) post-treatment. The use of mTOR inhibitors significantly decreased skeletal muscle area (mean 12.6 cm2 or 6.3 cm2/m2; P= 0.011) and lean body mass (mean 4.1 kg; P= 0.007) but had no effect on adipose tissue (P= 0.163) or body weight (P = 0.262). TTF did not differ between sarcopenic and non-sarcopenic patients and was not significantly associated with any other parameter. Conclusion: This study proves for the first time that the long term use of mTOR inhibitors lead to loss of muscle area and/or muscle mass. Because of the predictive and prognostic role of sarcopenia in cancer patients, this finding could have important clinical implications.