Original Study Prediction of Everolimus Toxicity and Prognostic Value of Skeletal Muscle Index in Patients With Metastatic Renal Cell Carcinoma Edouard Auclin, 1 Camille Bourillon, 2 Eleonora De Maio, 3 Marie Agnes By, 4 Sofiane Seddik, 5 Laure Fournier, 2 Marie Auvray, 1 Antoine Dautruche, 1 Yann-Alexandre Vano, 1,6,7 Constance Thibault, 1 Florence Joly, 5 Laurent Brunereau, 4 Carlos Gomez-Roca, 3 Christine Chevreau, 5 Reza Elaidi, 1,8 Stéphane Oudard 1,8,9 Abstract Patients with metastatic renal cell carcinoma with a skeletal muscle index (SMI) in the highest tercile have better overall survival with everolimus therapy versus those with an SMI in the lowest tercile. Low SMI did not influence the toxicity of everolimus. Whether SMI provides additional prognostic value to the International Metastatic Database Consortium prognostic group criteria remains to be determined. Background: The objective of the study was to assess the prognostic role of skeletal muscle index (SMI) in metastatic renal cell carcinoma (mRCC) patients treated with everolimus, and its effect of on everolimus-induced toxicity. Patients and Methods: Consecutive mRCC patients treated with everolimus between February 2007 and November 2014 underwent computed tomography scans at a single center performed by the same radiologist. SMI was assessed before everolimus treatment using the L3 cross-sectional area. Overall survival (OS) was analyzed according to SMI value. Results were adjusted using the International Metastatic Database Consortium (IMDC) prognostic group, body mass index (BMI), and/or number of previous tyrosine kinase inhibitor lines (NPL). Results: One hundred twenty- four mRCC patients (mean age, 60.21 years) were treated with everolimus as second- or third-line (82.3%) or > third- line (17.7%) therapy. Most patients (87.9%) had clear cell carcinoma. IMDC prognostic group was “favorable” (32.3%), “intermediate” (50%), or “poor” (17.7%). Median SMI was 40.75. OS was longer in patients from the highest versus lowest SMI tercile: 21.9 versus 10 months (P ¼ .002). Continuous SMI at baseline was not significantly associated with OS after adjustment for IMDC prognostic group, BMI, or NPL but the highest versus lowest SMI tercile was an in- dependent prognostic factor in multivariate analysis (P ¼ .025). There was no difference in everolimus toxicity between SMI tercile groups. Conclusion: SMI was an independent prognostic factor for mRCC patients treated with ever- olimus. Whether this provides additional prognostic value to IMDC criteria needs to be confirmed in a larger cohort. SMI does not seem to be predictive of everolimus-induced toxicity. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2017 Elsevier Inc. All rights reserved. Keywords: mTOR inhibitor, Sarcopenia, Survival, Treatment related toxicity, Treatment outcomes 1 Oncology Department 2 Radiology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France 3 Oncology Department, Institut Universitaire du Cancer de Toulouse (IUCT)/Institut Claudius Regaud, Toulouse, France 4 Oncology Department, Centre Hospitalier Bretonneau, Tours, France 5 Oncology Department, Centre François Baclesse, Caen, France 6 INSERM UMRS 1138, Cancer, Immune Control and Escape, Cordeliers Research Centre, Paris, France 7 Université Paris-Descartes, Sorbonne, Paris, France 8 Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie, Paris, France 9 U790 PARCC, European Georges Pompidou Hospital, René Descartes University, Paris, France Submitted: Jul 4, 2016; Revised: Jan 16, 2017; Accepted: Jan 23, 2017 Address for correspondence: Stéphane Oudard, MD, PhD, Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris 5, 20 rue Leblanc, 75015 Paris, France E-mail contact: stephane.oudard@aphp.fr 1558-7673/$ - see frontmatter ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2017.01.022 Clinical Genitourinary Cancer Month 2017 - 1