title: Prediction of Everolimus Toxicity and Prognostic Value of Skeletal Muscle Index in Patients With Metastatic Renal Cell Carcinoma.
abstract: 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.
  
  
  
  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).
  
  
  
  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 = .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 independent prognostic factor in multivariate analysis (P = .025). There was no difference in everolimus toxicity between SMI tercile groups.
  
  
  
  SMI was an independent prognostic factor for mRCC patients treated with everolimus. 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.
authors.affiliation: Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Auclin
authors.affiliation: Radiology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Bourillon
authors.affiliation: Oncology Department, Institut Universitaire du Cancer de Toulouse (IUCT)/Institut Claudius Regaud, Toulouse, France.
authors.forename: Eleonora
authors.initials: E
authors.lastname: De Maio
authors.affiliation: Oncology Department, Centre Hospitalier Bretonneau, Tours, France.
authors.forename: Marie Agnes
authors.initials: MA
authors.lastname: By
authors.affiliation: Oncology Department, Centre François Baclesse, Caen, France.
authors.forename: Sofiane
authors.initials: S
authors.lastname: Seddik
authors.affiliation: Radiology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Fournier
authors.affiliation: Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Auvray
authors.affiliation: Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Dautruche
authors.affiliation: Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France; INSERM UMRS 1138, Cancer, Immune Control and Escape, Cordeliers Research Centre, Paris, France; Université Paris-Descartes, Sorbonne, Paris, France.
authors.forename: Yann-Alexandre
authors.initials: YA
authors.lastname: Vano
authors.affiliation: Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Thibault
authors.affiliation: Oncology Department, Centre François Baclesse, Caen, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.affiliation: Oncology Department, Centre Hospitalier Bretonneau, Tours, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brunereau
authors.affiliation: Oncology Department, Institut Universitaire du Cancer de Toulouse (IUCT)/Institut Claudius Regaud, Toulouse, France.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gomez-Roca
authors.affiliation: Oncology Department, Centre François Baclesse, Caen, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.affiliation: Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France; Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie, Paris, France.
authors.forename: Reza
authors.initials: R
authors.lastname: Elaidi
authors.affiliation: Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France; Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie, Paris, France; U790 PARCC, European Georges Pompidou Hospital, René Descartes University, Paris, France. Electronic address: stephane.oudard@aphp.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018572:Disease-Free Survival; D000068338:Everolimus / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000187:drug effects; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus
keywords: Sarcopenia; Survival; Treatment outcomes; Treatment related toxicity; mTOR inhibitor