Body mass index and metastatic renal cell carcinoma: Clinical and biological correlations

Laurence Albiges, A. Ari Hakimi, Wanling Xie, Rana R. McKay, Ronit Simantov, Xun Lin, Jae Lyun Lee, Brian I. Rini, Sandy Srinivas, Georg A. Bjarnason, Scott Ernst, Lori A. Wood, Ulka N. Vaishamayan, Sun Young Rha, Neeraj Agarwal, Takeshi Yuasa, Sumanta K. Pal, Aristotelis Bamias, Emily C. Zabor, Anders J. SkanderupHelena Furberg, Andre P. Fay, Guillermo De Velasco, Mark A. Preston, Kathryn M. Wilson, Eunyoung Cho, David F. McDermott, Sabina Signoretti, Daniel Y.C. Heng, Toni K. Choueiri

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62 Citations (Scopus)

Abstract

Purpose: Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC. Methods: The impact of BMI (high BMI: ≥ 25 kg/m2 v low BMI:, 25 kg/m2) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients. Gene expression profiling focusing on fatty acid metabolism pathway, in The Cancer Genome Atlas data set, and immunohistochemistry staining for fatty acid synthase (FASN) were also investigated. Cox regression was undertaken to estimate the association of BMI with OS, adjusted for the IMDC prognostic factors. Results: In the IMDC cohort, median OS was 25.6 months (95% CI, 23.2 to 28.6) in patients with high BMI versus 17.1 months (95% CI, 15.5 to 18.5) in patients with low BMI (adjusted hazard ratio, 0.84; 95% CI, 0.73 to 0.95). In the validation cohort, high BMI was associated with improved OS (adjusted hazard ratio, 0.83; 95% CI, 0.74 to 0.93; medians: 23.4 months [95% CI, 21.9 to 25.3 months] v 14.5 months [95% CI, 13.8 to 15.9 months], respectively). In The Cancer Genome Atlas data set (n = 61), FASN gene expression inversely correlated with BMI (P =.034), and OS was longer in the low FASN expression group (medians: 36.8 v 15.0 months; P =.002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor (48%) and intermediate (34%) risk groups than in the favorable risk group (17%; P-trend =.015). Conclusion: High BMI is a prognostic factor for improved survival and progression-free survival in patients with metastatic RCC treated with targeted therapy. Underlying biology suggests a role for the FASN pathway.

Original languageEnglish
Pages (from-to)3655-3663
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number30
DOIs
Publication statusPublished - 2016 Oct 20

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Albiges, L., Ari Hakimi, A., Xie, W., McKay, R. R., Simantov, R., Lin, X., Lee, J. L., Rini, B. I., Srinivas, S., Bjarnason, G. A., Ernst, S., Wood, L. A., Vaishamayan, U. N., Rha, S. Y., Agarwal, N., Yuasa, T., Pal, S. K., Bamias, A., Zabor, E. C., ... Choueiri, T. K. (2016). Body mass index and metastatic renal cell carcinoma: Clinical and biological correlations. Journal of Clinical Oncology, 34(30), 3655-3663. https://doi.org/10.1200/JCO.2016.66.7311