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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations
Laurence Albiges1, A Ari Hakimi1, Wanling Xie1
1Laurence Albiges, Wanling Xie, Rana R. McKay, Andre P. Fay, Guillermo de Velasco, Sabina Signoretti, and Toni K. Choueiri, Dana-Farber Cancer Institute; Wanling Xie, Rana R. McKay, Mark A. Preston, Eunyoung Cho, Sabina Signoretti, and Toni K. Choueiri, Brigham and Women's Hospital; Laurence Albiges, Wanling Xie, Rana R. McKay, Andre P. Fay, Guillermo de Velasco, Eunyoung Cho, David F. McDermott, Sabina Signoretti, and Toni K. Choueiri, Harvard Medical School; Mark A. Preston and Kathryn M. Wilson, Harvard School of Public Health; David F. McDermott, Beth Israel Deaconess Medical Center, Boston, MA; Laurence Albiges, Gustave Roussy, Université Paris-Saclay, Villejuif, France; A. Ari Hakimi, Emily C. Zabor, Anders J. Skanderup, and Helena Furberg, Memorial Sloan Kettering Cancer Center, New York; Ronit Simantov and Xun Lin, Pfizer Oncology, New York, NY; Jae-Lyun Lee, University of Ulsan College of Medicine, Asan; Sun-Young Rha, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Sandy Srinivas, Stanford Cancer Institute, Stanford; Sumanta K. Pal, City of Hope Comprehensive Cancer Center, Duarte, CA; Georg A. Bjarnason, Sunnybrook Odette Cancer Center, Toronto; Scott Ernst, London Health Sciences Center, London, Ontario; Lori A. Wood, Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia; Daniel Y.C. Heng, Tom Baker Cancer Center; University of Calgary, Calgary, Alberta, Canada; Ulka N. Vaishamayan, Karmanos Cancer Center, Detroit, MI; Neeraj Agarwal, University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Takeshi Yuasa, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; Aristotelis Bamias, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; and Eunyoung Cho, The Warren Alpert Medical School of Brown University; Brown University School of Public Health, Providence, RI.
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.
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