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. 2016 Oct 20;34(30):3655-3663.
doi: 10.1200/JCO.2016.66.7311.

Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations

Laurence Albiges  1 , A Ari Hakimi  1 , Wanling Xie  1 , Rana R McKay  1 , Ronit Simantov  1 , Xun Lin  1 , Jae-Lyun Lee  1 , Brian I Rini  1 , Sandy Srinivas  1 , Georg A Bjarnason  1 , Scott Ernst  1 , Lori A Wood  1 , Ulka N Vaishamayan  1 , Sun-Young Rha  1 , Neeraj Agarwal  1 , Takeshi Yuasa  1 , Sumanta K Pal  1 , Aristotelis Bamias  1 , Emily C Zabor  1 , Anders J Skanderup  1 , Helena Furberg  1 , Andre P Fay  1 , Guillermo de Velasco  1 , Mark A Preston  1 , Kathryn M Wilson  1 , Eunyoung Cho  1 , David F McDermott  1 , Sabina Signoretti  1 , Daniel Y C Heng  1 , Toni K Choueiri  1
Affiliations

Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations

Laurence Albiges et al. J Clin Oncol. .

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.

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Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Kaplan-Meier estimates of overall survival (A) in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) cohort, and (B) in validation cohort, and Kaplan-Meier estimates of (C) time to treatment failure in the IMDC cohort and (D) progression-free survival in validation cohort, stratified by body mass index (BMI) group (total number of events = 1,221 and 1,671 for A and C; total number of events = 2,109 and 2,885 for B and D).
Fig 2.
Fig 2.
Fatty acid synthase (FASN) expression level in The Cancer Genome Atlas patients with metastatic clear cell renal cell carcinoma. (A) FASN expression level association with body mass index category. (B) FASN expression level association with overall survival (total N = 60; number of deaths = 50).
Fig 3.
Fig 3.
Association of fatty acid synthase (FASN) immunohistochemistry staining with overall survival (OS; total N = 146; number of deaths = 122).
Fig A1.
Fig A1.
Reason for treatment failure stratified by body mass index (BMI) group in the International Metastatic Renal Cell Carcinoma Database Consortium cohort. Estimates of the cumulative incidence of treatment failure because of toxicity did not differ between the underweight/normal and overweight/obese groups. Cumulative incidence of treatment failure because of progression/death favored the overweight/obese group after adjustment for the International Metastatic Renal Cell Carcinoma Database Consortium risk groups.
Fig A2.
Fig A2.
Fatty acid synthase immunohistochemistry staining: renal cell carcinoma tissues (A) positive, (B) negative.
See this image and copyright information in PMC

Comment in

References

    1. Chow WH, Gridley G, Fraumeni JF, Jr, et al. Obesity, hypertension, and the risk of kidney cancer in men. N Engl J Med. 2000;343:1305–1311. - PubMed
    1. Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569–578. - PubMed
    1. Chow W-H, Dong LM, Devesa SS. Epidemiology and risk factors for kidney cancer. Nat Rev Urol. 2010;7:245–257. - PMC - PubMed
    1. Choi Y, Park B, Jeong BC, et al. Body mass index and survival in patients with renal cell carcinoma: A clinical-based cohort and meta-analysis. Int J Cancer. 2013;132:625–634. - PubMed
    1. Choueiri TK, Xie W, Kollmannsberger CK, et al: The impact of body mass index (BMI) and body surface area (BSA) on treatment outcome to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma: Results from a large international collaboration. J Clin Oncol 28, 2010 (suppl; abstr 4524)