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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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

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Renal Cell Carcinoma
Body Mass Index
Fatty Acid Synthases
Survival
Atlases
Immunohistochemistry
Genome
Gene Expression Profiling
Disease-Free Survival
Neoplasms
Fatty Acids
Obesity
Databases
Staining and Labeling
Gene Expression
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Albiges, L., Ari Hakimi, A., Xie, W., McKay, R. R., Simantov, R., Lin, X., ... 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
Albiges, Laurence ; Ari Hakimi, A. ; Xie, Wanling ; McKay, Rana R. ; Simantov, Ronit ; Lin, Xun ; Lee, Jae Lyun ; Rini, Brian I. ; Srinivas, Sandy ; Bjarnason, Georg A. ; Ernst, Scott ; Wood, Lori A. ; Vaishamayan, Ulka N. ; Rha, Sun Young ; Agarwal, Neeraj ; Yuasa, Takeshi ; Pal, Sumanta K. ; Bamias, Aristotelis ; Zabor, Emily C. ; Skanderup, Anders J. ; Furberg, Helena ; Fay, Andre P. ; De Velasco, Guillermo ; Preston, Mark A. ; Wilson, Kathryn M. ; Cho, Eunyoung ; McDermott, David F. ; Signoretti, Sabina ; Heng, Daniel Y.C. ; Choueiri, Toni K. / Body mass index and metastatic renal cell carcinoma : Clinical and biological correlations. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 30. pp. 3655-3663.
@article{77d757ce32e34b78bbeb792c247b3823,
title = "Body mass index and metastatic renal cell carcinoma: Clinical and biological correlations",
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.",
author = "Laurence Albiges and {Ari Hakimi}, A. and Wanling Xie and McKay, {Rana R.} and Ronit Simantov and Xun Lin and Lee, {Jae Lyun} and Rini, {Brian I.} and Sandy Srinivas and Bjarnason, {Georg A.} and Scott Ernst and Wood, {Lori A.} and Vaishamayan, {Ulka N.} and Rha, {Sun Young} and Neeraj Agarwal and Takeshi Yuasa and Pal, {Sumanta K.} and Aristotelis Bamias and Zabor, {Emily C.} and Skanderup, {Anders J.} and Helena Furberg and Fay, {Andre P.} and {De Velasco}, Guillermo and Preston, {Mark A.} and Wilson, {Kathryn M.} and Eunyoung Cho and McDermott, {David F.} and Sabina Signoretti and Heng, {Daniel Y.C.} and Choueiri, {Toni K.}",
year = "2016",
month = "10",
day = "20",
doi = "10.1200/JCO.2016.66.7311",
language = "English",
volume = "34",
pages = "3655--3663",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "30",

}

Albiges, L, Ari Hakimi, A, Xie, W, McKay, RR, Simantov, R, Lin, X, Lee, JL, Rini, BI, Srinivas, S, Bjarnason, GA, Ernst, S, Wood, LA, Vaishamayan, UN, Rha, SY, Agarwal, N, Yuasa, T, Pal, SK, Bamias, A, Zabor, EC, Skanderup, AJ, Furberg, H, Fay, AP, De Velasco, G, Preston, MA, Wilson, KM, Cho, E, McDermott, DF, Signoretti, S, Heng, DYC & Choueiri, TK 2016, 'Body mass index and metastatic renal cell carcinoma: Clinical and biological correlations', Journal of Clinical Oncology, vol. 34, no. 30, pp. 3655-3663. https://doi.org/10.1200/JCO.2016.66.7311

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

In: Journal of Clinical Oncology, Vol. 34, No. 30, 20.10.2016, p. 3655-3663.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Body mass index and metastatic renal cell carcinoma

T2 - Clinical and biological correlations

AU - Albiges, Laurence

AU - Ari Hakimi, A.

AU - Xie, Wanling

AU - McKay, Rana R.

AU - Simantov, Ronit

AU - Lin, Xun

AU - Lee, Jae Lyun

AU - Rini, Brian I.

AU - Srinivas, Sandy

AU - Bjarnason, Georg A.

AU - Ernst, Scott

AU - Wood, Lori A.

AU - Vaishamayan, Ulka N.

AU - Rha, Sun Young

AU - Agarwal, Neeraj

AU - Yuasa, Takeshi

AU - Pal, Sumanta K.

AU - Bamias, Aristotelis

AU - Zabor, Emily C.

AU - Skanderup, Anders J.

AU - Furberg, Helena

AU - Fay, Andre P.

AU - De Velasco, Guillermo

AU - Preston, Mark A.

AU - Wilson, Kathryn M.

AU - Cho, Eunyoung

AU - McDermott, David F.

AU - Signoretti, Sabina

AU - Heng, Daniel Y.C.

AU - Choueiri, Toni K.

PY - 2016/10/20

Y1 - 2016/10/20

N2 - 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.

AB - 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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