Albiges Laurence, Hakimi A Ari, 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
Laurence 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.
J Clin Oncol. 2016 Oct 20;34(30):3655-3663. doi: 10.1200/JCO.2016.66.7311.
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.
The impact of BMI (high BMI: ≥ 25 kg/m v low BMI: < 25 kg/m) 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.
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).
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.
肥胖是肾透明细胞癌（RCC）公认的危险因素；然而，一些报告表明肥胖患者发生的RCC可能生长更缓慢。我们研究了体重指数（BMI）对转移性RCC患者治疗结局的临床和生物学影响。
在国际转移性肾细胞癌数据库联盟（IMDC）的1975例患者以及4657例患者的外部验证队列中，研究BMI（高BMI：≥25kg/m² vs 低BMI：<25kg/m²）对总生存期（OS）和靶向治疗疗效的影响。还研究了癌症基因组图谱数据集中聚焦脂肪酸代谢途径的基因表达谱以及脂肪酸合酶（FASN）的免疫组织化学染色。采用Cox回归评估BMI与OS的关联，并根据IMDC预后因素进行调整。
在IMDC队列中，高BMI患者的中位OS为25.6个月（95%CI，23.2至28.6），而低BMI患者为17.1个月（95%CI，15.5至18.5）（调整后风险比，0.84；95%CI，0.73至0.95）。在验证队列中，高BMI与OS改善相关（调整后风险比，0.83；95%CI，0.74至0.93；中位生存期分别为：23.4个月[95%CI，21.9至25.3个月] vs 14.5个月[95%CI，13.8至15.9个月]）。在癌症基因组图谱数据集（n = 61）中，FASN基因表达与BMI呈负相关（P = 0.034），低FASN表达组的OS更长（中位生存期：36.8 vs 15.0个月；P = 0.002）。FASN免疫组织化学阳性在IMDC预后不良（48%）和中度（34%）风险组中比在预后良好风险组中更常见（17%；P趋势 = 0.015）。
高BMI是接受靶向治疗的转移性RCC患者生存改善和无进展生存期延长的预后因素。潜在生物学机制提示FASN途径发挥了作用。
