Yip Steven M, Heng Daniel Y C, Tang Patricia A
Department of Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
J Kidney Cancer VHL. 2016 Mar 22;3(1):12-22. doi: 10.15586/jkcvhl.2016.45. eCollection 2016.
Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR) pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI) on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m), and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.
转移性肾细胞癌(mRCC)的治疗目前主要集中在抑制血管内皮生长因子途径和雷帕霉素哺乳动物靶点(mTOR)途径。肥胖会增加患肾细胞癌的风险。然而,在靶向治疗时代,肥胖对mRCC临床结局的影响尚不清楚。本综述重点关注身体组成对mRCC靶向治疗结局的影响。国际转移性肾细胞癌数据库联盟数据库拥有评估体重指数(BMI)对接受靶向治疗的mRCC患者结局影响的最大患者系列。超重患者(BMI≥25kg/m²)的总生存期显著改善,这一观察结果在参与辉瑞试验的患者中得到了外部验证。相比之下,肌肉减少症一直与血管生成抑制剂和mTOR抑制剂的毒性增加相关。通过结构化运动计划和饮食干预增强mRCC合并肌肉减少症的患者,可能会改善接受靶向治疗的mRCC患者的结局。同时,肥胖作为肾细胞癌的危险因素却在靶向治疗中具有更好的总生存期这一矛盾现象需要进一步评估。