Associations between Pretreatment Body Composition Features and Clinical Outcomes among Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Blockade.
Associations between Pretreatment Body Composition Features and Clinical Outcomes among Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Blockade.
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DOI：
10.1158/1078-0432.ccr-22-1389
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发表时间：
2022-12-01
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高体重指数（BMI）可能导致转移性透明细胞肾细胞癌（mccRCC）免疫检查点阻断（ICB）结果的改善。然而，身体质量指数是一种粗略的体型测量。我们调查了BMI，并通过x线摄影评估了与mccRCC ICB结果相关的身体成分（BC）参数。ICB治疗mccRCC患者的回顾性研究。使用预处理CT扫描确定BMI和BC变量（骨骼肌指数（SMI）和多种肥胖指数）。我们研究了BMI和BC变量与ICB结果之间的关系。根据RECIST V1.1确定治疗反应。我们在62个原发肿瘤样本的单独队列中比较了全转录组模式和BC变量。205例mccRCC患者纳入该队列（74%为男性，71%为超重/肥胖，53%为低重度精神障碍患者）。高BMI患者的总生存期（OS）比正常体重患者长(未调整HR 0.66 (95% CI: 0.45-0.97)；p = 0.035)。唯一与OS相关的BC变量是SMI(未调整的HR比较低与高SMI为1.65 (95% CI: 1.13-2.43)；p = 0.009)。然而，在调整了IMDC评分和治疗方案后，这种OS相关性变得不显著。没有发现OS与肥胖相关，也没有发现BC变量与无进展生存期或放射反应相关。低SMI患者的肿瘤显示血管生成、炎症和骨髓信号增加。我们的发现强调了骨骼肌在BMI悖论中的相关性。未来的研究应该调查是否解决低骨骼肌转移患者接受ICB治疗可以提高生存率。
High body mass index (BMI) may lead to improved immune-checkpoint blockade (ICB) outcomes in metastatic clear cell renal cell carcinoma (mccRCC). However, BMI is a crude body size measure. We investigated BMI and radiographically assessed body composition (BC) parameters association with mccRCC ICB outcomes. Retrospective study of ICB treated mccRCC patients. BMI and BC variables (skeletal muscle index (SMI), and multiple adiposity indexes) were determined using pre-treatment CT scans. We examined the associations between BMI and BC variables with ICB outcomes. Therapeutic responses per RECIST V1.1 were determined. We compared whole transcriptomic patterns with BC variables in a separate cohort of 62 primary tumor samples. 205 mccRCC patients included in the cohort (74% were male, 71% were overweight/obese, and 53% were classified as low SMI). High BMI patients experienced longer overall survival (OS) than normal weight patients (unadjusted HR 0.66 (95% CI: 0.45–0.97); p=0.035). The only BC variable associated with OS was SMI (unadjusted HR comparing low vs. high SMI 1.65 (95% CI: 1.13–2.43); p=0.009). However, this OS association became non-significant after adjusting for IMDC score and line of therapy. No OS association was seen for adiposity and no BC variable was associated with progression-free survival or radiological responses. Tumors from patients with low SMI displayed increased angiogenic, inflammatory, and myeloid signals. Our findings highlight the relevance of skeletal muscle in the BMI paradox. Future studies should investigate if addressing low skeletal muscle in metastatic patients treated with ICB can improve survival.