肥胖与接受化疗、免疫治疗或化疗免疫治疗的晚期非小细胞肺癌患者的生存：一项多中心队列研究。
Obesity and survival in advanced non-small cell lung cancer patients treated with chemotherapy, immunotherapy, or chemoimmunotherapy: a multicenter cohort study.
机构信息
Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Emergency Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
出版信息
BMC Med. 2024 Oct 14;22(1):463. doi: 10.1186/s12916-024-03688-2.
BACKGROUND
The association of body mass index (BMI) with survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy, immunotherapy, or chemoimmunotherapy is controversial. We aimed to investigate these associations, including associations in male and female patients specifically, in a multicenter cohort study.
METHODS
We retrospectively analyzed data from seven cohorts comprising 7021 advanced non-small cell lung cancer patients who received chemotherapy (three cohorts), immunotherapy (two cohorts), and chemoimmunotherapy (two cohorts) from five data sources, including a de-identified nationwide (US-based) NSCLC clinico-genomic database and two randomized, double-blind, phase 3 clinical trials. BMI was categorized as underweight, normal weight, overweight, or obese. Underweight patients were excluded because of their small proportion. The primary endpoints were the associations between BMI and progression-free survival (PFS) and overall survival (OS) stratified by treatment type and sex, which were assessed using Kaplan-Meier methods and adjusted Cox modeling. Meta-analyses were performed to combine the adjusted hazard ratios.
RESULTS
In the pooled analysis, obesity was significantly associated with improved OS in patients receiving chemotherapy (hazard ratios [HR] = 0.84, 95% confidence interval (CI) 0.76-0.93), but there was no association with PFS (HR = 0.91, 95% CI 0.82-1.02). The association of BMI with OS for patients receiving chemotherapy differed by sex, with an inverse association in men (HR = 0.74, 95% CI 0.64-0.84), but no association observed in women (HR = 0.96, 95% CI 0.81-1.13, P 0.018). No impact of BMI on OS or PFS was detected in patients receiving immunotherapy or chemoimmunotherapy. Obese patients had the lowest level of tumor mutational burden, similar level of programmed death-ligand 1 expression and ESTIMATE scores.
CONCLUSIONS
Obesity may be associated with an increased overall survival among male patients treated with chemotherapy, whereas not associated with the outcomes in patients treated with immunotherapy or chemoimmunotherapy.
背景
体重指数（BMI）与接受一线化疗、免疫治疗或化疗免疫治疗的晚期非小细胞肺癌（NSCLC）患者的生存结局之间的关系存在争议。我们旨在通过一项多中心队列研究来调查这些关联，包括男性和女性患者的具体关联。
方法
我们回顾性分析了来自五个数据源的七个队列的 7021 例接受化疗（三个队列）、免疫治疗（两个队列）和化疗免疫治疗（两个队列）的晚期非小细胞肺癌患者的数据，包括一个去识别的全国性（基于美国）NSCLC 临床基因组数据库和两项随机、双盲、III 期临床试验。BMI 分为体重不足、正常体重、超重或肥胖。由于患者比例较小，体重不足的患者被排除在外。主要终点是按治疗类型和性别分层的 BMI 与无进展生存期（PFS）和总生存期（OS）之间的关联，这些关联使用 Kaplan-Meier 方法和调整后的 Cox 模型进行评估。进行了荟萃分析以合并调整后的风险比。
结果
在汇总分析中，肥胖与接受化疗的患者的 OS 显著相关（风险比 [HR] = 0.84，95%置信区间 [CI] 0.76-0.93），但与 PFS 无关（HR = 0.91，95% CI 0.82-1.02）。BMI 与接受化疗的患者 OS 的关联因性别而异，男性呈负相关（HR = 0.74，95% CI 0.64-0.84），而女性则无关联（HR = 0.96，95% CI 0.81-1.13，P<0.018）。在接受免疫治疗或化疗免疫治疗的患者中，BMI 对 OS 或 PFS 没有影响。肥胖患者的肿瘤突变负担最低，程序性死亡配体 1 表达和 ESTIMATE 评分相似。
结论
肥胖可能与接受化疗的男性患者的总生存期延长有关，而与接受免疫治疗或化疗免疫治疗的患者的结局无关。
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