Purpose: This study aimed to explore metabolic tumor volume (tMTV) as assessed 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT), and understand its biological meaning in patients with NSCLC exposed to immune checkpoint blockers(ICBs). Experimental Design: In this study, patients with advanced NSCLC and a positive PET scan within 42 days of first line treatment were enrolled in 11 institutions across 4 countries. Total MTV (tMTV) was analyzed, with a 42% SUVmax threshold. Survival was analyzed according to high tMTV (≥ median). Plasma proteomic profile, whole exome, transcriptome and other analysis were performed on monocentric cohorts to explore its biological correlates. Results: Of the 518 patients included, 167 received ICBs, 257 had chemotherapy plus ICBs, and 94 had chemotherapy. Median tMTV was 99 cm3. Median overall survival (OS) for patients with high tMTV treated with ICBs was 11.4 months vs 29.6 months (P<0.0012) for those with low tMTV. In patients receiving chemotherapy-ICB tMTV did not correlate with OS (P=0.099). In patients with PD-L1≥1% and high tMTV, chemotherapy-ICB combination was associated with longer OS compared with ICBs alone (20 vs 11.4 months,p=0.026), while no survival differences observed in low tMTV group. High tMTV correlated (and its detrimental effect seems to be driven by) a specific proteomic profile and increase in genomic instability. Conclusion: Our analysis indicates high tTMV is linked to an increase in systemic inflammation, specific cytokines production and chromosomal instability. tTMV may serve as one of the biomarker to select the best upfront strategy in patients with PD-L1 positive advanced NSCLC.

中文翻译：

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通过 18F FDG - PET CT 扫描评估代谢肿瘤体积作为晚期 NSCLC 中免疫检查点阻滞剂的预测生物标志物及其生物学相关性


目的： 本研究旨在探讨评估 18F-氟脱氧葡萄糖正电子发射断层扫描-计算机断层扫描 （18F-FDG-PET/CT） 的代谢肿瘤体积 （tMTV），并了解其在暴露于免疫检查点阻滞剂 （ICB） 的 NSCLC 患者中的生物学意义。实验性设计： 在这项研究中，一线治疗后 42 天内 PET 扫描阳性的晚期 NSCLC 患者被纳入 4 个国家的 11 个机构。分析总 MTV （tMTV），SUVmax 阈值为 42%。根据高 tMTV （≥ 中位数） 分析生存率。对单中心队列进行血浆蛋白质组学谱、全外显子组、转录组和其他分析，以探讨其生物学相关性。结果： 在纳入的 518 例患者中，167 例接受了 ICB，257 例接受了化疗加 ICB，94 例接受了化疗。中位 tMTV 为 99 cm3。接受 ICBs 治疗的高 tMTV 患者的中位总生存期 （OS） 为 11.4 个月，而低 tMTV 患者的中位总生存期 （OS） 为 29.6 个月 （P<0.0012）。在接受化疗的患者中，ICB tMTV 与 OS 无关 （P=0.099）。在 PD-L1≥1% 和高 tMTV 患者中，与单独使用 ICB 相比，化疗-ICB 联合与更长的 OS 相关 （20 vs 11.4 个月，p=0.026），而在低 tMTV 组中未观察到生存差异。高 tMTV 与特定的蛋白质组学特征和基因组不稳定性的增加相关（其有害影响似乎是由其驱动的）。结论： 我们的分析表明，高 tTMV 与全身炎症、特异性细胞因子产生和染色体不稳定的增加有关。tTMV 可作为 PD-L1 阳性晚期 NSCLC 患者选择最佳前期策略的生物标志物之一。