Background: Nivolumab plus ipilimumab (Nivo-Ipi) is a standard treatments for metastatic or recurrent non-small cell lung cancer (NSCLC). Unlike programmed death-1 (PD-1) inhibitor monotherapy, the possible predictors of Nivo-Ipi treatment effectiveness remain unclear. Therefore, this retrospective study evaluated the prognostic relevance of 2-deoxy-2-[fluorine-18]-fluoro-d-glucose positron emission tomography (¹⁸F-FDG PET) after Nivo-Ipi treatment in patients with advanced NSCLC.

Methods: Among 130 eligible patients with metastatic or recurrent NSCLC who received Nivo-Ipi as initial treatment and underwent ¹⁸F-FDG PET prior to the initial treatment, the maximum standardized uptake value (SUV_max), SUV_peak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on ¹⁸F-FDG uptake were evaluated.

Results: High MTV and TLG on ¹⁸F-FDG uptake were significantly associated with poor performance status (PS), no response, high neutrophil-to-leukocyte ratio (NLR), low albumin levels, and high C-reactive protein (CRP) level, while SUV_max and SUV_peak showed no significant associations. Univariate analysis of all patients identified PS, bone metastases, NLR, MTV, and TLG as significant predictors of prognosis. By multivariate analysis, NLR and MTV were identified as independent predictors of prognosis. Sub-analysis based on histology and programmed death ligand-1 (PD-L1) expression identified MTV as an independent prognostic predictor for Nivo-Ipi treatment in patients with histological findings of adenocarcinoma (AC) and PD-L1 <1%. A high MTV with poor outcome was closely associated with a poor PS, lymph node metastases, bone metastases, high NLR, low albumin levels, and high CRP level.

Conclusions: MTV determined based on ¹⁸F-FDG uptake was a negative prognostic factor after Nivo-Ipi treatment, particularly in patients with histological findings of AC or PD-L1 <1%.

Keywords: 2-deoxy-2-[fluorine-18]-fluoro-d-glucose positron emission tomography (18F-FDG PET); Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4); metabolic tumor activity; non-small cell lung cancer (NSCLC); programmed death-1 (PD-1).

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背景： 纳武利尤单抗联合伊匹木单抗（Nivo-Ipi）是转移性或复发性非小细胞肺癌（NSCLC）的标准治疗方案。与程序性死亡受体-1 (PD-1) 单药抑制剂相比，Nivo-Ipi 治疗效果的可能预测因素仍不清楚。因此，这项回顾性研究评估了在晚期 NSCLC 患者中 Nivo-Ipi 治疗后 2-脱氧-2-[氟-18]-氟-d-葡萄糖正电子发射断层扫描 (¹⁸F-FDG PET) 对预后的相关性。

方法： 在符合条件的130名接受 Nivo-Ipi 作为初始治疗并进行了 ¹⁸F-FDG PET 检查的转移性或复发性 NSCLC 患者中，评估了最大标准摄取值 (SUV_max)、SUV_peak、代谢肿瘤体积 (MTV) 和总病变糖酵解量（TLG）等指标。

结果： 高 MTV 和 TLG 与较差的体能状态 (PS)、无应答、高水平中性粒细胞/白细胞比率 (NLR)、低血清白蛋白水平和高水平 C-反应蛋白 (CRP) 显著相关，而 SUV_max 和 SUV_peak 未显示出显著关联。单因素分析显示 PS、骨转移、NLR、MTV 和 TLG 是预后的显著预测因子。多变量分析发现 NLR 和 MTV 是独立的预后预测因子。基于组织学和程序性死亡配体-1 (PD-L1) 表达进行的亚组分析表明，对于具有腺癌（AC）组织学特征或 PD-L1

结论： 根据 ¹⁸F-FDG 摄取确定的 MTV 是接受 Nivo-Ipi 治疗后的负面预后因素，特别是在具有腺癌（AC）组织学特征或 PD-L1

关键词： 2-脱氧-2-[氟-18]-氟-d-葡萄糖正电子发射断层扫描 (¹⁸F-FDG PET)；细胞毒性 T 淋巴细胞相关抗原 4 (CTLA4)；代谢肿瘤活性；非小细胞肺癌（NSCLC）；程序性死亡受体-1 (PD-1)。

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