Minami Seigo, Ihara Shouichi, Tanaka Tsunehiro, Komuta Kiyoshi
Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan.
Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasugatsuji, Tennoji-ku, Osaka 543-8922, Japan.
World J Oncol. 2020 Feb;11(1):9-22. doi: 10.14740/wjon1225. Epub 2020 Feb 2.
This study aimed to investigate the association of computed tomography (CT)-assessed sarcopenia and visceral adiposity with efficacy and prognosis of immune-checkpoint inhibitor (ICI) therapy for pretreated non-small cell lung cancer (NSCLC).
We retrospectively collected 74 patients with pretreated NSCLC who had initiated programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor monotherapy between December 2015 and November 2018 at our hospital. As CT-assessed pretreatment markers, we used psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), visceral-to-subcutaneous ratio (VSR) and visceral fat area (VFA) at lumbar vertebra L3 level. We divided 74 patients into high and low groups according to each Japanese sex-specific cut-off value. Using Kaplan-Meier curves and log-rank tests, we compared overall survival (OS) and progression-free survival (PFS). Adjusted by serum albumin, neutrophil-to-lymphocyte ratio, performance status and driver mutations, multivariate Cox proportional hazard analyses evaluated various variables as independent prognostic factors of OS and PFS.
We could not find significant difference in response rate (RR) and disease control rate (DCR) between low and high groups according to any factors. The OS of patients with body mass index (BMI) < 18.5 was significantly shorter than that of patients with BMI ≥ 18.5 (median 3.3 vs. 15.8 months, P < 0.01), while there was no significant difference in OS and PFS according to PMI, IMAC, VSR and VFA. Multivariate analyses detected no significant prognostic factor in OS and PFS, except for low IMAC (hazard ratio 0.43, 95% confidence interval 0.18 - 0.998, P = 0.0496) as a favorable prognostic factor of longer OS.
Neither PMI nor VSR, VFA might be a significant prognostic factor of PFS and OS of ICI monotherapy for pretreated NSCLC. According to our multivariate analyses, IMAC was a significant prognostic factor of OS, but not of PFS. Thus, neither sarcopenia nor visceral adiposity may be associated with the efficacy of ICI therapy.
本研究旨在探讨计算机断层扫描（CT）评估的肌肉减少症和内脏脂肪与经治非小细胞肺癌（NSCLC）患者免疫检查点抑制剂（ICI）治疗疗效及预后的相关性。
我们回顾性收集了2015年12月至2018年11月期间在我院开始接受程序性细胞死亡蛋白1（PD-1）或程序性细胞死亡配体1（PD-L1）抑制剂单药治疗的74例经治NSCLC患者。作为CT评估的预处理指标，我们采用了第3腰椎水平的腰大肌指数（PMI）、肌内脂肪组织含量（IMAC）、内脏与皮下脂肪比率（VSR）和内脏脂肪面积（VFA）。我们根据日本特定性别的截断值将74例患者分为高、低两组。使用Kaplan-Meier曲线和对数秩检验，我们比较了总生存期（OS）和无进展生存期（PFS）。经血清白蛋白、中性粒细胞与淋巴细胞比率、体能状态和驱动基因突变校正后，多因素Cox比例风险分析评估了各种变量作为OS和PFS的独立预后因素。
根据任何因素，低分组和高分组之间的缓解率（RR）和疾病控制率（DCR）均无显著差异。体重指数（BMI）<18.5的患者的OS显著短于BMI≥18.5的患者（中位值3.3个月对15.8个月，P<0.01），而根据PMI、IMAC、VSR和VFA评估OS和PFS时无显著差异。多因素分析未发现OS和PFS的显著预后因素，但低IMAC（风险比0.43，95%置信区间0.18-0.998，P=0.0496）作为OS延长的有利预后因素。
对于经治NSCLC患者，PMI、VSR、VFA均可能不是ICI单药治疗PFS和OS的显著预后因素。根据我们的多因素分析，IMAC是OS的显著预后因素，但不是PFS的显著预后因素。因此，肌肉减少症和内脏脂肪过多均可能与ICI治疗疗效无关。
