Wang Haowei, Zhou Fei, Qiao Meng, Li Xuefei, Zhao Chao, Cheng Lei, Chen Xiaoxia, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Oncol. 2021 Jul 21;11:671874. doi: 10.3389/fonc.2021.671874. eCollection 2021.
The use of circulating tumor DNA (ctDNA) to reflect clinical benefits of advanced non-small cell lung cancer (NSCLC) patients during immune checkpoint inhibitor (ICI) therapy remains controversial. This study aimed to determine the association of pre-treatment and early dynamic changes of ctDNA with clinical outcomes in advanced NSCLC patients treated with ICIs.
Electronic databases (PubMed, Embase, Web of Science, and Cochrane) were systematically searched to include relevant studies published in English up to November 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS) and the secondary outcome was objective response rate (ORR) with RECIST criteria.
A total of 1017 patients from 10 studies were identified. The baseline ctDNA levels (detected not detected) showed no significant association with clinical outcomes regarding OS (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.93-1.51), PFS (HR, 0.98; 95% CI, 0.80-1.21), and ORR (odds ratio [OR], 0.89; 95% CI, 0.54-1.46). Interestingly, when taken early longitudinal assessment of ctDNA into consideration, the early reduction of the concentration of ctDNA was associated with significant improvements of OS (HR, 0.19; 95% CI, 0.10-0.35), PFS (HR, 0.30; 95% CI, 0.22-0.41) and ORR (OR, 0.07; 95% CI, 0.03-0.18). Further subgroup analyses revealed that the reduction magnitude did not significantly impact the association between ctDNA and clinical outcomes, suggesting that both patients with decreased ctDNA or a ≥50% reduction of ctDNA was associated with improved OS, PFS and ORR.
Early reduction of ctDNA was associated with improved OS, PFS and ORR in advanced NSCLC patients treated with ICIs.
https://www.crd.york.ac.uk/PROSPERO, CRD42021226255.
使用循环肿瘤DNA（ctDNA）来反映晚期非小细胞肺癌（NSCLC）患者在免疫检查点抑制剂（ICI）治疗期间的临床获益仍存在争议。本研究旨在确定晚期NSCLC患者接受ICI治疗时，ctDNA的治疗前水平及早期动态变化与临床结局之间的关联。
系统检索电子数据库（PubMed、Embase、Web of Science和Cochrane），纳入截至2020年11月发表的英文相关研究。主要结局为总生存期（OS）和无进展生存期（PFS），次要结局为根据实体瘤疗效评价标准（RECIST）评估的客观缓解率（ORR）。
共纳入10项研究中的1017例患者。基线ctDNA水平（检测到/未检测到）与OS（风险比[HR]，1.18；95%置信区间[CI]，0.93 - 1.51）、PFS（HR，0.98；95% CI，0.80 - 1.21）和ORR（优势比[OR]，0.89；95% CI，0.54 - 1.46）的临床结局无显著关联。有趣的是，考虑到ctDNA的早期纵向评估时，ctDNA浓度的早期降低与OS（HR，0.19；95% CI，0.10 - 0.35）、PFS（HR，0.30；95% CI，0.22 - 0.41）和ORR（OR，0.07；95% CI，0.
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