Plasma ctDNA kinetics as a predictor of systemic therapy response for advanced non-small cell lung cancer: a systematic review and meta-analysis

被引：0
作者：
da Silva, Luis F. Leite [1 ]
Saldanha, Erick F. [2 ]
de Menezes, Junior Samuel Alonso [3 ]
Pereira, Leonardo Halamy [1 ]
dos Santos, Joao Alexandre R. de Braganca [1 ]
Buonopane, Isabella Romagnoli [3 ]
de Souza, Erito M. [1 ]
de Menezes, Caio Ulysses Galvani [4 ]
Lopes, Gilberto [5 ]
机构：
[1] Univ Fed Fluminense, Dept Ciencias Med, Ave Marques Parana 349, BR-24033900 Niteroi, RJ, Brazil
[2] Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON M5G 2M9, Canada
[3] Univ Fed Bahia, Dept Ciencias Saude, BR-21941590 Salvador, BA, Brazil
[4] Univ Fed Sao Paulo, Dept Oncol Clin, BR-04023062 Sao Paulo, SP, Brazil
[5] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA
来源：
ONCOLOGIST | 2025年 / 30卷 / 02期
关键词：
NSCLC; ctDNA; precision oncology; molecular response; CIRCULATING TUMOR DNA; LIQUID BIOPSY; SURVIVAL; BIAS; STRATIFICATION; PROGRESSION; CONCOMITANT; DYNAMICS; NAIVE;
D O I：
10.1093/oncolo/oyae344
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background Predicting early treatment response in advanced non-small cell lung cancer (NSCLC) is challenging. Longitudinal monitoring of circulating tumor DNA (ctDNA) can track tumor response to treatments like immune checkpoint blockade (ICB) and correlate with outcomes. This meta-analysis evaluated whether ctDNA clearance or decrease is associated with improved survival across various settings in NSCLC. Methods A systematic review of MEDLINE, EMBASE, and Cochrane databases (up to April 2024) identified studies evaluating the impact of ctDNA kinetics on survival outcomes in non-curative NSCLC settings. Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were calculated using a random effects model. Results We included 32 studies with 3047 NSCLC patients receiving systemic therapies such as targeted therapy (TT), ICB, and chemotherapy. Meta-analysis of 31 studies showed that ctDNA decrease/clearance was linked to improved PFS (HR: 0.32 [0.26, 0.40], I-2 = 63%, P < .01). Subgroup analysis indicated strong PFS benefits from ctDNA clearance (HR: 0.27 [0.20, 0.36]). Similar improvements were seen across patients undergoing targeted therapy (HR: 0.34) and ICB (HR: 0.33). Analysis of 25 studies revealed a significant association between ctDNA reduction and better OS (HR: 0.31 [0.23, 0.42], I-2 = 47%, P < .01). Subgroup findings were consistent for both TT (HR: 0.41) and ICB (HR: 0.32). Sensitivity analysis demonstrated that ctDNA clearance/decrease was consistently associated with improved PFS across study designs and ctDNA analysis methods. There was no significant variation in hazard ratios for PFS based on NSCLC subtypes, smoking status, or sex. Conclusion Plasma ctDNA kinetics was associated with improved survival outcomes in patients diagnosed with advanced NSCLC undergoing treatment with TT and ICB.
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页数：12
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