Abstract 2295: Utility of circulating tumor DNA in lung cancer clinical research and practice: systematic review and meta-analysis
Authors: Peters Solange , Abrahamson Page , Ballew Nicholas , Kalilani Linda , Phiri Kelesitse , Bell Kelly , Slowley Alexander , Zajac Maglalena , Hofstatter Erin , Stojadinovic Alexander , Silvestro Angela , Wang Zebin , Aziez Amine , Sun Xuezheng 
Published: June 2023

Background: Circulating tumor DNA (ctDNA) has been increasingly used in the clinical care of patients with cancer. This systematic review summarized current data on the utility of ctDNA in lung cancer clinical research and practice and provides insights for integrating ctDNA into drug development and patient care.

Methods: The Embase database was used to identify clinical research articles of ctDNA in lung cancer from 2015 to 2020. ctDNA clinical utilities were reviewed and summarized into 3 areas: early diagnosis, prognostication, and monitoring disease progression/treatment response. Associations of ctDNA with progression-free survival (PFS) and overall survival (OS) were estimated in the embedded meta-analysis. Pooled estimates were calculated using fixed-effect or random-effect models depending on study heterogeneity.

Results: After screening and review, 111 studies were included. ctDNA testing has been increasing in recent years, with 54.1% of the selected studies published in 2019 or 2020. 73.0% of the studies were conducted in patients with advanced/metastatic disease; 79.3% included patients with non-small cell lung cancer (NSCLC). ctDNA was used mainly for prognostication (76.6%), demonstrating that the presence of ctDNA is associated with poor prognosis. In the meta-analyses, overall ctDNA detection/positivity was associated with shorter PFS (n=622; HR=2.34; 95% CI, 1.90-2.89) and OS (n=723; HR=2.33; 95% CI, 1.91-2.85). Studies focused specifically on EGFR mutations in ctDNA reported similar prognostication results. Heterogeneity by stage, histological type, and ctDNA measurement timing were evaluated and showed no significant impact on these pooled estimates. ctDNA clearance/decrease during treatment was associated with a lower risk of progression (n=552; HR=0.24; 95% CI, 0.19-0.31) and death (n=669; HR=0.40; 95% CI, 0.27-0.60). Few studies evaluated the utility of ctDNA in lung cancer for diagnosis or monitoring tumor progression across the treatment spectrum.

Conclusions: Recent studies demonstrated the clinical value of ctDNA in lung cancer prognostication/monitoring, primarily in advanced NSCLC. Large, multicenter clinical trials and real-world longitudinal data sets are needed to validate these findings, and prospective trials are required to address challenges related to integrating ctDNA testing into clinical practice.

Citation Format: Solange Peters, Page Abrahamson, Nicholas Ballew, Linda Kalilani, Kelesitse Phiri, Kelly Bell, Alexander Slowley, Maglalena Zajac, Erin Hofstatter, Alexander Stojadinovic, Angela Silvestro, Zebin Wang, Amine Aziez, Xuezheng Sun. Utility of circulating tumor DNA in lung cancer clinical research and practice: systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2295.