Abstract 1154P
Background
Circulating tumor DNA (ctDNA) has been proven as a tool for detecting minimal residual diseases (MRD) in mid-to-late stage non-small cell lung cancers (NSCLCs) that received radio-, chemo-, immuno-, and/or targeted therapies. However, its usefulness in monitoring diseases in resectable stage I-III NSCLCs after curative surgeries has not been validated. It also remains not fully understood whether tracking evolutionary dynamics of tissues in ctDNA could improve the risk stratification.
Methods
We recruited 127 patients with stage I-III NSCLCs who received curative surgical resections in the Lung Cancer Tempo-spatial Heterogeneity (LuCaTH) prospective cohort. Plasma samples were collected at baseline, 7 days post surgery, and every 3 months thereafter. We performed deep targeted sequencing on a total of 634 plasma samples and 593 matched tissue samples using a panel covering 425 cancer-associated genes. Tissue phylogeny of each patient was reconstructed.
Results
The detection of presurgical and longitudinal post-surgical ctDNA indicated higher risk of relapse (HR: 2.29 and 3.99; P = 0.019 and 0.00024, respectively). As early as 7 days after surgeries, ctDNA started showing significant prognostic values (HR: 3.17; P = 0.0015). ctDNA positivity at each time point positively correlated with lymph node metastasis. The longitudinal detection of tissue clonal mutations revealed higher risk of relapse than subclonal ones for lung adenocarcinomas (HR: 6.78; P = 0.033). Phylogenetic ctDNA profiling tracked the sublconal nature of lung cancer relapse.
Conclusions
ctDNA detection after curative NSCLC resection can provide evidence for MRD. Phylogenetic ctDNA profiling may identify patients at high risk of relapse.
Clinical trial identification
ChiCTR1900022521.
Editorial acknowledgement
Legal entity responsible for the study
Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research.
Funding
Key Project of Cutting-edge Clinical Technology of Jiangsu Province (BE2016797); National Science Foundation of China (81872378, 81672295, 81572261, 81501977); The Project of Jiangsu Provincial Medical Talent (ZDRCA2016033).
Disclosure
M. Wu: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. H. Bao: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. X. Wu: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. Y. Shao: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. All other authors have declared no conflicts of interest.