Abstract IA14: Circulating tumor DNA in early-stage NSCLC: A lung TRACERx study

Abstract

Abstract The Cancer Research UK-funded study TRACERx (TRAcking Cancer Evolution through therapy [Rx]) aims to recruit patients undergoing surgery for early-stage non-small cell lung cancer (NSCLC). Patients donate blood pre- and postoperatively alongside multi-region sampled primary tumor tissue. Up to 40% of patients undergoing surgery for NSCLC experience relapse of their disease. At this point patients are approached for relapse tissue sampling. TRACERx therefore provides a strong platform for evaluating circulating tumor DNA (ctDNA) in early-stage NSCLC and a minimal residual disease (MRD) setting. In this presentation we will describe data arising from a phylogenetic, patient-specific approach to ctDNA evaluation in the first 100 patients analyzed as part of TRACERx. We will discuss clinicopathologic factors associated with ctDNA detection in early-stage NSCLC and suggest the existence of distinct tumor phenotypic characteristics that predict the presence of ctDNA at measurable quantities in plasma. Additionally, we will discuss tumor volume limit of detection analyses and highlight potential implications of our findings within the context of early cancer detection. We will then examine data arising from the ctDNA profiling of postoperative plasma samples taken in the adjuvant setting. These data demonstrate that ctDNA detection is specific for NSCLC relapse and that ctDNA detection precedes clinical diagnosis of NSCLC relapse (median lead-time of 77 days, range 10 to 346 days). We will provide examples of using phylogenetic ctDNA profiling to characterize the subclonal nature of relapsing NSCLC as a potential method to personalize relapse therapeutic intervention. Finally, we will highlight potential advantages of patient-specific ctDNA profiling in an adjuvant MRD setting and suggest ways that this technology can be used to fuel adjuvant drug development in NSCLC by driving novel study designs. Citation Format: Christopher Abbosh. Circulating tumor DNA in early-stage NSCLC: A lung TRACERx study [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA14.