Detection of Tumor Recurrence via Circulating Tumor DNA Profiling in Patients with Localized Lung Cancer: Clinical Considerations and Challenges

Abstract

Approximately 30% of patients with non-small-cell lung cancer (NSCLC) present with localized/non-metastatic disease and are eligible for surgical resection or other "treatment with curative intent". Due to the high prevalence of recurrence after treatment, adjuvant therapy is standard care for most patients. The effect of adjuvant chemotherapy is, however, modest, and new tools are needed to identify candidates for adjuvant treatments (chemotherapy, immunotherapy, or targeted therapies), especially since expanded lung cancer screening programs will increase the rate of patients detected with localized NSCLC. Circulating tumor DNA (ctDNA) has shown strong potential to detect minimal residual disease (MRD) and to guide adjuvant therapies. In this manuscript, we review the technical aspects and performances of the main ctDNA sequencing platforms (TRACERx, CAPP-seq) investigated in this purpose, and discuss the potential of this approach to guide or spare adjuvant therapies after definitive treatment of NSCLC.

Keywords: NSCLC; circulating tumor DNA; liquid biopsy; minimal residual disease; non-small cell lung cancer.

Figure 1

The unique assay development of TRACERx and CAPP-Seq highlight their several differences which lay the foundation for their respective strengths and weakness. However, the deployment of each assay consisted of plasma monitoring from diagnosis to the post- treatment period. * Figure adopted from Skoulidis et al. [57].

Figure 2

Strategies using ctDNA profiling differ between patients with detectable ctDNA indicating MRD (orange line) and undetectable ctDNA indicating treatment success (green line).