Non-overlapping integrated reads (NOIR) sequencing of circulating tumor-derived DNA successfully predicts EGFR-TKI efficacy in EGFR-mutated NSCLC patients

In solid tumors, including lung cancer, it is recommended in guidelines to identify the driver gene mutations to be treated with the corresponding molecular targeted therapies when systemic chemotherapy is introduced, due to their efficacy. In lung cancer, the identification of targetable driver mutations is progressing, and it becomes to be essential to detect multiple targetable driver mutations before treatment. In order to identify these mutations, next generation sequencing (NGS) is being quickly implemented into clinical practice. However, ironically, unlike other cancer types, lung cancer requires successful NGS with relatively small biopsy specimens from bronchoscopic biopsies, especially in advanced cases, and it may not be possible to secure sufficient tumor tissue specimens for successful NGS analysis. In this situation, liquid biopsy, which is NGS analysis based on cell free DNA (cfDNA) or circulating tumor derived DNA (ctDNA) using peripheral blood plasma, can be an extremely powerful tool in lung cancer treatment because it does not require tissue samples. In the present study, we analyzed ctDNA by NOIR sequencing system from non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations to evaluate the therapeutic effect and behavior of tumor subclones during osimertinib treatment.