Personalized circulating tumor DNA detection for monitoring immunotherapy efficacy in locally advanced or metastatic non-small cell lung cancer

Immune checkpoint inhibitors (ICIs) or combined with chemotherapy have shown outstanding efficacy in treatment of advanced non-small cell lung cancer (NSCLC). However, efficient biomarkers for monitoring response to first-line ICIs ± chemotherapy remain unclear. In our study, 16 tumor tissues and 46 matched peripheral blood samples at baseline and during treatment from 19 locally advanced or metastatic NSCLC patients were collected. Circulating tumor DNA (ctDNA) burden by tumor-informed assay was detected to monitor and predict therapeutic response and survival of NSCLC patients treated with first-line ICIs or plus chemotherapy. We first compared the susceptibility of tumor-informed assay and tumor-agnostic assay to detect ctDNA, and found that ctDNA was only positively detected in one patient by tumor-agnostic assay with mean variant allele fraction (VAF) of 6.40%, while positively detected in three patients by tumor-informed assay with mean VAF of 8.83%, 0.154% and 0.176%, respectively. Moreover, tumor-informed assays demonstrated sensitive ctDNA detection in 93.75% (15/16) of patients. The trend of ctDNA level from baseline to first evaluation was consistent with radiographic changes. The decrease in ctDNA after treatment compared with baseline was more in patients with partial response than in patients with stable disease/progressive disease. Patients with more than 50% reduction had a significant progression-free survival and overall survival benefit. Our findings suggested that tumor-informed assay turned to be a better option for ctDNA detection, and plasma early ctDNA dynamic changes could be a valuable biomarker for monitoring efficacy and outcome prediction in advanced NSCLC patients treated with first-line ICIs ± chemotherapy.