CtDNA dynamic detection reflects the clinical efficacy following treatment in NSCLC patients.

Abstract

e15032 Background: EGFR is a major oncogene in non-small cell lung cancer (NSCLC) patients. Although EGFR tyrosine kinase inhibitors (TKIs) have effectively improved the survival of NSCLC patients, acquired drug resistance is a critical clinical challenge. Minimal residual disease (MRD) is the direct cause of tumor recurrence, and the abundance of circulating tumor DNA (ctDNA) can be used to reflect the status of MRD. We sought to identify the evaluation of effect of ctDNA on tumor therapeutic efficacy. Methods: Blood samples from 32 advanced NSCLC patients were dynamically collected at different timepoints (0, 4, 8, 12, months) with 1 sampling in 6 patients, 2 samplings in 15 patients, 3 samplings in 7 patients, 4 samplings in 3 patients, and 5 samplings in 1 patient. Targeted sequencing of 450 cancer-related genes were performed for genomic alteration identification at OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory in Shanghai, China. The average variant allele frequency of each sample was used to represent ctDNA abundance. Results: A total of 32 advanced NSCLC patients harboring EGFR sensitive mutations were enrolled in the study. Patients consisted of 12 (37.5%) males and 20 (62.5%) females, with a median age of 60 years old, ranged from 38 to 82 years old. These patients were randomly divided into TKI monotherapy group (N = 11) or TKI treatment combined with pemetrexed group (N = 21). The percentage of stable disease (SD) was more pronounced in patients receiving TKI combined with chemotherapy when compared to patients treated with TKI monotherapy (47.6% [10/21] vs. 36.4% [4/11], respectively). Less patients experienced the progression of disease (PD) when they were treated with TKI combined with chemotherapy than those receiving TKI monotherapy (52.4% [11/21] vs. 63.6% [7/11], respectively). For patients with PD, ctDNA abundance was progressively increased in 55.6% (10/18) during dynamic monitoring; whereas ctDNA abundance kept stable in 44.4% (8/18) patients, while 6/8 patients did not continue to perform ctDNA detection for more than half a year. In patients experienced SD, ctDNA abundance was declined in 78.6% (11/14) during dynamic monitoring, while 21.4% (3/14) patients displayed elevated ctDNA abundance. These 3 patients did not continue to perform ctDNA detection for more than 10 months. In majority of NSCLC patients (65.6% [21/32]), variation of ctDNA abundance was correlated to the treatment-induced clinical response. Conclusions: In conclusion, our results suggested that the variation of ctDNA abundance could promptly reflect the clinical response of treatment. The dynamic variation of ctDNA/MRD can possibly be considered as a biomarker of clinical efficacy following treatment in NSCLC patients.