Tumor-Agnostic Circulating Tumor DNA Analysis as a Comprehensive Predictive Biomarker of Recurrence after Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

Abstract

Purpose: This study aimed to evaluate whether pretreatment circulating tumor DNA (ctDNA) is a predictive biomarker for recurrence in patients with early-stage non-small cell lung cancer (ES-NSCLC), including those with pathologically unproven (PU) who received ablative radiotherapy.

Materials and methods: Patients clinically diagnosed with cT1-2N0M0 NSCLC treated with radiotherapy alone at a single institute were included. Pretreatment plasma and matched white blood cell samples were subjected to targeted sequencing to detect ctDNA. The association between ctDNA detection and prognosis was evaluated. Integrated analysis including non-squamous cell carcinoma (SQ) cohort and enhancement of recurrence prediction with radiographic features were also evaluated.

Results: Of the 19 patients (10 SQ, and 9 PU) who met the sequence quality criteria, ctDNA was detected in 6. At the median follow-up of 60 months, detectable ctDNA was significantly associated with inferior progression-free survival (PFS) in both the SQ and PU cohorts (P = .01 and .02). In an analysis of 62 patients combined with the non-SQ cohort, ctDNA detection was the only significant factor for PFS. The combination of ctDNA and a high positron emission tomography maximum standardized uptake value provided a better recurrence risk model than ctDNA alone (the C-index improved from 0.63 to 0.72).

Conclusion: These results suggest that pretreatment ctDNA detection can predict recurrence in patients with cT1-2N0M0 NSCLC, including those with PU tumors treated with ablative radiotherapy.