Detection of Pretreatment Circulating Tumor DNA Predicts Recurrence after High-Dose Proton Beam Therapy for Early-Stage Non-Small Cell Lung Cancer

Abstract

Circulating tumor DNA (ctDNA) has been studied as a rapid and noninvasive biomarker for predicting cancer treatment outcomes. However, published data on the usefulness of pretreatment ctDNA in patients with non-small cell lung cancer (NSCLC) who underwent radiotherapy are currently limited, especially in patients who received proton beam therapy. This study included patients with cT1-2N0M0 nonsquamous NSCLC treated with proton beam therapy. Pretreatment plasma and matched white blood cell samples were subjected to targeted sequencing. The incidence of tumor recurrence and prognosis of patients with and without ctDNA detection were statistically evaluated. Forty-three patients with nonsquamous NSCLC were analyzed in this study. Pretreatment ctDNA was detectable in 8 of 43 patients (18.6%). At the median follow-up of 59 months (range, 15-97 months) in the surviving patients, detectable ctDNA was associated with inferior progression-free survival (HR, 5.2; 95% CI, 1.9-14.6; P <0.01) and overall survival (HR, 4.7; 95% CI, 1.1-20.6; P=0.02). There was no significant difference in the cumulative incidence of in-field recurrence according to the ctDNA detection status (P=0.92), but the ctDNA-positive group showed a significantly higher cumulative incidence of out-of-field recurrence (P<0.01) than the ctDNA-negative group. These results suggest that pretreatment ctDNA detection can predict out-of-field recurrence in patients with cT1-2N0M0 nonsquamous NSCLC treated with high-dose proton beam therapy.