Real-time liquid biopsy guided assessment of radiation response: Longitudinal circulating free DNA kinetics during precision radiotherapy across solid tumors from India.

Abstract

e15056 Background: Precision radiotherapy has improved dose delivery, but biological response assessment is delayed, especially in high-volume Indian settings where early recognition of radio-resistance could alter outcomes. Circulating free DNA (cfDNA) reflects dynamic tumor burden and may offer a real-time biomarker. We assessed cfDNA kinetics during precision radiotherapy to predict response across diverse solid tumors. Methods: In this prospective, single-centre study we enrolled 22 adults undergoing image-guided radiotherapy for lung, esophageal, cervical, gastric or breast cancers. Peripheral blood was drawn at baseline, mid-course and completion. cfDNA was isolated from plasma via standardized EDTA-centrifugation protocol and quantified fluorometrically. Changes were calculated relative to baseline. End-of-treatment cfDNA below baseline defined a responder; mid-course decline defined early decline. Radiologic response was evaluated at 6–8 weeks post-RT using RECIST 1.1. Results: Baseline cfDNA values were heterogeneous. During treatment, cfDNA decreased in 8 patients and increased in 14. At completion, 10 patients (45%) had cfDNA decrease and were radiologic responders, while 12 (55%) had an increase and were non-responders. Early decline identified 5 of 10 final responders and early rise identified 9 of 12 final non-responders, so the early cfDNA trend matched the final trend in 14 of 22 cases (64%). cfDNA response agreed with imaging in 19 of 22 patients (90% concordance). In the breast-cancer subset (14 patients), 7 experienced cfDNA decline by the end of therapy. Conclusions: Real-time cfDNA monitoring during precision radiotherapy is feasible and provides an early indicator of treatment response across heterogeneous Indian cancers. Early cfDNA rise predicted resistance, whereas decline correlated with radiologic response. Though limited by sample size, this study shows that cfDNA trends are simple to measure and could be integrated into weekly clinic visits to guide adaptive dosing, prompt systemic therapy initiation, and engage patients. Further multicenter studies are needed to validate thresholds, interpret dynamics, and integrate cfDNA into personalized radiation oncology.