Liquid biopsy tracking during sequential chemo-radiotherapy identifies distinct prognostic phenotypes in nasopharyngeal carcinoma

TLDR

Liquid biopsies can detect minimal residual disease across several cancer types. The study investigates whether on‑treatment liquid biopsy tracking of circulating EBV DNA can inform tumour phenotypes in 673 nasopharyngeal carcinoma patients receiving induction chemotherapy and chemo‑radiotherapy. The authors applied supervised statistical clustering of relapse risk to classify eight clearance‑kinetics patterns into four prognostic phenotypes linked to chemotherapy intensity. They found significant inter‑patient heterogeneity with eight clearance patterns, including ~30% complete responders after a single induction cycle, and demonstrated that real‑time liquid biopsy monitoring provides prognostic information that could guide risk‑adapted treatment de‑intensification or intensification.

Abstract

Abstract Liquid biopsies have the utility for detecting minimal residual disease in several cancer types. Here, we investigate if liquid biopsy tracking on-treatment informs on tumour phenotypes by longitudinally quantifying circulating Epstein-barr virus (EBV) DNA copy number in 673 nasopharyngeal carcinoma patients undergoing radical induction chemotherapy (IC) and chemo-radiotherapy (CRT). We observe significant inter-patient heterogeneity in viral copy number clearance that is classifiable into eight distinct patterns based on clearance kinetics and bounce occurrence, including a substantial proportion of complete responders (≈30%) to only one IC cycle. Using a supervised statistical clustering of disease relapse risks, we further bin these eight subgroups into four prognostic phenotypes (early responders, intermediate responders, late responders, and treatment resistant) that are correlated with efficacy of chemotherapy intensity. Taken together, we show that real-time monitoring of liquid biopsy response adds prognostic information, and has the potential utility for risk-adapted treatment de-intensification/intensification in nasopharyngeal carcinoma.