Epstein-Barr virus DNA-guided chemoradiotherapy for patients with low-risk locoregionally advanced nasopharyngeal carcinoma: a secondary 5-year follow-up analysis of an open-label, randomised controlled, phase 2 non-inferiority trial.

Background: Intensity-modulated radiation therapy (IMRT) with two cycles of concurrent 100 mg/m Methods: This is a secondary analysis of an open-label, randomised, controlled, phase 2 non-inferiority trial, which enrolled patients with low-risk LA-NPC (pretreatment plasma Epstein-Barr virus DNA < 4000 copies/mL) at Sun Yat-sen University Cancer Center. Eligible participants were randomly assigned (1:1) to receive either two cycles or three cycles of concurrent cisplatin (100 mg/m Findings: Between Sept 28, 2016, to Oct 18, 2018, 332 patients were enrolled and randomly assigned to the two-cycle group (n = 166) or three-cycle group (n = 166). The final follow-up date was Oct 11, 2024. Data were analysed from Oct 11, 2024, to June 5, 2025. At median follow-up of 79.7 months (IQR, 75.4-88.3 months), 5-year PFS rates were 85.0% (95% CI, 79.4-90.4) for the two-cycle group vs. 87.3% (95% CI, 82.2-92.4) for the three-cycle group (difference 2.4%; 95% CI, -5.0%-9.8%; noninferiority Interpretation: Five-year outcomes support the viability of two cycles of concurrent DDP with IMRT as an alternative to the standard three-cycle regimen, offering comparable survival outcomes with fewer late toxicities in patients with low-risk LA-NPC. However, as the study was conducted at a single center, the generalisability of these findings to non-endemic regions warrants further validation. Funding: National Key Research and Development Program of China, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Science and Technology Program of Guangzhou, Sun Yat-sen University Clinical Research 5010 Program, and China Postdoctoral Science Foundation.