Five-year follow-up of a phase 2 trial of reduced-dose radiotherapy in patients with Epstein-Barr virus DNA-selected stage III NPC

Primary analysis of a phase 2 trial at Sun Yat-sen University Cancer Center (Guangzhou, China) found that reduced-dose (60 Gy) radiation was associated with favorable survival outcomes and limited toxicities in patients with low-risk stage III nasopharyngeal carcinoma (NPC) sensitive to induction chemotherapy (IC). Five-year follow-up results have now been published. The analysis enrolled patients with nonkeratinizing stage III NPC with pretreatment Epstein-Barr virus (EBV DNA < 4000 copies/ml. All 215 patients received two cycles of IC. After IC, 116 patients achieved complete or partial response (CR/PR) and undetectable EBV DNA, and they were assigned to IMRT at 60 Gy in 30 fractions. The remaining 99 patients were assigned to standard IMRT at 70 Gy in 33 fractions. The primary endpoint was progression-free survival (PFS). At a median follow-up of 68.1 months, the 5-year PFS rate was 90.5% (95% CI 85.3-96.0) in the 60-Gy cohort and 79.8% (72.3-88.1) in the 70-Gy cohort, with 5-year overall survival rate 96.6% (93.3-99.0) and 94.9% (90.7-99.4), respectively. The 5-year locoregional relapse-free survival rate was 93.1% in the 60-Gy cohort and 82.8% in the 70-Gy cohort, with 5-year distant metastasis-free survival rate 93.1% and 89.9%, respectively. No grade 3-4 late toxicity was observed in the 60-Gy group, whereas grade 3-4 late toxicities were observed in 10.1% of patients in the 70-Gy group. The authors conclude that in patients with low-risk stage III NPC selected by EBV DNA and IC response, reduced-dose IMRT achieved favorable survival outcomes with limited late toxicities.