Radiation dose de-escalation in early-stage extranodal natural killer/T-cell lymphoma treated with contemporary concurrent chemoradiotherapy in the intensity-modulated radiotherapy era

Purpose: This study aimed to evaluate whether radiation dose escalation improves survival outcomes in early-stage extranodal natural killer/T-cell lymphoma (ENKTL) treated with intensity-modulated radiotherapy (IMRT)-based concurrent chemoradiotherapy (CCRT). Materials and Methods: We retrospectively reviewed 72 patients with Ann Arbor stage I-II ENKTL treated at our institution from 2011 to 2025 with IMRT-based CCRT followed by sequential chemotherapy with etoposide, ifosfamide, dexamethasone, and L-asparaginase. Patients were stratified at the cohort median radiation dose and inverse probability of treatment weighting (IPTW) was applied to address potential confounding by indication. The primary endpoint was overall survival (OS); secondary endpoints were local progression-free survival (LPFS), progression-free survival (PFS), and toxicity. Results: Using the cohort median (54 Gy) as the cutoff, patients were divided into <54 Gy (n = 32) and ≥54 Gy (n = 40) groups. The ≥54 Gy group had more female patients (p = 0.007), with older age and higher prognostic index for natural killer lymphoma-Epstein-Barr virus (PINK-E) scores. IPTW was applied in 62 patients with available PINK-E data. No significant difference was observed between dose groups in OS (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.22 to 2.58), LPFS (HR, 1.87; 95% CI, 0.54 to 6.51), or PFS (HR, 0.53; 95% CI, 0.23 to 1.23). No grade ≥4 toxicities occurred, and grade ≥2 toxicities did not differ between groups. Conclusion: In early-stage ENKTL treated with IMRT-based CCRT, radiation dose escalation beyond 54 Gy did not improve survival or local disease control. These findings suggest that higher radiation doses may be unnecessary in the modern IMRT era.