De-escalating elective nodal irradiation dose to 45 Gy in nasopharyngeal carcinoma: A large-cohort study with 5-year outcomes.

PURPOSE: Although recent guidelinesrecommend de-escalatedelective nodal irradiation (ENI) for nasopharyngeal carcinoma (NPC), the optimal dose remains undefined (45-52.6 Gy dose in 2 Gy fractions, EQD2). Weevaluated the long-term efficacy of 45-Gy EQD2 ENI dose in a real-world cohortto inform dose optimization and guideline refinement. MATERIALS AND METHODS: Newly diagnosed, non-metastatic NPC patients treated with intensity-modulated radiotherapy (IMRT) and received 45-Gy EQD2 ENI dose at our institution were screened. Regional control (RC), overall survival (OS), local control (LC), and distant control (DC)were evaluated. Dosimetric comparisons between 45-Gy and 50-Gy EQD2 plans were performed on 20 randomly selected replanned cases using identical target volumes and organs at risk (OARs) constraints. Normal tissue complication probability (NTCP) rates for major toxicities were derived to predict clinical benefit. RESULTS: Totally,752 patients were included. With a median follow-up of 68 months, the 5-year RC, LC, DC, and OS rates were 97.3 %, 96.1 %, 90.6 %, and 89.7 %, respectively. Regional recurrence occurred in 23 patients; 14 were within the nodal clinical target volume, including 11 in-situ nodal gross target volume relapses and five isolated failures (0.7 %) within the 45-Gy volume. The 45-Gy EQD2 plan significantly reduced dose to all relevant OARs (P < 0.001) compared with 50-Gy EQD2 plan. Significant median NTCP reductions were observed for parotid gland function loss, dysphagia and hypothyroidism (all P < 0.001). CONCLUSION: A 45-Gy EQD2 ENI dose provides favorable long-termefficacywith superior OAR sparing and reduced NTCP, supporting further prospective evaluation of this de-escalation strategy in NPC.