Comparison of Local Control and Toxicity in T4 Nasopharyngeal Carcinoma Patients Treated with Induction Chemotherapy...

Background and Objectives: T4 nasopharyngeal carcinoma (NPC) is a locally advanced disease with a high risk of local recurrence despite advances in radiotherapy techniques. Induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) is a standard approach, but the optimal fractionation strategy remains uncertain. We conducted a retrospective study comparing survival and local control rates in T4 NPC patients treated with induction chemotherapy followed by IMRT using either conventional fractionation (CF) or hyperfractionation (HF). Methods: This study included 171 non-metastatic T4 NPC patients treated with induction chemotherapy and IMRT/arc therapy (volumetric-modulated arc therapy and TOMOTHERAPY) between 2003 and 2021. The patients were divided into two groups: the CF group (109 patients) received 70 Gy in 35 fractions, while the HF group (62 patients) received 76.8 Gy in 64 fractions (1.2 Gy twice daily). The most commonly used induction chemotherapy regimen was weekly cisplatin and fluorouracil/leucovorin. The primary endpoint was the local control rate between the two treatment groups. Secondary endpoints were adverse events, overall survival, regional recurrence, and distant metastasis rates. Competing risk analyses based on the subdistribution hazard model and cumulative incidences were calculated. Results: Over a median follow-up of 74 months, the 5-year local control rate was higher in the CF group than in the HF group (83.6% vs. 74.7%; p = 0.0336). Two prognostic factors were significantly associated with local control, namely hyperfractionated RT (subdistribution hazard ratio [SHR] 2.259, 95% confidence interval [CI] 1.159-4.403, p = 0.0167) and arc therapy (SHR 0.267, 95% CI 0.127-0.565, p = 0.0006). Acute toxicities (≥grade 3 dermatitis and mucositis) were more frequent in the HF group (16.1% vs. 11.9%; 22.6% vs. 11%), as were late adverse events (33.9% vs. 22%), particularly hearing loss. No significant differences were noted in 5-year regional control (99.0% vs. 96.3%; p = 0.0522), distant metastasis (84.7% vs. 78.0%; p = 0.3307), or overall survival (71.2% vs. 64.2%; p = 0.4704). Conclusions: Induction chemotherapy followed by CF-IMRT offers better local control and fewer adverse events than HF-IMRT in T4 NPC patients, making CF-IMRT the preferred treatment.