Sensorineural hearing loss after pediatric cranial radiotherapy: a multicenter analysis of dosimetric and clinical risk factors

BACKGROUND: No multicenter study has validated cochlear dose constraints for hearing preservation in pediatric brain tumor patients in a real-world setting. Although the PENTEC review proposed a 35 Gy mean cochlear dose threshold, supporting evidence from heterogeneous, multicenter pediatric cohorts remains scarce. PURPOSE: To evaluate dosimetric, therapeutic, and clinical risk factors for sensorineural hearing loss (SNHL) after pediatric cranial radiotherapy in a national multicenter cohort, with a specific focus on validating the clinical relevance of the 35 Gy mean cochlear dose threshold. METHODS: We retrospectively analyzed 88 children treated with cranial radiotherapy between 2014 and 2024 across four French pediatric radiotherapy centers participating in the national PediaRT registry. All patients had baseline and at least two post-radiotherapy audiograms graded according to the Chang Ototoxicity Scale, with SNHL defined as Chang grade ≥ 1a. Mean (Dmean) and minimum (Dmin) cochlear doses were extracted and analyzed using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: Over a median follow-up of 37 months, 17 patients (19.3%) developed SNHL. In multivariate analysis, both a mean cochlear dose ≥ 35 Gy (HR = 3.90; 95% CI: 1.24-12.23; p = 0.020) and cisplatin exposure (HR = 3.85; 95% CI: 1.40-10.64; p = 0.009) were independently associated with SNHL. The 5-year cumulative incidence of SNHL was 43.4% for Dmean ≥ 35 Gy versus 13.1% for < 35 Gy (p = 0.0014), and 51.6% with cisplatin versus 12.4% without (p < 0.001). A significant monotonic relationship between cochlear dose and SNHL severity was observed (p = 0.0011). CONCLUSION: This study provides the first national, multicenter validation of the 35 Gy mean cochlear dose threshold in a real-world pediatric population and identifies cisplatin exposure as a major independent risk factor. These findings support strict cochlear dose minimization during treatment planning and systematic long-term audiological surveillance in pediatric cancer survivorship care.