The cochlear dose and the age at radiotherapy predict severe hearing loss after passive scattering proton therapy and cisplatin in children with medulloblastoma

Neuro Oncol. 2024 Oct 3;26(10):1912-1920. doi: 10.1093/neuonc/noae114.

Abstract

Background: Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin.

Methods: We identified patients aged 3-21 years who were treated at our centers between 2007 and 2022. Audiograms were graded using the International Society of Pediatric Oncology (SIOP) Boston scale. Time to grades 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios and 95% confidence intervals (CI).

Results: Seventy-nine patients were treated with PSPT at a median age of 7.5 years (range: 3.1-21.1). The mean cochlear dose (Dmc) (±SD) was 31.5 ± 8.5 Gy, and the cumulative cisplatin dose was 295 ± 50 mg/m2. Fifty-nine patients (75%) received amifostine. Patients completed a median of 9 audiograms (range: 4-22) with a median audiogram follow-up of 49 months (range: 6-177). Twenty-seven patients (34%) had grades 3-4 HL. In adjusted Cox models, only higher Dmc (HR = 1.12, 95% CI:1.06-1.18) was associated with grades 3-4 HL. The predicted 3-year incidence of grades 3-4 HL was 40.0% (95% CI: 21.3-66.3) and 66.7% (95% CI: 35.4-93.7) for children with Dmc ≥36 Gy and age at radiotherapy ≥7 and <7 years, respectively (P = .042). It was 8.9% (95% CI: 2.3-31.6) and 15.6% (95% CI: 5.3-41.1) for children with Dmc <36 Gy and age at radiotherapy ≥7 and <7 years, respectively (P = .78).

Conclusions: Children <7 years at radiotherapy with a Dmc ≥36 Gy are at higher risk for HL.

Keywords: hearing loss; medulloblastoma; ototoxicity; passive scattering proton therapy; proton radiotherapy.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Cerebellar Neoplasms* / radiotherapy
  • Chemoradiotherapy / adverse effects
  • Child
  • Child, Preschool
  • Cisplatin* / administration & dosage
  • Cisplatin* / adverse effects
  • Cochlea* / drug effects
  • Cochlea* / radiation effects
  • Female
  • Follow-Up Studies
  • Hearing Loss* / etiology
  • Humans
  • Male
  • Medulloblastoma* / radiotherapy
  • Prognosis
  • Proton Therapy* / adverse effects
  • Retrospective Studies
  • Young Adult

Substances

  • Cisplatin
  • Antineoplastic Agents