Hearing Loss Risk in Pediatric Patients Treated with Cranial Irradiation and Cisplatin-Based Chemotherapy

Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1488-1495. doi: 10.1016/j.ijrobp.2021.02.050. Epub 2021 Mar 4.

Abstract

Purpose: Cranial radiation therapy (RT) and cisplatin-based chemotherapy are essential to treating many pediatric cancers but cause significant ototoxicity. The objective of this study is to determine the relationship between the RT dose and the risk of subsequent hearing loss in pediatric patients treated with cisplatin.

Methods and materials: This retrospective study of cisplatin-treated pediatric patients examined ototoxicity from cranial RT. Ototoxicity was graded for each ear according to the International Society of Pediatric Oncology (SIOP) consensus ototoxicity scale. The RT dose to the cochlea was calculated using the mean, median, maximum, and minimum dose received to determine the most predictive parameter for hearing loss. Multivariable logistic regression models then examined risk factors for hearing loss.

Results: In 96 children (161 ears) treated with RT + cisplatin, the minimum cochlear RT dose was most predictive of hearing loss. A higher cochlear RT dose was associated with increased hearing loss (odds ratio per 10 Gy dose increase = 1.64; P = .043), with an added risk in those receiving an autologous bone marrow transplantation (hazard ratio = 10.47; P < .001).

Conclusions: This research supports further testing of the minimum cochlear RT dose as a more predictive dose parameter for risk of ototoxicity. The cochlear RT dose was additive to the risk of hearing loss from underlying cisplatin-based chemotherapy. Exposure to autologous bone marrow transplantation was the strongest predictor of developing hearing loss, placing these children at particularly high risk for hearing loss across all cochlear doses. Future prospective studies are crucial to further inform RT dose thresholds and minimize the risk of hearing loss in childhood cancer survivors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Audiometry
  • Autografts
  • Bone Marrow Transplantation
  • Child
  • Child, Preschool
  • Cisplatin / adverse effects*
  • Cisplatin / therapeutic use
  • Cochlea / radiation effects*
  • Cranial Irradiation / adverse effects*
  • Female
  • Hearing Loss / etiology*
  • Humans
  • Infant
  • Logistic Models
  • Male
  • Odds Ratio
  • Organs at Risk / radiation effects
  • Ototoxicity / etiology
  • Radiation Dosage
  • Radiation-Sensitizing Agents / adverse effects*
  • Radiation-Sensitizing Agents / therapeutic use
  • Radiotherapy Dosage
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Radiation-Sensitizing Agents
  • Cisplatin