title: Early cisplatin induced ototoxicity profile may predict the need for hearing support in children with medulloblastoma.
abstract: BACKGROUND
  Cisplatin (CDDP) ototoxicity is a significant side effect of the current treatment of medulloblastoma (MB). Cumulative dose of CDDP and age are recognized risk factors for hearing loss, but inter-individual susceptibility limits our ability to identify patients at risk for hearing loss. We describe the kinetics of early audiometric changes during therapy and identify profiles associated with a higher risk of needing hearing aids.
  
  
  METHODS
  Serial audiometric evaluations were performed during and after completion of therapy in children with average risk (AR) and high-risk (HR) MB. Each audiogram was scored according to five grading systems. Variations of pure tone thresholds were analyzed at each frequency for each consecutive audiogram. CDDP dose modifications and hearing outcome were recorded.
  
  
  RESULTS
  A total of 258 audiograms from 35 patients (22 AR, 13 HR) were analyzed. Eighteen AR patients (81.3%) required dose reduction and the median cumulative dose of CDDP administered was 412.5 mg/m(2) (150-600), corresponding to 68% of the intended dose. Three HR patients (23.0%) required dose reduction. At a median follow-up of 67 months (11-117), nine patients (25.7%) required hearing support: After two cycles of CDDP (150 mg/m(2) ), the average hearing loss at 8,000 Hz was twice higher in the group that eventually required hearing support.
  
  
  CONCLUSIONS
  Early alteration of high-frequency thresholds may help identify individuals who will require hearing support. In the MB population, alternative strategies should be developed to limit the cumulative dose of CDDP to prevent significant ototoxicity.
authors.affiliation: Division of Pediatric Hematology Oncology and Bone Marrow Transplantation, Alberta Children's Hospital, Calgary, Canada. lucie.lafay-cousin@albertahealthservices.ca
authors.forename: Lucie
authors.initials: L
authors.lastname: Lafay-Cousin
authors.forename: Eve
authors.initials: E
authors.lastname: Purdy
authors.forename: Annie
authors.initials: A
authors.lastname: Huang
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Cushing
authors.forename: Vicky
authors.initials: V
authors.lastname: Papaioannou
authors.forename: Alberto
authors.initials: A
authors.lastname: Nettel-Aguirre
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001299:Audiometry; D002528:Cerebellar Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin