title: Ototoxicity in children with high-risk neuroblastoma: prevalence, risk factors, and concordance of grading scales--a report from the Children's Oncology Group.
abstract: OBJECTIVE
  Platinum-based therapy is the mainstay for management of high-risk neuroblastoma. Prevalence of platinum-related ototoxicity has ranged from 13% to 95% in previous reports; variability is attributable to small samples and disparate grading scales. There is no consensus regarding optimal ototoxicity grading. Furthermore, prevalence and predictors of hearing loss in a large uniformly treated high-risk neuroblastoma population are unknown. We address these gaps in our study.
  
  
  METHODS
  Audiologic testing was completed after administration of cisplatin alone (< 400 mg/m(2); exposure one) or after cisplatin (400 mg/m(2)) plus carboplatin (1,700 mg/m(2); exposure two). Hearing loss was graded using four scales (American Speech-Language-Hearing Association; Brock; Chang; and Common Terminology Criteria for Adverse Events, version 3 [CTCAEv3]).
  
  
  RESULTS
  Of 489 eligible patients, 333 had evaluable audiologic data. Median age at diagnosis was 3.3 years. Prevalence of severe hearing loss differed by scale. For those in the exposure-one group, prevalence ranged from 8% per Brock to 47% per CTCAEv3 (Brock v CTCAEv3 and Chang, P < .01; CTCAEv3 v Chang, P = .16); for those in the exposure-two group, prevalence ranged from 30% per Brock to 71% per CTCAEv3 (all pair-wise comparisons, P < .01). In patients requiring hearing aids, hearing loss was graded as severe in 49% (Brock), 91% (Chang), and 100% (CTCAEv3). Risk factors for severe hearing loss included exposure to cisplatin and carboplatin compared with cisplatin alone and hospitalization for infection.
  
  
  CONCLUSIONS
  Severe hearing loss is prevalent among children with high-risk neuroblastoma. Exposure to cisplatin combined with myeloablative carboplatin significantly increases risk. The Brock scale underestimates severe hearing loss and should be used with caution in this setting.
authors.affiliation: Wendy Landier, F. Lennie Wong, Jin Lee, Ola Thomas, Heeyoung Kim, and Smita Bhatia, City of Hope, Duarte; Lu Chen, Children's Oncology Group, Monrovia, CA; Kristin Knight, Oregon Health and Science University, Portland, OR; Susan G. Kreissman, Duke University Medical Center, Durham, NC; Mary Lou Schmidt, University of Illinois at Chicago, Chicago, IL; Wendy B. London, Dana-Farber/Harvard Cancer Care, Children's Hospital Boston, Boston, MA; and James G. Gurney, University of Memphis School of Public Health, Memphis, TN.
authors.forename: Wendy
authors.initials: W
authors.lastname: Landier
authors.forename: Kristin
authors.initials: K
authors.lastname: Knight
authors.forename: F Lennie
authors.initials: FL
authors.lastname: Wong
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.forename: Ola
authors.initials: O
authors.lastname: Thomas
authors.forename: Heeyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Susan G
authors.initials: SG
authors.lastname: Kreissman
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Schmidt
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: James G
authors.initials: JG
authors.lastname: Gurney
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D015995:Prevalence; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin