Ototoxicity in children with high-risk neuroblastoma: Prevalence, risk factors, and concordance of grading scales-A report from the Children's Oncology Group (COG).
9515 Background: Management of high-risk neuroblastoma relies on potentially ototoxic platinum-based therapy. In previous reports, the proportion of children with ototoxicity has ranged from 20-90%, with variability likely due to small samples and disparate grading scales. Currently there is no consensus regarding an optimal pediatric ototoxicity grading scale, and no reports of prevalence and risk factors for hearing loss (HL) in a large uniformly-treated cohort. We address these gaps using data from COG A3973. METHODS: Audiologic testing (AT) was completed after cisplatin (up to 400 mg/m(2): t1) and carboplatin (1700 mg/m(2): t2). HL was graded independently by 2 investigators using 3 grading scales (Brock, Chang, CTCv3). Concordance between scales was evaluated by McNemar's test, and risks for HL by logistic regression. RESULTS: Of 334 evaluable patients, 56% were male; median age at diagnosis was 3.3 yrs; the most recent evaluable AT was done at t1 for 20% and t2 for 80%. Cohen's kappa for inter-rater reliability was >0.95. HL was graded severe at t2 in 30% per Brock, 59% per Chang and 71% per CTCv3. In patients with hearing aids, HL was graded severe in 49% per Brock, 91% per Chang and 100% per CTCv3. Risk factors for severe HL included carboplatin conditioning and hospitalization for infection; scales were significantly discordant in detecting severe HL (p<.0001; Table). CONCLUSIONS: The study is the first to report conclusively that prevalence of severe hearing loss approaches 70% (CTCv3); risk is significantly increased after consolidation with carboplatin and hospitalization for infection; and the commonly-used Brock scale underestimates severe hearing loss, and should be used with caution in this setting. [Table: see text].
Landier, W; Knight, KR; Wong, FL; Lee, JK; Thomas, O; Kim, H; Kreissman, SG; Schmidt, ML; Chen, L; London, WB; Bhatia, S; Gurney, JG; Children's Oncology Group,
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