Contemporary Ototoxicity Among Patients With High-Risk Neuroblastoma: A Report From the Children's Oncology Group Study ANBL1531

PURPOSE Cisplatin is a component of many high-risk neuroblastoma (HRNBL) induction regimens and causes irreversible destruction of cochlear hair cells. Historical cisplatin-induced hearing loss (CIHL) rates in patients with HRNBL range from 13% to 95%, with considerable heterogeneity due to treatment, assessment timing, and audiologic grading scales. Contemporary rates of CIHL in this vulnerable population are unknown. The purpose of this study was to describe the prevalence of end-induction CIHL using international consensus grading among patients with HRNBL enrolled on the Children's Oncology Group (COG) study ANBL1531. METHODS Enrolled patients were randomized or assigned therapy that included a total of 360 mg/m 2 of cisplatin during induction. Audiologic evaluations were completed at baseline and end of induction (EOI). A subset of trial centers submitted EOI audiograms, which were centrally graded using the International Society of Pediatric Oncology (SIOP) ototoxicity grading scale. Evaluable participants were those with interpretable audiology results for frequencies 2-8 kHz available for central review. Communication-impacting CIHL was defined as SIOP grade ≥2. RESULTS Among evaluable patients (n = 87), 56% (49/87) had SIOP grade >2 CIHL in the better ear following induction chemotherapy and 69% (51/74 of patients with ear-specific testing) had SIOP >2 hearing loss in the worse ear. There were no statistically significant differences in CIHL across patient demographic factors. A higher rate of CIHL was observed among patients receiving concurrent ALK inhibitor therapy (11/14, 79%), but this did not reach statistical significance. CONCLUSION In this contemporary HRNBL cohort with central audiometry using uniform SIOP ototoxicity grading, communication-impacting CIHL affected over half of patients at EOI. Otoprotection strategies are urgently needed for patients with HRNBL who receive cisplatin.