Abstract
BACKGROUND
The purpose of this study was to examine the prevalence, severity and time to develop Chemotherapy-induced hearing loss (HL) in a cohort of embryonal brain tumors(ET) treated with cisplatin and cranial radiation(RT).
METHODS
Our cohort included children 3-15years treated between January2022 and June2023 for medulloblastoma and other ETs with surgery, craniospinal RT and 6 cycles of CET chemotherapy (cyclophosphamide,vincristine,cisplatin). Cisplatin 75mg/m2 was given in alternate cycles with a cumulative dose of 225 mg/m2. Children underwent clinical evaluation and age-appropriate audiological assessment at diagnosis,every 1-2cycles of cisplatin and end-of-treatment. Grading of ototoxicity was done per SIOP-Boston grading. Children with grade2 and above HL did not receive further cisplatin.Children with grade1HL underwent frequent monitoring.For this study, pure-tone-audiometry from start of treatment to end of treatment were analyzed and ≥Grade2HL was considered significant.
RESULTS
A total of 63 children were included in the study, 28(44.%)female, median age 7years (range 3-15years). Twenty (31.7%) children developed >grade2HL; the worse ear had grade 4 HL in 1(1.6%),grade 3 in 13(20.6%) and grade 2 in 6(9.5%).One had grade 2HL and 4 had grade 1HL even prior to start of cisplatin.The median cumulative cisplatin dose at developing >grade2HL was 0mg/m2(n=1), 75mg/m2(n=8), 150mg/m2(n=3) and 225mg/m2(n=9; 5 at end-of-treatment and 4 at follow-up). Age, gender and diagnosis were not associated with development of HL.
CONCLUSION
The high prevalence of early-onset ototoxicity in children with embryonal brain tumours is concerning.We recommend close monitoring of hearing function,at least every 2 cycles of cisplatin chemotherapy, if not more frequently. Incorporation of pharmacogenomics to identify highly susceptible individuals and therapeutic interventions such as cessation of cisplatin or replacement with alternatives in early ototoxicity would help reduce a potentially life-altering and long-term health concern.