Long term ototoxic effects of cisplatin in survivors of pediatric solid tumors

Abstract

ackground: Cisplatin is an integral component of chemotherapeutic regimes of childhood tumors, but their use may impart a significant hearing deficit in long-term survivors. We aim to evaluate the long-term auditory effects of Cisplatin in survivors of pediatric solid tumors Methods: The study included a cohort of survivors of Hepatoblastoma(HB) and Malignant Germ Cell tumors(MGCT) registered at pediatric surgical-oncology clinic from 1994 to 2016. The ototoxic effects of Cisplatin were evaluated by pure-tone audiometry(PTA) done during follow up. Results: A total 129 patients were deemed as survivors, with a mean duration of follow-up in HB and MGCT of 8.47(SD 4.27) years and 7.84(SD 4.25) years. Of the 117 survivors receiving Cisplatin, one patient had hearing difficulty at follow up. PTA was performed in 83 survivors, of which an audiogram was available for 51 survivors for evaluation, 28(54.9%) of which were reported normal. Hearing loss was detected in 39(76.4%) out of 51 survivors by the SIOP grading system. Severe hearing loss was detected in 32(62.7%) survivors (grade 3,4). Hearing loss was detected in 26(51%) survivors according to the Brocks Grading system. Severe hearing loss was detected in 6(11.7%) survivors. The survivors of MGCT had a significantly higher (92.3%) chance at developing hearing loss compared to 60% of HB survivors (p=0.012). A dose of Cisplatin of >/=420mg/m2 was found to be associated with hearing loss, with a sensitivity of 75% and specificity of 66.67%. The mean age at diagnosis was significantly higher in children with hearing loss(48.50,SD 47.54months) as compared to children without hearing loss(24.5,SD 32.12months) (p=0.01928). Age at audiometry did not correlate with hearing loss. Conclusions: The SIOP grading system, being more sensitive, must be uniformly used to screen for hearing loss. Older age at diagnosis, higher dose and MGCT survivors need close monitoring.