Evoked otoacoustic emissions - an approach for monitoring cisplatin induced ototoxicity in children

Ohjectives: Cisplatin chemotherapy is associated with an increased risk of ototoxic changes. The incidence of hearing loss after the Ist cisplatin-inf usion session is only scarcely mentioned in the international literature. W ith increasing survival rates, prevention and/or early detection of ototoxi city are important for providing management options. The predictive value o f pure-tone audiometry in early detection of ototoxicity has been questione d, particularly in the higher frequencies. Otoacoustic emissions appear to be more sensitive to cochlear insult than the conventional pure-tone audiom etry. The aims of our study was (a) to define the extent of hearing damage in children after the Ist cisplatin-infusion session (50 mg/m(2)); and (b) to compare the efficacy of otoacoustic emissions (transient evoked otoacous tic emissions, distortion-product otoacoustic emissions) with that of pure- tone audiometry as methods of audiological monitoring. Methods: Baseline au diometric (0.25-8 kHz) and otoacoustic emission testing (transient evoked o toacoustic emissions, distortion-product otoacoustic emissions) was conduct ed in 19 children, 12 of whom met the criteria for inclusion in the final s tudy. Comparisons were performed between baseline measurements and those re corded after the Ist cisplatin course. Transient evoked otoacoustic emissio ns were analyzed in terms of emission level and reproducibility as a functi on of frequency (0.8-4 kHz). Distortion-product otoacoustic emissions were obtained as DP-grams and I/Q functions at 4,6 and 8 kHz. The DP-gram amplit ude, the dynamic range and the detection thresholds from the I/Q functions were determined for each child. Results: Threshold changes from baseline we re founded to be statistically significant from 4-8 kHz in 50% of the child ren (P<0.01). Transient evoked otoacoustic emissions revealed a significant decrease in the emission level and in the reproducibility at the highest f requency tested (4 kHz, P<0.01), reflecting the results seen in pure-tone a udiometry. Distortion-product otoacoustic emissions demonstrated a signific ant threshold shift, a reduced dynamic range and a decreased amplitude in t he frequencies >3 kHz (P<0.05). Furthermore, DP-gram amplitude also reduced significantly at 3 kHz (P<0.05) without any similar change in pure-tone au diometry. Conclusions: A significant high-frequency hearing loss is identif ied in children even after one low-dose cisplatin-infusion session. As otot oxicity screening tools DP-grams were extremely sensitive and superior to p ure-tone audiometry and/or transient evoked otoacoustic emissions. Their us e is recommended for regular monitoring of cochlear function, aiming in pre vention of permanent damage. Some suggestions for reducing the potential fo r cisplatin ototoxicity (chemoprotective agents, gene therapy, inhibition o f apoptosis) are also discussed. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.