Evoked otoacoustic emissions--an approach for monitoring cisplatin induced ototoxicity in children.
OBJECTIVE
Cisplatin chemotherapy is associated with an increased risk of ototoxic changes. The incidence of hearing loss after the 1st cisplatin-infusion session is only scarcely mentioned in the international literature. With increasing survival rates, prevention and/or early detection of ototoxicity are important for providing management options. The predictive value of pure-tone audiometry in early detection of ototoxicity has been questioned, particularly in the higher frequencies. Otoacoustic emissions appear to be more sensitive to cochlear insult than the conventional pure-tone audiometry. The aims of our study was (a) to define the extent of hearing damage in children after the 1st cisplatin-infusion session (50 mg/m(2)); and (b) to compare the efficacy of otoacoustic emissions (transient evoked otoacoustic emissions, distortion-product otoacoustic emissions) with that of pure-tone audiometry as methods of audiological monitoring.


METHODS
Baseline audiometric (0.25-8 kHz) and otoacoustic emission testing (transient evoked otoacoustic emissions, distortion-product otoacoustic emissions) was conducted in 19 children, 12 of whom met the criteria for inclusion in the final study. Comparisons were performed between baseline measurements and those recorded after the 1st cisplatin course. Transient evoked otoacoustic emissions were analyzed in terms of emission level and reproducibility as a function 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 amplitude, the dynamic range and the detection thresholds from the I/Q functions were determined for each child.


RESULTS
Threshold changes from baseline were founded to be statistically significant from 4-8 kHz in 50% of the children (P<0.01). Transient evoked otoacoustic emissions revealed a significant decrease in the emission level and in the reproducibility at the highest frequency tested (4 kHz, P<0.01), reflecting the results seen in pure-tone audiometry. Distortion-product otoacoustic emissions demonstrated a significant threshold shift, a reduced dynamic range and a decreased amplitude in the 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 audiometry.


CONCLUSIONS
A significant high-frequency hearing loss is identified in children even after one low-dose cisplatin-infusion session. As ototoxicity screening tools DP-grams were extremely sensitive and superior to pure-tone audiometry and/or transient evoked otoacoustic emissions. Their use is recommended for regular monitoring of cochlear function, aiming in prevention of permanent damage. Some suggestions for reducing the potential for cisplatin ototoxicity (chemoprotective agents, gene therapy, inhibition of apoptosis) are also discussed.
Stavroulaki
P
P
University Department of Otolaryngology Head and Neck Surgery, Southinead Hospital, BS10 5NB, Bristol, UK. yannisx@vossinakis@freeserve.co.uk
Apostolopoulos
N
N
Segas
J
J
Tsakanikos
M
M
Adamopoulos
G
G
D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001301:Audiometry, Pure-Tone / Q000379:methods; D001309:Auditory Threshold / Q000502:physiology; D002648:Child; D002945:Cisplatin / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects / Q000503:physiopathology; D006311:Hearing Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D006316:Hearing Loss, High-Frequency / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*
D000970:Antineoplastic Agents; D002945:Cisplatin