Monitoring carboplatin ototoxicity with distortion-product otoacoustic emissions in children with retinoblastoma

Abstract

Objective: Carboplatin is a common chemotherapy agent with potential ototoxic side effects that is used to treat a variety of pediatric cancers, including retinoblastoma. Retinoblastoma is a malignant tumor of the retina that is usually diagnosed in young children. Distortion-product otoacoustic emission tests offer an effective method of monitoring for ototoxicity in young children. This study was designed to compare measurements of distortion-product otoacoustic emissions obtained before and after several courses of carboplatin chemotherapy in order to examine if (a) mean distortion-product otoacoustic emission levels were significantly different; and (b) if criterion reductions in distortion-product otoacoustic emission levels were observed in individual children.

Methods: A prospective repeated measures study. Ten children with a median age of 7.6 months (range, 3-72 months) diagnosed with unilateral or bilateral retinoblastoma were examined. Distortion-product otoacoustic emissions were acquired from both ears of the children with 65/55 dB SPL primary tones (f(2)=793-7996 Hz) and a frequency resolution of 3 points/octave. Distortion-product otoacoustic emission levels in dB SPL were measured before chemotherapy treatment (baseline measurement) and after 3-4 courses of chemotherapy (interim measurement). Comparisons were made between baseline and interim distortion-product otoacoustic emission levels (collapsed across ears). Evidence of ototoxicity was based on criterion reductions (≥ 6 dB) in distortion-product otoacoustic emission levels.

Results: Significant differences between baseline and interim mean distortion-product otoacoustic emission levels were only observed at f(2) = 7996 Hz. Four children exhibited criterion reductions in distortion-product otoacoustic emission levels.

Conclusions: Mean distortion-product otoacoustic emission levels at most frequencies were not changed following 3-4 courses of carboplatin chemotherapy in children with retinoblastoma. However, on an individual basis, children receiving higher doses of carboplatin exhibited criterion reductions in distortion-product otoacoustic emission level at several frequencies. These findings suggest that higher doses of carboplatin affect outer hair cell function, and distortion-product otoacoustic emission tests can provide useful information when monitoring children at risk of developing carboplatin ototoxicity.