Distortion-Product Otoacoustic Emission Test Performance for Ototoxicity Monitoring

In Brief Introduction: A nonbehavioral method for monitoring ototoxicity in patients treated with cisplatin is needed because patients enduring chemotherapy may not be well or cooperative enough to undergo repeated hearing tests. Distortion-product otoacoustic emissions (DPOAEs) provide a nonbehavioral measure of auditory function that is sensitive to cisplatin exposure. However, interpreting DPOAE findings in the context of ototoxicity monitoring requires that their accuracy be determined in relation to a clinically accepted gold standard test. Objectives: Among patients receiving cisplatin for the treatment of cancer, we sought to (1) identify the combination of DPOAE metrics and ototoxicity risk factors that best classified ears with and without ototoxic-induced hearing changes; and (2) evaluate the test performance achieved by the composite measure as well as by DPOAEs alone. Design: Odds of experiencing hearing changes at a given patient visit were determined using data collected prospectively from 24 Veterans receiving cisplatin. Pure-tone thresholds were examined within an octave of each subject's high-frequency hearing limit. DPOAE were collected as a set of four response growth (input/output) functions near the highest f2 frequency that yielded a robust response at L2 = L1 = 65 dB SPL. Logistic regression modeled the risk of hearing change using several DPOAE metrics, drug treatment factors, and other patient factors as independent variables. An optimal discriminant function was derived by reducing the model so that only statistically significant variables were included. Receiver operating characteristic curve analyses were used to evaluate test performance. Results: At higher cisplatin doses, ears with better hearing at baseline were more likely to exhibit ototoxic hearing changes than those with poorer hearing. Measures of pre-exposure hearing, cumulative drug dose, and DPOAEs generated a highly accurate discriminant function with a cross-validated area under the receiver operating characteristic curve of 0.9. DPOAEs alone also provided an indication of ototoxic hearing change when measured at the highest DPOAE test frequency that yielded a robust response. Conclusions: DPOAEs alone and especially in combination with pre-exposure hearing and cisplatin dose provide an indication of whether or not hearing has changed as a result of cisplatin administration. These promising results need to be validated in a separate sample. Distortion-product otoacoustic emissions (DPOAEs) have been proposed as a clinical tool for ototoxicity monitoring. A prospective, observational study design was undertaken to determine the test accuracy (sensitivity and specificity) of DPOAEs compared with repeated measures of high-frequency pure-tone thresholds to detect ototoxicity in subjects receiving cisplatin. DPOAEs alone and in combination with a variety of other risk factors for ototoxicity were evaluated for their utility to categorize ears of patients as having hearing changes or as having no hearing change. The result was a discriminant function that included measures of pre-exposure hearing, drug dose, and DPOAEs that accurately predicted significant hearing change in ears of patients exposed to cisplatin.