Distortion-product otoacoustic emission test performance for ototoxicity monitoring.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.
Reavis
Kelly M
KM
VA RR&D, National Center for Rehabilitative Auditory Research, Portland VA Medical Center, Portland, Oregon, USA. reavisk@uci.edu
McMillan
Garnett
G
Austin
Donald
D
Gallun
Frederick
F
Fausti
Stephen A
SA
Gordon
Jane S
JS
Helt
Wendy J
WJ
Konrad-Martin
Dawn
D
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D011237:Predictive Value of Tests; D012015:Reference Standards
D000970:Antineoplastic Agents; D002945:Cisplatin