title: Ototoxicity risk assessment combining distortion product otoacoustic emissions with a cisplatin dose model.
abstract: An objective method for identifying ototoxic hearing loss among patients receiving cisplatin is necessary since the ability of patients to take a behavioral test may change over the course of treatment. Data from 56 monitoring visits by 19 Veterans taking cisplatin were used to identify combinations of distortion-product otoacoustic emission (DPOAE) metrics and ototoxicity risk factors that best identified ototoxic hearing loss. Models were tested that incorporated DPOAE metrics generated statistically using partial least-squares analysis. Models were also tested that incorporated a priori DPOAE change criteria, such as a minimum DPOAE level shift of 6 dB. Receiver Operating Characteristic analysis was used to compare the accuracy of these models. The best performing model incorporated weighted combinations of pre-treatment hearing, cumulative cisplatin dose and DPOAE metrics that were determined using partial least-squares and evaluated over a quarter octave range near each subjects' high frequency DPOAE limit. Using this model and the DPOAE recording methods described herein, the chance of ototoxic hearing change can be determined at any given observed change in DPOAE level. This approach appears to provide an accurate and rapid ototoxicity risk assessment (ORA) that once validated can be used clinically.
authors.affiliation: National Center for Rehabilitative Auditory Research, VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA. marilyn.dille@va.gov
authors.forename: Marilyn F
authors.initials: MF
authors.lastname: Dille
authors.forename: Garnett P
authors.initials: GP
authors.lastname: McMillan
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Reavis
authors.forename: Peter
authors.initials: P
authors.lastname: Jacobs
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Fausti
authors.forename: Dawn
authors.initials: D
authors.lastname: Konrad-Martin
mesh_terms: D000161:Acoustic Stimulation; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D002945:Cisplatin / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D034381:Hearing Loss / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D016018:Least-Squares Analysis; D008875:Middle Aged; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D011237:Predictive Value of Tests; D011571:Psychoacoustics; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D014728:Veterans
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin