Early Markers of Sensorineural Hearing Loss After Platinum-Based Chemotherapy

Objectives: Platinum-based chemotherapy, cisplatin as well as carboplatin, can cause ototoxicity, which refers to drug-related damage affecting inner ear structures. At present, most ototoxicity monitoring programs rely on pure-tone audiometry, which is inadequate for detecting early outer hair cell (OHC) damage. Recent animal studies have shown that platinum derivatives can damage auditory nerve fibers (ANF), leading to cochlear synaptopathy (CS). The envelope-following response (EFR) is shown to be a noninvasive marker of CS. This study aims to assess the impact of platinum derivatives on auditory outcomes, including noninvasive EEG measurements for detecting CS. Design: Thirty-seven patients, divided into two subgroups (cisplatin group and carboplatin group), underwent a baseline hearing assessment before the chemotherapy and a follow-up evaluation approximately 2 to 10 mo post-treatment. The test battery included audiometry at conventional and extended high frequencies (EHFs), distortion product otoacoustic emissions (DPOAEs), and supra-threshold auditory evoked potentials (AEPs), that is, auditory brainstem response (ABR) and EFRs. Paired-samples t tests were used to evaluate the difference between baseline and follow-up, and regression analyses determined the impact of the cumulative dose and baseline hearing status on changes in hearing outcomes and EFR magnitude. The 95% confidence intervals (95% CIs) were applied to assess individual significant differences between baseline and follow-up. Results: Paired sample t tests revealed a significant ( p < 0.05) audiometric threshold shift at 8.0 kHz for the cisplatin subgroup and at 10.0 and 12.5 kHz for the carboplatin subgroup. A regression analysis confirmed that the cumulative chemotherapy dose significantly contributed to deteriorated hearing thresholds. For the total group, a significant difference in DP amplitude was determined between baseline and follow-up at 6.0 kHz. No significant differences were established between baseline and follow-up ABR parameters for the total group or for the two subgroups separately. A paired samples t test showed a significant decrease in the EFR magnitude between baseline and follow-up for the total group as well as for the cisplatin subgroup, but not for the carboplatin subgroup. Two patients receiving cisplatin presented a significant individual decline in EFR magnitude. A regression analysis confirmed that after chemotherapy, patients with the largest EFR magnitudes at baseline presented the largest EFR reductions. Conclusions: This study underscores the need for audiometric monitoring, including EHFs as well as ototoxicity grading systems. Furthermore, our results confirm that EFR magnitude may represent a valuable noninvasive marker of CS caused by platinum-based chemotherapy. A decline in EFR magnitude was observed before the onset of subjective complaints or significant audiometric threshold changes. These findings support the inclusion of objective measures, such as the EFR, in monitoring protocols to enhance early detection of ototoxicity.