Age-Dependent Patterns of Cisplatin-Induced Ototoxicity in Head and Neck Cancer: A Longitudinal Audiologic Analysis.

Abstract

Background: Cisplatin (CDDP) is a key chemotherapeutic agent used to treat head and neck cancer. Improved survival rates have increased concerns about CDDP-induced ototoxicity, as this toxicity significantly impacts survivors' quality of life. However, the dose-dependent and age-related patterns of CDDP-induced ototoxicity remain incompletely defined. Therefore, in this study, we aimed to characterize CDDP-induced ototoxicity by tracking longitudinal hearing data and evaluating the associated factors.

Patients and methods: We retrospectively analyzed a cohort of 316 patients with head and neck cancer who received CDDP-based chemotherapy at a tertiary cancer center between January 2009 and June 2023. Hearing function was longitudinally assessed using pure-tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAE) across the cumulative CDDP dose. Multivariate logistic regression analyses were performed to identify the factors associated with ototoxicity, including the cumulative dose, age, radiotherapy, and the primary tumor site.

Results: At baseline, older patients exhibited substantially impaired high-frequency hearing compared with younger patients. Across all age groups, hearing deteriorated in a dose-dependent manner following CDDP exposure. However, despite smaller apparent longitudinal threshold shifts, older patients developed clinically relevant PTA-defined ototoxicity at lower cumulative CDDP doses than younger patients, reflecting limited auditory reserve. Contrastingly, larger threshold shifts observed in younger patients reflected greater measurable dynamic range from preserved baseline hearing rather than an increased vulnerability. DPOAE changes were attenuated in older patients, suggesting that DPOAE had reduced sensitivity for detecting CDDP-induced ototoxicity in the presence of pre-existing cochlear damage.

Conclusion: CDDP-induced ototoxicity shows distinct age-dependent patterns, with older patients experiencing clinically significant hearing impairment at lower cumulative doses despite smaller longitudinal changes. These findings highlight the need for age-adapted monitoring strategies and cumulative dose-conscious treatment planning to preserve auditory function in cancer survivors.