Article record

头颈癌中顺铂诱导耳毒性的年龄依赖性模式：一项纵向听力学分析

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

临床研究耳科IF 3.6Q2

文献信息

PMID	42839385
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	C Suzuki 查看其他 8 位作者 Y Kishimoto；M Yamamoto；N Yamamoto；M Kitamura；S Hiraoka；R Nakashima；S Morita；K Omori
作者单位	Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 查看其他 9 条单位信息 Department of Early Clinical Development, Graduate School of Medicine, Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki-CONNECT), Kyoto University Hospital, Kyoto, Japan.；Division of Behavioral Statistics, Graduate School of Human Sciences, The University of Osaka, Osaka, Japan.；RIKEN Center for Advanced Intelligence Project, Tokyo, Japan.；Data Science and AI Innovation Research Promotion Center, Shiga University, Shiga, Japan.；Department of Otolaryngology-Head and Neck Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.；Department of Head and Neck Surgery, Kanazawa Medical University, Kahoku, Japan.；Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.；Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Kyoto, Kyoto, Japan.；Department of Head and Neck Oncology and Innovative Treatment, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
期刊	Cancer medicine
SCI 分区	Q2
IF	3.6
研究类型	临床研究 · 临床
所属专科	耳科

中文摘要

背景： 顺铂（CDDP）是治疗头颈癌的关键化疗药物。生存率的提高增加了对CDDP诱导耳毒性的关注，因为这种毒性显著影响幸存者的生活质量。然而，CDDP诱导耳毒性的剂量依赖性和年龄相关模式仍未完全明确。因此，在本研究中，我们旨在通过追踪纵向听力数据并评估相关因素来表征CDDP诱导的耳毒性。
患者和方法： 我们回顾性分析了2009年1月至2023年6月期间在一家三级癌症中心接受基于CDDP化疗的316例头颈癌患者队列。使用纯音测听（PTA）和畸变产物耳声发射（DPOAE）在累积CDDP剂量范围内纵向评估听力功能。进行多变量逻辑回归分析以确定与耳毒性相关的因素，包括累积剂量、年龄、放疗和原发肿瘤部位。
结果： 在基线时，与年轻患者相比，老年患者表现出明显受损的高频听力。在所有年龄组中，暴露于CDDP后听力以剂量依赖性方式恶化。然而，尽管纵向阈值变化较小，老年患者比年轻患者在更低的累积CDDP剂量下就出现临床相关的PTA定义耳毒性，反映了有限的听觉储备。相反，在年轻患者中观察到的较大阈值变化反映了保留的基线听力带来的更大可测量动态范围，而不是增加的易感性。老年患者的DPOAE变化减弱，表明在存在预先存在的耳蜗损伤时，DPOAE检测CDDP诱导耳毒性的敏感性降低。
结论： CDDP诱导的耳毒性显示出明显的年龄依赖性模式，老年患者在较低累积剂量下就出现临床显著的听力损害，尽管纵向变化较小。这些发现强调需要年龄适应的监测策略和考虑累积剂量的治疗计划，以保护癌症幸存者的听觉功能。

英文摘要

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.