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新辅助免疫疗法对头颈鳞状细胞癌患者听力的影响。

Effects of neoadjuvant immunotherapy on hearing in patients with head and neck squamous cell carcinoma.

作者信息

Hambach Bryce, Bilokon Anhelina, Lee John, Allemang L Noelle, Chisholm Jennifer, Zalewski Chris K, Christensen Julie, Brewer Carmen C, Gulley James L, Allen Clint T, Cunningham Lisa L, Fernandez Katharine A

机构信息

Laboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD, USA.

Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

出版信息

Sci Rep. 2025 Jul 29;15(1):27558. doi: 10.1038/s41598-025-13706-9.

Abstract

Immune checkpoint blockade (ICB) is a commonly used treatment modality for cancer with a growing list of oncologic indications. Ototoxicity is a potential immune-related adverse event of ICB treatment, but the risk of hearing loss after ICB remains unknown. This retrospective chart review sought to identify individuals who received ICB and had available audiometric data before and after treatment in order to identify clinically meaningful changes in hearing. This single center, institutional chart review examined hearing function data in patients who underwent audiometry before and after ICB treatment. Measures included pure tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and word recognition scores. Ototoxicity was assessed using the American Speech-Language-Hearing-Association (ASHA) and Common Terminology Criteria for Adverse Events (CTCAEv5.0) guidelines where applicable. We identified twelve individuals with newly diagnosed, advanced-stage Head and Neck Squamous Cell Carcinoma (HNSCC) who received neoadjuvant ICB on a clinical trial. Eleven of twelve (92%) patients (8 male, 4 female, age 41-79 years) did not meet criteria for hearing threshold changes. One patient demonstrated a 10 dB shift at two consecutive frequencies in one ear, meeting the minimum ASHA criteria for significant change. Speech audiometry and tympanometry identified no differences in speech understanding or middle ear function pre-and post-treatment. Variations in DPOAE amplitudes were noted, potentially indicating early outer hair cell damage despite stable audiometric thresholds. In this small data set of newly diagnosed advanced-stage HNSCC, there appears to be a low incidence of significant hearing changes following neoadjuvant ICB treatment. Larger, prospective studies with long-term follow-up are needed to evaluate late-onset ototoxicity. Cancer survivors treated with neoadjuvant immune checkpoint blockade for advanced-stage head and neck squamous cell carcinoma (HNSCC) appear to have a low risk of acute hearing loss based on this study. While significant changes in hearing thresholds were not observed, subtle alterations in cochlear outer hair cell function were detected, suggesting the importance of long-term monitoring to capture potential delayed effects on hearing. This insight helps reassure patients about the immediate ototoxic risks while highlighting the need for continued vigilance in hearing assessment during follow-up.

摘要

免疫检查点阻断(ICB)是一种常用的癌症治疗方式,其肿瘤学适应症的清单不断增加。耳毒性是ICB治疗潜在的免疫相关不良事件,但ICB治疗后听力丧失的风险仍不明确。这项回顾性图表审查旨在识别接受ICB治疗且治疗前后有可用听力测定数据的个体,以确定听力方面具有临床意义的变化。这项单中心机构图表审查检查了ICB治疗前后接受听力测定的患者的听力功能数据。测量指标包括纯音阈值、畸变产物耳声发射(DPOAE)、鼓室图和言语识别分数。在适用的情况下,使用美国言语语言听力协会(ASHA)和不良事件通用术语标准(CTCAEv5.0)指南评估耳毒性。我们识别出12例新诊断的晚期头颈部鳞状细胞癌(HNSCC)患者,他们在一项临床试验中接受了新辅助ICB治疗。12例患者中有11例(92%)(8例男性,4例女性,年龄41 - 79岁)不符合听力阈值变化标准。1例患者一只耳朵在两个连续频率上出现了10 dB的变化,符合ASHA关于显著变化的最低标准。言语听力测定和鼓室图显示治疗前后言语理解或中耳功能无差异。注意到DPOAE振幅存在变化,这可能表明尽管听力测定阈值稳定,但早期外毛细胞已受损。在这个新诊断的晚期HNSCC的小数据集中,新辅助ICB治疗后出现显著听力变化的发生率似乎较低。需要进行更大规模的、具有长期随访的前瞻性研究来评估迟发性耳毒性。基于这项研究,接受新辅助免疫检查点阻断治疗的晚期头颈部鳞状细胞癌(HNSCC)癌症幸存者似乎急性听力丧失风险较低。虽然未观察到听力阈值的显著变化,但检测到耳蜗外毛细胞功能存在细微改变,这表明长期监测对于捕捉对听力的潜在延迟影响很重要。这一见解有助于让患者放心当前的耳毒性风险,同时强调在随访期间持续进行听力评估的必要性。

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