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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.

DOI:10.1038/s41598-025-13706-9
PMID:40730889
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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本文引用的文献

1
Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据:全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-β blockade in HPV-unrelated head and neck cancer.在人乳头瘤病毒无关的头颈癌中,新辅助程序性死亡受体配体1和转化生长因子-β阻断后增强的新表位特异性免疫。
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The World Report on Hearing, what does it mean for me and how can it improve access to hearing devices?
《世界听力报告》对我意味着什么,它如何能改善听力设备的获取情况?
Ear Nose Throat J. 2023 Feb 15:1455613231157937. doi: 10.1177/01455613231157937.
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Audiovestibular Toxicity Secondary to Immunotherapy: Case Series and Literature Review.免疫治疗继发的听觉前庭毒性:病例系列及文献综述
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Phase II Clinical Trial of Neoadjuvant and Adjuvant Pembrolizumab in Resectable Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma.可切除局部晚期头颈部鳞状细胞癌新辅助和辅助派姆单抗的 II 期临床试验。
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Immune-mediated ototoxicity associated with immune checkpoint inhibitors in patients with melanoma.黑色素瘤患者的免疫检查点抑制剂相关免疫介导性耳毒性。
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Bilateral Sensorineural Hearing Loss Associated With Nivolumab Therapy for Stage IV Malignant Melanoma.与纳武单抗治疗IV期恶性黑色素瘤相关的双侧感音神经性听力损失
Ear Nose Throat J. 2021 Jun;100(3_suppl):286S-291S. doi: 10.1177/0145561320940847. Epub 2020 Jul 23.
9
Evaluation of Nivolumab for Ototoxic Effects: An Animal Study in Rats.尼伏鲁单抗的耳毒性评估:大鼠动物研究。
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Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study.帕博利珠单抗单药或联合化疗对比西妥昔单抗联合化疗用于治疗复发性或转移性头颈部鳞状细胞癌(KEYNOTE-048):一项随机、开放标签、III 期研究。
Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.