头颈癌放化疗后耳蜗辐射剂量与早期听力变化：一项单中心回顾性队列研究

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中文摘要

背景/目的： 听力损伤是头颈癌（HNC）放化疗常见但未被充分认识的后遗症。我们评估了治疗后早期听力变化的发生率及其与耳蜗辐射暴露和同步铂类化疗的关联。
方法： 我们开展了一项单中心回顾性队列研究，纳入2024年11月至2025年9月期间接受放疗的70例连续HNC患者。将接受同步放化疗（CRT，n=48）的患者与接受单纯放疗（RT，n=22）的患者进行比较。主要结局为临床记录的治疗后听力变化。从治疗计划中提取耳蜗最大点剂量（Dmax）。分析包括Fisher精确检验和Mann-Whitney U检验、Spearman相关性分析、Firth惩罚逻辑回归、Cochran-Armitage趋势检验以及限制性立方样条。
结果： 70例患者中有38例（54.3%）记录了治疗后听力变化：CRT后为58.3%，单纯RT后为45.5%（比值比（OR）1.68，95%置信区间（CI）0.61-4.49，p=0.439）。发生听力变化患者的平均耳蜗Dmax更高（中位数5.5 Gy vs. 2.5 Gy，p=0.045），且与结局相关（ρ=0.244，p=0.043），耳蜗剂量三分位组的听力变化率分别为34.8%、65.2%和65.2%（趋势p=0.038）。在调整年龄、治疗前听力损失和同步CRT的Firth回归中，该关联减弱且无统计学显著性（每10 Gy调整OR 1.31，95%CI 0.82-2.08，p=0.253），在考虑肿瘤部位后进一步减弱（每10 Gy OR 1.09，95%CI 0.66-1.80，p=0.735），其中口咽原发是听力变化最强的相关因素（OR 4.02，95%CI 1.28-12.6）。仅10例患者有配对听力图，其中7例显示听力学恶化；38例事件中有14例不能排除传导性成分。没有患者超过QUANTEC耳蜗平均剂量限制45 Gy。
结论： 在这一当代队列中，早期临床可见的听力变化影响了超过一半的患者。与耳蜗剂量的单变量关联在调整后未能持续存在，尤其是调整肿瘤部位后，且现有听力学数据无法将听力变化特异性地归因于耳蜗损伤。这些发现强调需要系统性的基线和随访听力测定，而非证明进一步降低耳蜗剂量会改善听力结局。

英文摘要

Background/Objectives: Hearing impairment is a frequent but under-recognized sequela of (chemo)radiotherapy for head and neck cancer (HNC). We assessed the frequency of early post-treatment hearing changes and their association with cochlear radiation exposure and concurrent platinum-based chemotherapy. Methods: We conducted a single-center retrospective cohort study of 70 consecutive patients with HNC treated with radiotherapy between November 2024 and September 2025. Patients receiving concurrent chemoradiotherapy (CRT, n = 48) were compared with patients receiving radiotherapy alone (RT, n = 22). The primary outcome was clinically documented post-treatment hearing change. Cochlear maximum point doses (Dmax) were extracted from treatment plans. Analyses included Fisher exact and Mann-Whitney U tests, Spearman correlations, Firth penalized logistic regression, a Cochran-Armitage trend test, and restricted cubic splines. Results: Post-treatment hearing changes were documented in 38/70 patients (54.3%): 58.3% after CRT versus 45.5% after RT alone (odds ratio (OR) 1.68, 95% confidence interval (CI) 0.61-4.49, p = 0.439). Mean cochlear Dmax was higher in patients with hearing change (median 5.5 vs. 2.5 Gy, p = 0.045) and correlated with the outcome (ρ = 0.244, p = 0.043), with hearing-change rates of 34.8%, 65.2%, and 65.2% across cochlear-dose tertiles (trend p = 0.038). In Firth regression adjusted for age, pre-treatment hearing loss, and concurrent CRT, the association was attenuated and not statistically significant (adjusted OR 1.31 per 10 Gy, 95% CI 0.82-2.08, p = 0.253), and it was attenuated further after accounting for tumor site (OR 1.09 per 10 Gy, 95% CI 0.66-1.80, p = 0.735), with oropharyngeal primary the strongest correlate of hearing change (OR 4.02, 95% CI 1.28-12.6). Paired audiograms were available in only 10 patients, seven of whom showed audiometric deterioration; a conductive component could not be excluded in 14/38 events. No patient exceeded the QUANTEC mean cochlear-dose constraint of 45 Gy. Conclusions: Early, clinically apparent hearing changes affected more than half of this contemporary cohort. The univariable association with cochlear dose did not persist after adjustment, particularly for tumor site, and the available audiometric data do not allow hearing changes to be attributed specifically to cochlear injury. These findings underscore the need for systematic baseline and follow-up audiometry rather than demonstrating that further cochlear-dose reduction would improve hearing outcomes.