非头颈癌患者的免疫检查点抑制剂与喉科结局
Immune Checkpoint Inhibitors and Laryngological Outcomes in Patients with Non-Head and Neck Cancer.
文献信息
| PMID | 42838783 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Neil S Dogra |
| 作者单位 | University of Rochester, School of Medicine & Dentistry, Rochester, New York. Electronic address: Neil_Dogra@URMC.Rochester.edu. |
| 期刊 | Journal of voice : official journal of the Voice Foundation |
| SCI 分区 | Q1 |
| IF | 2.4 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 咽喉科 |
中文摘要
目的： 随着免疫检查点抑制剂（ICI）在癌症治疗中的应用日益增多，免疫相关不良事件不断被认识。声音、吞咽和口腔功能障碍会显著损害癌症患者的生活质量和治疗耐受性，但ICI治疗的喉科风险仍不明确。我们比较了ICI与非ICI抗肿瘤治疗后这些功能的相关结局。
方法： 利用TriNetX研究网络，我们识别了接受ICI治疗与接受非ICI全身抗肿瘤药物治疗的非头颈部恶性肿瘤成人患者。为将脱靶不良事件与癌症及其治疗的影响区分开来，两个队列均排除了既往头颈部恶性肿瘤、喉切除术或咽切除术以及头颈部放疗。队列按人口学特征、恶性肿瘤亚型、自身免疫性疾病和相关合并症进行1:1匹配。在治疗开始后6个月、1年和5年，使用Cox比例风险回归的风险比（HR）评估新发喉部诊断。
结果： 匹配后，每个队列各保留123,628例患者，所有协变量均平衡良好。ICI暴露显示声音障碍风险显著更高（6个月：HR 1.59，95% CI 1.44-1.75；1年：1.61，1.48-1.74；5年：1.43，1.35-1.52）、声带麻痹（6个月：1.31，1.13-1.51；1年：1.37，1.21-1.54；5年：1.44，1.30-1.58）、口干症（6个月：2.52，2.29-2.78；1年：2.65，2.45-2.87；5年：2.33，2.19-2.48）、吞咽困难（6个月：1.35，1.29-1.41；1年：1.44，1.38-1.49；5年：1.47，1.43-1.51）和口腔黏膜炎（6个月：1.25，1.18-1.31；1年：1.41，1.34-1.47；5年：1.52，1.46-1.58）。喉痉挛在ICI暴露后5年显著升高（HR 1.53，95% CI 1.09-2.13）。急性和慢性喉炎、喉水肿以及慢性咽炎在任何时间间隔均无显著差异。
结论： ICI启动与急性期和长期随访期间声音、口腔和吞咽功能障碍风险升高相关。这些不良效应值得在治疗前咨询和治疗目标讨论中加以考虑，临床医生应在整个ICI治疗期间及时评估新出现的声音、口腔或吞咽主诉。
英文摘要
OBJECTIVES: As immune checkpoint inhibitor (ICI) utilization increases in cancer treatment, immune-related adverse events continue to be recognized. Voice, swallowing, and oral dysfunction substantially impair quality of life and treatment tolerance in cancer patients, but the laryngological risks of ICI therapy remain unclear. We compared outcomes for these functions after ICI versus non-ICI antineoplastic therapies.
METHODS: Using the TriNetX research network, we identified adults with non-head and neck malignancies treated with ICIs versus non-ICI systemic antineoplastics. To isolate off-target adverse events from the effects of cancer and its treatment, both cohorts excluded prior head and neck malignancy, laryngectomy or pharyngectomy, and head and neck radiotherapy. Cohorts were matched 1:1 on demographics, malignancy subtype, autoimmune conditions, and pertinent comorbidities. Incident laryngeal diagnoses were assessed at 6 months, 1 year, and 5 years after treatment initiation using hazard ratios (HR) from Cox proportional hazards regressions.
RESULTS: After matching, 123,628 patients remained in each cohort with all covariates well balanced. ICI exposure showed significantly higher hazards of voice disturbance (6 months: HR 1.59, 95% CI 1.44-1.75; 1 year: 1.61, 1.48-1.74; 5 years: 1.43, 1.35-1.52), vocal fold paralysis (6 months: 1.31, 1.13-1.51; 1 year: 1.37, 1.21-1.54; 5 years: 1.44, 1.30-1.58), xerostomia (6 months: 2.52, 2.29-2.78; 1 year: 2.65, 2.45-2.87; 5 years: 2.33, 2.19-2.48), dysphagia (6 months: 1.35, 1.29-1.41; 1 year: 1.44, 1.38-1.49; 5 years: 1.47, 1.43-1.51), and oral mucositis (6 months: 1.25, 1.18-1.31; 1 year: 1.41, 1.34-1.47; 5 years: 1.52, 1.46-1.58). Laryngospasm was elevated significantly with ICI exposure at 5 years (HR 1.53, 95% CI 1.09-2.13). Acute and chronic laryngitis, laryngeal edema, and chronic pharyngitis did not differ significantly at any interval.
CONCLUSIONS: ICI initiation was associated with elevated hazards of voice, oral, and swallowing dysfunction across acute and long-term intervals. These adverse effects warrant consideration in pretreatment counseling and goals-of-care discussions, and clinicians should evaluate new voice, oral, or swallowing complaints promptly throughout ICI treatment.