STOP 下组颅神经病：大剂量皮质类固醇治疗口咽癌幸存者迟发性放射性相关下组颅神经病：一项 I 期剂量探索试验的中期分析。
STOP Lower Cranial Neuropathy: High-Dose Corticosteroid Therapy for Late Radiation-Associated Lower Cranial Neuropathy in Oropharyngeal Cancer Survivors: Interim Analysis of a Phase I Dose-Finding Trial.
文献信息
| PMID | 42782239 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Zayne A S Belal |
| 作者单位 | Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiation Oncology, The University of Texas Medical Branch, Galveston, Texas. |
| 期刊 | International journal of radiation oncology, biology, physics |
| SCI 分区 | Q1 |
| IF | 7.1 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 咽喉科 |
中文摘要
目的： 放射性相关下组颅神经病（LCNP）是头颈癌（HNC）幸存者中一种使人衰弱的晚期并发症，导致进行性吞咽困难、误吸和丧失营养独立性。LCNP 尚无经过验证的疗法。这项 I/II 期剂量探索试验（STOP LCNP，NCT04151082）及平行注册研究前瞻性评估了大剂量皮质类固醇治疗放射性相关 LCNP 的安全性、可行性、耐受性和症状缓解情况。
方法与材料： 来自 STOP LCNP 试验的 I 期剂量探索中期报告。符合条件的参与者为无病或口咽癌幸存者，放疗后 ≥2 年，经肌电图证实为 LCNP（CN XII ± X），且无结构性/恶性病因。I 期测试包括口服泼尼松 1 mg/kg（剂量 1，n = 3）或 3 mg/kg（剂量 2，n = 5），每日一次，共 5 天（2 周逐渐减量）。一个平行注册研究（n = 6）纳入了更广泛接受 1 mg/kg 治疗的 HNC 幸存者。基于规则的 I 期剂量递增决策已预先指定，用于评估耐受性和症状缓解（主要终点）；从基线至减量后 1 至 2 周，MD Anderson 症状量表-头颈模块前 5 项平均症状评分下降 ≥1.315 个单位表明具有临床意义的改善。次要终点包括临床医生评定的延髓功能指标、肌电图和患者报告结局指标。
结果： 所有方案均可行且耐受良好。失眠（n = 5，1 级）是最常见的不良事件，无治疗中止。在减量后 1 至 2 周，MD Anderson 症状量表-头颈模块前 5 项变化的中位数在 1 mg/kg 组为 -0.2，在 3 mg/kg 组为 -1.6；接受 3 mg/kg 的 5 例患者中有 3 例达到具有临床意义的改善，但在 6 至 10 周时未能维持。在两个剂量水平下，客观功能或电生理指标均未观察到一致的改善。
结论： 大剂量皮质类固醇治疗在患有 LCNP 的长期 HNC 幸存者中可行且可耐受。接受 3 mg/kg 治疗的大多数患者获得了短期症状改善，但未反映在临床医生评定的延髓功能指标中，并且在两个剂量下至 6 至 10 周时均不持久。
英文摘要
PURPOSE: Radiation-associated lower cranial neuropathy (LCNP) is a debilitating late complication among head and neck cancer (HNC) survivors, leading to progressive dysphagia, aspiration, and loss of nutritional independence. No proven therapies exist for LCNP. This phase I/II dose-finding trial (STOP LCNP, NCT04151082) and parallel registry study prospectively evaluated the safety, feasibility, tolerability, and symptomatic response of high-dose corticosteroid therapy for radiation-associated LCNP.
METHODS AND MATERIALS: Interim phase I dose-finding report from the STOP LCNP trial. Eligible participants were disease-free oropharyngeal cancer survivors ≥2 years after radiation therapy with electromyography-confirmed LCNP (CN XII ± X) absent structural/malignant etiology. Phase I testing included oral prednisone 1 mg/kg (dose 1, n = 3) or 3 mg/kg (dose 2, n = 5) daily for 5 days (2-week taper). A parallel registry (n = 6) enrolled broader HNC survivors treated with 1 mg/kg. Rule-based phase I dose-escalation decisions were prespecified for tolerability and symptom response (primary endpoint); ≥1.315-unit decrease in MD Anderson Symptom Inventory-Head and Neck Module Top 5 mean symptom score from baseline to 1 to 2 weeks posttaper indicated clinically meaningful improvement. Secondary endpoints included clinician-graded measures of bulbar function, electromyography, and patient-reported outcome measures.
RESULTS: All regimens were feasible and well tolerated. Insomnia (n = 5, grade 1) was the most frequent adverse event with no treatment discontinuations. At 1 to 2 weeks posttaper, the median MD Anderson Symptom Inventory-Head and Neck Module Top 5 change was -0.2 in 1 mg/kg and -1.6 in 3 mg/kg; 3 of 5 patients receiving 3 mg/kg achieved clinically meaningful improvement not maintained at 6 to 10 weeks. No consistent improvements were observed in objective functional or electrophysiologic measures at either dose level.
CONCLUSIONS: High-dose corticosteroid therapy was feasible and tolerable in long-term HNC survivors with LCNP. Short-term symptomatic improvement was achieved in the majority treated with 3 mg/kg but was not reflected in clinician-graded measures of bulbar function and not durable by 6 to 10 weeks at either dosing.