Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
JAMA. 2023 Aug 1;330(5):421-431. doi: 10.1001/jama.2023.12222.
Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically.
To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma.
DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 100 patients with a newly diagnosed (<6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. Participants were enrolled at the Norwegian National Unit for Vestibular Schwannoma from October 28, 2014, through October 3, 2017; 4-year follow-up ended on October 20, 2021.
Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires.
The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications.
Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P = .002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed.
Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed.
ClinicalTrials.gov Identifier: NCT02249572.
目前治疗小至中型前庭神经鞘瘤的指南建议采用 upfront 放射外科手术或等待至肿瘤生长在影像学上被检测到时再进行治疗。
确定 upfront 放射外科手术是否能提供比等待和扫描方法更优越的肿瘤体积缩小效果，用于治疗小至中型前庭神经鞘瘤。
设计、地点和参与者：这是一项在挪威前庭神经鞘瘤国家单位进行的 100 名新诊断（<6 个月）单侧前庭神经鞘瘤患者的随机临床试验，最大肿瘤直径在桥小脑角处的磁共振成像上小于 2 厘米。参与者于 2014 年 10 月 28 日至 2017 年 10 月 3 日入组；4 年随访于 2021 年 10 月 20 日结束。
参与者被随机分配接受 upfront 放射外科手术（n = 50）或进行等待和扫描方案，该方案仅在影像学记录到肿瘤生长时才给予治疗（n = 50）。参与者接受了 5 次年度研究访问，包括临床评估、影像学检查、听觉前庭测试和问卷调查。
主要结果是试验结束时（4 年）和基线时（V4:V0）肿瘤体积的比值。有 26 个预先指定的次要结局，包括患者报告的症状、临床检查、听觉前庭测试和生活质量结局。安全性结局是挽救性微创手术和放射相关并发症的风险。
在 100 名随机患者中，98 名完成了试验并被纳入主要分析（平均年龄 54 岁；42%为女性）。在 upfront 放射外科手术组中，有 1 名患者（2%）在肿瘤生长时接受了重复放射外科手术，2 名患者（4%）需要挽救性微创手术，45 名患者（94%）没有接受其他治疗。在等待和扫描组中，有 21 名患者（42%）在肿瘤生长时接受了放射外科手术，1 名患者（2%）接受了挽救性微创手术，28 名患者（56%）未接受治疗。对于肿瘤体积比值的主要结局，upfront 放射外科手术组的试验结束时（V4:V0）的几何平均值为 0.87（95%CI，0.66-1.15），而等待和扫描组为 1.51（95%CI，1.23-1.84），表明 upfront 放射外科手术组的肿瘤体积缩小更明显（等待和扫描组到 upfront 放射外科手术组的比值，1.73；95%CI，1.23-2.44；P = 0.002）。在 26 个次要结局中，有 25 个没有显著差异。没有观察到放射相关并发症。
在新诊断的小至中型前庭神经鞘瘤患者中，upfront 放射外科手术在 4 年时显示出比等待和扫描方法（在肿瘤生长时进行治疗）更显著的肿瘤体积缩小效果。这些发现可能有助于为前庭神经鞘瘤患者的治疗决策提供信息，并且需要进一步研究长期的临床结局。
ClinicalTrials.gov 标识符：NCT02249572。
