Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial
Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial
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DOI：
10.1016/s1470-2045(21)00196-0
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发表时间：
2021-06-28
期刊：
影响因子：
51.1
通讯作者：
Parulekar, Wendy R.
中科院分区：
文献类型：
--
作者：
Sahgal, Arjun;Myrehaug, Sten D.;Parulekar, Wendy R.
背景常规外照射放射治疗是脊柱转移瘤的标准姑息治疗;然而，疼痛的完全缓解率低至10 - 20%。立体定向体部放射治疗提供高剂量、消融性放射治疗。我们的目的是比较完全缓解率疼痛后，立体定向体部放疗或传统的外照射放疗疼痛的脊柱transferation.Methods患者开放标签，多中心，随机，对照，2/3期试验在13家医院在加拿大和5家医院在澳大利亚。如果患者年龄在18岁及以上，（定义为简明疼痛量表≥ 2分）MRI证实的脊柱转移，治疗体积中包含的不超过3个连续椎体节段，东部肿瘤协作组体能状态为0 - 2，脊柱不稳定性肿瘤评分小于12，也没有神经系统症状的脊髓或马尾压迫。使用基于网络的计算机生成的分配序列将患者随机分配（1：1）接受立体定向体部放疗，剂量为24戈伊，每日2次，或使用标准技术接受常规外照射放疗，剂量为20戈伊，每日5次。通过使用最小化方法在中心进行治疗分配，以实现放射敏感性分层因素、影像学上是否存在肿块型肿瘤（骨外或硬膜外疾病扩展，或两者兼有）和中心的平衡。主要终点是放疗后3个月疼痛完全缓解的患者比例。在意向治疗人群中分析主要终点，在实际治疗人群中进行所有安全性和质量保证分析（即，所有接受至少一次放疗的患者）。结果在2016年1月4日至2019年9月27日期间，229例患者入组并随机分配接受常规外照射放疗（n = 115）或立体定向体部放疗（n = 114）。所有229例患者均纳入意向治疗分析。中位随访时间为6.7个月（IQR 6.3 - 6.9）。在3个月时，立体定向体部放疗组114例患者中的40例（35%）和常规外照射放疗组115例患者中的16例（14%）疼痛完全缓解（风险比1.33，95% CI 1.14 - 1.55; p = 0.0002）。在多变量校正分析中维持了这一显著差异（比值比3.47，95% CI 1.77 - 6.80; p = 0.0003）。最常见的3 - 4级不良事件是3级疼痛（常规外照射放疗组115例患者中的5例[4%] vs立体定向体部放疗组110例患者中的5例（5%））。没有治疗相关的死亡observed.Interpretation立体定向体放射治疗的剂量为24戈伊，在两个每日分数优于传统的外照射放射治疗的剂量为20戈伊，在5个每日分数在改善疼痛的完全反应率。这些结果表明，使用适形，图像引导，立体定向剂量递增放射治疗是适当的姑息治疗设置疼痛性脊柱转移瘤的患者的症状控制，并需要提高认识，需要专业和多学科参与提供临终关怀。版权所有（C）2021爱思唯尔有限公司保留所有权利。
Background Conventional external beam radiotherapy is the standard palliative treatment for spinal metastases; however, complete response rates for pain are as low as 10-20%. Stereotactic body radiotherapy delivers high-dose, ablative radiotherapy. We aimed to compare complete response rates for pain after stereotactic body radiotherapy or conventional external beam radiotherapy in patients with painful spinal metastasis.Methods This open-label, multicentre, randomised, controlled, phase 2/3 trial was done at 13 hospitals in Canada and five hospitals in Australia. Patients were eligible if they were aged 18 years and older, and had painful (defined as =2 points with the Brief Pain Inventory) MRI-confirmed spinal metastasis, no more than three consecutive vertebral segments to be included in the treatment volume, an Eastern Cooperative Oncology Group performance status of 0-2, a Spinal Instability Neoplasia Score of less than 12, and no neurologically symptomatic spinal cord or cauda equina compression. Patients were randomly assigned (1:1) with a web-based, computer-generated allocation sequence to receive either stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions or conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions using standard techniques. Treatment assignment was done centrally by use of a minimisation method to achieve balance for the stratification factors of radiosensitivity, the presence or absence of mass-type tumour (extraosseous or epidural disease extension, or both) on imaging, and centre. The primary endpoint was the proportion of patients with a complete response for pain at 3 months after radiotherapy. The primary endpoint was analysed in the intention-to-treat population and all safety and quality assurance analyses were done in the as-treated population (ie, all patients who received at least one fraction of radiotherapy).Findings Between Jan 4, 2016, and Sept 27, 2019, 229 patients were enrolled and randomly assigned to receive conventional external beam radiotherapy (n=115) or stereotactic body radiotherapy (n=114). All 229 patients were included in the intention-to-treat analysis. The median follow-up was 6.7 months (IQR 6.3-6.9). At 3 months, 40 (35%) of 114 patients in the stereotactic body radiotherapy group, and 16 (14%) of 115 patients in the conventional external beam radiotherapy group had a complete response for pain (risk ratio 1.33, 95% CI 1.14-1.55; p=0.0002). This significant difference was maintained in multivariable-adjusted analyses (odds ratio 3.47, 95% CI 1.77-6.80; p=0.0003). The most common grade 3-4 adverse event was grade 3 pain (five [4%] of 115 patients in the conventional external beam radiotherapy group vs five (5%) of 110 patients in the stereotactic body radiotherapy group). No treatment-related deaths were observed.Interpretation Stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions was superior to conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions in improving the complete response rate for pain. These results suggest that use of conformal, image-guided, stereotactically dose-escalated radiotherapy is appropriate in the palliative setting for symptom control for selected patients with painful spinal metastases, and an increased awareness of the need for specialised and multidisciplinary involvement in the delivery of end-of-life care is needed. Copyright (C) 2021 Elsevier Ltd. All rights reserved.