Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands.
Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):358-367. doi: 10.1016/j.ijrobp.2020.11.060. Epub 2020 Dec 14.
Pain response after conventional external beam radiation therapy (cRT) in patients with painful bone metastases is observed in 60% to 70% of patients. The aim of the VERTICAL trial was to investigate whether stereotactic body radiation therapy (SBRT) improves pain response.
This single-center, phase 2, randomized controlled trial was conducted within the PRESENT cohort, which consists of patients referred for radiation therapy of bone metastases to our tertiary center. Cohort participants with painful bone metastases who gave broad informed consent for randomization were randomly assigned to cRT or SBRT. Only patients in the intervention arm received information about the trial and were offered SBRT (1 × 18 Gy, 3 × 10 Gy, or 5 × 7 Gy), which they could accept or refuse. Patients who refused SBRT underwent standard cRT (1 × 8 Gy, 5 × 4 Gy, or 10 × 3 Gy). Patients in the control arm were not informed. Primary endpoint was pain response at 3 months after radiation therapy. Secondary outcomes were pain response at any point within 3 months, mean pain scores, and toxicity. Data were analyzed intention to treat (ITT) and per protocol (PP). This trial was registered with Clinicaltrials.gov, NCT02364115.
Between January 29, 2015, and March 20, 2019, 110 patients were randomized. ITT analysis included 44 patients in the cRT arm and 45 patients in the SBRT arm. In the intervention arm, 12 patients (27%) declined SBRT, and 7 patients (16%) were unable to complete the SBRT treatment. In ITT, 14 of 44 patients (32%; 95% confidence interval [CI], 18%-45%) in the control arm and 18 of 45 patients (40%; 95% CI, 26%-54%) in the SBRT arm reported a pain response at 3 months (P = .42). In PP, these proportions were 14 of 44 (32%; 95% CI, 18%-45%) and 12 of 23 patients (46%; 95% CI, 27%-66%), respectively (P = .55). In ITT, a pain response within 3 months was reported by 30 of 44 control patients (82%; 95% CI, 68%-90%) and 38 of 45 patients (84%; 95% CI, 71%-92%) in the SBRT arm (P = .12). In PP, these proportions were 36 of 44 (82%; 95% CI, 68%-90%) and 26 of 27 patients (96%; 95% CI; 81%-100%), respectively (P = .12). No grade 3 or 4 toxicity was observed in either arm.
SBRT did not significantly improve pain response in patients with painful bone metastases. One in 4 patients preferred to undergo cRT over SBRT, and 1 in 5 patients starting SBRT was unable to complete this treatment. Because of this selective dropout, which can be attributed to the character of the intervention, the trial was underpowered to detect the prespecified difference in pain response.
在接受常规体外放射治疗（cRT）的伴有疼痛性骨转移的患者中，约有 60%至 70%观察到疼痛反应。VERTICAL 试验的目的是研究立体定向体部放射治疗（SBRT）是否能改善疼痛反应。
这是一项在 PRESENT 队列内进行的单中心、2 期、随机对照试验，该队列由转诊至我们的三级中心进行骨转移放射治疗的患者组成。有疼痛性骨转移且对随机分组有广泛知情同意的队列参与者被随机分配至 cRT 或 SBRT 组。只有干预组的患者才会收到有关试验的信息并被提供 SBRT（1×18Gy、3×10Gy 或 5×7Gy），他们可以接受或拒绝。拒绝 SBRT 的患者接受标准 cRT（1×8Gy、5×4Gy 或 10×3Gy）。对照组的患者未被告知。主要终点是放射治疗后 3 个月的疼痛反应。次要终点是 3 个月内任何时候的疼痛反应、平均疼痛评分和毒性。数据按意向治疗（ITT）和方案（PP）进行分析。该试验在 Clinicaltrials.gov 上注册，NCT02364115。
2015 年 1 月 29 日至 2019 年 3 月 20 日期间，共有 110 名患者被随机分组。ITT 分析包括 cRT 组的 44 名患者和 SBRT 组的 45 名患者。在干预组中，12 名患者（27%）拒绝 SBRT，7 名患者（16%）无法完成 SBRT 治疗。在 ITT 中，对照组的 44 名患者中有 14 名（32%；95%CI，18%-45%）和 SBRT 组的 45 名患者中有 18 名（40%；95%CI，26%-54%）报告在 3 个月时有疼痛反应（P=0.42）。在 PP 中，这些比例分别为 44 名患者中的 14 名（32%；95%CI，18%-45%）和 23 名患者中的 12 名（46%；95%CI，27%-66%）（P=0.55）。在 ITT 中，对照组的 44 名患者中有 30 名（82%；95%CI，68%-90%）和 SBRT 组的 45 名患者中有 38 名（84%；95%CI，71%-92%）报告在 3 个月内有疼痛反应（P=0.12）。在 PP 中，这些比例分别为 44 名患者中的 36 名（82%；95%CI，68%-90%）和 27 名患者中的 26 名（96%；95%CI，81%-100%）（P=0.12）。在两个治疗组中均未观察到 3 级或 4 级毒性。
SBRT 并未显著改善伴有疼痛性骨转移的患者的疼痛反应。每 4 名患者中就有 1 名更愿意接受 cRT 而不是 SBRT，而开始 SBRT 的患者中每 5 名就有 1 名无法完成这种治疗。由于这种选择性脱落，这可以归因于干预的性质，该试验在检测预先规定的疼痛反应差异方面的效力不足。
