Department for Orthopedic and Trauma Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Department of Radiation Oncology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Spine J. 2018 May;18(5):776-781. doi: 10.1016/j.spinee.2017.09.011. Epub 2017 Sep 28.
Spinal metastases occur in 30%-50% of patients with systemic cancer. The primary goals of palliation are pain control and prevention of local recurrence.
This study aimed to test the safety and efficacy of a combined modality approach consisting of kyphoplasty and intraoperative radiotherapy (Kypho-IORT).
STUDY DESIGN/SETTING: Kyphoplasty and intraoperative radiotherapy was a prospective, single-center phase I/II trial. Patients were enrolled in a classical 3+3 scheme within the initial phase I, where Kypho-IORT was applied using a needle-shaped 50 kV X-ray source at three radiation dose levels (8 Gy in 8-mm, 8 Gy in 11-mm, and 8 Gy in 13-mm depth). Thereafter, cohort expansion was performed as phase II of the trial. The trial is registered with clinicaltrials.gov, number NCT01280032.
Patients aged 50 years and older with a Karnofsky Performance Status of at least 60% and with one to three painful vertebral metastases confined to the vertebral body were eligible to participate.
The primary end point was safety as per the occurrence of dose-limiting toxicities. The secondary end points were pain reduction, local progression-free survival (L-PFS), and overall survival (OS).
Pain was measured using the visual analog scale (VAS) and local control was assessed in serial computed tomography or magnetic resonance imaging scans.
None of the nine patients enrolled in the phase I showed dose-limiting toxicities at any level and thus, 52 patients were subsequently enrolled into a phase II, where Kypho-IORT was performed at various dose levels. The median pain score significantly dropped from 5 preoperatively to 2 at the first postoperative day (p<.001). Of 43 patients who reported a pre-interventional pain level of 3 or more, 30 (69.8%) reported a reduction of ≥3 points on the first postoperative day. A persistent pain reduction beyond the first postoperative day of ≥3 points was seen in 34 (79.1%) patients. The 3, 6, and 12 month L-PFS was excellent with 97.5%, 93.8%, and 93.8%. The 3, 6, and 12 months OS was 76.9%, 64.0%, and 48.4%.
Kyphoplasty and intraoperative radiotherapy is safe and immediately provided sustained pain relief with excellent local control rates in patients with painful vertebral metastases.
脊柱转移发生在 30%-50%的全身癌症患者中。缓解的主要目标是控制疼痛和预防局部复发。
本研究旨在测试椎体成形术和术中放疗（Kypho-IORT）联合治疗方法的安全性和疗效。
研究设计/地点：椎体成形术和术中放疗是一项前瞻性、单中心的 I/II 期试验。在初始 I 期的经典 3+3 方案中，使用 50kV 针状 X 射线源在三个辐射剂量水平（8Gy 深度 8mm、8Gy 深度 11mm 和 8Gy 深度 13mm）下应用 Kypho-IORT。此后，作为试验的 II 期进行了队列扩展。该试验在 clinicaltrials.gov 上注册，编号为 NCT01280032。
年龄在 50 岁及以上、卡氏功能状态评分至少为 60%、有 1 至 3 处疼痛性椎体转移局限于椎体的患者有资格参加。
主要终点为根据剂量限制毒性的发生情况评估安全性。次要终点为疼痛缓解、局部无进展生存期（L-PFS）和总生存期（OS）。
使用视觉模拟量表（VAS）测量疼痛，在连续 CT 或磁共振成像扫描中评估局部控制情况。
在 I 期入组的 9 名患者中，没有任何患者出现任何水平的剂量限制毒性，因此随后入组了 52 名患者进行 II 期治疗，在不同剂量水平下进行 Kypho-IORT。中位疼痛评分从术前的 5 分显著下降至术后第 1 天的 2 分（p<.001）。在 43 名报告术前疼痛水平为 3 或更高的患者中，30 名（69.8%）在术后第 1 天报告疼痛减轻≥3 分。34 名（79.1%）患者在术后第 1 天持续疼痛缓解≥3 分。3、6 和 12 个月的 L-PFS 分别为 97.5%、93.8%和 93.8%，局部控制率极佳。3、6 和 12 个月的 OS 分别为 76.9%、64.0%和 48.4%。
在患有疼痛性椎体转移的患者中，椎体成形术和术中放疗是安全的，能立即提供持续的疼痛缓解，并能获得出色的局部控制率。
