Phase I/II trial of combined kyphoplasty and intraoperative radiotherapy in spinal metastases

BACKGROUND CONTEXT: Spinal metastases occur in 30%-50% of patients with systemic cancer. The primary goals of palliation are pain control and prevention of local recurrence. PURPOSE: 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. PATIENT SAMPLE: 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. OUTCOME MEASURES: The primary end point was safety as per the occurrence of doselimiting toxicities. The secondary end points were pain reduction, local progression-free survival (LPFS), and overall survival (OS). METHODS: Pain was measured using the visual analog scale (VAS) and local control was assessed in serial computed tomography or magnetic resonance imaging scans. RESULTS: 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%. CONCLUSION: Kyphoplasty and intraoperative radiotherapy is safe and immediately provided sustained pain relief with excellent local control rates in patients with painful vertebral metastases. (C) 2017 Elsevier Inc. All rights reserved.