Phase II Randomized Trial of Single- vs. Two-Fraction Spine Stereotactic Radiosurgery for the Treatment of Vertebral Metastases

• Published in: International journal of radiation oncology, biology, physics Vol. 117; no. 2; p. e89
• Main Authors: Billena, C., Angelov, L., Balagamwala, E.H., Miller, J.A., Reddy, C.A., Koro, S., Bommireddy, A., Emch, T., Suh, J.H., Murphy, E.S., Xia, P., Magnelli, A., Chao, S.T.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2023
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2023.06.845

As systemic therapies improve significantly, more patients with limited metastatic disease are undergoing spine stereotactic radiosurgery (sSRS). High dose (≥24 Gy) single fraction sSRS has been associated with a vertebral compression fracture (VCF) risk of up to 40%. Comparatively, lower dose (16-18 Gy) single fraction sSRS is associated with a fracture risk of 15-20%, with the risk increasing as the dose increases. To mitigate the risk of VCF, while optimizing higher dose delivery, some have advocated utilizing two-fraction sSRS regimen. Therefore, we designed a phase II randomized trial in which we hypothesized that single fraction sSRS is non-inferior to two-fraction sSRS with respect to VCF but offers patients greater convenience. Inclusion criteria include age ≥18, Karnofsky performance score ≥70, vertebral metastasis from C3 to L5, maximum of three separate sites of metastases, limited paraspinal extension (<5 cm), and no rapid neurological decline. Patients must also be either Recursive Partitioning Analysis Class 1 (KPS >70 AND controlled systemic disease) or Class 2 (KPS >70, uncontrolled systemic disease OR KPS ≤70, age ≥54, no visceral metastases). Exclusion criteria include multiple primary cancers, primary neoplasm of the spine, prior surgery at the site of sSRS, spinal cord compression, bony retropulsion resulting in neurologic deficit, inability to undergo/contraindication to MRI, or diffuse multi-level metastatic spine disease. Our primary hypothesis is that single fraction sSRS (experimental arm – 16-18 Gy) is non-inferior to two fraction sSRS (standard arm – 24 Gy). Furthermore, we hypothesize that both treatment arms will have similar local control, pain control, quality of life and toxicity profiles. The primary endpoint of this trial is the development or progression of VCF at 6 months. Secondary endpoints include local control, pain control, quality of life and toxicity all of which will be assessed at 12 months. For the sample size calculation, we assumed a VCF risk of 17% in the experimental arm and a 7% risk in the standard arm. Based on these calculations, we aim to enroll 130 patients, 65 in each arm. This trial is currently enrolling patients actively, and approximately 30% of expected enrollment has been completed to date. This trial is registered on clinicaltrials.gov: NCT04218617. Pending full accrual. Pending full accrual.