Single- Versus Multi-Fraction Spine Stereotactic Radiosurgery (ALL-STAR) for Patients with Spinal Metastases: a Randomized Phase III Trial

Abstract

Background: For patients with spine metastases, stereotactic radiosurgery (SRS) provides excellent local control and pain response. Despite increasing use of this treatment modality, there is no consensus on the optimal dose and fractionation of spine SRS for efficacy and toxicity. We have initiated a phase III randomized trial that compares two dose regimens with similar biological equivalent dose (BED) to determine the isolated effect of SRS fractionation on local control. Methods: Patients with one to three cervical, thoracic, or lumbar spine metastases spanning no more than two contiguous vertebral levels in need of radiation will be eligible for enrollment. Patients will be assigned 1:1 to receive either 22 Gy in 1 fraction or 28 Gy in 2 fractions. Biased coin randomization will be used to minimize the size difference between arms, and randomization will incorporate the following strata: gastrointestinal histology (yes/no), paraspinal tissue extension (yes/no), epidural compression (low-/high-grade), and number of sites treated (one to three). The primary endpoint is one-year local control, defined per Spine Response Assessment in Neuro-Oncology (SPINO) criteria. The secondary endpoints include patient-reported health-related quality of life (HRQOL), pain associated with the treated site, vertebral compression fracture (VCF), and two-year local control. Patients will be followed for these outcomes at one to two weeks, one month, three months, and six months after treatment, and every six months thereafter until 24 months after treatment. Discussion: The studies published thus far comparing the single- and multi-fraction SRS are lacking long-term local control outcomes and are limited by selection bias as well as single-fraction arms with higher BED, which is correlated with improved local control. Our study will compare one-year local control in patients treated with 28 Gy in 2 fractions and the biologically equivalent single-fraction dose of 22 Gy. We will additionally compare the two arms with respect to two-year local control, pain response, adverse events, VCF, and HRQOL.