RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized (1-3) spine metastases: Phase 2 results

Abstract

Purpose The phase II component of RTOG 0631 assessed the feasibility and safety of spine radiosurgery (SRS) for localized spine metastases in a cooperative group setting. Materials and Methods Patients with 1-3 spine metastasis with a Numerical Rating Pain Scale (NRPS) score ≥ 5 received 16 Gy single fraction SRS. The primary endpoint was SRS feasibility: image-guidance RT (IGRT) targeting accuracy ≤ 2mm, target volume coverage > 90% of prescription dose, maintaining spinal cord dose constraints (10 Gy to ≤ 10% of the cord volume from 5-6mm above to 5-6mm below the target or absolute spinal cord volume < 0.35cc) and other normal tissue dose constraints. A feasibility success rate < 70% was considered unacceptable for continuation of the phase III component. Based on the one-sample exact binomial test with α=0.10 (1-sided), 41 patients were required. Acute toxicity was assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. Results Sixty-five institutions were credentialed with spine phantom dosimetry and IGRT compliance. Forty-six patients were accrued, and 44 were eligible. There were 4 cervical, 21 thoracic and 19 lumbar sites. Median NRPS was 7 at presentation. Final pre-treatment rapid review was approved in 100%. Accuracy of image-guided SRS targeting was in compliance with the protocol in 95%. The target coverage and spinal cord dose constraint were in accordance with the protocol requirements in 100% and 97%. Overall compliance for other normal tissue constraints was per protocol in 74%. There were no cases of grade 4-5 acute treatment-related toxicity. Conclusion The phase II results demonstrate the feasibility and accurate use of SRS to treat spinal metastases, with rigorous quality control, in a cooperative group setting. The planned RTOG 0631 phase III component will proceed to compare pain relief and quality of life between SRS and external beam radiotherapy.

Improving accuracy for stereotactic body radiotherapy treatments of spinal metastases

“…Four previously treated and anonymized SBRT spine CT and contour datasets were selected with differing vertebra and target volume shapes (targeting had been previously performed by radiation oncologists according to international guidelines,3, 13 CT was performed with 2 mm slices). Eight different SBRT spine plans were created on each CT image dataset, utilizing both the 6 MV and 6 MV FFF beam.…”

“…Plans were created within the TPS each with the same fractionation and dose constraints currently used clinically: 30 Gy in 3 fractions, with 100% of planned target volume (PTV) to be covered by 80% of prescribed dose,17 but ideally covered by 90% as per RTOG 0631 13. The other main metric concerned was assessment of the Paddick conformity index (CI) for target coverage (CI <1.0 implies poorer conformity)18 as per ICRU 91 19.…”

Spinal metastases: From conventional fractionated radiotherapy to single-dose SBRT

“…The RTOG 0631 prospective phase III trial compares 8 Gy with 16 Gy in single fractions to establish dose level effect on pain. 20 A prospective randomized phase III trial at Memorial Sloan Kettering Cancer Center (MSKCC) in New York compares 24 Gy in a single fraction versus 3 sessions of 9 Gy (total 27 Gy) in effecting durable local control in oligometastatic tumors, including oligometastatic spine disease (MSKCC 10-154). This study targets 200 patients, and spine lesions are eligible if the cord is >3 mm away from the edge of the planned target volume (PTV).…”

“…The RTOG 0631 trial has been designed to address this issue, exploring in a prospective randomized phase III trial pain relief with single dose 8 Gy versus 16 Gy. 20 An initial phase II study was designed to establish a baseline technical uniformity in accurate and reproducible delivery of 16 Gy single dose SBRT within the institutions participating in this cooperative group study, with rigorous quality control requirements. The phase II base-line study was completed with 44 patients with 1-3 spine metastases with a Numerical Rating Pain Scale (NRPS) score ≥5 accrued and treated with 16 Gy.…”

Comparison of four techniques for spine stereotactic body radiotherapy: Dosimetric and efficiency analysis

“…Various techniques, including dose‐escalated radiotherapy, have been utilized to improve local control and symptom palliation 2, 3, 4, 5. Safe dose escalation using stereotactic body radiotherapy (SBRT) translates into durable pain relief, decompression of epidural extensions and local control rates of 70%–90% 6, 7, 8, 9, 10, 11, 12…”