Single fraction radiosurgery, fractionated radiosurgery, and conventional radiotherapy for spinal oligometastasis (SAFFRON): A systematic review and meta-analysis

Raj Singh; Eric J Lehrer; Basem Dahshan; Joshua D Palmer; Arjun Sahgal; Peter C Gerszten; Nicholas G Zaorsky; Daniel M Trifiletti

doi:10.1016/j.radonc.2020.01.030

Single fraction radiosurgery, fractionated radiosurgery, and conventional radiotherapy for spinal oligometastasis (SAFFRON): A systematic review and meta-analysis

Radiother Oncol. 2020 May:146:76-89. doi: 10.1016/j.radonc.2020.01.030. Epub 2020 Feb 28.

Authors

Raj Singh¹, Eric J Lehrer², Basem Dahshan³, Joshua D Palmer⁴, Arjun Sahgal⁵, Peter C Gerszten⁶, Nicholas G Zaorsky⁷, Daniel M Trifiletti⁸

Affiliations

¹ Department of Radiation Oncology, Virginia Commonwealth University Health System, Richmond, USA.
² Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, USA.
³ Department of Radiation Oncology, West Virginia University School of Medicine, Morgantown, USA.
⁴ Department of Radiation Oncology and Neurosurgery, The James Cancer Hospital at the Ohio State University Wexner Medical Center, Columbus, USA.
⁵ Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.
⁶ Departments of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
⁷ Department of Radiation Oncology, Penn State Cancer Institute, Hershey, USA.
⁸ Department of Radiation Oncology, Mayo Clinic, Jacksonville, USA. Electronic address: trifiletti.daniel@mayo.edu.

PMID: 32114269
DOI: 10.1016/j.radonc.2020.01.030

Abstract

Background and purpose: To perform a systematic review/meta-analysis of outcomes for patients with spinal metastases treated with stereotactic radiosurgery (SRS) (either single-fraction (SF-SRS) or multiple-fraction (MF-SRS)) or conventional radiotherapy (RT).

Materials and methods: Thirty-seven studies were identified. Primary outcomes were 1-year local control (LC) and acute/late grade 3-5 toxicities (including vertebral compression fractures (VCF)). Weighted random effects meta-analyses using the DerSimonian and Laird methods and meta-regressions were conducted to characterize and compare effect sizes. Mixed effects regression models were used in dose analyses.

Results: A total of 3237 patients with 4911 lesions were included; 43.8%, 19.7%, and 36.5% of lesions received SF-SRS, MF-SRS, or RT, respectively. SF-SRS resulted in improved 1-year LC (92.9% (95% CI: 86.4-97.4%); p = 0.007) compared to RT (81.0% (95% CI: 69.2-90.5%)) with no difference between MF-SRS (82.1%; p = 0.86) and RT. On subgroup analysis of de novo metastases, superior 1-year LC following SF-SRS (95.5% (95% CI: 87.4-99.6%)) was maintained compared to RT (83.6% (95% CI: 70.4-93.5%); p = 0.007). A 4.7% increase in LC was noted for each 10 Gy₁₀ increase in biologically effective dose (BED₁₀, assuming an alpha/beta = 10) with SRS (p < 0.001). No difference in toxicities were found between SF-SRS (0.4%), MF-SRS (0.2%), or RT (0%). Higher VCF rates were noted following SF-SRS (19.5%) vs. MF-SRS (9.6%; p = 0.039)) with no correlation between dose and VCF rates.

Conclusion: SF-SRS resulted in superior LC with a roughly 5% LC benefit for every 10 Gy₁₀ increase in BED₁₀ with higher VCF rates compared to MF-SRS. If LC is the goal of treatment, then SRS may be a preferred treatment modality. However, these results are hypothesis-generating, and prospective randomized clinical trials are indicated to definitively address the question of whether SRS results in improved LC compared to RT.

Keywords: Local control; Meta-analysis; Radiotherapy; SRS; Spinal metastases; Toxicity.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Brain Neoplasms*
Crocus*
Fractures, Compression*
Humans
Prospective Studies
Radiosurgery* / adverse effects
Retrospective Studies
Spinal Fractures*
Spinal Neoplasms* / radiotherapy
Spinal Neoplasms* / surgery
Treatment Outcome