Accepted for Publication: September 9, 2019.
Published Online: January 2, 2020. doi:10.1001/jamaoncol.2019.5351
Correction: This article was corrected on June 18, 2020, to fix a typographical error in the third paragraph of the Results, where an instance of “local failure” was incorrectly published as “local control.”
Corresponding Author: Fabio Y. Moraes, MD, Division of Radiation Oncology, Department of Oncology, Kingston General Hospital, Queen’s University, 25 King St W, Kingston, ON K7L 5P9, Canada (fabio.ynoedemoraes@kingstonhsc.ca).
Author Contributions: Dr Moraes had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Glicksman, Tjong, Neves-Junior, Berlin, Slotman, Shultz, Maldaun, Szerlip, Yamada, Vera-Badillo, Marta, Moraes.
Acquisition, analysis, or interpretation of data: Glicksman, Tjong, Spratt, K. L. M. Chua, Mansouri, M. L. K. Chua, Winter, Dahele, Bilsky, Maldaun, Lo, Marta, Moraes.
Drafting of the manuscript: Glicksman, Tjong, K. L. M. Chua, Mansouri, Winter, Maldaun, Yamada, Marta, Moraes.
Critical revision of the manuscript for important intellectual content: Glicksman, Tjong, Neves-Junior, Spratt, K. L. M. Chua, Mansouri, M. Chua, Berlin, Winter, Dahele, Slotman, Bilsky, Shultz, Maldaun, Szerlip, Lo, Vera-Badillo, Marta, Moraes.
Statistical analysis: Glicksman, K. L. M. Chua, Maldaun, Moraes.
Administrative, technical, or material support: Glicksman, Neves-Junior, K. L. M. Chua, M. L. K. Chua, Winter, Bilsky, Marta, Moraes.
Supervision: Spratt, Berlin, Slotman, Shultz, Maldaun, Lo, Yamada, Vera-Badillo, Moraes.
Conflict of Interest Disclosures: Dr Spratt reported receiving personal fees from Blue Earth and AstraZeneca outside of the submitted work. Dr K. L. M. Chua reported receiving personal fees from AstraZeneca and Varian Medical Systems and travel support from Brainlab. Dr M. L. K. Chua reported receiving personal fees from MSD, Illumina, Astellas Pharma, Inc, and Janssen Pharmaceutica, grants and personal fees from Ferring Pharmaceuticals, personal fees and nonfinancial support from Varian Medical Systems, grants from Sanofi Canada, and nonfinancial support from AstraZeneca, GenomeDx, BioScience, MedLever, and PVMed, Inc, outside the submitted work. Dr Dahele reported receiving research grants from Varian Medical Systems. Dr Lo reported being a member of the Elekta ICON Gamma Knife expert group. No other disclosures were reported.
Funding/Support: This study was supported by Clinician Scientist Award INV/0027/2018 from the National Medical Research Council and the Duke University-NUS Oncology Academic Clinical Programme Proton Research Fund (Dr M. L. K. Chua).
Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
1.Allemani
C , Matsuda
T , Di Carlo
V ,
et al; CONCORD Working Group. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries.
Lancet. 2018;391(10125):1023-1075. doi:
10.1016/S0140-6736(17)33326-3
PubMedGoogle ScholarCrossref 4.Palma
DA , Olson
R , Harrow
S ,
et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial.
Lancet. 2019;393(10185):2051-2058. doi:
10.1016/S0140-6736(18)32487-5
PubMedGoogle ScholarCrossref 6.Howell
DD , James
JL , Hartsell
WF ,
et al. Single-fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases-equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97-14.
Cancer. 2013;119(4):888-896. doi:
10.1002/cncr.27616
PubMedGoogle ScholarCrossref 8.Bone Pain Trial Working Party. 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up.
Radiother Oncol. 1999;52(2):111-121. doi:
10.1016/S0167-8140(99)00097-3
PubMedGoogle ScholarCrossref 9.Rades
D , Lange
M , Veninga
T ,
et al. Final results of a prospective study comparing the local control of short-course and long-course radiotherapy for metastatic spinal cord compression.
Int J Radiat Oncol Biol Phys. 2011;79(2):524-530. doi:
10.1016/j.ijrobp.2009.10.073
PubMedGoogle ScholarCrossref 12.Seung
SK , Larson
DA , Galvin
JM ,
et al. American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) practice guideline for the performance of stereotactic radiosurgery (SRS).
Am J Clin Oncol. 2013;36(3):310-315. doi:
10.1097/COC.0b013e31826e053d
PubMedGoogle ScholarCrossref 13.Sahgal
A , Roberge
D , Schellenberg
D ,
et al; The Canadian Association of Radiation Oncology-Stereotactic Body Radiotherapy Task Force. Canadian Association of Radiation Oncology scope of practice guidelines for lung, liver and spine stereotactic body radiotherapy.
Clin Oncol (R Coll Radiol). 2012;24(9):629-639. doi:
10.1016/j.clon.2012.04.006PubMedGoogle ScholarCrossref 14.Hall
WA , Stapleford
LJ , Hadjipanayis
CG , Curran
WJ , Crocker
I , Shu
HK . Stereotactic body radiosurgery for spinal metastatic disease: an evidence-based review.
Int J Surg Oncol. 2011;2011:979214. doi:
10.1155/2011/979214
PubMedGoogle Scholar 15.Tseng
CL , Soliman
H , Myrehaug
S ,
et al. Imaging-based outcomes for 24 Gy in 2 daily fractions for patients with de novo spinal metastases treated with spine stereotactic body radiation therapy (SBRT).
Int J Radiat Oncol Biol Phys. 2018;102(3):499-507. doi:
10.1016/j.ijrobp.2018.06.047
PubMedGoogle ScholarCrossref 18.Sprave
T , Verma
V , Förster
R ,
et al. Randomized phase II trial evaluating pain response in patients with spinal metastases following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy.
Radiother Oncol. 2018;128(2):274-282. doi:
10.1016/j.radonc.2018.04.030
PubMedGoogle ScholarCrossref 21.Jawad
MS , Fahim
DK , Gerszten
PC ,
et al; Elekta Spine Radiosurgery Research Consortium. Vertebral compression fractures after stereotactic body radiation therapy: a large, multi-institutional, multinational evaluation.
J Neurosurg Spine. 2016;24(6):928-936. doi:
10.3171/2015.10.SPINE141261
PubMedGoogle ScholarCrossref 24.Yamada
Y , Katsoulakis
E , Laufer
I ,
et al. The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery.
Neurosurg Focus. 2017;42(1):E6. doi:
10.3171/2016.9.FOCUS16369
PubMedGoogle Scholar 25.Virk
MS , Han
JE , Reiner
AS ,
et al. Frequency of symptomatic vertebral body compression fractures requiring intervention following single-fraction stereotactic radiosurgery for spinal metastases.
Neurosurg Focus. 2017;42(1):E8. doi:
10.3171/2016.10.FOCUS16359
PubMedGoogle Scholar 33.Tao
R , Bishop
AJ , Brownlee
Z ,
et al. Stereotactic body radiation therapy for spinal metastases in the postoperative setting: a secondary analysis of mature phase 1-2 trials.
Int J Radiat Oncol Biol Phys. 2016;95(5):1405-1413. doi:
10.1016/j.ijrobp.2016.03.022
PubMedGoogle ScholarCrossref 34.Barzilai
O , Laufer
I , Robin
A , Xu
R , Yamada
Y , Bilsky
MH . Hybrid therapy for metastatic epidural spinal cord compression: technique for separation surgery and spine radiosurgery.
Oper Neurosurg (Hagerstown). 2019;16(3):310-318. doi:
10.1093/ons/opy137
PubMedGoogle ScholarCrossref 37.Barzilai
O , DiStefano
N , Lis
E ,
et al. Safety and utility of kyphoplasty prior to spine stereotactic radiosurgery for metastatic tumors: a clinical and dosimetric analysis.
J Neurosurg Spine. 2018;28(1):72-78. doi:
10.3171/2017.5.SPINE1746
PubMedGoogle ScholarCrossref 40.Lo
SS , Ryu
S , Chang
EL ,
et al; Expert Panel on Radiation Oncology-Bone Metastases. ACR Appropriateness Criteria® metastatic epidural spinal cord compression and recurrent spinal metastasis.
J Palliat Med. 2015;18(7):573-584. doi:
10.1089/jpm.2015.28999.sml
PubMedGoogle ScholarCrossref 41.Huisman
M , van den Bosch
MA , Wijlemans
JW , van Vulpen
M , van der Linden
YM , Verkooijen
HM . Effectiveness of reirradiation for painful bone metastases: a systematic review and meta-analysis.
Int J Radiat Oncol Biol Phys. 2012;84(1):8-14. doi:
10.1016/j.ijrobp.2011.10.080
PubMedGoogle ScholarCrossref 45.Chiang
A , Zeng
L , Zhang
L ,
et al. Pain flare is a common adverse event in steroid-naïve patients after spine stereotactic body radiation therapy: a prospective clinical trial.
Int J Radiat Oncol Biol Phys. 2013;86(4):638-642. doi:
10.1016/j.ijrobp.2013.03.022
PubMedGoogle ScholarCrossref 47.Khan
L , Chiang
A , Zhang
L ,
et al. Prophylactic dexamethasone effectively reduces the incidence of pain flare following spine stereotactic body radiotherapy (SBRT): a prospective observational study.
Support Care Cancer. 2015;23(10):2937-2943. doi:
10.1007/s00520-015-2659-zPubMedGoogle ScholarCrossref 48.Faruqi
S , Tseng
CL , Whyne
C ,
et al. Vertebral compression fracture after spine stereotactic body radiation therapy: a review of the pathophysiology and risk factors.
Neurosurgery. 2018;83(3):314-322. doi:
10.1093/neuros/nyx493
PubMedGoogle ScholarCrossref 49.Sahgal
A , Atenafu
EG , Chao
S ,
et al. Vertebral compression fracture after spine stereotactic body radiotherapy: a multi-institutional analysis with a focus on radiation dose and the spinal instability neoplastic score.
J Clin Oncol. 2013;31(27):3426-3431. doi:
10.1200/JCO.2013.50.1411
PubMedGoogle ScholarCrossref 51.Fisher
CG , Schouten
R , Versteeg
AL ,
et al. Reliability of the Spinal Instability Neoplastic Score (SINS) among radiation oncologists: an assessment of instability secondary to spinal metastases.
Radiat Oncol. 2014;9:69. doi:
10.1186/1748-717X-9-69
PubMedGoogle ScholarCrossref 53.Barney
BM , Markovic
SN , Laack
NN ,
et al. Increased bowel toxicity in patients treated with a vascular endothelial growth factor inhibitor (VEGFI) after stereotactic body radiation therapy (SBRT).
Int J Radiat Oncol Biol Phys. 2013;87(1):73-80. doi:
10.1016/j.ijrobp.2013.05.012
PubMedGoogle ScholarCrossref 54.Anker
CJ , Grossmann
KF , Atkins
MB , Suneja
G , Tarhini
AA , Kirkwood
JM . Avoiding severe toxicity from combined
BRAF inhibitor and radiation treatment: consensus guidelines from the Eastern Cooperative Oncology Group (ECOG).
Int J Radiat Oncol Biol Phys. 2016;95(2):632-646. doi:
10.1016/j.ijrobp.2016.01.038
PubMedGoogle ScholarCrossref 56.Chaft
JE , Oxnard
GR , Sima
CS , Kris
MG , Miller
VA , Riely
GJ . Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design.
Clin Cancer Res. 2011;17(19):6298-6303. doi:
10.1158/1078-0432.CCR-11-1468PubMedGoogle ScholarCrossref 57.Thibault
I , Chang
EL , Sheehan
J ,
et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the Spine Response Assessment in Neuro-oncology (SPINO) group.
Lancet Oncol. 2015;16(16):e595-e603. doi:
10.1016/S1470-2045(15)00166-7
PubMedGoogle ScholarCrossref 61.Chow
E , Hoskin
P , Mitera
G ,
et al; International Bone Metastases Consensus Working Party. Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases.
Int J Radiat Oncol Biol Phys. 2012;82(5):1730-1737. doi:
10.1016/j.ijrobp.2011.02.008
PubMedGoogle ScholarCrossref 66.Single-fraction IMRT versus external beam radiotherapy for patients with spine bone metastases (SMART). Clinicaltrials.gov identifier: NCT02358720.
https://clinicaltrials.gov/ct2/show/NCT02358720. Updated February 9, 2015. Accessed November 1, 2018.
71.Image-guided radiosurgery or stereotactic body radiation therapy in treating patients with localized spine metastasis. Clinicaltrials.gov identifier: NCT00922974.
https://clinicaltrials.gov/ct2/show/NCT00922974. Updated June 19, 2019. Accessed November 1, 2018.
73.A prospective study using implanted fiducial markers to assess treatment accuracy and esophageal toxicity in spinal stereotactic body radiation therapy. Clinicaltrials.gov identifier: NCT01624220.
https://clinicaltrials.gov/ct2/show/NCT01624220. Updated May 10, 2019. Accessed November 1, 2018.
76.Phase I study of feasibility of single session spine stereotactic radiosurgery (SSRS) in the primary management in patients with inoperable, previously unirradiated metastatic epidural spinal cord compression (MESCC). Clinicaltrials.gov identifier: NCT01254903.
https://clinicaltrials.gov/ct2/show/NCT01254903. Updated May 9, 2019. Accessed November 1, 2018.
79.A study to quantify tumour perfusion for spine metastasis treated with stereotactic body radiotherapy (SBRT). Clinicaltrials.gov identifier: NCT03072979.
https://clinicaltrials.gov/ct2/show/NCT03072979. Updated March 8, 2017. Accessed November 1, 2018.
81.Stereotactic body radiation therapy and vertebroplasty in treating patients with localized spinal metastasis. Clinicaltrials.gov identifier: NCT00855803.
https://clinicaltrials.gov/ct2/show/NCT00855803. Updated January 7, 2019. Accessed November 1, 2018.
82.Study comparing stereotactic body radiotherapy vs conventional palliative radiotherapy (CRT) for spinal metastases. Clinicaltrials.gov identifier: NCT02512965.
https://clinicaltrials.gov/ct2/show/NCT02512965. Updated September 30, 2019. Accessed November 1, 2018.
87.Conventional care versus radioablation (stereotactic body radiotherapy) for extracranial oligometastases (CORE). Clinicaltrials.gov identifier: NCT02759783.
https://clinicaltrials.gov/ct2/show/NCT02759783. Updated August 21, 2019. Accessed November 1, 2018.
88.Standard of care therapy with or without stereotactic radiosurgery and/or surgery in treating patients with limited metastatic breast cancer. Clinicaltrials.gov identifier: NCT02364557.
https://clinicaltrials.gov/ct2/show/NCT02364557. Updated November 6, 2019. Accessed November 1, 2018.
89.Maintenance chemotherapy with or without local consolidative therapy in treating patients with stage IV non–small cell lung cancer. Clinicaltrials.gov identifier: NCT03137771.
https://clinicaltrials.gov/ct2/show/NCT03137771. Updated September 5, 2019. Accessed November 1, 2018.
90.Marciscano
AE , Haimovitz-Friedman
A , Lee
P ,
et al. Immunomodulatory effects of stereotactic body radiation therapy: preclinical insights and clinical opportunities [published online March 2, 2019].
Int J Radiat Oncol Biol Phys. doi:
10.1016/j.ijrobp.2019.02.046PubMedGoogle Scholar 93.Tubin
S , Popper
HH , Brcic
L . Novel stereotactic body radiation therapy (SBRT)–based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects.
Radiat Oncol. 2019;14(1):21. doi:
10.1186/s13014-019-1227-y
PubMedGoogle ScholarCrossref 95.McGee
HM , Daly
ME , Azghadi
S ,
et al. Stereotactic ablative radiation therapy induces systemic differences in peripheral blood immunophenotype dependent on irradiated site.
Int J Radiat Oncol Biol Phys. 2018;101(5):1259-1270. doi:
10.1016/j.ijrobp.2018.04.038
PubMedGoogle ScholarCrossref