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Stereotactic Ablative Radiotherapy for the Management of Spinal MetastasesA Review

Educational Objective
To learn the role of stereotactic ablative radiotherapy for the management of spinal metastases.
1 Credit CME
Key Points

Question  What leads to decisions concerning stereotactic ablative radiotherapy application, patient selection, and personalized high-quality care for spinal metastases?

Findings  In this review of 5655 patients who underwent SABR for spinal metastases in 59 unique studies, optimal patient selection and stereotactic ablative radiotherapy were associated with high rates of local tumor control with moderate rates of adverse effects.

Meaning  This study suggests that spinal stereotactic ablative radiotherapy is an effective treatment option for well-selected patients with spinal metastases; future studies might explore the potential for broader applications of spinal stereotactic ablative radiotherapy and enhanced personalization of care.

Abstract

Importance  Rising cancer incidence combined with improvements in systemic and local therapies extending life expectancy are translating into more patients with spinal metastases. This makes the multidisciplinary management of spinal metastases and development of new therapies increasingly important. Spinal metastases may cause significant pain and reduced quality of life and lead to permanent neurological disability if compression of the spinal cord and/or nerve root occurs. Until recently, treatments for spinal metastases were not optimal and provided temporary local control and pain relief. Spinal stereotactic ablative radiotherapy (SABR) is an effective approach associated with an improved therapeutic ratio, with evolving clinical application.

Objective  To review the literature of spinal SABR for spinal metastases, discuss a multidisciplinary approach to appropriate patient selection and technical considerations, and summarize current efforts to combine spinal SABR with systemic therapies.

Evidence Review  The MEDLINE database was searched to identify articles reporting on spinal SABR to September 30, 2018. Articles including clinical trials, prospective and retrospective studies, systematic reviews, and consensus recommendations were selected for relevance to multidisciplinary management of spinal metastases.

Results  Fifty-nine unique publications with 5655 patients who underwent SABR for spinal metastases were included. Four comprehensive frameworks for patient selection were discussed. Spinal SABR was associated with 1-year local control rates of approximately 80% to 90% in the de novo setting, greater than 80% in the postoperative setting, and greater than 65% in the reirradiation setting. The most commonly discussed adverse effect was development of a vertebral compression fracture with variable rates, most commonly reported as approximately 10% to 15%. High-level data on the combination of SABR with modern therapies are still lacking. At present, 19 clinical trials are ongoing, mainly focusing on combined modality therapies, radiotherapy prescription dose, and oligometastic disease.

Conclusions and Relevance  These findings suggest that spinal SABR may be an effective treatment option for well-selected patients with spinal metastases, achieving high rates of local tumor control with moderate rates of adverse effects. Optimal management should include review by a multidisciplinary care team.

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Article Information

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.

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Stereotactic radiosurgery in treating patients with spinal metastases. Clinicaltrials.gov identifier: NCT00853528. https://www.clinicaltrials.gov/ct2/show/NCT00853528. Updated July 19, 2017. Accessed November 1, 2018.
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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.
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Stereotactic body radiotherapy for spine tumors. Clinicaltrials.gov identifier: NCT01347307. https://clinicaltrials.gov/ct2/show/NCT01347307. Updated September 25, 2017. Accessed November 1, 2018.
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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.
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Evaluation of single session stereotactic body radiotherapy. Clinicaltrials.gov identifier: NCT00492817. https://clinicaltrials.gov/ct2/show/NCT00492817. Updated May 9, 2019. Accessed November 1, 2018.
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Conformal high dose intensity modulated radiation therapy for disease to thoracic and lumbar spine. Clinicaltrials.gov identifier: NCT01654068. https://clinicaltrials.gov/ct2/show/NCT01654068. Updated April 19, 2019. Accessed November 1, 2018.
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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.
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Radiotherapy for solid tumor spine metastases. Clinicaltrials.gov identifier: NCT01752036. https://clinicaltrials.gov/ct2/show/NCT01752036. Updated November 7, 2018. Accessed November 1, 2018.
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Randomized study comparing two dosing schedules for hypofractionated image-guided radiation therapy. Clinicaltrials.gov identifier: NCT01223248. https://clinicaltrials.gov/ct2/show/NCT01223248. Updated June 5, 2019. Accessed November 1, 2018.
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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.
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Study of image-guided SBRT for vertebral metastases. Clinicaltrials.gov identifier: NCT02616887. https://www.clinicaltrials.gov/ct2/show/NCT02616887. Updated October 24, 2018. Accessed November 1, 2018.
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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.
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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.
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Evaluating stereotactic body radiation therapy for oligometastatic disease of the bone. Clinicaltrials.gov identifier: NCT02880319. https://clinicaltrials.gov/ct2/show/NCT02880319. Updated January 25, 2019. Accessed November 1, 2018.
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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.
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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.
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