Stereotactic Body Radiotherapy for Spinal Metastases Practice Guidelines, Outcomes, and Risks Siavash Jabbari, MD,* Peter C. Gerszten, MD,† Mark Ruschin, PhD,‡ David A. Larson, MD, PhD,§ Simon S. Lo, MB, ChB, FACR,∥ and Arjun Sahgal, MD, FRCPC‡ Abstract: Spine metastases can be a debilitating and difficult therapeutic challenge for a significant number of cancer patients. Surgical manage- ment of spine metastases is often limited because of the complexity, risks, and recovery delays associated with open invasive surgical procedures. Conventional palliative external beam radiation therapy is the most com- mon treatment modality. However, it is associated with limited palliative ef- ficacy and local tumor control, including in the postoperative setting. In the era of improving systemic disease control, spine stereotactic body radio- therapy is fast emerging as the therapeutic modality of choice for selected de novo, postoperative, and salvage reirradiation spine metastases patients. Considerable expertise, multidisciplinary collaboration, and rigid adher- ence to quality metrics are required for the safe application of this highly conformal ablative therapy. This review highlights the current state of the evidence, understanding of the late effects, and technological requirements for spine stereotactic body radiotherapy specific to spinal metastases. Key Words: Salvage, spinal metastases, stereotactic body radiotherapy, stereotactic radiosurgery (Cancer J 2016;22: 280–289) INTRODUCTION AND RATIONALE FOR SPINE STEREOTACTIC BODY RADIOTHERAPY Affecting more than 20,000 cancer patients each year, meta- static spine disease is a common and often devastating sequela of malignancy. Palliative conventional external beam radiation ther- apy (cEBRT) has classically proven to be minimally effective with respect to durable palliation of metastatic spine pain and local tu- mors control. 1 The major limitation of cEBRT is the relatively low dose tolerance of critical adjacent organs at risk (OARs), such as the spinal cord and the gastrointestinal tract. Therefore, the choice of prescribed dose has been based on tolerance to the OAR as op- posed to the desired dose to the tumor volume. As a result, dose escalation of spine tumors within the “ablative” range has histori- cally not been considered safe or practical. Randomized prospective trials of cEBRT for bone metas- tases, which typically include a significant proportion of spinal metastases, have documented partial pain relief in most patients after doses ranging from a single 8-Gy fraction to 30 Gy in 10 fractions. 2–4 A challenge in interpreting these data has been the variability in the pain-reporting tools and the definition of re- sponse. 5 When more robust reporting instruments such as the Brief Pain Inventory (BPI) and International Consensus Palliative Radiotherapy End Point Definitions are utilized, the complete pain response of bone metastases cohorts has ranged from 0% to 14% following cEBRT. 2,4 These data suggest a potential for thera- peutic improvement with stereotactic body radiotherapy (SBRT) if in fact a dose-response relationship can be demonstrated. While the trials addressing the efficacy of cEBRT in bone and spinal metastases were designed with a primary endpoint of pain, few attempts were made to determine local control. In fact, very little literature addresses imaging-based local control rates following cEBRT. One of the largest series to date assessing spinal metastases with various imaging modalities was reported by Mizumoto et al. 1 This series reviewed more than 600 patients treated with either short-course or long-course cEBRT for spine metastases. With a median survival of 6.2 months, multivariate analysis revealed factors such as non-mass tumor type, breast cancer histology, and no prior chemotherapy as predictors of local spine control. In particular, while a 1-year local control rate of 86.3% was documented for non–mass-type spine lesions, only 45.7% of mass-type lesions were controlled at 1 year. From these data, we can conclude that those metastases with significant tumor bulk are poorly controlled with cEBRT. If in fact a dose-response relationship is inherent to spine metastases, as in brain metasta- ses, then tumor dose intensification with SBRT would be a rea- sonable strategy to maximize local control specific to mass-type spinal metastases. The reirradiation of nonresponding spine metastasis with cEBRT has predictably been even more limited in efficacy. The second course of cEBRT typically delivers an equal or lower bio- logically effective dose than that of the first course of treatment, in order to respect OAR tolerance. However, a metastatic lesion biologically resistant to a first radiation course will be unlikely to respond to a second lower-dose treatment. Until recently, level 1 evidence had been lacking with respect to the clinical efficacy of reirradiation for bone and spinal metastases. Chow et al. 6 random- ized 425 patients with previously radiated painful bone metastasis (spine and other sites) to 8 Gy of repeat irradiation in a single frac- tion versus 20 Gy in multiple fractions. Complete pain response rates of only 7% to 8% and partial pain response rates of only 19% to 25% were reported in the intention-to-treat analysis. These data confirm that reirradiation with cEBRTyields limited efficacy. With respect to imaging-based local control, there are essentially no data documenting the efficacy of reirradiation cEBRT. Spine SBRT may thus represent a significant opportunity for improving pain and local control in the retreatment setting. Postoperative cEBRT has been the historical standard of care after spine surgery for metastatic disease, typically treating with 30 Gy in 10 fractions. 7 Again, scant data are available specific to imaging-based local control rates or even pain control rates in this population. Even in the few prospective studies that have been published in this context, imaging surveillance has not been From the *Department of Radiation Oncology, The Laurel Amtower Cancer Institute and Neuro-oncology Center, Sharp Healthcare, San Diego, CA; †Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA; ‡Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; §Department of Radiation Oncology, University of California San Francisco, San Francisco, CA; and ∥Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH. A.S. has received honoraria for past educational seminars from Medtronic and Elekta AB and research grants from Elekta AB. S.S.L. is a member of a research group supported by Elekta AB and honorarium from Varian Medical Systems and Accuray. The other authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Reprints: Arjun Sahgal, MD, FRCPC, Department of Radiation Oncology, University of Toronto Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, Ontario, Canada M4N 3M5. E-mail: arjun.sahgal@sunnybrook.ca. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1528-9117 REVIEW ARTICLE 280 www.journalppo.com The Cancer Journal • Volume 22, Number 4, July/August 2016 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.