Spinal Cord Dose Tolerance to Stereotactic Body Radiation Therapy

Spinal cord tolerance data for stereotactic body radiation therapy (SBRT) were extracted from published reports, reviewed, and modelled. For de novo SBRT delivered in 1 to 5 fractions, the following spinal cord point maximum doses (Dmax) are estimated to be associated with a 1% to 5% risk of radiation myelopathy (RM): 12.4 to 14.0 Gy in 1 fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. For reirradiation SBRT delivered in 1 to 5 fractions, reported factors associated with a lower risk of RM include cumulative thecal sac equivalent dose in 2 Gy fractions with an alpha/beta of 2 (EQD22) Dmax ≤70 Gy; SBRT thecal sac EQD22 Dmax ≤25 Gy, thecal sac SBRT EQD22 Dmax to cumulative EQD22 Dmax ratio ≤0.5, and a minimum time interval to reirradiation of ≥5 months. Larger studies containing complete institutional cohorts with dosimetric data of patients treated with spine SBRT, with and without RM, are required to refine RM risk estimates. Spinal cord tolerance data for stereotactic body radiation therapy (SBRT) were extracted from published reports, reviewed, and modelled. For de novo SBRT delivered in 1 to 5 fractions, the following spinal cord point maximum doses (Dmax) are estimated to be associated with a 1% to 5% risk of radiation myelopathy (RM): 12.4 to 14.0 Gy in 1 fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. For reirradiation SBRT delivered in 1 to 5 fractions, reported factors associated with a lower risk of RM include cumulative thecal sac equivalent dose in 2 Gy fractions with an alpha/beta of 2 (EQD22) Dmax ≤70 Gy; SBRT thecal sac EQD22 Dmax ≤25 Gy, thecal sac SBRT EQD22 Dmax to cumulative EQD22 Dmax ratio ≤0.5, and a minimum time interval to reirradiation of ≥5 months. Larger studies containing complete institutional cohorts with dosimetric data of patients treated with spine SBRT, with and without RM, are required to refine RM risk estimates. SummaryA review of published reports of spinal cord tolerance after stereotactic body radiation therapy was performed. This report presents several dose-response models, recommends dose limits for the spinal cord, and outlines standards for future reporting of spinal cord dosimetric and clinical data. A review of published reports of spinal cord tolerance after stereotactic body radiation therapy was performed. This report presents several dose-response models, recommends dose limits for the spinal cord, and outlines standards for future reporting of spinal cord dosimetric and clinical data. Stereotactic body radiation therapy (SBRT) for spinal metastases is emerging as a clinical standard of care for patients with spinal oligometastases,1Chang J.H. Gandhidasan S. Finnigan R. et al.Stereotactic ablative body radiotherapy for the treatment of spinal oligometastases.Clin Oncol (R Coll Radiol). 2017; 29: e119-e125Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar radioresistant histologies,2Kothari G. Foroudi F. Gill S. Corcoran N.M. Siva S. Outcomes of stereotactic radiotherapy for cranial and extracranial metastatic renal cell carcinoma: A systematic review.Acta Oncol. 2015; 54: 148-157Crossref PubMed Scopus (57) Google Scholar or prior spinal radiation therapy, both as a sole modality3Mantel F. Flentje M. Guckenberger M. Stereotactic body radiation therapy in the re-irradiation situation—a review.Radiat Oncol. 2013; 8: 7Crossref PubMed Scopus (57) Google Scholar or in the postoperative setting.4Redmond K.J. Lo S.S. Soltys S.G. et al.Consensus guidelines for postoperative stereotactic body radiation therapy for spinal metastases: Results of an international survey.J Neurosurg Spine. 2017; 26: 299-306Crossref PubMed Scopus (46) Google Scholar The main benefit of this technique is the ability to dose escalate the tumor volume while sparing the adjacent organs at risk (OARs). At the inception of spine SBRT, owing to uncertainties regarding the response of the spinal cord to extreme inhomogeneous and hypofractionated SBRT, there was much variation in clinical practice among early adopters. Some applied traditional conservative point maximum dose (Dmax) limits within the spinal cord, and others assumed small volumes of the spinal cord could tolerate a much greater dose as long as volumetric thresholds were respected. There was also considerable variation with respect to how the spinal cord was delineated and to what structure the spinal cord dose limit was being applied. These variations have persisted, and there is much uncertainty in the field regarding “safe” dose/volume guidelines for spinal SBRT. With over a decade of worldwide experience in spinal SBRT and an initial spate of radiation myelopathy (RM) cases among early adopters, this Hypofractionation Treatment Effects in the Clinic (HyTEC) report aims to summarize the current understanding of the dose, volume, and outcome data for the human spinal cord specific to image guided, hypofractionated (1-5 fractions and a dose per fraction of >6 Gy) SBRT. Data and estimates are provided for patients with and without prior radiation exposure (termed reirradiation and de novo SBRT, respectively). This report provides updated recommendations based on dose, volume, and outcome data published since the American Association of Physicists in Medicine Task Group 101 (TG101) report.5Benedict S.H. Yenice K.M. Followill D. et al.Stereotactic body radiation therapy: The report of AAPM Task Group 101.Med Phys. 2010; 37: 4078-4101Crossref PubMed Scopus (1053) Google Scholar Several other potential spine-based toxicities associated with spine SBRT, such as vertebral compression fracture6Sahgal A. Grosshans D.R. Allen P.K. et al.Vertebral compression fracture after stereotactic body radiotherapy for spinal metastases.Lancet Oncol. 2013; 14: e310-e320Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar and pain flare,7McDonald R. Chow E. Rowbottom L. DeAngelis C. Soliman H. Incidence of pain flare in radiation treatment of bone metastases: A literature review.J Bone Oncol. 2014; 3: 84-89Crossref PubMed Scopus (30) Google Scholar are outside of the scope of this report. The clinical endpoint of interest in this review is RM, a diagnosis of exclusion based on neurologic signs and symptoms consistent with damage to the irradiated spinal cord segment without evidence of a recurrent or progressive tumor affecting the spinal cord.8Wong C.S. Fehlings M.G. Sahgal A. Pathobiology of radiation myelopathy and strategies to mitigate injury.Spinal Cord. 2015; 53: 574-580Crossref PubMed Scopus (37) Google Scholar Clinical manifestations range from minor sensory or motor deficits, to complete paraplegia/quadriplegia and loss of autonomic functioning. With conventionally fractionated radiation therapy, the latent time to the development of RM is approximately 18 months after de novo treatment and 11 months after reirradiation,8Wong C.S. Fehlings M.G. Sahgal A. Pathobiology of radiation myelopathy and strategies to mitigate injury.Spinal Cord. 2015; 53: 574-580Crossref PubMed Scopus (37) Google Scholar with higher total doses and doses per fraction associated with shorter latency times.9Schultheiss T.E. Higgins E.M. El-Mahdi A.M. The latent period in clinical radiation myelopathy.Int J Radiat Oncol Biol Phys. 1984; 10: 1109-1115Abstract Full Text PDF PubMed Scopus (99) Google Scholar With SBRT, the median latent time to the development of RM in the series reviewed in this report (Tables 1 and 2) was 12 months after de novo treatment and 6 months after reirradiation. The shortened latency time to development of RM likely reflects the greater biological effect of the higher, and more extreme, doses per fraction inherent to SBRT.Table 1De novo spine SBRT literature that met the inclusion criteria for this reviewSeriesNo. of patientsDose reporting structureMedian prescribed dose in Gy (range)/number of fractions (range)Median spinal cord Dmax, GyMedian spinal cord Dmax EQD22, GyMedian follow-up, moNo. of cases of RMChang 201245Chang U.K. Cho W.I. Kim M.S. Cho C.K. Lee D.H. Rhee C.H. Local tumor control after retreatment of spinal metastasis using stereotactic body radiotherapy; comparison with initial treatment group.Acta Oncol. 2012; 51: 589-595Crossref PubMed Scopus (53) Google Scholar,∗The results from only the patients who met the inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).131Thecal sacMean EQD22 50.7/NSNSMean 48.68 ± 29.97Mean 23.70Daly 201142Daly M.E. Choi C.Y. Gibbs I.C. et al.Tolerance of the spinal cord to stereotactic radiosurgery: Insights from hemangioblastomas.Int J Radiat Oncol Biol Phys. 2011; 80: 213-220Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar19Cord20 (18-30)/1 (1-3)1 Fx: 22.7 (range, 17.8-30.9);2 Fx 22.0 (range, 21.3-26.6);3 Fx: 21.9 (range, 19.7-25.4)1 Fx: 140.17;2 Fx: 71.5;3 Fx: 50.92†Cumulative EQD22 estimated using summary data presented in paper.33.71Gerszten 201253Gerszten P.C. Chen S. Quader M. Xu Y. Novotny Jr., J. Flickinger J.C. Radiosurgery for benign tumors of the spine using the Synergy S with cone-beam computed tomography image guidance.J Neurosurg. 2012; 117: 197-202Crossref PubMed Google Scholar,∗The results from only the patients who met the inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).26CordMean 16 (12-24)/1 (1-3)Mean 8.7 (range, 4-11.5)Mean 23.27†Cumulative EQD22 estimated using summary data presented in paper.320Sahgal 200754Sahgal A. Chou D. Ames C. et al.Image-guided robotic stereotactic body radiotherapy for benign spinal tumors: The University of California San Francisco preliminary experience.Technol Cancer Res Treat. 2007; 6: 595-604Crossref PubMed Scopus (68) Google Scholar,∗The results from only the patients who met the inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).12Thecal sac21 (10-40)/3 (1-5)20.9 (range, 4.3-23.1)46.85†Cumulative EQD22 estimated using summary data presented in paper.250Sahgal 200955Sahgal A. Ames C. Chou D. et al.Stereotactic body radiotherapy is effective salvage therapy for patients with prior radiation of spinal metastases.Int J Radiat Oncol Biol Phys. 2009; 74: 723-731Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar,∗The results from only the patients who met the inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).14Thecal sac24 (7-40)/3 (1-5)16.8 (range, 10.7-26)28 (range, 15-57)90Sahgal 201333Sahgal A. Weinberg V. Ma L. et al.Probabilities of radiation myelopathy specific to stereotactic body radiation therapy to guide safe practice.Int J Radiat Oncol Biol Phys. 2013; 85: 341-347Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar,∗The results from only the patients who met the inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).,‡The data presented are the controls, not the cases of radiation myelopathy.66Thecal sacNS / (1-5)NS35.69150Katsoulakis 201734Katsoulakis E. Jackson A. Cox B. Lovelock M. Yamada Y. A detailed dosimetric analysis of spinal cord tolerance in high-dose spine radiosurgery.Int J Radiat Oncol Biol Phys. 2017; 99: 598-607Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar228Cord24 (18-24) / 113.85 (range, 9.61-15.21)54.88 (range, 27.89-65.44)152Abbreviations: Dmax = maximum dose; EQD22 = equivalent dose in 2 Gy fractions (α/β = 2 Gy); Fx = fraction; NS = not specified; RM = radiation myelopathy; SBRT = stereotactic body radiation therapy.∗ The results from only the patients who met the inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).† Cumulative EQD22 estimated using summary data presented in paper.‡ The data presented are the controls, not the cases of radiation myelopathy. Open table in a new tab Table 2Reirradiation spine SBRT literature that met the inclusion criteria for this reviewPaperNo. of patientsDose reporting structureMedian prescribed dose (range) / number of fractions (range)Median prescribed dose of prior RT (range) / number of fractions (range)Median spinal cord Dmax, GyMedian spinal cord Dmax EQD22 for SBRT, GyMedian cumulative spinal cord Dmax EQD22 of all RT, GyMedian follow-up, moNo. cases of RMChang 201245Chang U.K. Cho W.I. Kim M.S. Cho C.K. Lee D.H. Rhee C.H. Local tumor control after retreatment of spinal metastasis using stereotactic body radiotherapy; comparison with initial treatment group.Acta Oncol. 2012; 51: 589-595Crossref PubMed Scopus (53) Google Scholar,∗The results from only the patients who met inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).54Thecal sacMean EQD22 51.1 / NSNSNSMean 46.19 ± 35.21Mean 83.37Mean 21.80Gwak 200544Gwak H.S. Yoo H.J. Youn S.M. et al.Hypofractionated stereotactic radiation therapy for skull base and upper cervical chordoma and chondrosarcoma: Preliminary results.Stereotact Funct Neurosurg. 2005; 83: 233-243Crossref PubMed Scopus (43) Google Scholar,∗The results from only the patients who met inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).3Cord33 (21-35) Gy / 350.4 Gy (30-50.4) Gy/ 28 (10-28)24.1 (19.9-32.9)60.45†Cumulative EQD22 estimated using summary data presented in paper.NS241Sahgal 200955Sahgal A. Ames C. Chou D. et al.Stereotactic body radiotherapy is effective salvage therapy for patients with prior radiation of spinal metastases.Int J Radiat Oncol Biol Phys. 2009; 74: 723-731Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar,∗The results from only the patients who met inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).25Thecal sac24 (8-30) Gy / 3 (1-5)36 Gy / 1412.8 (5.4-27)18 (10-49)41.5†Cumulative EQD22 estimated using summary data presented in paper.70Sahgal 201243Sahgal A. Ma L. Weinberg V. et al.Reirradiation human spinal cord tolerance for stereotactic body radiotherapy.Int J Radiat Oncol Biol Phys. 2012; 82: 107-116Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar,∗The results from only the patients who met inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).,‡The data presented are the controls, not the cases of radiation myelopathy.14Thecal sac24 (10-30) Gy / 3 (1-5)EQD22 = 39.8 (29.0-64.5)NS12.5 (1.9-58.7)52.4 (39.1-111.2)120Thibault 201535Thibault I. Campbell M. Tseng C.L. et al.Salvage stereotactic body radiotherapy (SBRT) following in-field failure of initial SBRT for spinal metastases.Int J Radiat Oncol Biol Phys. 2015; 93: 353-360Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar,§The same study was broken into 2 cohorts and reported on different rows.16Cord PRV (+1.5 mm)30 (20-35) Gy / 4 (2-5)SBRT 24 (20-35)/ 2 (1-5)NS21.9 (12.4-25.0)51.36.80Thibault 201535Thibault I. Campbell M. Tseng C.L. et al.Salvage stereotactic body radiotherapy (SBRT) following in-field failure of initial SBRT for spinal metastases.Int J Radiat Oncol Biol Phys. 2015; 93: 353-360Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar,§The same study was broken into 2 cohorts and reported on different rows.24Cord PRV (+1.5 mm)30 (24-35) Gy / 4 (2-5)cEBRT: 22.5 (20-30); SBRT 24 (20-30)/ 2 (2-5)NS21.9 (17.5-26.7)73.96.80Abbreviations: Dmax = maximum dose; cEBRT = conventional external beam radiation therapy; EQD22 = equivalent dose in 2 Gy fractions (α/β = 2 Gy); NS = not specified; PRV = planning organ-at-risk volume; RM = radiation myelopathy; RT = radiation therapy; SBRT = stereotactic body radiation therapy.∗ The results from only the patients who met inclusion criteria are reported in this row (instead of the full cohort of patients from the original study).† Cumulative EQD22 estimated using summary data presented in paper.‡ The data presented are the controls, not the cases of radiation myelopathy.§ The same study was broken into 2 cohorts and reported on different rows. Open table in a new tab Abbreviations: Dmax = maximum dose; EQD22 = equivalent dose in 2 Gy fractions (α/β = 2 Gy); Fx = fraction; NS = not specified; RM = radiation myelopathy; SBRT = stereotactic body radiation therapy. Abbreviations: Dmax = maximum dose; cEBRT = conventional external beam radiation therapy; EQD22 = equivalent dose in 2 Gy fractions (α/β = 2 Gy); NS = not specified; PRV = planning organ-at-risk volume; RM = radiation myelopathy; RT = radiation therapy; SBRT = stereotactic body radiation therapy. In addition to clinical signs and symptoms, the diagnosis is further supported by evidence of spinal cord injury within the irradiated segment on contrast-enhanced magnetic resonance imaging (MRI).8Wong C.S. Fehlings M.G. Sahgal A. Pathobiology of radiation myelopathy and strategies to mitigate injury.Spinal Cord. 2015; 53: 574-580Crossref PubMed Scopus (37) Google Scholar Characteristic MRI findings include low signal on T1-weighted images, high signal on T2-weighted images, and focal contrast enhancement in the irradiated spinal cord segment. Experiments in rodents confirm that the high signal intensity on T2-weighted imaging correlates histopathologically with demyelination, edema, and necrosis, and enhancement postcontrast administration correlates with blood–spinal cord barrier disruption.8Wong C.S. Fehlings M.G. Sahgal A. Pathobiology of radiation myelopathy and strategies to mitigate injury.Spinal Cord. 2015; 53: 574-580Crossref PubMed Scopus (37) Google Scholar The main histologic features of RM are demyelination and necrosis of the spinal cord, typically confined to the white matter, although they are not pathognomonic of radiation injury.8Wong C.S. Fehlings M.G. Sahgal A. Pathobiology of radiation myelopathy and strategies to mitigate injury.Spinal Cord. 2015; 53: 574-580Crossref PubMed Scopus (37) Google Scholar Other changes include varying degrees of vascular damage and glial reaction. Injury of the microvasculature, including disruption of the blood–spinal cord barrier, has been implicated in the pathogenesis of RM; although, vascular changes may be absent or inconspicuous histologically.8Wong C.S. Fehlings M.G. Sahgal A. Pathobiology of radiation myelopathy and strategies to mitigate injury.Spinal Cord. 2015; 53: 574-580Crossref PubMed Scopus (37) Google Scholar Various toxicity grading systems exist. At present, the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.010National Cancer InstituteCommon Terminology Criteria for Adverse Events (CTCAE) Version 4.0.https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdfDate accessed: September 22, 2019Google Scholar and the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring System11Cox J.D. Stetz J. Pajak T.F. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC).Int J Radiat Oncol Biol Phys. 1995; 31: 1341-1346Abstract Full Text PDF PubMed Scopus (3432) Google Scholar are accepted standards. Myelitis is defined in the NCI CTCAE as a disorder characterized by inflammation involving the spinal cord with symptoms that include weakness, paresthesia, sensory loss, marked discomfort, and incontinence.10National Cancer InstituteCommon Terminology Criteria for Adverse Events (CTCAE) Version 4.0.https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdfDate accessed: September 22, 2019Google Scholar Using either scale, low-grade (1 and 2) RM is a challenge to diagnose in this population because spinal metastases requiring treatment are often painful and can mask the subtle signs and symptoms of motor or sensory abnormalities. Therefore, minor sensory and motor dysfunctions are easily attributed to the disease process as opposed to spinal cord radiation toxicity. However, high-grade (3 and 4) RM is clinically significant and is associated with permanent signs and symptoms of sensory dysfunction, motor weakness, and sphincter compromise. If the clinical signs are not attributable to disease progression and abnormal imaging findings are observed within the previously irradiated spinal cord, a diagnosis (of exclusion) of RM may be made. Thus, most of the cases of RM reported in the literature, and considered in this review, were high-grade (≥3) cases based on the NCI CTCAE or the RTOG/EORTC Late Radiation Morbidity Scoring System. Segmenting the spinal cord can be challenging on imaging and requires a stringent technique. A common approach is to fuse axial volumetric T1 and T2 MRI images to the treatment planning computed tomography (CT) and define the MRI–based spinal cord.4Redmond K.J. Lo S.S. Soltys S.G. et al.Consensus guidelines for postoperative stereotactic body radiation therapy for spinal metastases: Results of an international survey.J Neurosurg Spine. 2017; 26: 299-306Crossref PubMed Scopus (46) Google Scholar,5Benedict S.H. Yenice K.M. Followill D. et al.Stereotactic body radiation therapy: The report of AAPM Task Group 101.Med Phys. 2010; 37: 4078-4101Crossref PubMed Scopus (1053) Google Scholar,12Cox B.W. Spratt D.E. Lovelock M. et al.International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery.Int J Radiat Oncol Biol Phys. 2012; 83: e597-e605Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar There are often inherent challenges with image fusion (eg, positional variations between the various scans) that must be recognized because they can be associated with a clinically meaningful level of uncertainty. Another approach is to visualize the spinal cord on a CT myelogram4Redmond K.J. Lo S.S. Soltys S.G. et al.Consensus guidelines for postoperative stereotactic body radiation therapy for spinal metastases: Results of an international survey.J Neurosurg Spine. 2017; 26: 299-306Crossref PubMed Scopus (46) Google Scholar,12Cox B.W. Spratt D.E. Lovelock M. et al.International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery.Int J Radiat Oncol Biol Phys. 2012; 83: e597-e605Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar by applying the myelogram contrast agent immediately before performing the treatment-planning CT, with the patient immobilized in the treatment position. Although a CT myelogram may be regarded as the gold standard by some, it is an invasive procedure and can be associated with complications.13Thariat J. Castelli J. Chanalet S. Marcie S. Mammar H. Bondiau P.Y. CyberKnife stereotactic radiotherapy for spinal tumors: Value of computed tomographic myelography in spinal cord delineation.Neurosurgery. 2009; 64: A60-A66Crossref PubMed Scopus (30) Google Scholar Therefore, MRI– and CT-based approaches have their pros and cons. For both, the apparent edge of the spinal cord can change by adjusting the image viewing parameters (eg, CT window levels).14Seibert C.E. Barnes J.E. Dreisbach J.N. Swanson W.B. Heck R.J. Accurate CT measurement of the spinal cord using metrizamide: Physical factors.AJR Am J Roentgenol. 1981; 136: 777-780Crossref PubMed Scopus (17) Google Scholar Importantly, CT alone (without myelogram contrast) is not considered sufficient to define the spinal cord or even the thecal sac; only the spinal canal can be reliably contoured with CT alone. Because setup errors can alter the spinal cord position, most clinicians use a safety margin around the imaging-defined “true” spinal cord.15Guckenberger M. Sweeney R.A. Flickinger J.C. et al.Clinical practice of image-guided spine radiosurgery—results from an international research consortium.Radiat Oncol. 2011; 6: 172Crossref PubMed Scopus (34) Google Scholar This margin can be applied by segmenting the spinal cord using one of the techniques described, and applying a uniform planning OAR volume (PRV) expansion margin (1.0, 1.5, or 2.0 mm have been used). Alternatively, a surrogate structure for the spinal cord that is larger than the spinal cord itself can be defined, such as the thecal sac or spinal canal. The practice of constraining the entire spinal canal in SBRT treatment planning is generally not advised for several reasons. First, the clinical target volume in spinal SBRT usually extends to the edge of the spinal canal and, in the case of epidural disease, extends into the spinal canal. Defining the spinal canal as the avoidance structure upon which to apply the spinal cord dose limit will compromise coverage of disease (ie, underdose) within the canal and in the adjacent affected bone.12Cox B.W. Spratt D.E. Lovelock M. et al.International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery.Int J Radiat Oncol Biol Phys. 2012; 83: e597-e605Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar,16Chan M.W. Thibault I. Atenafu E.G. et al.Patterns of epidural progression following postoperative spine stereotactic body radiotherapy: Implications for clinical target volume delineation.J Neurosurg Spine. 2016; 24: 652-659Crossref PubMed Scopus (26) Google Scholar In most instances, the setup errors in spinal cord position with a rigorous SBRT technique are smaller than the “safety margin” applied by using the spinal canal as the PRV. The thecal sac has been used by many practitioners as a surrogate for the true cord, with the dose limit applied to the thecal sac and no further PRV margin; that is, the thecal sac essentially represents the spinal cord with an anatomic PRV and is a dosimetric compromise to respect safety. At the level of the thoracic spine, the thecal sac typically represents a 1.5-mm margin beyond the spinal cord. However, at the level of the upper cervical spine, the thecal sac may represent a larger margin (2-3 mm) than the typically applied 1- to 3-mm PRV margin, owing to the natural enlargement of the cervical spinal canal and associated thecal sac.17Ulbrich E.J. Schraner C. Boesch C. et al.Normative MR cervical spinal canal dimensions.Radiology. 2014; 271: 172-182Crossref PubMed Scopus (37) Google Scholar At the level of the cauda equina, the thecal sac is contoured as the avoidance structure and is often equivalent to the canal because individual nerve rootlets are not reliably definable and motion may be an issue. It is important to note that the dose/response of the spinal cord and cauda equina cannot be assumed to be equivalent, and data from the sites generally should not be grouped together. The most consistent and modern method of defining a spinal cord OAR may be contouring the spinal cord using a stringent technique described earlier and applying a PRV expansion margin. PRV margins of 1 mm, 1.5 mm, and 2.0 mm have been applied. However, some clinicians assume the known uncertainties associated with intrafraction patient movement (at a minimum 1 mm and 1°),18Hyde D. Lochray F. Korol R. et al.Spine stereotactic body radiotherapy utilizing cone-beam CT image-guidance with a robotic couch: Intrafraction motion analysis accounting for all six degrees of freedom.Int J Radiat Oncol Biol Phys. 2012; 82: e555-e562Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar spinal cord motion (reported to be submillimeter),19Tseng C.L. Sussman M.S. Atenafu E.G. et al.Magnetic resonance imaging assessment of spinal cord and cauda equina motion in supine patients with spinal metastases planned for spine stereotactic body radiation therapy.Int J Radiat Oncol Biol Phys. 2015; 91: 995-1002Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar image fusion, dose calculation, and image guidance systems to be negligible enough that it is safe to not apply a PRV. In fact, the spinal cord dose/response data listed in the American Association of Physicists in Medicine Task Group 101 report pertain to the spinal cord itself rather than a PRV or another surrogate structure.5Benedict S.H. Yenice K.M. Followill D. et al.Stereotactic body radiation therapy: The report of AAPM Task Group 101.Med Phys. 2010; 37: 4078-4101Crossref PubMed Scopus (1053) Google Scholar However, because the steepest dose gradient with SBRT is almost always adjacent to the spinal cord and even small motions can be dosimetrically significant,20Wang H. Shiu A. Wang C. et al.Dosimetric effect of translational and rotational errors for patients undergoing image-guided stereotactic body radiotherapy for spinal metastases.Int J Radiat Oncol Biol Phys. 2008; 71: 1261-1271Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar,21Guckenberger M. Meyer J. Wilbert J. et al.Precision required for dose-escalated treatment of spinal metastases and implications for image-guided radiation therapy (IGRT).Radiother Oncol. 2007; 84: 56-63Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar many prefer applying the dose limit to the spinal cord PRV structure as an additional means to respect safety. Ideally, institutions should determine the errors associated with their own setup reproducibility, contouring accuracy, and intra- and interfraction motion to determine center-specific appropriate PRV margins.15Guckenberger M. Sweeney R.A. Flickinger J.C. et al.Clinical practice of image-guided spine radiosurgery—results from an international research consortium.Radiat Oncol. 2011; 6: 172Crossref PubMed Scopus (34) Google Scholar,22Chang J.H. Sangha A. Hyde D. et al.Positional accuracy of treating multiple versus sing