MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE): Simultaneous quantification of permeability and leakage-insensitive perfusion by dynamic T 1 / T 2 * mapping.

PURPOSE: To develop an MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE) technique for simultaneous quantification of permeability and leakage-insensitive perfusion with a single-dose contrast injection. METHODS: MT-DICE builds on a saturation-recovery prepared multi-echo fast low-angle shot sequence. The k-space is randomly sampled for 7.6 min, with single-dose contrast agent injected 1.5 min into the scan. MR multitasking is used to model the data into six dimensions, including three spatial dimensions for whole-brain coverage, a saturation-recovery time dimension, and a TE dimension for dynamic T 1 $$ {\mathrm{T}}_1 $$ and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ quantification, respectively, and a contrast dynamics dimension for capturing contrast kinetics. The derived pixel-wise T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ time series are converted into contrast concentration-time curves for calculation of kinetic metrics. The technique was assessed for its agreement with reference methods in T 1 $$ {\mathrm{T}}_1 $$ and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ measurements in eight healthy subjects and, in three of them, inter-session repeatability of permeability and leakage-insensitive perfusion parameters. Its feasibility was also demonstrated in four patients with brain tumors. RESULTS: MT-DICE T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ values of normal gray matter and white matter were in excellent agreement with reference values (intraclass correlation coefficients = 0.860/0.962 for gray matter and 0.925/0.975 for white matter ). Both permeability and perfusion parameters demonstrated good to excellent intersession agreement with the lowest intraclass correlation coefficients at 0.694. Contrast kinetic parameters in all healthy subjects and patients were within the literature range. CONCLUSION: Based on dynamic T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ mapping, MT-DICE allows for simultaneous quantification of permeability and leakage-insensitive perfusion metrics with a single-dose contrast injection.

Radiation Necrosis from Stereotactic Radiosurgery-How Do We Mitigate?

OPINION STATEMENT: Intracranial stereotactic radiosurgery (SRS) is an effective and convenient treatment for many brain conditions. Data regarding safety come mostly from retrospective single institutional studies and a small number of prospective studies. Variations in target delineation, treatment delivery, imaging follow-up protocols and dose prescription limit the interpretation of this data. There has been much clinical focus on radiation necrosis (RN) in particular, as it is being increasingly recognized on follow-up imaging. Symptomatic RN may be treated with medical therapy (such as corticosteroids and bevacizumab) with surgical resection being reserved for refractory patients. Nevertheless, RN remains a challenging condition to manage, and therefore upfront patient selection for SRS remains critical to provide complication-free control. Mitigation strategies need to be considered in situations where the baseline risk of RN is expected to be high-such as large target volume or re-irradiation. These may involve reduction in the prescribed dose or hypofractionated stereotactic radiation therapy (HSRT). Recently published guidelines and international meta-analysis report the benefit of HSRT in larger lesions, without compromising control rates. However, careful attention to planning parameters and SRS techniques still need to be adhered, even with HSRT. In cases where the risk is deemed to be high despite mitigation, a combination approach of surgery with or without post-operative radiation should be considered.

Stereotactic radiosurgery for clinoid meningiomas: a multi-institutional study.

PURPOSE: Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas. METHODS: From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas. RESULTS: Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm3, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR = 2.938, p = 0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy. CONCLUSIONS: SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.

Safety-net versus private hospital setting for brain metastasis patients treated with radiosurgery alone: Disparities in follow-up care and outcomes.

BACKGROUND: Stereotactic radiosurgery (SRS) alone is an increasingly accepted treatment for brain metastases, but it requires adherence to frequently scheduled follow-up neuroimaging because of the risk of distant brain metastasis. The effect of disparities in access to follow-up care on outcomes after SRS alone is unknown. METHODS: This retrospective study included 153 brain metastasis patients treated consecutively with SRS alone from 2010 through 2016 at an academic medical center and a safety-net hospital (SNH) located in Los Angeles, California. Outcomes included neurologic symptoms, hospitalization, steroid use and dependency, salvage SRS, salvage whole-brain radiotherapy, salvage neurosurgery, and overall survival. RESULTS: Ninety-three of the 153 patients were private hospital (PH) patients, and 60 were SNH patients. The median follow-up time was 7.7 months. SNH patients received fewer follow-up neuroimaging studies (1.5 vs 3; P = .008). In a multivariate analysis, the SNH setting was a significant risk factor for salvage neurosurgery (hazard ratio [HR], 13.65; P < .001), neurologic symptoms (HR, 3.74; P = .002), and hospitalization due to brain metastases (HR, 6.25; P < .001). More clinical visits were protective against hospitalizations due to brain metastases (HR, 0.75; P = .002), whereas more neuroimaging studies were protective against death (HR, 0.65; P < .001). CONCLUSIONS: SNH patients with brain metastases treated with SRS alone had fewer follow-up neuroimaging studies and were at higher risk for neurologic symptoms, hospitalization for brain metastases, and salvage neurosurgery in comparison with PH patients. Clinicians should consider the practice setting and patient access to follow-up care when they are deciding on the optimal strategy for the treatment of brain metastases. Cancer 2018;124:167-75. © 2017 American Cancer Society.

Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity.

INTRODUCTION: There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases. METHODS: We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan-Meier method. OS was analyzed with Cox regression. RESULTS: Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab. CONCLUSIONS: Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.

Submillimeter alignment of more than three contiguous vertebrae in spinal SRS/SBRT with 6-degree couch.

The purpose of this study is to identify regions of spinal column in which more than three contiguous vertebrae can be reliably and quickly aligned within 1 mm using a 6-degree (6D) couch and full body immobilization device. We analyzed 45 cases treated over a 3-month period. Each case was aligned using ExacTrac x-ray positioning system with integrated 6D couch to be within 1° and 1 mm in all six dimensions. Cone-Beam computed tomography (CBCT) with at least 17.5 cm field of view (FOV) in the superior-inferior direction was taken immediately after ExacTrac positioning. It was used to examine the residual error of five to nine contiguous vertebrae visible in the FOV. The residual error of each vertebra was determined by expanding/contracting the vertebrae contour with a margin in millimeter integrals on the planning CT such that the new contours would enclose the corresponding vertebrae contour on CBCT. Submillimeter initial setup accuracy was consistently achieved in 98% (40/41) cases for a span of five or more vertebrae starting from T2 vertebra and extending caudally to S5. The curvature of spinal column along the cervical region and cervicothoracic junction was not easily reproducible between treatment and simulation. Fifty-seven percent (8/14) of cases in this region had residual setup error of more than 1 mm in nearby vertebrae after alignment using 6D couch with image guidance. In conclusion, 6D couch integrated with image guidance is convenient and accurately corrects small rotational shifts. Consequently, more than three contiguous vertebrae can be aligned within 1 mm with immobilization that reliably reproduces the curvature of the thoracic and lumbar spinal column. Ability of accurate setup is becoming less a concern in limiting the use of stereotactic radiosurgery or stereotactic body radiation therapy to treat multilevel spinal target.

A quantitative analysis of craniopharyngioma cyst expansion during and after radiation therapy and surgical implications.

OBJECTIVE When complete resection of craniopharyngioma is not achievable or the sequelae are prohibitive, limited surgery and radiation therapy have demonstrated excellent local disease control while minimizing treatment-related sequelae. When residual tissue exists, there is a propensity for further cyst development and expansion during and after radiation therapy. This can result in obstructive hydrocephalus, visual changes, and/or clinical decline. The authors present a quantitative analysis of cyst expansion during and after radiotherapy and examine how it affected subsequent management. METHODS The authors performed an institutional review board-approved retrospective study of patients with histologically confirmed craniopharyngioma treated between 2000 and 2015 with surgery and intensity-modulated radiation therapy (IMRT) at a single institution. Volumetric measurements of cyst contours were generated by radiation oncology treatment planning software postoperatively, during IMRT, and up to 12 months after IMRT. Patient, tumor, and treatment-related variables were collected until the last known follow-up and were analyzed. RESULTS Twenty-seven patients underwent surgery and IMRT. The median total radiation dose was 54 Gy. Of the 27 patients, 11 patients (40.7%) demonstrated cyst expansions within 1 year of IMRT. Of note, all tumors with cyst expansion were radiographically Puget Grade 2. Maximal cyst expansion peaked at 4.27 months following radiation therapy, with a median volume growth of 4.1 cm3 (mean 9.61 cm3) above the postoperative cyst volume. Eight patients experienced spontaneous cyst regression without therapeutic intervention. Three patients experienced MRI-confirmed cyst enlargement during IMRT, all of whom required adaptive planning to ensure adequate coverage of the entire tumor volume. Two of these 3 patients required ventriculoperitoneal shunt placement and additional intervention. One underwent additional resection, and the other had placement of an intracystic catheter for aspiration and delivery of intracystic interferon within 12 months of completing IMRT. All 3 patients now have stable disease. CONCLUSIONS Craniopharyngioma cyst expansion occurred in approximately 40% of the patients during or after radiotherapy. In the majority of patients, cyst expansion was a self-limiting process and did not confer a worse outcome. During radiotherapy, cyst expansion may be apparent on image-guided radiation therapy. Adaptive IMRT planning may be required to ensure that the intended IMRT dose covers the entire tumor and cyst volume. The sequelae of cyst expansion include progressive hydrocephalus, which may be treated with a shunt. For patients with solitary cyst expansion, cyst aspiration and/or intracystic interferon may result in disease control.

Treatment of high numbers of brain metastases with Gamma Knife radiosurgery: a review.

Effectiveness of stereotactic radiosurgery (SRS) has been shown in patients with one to four brain metastases. Work has been done to evaluate the role of SRS alone treatment without whole-brain radiation therapy in patients with more than four metastases. A recent multiinstitutional JLGK 0901 prospective study revealed the class-2 evidence that SRS without whole-brain radiation therapy is an effective treatment for patients up to 10 metastatic lesions. Several retrospective studies exist to show the efficacy and safety of SRS for patients with even more than 10 lesions. However, patient selection is very critical for SRS alone treatment. The PubMed database was searched using combinations of search terms and synonyms for multiple brain metastases, Gamma Knife and SRS published between January 1, 2005 and January 1, 2015 in order to address the effectiveness of Gamma Knife for patients with multiple brain metastases. Good performance status, controlled primary disease, total treated tumor volume of 15 cm(3) or less have been found to be significant predictors for survival among patients with two or more brain lesions. The data suggest that SRS can be used and whole brain radiation therapy can be withheld in selected patients with multiple lesions to avoid acute or chronic adverse effects, especially neurocognitive decline, without causing survival disadvantage. In this review, we assessed the evidence for SRS treatment of patients with multiple brain metastases.

Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group.

The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.

The development of stereotactic body radiotherapy in the past decade: a global perspective.

In the past 10 years, there has been an exponential increase in the incorporation of stereotactic body radiotherapy, also known as stereotactic ablative radiotherapy, into the armamentarium against various types of cancer in different settings worldwide. In this article in the 10th year anniversary issue of Future Oncology, representatives from the USA, Canada, Japan, Germany, The Netherlands, Australia and Singapore will provide individual perspectives of the development of stereotactic body radiotherapy in their respective countries.

Single versus multiple session stereotactic body radiotherapy for spinal metastasis: the risk-benefit ratio.

Spine stereotactic body radiation therapy represents an important advancement in the management of spinal metastases that allows precise delivery of ablative doses of radiation therapy with excellent local control. Although the technique is being increasingly used in clinical practice, the optimal fractionation schedule remains uncertain. In this perspective paper, we review radiobiologic principles that support the use of multiple- versus single-fraction spine stereotactic body radiation therapy schedules and clinical data supporting the multiple-fraction approach. Specifically, we suggest that there may be a local control benefit of fractionation, while helping to limit the risk of toxicities such as vertebral body fracture, pain flare and radiation myelopathy. We conclude with future directions and the need for future study on this important topic.

Emerging applications of stereotactic body radiotherapy.

Stereotactic body radiotherapy (SBRT) has been used extensively in patients with lung, liver and spinal tumors, and the treatment outcomes are very favorable. For certain conditions such as medically inoperable stage I non-small-cell lung cancer, liver and lung oligometastases, primary liver cancer and spinal metastases, SBRT is regarded as one of the standard therapies. In the recent years, the use of SBRT has been extended to other disease conditions and sites such as recurrent head and neck cancer, renal cell carcinoma, prostate cancer, adrenal metastasis, pancreatic cancer, gynecological malignancies, spinal cord compression, breast cancer, and stage II-III non-small-cell lung cancer. Preliminary data in the literature show promising results but the follow-up intervals are short for most studies. This paper will provide an overview of these emerging applications.

Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. METHODS: For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. KEY CONTENT AND FINDINGS: In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. CONCLUSIONS: Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer.

The American Radium Society (ARS) Central Nervous System (CNS) committee reviewed literature on epidermal growth factor receptor mutated (EGFRm) and ALK-fusion (ALK+) tyrosine kinase inhibitors (TKIs) for the treatment of brain metastases (BrMs) from non-small cell lung cancers (NSCLC) to generate appropriate use guidelines addressing use of TKIs in conjunction with or in lieu of radiotherapy (RT). The panel developed three key questions to guide systematic review: can radiotherapy be deferred in patients receiving EGFR or ALK TKIs at (1) diagnosis or (2) recurrence? Should TKI be administered concurrently with RT (3)? Two literature searches were performed (May 2019 and December 2023). The panel developed 8 model cases and voted on treatment options using a 9-point scale, with 1-3, 4-6 and 7-9 corresponding to usually not appropriate, may be appropriate, and usually appropriate (respectively), per the UCLA/RAND Appropriateness Method. Consensus was achieved in only 4 treatment scenarios, all consistent with existing ARS-AUC guidelines for multiple BrM. The panel did not reach consensus that RT can be appropriately deferred in patients with BrM receiving CNS penetrant ALK or EGFR TKIs, though median scores indicated deferral may be appropriate under most circumstances. Whole brain RT with concurrent TKI generated broad disagreement except in cases with 2-4 BrM, where it was considered usually not appropriate. We identified no definitive studies dictating optimal sequencing of TKIs and RT for EGFRm and ALK+ BrM. Until such studies are completed, the committee hopes these cases guide decision- making in this complex clinical space.

A Case-based Guide for World Health Organization (WHO) Grade 2 Meningioma Radiosurgery and Radiation Therapy from The Radiosurgery Society.

PURPOSE: Meningiomas represent the most common primary tumor of the central nervous system. Current treatment options include surgical resection with or without adjuvant radiation therapy (RT), definitive RT, and observation. However, the radiation dose, fractionation, and margins used to treat patients with WHO grade 2 meningiomas, which account for approximately 20% of all meningiomas, are not clearly defined, and deciding on the optimal treatment modality can be challenging owing to the lack of randomized data. METHODS AND MATERIALS: In this manuscript, 3 cases of patients with WHO grade 2 meningiomas are presented with descriptions of treatment options after gross total resection, subtotal resection, and previous irradiation. Treatment recommendations were compiled from 9 central nervous system radiation oncology and neurosurgery experts from The Radiosurgery Society, and the consensus of treatment recommendations is reported. RESULTS: Both conventional and stereotactic RT are treatment options for WHO grade 2 meningiomas. The majority of prospective data in the setting of WHO grade 2 meningiomas involve larger margins. Stereotactic radiosurgery/hypofractionated stereotactic RT are less appropriate in this setting. Conventionally fractionated RT to at least 59.4 Gy is considered standard of care with utilization of preoperative and postoperative imaging to evaluate the extent of disease and possible osseous involvement. After careful discussion, stereotactic radiosurgery/hypofractionated stereotactic RT may play a role for the subset of patients who are unable to tolerate the standard lengthy conventionally fractionated treatment course, for those with prior RT, or for small residual tumors. However, more studies are needed to determine the optimal approach. CONCLUSIONS: This case-based evaluation of the current literature seeks to provide examples for the management of grade 2 meningiomas and give examples of both conventional and stereotactic RT.

Best of International Stereotactic Radiosurgery Society Congress 2013: stereotactic body radiation therapy. Part I: spinal tumors.

The 11th biennial International Stereotactic Radiosurgery Society Congress represented another historical gathering of professionals in the field of stereotactic radiosurgery. This congress was held on 16-20 June 2013 in Toronto (ON, Canada), and the chairman was Arjun Sahgal, the co-chair was Michael Schwartz and president of the society was Jean Regis. The congress attracted 550 attendants from all over the world and over 300 abstracts were presented. Among the abstracts presented, 62 (36 oral) were pertaining to stereotactic body radiation therapy (SBRT). Exciting new findings were presented by colleagues from North America, Europe and Asia. This short conference scene (part I) provides a summary of the best abstracts on SBRT for spinal tumors presented in the congress. A separate conference scene on SBRT for nonspinal tumors (part II) also appears in this issue of Future Oncology.

Best of International Stereotactic Radiosurgery Society Congress 2013: stereotactic body radiation therapy. Part II: nonspinal tumors.

The 11th biennial International Stereotactic Radiosurgery Society Congress represented another historical gathering of professionals in the field of stereotactic radiosurgery. This congress was held on 16-20 June 2013 in Toronto (ON, Canada), and the chairman was Arjun Sahgal, co-chair was Michael Schwartz and president of the society was Jean Regis. The congress attracted 550 attendants from all over the world and over 300 abstracts were presented. Among the abstracts presented, 62 (36 oral) were pertaining to stereotactic body radiation therapy (SBRT). Exciting new findings were presented by colleagues from North America, Europe and Asia. This short conference scene (part II) provides a summary of the best abstracts on SBRT for nonspinal tumors presented in the congress. A separate conference scene on SBRT for spinal tumors (part I) also appears in this issue of Future Oncology.

Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial.

BACKGROUND: Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the technique's effectiveness in controlling the symptom burden of spinal metastases has not been well described. We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms. METHODS: 149 patients with mechanically stable, non-cord-compressing spinal metastases (166 lesions) were given SBRT in a phase 1-2 study. Patients received a total dose of 27-30 Gy, typically in three fractions. Symptoms were measured before SBRT and at several time points up to 6 months after treatment, by the Brief Pain Inventory (BPI) and the M D Anderson Symptom Inventory (MDASI). The primary endpoint was frequency and duration of complete pain relief. The study is completed and is registered with ClinicalTrials.gov, number NCT00508443. FINDINGS: Median follow-up was 15·9 months (IQR 9·5-30·3). The number of patients reporting no pain from bone metastases, as measured by the BPI, increased from 39 of 149 (26%) before SBRT to 55 of 102 (54%) 6 months after SBRT (p<0·0001). BPI-reported pain reduction from baseline to 4 weeks after SBRT was clinically meaningful (mean 3·4 [SD 2·9] on the BPI pain-at-its-worst item at baseline, 2·1 [2·4] at 4 weeks; effect size 0·47, p=0·00076). These improvements were accompanied by significant reduction in opioid use during the first 6 months after SBRT (43 [28·9%] of 149 patients with strong opioid use at baseline vs 20 [20·0%] of 100 at 6 months; p=0·011). Ordinal regression modelling showed that patients reported significant pain reduction according to the MDASI during the first 6 months after SBRT (p=0·00003), and significant reductions in a composite score of the six MDASI symptom interference with daily life items (p=0·0066). Only a few instances of non-neurological grade 3 toxicities occurred: nausea (one event), vomiting (one), diarrhoea (one), fatigue (one), dysphagia (one), neck pain (one), and diaphoresis (one); pain associated with severe tongue oedema and trismus occurred twice; and non-cardiac chest pain was reported three times. No grade 4 toxicities occurred. Progression-free survival after SBRT was 80·5% (95% CI 72·9-86·1) at 1 year and 72·4% (63·1-79·7) at 2 years. INTERPRETATION: SBRT is an effective primary or salvage treatment for mechanically stable spinal metastasis. Significant reductions in patient-reported pain and other symptoms were evident 6 months after SBRT, along with satisfactory progression-free survival and no late spinal cord toxicities. FUNDING: National Cancer Institute of the US National Institutes of Health.