Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN): a randomized phase II study protocol.

Background: Approximately 40% of patients with metastatic cancer will have spinal metastatic disease. Historically treated with external beam radiation therapy (EBRT) with limited durability in pain control, the increased lifespan of this patient population has necessitated more durable treatment results via spine radiosurgery/stereotactic body radiation therapy (SBRT). The goal of this study is to assess three-month pain freedom rates via the Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN) randomized trial. Materials and methods: This study is a prospective randomized three-arm phase II trial which will recruit patients with symptomatic spine metastases. All patients will be randomized to standard-of care SBRT (24 Gy in 2 fractions), single-fraction SBRT (19 Gy in 1 fraction), or EBRT (8 Gy in 1 fraction), with the primary endpoint of three-month pain freedom (using the Brief Pain Inventory). We expect that SPORTSMEN will help definitively answer the efficacy of spine SBRT versus EBRT for achieving pain freedom, while defining the safety and efficacy of 19 Gy single-fraction spine SBRT. Local control will be defined according to Spine Response Assessment in Neuro-Oncology (SPINO) criteria. Discussion: This is the first phase II trial to objectively assess optimal spine SBRT dosing in the treatment of symptomatic spine metastatic disease, while assessing spine SBRT versus EBRT. Findings should allow for better determination of the efficacy of two-fraction spine SBRT versus EBRT in the United States, as well as for the novel single-fraction 19 Gy spine SBRT regimen in patients with symptomatic spine metastases. Trial Registration: Clinicaltrials.gov identifier: NCT05617716 (registration date: November 14, 2022).

A quantitative and comparative evaluation of stereotactic spine radiosurgery local control: proposing a consistent measurement methodology.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) is a precise and conformal treatment modality used in the management of metastatic spine tumors. Multiple studies have demonstrated its safety and efficacy for pain and tumor control. However, no uniform quantitative imaging methodology exists to evaluate response to treatment in these patients. This study presents radiographic local control rates post-SBRT, systematically compares measurements acquired according to WHO and Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and explores the relationship to patient outcome. METHODS: The authors performed a retrospective review of prospectively obtained data from a cohort of 59 consecutive patients (81 metastatic isocenters) treated with SBRT and followed with serial MRI scans. Measurements were performed by a neuroradiologist blinded to the patients' clinical course. Local control status was determined according to both WHO and RECIST measurements, and agreement between the measuring methodologies was calculated and reported. RESULTS: Eighty-one isocenters (111 vertebral bodies) were treated with SBRT. The mean treatment dose was 13.96 Gy and the median follow-up duration was 10.8 months, during which 408 MRI scans were evaluated with both WHO and RECIST criteria for each scan point. Imaging demonstrated a mean unidimensional size decrease of 0.2 cm (p = 0.14) and a mean area size decrease of 0.99 cm2 (p = 0.03). Although 88% of the case classifications were concordant and the agreement was significant, WHO criteria were found to be more sensitive to tumor size change. The local control rates according to WHO and RECIST were 95% and 98%, respectively. CONCLUSIONS: Although WHO volumetric measurements are admittedly superior for tumor size measurement, RECIST is simpler, reproducible, and for the first time is shown here to be comparable to WHO criteria. Thus, the application of RECIST methodology appears to be a suitable standard for evaluating post-SBRT treatment response. Moreover, using comprehensive and consistent measuring approaches, this study substantiates the efficacy of SBRT in the treatment of spine metastases.

Stereotactic radiosurgery for intradural spine tumors using cone-beam CT image guidance.

OBJECTIVE Cone-beam CT (CBCT) image guidance technology has been widely adopted for spine radiosurgery delivery. There is relatively little experience with spine radiosurgery for intradural tumors using CBCT image guidance. This study prospectively evaluated a series of intradural spine tumors treated with radiosurgery. Patient setup accuracy for spine radiosurgery delivery using CBCT image guidance for intradural spine tumors was determined. METHODS Eighty-two patients with intradural tumors were treated and prospectively evaluated. The positioning deviations of the spine radiosurgery treatments in patients were recorded. Radiosurgery was delivered using a linear accelerator with a beam modulator and CBCT image guidance combined with a robotic couch that allows positioning correction in 3 translational and 3 rotational directions. To measure patient movement, 3 quality assurance CBCTs were performed and recorded in 30 patients: before, halfway, and after the radiosurgery treatment. The positioning data and fused images of planning CT and CBCT from the treatments were analyzed to determine intrafraction patient movements. From each of 3 CBCTs, 3 translational and 3 rotational coordinates were obtained. RESULTS The radiosurgery procedure was successfully completed for all patients. Lesion locations included cervical (22), thoracic (17), lumbar (38), and sacral (5). Tumor histologies included schwannoma (27), neurofibromas (18), meningioma (16), hemangioblastoma (8), and ependymoma (5). The mean prescription dose was 17 Gy (range 12-27 Gy) delivered in 1-3 fractions. At the halfway point of the radiation, the translational variations and standard deviations were 0.4 ± 0.5, 0.5 ± 0.8, and 0.4 ± 0.5 mm in the lateral (x), longitudinal (y), and anteroposterior (z) directions, respectively. Similarly, the variations immediately after treatment were 0.5 ± 0.4, 0.5 ± 0.6, and 0.6 ± 0.5 mm along x, y, and z directions, respectively. The mean rotational angles were 0.3° ± 0.4°, 0.3° ± 0.4°, and 0.3° ± 0.4° along yaw, roll, and pitch, respectively, at the halfway point and 0.5° ± 0.5°, 0.4° ± 0.5°, and 0.2° ± 0.3° immediately after treatment. CONCLUSIONS Radiosurgery offers an alternative treatment option for intradural spine tumors in patients who may not be optimal candidates for open surgery. CBCT image guidance for patient setup for spine radiosurgery is accurate and successful in patients with intradural tumors.

Spine radiosurgery: lessons learned from the first 100 treatment sessions.

OBJECTIVE Local therapy to spine tumors has been shown to be effective in selected cases. Spinal radiosurgery (SRS) is an evolving radiotherapy regimen allowing for noninvasive, highly efficacious local treatment. The learning curve can compromise the results of any newly employed technology and should be studied to minimize its effects. In this paper the first 100 SRSs performed at several medical centers are presented and analyzed for the effects of the learning curve on outcome. METHODS A retrospective analysis was undertaken to evaluate data from patients treated with SRS at Sheba Medical Center and Assuta Medical Centers in the period from September 2011 to February 2016. Medical history, clinical and neurological findings, pathological diagnoses, SRS variables, complications, and follow-up data were collected and analyzed. Local control rates were calculated, and local treatment failure cases were qualitatively studied. RESULTS One hundred treatment sessions were performed for 118 lesions at 179 spinal levels in 80 patients. The complication rate was low and did not correlate with a learning curve. Mean follow-up time was 302 days, and the overall local control rate was 95%. The local control rate was dose dependent and increased from 87% (among 35 patients receiving a dose of 16 Gy) to 97% (among 65 patients receiving a dose of 18 Gy). The 6 treatment failure cases are discussed in detail. CONCLUSIONS Spinal radiosurgery is a safe and effective treatment. Comprehensive education of the treating team and continuous communication are essential to limit the effects of the learning curve on outcome.

Impact of cervicothoracic region stereotactic spine radiosurgery on adjacent organs at risk.

OBJECTIVE Stereotactic radiosurgery (SRS) of the spine is a conformal method of delivering a high radiation dose to a target in a single or few (usually ≤ 5) fractions with a sharp fall-off outside the target volume. Although efforts have been focused on evaluating spinal cord tolerance when treating spinal column metastases, no study has formally evaluated toxicity to the surrounding organs at risk (OAR), such as the brachial plexus or the oropharynx, when performing SRS in the cervicothoracic region. The aim of this study was to evaluate the radiation dosimetry and the acute and delayed toxicities of SRS on OAR in such patients. METHODS Fifty-six consecutive patients (60 procedures) with a cervicothoracic spine tumor involving segments within C5-T1 who were treated using single-fraction SRS between February 2006 and July 2014 were included in the study. Each patient underwent CT simulation and high-definition MRI before treatment. The clinical target volume and OAR were contoured on BrainScan and iPlan software after image fusion. Radiation toxicity was evaluated using the common toxicity criteria for adverse events and correlated to the radiation doses delivered to these regions. The incidence of vertebral body compression fracture (VCF) before and after SRS was evaluated also. RESULTS Metastatic lesions constituted the majority (n = 52 [93%]) of tumors treated with SRS. Each patient was treated with a median single prescription dose of 16 Gy to the target. The median percentage of tumor covered by SRS was 93% (maximum target dose 18.21 Gy). The brachial plexus received the highest mean maximum dose of 17 Gy, followed by the esophagus (13.8 Gy) and spinal cord (13 Gy). A total of 14 toxicities were encountered in 56 patients (25%) during the study period. Overall, 14% (n = 8) of the patients had Grade 1 toxicity, 9% (n = 5) had Grade 2 toxicity, 2% (n = 1) had Grade 3 toxicity, and none of the patients had Grade 4 or 5 toxicity. The most common (12%) toxicity was dysphagia/odynophagia, followed by axial spine pain flare or painful radiculopathy (9%). The maximum radiation dose to the brachial plexus showed a trend toward significance (p = 0.066) in patients with worsening post-SRS pain. De novo and progressive VCFs after SRS were noted in 3% (3 of 98) and 4% (4 of 98) of vertebral segments, respectively. CONCLUSIONS From the analysis, the current SRS doses used at the Cleveland Clinic seem safe and well tolerated at the cervicothoracic junction. These preliminary data provide tolerance benchmarks for OAR in this region. Because the effect of dose-escalation SRS strategies aimed at improving local tumor control needs to be balanced carefully with associated treatment-related toxicity on adjacent OAR, larger prospective studies using such approaches are needed.

Long-Term Clinical Outcomes of Patients with Colorectal Cancer with Metastatic Epidural Spinal Cord Compression Treated with Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy).

BACKGROUND: Hybrid therapy, consisting of separation surgery followed by stereotactic body radiation therapy, has become the mainstay treatment for radioresistant spinal metastases. Histology-specific outcomes for hybrid therapy are scarce. In clinical practice, colorectal cancer (CRC) is particularly thought to have poor outcomes regarding spinal metastases. The goal of this study was to evaluate clinical outcomes for patients treated with hybrid therapy for spinal metastases from CRC. METHODS: This retrospective study was performed at a tertiary cancer center. Adult patients with CRC spinal metastasis who were treated with hybrid therapy for high-grade epidural spinal cord or nerve root compression from 2005 to 2020 were included. Outcome variables evaluated included patient demographics, overall survival and progression-free survival, surgical and radiation complications, and clinical-genomic correlations. RESULTS: Inclusion criteria were met by 50 patients. Progression of disease occurred in 7 (14%) patients at the index level, requiring reoperation and/or reirradiation at a mean of 400 days after surgery. Postoperative complications occurred in 16% of patients, with 3 (6%) requiring intervention. APC exon 14 and 16 mutations were found in 15 of 17 patients tested and in all 3 of 7 local failures tested. Twenty patients (40%) underwent further radiation due to disease progression at other spinal levels. CONCLUSIONS: Hybrid therapy in patients with CRC resulted in 86.7% local control at 2 years after surgery, with limited complications. APC mutations are commonly present in CRC patients with spine metastases and may suggest worse prognosis. Patients with CRC spinal metastases commonly progress outside the index treatment level.

Cervicothoracic junction instrumentation strategies following separation surgery for spinal metastases.

OBJECTIVE: The cervicothoracic junction (CTJ) is a challenging region to stabilize after tumor resection for metastatic spine disease. The objective of this study was to describe the outcomes of patients who underwent posterolateral decompression and instrumented fusion (i.e., separation surgery across the CTJ for instability due to metastatic disease). METHODS: The authors performed a single-institution retrospective study of a prospectively collected cohort of patients who underwent single-approach posterior decompression and instrumented fusion across the CTJ for metastatic spine disease between 2011 and 2018. Adult patients (≥ 18 years old) who presented with mechanical instability, myelopathy, and radiculopathy secondary to metastatic epidural spinal cord compression (MESCC) of the CTJ (C7-T1) from 2011 to 2018 were included. RESULTS: Seventy-nine patients were included, with a mean age of 62.1 years. The most common primary malignancies were non-small cell lung (n = 17), renal cell (11), and prostate (8) carcinoma. The median number of levels decompressed and construct length were 3 and 7, respectively. The average operative time, blood loss, and length of stay were 179.2 minutes, 600.5 ml, and 7.7 days, respectively. Overall, 58 patients received adjuvant radiation, and median dose, fractions, and time from surgery were 27 Gy, 3 fractions, and 20 days, respectively. All patients underwent lateral mass and pedicle screw instrumentation. Forty-nine patients had tapered rods (4.0/5.5 mm or 3.5/5.5 mm), 29 had fixed-diameter rods (3.5 mm or 4.0 mm), and 1 had both. Ten patients required anterior reconstruction with poly-methyl-methacrylate. The overall complication rate was 18.8% (6 patients with wound-related complications, 7 with hardware-related complications, 1 with both, and 1 with other). For the 8 patients (10%) with hardware failure, 7 had tapered rods, all 8 had cervical screw pullout, and 1 patient also experienced rod/screw fracture. The average time to hardware failure was 146.8 days. The 2-year cumulative incidence rate of hardware failure was 11.1% (95% CI 3.7%-18.5%). There were 55 deceased patients, and the median (95% CI) overall survival period was 7.97 (5.79-12.60) months. For survivors, the median (range) follow-up was 12.94 (1.94-71.80) months. CONCLUSIONS: Instrumented fusion across the CTJ demonstrated an 18.8% rate of postoperative complications and an 11% overall 2-year rate of hardware failure in patients who underwent metastatic epidural tumor decompression and stabilization.

Evolving Role of Stereotactic Body Radiation Therapy in the Management of Spine Metastases: Defining Dose and Dose Constraints.

When treating solid tumor spine metastases, stereotactic high-dose-per-fraction radiation, given in a single fraction or in a hypofractionated approach, has proved to be a highly effective and safe therapeutic option for any tumor histology, in the setting of de novo therapy, as salvage treatment of local progression after previous radiation, and in the postoperative setting. There are variations in practice based on the clinical presentation, goals of therapy, as well as institutional preferences. As a biologically potent therapy, a thoughtful and careful attention to detail with patient selection, treatment planning, and delivery is crucial for treatment success.

Neuro-Oncology Practice resources for optimizing care and practice in spinal oncology.

As the diagnosis and treatment of systemic cancers continues to improve, increased patient survival has resulted in a rise in the number of patients who develop spinal metastases (SM). Within many areas of oncology, utilization of multidisciplinary care models in the management and decision making of SM patients has proven effective for optimizing care and improving patient safety. Three main goals of an effective clinical pathway include improving outcomes and quality, improving the patient experience, and lowering cost. This paper outlines the strategies employed to optimally establish such a collaborative program for the management of patients with SM, as well as direct providers in and out of the field, patients and caregivers, and practice managers to the appropriate resources.

Evaluation of Elements Spine SRS Plan Quality for SRS and SBRT Treatment of Spine Metastases.

Purpose: The Elements Spine Stereotactic Radiosurgery treatment planning system uses automated volumetric modulated arc radiotherapy that can provide a highly conformal dose distribution to targets, which can provide superior sparing of the spinal cord. This study compares the dosimetric quality of Elements plans with the clinical plans of 20 spine stereotactic radiosurgery/stereotactic body radiation therapy (SRS/SBRT) patients treated at our institution. Methods: Twenty spine SRS/SBRT patients who were clinically treated at our institution were replanned using the automated Elements planning workflow with prespecified templates. Elements automatically evaluates the size and shape of the target to determine if splitting the PTV into simplistic subvolumes, each treated by their own arc(s), would increase conformity and spinal cord sparing. The conformity index, gradient index, PTV D 5%, and maximum and mean cord dose were evaluated for the Elements and clinical plans. Treatment delivery efficiency was also analyzed by comparing the total number of monitor units and the modulation factor. Wilcoxon rank-sum tests were performed on the statistics. Results: Elements split the PTV for 50% of cases, requiring four or six arcs. Overall, Elements plans were found to be superior to clinical plans in conformity index, gradient index, and maximum cord dose. The PTV D 5% and cord mean dose for the Elements plans trended higher and lower, respectively. The numbers of monitor units and modulation factor were also higher for Elements plans, although the differences were not significant. Conclusion: Automated Elements plans achieved superior conformity and cord dose sparing compared to clinical plans and PTV splitting successfully improved spinal cord sparing.

Spine radiosurgery in adolescents and young adults: early outcomes and toxicity in patients with metastatic Ewing sarcoma and osteosarcoma.

OBJECTIVE: There are limited data on spine stereotactic radiosurgery (SRS) in treating adolescent and young adult (AYA) patients. SRS has the advantages of highly conformal radiation dose delivery in the upfront and retreatment settings, means for dose intensification, and administration over a limited number of sessions leading to a decreased treatment burden. In this study, the authors report the oncological and toxicity outcomes for AYA patients with metastatic sarcoma treated with spine radiosurgery and provide clinicians a guide for considerations in dose, volume, and fractionation. METHODS: An institutional review board-approved database of patients treated with SRS in the period from October 2014 through December 2018 was queried. AYA patients, defined by ages 15-29 years, who had been treated with SRS for spine metastases from Ewing sarcoma or osteosarcoma were included in this analysis. Patients with follow-ups shorter than 6 months after SRS were excluded. Local control, overall survival, and toxicity were reported. RESULTS: Seven patients with a total of 11 treated lesions were included in this study. Median patient age was 20.3 years (range 15.1-26.1 years). Three patients had Ewing sarcoma (6 lesions) and 4 patients had osteosarcoma (5 lesions). The median dose delivered was 35 Gy in 5 fractions (range 16-40 Gy, 1-5 fractions). The median follow-up was 11.1 months (range 6.8-26.0 months). Three local failures were observed within the follow-up period. No acute grade 3 or greater toxicity was observed. One patient developed late grade 3 toxicity consisting of radiation enteritis. This patient had previously received radiation to an overlapping volume with conventional fractionation. SRS re-irradiation for this patient was also performed concurrently with chemotherapy administration. No late grade 4 or higher toxicities were observed. No pain flare or vertebral compression fracture was observed. Three patients died within the follow-up period. CONCLUSIONS: SRS for spine metastases from Ewing sarcoma and osteosarcoma can be considered as a treatment option in AYA patients and is associated with acceptable toxicity rates. Further studies must be conducted to determine long-term local control and toxicity for this treatment modality.

Pain flare after stereotactic radiosurgery for spine metastases.

PURPOSE: Understanding of pain flare (PF) following spine stereotactic radiosurgery (sSRS) is lacking. This study sought to determine the incidence and risk factors associated with PF following single fraction sSRS. MATERIALS/METHODS: An IRB-approved database was compiled to include patients who underwent sSRS. Patient and disease characteristics as well as treatment and dosimetric details were collected retrospectively. Pain relief post-sSRS was prospectively collected using the Brief Pain Inventory (BPI). These factors were correlated to the development of PF (defined as an increase in pain within 7 days of treatment which resolved with steroids). Survival was calculated using Kaplan-Meier analysis and logistic regression was utilized to evaluate the association between the clinical and treatment factors and occurrence of PF. RESULTS: A total of 348 patients with 507 treatments were included. Median age and prescription dose were 59 years and 15 Gy (range: 7-18), respectively, and 62% of patients were male. Renal cell carcinoma (24%), lung cancer (14%), and breast cancer (11%) were the most common histologies, and 74% had epidural disease and 43% had thecal sac compression. The most common location of metastases was in the cervical/thoracic spine (59%), followed by lumbar spine (32%), and sacral spine (9%). Most common reason for treatment was pain (73%), followed by pain and neurological deficit (13%), asymptomatic disease (10%), and neurologic deficit only (3%). Median time to pain relief was 1.8 months. Median overall survival, time to radiographic failure, and time to pain progression were 13.6 months, 26.5 months, and 56.6 months, respectively. Only 14.4% of treatments resulted in the development of PF. Univariate analysis showed that higher Karnofsky performance score (KPS) (OR=1.03, p=0.03), female gender (OR=1.80, p=0.02), higher prescription dose (OR=1.30, p=0.008), and tumor location of cervical/thoracic spine vs lumbar spine (OR=1.81, p=0.047) were predictors for the development of PF. On multivariate analysis, higher consult KPS (OR=1.03, p=0.04), female gender (OR=1.93, p=0.01), higher prescription dose (OR=1.27, p=0.02), and tumor location of cervical/thoracic spine vs lumbar spine (OR=1.81, p=0.05) remained predictors of PF. No other dosimetric parameters were associated with the development of PF. CONCLUSION: PF is an infrequent complication of sSRS. Predictors for the development of PF include higher consult KPS, female gender, higher prescription dose, and cervical/thoracic tumor location. Dose to the spinal cord was not a predictor of PF. Since a minority (14.4%) of treatments result in PF, we do not routinely utilize prophylactic steroid treatment; however, prophylactic steroids may be considered in female patients with cervical/thoracic metastases receiving higher dose sSRS.

Myositis following spine radiosurgery for metastatic disease: a case series.

OBJECTIVE Spinal stereotactic body radiation therapy (SBRT) has emerged as an attractive method to deliver high doses of radiation to oligometastatic spinal tumors with radioresistant histology. Because SBRT is a palliative therapy, attention to potential radiation toxicities is paramount when counseling patients. The objective of this study was to report radiation-induced myositis after SBRT, a previously undescribed complication. METHODS A total of 667 patients received 891 spine SBRT treatments (either 24 Gy in 1 fraction or 27 Gy in 3 fractions) from 2011 to 2016 and underwent retrospective review. Eleven patients were identified as having radiographic evidence of myositis following SBRT. Clinical and pathologic results were collected, including receipt of anti-vascular endothelial growth factor (VEGF) therapy, radiation dose, equivalent dose in 2-Gy fractions (EQD2), biologically effective dose (BED), and volume of muscle treated. Treatment toxicities were classified according to the Common Terminology Criteria for Adverse Events (CTCAE; version 4.03). Univariate statistical analyses were performed to evaluate the relationships between radiation fractionation schedule and myositis and between anti-VEGF therapy and myositis. RESULTS The cumulative incidence of myositis was 1.9% at 1 year. The median of the mean dose administered to muscle with myositis was 17.5 Gy. The median EQD2 was 55.1 Gy, and the median BED was 82.7 Gy. The median time to the development of clinical symptoms was 1.4 months, while the median time to imaging evidence was 4.7 months. Two patients (18.2%) had CTCAE grade 3 complications. Single-fraction spine SBRT (HR 4.5, 95% CI 1.2-16.9; p = 0.027) was associated with increased risk of developing myositis whereas receipt of anti-VEGF therapy was not (HR 2.2, 95% CI 0.6-7.1; p = 0.2). CONCLUSIONS Radiation myositis following spinal radiosurgery is a rare but important complication. Single-fraction treatment schedules may be associated with increased risk of myositis but should be validated in a larger series.

Feasibility of radiosurgery for patients with spinal tumors treated in lateral decubitus position: A case series from Memorial Sloan Kettering Cancer Center.

INTRODUCTION: Often in clinical practice radiation oncologists encounter patients who require treatment to the spine commonly in the setting of metastatic disease. These metastases usually cause pain, immobility, or neurologic deficits mandating expedited therapy to alleviate the suffering of our patients. Spine radiosurgery techniques have been used extensively for palliation purposes; however, given the patients' deteriorating condition or pain and inability to tolerate anesthesia the radiation oncologist is often left with the conundrum of how to best set up his or her patient in preparation for radiosurgery if supine is not a viable option. In the Memorial Sloan Kettering Cancer Center several patients have been treated successfully in the lateral decubitus position to overcome this set-up issue. In this report, the feasibility of the lateral decubitus set-up for patients who benefit from radiosurgery to the spine when and if they cannot tolerate standard supine position is explored. OBJECTIVE: To report on a retrospective case series of three patients with a total of four lesions who were treated with radiosurgery for spinal metastases while set up in the lateral decubitus position. METHODS AND MATERIALS: This is a retrospective case series of 3 patients who were treated with radiosurgery to the spine for palliation of painful metastatic foci. Patients were treated in the lateral decubitus position in 1-5 fractions in order to be eligible for this retrospective case series. Their set-up data, and clinical outcomes were then compared with historic controls. RESULTS: Patients who were treated in the lateral decubitus position were set up reliably and reproducibly. Additionally clinical outcomes on routine follow-up and imaging, and toxicity profiles also corroborated the utility of this treatment set-up. CONCLUSIONS: Routinely employing optical surface tracking during patient setup followed by KVCBCT prior to treatment delivery along with intra-fractional monitoring is safe and effective while utilizing the lateral decubitus position for the treatment of spinal metastases for patients who cannot tolerate the supine position. Finally the patient follow-up also corroborated that treatments were successful thus lending credence to the safety, ease, effectiveness, and feasibility of this patient set-up.

Spine Stereotactic Body Radiotherapy: Indications, Outcomes, and Points of Caution.

STUDY DESIGN: A broad narrative review. OBJECTIVES: The objective of this article is to provide a technical review of spine stereotactic body radiotherapy (SBRT) planning and delivery, indications for treatment, outcomes, complications, and the challenges of response assessment. The surgical approach to spinal metastases is discussed with an overview of emerging minimally invasive techniques. METHODS: A comprehensive review of the literature was conducted on the techniques, outcomes, and developments in SBRT and surgery for spinal metastases. RESULTS: The optimal management of patients with spinal metastases is complex and requires multidisciplinary assessment from an oncologic team that is familiar with the shifting paradigm as a consequence of evolving techniques in surgery and stereotactic radiation, as well as new developments in systemic agents. The Spinal Instability Neoplastic Score and the epidural spinal cord compression (Bilsky) grading system are useful tools that facilitate communication among oncologic team members and can direct management by providing a baseline assessment of risks prior to therapy. The combined multimodality approach with "separation surgery" followed by postoperative spine SBRT achieves thecal sac decompression, improves tumor control, and avoids complications that may be associated with more extensive surgery. CONCLUSION: Spine SBRT is a highly effective treatment that is capable of delivering ablative doses to the target while sparing the critical organs-at-risk, chiefly the critical neural tissues, within a short and manageable schedule. At the same time, surgery occupies an important role in select patients, particularly with the expanding availability and expertise in minimally invasive techniques. With rapid adoption of spine SBRT in centers outside of the academic setting, it is imperative for the practicing oncologist to understand the relevance and application of these evolving concepts.

Spine stereotactic radiosurgery for the treatment of multiple myeloma.

OBJECTIVE The objective of this study was to define symptomatic and radiographic outcomes following spine stereotactic radiosurgery (SRS) for the treatment of multiple myeloma. METHODS All patients with pathological diagnoses of myeloma undergoing spine SRS at a single institution were included. Patients with less than 1 month of follow-up were excluded. The primary outcome measure was the cumulative incidence of pain relief after spine SRS, while secondary outcomes included the cumulative incidences of radiographic failure and vertebral fracture. Pain scores before and after treatment were prospectively collected using the Brief Pain Inventory (BPI), a validated questionnaire used to assess severity and impact of pain upon daily functions. RESULTS Fifty-six treatments (in 38 patients) were eligible for inclusion. Epidural disease was present in nearly all treatment sites (77%). Moreover, preexisting vertebral fracture (63%), thecal sac compression (55%), and neural foraminal involvement (48%) were common. Many treatment sites had undergone prior local therapy, including external beam radiation therapy (EBRT; 30%), surgery (23%), and kyphoplasty (21%). At the time of consultation for SRS, the worst, current, and average BPI pain scores at these treatment sites were 6, 4, and 4, respectively. The median prescription dose was 16 Gy in a single fraction. The median clinical follow-up duration after SRS was 26 months. The 6- and 12-month cumulative incidences of radiographic failure were 6% and 9%, respectively. Among painful treatment sites, 41% achieved pain relief adjusted for narcotic usage, with a median time to relief of 1.6 months. The 6- and 12-month cumulative incidences of adjusted pain progression were 13% and 15%, respectively. After SRS, 1-month and 3-month worst, current, and average BPI scores all significantly decreased (p < 0.01). Vertebral fracture occurred following 12 treatments (21%), with an 18% cumulative incidence of fracture at 6 and 12 months. Two patients (4%) developed pain flare following spine SRS. CONCLUSIONS This study reports the largest series of myeloma lesions treated with spine SRS. A rapid and durable symptomatic response was observed, with a median time to pain relief of 1.6 months. This response was durable among 85% of patients at 12 months following treatment, with 91% local control. The efficacy and minimal toxicity of spine SRS is likely related to the delivery of ablative and conformal radiation doses to the target. SRS should be considered with doses of 14-16 Gy in a single fraction for patients with multiple myeloma and limited spinal disease, myelosuppression requiring "marrow-sparing" radiation therapy, or recurrent disease after EBRT.

Quantitative Evaluation of Local Control and Wound Healing Following Surgery and Stereotactic Spine Radiosurgery for Spine Tumors.

OBJECTIVE: The present study evaluated the optimal measuring criteria to assess spinal tumor response to surgery followed by stereotactic spine radiosurgery (SRS) and reports the local control and wound complication rates following combined multimodality treatment. METHODS AND MATERIALS: Prospectively collected patient information was retrospectively reviewed to identify patients treated with spine surgery followed by SRS. Tumor sizes and volumetric assessment were formally measured. Local control status was defined according to World Health Organization (WHO, bidimensional), RECIST (unidimensional), or volumetric size change. Statistical comparative assessments of tumor measurements were performed. RESULTS: Twenty-two patients were eligible for evaluation after having undergone surgery followed by single-fraction SRS within a 2-month period. Seventeen had follow-up magnetic resonance imaging (MRI) with a mean patient follow-up of 12.59 months (range 3-36 months). None developed wound complication after radiation therapy (95% lower confidence bound 13%). Two patients had clinical recurrence while 15 of 17 achieved local control (88.3%). A test of marginal homogeneity for RECIST versus WHO was not statistically significant, P = 1.0 suggesting similar response classifications with both systems. Spearman correlations among 1) volumetric assessment, 2) bidimensional size, and 3) unidimensional size were significant for all groups (P < 0.05). CONCLUSION: High local control rates can be achieved with surgery followed by SRS. Further, adjuvant SRS following spine tumor surgery delivers less radiation to the wound than conventional radiation and thus potentially reduces wound complications. Unidimensional, bidimensional, and volumetric tumor assessments demonstrate similar results. Hence the use of the simpler RECIST criteria is suitable and appropriate for evaluating the response to treatment after spine radiosurgery.

Clinical outcome of vertebral compression fracture after single fraction spine radiosurgery for spinal metastases.

Vertebral compression fracture (VCF) occurs after stereotactic body radiation therapy (SBRT) for spine metastasis. Recently, single fraction radiosurgery (sfSRS) is used more frequently. The aim of this study is to determine the clinical outcome of VCF after sfSRS. Spinal instability neoplastic score (SINS) criteria were used to retrospectively score 143 consecutive vertebral segments in 79 patients treated with SRS. Follow-up MRI, pain, and neurologic assessments obtained every 3-6 months. Pain also scored at 7, 14, and 30 days after sfSRS. Follow up was 16 ± 18 months ±SD, range 3-78. Long-term radiographic control occurred in 94 % of cases. Pain improvement resulted within 7 days in 100 % of cases with severe pain and sustained long-term in 95 %. VCF occurred in 21 % of segments: 30 % were de novo VCF. The overall 1 year fracture free probability (1yFFP) was 76 %. Pre-existing VCF resulted in higher probability to progress: 1yFFP 90 versus 60 %. Symptoms presented in 6 % of cases with de novo VCF and 39 % with progressive. The former were treated with vertebral augmentation (VA), the latter with open surgery. Surgery/VA prior to SRS did not change risk of progressive VCF. Univariate but not multivariate analysis identified histology (colorectal), pre-existing VCF, and pain (severe) as significant predictors of VCF. In conclusion, sfSRS compares favourably to SBRT for radiographic and pain control with similar VCF risk. Patients with pre-existing VCF have a higher probability to progress, become symptomatic, and require surgery. These results may help discussing risk and benefits with patients undergoing sfSRS for spinal metastasis and developing new treatment algorithms.

Variability in spine radiosurgery treatment planning - results of an international multi-institutional study.

BACKGROUND: The aim of this study was to quantify the variability in spinal radiosurgery (SRS) planning practices between five international institutions, all member of the Elekta Spine Radiosurgery Research Consortium. METHODS: Four institutions provided one representative patient case each consisting of the medical history, CT and MR imaging. A step-wise planning approach was used where, after each planning step a consensus was generated that formed the basis for the next planning step. This allowed independent analysis of all planning steps of CT-MR image registration, GTV definition, CTV definition, PTV definition and SRS treatment planning. In addition, each institution generated one additional SRS plan for each case based on intra-institutional image registration and contouring, independent of consensus results. RESULTS: Averaged over the four cases, image registration variability ranged between translational 1.1 mm and 2.4 mm and rotational 1.1° and 2.0° in all three directions. GTV delineation variability was 1.5 mm in axial and 1.6 mm in longitudinal direction averaged for the four cases. CTV delineation variability was 0.8 mm in axial and 1.2 mm in longitudinal direction. CTV-to-PTV margins ranged between 0 mm and 2 mm according to institutional protocol. Delineation variability was 1 mm in axial directions for the spinal cord. Average PTV coverage for a single fraction18 Gy prescription was 87 ± 5 %; Dmin to the PTV was 7.5 ± 1.8 Gy averaged over all cases and institutions. Average Dmax to the PRV_SC (spinal cord + 1 mm) was 10.5 ± 1.6 Gy and the average Paddick conformity index was 0.69 ± 0.06. CONCLUSIONS: Results of this study reflect the variability in current practice of spine radiosurgery in large and highly experienced academic centers. Despite close methodical agreement in the daily workflow, clinically significant variability in all steps of the treatment planning process was demonstrated. This may translate into differences in patient clinical outcome and highlights the need for consensus and established delineation and planning criteria.

Stereotactic radiosurgery versus decompressive surgery followed by postoperative radiotherapy for metastatic spinal cord compression (STEREOCORD): Study protocol of a randomized non-inferiority trial.

Current treatment standard for patients with metastatic spinal cord compression (MSCC) is decompressive surgery followed by radiotherapy. Stereotactic radiosurgery (SRS) could be considered a treatment option for MSCC for patients with minor neurologic deficits. If SRS is safely and effectively delivered with equivalent functional outcome, the patients would avoid the risks associated with an invasive procedure. This paper presents the design of a non-inferiority clinical trial evaluating the safety, tolerability and feasibility of SRS vs. current standard treatment for patients with MSCC. Patients fulfilling inclusion criteria will be randomized 1:1 to each arm. The primary endpoint is ability to walk six weeks after treatment. Secondary endpoints are levels of pain, bladder control, quality of life, response rate, toxicity and number of treatment days. 65 patients in each arm are required for the power of 89% to detect a clinically relevant inferior outcome.