Mark H. Bilsky

High-Dose, Single-Fraction Image-Guided Intensity-Modulated Radiotherapy for Metastatic Spinal Lesions

PURPOSE To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. METHODS AND MATERIALS A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. RESULTS The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. CONCLUSION High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group.

Study Design. Systematic review and modified Delphi technique. Objective. To use an evidence-based medicine process using the best available literature and expert opinion consensus to develop a comprehensive classification system to diagnose neoplastic spinal instability. Summary of Background Data. Spinal instability is poorly defined in the literature and presently there is a lack of guidelines available to aid in defining the degree of spinal instability in the setting of neoplastic spinal disease. The concept of spinal instability remains important in the clinical decision-making process for patients with spine tumors. Methods. We have integrated the evidence provided by systematic reviews through a modified Delphi technique to generate a consensus of best evidence and expert opinion to develop a classification system to define neoplastic spinal instability. Results. A comprehensive classification system based on patient symptoms and radiographic criteria of the spine was developed to aid in predicting spine stability of neoplastic lesions. The classification system includes global spinal location of the tumor, type and presence of pain, bone lesion quality, spinal alignment, extent of vertebral body collapse, and posterolateral spinal element involvement. Qualitative scores were assigned based on relative importance of particular factors gleaned from the literature and refined by expert consensus. Conclusion. The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation. It can also aid surgeons in assessing the key components of spinal instability due to neoplasia and may become a prognostic tool for surgical decision-making when put in context with other key elements such as neurologic symptoms, extent of disease, prognosis, patient health factors, oncologic subtype, and radiosensitivity of the tumor.

An Integrated Functional Magnetic Resonance Imaging Procedure for Preoperative Mapping of Cortical Areas Associated with Tactile, Motor, Language, and Visual Functions

OBJECTIVETo evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions. METHODSSensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6). RESULTSFor healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke’s area, and 93% for the putative Broca’s area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke’s area, and 77% for the putative Broca’s area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results. CONCLUSIONThis integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.

Spinal Instability Neoplastic Score: An Analysis of Reliability and Validity From the Spine Oncology Study Group

PURPOSE Standardized indications for treatment of tumor-related spinal instability are hampered by the lack of a valid and reliable classification system. The objective of this study was to determine the interobserver reliability, intraobserver reliability, and predictive validity of the Spinal Instability Neoplastic Score (SINS). METHODS Clinical and radiographic data from 30 patients with spinal tumors were classified as stable, potentially unstable, and unstable by members of the Spine Oncology Study Group. The median category for each patient case (consensus opinion) was used as the gold standard for predictive validity testing. On two occasions at least 6 weeks apart, each rater also scored each patient using SINS. Each total score was converted into a three-category data field, with 0 to 6 as stable, 7 to 12 as potentially unstable, and 13 to 18 as unstable. RESULTS The κ statistics for interobserver reliability were 0.790, 0.841, 0.244, 0.456, 0.462, and 0.492 for the fields of location, pain, bone quality, alignment, vertebral body collapse, and posterolateral involvement, respectively. The κ statistics for intraobserver reliability were 0.806, 0.859, 0.528, 0.614, 0.590, and 0.662 for the same respective fields. Intraclass correlation coefficients for inter- and intraobserver reliability of total SINS score were 0.846 (95% CI, 0.773 to 0.911) and 0.886 (95% CI, 0.868 to 0.902), respectively. The κ statistic for predictive validity was 0.712 (95% CI, 0.676 to 0.766). CONCLUSION SINS demonstrated near-perfect inter- and intraobserver reliability in determining three clinically relevant categories of stability. The sensitivity and specificity of SINS for potentially unstable or unstable lesions were 95.7% and 79.5%, respectively.

Risk of Fracture After Single Fraction Image-Guided Intensity-Modulated Radiation Therapy to Spinal Metastases

PURPOSE Single-fraction image-guided intensity-modulated radiation therapy (IG-IMRT) allows for tumoricidal treatment of traditionally radioresistant cancers while sparing critical adjacent structures. Risk of vertebral fracture after IG-IMRT for spinal metastases has not been defined. PATIENTS AND METHODS We evaluated 62 consecutive patients undergoing single fraction IG-IMRT at 71 sites for solid organ metastases. A neuroradiologist and three spine surgeons evaluated prospectively obtained magnetic resonance/computed tomography (CT) imaging studies for post-treatment fracture development and tumor recurrence. RESULTS Fracture progression was noted in 27 vertebrae (39%). Multivariate logistic regression analysis showed that CT appearance, lesion location, and percent vertebral body involvement independently predicted fracture progression. Lesions located between T10 and the sacrum were 4.6 times more likely to fracture than were lesions above T10 (95% CI, 1.1 to 19.7). Lytic lesions were 6.8 times more likely to fracture than were sclerotic and mixed lesions (95% CI, 1.4 to 33.3). As percent vertebral body involvement increased, odds of fracture also increased. Patients with fracture progression had significantly higher narcotic use, change in Karnofsky performance score, and a strong trend toward higher pain scores. Local tumor progression occurred in seven patients and contributed to one fracture. Obesity, posterior element involvement, bisphosphonate use, and local kyphosis did not confer increased risk. CONCLUSION Vertebral fracture is common after single fraction IG-IMRT for metastatic spine lesions. Lytic disease involving more than 40% of the vertebral body and location at or below T10 confer a high risk of fracture, the presence of which yields significantly poorer clinical outcomes. These results may help clinicians identify high-risk patients who would benefit from prophylactic vertebro- or kyphoplasty.

Local disease control for spinal metastases following "separation surgery" and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: outcome analysis in 186 patients.

OBJECT Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurological function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression (ESCC). The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control. METHODS A retrospective chart review identified 186 patients with ESCC from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (21.5%), high-dose hypofractionated SRS (24-30 Gy in 3 fractions) in 37 patients (19.9%), or low-dose hypofractionated SRS (18-36 Gy in 5 or 6 fractions) in 109 patients (58.6%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics, tumor histology-specific radiosensitivity, grade of ESCC, extent of surgical decompression, response to preoperative radiotherapy, and local tumor control were evaluated by competing risks analysis. RESULTS The total cumulative incidence of local progression was 16.4% 1 year after SRS. Multivariate Gray competing risks analysis revealed a significant improvement in local control with high-dose hypofractionated SRS (4.1% cumulative incidence of local progression at 1 year, HR 0.12, p = 0.04) as compared with low-dose hypofractionated SRS (22.6% local progression at 1 year, HR 1). Although univariate analysis demonstrated a trend toward greater risk of local progression for patients in whom preoperative conventional external beam radiation therapy failed (22.2% local progression at 1 year, HR 1.96, p = 0.07) compared with patients who did not receive any preoperative radiotherapy (11.2% local progression at 1 year, HR 1), this association was not confirmed with multivariate analysis. No other variable significantly correlated with progression-free survival, including radiation sensitivity of tumor histology, grade of ESCC, extent of surgical decompression, or patient sex. CONCLUSIONS Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology-specific radiosensitivity. Patients who received high-dose hypofractionated SRS demonstrated 1-year local progression rates of less than 5% (95% CI 0%-12.2%), which were superior to the results of low-dose hypofractionated SRS. The local progression rate after single-fraction SRS was less than 10% (95% CI 0%-19.0%).

International spine radiosurgery consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery

PURPOSE Spinal stereotactic radiosurgery (SRS) is increasingly used to manage spinal metastases. However, target volume definition varies considerably and no consensus target volume guidelines exist. This study proposes consensus target volume definitions using common scenarios in metastatic spine radiosurgery. METHODS AND MATERIALS Seven radiation oncologists and 3 neurological surgeons with spinal radiosurgery expertise independently contoured target and critical normal structures for 10 cases representing common scenarios in metastatic spine radiosurgery. Each set of volumes was imported into the Computational Environment for Radiotherapy Research. Quantitative analysis was performed using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) with kappa statistics calculating agreement between physicians. Optimized confidence level consensus contours were identified using histogram agreement analysis and characterized to create target volume definition guidelines. RESULTS Mean STAPLE agreement sensitivity and specificity was 0.76 (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98), respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65 (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and CTV in all cases). STAPLE histogram agreement analysis identified optimal consensus contours (80% confidence limit). Consensus recommendations include that the CTV should include abnormal marrow signal suspicious for microscopic invasion and an adjacent normal bony expansion to account for subclinical tumor spread in the marrow space. No epidural CTV expansion is recommended without epidural disease, and circumferential CTVs encircling the cord should be used only when the vertebral body, bilateral pedicles/lamina, and spinous process are all involved or there is extensive metastatic disease along the circumference of the epidural space. CONCLUSIONS This report provides consensus guidelines for target volume definition for spinal metastases receiving upfront SRS in common clinical situations.

Single-stage posterolateral transpedicle approach for spondylectomy, epidural decompression, and circumferential fusion of spinal metastases

Study Design. Retrospective review of prospectively maintained institutional spine database. Objectives. To assess the pain, neurologic, and functional outcome of patients with metastatic spinal cord compression using a posterolateral transpedicular approach with circumferential fusion. Summary of Background Data. Patients with spinal metastases often have patterns of disease requiring both an anterior and posterior surgical decompression and spinal fusion. For patients whose concurrent illness or previous surgery makes an anterior approach difficult, a posterior transpedicular approach was used to resect the involved vertebral bodies, posterior elements, and epidural tumor. This approach provides exposure sufficient to decompress and instrument the anterior and posterior columns.— Methods. During the past 15 months, 25 patients were operated on using a posterolateral transpedicular approach. The primary indications for surgery were back pain (15 patients) and neurologic progression (10 patients). All patients had vertebral body disease, and 21 patients had high-grade spinal cord compression from epidural disease as assessed by magnetic resonance imaging. Seven patients underwent preoperative embolization for vascular tumors. In each patient, the anterior column was reconstructed with polymethyl methacrylate and Steinmann pins and the posterior column with long segmental fixation. Results. All patients achieved immediate stability. Pain relief was significant in all 23 patients who had had moderate or severe pain. Neurologic symptoms were stable or improved in 23 patients. One patient with an acutely evolving myelopathy was immediately worse after surgery, and one patient had a delayed neurologic worsening, progressing to paraplegia. Conclusions. The posterolateral transpedicular approach provides a wide surgical exposure to decompress and instrument the anterior and posterior spine. This technique avoids the morbidity associated with anterior approaches and provides immediate stability. Vascular tumors may be removed safely after embolization. Patients can be mobilized early after surgery.

Stereotactic body radiotherapy for spinal metastases: current status, with a focus on its application in the postoperative patient. A review

Stereotactic body radiotherapy (SBRT) for spinal metastases is an emerging therapeutic option aimed at delivering high biologically effective doses to metastases while sparing the adjacent normal tissues. This technique has emerged following advances in radiation delivery that include sophisticated radiation treatment planning software, body immobilization devices, and capabilities of detecting and correcting patient positional deviations with image-guided radiotherapy. There are limited clinical data specifically supporting the role of SBRT as a superior alternative to conventional radiation in the postoperative patient. The focus of this review was to examine the evidence pertaining to spine SBRT in the treatment of spinal metastases and to provide a comprehensive analysis of published patterns of failure, with emphasis on the postoperative patient.

Reliability analysis of the epidural spinal cord compression scale.

OBJECTIVE The evolution of imaging techniques, along with highly effective radiation options has changed the way metastatic epidural tumors are treated. While high-grade epidural spinal cord compression (ESCC) frequently serves as an indication for surgical decompression, no consensus exists in the literature about the precise definition of this term. The advancement of the treatment paradigms in patients with metastatic tumors for the spine requires a clear grading scheme of ESCC. The degree of ESCC often serves as a major determinant in the decision to operate or irradiate. The purpose of this study was to determine the reliability and validity of a 6-point, MR imaging-based grading system for ESCC. METHODS To determine the reliability of the grading scale, a survey was distributed to 7 spine surgeons who participate in the Spine Oncology Study Group. The MR images of 25 cervical or thoracic spinal tumors were distributed consisting of 1 sagittal image and 3 axial images at the identical level including T1-weighted, T2-weighted, and Gd-enhanced T1-weighted images. The survey was administered 3 times at 2-week intervals. The inter- and intrarater reliability was assessed. RESULTS The inter- and intrarater reliability ranged from good to excellent when surgeons were asked to rate the degree of spinal cord compression using T2-weighted axial images. The T2-weighted images were superior indicators of ESCC compared with T1-weighted images with and without Gd. CONCLUSIONS The ESCC scale provides a valid and reliable instrument that may be used to describe the degree of ESCC based on T2-weighted MR images. This scale accounts for recent advances in the treatment of spinal metastases and may be used to provide an ESCC classification scheme for multicenter clinical trial and outcome studies.