Peter C. Gerszten

Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution.

Study Design. A prospective nonrandomized, longitudinal cohort study. Objective. To evaluate the clinical outcomes of single-fraction radiosurgery as part of the management of metastatic spine tumors. Summary of Background Data. The role of stereotactic radiosurgery for the treatment of spinal lesions has previously been limited by the availability of effective target immobilization and target tracking devices. Large clinical experience with spinal radiosurgery to properly assess clinical experience has previously been limited. Methods. A cohort of 500 cases of spinal metastases underwent radiosurgery. Ages ranged from 18 to 85 years (mean 56). Lesion location included 73 cervical, 212 thoracic, 112 lumbar, and 103 sacral. Results. The maximum intratumoral dose ranged from 12.5 to 25 Gy (mean 20). Tumor volume ranged from 0.20 to 264 mL (mean 46). Long-term pain improvement occurred in 290 of 336 cases (86%). Long-term tumor control was demonstrated in 90% of lesions treated with radiosurgery as a primary treatment modality and in 88% of lesions treated for radiographic tumor progression. Twenty-seven of 32 cases (84%) with a progressive neurologic deficit before treatment experienced at least some clinical improvement. Conclusions. The results indicate the potential of radiosurgery in the treatment of patients with spinal metastases, especially those with solitary sites of spine involvement, to improve long-term palliation.

Intracranial ependymomas of childhood: long-term outcome and prognostic factors.

A detailed outcome analysis was performed on 40 children with intracranial ependymomas treated at our institution between 1975 and 1993 to identify those factors that were predictive of overall and progression-free survival. Three patients (7.5%) who were treated in the first 5 years of the study died within 3 months of surgery and were excluded from further outcome assessments. Eight (22%) of the 37 patients who survived the perioperative period had evidence of leptomeningeal dissemination at presentation, on the basis of either imaging (three children) and/or cytological (six children) results. The 5- and 10-year progression-free survival rates among these 37 patients were 45.1 and 36.1%, respectively; overall survival rates were 57.1 and 45.0%, respectively. The site of progression was local in 17 of 19 patients with progressive disease. Three factors were found to have a significant association (P < or = 0.05) with the outcome on both univariate and multivariate analyses: 1) the extent of the resection, 2) the age of the patient at diagnosis, and 3) the duration of the symptoms before diagnosis. The 5-year progression-free and overall survivals were 8.9 and 22%, respectively, among patients who had evidence of residual disease on postoperative imaging studies, compared with 68 and 80% rates among patients with no apparent residual disease (P = 0.0001 and P < 0.0001, respectively). Patients younger than 3 years fared significantly worse than older children (5-year progression-free and overall survival rates of 12 and 22%, respectively, in the younger children versus 60 and 75% in older children (P = 0.003 and P = 0.01, respectively). In addition, patients with a duration of symptoms before diagnosis of < 1 month had a worse outcome than those with a more protracted course (5-year progression-free and overall survival rates of 33 and 33%, respectively, versus rates of 53 and 64%, respectively (P = 0.02 for both). Neither the finding of evidence for dissemination at presentation nor the detection of anaplastic histological features (e.g., dense cellularity or high numbers of mitoses) were associated with a significantly worse outcome in this series. The combination of variables that had the strongest association with both favorable and unfavorable outcomes was the combination of the age of the patient and the resection extent. Only 2 of 17 patients older than 3 years with gross total resections have died, whereas 13 of 20 children who were either younger than 3 years or had radiologically incomplete resections have died (P < 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

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.

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.

CyberKnife Frameless Stereotactic Radiosurgery for Spinal Lesions: Clinical Experience in 125 Cases

OBJECTIVE: The role of stereotactic radiosurgery for the treatment of intracranial lesions is well established. Its use for the treatment of spinal lesions has been limited by the availability of effective targe-immobilizing devices. Conventional external beam radiotherapy lacks the precision to allow delivery of large doses of radiation near radiosensitive structures such as the spinal cord. The CyberKnife (Accuray, Inc., Sunnyvale, CA) is an image-guided frameless stereotactic radiosurgery system that allows for the radiosurgical treatment of spinal lesions. This study evaluated the feasibility and effectiveness of the treatment of spinal lesions with a single-fraction radiosurgical technique using the CyberKnife. METHODS: The CyberKnife system uses the coupling of an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator with six degrees of freedom that guides the therapy beam to the intended target without the use of frame-based fixation. Real-time imaging allows the tracking of patient movement. Cervical spine lesions were located and tracked relative to cranial bony landmarks lower spinal lesions were tracked relative to fiducial bone markers. In this prospective cohort evaluation of a spine radiosurgery technique, 125 spinal lesions in 115 consecutive patients were treated with a single-fraction radiosurgery technique (45 cervical, 30 thoracic, 36 lumbar, and 14 sacral). There were 17 benign tumors and 108 metastatic lesions. All dose plans were calculated on the basis of computed tomographic images acquired from 1.25-mm slices with an inverse treatment planning technique. Radiosurgical circular cones ranging in diameter from 5 to 40 mm were used. RESULTS: Tumor volume ranged from 0l3 to 232 cm 3 (mean, 27.8 cm 3 ). Seventy-eight lesions had received external beam irradiation previously. Tumor dose was maintained at 12 to 20 Cy to the 80% isodose line (mean, 14 Gy); canal volume receiving more than 8 Gy ranged from 0.0 to 1.7 cm 3 (mean, 0.2 cm 3 ). No acute radiation toxicity or new neurological deficits occurred during the follow up period (range, 9-30 mo median, 18 mo). Axial and radicular pain improved in 74 of 79 patients who were symptomatic before treatment. CONCLUSION: This is the first large prospective evaluation of this frameless imageguided spinal radiosurgery system. The Cyberknife system was found to be feasbile, safe, and effective. The major potential benetits of radiosurgical ablation of spinal lesions are short treatment time in an outpatient setting with rapid recovery and symptomatic response. This technique offers a successial therapeutic modality for the treatment of a variety of spinal lesions as a primary treatment or for lesions not amenable to open surgical techniques, in medically inoperable patients, in lesions located in previously irradiated sites or as an adjunct to surgery.

Intracranial Ependymomas of ChildhoodLong-term Outcome and Prognostic Factors

A detailed outcome analysis was performed on 40 children with intracranial ependymomas treated at our institution between 1975 and 1993 to identify those factors that were predictive of overall and progression-free survival. Three patients (7.5%) who were treated in the first 5 years of the study died within 3 months of surgery and were excluded from further outcome assessments. Eight (22%) of the 37 patients who survived the perioperative period had evidence of leptomeningeal dissemination at presentation, on the basis of either imaging (three children) and/or cytological (six children) results. The 5- and 10-year progression-free survival rates among these 37 patients were 45.1 and 36.1%, respectively; overall survival rates were 57.1 and 45.0%, respectively. The site of progression was local in 17 of 19 patients with progressive disease. Three factors were found to have a significant association (P < or = 0.05) with the outcome on both univariate and multivariate analyses: 1) the extent of the resection, 2) the age of the patient at diagnosis, and 3) the duration of the symptoms before diagnosis. The 5-year progression-free and overall survivals were 8.9 and 22%, respectively, among patients who had evidence of residual disease on postoperative imaging studies, compared with 68 and 80% rates among patients with no apparent residual disease (P = 0.0001 and P < 0.0001, respectively). Patients younger than 3 years fared significantly worse than older children (5-year progression-free and overall survival rates of 12 and 22%, respectively, in the younger children versus 60 and 75% in older children (P = 0.003 and P = 0.01, respectively). In addition, patients with a duration of symptoms before diagnosis of < 1 month had a worse outcome than those with a more protracted course (5-year progression-free and overall survival rates of 33 and 33%, respectively, versus rates of 53 and 64%, respectively (P = 0.02 for both). Neither the finding of evidence for dissemination at presentation nor the detection of anaplastic histological features (e.g., dense cellularity or high numbers of mitoses) were associated with a significantly worse outcome in this series. The combination of variables that had the strongest association with both favorable and unfavorable outcomes was the combination of the age of the patient and the resection extent. Only 2 of 17 patients older than 3 years with gross total resections have died, whereas 13 of 20 children who were either younger than 3 years or had radiologically incomplete resections have died (P < 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Spinal cord tolerance for stereotactic body radiotherapy.

PURPOSE Dosimetric data are reported for five cases of radiation-induced myelopathy after stereotactic body radiotherapy (SBRT) to spinal tumors. Analysis per the biologically effective dose (BED) model was performed. METHODS AND MATERIALS Five patients with radiation myelopathy were compared to a subset of 19 patients with no radiation myelopathy post-SBRT. In all patients, the thecal sac was contoured to represent the spinal cord, and doses to the maximum point, 0.1-, 1-, 2-, and 5-cc volumes, were analyzed. The mean normalized 2-Gy-equivalent BEDs (nBEDs), calculated using an alpha/beta value of 2 for late toxicity with units Gy 2/2, were compared using the t test and analysis of variance test. RESULTS Radiation myelopathy was observed at the maximum point with doses of 25.6 Gy in two fractions, 30.9 Gy in three fractions, and 14.8, 13.1, and 10.6 Gy in one fraction. Overall, there was a significant interaction between patient subsets and volume based on the nBED (p = 0.0003). Given individual volumes, a significant difference was observed for the mean maximum point nBED (p = 0.01). CONCLUSIONS The maximum point dose should be respected for spine SBRT. For single-fraction SBRT 10 Gy to a maximum point is safe, and up to five fractions an nBED of 30 to 35 Gy 2/2 to the thecal sac also poses a low risk of radiation myelopathy.

Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological fractures

OBJECT Patients with symptomatic pathological compression fractures require spinal stabilization surgery for mechanical back pain control and irradiation for the underlying malignant process. The authors evaluated a treatment paradigm of closed fracture reduction and fixation involving kyphoplasty and subsequent spinal radiosurgery. METHODS Twenty-six patients (six men and 20 women, mean age 72 years) with pathological compression fractures (16 thoracic and 10 lumbar) were prospectively evaluated. Histological diagnoses included 11 lung, nine breast, four renal, one cholangiocarcioma, and one ocular melanoma. Seven lesions had received prior external-beam radiation therapy. All patients underwent kyphoplasty that involved the percutaneous transpedicular technique. Fiducial markers allowing for image guidance during CyberKnife treatment were placed, at time of the kyphoplasty, in the pedicles at adjacent levels. Patients underwent single-fraction radiosurgery (mean time after kyphoplasty 12 days) in an outpatient setting. The tumor dose was maintained at 16 to 20 Gy (mean 18 Gy) to the 80% isodose line. The treated tumor volume ranged from 12.7 to 37.1 cm3. No acute radiation-induced toxicity or new neurological deficit occurred during the follow-up period (range 11-24 months, median 16 months). Axial pain improved in 24 (92%) of 26 patients. CONCLUSIONS The combined kyphoplasty and spinal radiosurgery treatment paradigm was found to be clinically effective in patients with pathological fractures; there was no significant spinal canal compromise. In this technique two minimally invasive surgical procedures are combined to avoid the morbidity associated with open surgery while providing both immediate fracture fixation and administering a single-fraction tumoricidal radiation dose.

Radiotherapy and Radiosurgery for Metastatic Spine Disease: What Are the Options, Indications, and Outcomes?

Study Design. Systematic literature review. Objective. To determine the options, indications, and outcomes for conventional radiotherapy and radiosurgery for metastatic spine disease. Methods. Three research questions were determined through a consensus among a multidisciplinary panel of spine oncology experts. A systematic review of the literature was conducted regarding radiotherapy and radiosurgery for metastatic spine disease using PubMed, Embase, the Cochrane Evidence Based Medicine Database, and a review of bibliographies of reviewed articles. Research questions:What are the clinical outcomes of the current indications for conventional radiotherapy alone and stereotactic radiosurgery for metastatic spine disease?What are the current dose recommendations and fractionation schedules for conventional spine radiotherapy and stereotactic radiosurgery for metastatic spine disease?What are the current known patterns of failure and complications after conventional spine radiation and stereotactic radiosurgery for metastatic spine disease? Results. For conventional radiotherapy, the initial literature search yielded a total of 531 potentially relevant abstracts. Each of these abstracts was reviewed for relevance, and 62 were selected for in-depth review. Forty-nine studies met all the inclusion criteria. References from the articles included in the analysis and review articles were also examined for potential inclusion in the study. For conventional radiotherapy, 3 randomized trials (high-quality evidence), 4 prospective studies (moderate-quality evidence), and over 40 nonprospective data sets (low- or very-low-quality evidence) that included over 5000 patients in the literature were included in this review. Drawing from the same databases, a systematic search for radiosurgery yielded 195 abstracts, of which 29 met all inclusion criteria. They all represented single-institution reports (low- or very-low-quality data). No randomized data are available for spine radiosurgery. Conclusion. A systematic review of the available evidence suggests that conventional radiotherapy is safe and effective with good symptomatic response and local control, particularly for radiosensitive histologies. A strong recommendation can be made with moderate quality evidence that conventional fractionated radiotherapy is an appropriate initial therapy option for patients with spine metastases in cases in which no relative contraindication exists. A systematic review of the available evidence suggests that radiosurgery is safe and provides an incremental benefit over conventional radiotherapy with more durable symptomatic response and local control independent of histology, even in the setting of prior fractionated radiotherapy. A strong recommendation can be made with low-quality evidence that radiosurgery should be considered over conventional fractionated radiotherapy for the treatment of solid tumor spine metastases in the setting of oligometastatic disease and/or radioresistant histology.

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.