Faculty Bibliography

OBJECTIVE:The current treatment of chordomas is associated with significant morbidity, high rates of local recurrence, and the potential for metastases. Stereotactic radiosurgery (SRS) as a primary treatment could reduce the need for en bloc resection to achieve wide or marginal margins. Spinal SRS outcomes support the exploration of SRS's role in the durable control of these conventionally radioresistant tumors. The goal of the study was to evaluate outcomes of patients with primary chordomas treated with spinal SRS alone or in combination with surgery. METHODS:Clinical records were reviewed for outcomes of patients with primary chordomas of the mobile spine and sacrum who underwent single-fraction SRS between 2006 and 2017. Radiographic local recurrence-free survival (LRFS), overall survival (OS), symptom response, and toxicity were assessed in relation to the extent of surgery. RESULTS:In total, 35 patients with de novo chordomas of the mobile spine (n = 17) and sacrum (n = 18) received SRS and had a median post-SRS follow-up duration of 38.8 months (range 2.0-122.9 months). The median planning target volume dose was a 24-Gy single fraction (range 18-24 Gy). Overall, 12 patients (34%) underwent definitive SRS and 23 patients (66%) underwent surgery and either neoadjuvant or postoperative adjuvant SRS. Definitive SRS was selectively used to treat both sacral (n = 7) and mobile spine (n = 5) chordomas. Surgical strategies for the mobile spine were either intralesional, gross-total resection (n = 5) or separation surgery (n = 7) and for the sacrum en bloc sacrectomy (n = 11). The 3- and 5-year LRFS rates were 86.2% and 80.5%, respectively. Among 32 patients (91%) receiving 24-Gy radiation doses, the 3- and 5-year LRFS rates were 96.3% and 89.9%, respectively. The 3- and 5-year OS rates were 90.0% and 84.3%, respectively. The symptom response rate to treatment was 88% for pain and radiculopathy. The extent or type of surgery was not associated with LRFS, OS, or symptom response rates (p > 0.05), but en bloc resection was associated with higher surgical toxicity, as measured using the Common Terminology Criteria for Adverse Events (version 5.0) classification tool, than epidural decompression and curettage/intralesional resection (p = 0.03). The long-term rate of toxicity ≥ grade 2 was 31%, including 20% grade 3 tissue necrosis, recurrent laryngeal nerve palsy, myelopathy, fracture, and secondary malignancy. CONCLUSIONS:High-dose spinal SRS offers the chance for durable radiological control and effective symptom relief with acceptable toxicity in patients with primary chordomas as either a definitive or adjuvant therapy.

Background/UNASSIGNED:Patient-reported outcomes (PRO) represent an important measure of cancer therapy effect. For patients with metastatic epidural spinal cord compression (MESCC), hybrid therapy using separation surgery and stereotactic radiosurgery preserves neurologic function and provides tumor control. There is currently a paucity of data reporting PRO after such combined modality therapy for MESCC. Delineation of hybrid surgery-radiosurgery therapy effect on PRO validates the hybrid approach as an effective therapy resulting in meaningful symptom relief. Patients and Methods/UNASSIGNED:Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP), PROs validated in the cancer population, were prospectively collected. Patients with MESCC who underwent separation surgery followed by stereotactic radiosurgery were included. Separation surgery included a posterolateral approach without extensive cytoreductive tumor excision. A median postoperative radiosurgery dose of 2700 cGy was delivered. The change in PRO 3 months after the hybrid therapy represented the primary study outcome. Preoperative and postoperative evaluations were analyzed using the Wilcoxon signed-rank test for matched pairs. Results/UNASSIGNED:< .001). Conclusions/UNASSIGNED:Validated PRO instruments showed that in patients with MESCC, hybrid therapy with separation surgery and radiosurgery results in a significant decrease in pain severity and symptom interference. These prospective data confirm the benefit of hybrid therapy for treatment of MESCC and should facilitate referral of patients with MESCC for surgical evaluation.

Study Design/UNASSIGNED:Systematic review. Objectives/UNASSIGNED:The objective of this systematic review was to answer 2 key questions: (1) What is the clinical presentation and probability of symptomatic improvement following treatment for patients with renal cell carcinoma (RCC) of the spine? (2) What is the overall survival of patients diagnosed with spinal metastases from RCC? Methods/UNASSIGNED:A literature review was performed to identify articles that reported on survival, clinical outcomes, and/or prognostic factors in the RCC population with spinal metastases from 1986 to 2016. Results/UNASSIGNED:Forty-eight articles (807 patients) were included. The Fuhrman Nuclear Grade has been significantly associated with survival in previous studies but was underpowered in the current study. The Memorial Sloan-Kettering Cancer Center Score (MSKCC/Motzer) was also underpowered in the current study. From the time of spinal metastasis, the mean and median survival for patients with previously diagnosed primary RCC was 8.75 and 11.7 months, respectively, whereas synchronously diagnosed patients (primary RCC and spinal metastasis) had a mean and median survival of 6.75 and 11 months, respectively. Patients with a "low" (0-8), "intermediate" (9-11), or "high" (12-15) revised Tokuhashi score at initial presentation had a median survival of 5.4, 11.7, and 32.9 months, respectively. Conclusion/UNASSIGNED:Patients with either a synchronous or latent diagnosis of RCC survived greater than 6 months from the time of presentation. Initial Furhman grade, Tokuhashi score, and MSKCC/Motzer can be useful tools in informing patient-specific prognosis for those with metastatic RCC of the spine.

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.

One of the major determinants of surgical candidacy in patients with symptomatic spinal metastases is the ability of the patient to tolerate the procedure-associated morbidity. In other pathologies, minimally invasive (MIS) procedures have been suggested to have lower intra-operative morbidity while providing similar outcomes. We conducted a systematic review of the PubMed library searching for articles that directly compared the operative and post-operative outcomes of patients treated for symptomatic spinal metastases. Inclusion criteria were articles reporting two or more cases of patients >18 years old treated with MIS or open approaches for spinal metastases. Studies reporting results in spinal metastases patients that could not be disentangled from other pathologies were excluded. Our search returned 1,568 articles, of which 9 articles met the criteria for inclusion. All articles were level III evidence. Patients treated with MIS approaches tended to have lower intraoperative blood loss, shorter operative times, shorter inpatient stays, and fewer complications relative to patients undergoing surgeries with conventional approaches. Patients in the MIS and open groups had similar pain improvement, neurological improvement, and functional outcomes. Recent advances in MIS techniques may reduce surgical morbidity while providing similar symptomatic improvement in patients treated for spinal metastases. As a result, MIS techniques may expand the pool of patients with spinal metastases who are candidates for operative management.

This paper provides a detailed report of the "First Annual Spinal Navigation, Emerging Technologies and Systems Integration" meeting held December 3, 2016 at the Seattle Science Foundation.

Background:Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group. Methods:The SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials, and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches. Results:Published literature, expert survey, and ongoing clinical trials were used to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurological and functional status, and symptom severity. Conclusions:Accurate description of patient population and therapy effects requires a combination of clinician-based and patient-reported outcome measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and postoperative spine stereotactic body radiotherapy (SBRT).

BACKGROUND:Chordomas are rare primary bone tumors that arise from the axial skeleton. Our objective was to analyze trends in radiation and surgery over time and determine location-based survival predictors for chordomas of the skull base, mobile spine, and sacrum. METHODS:A retrospective cohort study of the SEER (Surveillance Epidemiology and End Results) database from 1973 to 2013 was conducted. All patients had histologically confirmed chordomas. The principal outcome measure was overall survival (OS). RESULTS:The cohort included 1616 patients: skull base (664), mobile spine (444), and sacrum (508). Skull base tumors presented earliest in life (47.4 years) and sacral tumors presented latest (62.7 years). Rates of radiation remained stable for skull base and mobile spine tumors but declined for sacral tumors (P = 0.006). Rates of surgical resection remained stable for skull base and sacral tumors but declined for mobile spine tumors (P = 0.046). Skull base chordomas had the longest median survival (162 months) compared with mobile spine (94 months) and sacral tumors (87 months). Being married was independently associated with improved OS for skull base tumors (hazard ratio, 0.73; 95% confidence interval, 0.53-0.99; P = 0.044). Surgical resection was independently associated with improved OS for sacral chordomas (hazard ratio, 0.48; 95% confidence interval, 0.34-0.69; P < 0.001). CONCLUSIONS:Surgical resection for mobile spine chordomas and radiation for sacral chordomas decreased over time. Patients with skull base tumors survived longer than did patients with mobile spine and sacral chordomas, and surgical resection was associated with improved survival in sacral chordomas only. Understanding the behavior of these tumors can help cranial and spinal surgeons improve treatment in this patient population.

BACKGROUND CONTEXT:Neoplastic spinal instability is movement-related pain or neurologic compromise under physiologic loads with the Spinal Instability Neoplastic Score (SINS) developed to facilitate diagnosis. There is a paucity of evidence that mechanical instability correlates with patient-reported symptoms and that surgical stabilization significantly improves these patient-reported outcomes (PROs). PURPOSE:The objective of this study was to determine if SINS correlates with patient-reported preoperative pain and disability, and if surgical stabilization significantly improves PRO. STUDY DESIGN:A single-institution prospective cohort study was carried out. PATIENT SAMPLE:A total of 131 patients who underwent stabilization for metastatic spinal tumor treatment between July 2014 and August 2016 were included. OUTCOMES MEASURES:Preoperative baseline and mean difference in perioperative PROs as assessed by the Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory (MDASI) were the outcome measures. METHODS:The SINS was analyzed as a continuous, ordinal, and categorical variable (Stable: 0-6, Indeterminate: 7-12, Unstable: 13-18). Statistical analysis was performed using Spearman rank coefficient (rho), the Kruskal-Wallis test, and an extension of the Cochran-Armitage trend test. The SINS and association between the mean differences in post- and preoperative PRO scores was analyzed using the Wilcoxon signed-rank test. RESULTS:There was a statistically significant positive correlation between increasing SINS and severity of preoperative pain with BPI average pain (rho=0.20; p=.03) and MDASI pain (rho=0.19; p=.03). Increasing SINS correlated with severity of preoperative disability with BPI walking (rho=0.19; p=.04), MDASI activity (rho=0.24; p=.006), and MDASI walking (rho=0.20; p=.03). Similar associations were noted when SINS was analyzed as an ordinal categorical variable. Stabilization significantly improved nearly all PRO measures for patients with indeterminate and unstable SINS. Significant correlations persisted when controlling for neurologic status and were not affected based on the technique of surgical stabilization used. CONCLUSIONS:Patient-related outcome-based validation of SINS confirms this scoring system for diagnosing neoplastic spinal instability and provides surgeons with a tool to determine which patients will benefit from stabilization. Surgical stabilization of cancer patients with SINS consistent with mechanical instability provides significant reduction in pain and improves patient mobility independent of neurologic status and stabilization technique.