Faculty Bibliography

BACKGROUND CONTEXT:Surgical decompression and stabilization followed by radiosurgery represents an effective method for local tumor control and neurologic preservation for patients with metastatic epidural spinal cord compression (MESCC). We have previously demonstrated improvement in health-related quality of life (HrQOL) after this combined modality treatment ("hybrid therapy"). PURPOSE:The current analysis focuses on delineation of patient-specific prognostic factors predictive of HrQOL change after combined surgery-stereotactic radiosurgery (SRS) treatment of MESCC. STUDY DESIGN:This is a prospective, single-center, cohort study. PATIENT SAMPLE:One hundred and eleven patients with MESCC who underwent separation surgery followed by SRS were included. OUTCOME MEASURES:Prognostic factors associated with improved patient-reported outcome (PRO) measures. METHODS:Patient-reported outcome tools, that is, Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP), both validated in the cancer population, were prospectively collected. Numeric prognostic factors were correlated with PRO measures using the Spearman rank correlation coefficient. Categorical prognostic factors were correlated with PRO measures using the Wilcoxon two-sample test (for two categories) or the Kruskal-Wallis test (for three or more categories). All statistical tests were two-sided with a level of significance <.05 for correlation of prognostic factors with PRO constructs and a level of significance <.0014 for correlation of prognostic factors with PRO items. Statistical analyses were done in SAS (version 9.4, Cary, NC, USA). RESULTS:One hundred and eleven patients were included in this analysis. Patients with lower preoperative Medical Research Council (MRC) motor scores experienced a greater decrease in symptom interference (BPI interference construct (p=.03) and individual functional measures including general activity (p=.001), walking (p=.001), and normal work (p=.006)). Lumbar location was associated with better outcomes than cervical or thoracic as noted on the BPI pain experience construct (p=.03) and MDASI-SP interference (p=.01) and core symptom (p=.002) constructs. Patients with American Spinal Injury Association (ASIA) scores of C or D benefit more than those with ASIA E on BPI interference construct (p=.04). Patients with higher Eastern Cooperative Oncology Group (ECOG) scores at presentation benefit more than those with low ECOG scores on MDASI-SP interference construct (p=.03). Women benefit more than men on BPI interference (p=.03) and pain experience (p=.04) constructs. Patients with prior spinal surgery at the current level of interest benefit less than those who are naïve surgical patients in MDASI-SP interference construct (p=.04). CONCLUSIONS:Delineation of patient characteristics associated with HrQOL improvement provides crucial information for patient selection, patient education, and setting treatment expectations. For patients with MESCC treated with hybrid therapy using surgery and radiosurgery, the presence of neurologic deficits and diminished performance status, lumbar tumor level, and female gender were associated with greater PRO improvement.

BACKGROUND:Spine and nonspine skeletal metastases occur in more than 80% of patients with prostate cancer. OBJECTIVE:To examine the characteristics of the patient population undergoing surgery for the treatment of prostate cancer metastatic to the spine. METHODS:A retrospective chart review was performed on all patients treated at our institution from June 1993 to August 2014 for surgical management of metastatic spine disease from prostate cancer. RESULTS:During the study period, 139 patients with 157 surgical lesions underwent surgery for metastatic spine disease. Decompression for high-grade epidural spinal cord compression was required for 126 patients with 143 lesions. Preoperatively, 69% had a motor deficit and 21% were nonambulatory, with 32% due to motor weakness. At surgery, 87% of patients had hormone-refractory prostate cancer (HRPC) and 61% failed prior radiation. Median overall survival for HRPC patients was 6.6 mo (95% confidence interval [CI]: 5.6-8.6) while the median overall survival for hormone-sensitive patients was 16.3 mo (95% CI: 4.0-26.6). CONCLUSION:The majority of patients undergoing surgery for prostate cancer metastases to the spine were refractory to hormone therapy, indicating that patients with hormone-sensitive prostate cancer are unlikely to develop symptomatic spinal cord compression or spinal instability. A significant number of HRPC patients presented with neurological deficits attributable to spinal cord compression. Vigilant monitoring for the development of signs and symptoms of epidural spinal cord compression and spinal instability in hormone-refractory patients is recommended. Surgical decision making may be affected by the much shorter postoperative survival for HRPC patients as compared to patients with hormone-sensitive cancer.

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.

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.

[This corrects the article DOI: 10.1093/nop/npx017.][This corrects the article DOI: 10.1093/nop/npx017.].

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 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.

OBJECTIVE Myxopapillary ependymoma is a benign WHO Grade I tumor most commonly located in the conus-cauda equina region of the spine. Although this tumor is defined by an overall excellent survival, dissemination throughout the whole neuraxis occurs frequently. The current study evaluated the clinical characteristics and significance of myxopapillary ependymoma metastases. METHODS Patients who underwent surgery from 2005 to 2015 for treatment of spinal myxopapillary ependymoma were included in the study. Charts were reviewed for primary tumor symptoms and initial treatment, local recurrence, response to salvage therapy, and presence and behavior of distant metastases. RESULTS Nineteen patients with spinal myxopapillary ependymoma were included in the study (52.6% female). The median age at first diagnosis was 32 years old (range 9-58 years old), and 26.3% were ≤ 18 years old. The median follow-up of all included patients was 48 months (range 6-456 months). Of the primary tumors, 84.2% were located in the lower thoracic or upper lumbar spine, spanning 1-3 levels in 94.7%. All patients underwent surgery for initial treatment: in 78.9% a gross-total resection (GTR) was achieved, with adjuvant radiation therapy (RT) in 20%. Of the 21.2% who underwent a subtotal resection (STR), 75% underwent postoperative RT. Tumor progression was noted in 26.3% of patients after a median 36-month follow-up (range 12-240 months). In 57.9% of patients, distant metastases were found, of which 36.4% were present at initial diagnosis. Further metastases occurred within a median of 20 months (range 2-360 months). Following a diagnosis of metastatic tumor, 72.7% did not show progression and no symptoms were observed during a median follow-up of 36 months (range 6-216 months). Metastases occurred in all parts of the neuroaxis, but were principally localized in the thoracic and sacral spine in 38.9% and 33.3%, respectively; the brain was involved in 11.1%. In 54.5%, more than 1 level was affected. Overall survival was 100% with an excellent clinical and neurological outcome in 78.9% of cases. CONCLUSIONS Metastatic dissemination within the CNS can be observed in many patients with myxopapillary ependymoma. GTR of the primary tumor should be the primary treatment goal, and additional RT is recommended after STR. For distant metastases of myxopapillary ependymoma without clinical manifestation, close clinical and MRI follow-up represents a sufficient strategy because most of the metastases remain asymptomatic and do not show progression over time. Additional resection or irradiation as salvage therapy would be recommended if metastases become symptomatic.