Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:The palliative impact of spine surgery for metastatic disease is evolving with improvements in surgical technique and multidisciplinary cancer care. The goal of this study was to prospectively evaluate long-term clinical outcomes including health-related quality-of-life (HRQOL) measures, using spine cancer-specific patient-reported-outcome (PRO) measures, in patients with symptomatic spinal metastases who underwent surgical management. METHODS:The Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO, ClinicalTrials.gov identifier: NCT01825161) trial is a prospective-observational cohort study that included 10 specialist centers in North America and Europe. Patients aged 18 to 75 years who underwent surgery for spinal metastases were included. Prospective assessments included both spine tumor-specific and generic PRO tools which were collected for a minimum of 2 years post-treatment or until death. RESULTS:Two hundred and eighty patients (51.8% female, mean age 57.9 years) were included. At presentation, the mean Charlson Comorbidity Index was 6.0, 35.7% had neurological deficits as defined by the American Spinal Cord Injury Association scores, 47.2% had high-grade epidural spinal cord compression (2-3), and 89.6% had impending or frank instability as measured by a Spinal Instability Neoplastic Score of ≥7. The most common primary tumor sites were breast (20.2%), lung (18.8%), kidney (16.2%), and prostate (6.5%). The median overall survival postsurgery was 501 days, and the 2-year progression-free-survival rate was 38.4%. Compared with baseline, significant and durable improvements in HRQOL were observed at the 6-week, 12-week, 26-week, 1-year, and 2-year follow-up assessments from a battery of PRO questionnaires including the spine cancer-specific, validated, Spine Oncology Study Group Outcomes Questionnaire v2.0, the Short Form 36 version 2, EuroQol-5 Dimension (3L), and pain numerical rating scale score. CONCLUSION/CONCLUSIONS:Multi-institutional, prospective-outcomes data confirm that surgical decompression and/or stabilization provides meaningful and durable improvements in multiple HRQOL domains, including spine-specific outcomes based on the Spine Oncology Study Group Outcomes Questionnaire v2.0, for patients with metastatic spine disease.

PURPOSE:To evaluate the safety and effectiveness of preoperative embolization with n-butyl cyanoacrylate (nBCA) performed for metastatic spinal cord compression (MSCC) in limiting blood loss (BL). MATERIALS AND METHODS:In this institutional review board-approved retrospective study, clinical records from 2017 to 2022 were reviewed. Twenty consecutive patients (11 men and 9 women; mean age, 65.8 years ± 10.0; range, 45-82 years) underwent 21 preoperative spine tumor embolizations with nBCA. Angiograms were used to calculate the percentage reduction in tumor vascularity, and relevant clinical data (levels studied and embolized, fluoroscopy time [FT], reference dose [RD], and Kerma area product [KAP]) and operative data (BL and operative time [OT]) were analyzed. Adverse events and outcomes were recorded. RESULTS:). The adverse event rate was 1 (4.7%) of the 21 embolizations because a weakness of lower extremities related to swelling was observed. Surgery was performed at a mean of 1.4 days ± 1 (range, 1-5 days) after embolization. The mean surgical estimated BL was 432.5 mL ± 328.5 (range, 25-1,100 mL), and the mean OT was 210.1 minutes ± 97.4 (range, 57-489 minutes). CONCLUSIONS:Preoperative embolization of tumors resected for MSCC with nBCA is a safe procedure allowing for performance of surgery with acceptable BL.

OBJECTIVES/OBJECTIVE:Cancer pain has traditionally been managed with opioids, adjuvant medications, and interventions including injections, neural blockade, and intrathecal pump (ITP). Spinal cord stimulation (SCS), although increasingly used for conditions such as failed back surgery syndrome and complex regional pain syndrome, is not currently recommended for cancer pain. However, patients with cancer-related pain have demonstrated benefit with SCS. We sought to better characterize these patients and the benefit of SCS in exceptional cases of refractory pain secondary to progression of disease or evolving treatment-related complications. MATERIALS AND METHODS/METHODS:This was a single-center, retrospective case series at a tertiary cancer center. Adults ≥18 years old with active cancer and evolving pain secondary to disease progression or treatment, whose symptoms were refractory to systemic opioids, and who underwent SCS trial followed by percutaneous implantation between 2016 and 2021 were included. Descriptive statistics included mean, SD, median, and interquartile range (IQR). RESULTS:Eight patients met the inclusion criteria. The average age at SCS trial was 60.0 (SD: ±11.6) years, and 50% were men. Compared with baseline, the median (IQR) change in pain score by numeric rating scale (NRS) after trial was -3 (2). At an average of 14 days after implant, the median (IQR) change in NRS and daily oral morphine equivalents were -2 (3.5) and -126 mg (1095 mg), respectively. At a median of 63 days after implant, the corresponding values were -3 (0.75) and -96 mg (711 mg). There was no significant change in adjuvant therapies after SCS implantation at follow-up. Six patients were discharged within two days after implantation. Two patients were readmitted for pain control within the follow-up period. CONCLUSIONS:In patients with cancer-related pain, SCS may significantly relieve pain, reduce systemic daily opioid consumption, and potentially decrease hospital length of stay and readmission for pain control. It may be appropriate to consider an SCS trial before ITP in select cases of cancer-related pain.

STUDY DESIGN/UNASSIGNED:Retrospective Cohort Study. OBJECTIVE/UNASSIGNED:Octogenarians living with spinal metastases are a challenging population to treat. Our objective was to identify the rate, types, management, and predictors of complications and survival in octogenarians following surgery for spinal metastases. METHODS/UNASSIGNED:A retrospective review of a prospectively collected cohort of patients aged 80 years or older who underwent surgery for metastatic spinal tumor treatment between 2008 and 2019 were included. Demographic, intraoperative, complications, and postoperative follow-up data was collected. Cox proportional hazards regression and logistic regression were used to associate variables with overall survival and postoperative complications, respectively. RESULTS/UNASSIGNED:= 0.04). Significant associations of increased risk of death were also noted with surgeries with decompression, and cervical/cervicothoracic index level of disease. For deceased patients, median time to death was 4.5 months. For living patients, median follow-up was 14.5 months. The Kaplan-Meier based median overall survival for the cohort was 11.6 months (95% CI: 6.2-19.1). CONCLUSIONS/UNASSIGNED:In octogenarians undergoing surgery with instrumentation for spinal metastases, the median overall survival is 11.6 months. There is an increased complication rate, but only 7% are life-threatening or fatal. Patients are at increased risk for complications and mortality particularly when performing decompression with stabilization, with increasing intraoperative blood loss, and with cervical/cervicothoracic tumors.

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.

BACKGROUND:In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC). OBJECTIVE:To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors. METHODS:This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations. RESULTS:One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival. CONCLUSION/CONCLUSIONS:Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.

BACKGROUND:"Hybrid-therapy", consisting of separation-surgery followed by stereotactic body radiation therapy (SBRT) 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 is to evaluate clinical outcomes for patients treated with hybrid therapy for spinal metastases from CRC. METHODS:This is a retrospective study 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 2005-2020 were included. Outcome variables evaluated included patient demographics, overall survival (OS) and progression-free survival (PFS), surgical and radiation complications, and clinical-genomic correlations. RESULTS:Fifty patients met inclusion criteria. 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. Adenomatous polyposis coli (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 another spinal levels. CONCLUSIONS:Hybrid-therapy in CRC patients resulted in 86.7% local control at two 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.

OBJECTIVE:Paraspinal ganglioneuromas are rare tumors that arise from neural crest tissue and can cause morbidity via compression of adjacent organs and neurovascular structures. The authors investigated a case series of these tumors treated at their institution to determine clinical outcomes following resection. METHODS:A retrospective review of a prospectively collected cohort of consecutive, pathology-confirmed, surgically treated paraspinal ganglioneuromas from 2001 to 2019 was performed at a tertiary cancer center. RESULTS:Fifteen cases of paraspinal ganglioneuroma were identified: 47% were female and the median age at the time of surgery was 30 years (range 10-67 years). Resected tumors included 9 thoracic, 1 lumbar, and 5 sacral, with an average maximum tumor dimension of 6.8 cm (range 1-13.5 cm). Two patients had treated neuroblastomas that matured into ganglioneuromas. One patient had a secretory tumor causing systemic symptoms. Surgical approaches were anterior (n = 11), posterior (n = 2), or combined (n = 2). Seven (47%) and 5 (33%) patients underwent gross-total resection (GTR) or subtotal resection with minimal residual tumor, respectively. The complication rate was 20%, with no permanent neurological deficits or deaths. No patient had evidence of tumor recurrence or progression after a median follow-up of 68 months. CONCLUSIONS:Surgical approaches and extent of resection for paraspinal ganglioneuromas must be heavily weighed against the advantages of aggressive debulking and decompression given the complication risk of these procedures. GTR can be curative, but even patients without complete tumor removal can show evidence of excellent long-term local control and clinical outcomes.

OBJECTIVE:Aneurysmal bone cysts (ABCs) are benign cystic lesions most commonly occurring in the long bones of pediatric patients. Spinal ABCs may be difficult to resect given their invasive, locally destructive nature, proximity to critical structures such as the spinal cord, and their intrinsic hypervascularity, for which complete embolization is often constrained by radiculomedullary segmental feeders. Denosumab, a monoclonal antibody that binds the receptor activator of nuclear factor kappa B (NF-κB) ligand, has been utilized in the treatment of ABCs most often as a rescue therapy for recurrent disease. Here, the authors present 3 cases of neoadjuvant denosumab use in surgically unresectable tumors to calcify and devascularize the lesions, allowing for safer, more complete resection. METHODS:This is a single-center, retrospective case series treated at a tertiary care cancer center. The authors present 3 cases of spinal ABC treated with neoadjuvant denosumab. RESULTS:All 3 patients experienced calcification, size reduction, and a significant decrease in the vascularity of their ABCs on denosumab therapy. None of the patients developed new neurological deficits while on denosumab. Subsequently, all underwent resection. One patient continued denosumab during the immediate postoperative period because a subtotal resection had been performed, with stabilization of the residual disease. No complications were associated with denosumab administration. CONCLUSIONS:The use of denosumab in unresectable ABCs can cause calcification and devascularization, making safe resection more likely.

BACKGROUND:The management of spinal metastatic renal cell carcinoma (mRCC) is controversial regarding extent of resection and radiation dosing. OBJECTIVE:To determine outcomes in patients treated with hybrid therapy (separation surgery plus adjuvant stereotactic body radiation therapy [SBRT]) for mRCC. METHODS:A retrospective study of a prospectively collected cohort of patients undergoing hybrid therapy for mRCC between 2003 and 2017 was performed. SBRT was delivered as high-dose single-fraction, high-dose hypofractionated, or low-dose hypofractionated. Extent of disease, clinical and operative outcomes, and complications data were collected, and associations with overall survival (OS) and progression-free survival were determined. RESULTS:Ninety patients with mRCC with high-grade epidural spinal cord compression (ESCC grades 2 and 3) were treated. Metastases were widespread, oligometastatic, and solitary in 56%, 33%, and 11% of patients, respectively. SBRT delivered was high-dose single-fraction, high-dose hypofractionated, and low-dose hypofractionated in 24%, 56%, and 20% of patients, respectively. The 1-yr cumulative incidence of major complications was 3.4% (95% confidence interval [CI]: 0.0%-7.2%). The median follow-up was 14.2 mo for the entire cohort and 38.3 mo for survivors. The 1-yr cumulative incidence of progression was 4.6% (95% CI: 0.2%-9.0%), which translates to a local control rate of 95.4% (95% CI: 91.0%-99.8%) 1 yr after surgery. The median OS for the cohort was 14.8 mo. CONCLUSION:These data support the use of hybrid therapy as a safe and effective strategy for the treatment of renal cell spine metastases.