Fehlings, Michael G.

Abstract Introduction As the incidence of metastatic spine disease (MSD) increases, treatments to manage refractory pain, pathologic vertebral body fractures, and spinal cord compression are becoming increasingly common. Given the palliative nature of surgical intervention used to achieve tumor control and thus mitigate loss of neurologic function and compromised ambulatory function, it is essential to mitigate the risk of such procedures. Methods The AO Spine Knowledge Forum Tumor’s Metastatic Tumor Research and Outcomes Network (MTRON), an international, prospective registry for patients with spinal metastases, was used for this query. Prospective collection included baseline health and demographic information, oncologic data (including Spinal Instability Neoplastic Score (SINS) score and Bilksy epidural compression classification), and baseline functional status (preoperative American Spinal Injury Association (ASIA) and ECOG scores). Health related quality of life (HRQoL) data included Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) and Euro-QoL measures. Surgery related adverse events (AE’s) were collected using the Spine Adverse Events Severity (SAVES V2) framework. Kaplan-Meir curves were used to assess survival. Results The cohort consisted of 1267 patients, 701 male (55.3%). A total of 245 (19.3%) experienced at least one postoperative AE, the majority of which were considered minor (grade 3 or less). Among the most common were deep wound infections (3.2%), wound dehiscence (2.5%), and urinary infections (2.4%). A multivariate analysis demonstrated that age, smoking status, ECOG performance, prior radiotherapy, presence of multiple metastases at other sites, and multiple spine metastases were significant risk factors for a postoperative AE. Postoperative AE’s (p = 0.049) and major postoperative AE’s (p = 0.0038) were found to be related to survival as well as a significant change in HRQoL scores (p < 0.001). Conclusion Postoperative AE’s are extremely relevant to the care of patients with MSD and impact both HRQoL and survival.

BACKGROUND AND OBJECTIVES: The Patient-Generated Subjective Global Assessment (PG-SGA) is a standardized tool for assessing malnutrition in patients with cancer. The primary aim of this study was to assess the impact of preoperative nutritional status as measured by PG-SGA on survival in patients requiring surgical intervention and/or radiotherapy for spinal metastases. METHODS: Patients with spinal metastases who underwent surgery and/or radiation therapy for symptomatic spinal metastases were enrolled in the AO Spine Metastatic Tumor Research and Outcomes Network, a prospective international multicenter research registry, between September 2017 and August 2022. Using the PG-SGA, nutritional status was classified into 3 categories: A, well nourished; B, moderately malnourished; and C, severely malnourished. RESULTS: A total of 589 patients met the inclusion criteria; 362 were classified as well nourished (61%), 159 were moderately malnourished (27%), and 68 were severely malnourished (12%). The median survival was 491 days, 328 days, and 117 days for well-nourished, moderately malnourished, and severely malnourished patients, respectively. In the multivariate analyses, severe malnourishment (HR 2.5 95% CI 1.4-4.3, P < .01) and an ECOG performance status of 3 or 4 (HR 2.7 95% CI 1.2-6.0) remained associated with significantly worse survival. CONCLUSION: Malnutrition as measured by the PG-SGA demonstrated to be significantly and independently associated with postoperative survival. The PG-SGA is a simple and useful tool to identify spinal metastases patients at risk of early postoperative mortality, and inclusion in the preoperative evaluation of these patients should be considered.

Study Design This study is part of the AO Spine Metastatic Tumor Research and Outcomes Network [MTRON], an international multicenter prospective observational registry including patients with spinal metastases. Objectives This study aims to elucidate the incidence of surgical complications, their risk factors and consequent effects on survival outcomes, hospital length of stay, and overall health-related quality of life (HRQOL) parameters in a large cohort of patients affected by spinal metastases who were surgically treated. Methods Available data from February 2017 to July 2023 were analyzed. The primary outcome of this study was the evaluation of the incidence of intraoperative and postoperative adverse events (AEs). The secondary outcomes included the assessment of risk factors for surgery-related AEs and the impact of AEs on survival, length of hospital stay and quality of life. Results Among the 1267 patients analyzed, 6.9% experienced intraoperative AEs and 19.3% experienced at least 1 postoperative AE. Several factors resulted to be associated to the occurrence of postoperative AEs: age, smoking habit, poor Eastern Cooperative Oncology Group (ECOG) Performance status, previous radiation therapy at the index target, duration of surgery, number of instrumented levels, simultaneous anterior and posterior approach, presence of metastases at other sites, multiple spinal metastases. Postoperative AEs were associated with reduced survival rates, increased hospital length of stay and poorer HRQOL outcomes, particularly in domains such as neurological function and mental health. In general, surgery substantially improves HRQOL across multiple domains, with these benefits persisting over time despite the occurrence of AEs. However, patients with preoperative risk factors, including comorbidities, smoking, neurological impairment, and prior radiation therapy, experienced less improvement. Conclusions The negative impact of AEs on overall survival and HRQOL could be associated with the presence of some preoperative parameters of frailty that are detected as risk factors for AEs occurrence. This finding emphasizes the need for personalized preoperative assessments and optimized perioperative care strategies.

OBJECTIVE Surgery is typically indicated for mechanical pain in metastatic spine disease or severe neurological compromise, but how radicular pain responds to oncological treatment is not well described. The primary aim of this study was to describe how radicular pain responds to oncological treatment, while secondary aims included pain outcomes between patients with mechanical and tumoral pain and motor improvement in patients with weakness due to nerve root compression. METHODS Patients treated with surgery and/or radiotherapy for spinal metastases were identified from an international multicenter prospective cohort. The primary outcome was the numeric rating scale (NRS) score for pain at 3 months posttreatment. Motor recovery from radicular compression in patients with myotomic weakness and low-grade epidural compression was also analyzed. RESULTS Of 284 patients, 129 (45%) had radicular pain ± axial pain and 155 (55%) had axial pain alone. The two groups did not significantly differ in age, comorbidities, tumor characteristics, or treatment. Two hundred two patients (71%) underwent surgery ± radiotherapy, whereas 82 (29%) had radiotherapy alone. The NRS score of patients with radicular pain improved from 6.7 to 3.4 at 3 months, a statistically significantly higher magnitude than in patients with isolated axial pain (p = 0.021). The NRS score at 3 months was similar for both groups (p = 0.876). Patients with radicular pain experienced a larger improvement with surgery compared with radiotherapy alone (p = 0.007) but had higher pretreatment pain (mean NRS score 7.0 vs 5.6, p = 0.013). Twenty-three patients identified with radicular/myotomic weakness (mean American Spinal Injury Association score 96.3 ± 3.2) at baseline improved 2.1 ± 3.8 points at 3 months. CONCLUSIONS The magnitude of pain improvement for patients with radicular pain following surgery and radiotherapy for metastatic spine disease is higher than for patients with axial pain alone. Surgery is associated with a larger improvement in radicular pain than radiotherapy alone. These results will allow clinicians to tailor treatment options for patients with metastatic spine disease.

Study Design Narrative Review. Objectives To summarize the work of the AO Spine Knowledge Forum Tumor, specifically studies from the Epidemiology, Process and Outcomes in Spine Oncology (EPOSO) study. Methods A narrative review of all published manuscripts from the EPOSO study was undertaken. EPOSO represents a multicenter, prospective registry effort across 10 North American and European sites to enroll patients with metastatic disease of the spine. Results The current review summarized all studies from the EPOSO network, divided into the following five sections: (1) quality of life and satisfaction, (2) overall survival, (3) spinal instability, (4) neurologic outcome in patients with metastatic epidural spinal cord compression or radicular pain, and (5) patient and tumor-specific factors. Several important findings were elucidated. Patient evaluation should include SINS, nutritional status, severity and duration of neurologic deficit, extent of metastatic tumor burden, and differentiation of axial from radicular pain. Moreover, SOSGOQ2.0 serves as a useful and validated instrument for patient-reported outcome instrument. Despite the palliative nature of metastatic spine surgery, clear improvement in quality-of-life is seen. Even in patients with short-survival, the remaining weeks and months of life result in improved quality-of-life. Metastatic spine surgery often improves neurologic function, potentially enhancing survival through increased performance status. Conclusions Several noteworthy results have come from the EPOSO network, highlighting important trends in metastatic spine care. The AO Spine Knowledge Forum Tumor has helped advancing metastatic spine tumor research as well as ensure these new findings reach and benefit clinicians and their patients.

Study Design: Cross-sectional study. Objective: To evaluate for areas of consensus and divergence of opinion within the spine community regarding the management of cervical spondylotic conditions and acute traumatic central cord syndrome (ATCCS) and the influence of the patient's age, disease severity, and myelomalacia. Summary of Background Data: There is ongoing disagreement regarding the indications for, and urgency of, operative intervention in patients with mild degenerative myelopathy, moderate to severe radiculopathy, isolated axial symptomatology with evidence of spinal cord compression, and ATCCS without myelomalacia. Methods: A survey request was sent to 330 attendees of the Cervical Spine Research Society (CSRS) 2021 Annual Meeting to assess practice patterns regarding the treatment of cervical stenosis, myelopathy, radiculopathy, and ATCCS in 16 unique clinical vignettes with associated MRIs. Operative versus nonoperative treatment consensus was defined by a management option selected by >80% of survey participants. Results: Overall, 116 meeting attendees completed the survey. Consensus supported nonoperative management for elderly patients with axial neck pain and adults with axial neck pain without myelomalacia. Operative management was indicated for adult patients with mild myelopathy and myelomalacia, adult patients with severe radiculopathy, elderly patients with severe radiculopathy and myelomalacia, and elderly ATCCS patients with pre-existing myelopathic symptoms. Treatment discrepancy in favor of nonoperative management was found for adult patients with isolated axial symptomatology and myelomalacia. Treatment discrepancy favored operative management for elderly patients with mild myelopathy, adult patients with mild myelopathy without myelomalacia, elderly patients with severe radiculopathy without myelomalacia, and elderly ATCCS patients without preceding symptoms. Conclusions: Although there is uncertainty regarding the treatment of mild myelopathy, operative intervention was favored for nonelderly patients with evidence of myelomalacia or radiculopathy and for elderly patients with ATCCS, especially if pre-injury myelopathic symptoms were present. Level of Evidence: Level V.

Importance The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, −0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

BACKGROUND AND OBJECTIVES: 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: 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.

Study Design. Retrospective cohort study of prospectively accrued data. Objective. To evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach. Summary of Background Data. The influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data. Methods. Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy. Results. A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P=0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy (P=0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches. Conclusion. The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM. Level of Evidence. Therapeutic Level—II

Study Design. Retrospective review of prospective, multicenter and international cohort study. Objective. To describe the effect of gender on HRQoL, clinical outcomes and survival for patients with spinal metastases treated with either surgery and/or radiation. Summary of Background Data. Gender differences in health-related outcomes are demonstrated in numerous studies, with women experiencing worse outcomes and receiving lower standards of care than men, however, the influence that gender has on low health-related quality of life (HRQoL) and clinical outcomes after spine surgery remains unclear. Methods. Patient demographic data, overall survival, treatment details, perioperative complications, and HRQoL measures including EQ-5D, pain NRS, the short form 36 version 2 (SF-36v2) and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) were reviewed. Patients were stratified by sex, and a separate sensitivity analysis that excluded gender-specific cancers (i.e., breast, prostate, etc.) was performed. Results. The study cohort included 207 female and 183 male patients, with age, smoking status, and site of primary cancer being significantly different between the two cohorts (P<0.001). Both males and females experienced significantly improved SOSGOQ2.0, EQ-5D, and pain NRS scores at all study time points from baseline (P<0.001). Upon sensitivity analysis, (gender-specific cancers removed from analysis), the significant improvement in SOSGOQ physical, mental, and social subdomains and on SF-36 domains disappeared for females. Males experienced higher rates of postoperative complications. Kaplan-Meier survival analysis of both the overall and sensitivity analysis cohorts showed females lived longer than males after treatment (P=0.001 and 0.043, respectively). Conclusion. Both males and females experienced significantly improved HRQoL scores after treatment, but females demonstrated longer survival and a lower complication rate. This study suggests that gender may be a prognostic factor in survival and clinical outcomes for patients undergoing treatment for spine metastases and should be taken into consideration when counseling patients accordingly.