Fisher, Charles G.

OBJECTIVE Chordomas are rare, locally aggressive primary neoplasms. Resection with negative margins is the primary recommended therapeutic approach, while adjuvant radiotherapy and chemotherapy can also play a role in their treatment in certain situations, including lesions with positive margins or those that are poorly differentiated or dedifferentiated. Cervical spine chordomas pose significant surgical challenges given their proximity to critical anatomical structures and the mechanical constraints of the cervical spine. In the current case series, authors aimed to explore the clinical and patient-reported outcomes (PROs) of the surgical treatment of cervical chordomas in a large multicenter cohort. METHODS This multicenter case series analysis utilized data from the prospectively collected Primary Tumor Research and Outcomes Network (PTRON) registry, from its inception (May 16, 2016) to data extraction (February 29, 2024). The study population was restricted to patients with histologically confirmed cervical chordomas involving levels C0–7, who underwent surgical treatment at one of the participating centers, and for whom both the initially planned and postoperatively pathologically confirmed surgical margins were documented. Patient demographics, tumor characteristics, surgical and adjuvant treatments, local recurrence–free survival (LRFS), overall survival (OS), and perioperative adverse events were retrieved. PROs included the Spine Oncology Study Group Outcomes Questionnaire version 2.0 (SOSGOQ2.0), EQ-5D, and SF-36 version 2.0 (SF-36v2). RESULTS Thirty-eight patients were identified, 12 of whom underwent true en bloc resection (EBR), 18 of whom underwent deliberate intralesional resection, and 8 of whom underwent EBR after intralesional surgery or in whom EBR failed. True EBR led to better LRFS (92% vs 83% vs 63%, respectively) and OS (83% vs 39% vs 50%, respectively). Surgical adverse events within 1 year were more frequent with true EBR (100% vs 39% vs 75%, respectively). EQ-5D, SOSGOQ2.0, and SF-36v2 showed improvement with true EBR, whereas the trends for PROs from the other groups were more variable. CONCLUSIONS This multicenter case series analysis provides critical insights into the clinical outcomes and PROs in the largest cohort of surgically treated cervical spine chordomas described to date. It underscores the importance and challenges of wide resection for oncological control. It establishes the associated morbidity and provides an overview of PROs following surgery. These findings contribute valuable evidence to inform shared decision-making and optimize patient care.

Study Design Narrative Review. Objectives To summarize the scientific contributions generated from the AO Spine Knowledge Forum Tumor (AOSKFT) databases, focusing on primary spine tumors, and highlight key findings, research trends, and future directions. Methods Data from the Primary Tumor Retrospective (PT-Retro) and Primary Tumor Research Outcome Network (PTRON) registries were analyzed. The nineteen studies included were peer-reviewed manuscripts focused on primary spine tumors, excluding abstracts, book chapters, systematic reviews, and metastatic studies. Results The PT-Retro registry compiled data from 1495 patients across 18 primary tumor histologies, offering insights into recurrence, survival, and treatment paradigms. Key findings emphasize the importance of Enneking-appropriate (EA) resection in improving survival and reducing recurrence in tumors such as chordoma, chondrosarcoma, and osteosarcoma. Genetic markers, including hTERT promoter mutations and rs2305089 SNP, were linked to prognosis in specific histologies. Benign tumors, such as giant cell tumors and aneurysmal bone cysts, demonstrated variable outcomes with different surgical approaches and selective arterial embolization. Conclusions The AOSKFT registries have significantly advanced knowledge in primary spine tumor management, emphasizing preoperative staging, surgical margins, and multidisciplinary approaches. International, multicentric registries are essential for studying rare diseases like primary spine tumors, enabling robust data collection, improved statistical power, and broader applicability of findings across diverse clinical settings. Ongoing prospective data collection through PTRON will further refine evidence-based care for these rare and challenging conditions.

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.

BACKGROUND AND OBJECTIVES: Aggressive resection for primary tumors of the spine are associated with a high rate of adverse events (AEs), but the impact of AEs on patient-reported outcomes (PROs) remains unknown and is critical to the shared decision-making. Our primary objective was to assess the impact of surgical AEs on PROs using an international registry. Assessing the impact on clinical outcomes and identifying risk factors for AEs were our secondary objectives. METHODS: Patients who underwent surgery for a primary spinal tumor were selected through the Primary Tumor Research and Outcomes Network. Our primary outcome was the impact of AEs on PROs at 3 and 12 months after surgery (measured with Spinal Oncology Study Group Outcomes Questionnaire, Short-Form 36, and EuroQol 5 Dimension). We also assessed the impact on clinical outcomes (local control, surgical margins, readmission, reoperation, and mortality). We stratified our results according to severity of AEs, histology, and type of resection. RESULTS: 374 patients met inclusion criteria (219 males/155 females). The mean age of the cohort was 48.7 years. The most frequent histology was chordoma (37.3%) followed by chondrosarcoma (8.8%). Sixty-seven patients (17.9%) experienced at least 1 intraoperative AE and 117 patients (31.3%) had at least 1 postoperative AE within 3 months. Overall, 159 patients (42.5%) experienced AEs. The readmission rate was significantly higher in patients who experienced AEs (Any AE: 10.1% vs no AE: 1.9% within 3 months; P = <0.001). PROs were not significantly affected by AEs in most questionnaires. Local control, risk of reoperation, mortality, and achieving preplanned margins were similar between AE groups. CONCLUSION: The rate of surgical AEs is considerable in this population. Surgical AEs seem to be associated with a higher number of readmissions, but do not seem to result in significant differences in PROs or in a higher risk of reoperation, mortality, and failure to achieve preplanned margins.

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 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.

Extradural malignant primary spinal tumors are rare and outcome data, especially for younger patients, is limited. In a worldwide (11 centers) study (Predictors of Mortality and Morbidity in the Surgical Management of Primary Tumors of the Spine study; ClinicalTrials.gov Identifier NCT01643174) by the AO Spine Knowledge Forum Tumor, patients surgically treated for primary tumors of the spine between 1992 and 2012, were retrospectively analyzed from a prospective database of their medical history. Medical history, tumor characteristics, diagnostics, treatments, cross-sectional survival, and local recurrences were analyzed. Sixty-eight cases (32 f; 36 m), at an average age of 18.6 ± 4.7 years at the time of diagnosis, were identified (median follow-up 2.9 years). The most common entities were Ewing’s sarcoma (42.6%). Of the patients, 28% had undergone previous spine tumor surgery in another center (84% with intralesional margins). Resection was considered “Enneking appropriate” (EA) in 47.8% of the cases. Of the patients, 77.9% underwent chemotherapy and 50% radiotherapy. A local recurrence occurred in 36.4%. Over a third of patients died within a 10-year follow-up period. Kaplan-Meier-analysis demonstrated statistically significant overall survival (p = 0.007) and local recurrence rates (p = 0.042) for tumors treated with EA surgery versus Enneking inappropriate surgery. Aggressive resection of extradural primary malignant spinal tumors combined with adjuvant therapy reveals low local recurrence rates and better outcomes overall in younger patients.

Extradural primary spinal tumors were retrospectively analyzed from a prospective database of 1495 cases. All subjects with benign primary tumors under the age of 25 years, who were enrolled between 1990 and 2012 (Median FU was 2.4 years), were identified. Patient- and case-related characteristics were collected and statistically analyzed. Results: 161 patients (66f;95m; age 17.0 ± 4.7 years at time of diagnosis) were identified. The most common tumors were osteoblastomas n = 53 (32.9%), osteoid osteomas n = 45 (28.0%), and aneurysmal bone cysts n = 32 (19.9%). The tumor grade, according to the Enneking Classification S1/S2/S3, was 14/73/74 (8.7/45.3/46.0%), respectively. Tumor-related pain was present in 156 (96.9%) patients. Diagnosis was achieved by biopsies in 2/3 of the cases. Spinal fixation was used in >50% of the cases. Resection was Enneking appropriate in n = 100 (62.1%) of cases. Local recurrence occurred in 21 (13.1%) patients. Two patients died within a 10-year follow-up period. Conclusion: This is one of the largest international multicenter cohorts of young patients surgically treated for benign spinal tumors. The heterogenic young patient cohort presented at a mid-term follow-up without a correlation between the grade of aggressiveness in resection and local recurrence rates. Further prospective data are required to identify prognostic factors that determine oncological and functional outcomes for young patients suffering from these rare tumors.

Study Design: International multicenter prospective observational cohort study on patients undergoing radiation +/− surgical intervention for the treatment of symptomatic spinal metastases. Objectives: To investigate the association between the total Spinal Instability Neoplastic Score (SINS), individual SINS components and PROs. Methods: Data regarding patient demographics, diagnostics, treatment, and PROs (SF-36, SOSGOQ, EQ-5D) was collected at baseline, 6 weeks, and 12 weeks post-treatment. The SINS was assessed using routine diagnostic imaging. The association between SINS, PRO at baseline and change in PROs was examined with the Spearmans rank test. Results: A total of 307 patients, including 174 patients who underwent surgery+/− radiotherapy and 133 patients who underwent radiotherapy were eligible for analyses. In the surgery+/− radiotherapy group, 18 (10.3%) patients with SINS score between 0-6, 118 (67.8%) with a SINS between 7-12 and 38 (21.8%) with a SINS between 13-18, as compared to 55 (41.4%) SINS 0-6, 71(53.4%) SINS 7-12 and 7 (5.2%) SINS 13-18 in the radiotherapy alone group. At baseline, the total SINS and the presence of mechanical pain was significantly associated with the SOSGOQ pain domain (r = −0.519, P < 0.001) and the NRS pain score (r = 0.445, P < 0.001) for all patients. The presence of mechanical pain demonstrated to be moderately associated with a positive change in PROs at 12 weeks post-treatment. Conclusion: Spinal instability, as defined by the SINS, was significantly correlated with PROs at baseline and change in PROs post-treatment. Mechanical pain, as a single SINS component, showed the highest correlations with PROs.