Spinal column chordoma: prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival.

Background: Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined. Methods: In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP. Results: The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (≥100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P = .003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P = .002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P = .012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P = .038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876). Conclusions: The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification.

A multicenter cohort study of spinal osteoid osteomas: results of surgical treatment and analysis of local recurrence.

BACKGROUND CONTEXT: Spinal osteoid osteomas are benign primary tumors arising predominantly from the posterior column of the spine. These "osteoblastic" lesions have traditionally been treated with intralesional excision. PURPOSE: The purpose of the present study was to review the treatment and local recurrence rates for symptomatic spinal osteoid osteomas. STUDY DESIGN/SETTING: Multicenter ambispective cross-sectional observational cohort study. PATIENT SAMPLE: During the study period, a total of 84 patients (65 males, 19 females) were diagnosed with a spinal osteoid osteoma and received surgical treatment. The mean age at surgery was 21.8 ± 9.0 years (range: 6.7-52.4 years) and the mean follow-up was 2.7 years (13 days-14.5 years). OUTCOME MEASURES: Local recurrence, perioperative morbidity, and cross-sectional survival. METHODS: Using the AOSpine Knowledge Forum Tumor multicenter ambispective database, surgically treated osteoid osteoma cases were identified. Patient demographic, clinical and diagnostic, treatment, local recurrence, perioperative morbidity, and cross-sectional survival data were collected and retrieved. Descriptive statistics were summarized using mean/standard deviation or frequency/percentage. RESULTS: In our study, most of the tumors were localized in the mobile spine (81 of 84 [96%]); all patients reported pain as a symptom. According to the postoperative assessment, 10 (12%) patients received an en bloc resection with marginal or wide margins, whereas two (2%) patients received en bloc resections with intralesional margins, 69 (82%) patients were treated by piecemeal "intralesional" resection, and three (4%) patients were not assessed. A total of six patients (7%) experienced a local recurrence, all of which occurred in patients who had received an intralesional resection. CONCLUSIONS: Benign bone-forming tumors of the spine are uncommon. Most patients in our series underwent a piecemeal resection with intralesional margins. This remains safe with a low local recurrence rate. En bloc excision may provide more chance of complete excision of the nidus but is not mandatory. The importance of complete excision of the nidus cannot be overemphasized.

Surgical Management of Spinal Chondrosarcomas.

STUDY DESIGN: An ambispective cohort study. OBJECTIVE: The aim of this study was to determine whether the application of the Enneking classification in the management of spinal chondrosarcomas influences local recurrence and survival. SUMMARY OF BACKGROUND DATA: Primary spinal chondrosarcomas are rare. Best available evidence is based on small case series, thus making it difficult to determine optimal management and risk factors for local recurrence and survival. METHODS: The AOSpine Knowledge Forum Tumor developed a multicenter ambispective database of surgically treated patients with spinal chondrosarcoma. Patient data pertaining to demographics, diagnosis, treatment, cross-sectional survival, and local recurrence were collected. Tumors were classified according to the Enneking classification. Patients were divided into two cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI). They were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation, and otherwise, they were categorized as EI. RESULTS: Between 1987 and 2011, 111 patients (37 female; 74 male) received surgical treatment for a primary spinal chondrosarcoma at a mean age of 47.4 ±â€Š15.8 years. Patients were followed for a median period of 3.1 years (range = 203 d-18.7 yrs). Median survival for the entire cohort was 8.4 years postoperative. After 10 years postoperative, 36 (32%) patients died and 37 (35%) patients suffered a local recurrence. Twenty-three of these 37 patients who suffered a local recurrence died. Sixty (58%) patients received an EA procedure while 44 (42%) received an EI procedure. EI patients had a higher hazard ratio for local recurrence than those who received an EA procedure (P = 0.052). Local recurrence was strongly associated with chondrosarcoma-related death (risk ratio = 3.6, P < 0.010). CONCLUSION: This is the largest multicenter cohort of spinal chondrosarcomas. EA surgical management appeared to correlate with a decreased risk of local recurrence, yet no relationship with survival was found. Where possible, surgeons should strive to achieve EA margins to minimize the risk of local recurrence. LEVEL OF EVIDENCE: 4.

Mobile spine chordoma: results of 166 patients from the AOSpine Knowledge Forum Tumor database.

OBJECT: A chordoma is an indolent primary spinal tumor that has devastating effects on the patient's life. These lesions are chemoresistant, resistant to conventional radiotherapy, and moderately sensitive to proton therapy; however, en bloc resection remains the preferred treatment for optimizing patient outcomes. While multiple small and largely retrospective studies have investigated the outcomes following en bloc resection of chordomas in the sacrum, there have been few large-scale studies on patients with chordomas of the mobile spine. The goal of this study was to review the outcomes of surgically treated patients with mobile spine chordomas at multiple international centers with respect to local recurrence and survival. This multiinstitutional retrospective study collected data between 1988 and 2012 about prognosis-predicting factors, including various clinical characteristics and surgical techniques for mobile spine chordoma. Tumors were classified according to the Enneking principles and analyzed in 2 treatment cohorts: Enneking-appropriate (EA) and Enneking-inappropriate (EI) cohorts. Patients were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation; otherwise, they were categorized as EI. METHODS: Descriptive statistics were used to summarize the data (Student t-test, chi-square, and Fisher exact tests). Recurrence and survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazard modeling. RESULTS: A total of 166 patients (55 female and 111 male patients) with mobile spine chordoma were included. The median patient follow-up was 2.6 years (range 1 day to 22.5 years). Fifty-eight (41%) patients were EA and 84 (59%) patients were EI. The type of biopsy (p < 0.001), spinal location (p = 0.018), and if the patient received adjuvant therapy (p < 0.001) were significantly different between the 2 cohorts. Overall, 58 (35%) patients developed local recurrence and 57 (34%) patients died. Median survival was 7.0 years postoperative: 8.4 years postoperative for EA patients and 6.4 years postoperative for EI patients (p = 0.023). The multivariate analysis showed that the EI cohort was significantly associated with an increased risk of local recurrence in comparison with the EA cohort (HR 7.02; 95% CI 2.96-16.6; p < 0.001), although no significant difference in survival was observed. CONCLUSIONS: EA resection plays a major role in decreasing the risk for local recurrence in patients with chordoma of the mobile spine.

Spinal hemangiomas: results of surgical management for local recurrence and mortality in a multicenter study.

STUDY DESIGN: Multicenter, ambispective observational study. OBJECTIVE: To quantify local recurrence and mortality rates after surgical treatment of symptomatic spinal hemangiomas and identify prognostic variables for local disease control. SUMMARY OF BACKGROUND DATA: Spinal hemangiomas are the most common primary tumors of the spine and are generally benign and usually asymptomatic. Because of the rarity of symptomatic spinal hemangiomas, optimal surgical treatment remains unclear. METHODS: AOSpine Knowledge Forum Tumor Investigators created a multicenter database of primary spinal tumors including demographics, presentation, diagnosis, treatment, survival, and recurrence data. Tumors were classified according to Enneking and Weinstein-Boriani-Biagini. Descriptive statistics were summarized and time to mortality and recurrence was determined. RESULTS: Between 1996 and 2012, 68 patients (mean age = 51 yr, SD = 16) underwent surgical treatment of a spinal hemangioma. Epidural disease was present in 55% of patients (n = 33). Pain and neurological compromise were presenting symptoms in 82% (n = 54) and 37% (n = 24) of patients, respectively. Preoperative embolization was performed in 35% of patients (n = 23), 10% (n = 7) had adjuvant radiotherapy, and 81% (n = 55) underwent posterior-alone surgery. The local recurrence rate was 3% (n = 2). Mortality secondary to spinal hemangioma was not observed (mean follow-up = 3.9 yr, SD = 3.8). CONCLUSION: This is the largest multicenter surgical cohort of spinal hemangiomas. Symptomatic spinal hemangiomas are a benign tumor despite frequently presenting with epidural disease and neurological compromise. Thus, formal en bloc resection is not required, and excellent rates of local control and long-term survival can result from aggressive intralesional resection during index surgery. LEVEL OF EVIDENCE: 3.

An evidence-based medicine model for rare and often neglected neoplastic conditions.

OBJECT: The National Institutes of Health recommends strategies to obtain evidence for the treatment of rare conditions such as primary tumors of the spine (PTSs). These tumors have a low incidence and are pathologically heterogeneous, and treatment approaches are diverse. Appropriate evidence-based care is imperative. Failure to follow validated oncological principles may lead to unnecessary mortality and profound morbidity. This paper outlines a scientific model that provides significant evidence guiding the treatment of PTSs. METHODS: A four-stage approach was used: 1) planning: data from large-volume centers were reviewed to provide insight; 2) recruitment: centers were enrolled and provided the necessary infrastructure; 3) retrospective stage: existing medical records were reviewed and completed with survival data; and 4) prospective stage: prospective data collection has been implemented. The AOSpine Knowledge Forum Tumor designed six modules: demographic, clinical, diagnostic, therapeutic, local recurrence, survival, and perioperative morbidity data fields and provided funding. RESULTS: It took 18 months to implement Stages 1-3, while Stage 4 is ongoing. A total of 1495 tumor cases were captured and diagnosed as one of 18 PTS histotypes. In addition, a PTS biobank network has been created to link clinical data with tumor pathology and molecular analysis. CONCLUSIONS: This scientific model has not only aggregated a large amount of PTS data, but has also established an international collaborative network of spine oncology centers. Access to large volumes of data will generate further research to guide and enhance PTS clinical management. This model could be applied to other rare neoplastic conditions. Clinical trial registration no.: NCT01643174 (ClinicalTrials.gov).

Aneurysmal bone cysts of the spine: treatment options and considerations.

Aneurysmal bone cysts (ABCs) are benign bone lesions with annual incidences ranging from 1.4 to 3.2 cases per million people. Approximately, 10-30% of ABCs are found in the spine. Such lesions are traditionally treated with curettage or other intralesional techniques. Because ABCs can be locally aggressive, intralesional resection can be incomplete and result in recurrence. This has led to increased use of novel techniques, including selective arterial embolization (SAE). This study aims to: (1) compare outcomes based on extent of surgical resection, and (2) compare the efficacy of SAE versus surgical resection. Clinical data pertaining to 71 cases of spinal ABCs were ambispectively collected from nine institutions in Europe, North America, and Australia. Twenty-two spinal ABCs were treated with surgery, 32 received preoperative embolization and surgery, and 17 were treated with SAE. Most tumors were classified as Enneking stage 2 (n = 29, 41%) and stage 3 (n = 29, 41%). Local recurrence and survival were investigated and a significant difference was not observed between treatment groups. However, all three local recurrences occurred following surgical resection. Surgical resection was further categorized based on Enneking appropriateness. Recurrences only occurred following intralesional Enneking inappropriate (EI) resections (P = 0.10), a classification that characterized 47% of all surgical resections. Furthermore, 56% of intralesional resections were EI, compared to only 10% of en bloc resections (P = 0.01). Although SAE treatment did not result in any local recurrences, 35% involved more than five embolization procedures. Spinal ABCs can be effectively treated with intralesional resection, en bloc resection, or SAE. Preoperative embolization should be considered before intralesional resection to limit intraoperative bleeding. Treatment plans must be guided by lesion characteristics and clinical presentation.

A novel scientific model for rare and often neglected neoplastic conditions.

Study Type Retrospective cohort. Introduction The treatment of rare neoplastic conditions is challenging, especially because studies providing high levels of evidence are often lacking. Such is the case with primary tumors of the spine (PTS), which have a low incidence, are pathologically heterogeneous, and have diverse treatment approaches.1 Despite these difficulties, appropriate evidence-based care of these complex patients is imperative. Failure to follow validated oncologic principles may lead to unnecessary mortality and profound morbidity. Objective With the aim of offering patients the most appropriate treatment based on the best available evidence, a novel scientific model was developed and employed. This article outlines this model, which has not only provided significant evidence guiding treatment of this rare condition, but we believe is readily transferrable to other similarly rare conditions. Methods A four-stage approach was employed. (1) Planning: Data from large volume centers were reviewed together with results from a feasibility questionnaire to provide insight into epidemiology, patient volumes, tumor pathology, treatment modalities, and outcomes. (2) Recruitment: Centers with sufficient volume and valid data were enrolled and provided with the necessary infrastructure. This included study coordinators and a secure, Web-based database (REDCap, Vanderbilt University, Nashville, Tennessee, United States) to capture international data from six modules comprising: demographic, clinical, diagnostic, therapeutic, local recurrence, perioperative morbidity fields, and a cross-sectional survey to update survival information. The AOSpine Knowledge Forum Tumor designed these modules and provided funding. Each center received institutional ethics approval. (3) Retrospective stage: Prospectively collected data from all recruited centers were reviewed and analyzed retrospectively. (4) Prospective stage: Following interim analysis, prospective data collection has been implemented. In addition, a PTS bio-bank network has been created to link clinical data with tumor pathology and molecular analysis. Results It took 18 months to implement stages 1 to 3 of this model and stage 4 is ongoing. A total of 1,495 tumor cases were captured and diagnosed as one of the 18 primary spine tumor subtypes listed (Fig. 1). The most prevalent diagnosis was chordoma (n = 344, 23%). There were 674 females and 821 males with a mean age of 43 ± 19 years at the time of surgery. Surgical treatment was performed between 1981 and 2012. The survival at 5 and 10 years postsurgery was 71.9 and 53.3%, respectively, with a median survival of 13 years postsurgery (Fig. 2). Conclusions To date, this is the largest international collection of PTS. This novel scientific model has not only aggregated a large amount of PTS data, but has also established an international collaborative network of spine oncology centers. The access to large volumes of clinical and bio-bank data will generate further research to guide and enhance the clinical management of PTS. This novel scientific model could be of similar tremendous value if applied to other rare neoplastic conditions.