Germscheid, Niccole

Abstract Background Spinal chordomas, a subtype of primary spinal column malignancies (PSCM), are rare tumors with poor prognosis, and we have limited understanding of the molecular drivers of neoplasia. Methods Study design was a retrospective review of prospectively collected data with cross-sectional survival. Archived paraffin embedded pathologic specimens were collected for 133 patients from 6 centers within Europe and North America between 1987 and 2012. Tumor DNA was extracted and the human telomerase reverse transcriptase (hTERT) promoter was sequenced. The hTERT mutational status was correlated with overall survival (OS) and time to first local recurrence. Results Ninety-two chordomas, 26 chondrosarcomas, 7 osteosarcomas, 3 Ewing’s sarcomas, and 5 other malignant spinal tumors were analyzed. Median OS following surgery was 5.8 years (95% CI: 4.6 to 6.9) and median time to first local recurrence was 3.9 years (95% CI: 2.5 to 6.7). Eight chordomas, 2 chondrosarcomas, 1 Ewing’s sarcoma, and 1 other malignant spinal tumor harbored either a C228T or C250T mutation in the hTERT promoter. In the overall cohort, all patients with hTERT mutation were alive at 10 years postoperative with a median OS of 5.1 years (95% CI: 4.5 to 6.6) (P = 0.03). hTERT promoter mutation was observed in 8.7% of spinal chordomas, and 100% of chordoma patients harboring the mutation were alive at 10 years postoperative compared with 67% patients without the mutation (P = 0.05). Conclusions We report for the first time that hTERT promoter mutations C228T and C250T are present in approximately 8.7% of spinal chordomas. The presence of hTERT mutations conferred a survival benefit and could potentially be a valuable positive prognostic molecular marker in spinal chordomas.

Study Design: Systematic review. Objectives: The objective of this systematic review was to answer 2 key questions: (1) What is the clinical presentation and probability of symptomatic improvement following treatment for patients with renal cell carcinoma (RCC) of the spine? (2) What is the overall survival of patients diagnosed with spinal metastases from RCC? Methods: A literature review was performed to identify articles that reported on survival, clinical outcomes, and/or prognostic factors in the RCC population with spinal metastases from 1986 to 2016. Results: Forty-eight articles (807 patients) were included. The Fuhrman Nuclear Grade has been significantly associated with survival in previous studies but was underpowered in the current study. The Memorial Sloan-Kettering Cancer Center Score (MSKCC/Motzer) was also underpowered in the current study. From the time of spinal metastasis, the mean and median survival for patients with previously diagnosed primary RCC was 8.75 and 11.7 months, respectively, whereas synchronously diagnosed patients (primary RCC and spinal metastasis) had a mean and median survival of 6.75 and 11 months, respectively. Patients with a “low” (0-8), “intermediate” (9-11), or “high” (12-15) revised Tokuhashi score at initial presentation had a median survival of 5.4, 11.7, and 32.9 months, respectively. Conclusion: Patients with either a synchronous or latent diagnosis of RCC survived greater than 6 months from the time of presentation. Initial Furhman grade, Tokuhashi score, and MSKCC/Motzer can be useful tools in informing patient-specific prognosis for those with metastatic RCC of the spine.

OBJECTIVE Primary spinal osteosarcomas are rare and aggressive neoplasms. Poor outcomes can occur, as obtaining marginal margins is technically demanding; further Enneking-appropriate en bloc resection can have significant morbidity. The goal of this study is to identify prognostic variables for local recurrence and mortality in surgically treated patients diagnosed with a primary osteosarcoma of the spine. METHODS A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by AOSpine Knowledge Forum Tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified in 2 cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI), as defined by pathology margin matching Enneking-recommended surgical margins. Prognostic variables were analyzed in reference to local recurrence and survival. RESULTS Between 1987 and 2012, 58 patients (32 female patients) underwent surgical treatment for primary spinal osteosarcoma. Patients were followed for a mean period of 3.5 ± 3.5 years (range 0.5 days to 14.3 years). The median survival for the entire cohort was 6.7 years postoperative. Twenty-four (41%) patients died, and 17 (30%) patients suffered a local recurrence, 10 (59%) of whom died. Twenty-nine (53%) patients underwent EA resection while 26 (47%) patients underwent EI resection with a postoperative median survival of 6.8 and 3.7 years, respectively (p = 0.048). EI patients had a higher rate of local recurrence than EA patients (p = 0.001). Patient age, previous surgery, biopsy type, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. CONCLUSIONS Osteosarcoma of the spine presents a significant challenge, and most patients die in spite of aggressive surgery. There is a significant decrease in recurrence and an increase in survival with en bloc resection (EA) when compared with intralesional resection (EI). The effect of adjuvant and neoadjuvant chemotherapeutics, as well as method of biopsy, requires further exploration.

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.

Introduction Primary spinal osteosarcomas are rare and aggressive neoplasms with poor outcomes. Enneking appropriate, en bloc resection is recommended for appendicular osteosarcomas. Obtaining even marginal margins is technically demanding in the spine, resulting in significant morbidity and possible functional sacrifice. The aim of this study was to identify prognostic variables on local recurrence and mortality, in surgically treated patients diagnosed with a primary osteosarcoma of the spine. Methods A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by the AOSpine knowledge forum tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified according to Enneking principles and analyzed in the following two cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI). EA was defined by the final pathology margin matching the Enneking recommended surgical margin and EI by not matching. Prognostic variables including age, previous spine tumor operation, biopsy type, spine level, tumor size, and chemotherapy timing were analyzed in reference to local recurrence and survival. Results Between 1987 and 2012, 57 patients (31 females and 26 males) underwent surgical treatment for a primary spinal osteosarcoma at a mean age of 36 ± 16 years. Patients were followed for a mean period of 3.4 ± 3.5 years (range, 0.5 days–14.3 years). Median survival for the entire cohort was 6.7 years postoperative. Overall, 24 (42%) patients died and 17 (30%) patients suffered a local recurrence, 10 (59%) of which died. Overall, 28 (52%) patients underwent EA resection while 26 (48%) patients were treated by EI resection. Median survival for patients with EA was 6.8 years postoperative, whereas median survival for EI patients was 3.7 years postoperatively ( p = 0.062). EI patients were at a higher risk of local recurrence than EA patients ( p = 0.002). Patient age, previous spine tumor operation, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. Conclusion Osteosarcoma of the spine presents a significant challenge and most patients die from their disease in spite of aggressive surgery. There is a significant decrease in recurrence with en bloc resection when compared with intralesional resection.