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Daipayan Guha, Benjamin Davidson, Mustafa Nadi, Naif M. Alotaibi, Michael G. Fehlings, Fred Gentili, Taufik A. Valiante, Charles H. Tator, Michael Tymianski, Abhijit Guha and Gelareh Zadeh

OBJECTIVE

A surgical series of 201 benign and malignant peripheral nerve sheath tumors (PNSTs) was assessed to characterize the anatomical and clinical presentation of tumors and identify predictors of neurological outcome, recurrence, and extent of resection.

METHODS

All surgically treated PNSTs from the Division of Neurosurgery at Toronto Western Hospital from 1993 to 2010 were reviewed retrospectively. Data were collected on patient demographics, clinical presentation, surgical technique, extent of resection, postoperative neurological outcomes, and recurrence.

RESULTS

One hundred seventy-five patients with 201 tumors had adequate follow-up for analysis. There were 182 benign and 19 malignant PNSTs. Of the benign lesions, 133 were schwannomas, 21 of which were associated with a diagnosis of schwannomatosis. There were 49 neurofibromas, and 26 were associated with neurofibromatosis Type 1 (NF1). Patients presenting with schwannomas were significantly older than those with neurofibromas. Schwannomas were more readily resected than neurofibromas, with the extent of resection of the former influenced by tumor location. Patients with benign PNSTs typically presented with a painful mass and less frequently with motor deficits. The likelihood of worsened postoperative motor function was decreased in patients with fully resected tumors or preoperative deficits. Recurrence of schwannomas and neurofibromas were seen more frequently in patients diagnosed with NF3 and NF1, respectively. Subtotal resection was associated with the increased recurrence of all benign lesions.

CONCLUSIONS

Outcomes following resection of benign PNSTs depend on tumor histopathology, tumor location, and genetic predisposition syndrome. Gross-total resection should be attempted for benign lesions where possible. The management of malignant PNSTs remains challenging, requiring a multimodal approach.

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Anne L. Versteeg, Nicolas Dea, Stefano Boriani, Peter P. Varga, Alessandro Luzzati, Michael G. Fehlings, Mark H. Bilsky, Laurence D. Rhines, Jeremy J. Reynolds, Mark. B. Dekutoski, Ziya L. Gokaslan, Niccole M. Germscheid and Charles G. Fisher

OBJECTIVE

Osteoblastoma is a rare primary benign bone tumor with a predilection for the spinal column. Although of benign origin, osteoblastomas tend to behave more aggressively clinically than other benign tumors. Because of the low incidence of osteoblastomas, evidence-based treatment guidelines and high-quality research are lacking, which has resulted in inconsistent treatment. The goal of this study was to determine whether application of the Enneking classification in the management of spinal osteoblastomas influences local recurrence and survival time.

METHODS

A multicenter database of patients who underwent surgical intervention for spinal osteoblastoma was developed by the AOSpine Knowledge Forum Tumor. Patient data pertaining to demographics, diagnosis, treatment, cross-sectional survival, and local recurrence were collected. Patients in 2 cohorts, based on the Enneking classification of the tumor (Enneking appropriate [EA] and Enneking inappropriate [EI]), were analyzed. If the final pathology margin matched the Enneking-recommended surgical margin, the tumor was classified as EA; if not, it was classified as EI.

RESULTS

A total of 102 patients diagnosed with a spinal osteoblastoma were identified between November 1991 and June 2012. Twenty-nine patients were omitted from the analysis because of short follow-up time, incomplete survival data, or invalid staging, which left 73 patients for the final analysis. Thirteen (18%) patients suffered a local recurrence, and 6 (8%) patients died during the study period. Local recurrence was strongly associated with mortality (relative risk 9.2; p = 0.008). When adjusted for Enneking appropriateness, this result was not altered significantly. No significant differences were found between the EA and EI groups in regard to local recurrence and mortality.

CONCLUSIONS

In this evaluation of the largest multicenter cohort of spinal osteoblastomas, local recurrence was found to be strongly associated with mortality. Application of the Enneking classification as a treatment guide for preventing local recurrence was not validated.

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Michael P. Kelly, Lawrence G. Lenke, Jakub Godzik, Ferran Pellise, Christopher I. Shaffrey, Justin S. Smith, Stephen J. Lewis, Christopher P. Ames, Leah Y. Carreon, Michael G. Fehlings, Frank Schwab and Adam L. Shimer

OBJECTIVE

The authors conducted a study to compare neurological deficit rates associated with complex adult spinal deformity (ASD) surgery when recorded in retrospective and prospective studies. Retrospective studies may underreport neurological deficits due to selection, detection, and recall biases. Prospective studies are expensive and more difficult to perform, but they likely provide more accurate estimates of new neurological deficit rates.

METHODS

New neurological deficits were recorded in a prospective study of complex ASD surgeries (pSR1) with a defined outcomes measure (decrement in American Spinal Injury Association lower-extremity motor score) for neurological deficits. Using identical inclusion criteria and a subset of participating surgeons, a retrospective study was created (rSR1) and neurological deficit rates were collected. Continuous variables were compared with the Student t-test, with correction for multiple comparisons. Neurological deficit rates were compared using the Mantel-Haenszel method for standardized risks. Statistical significance for the primary outcome measure was p < 0.05.

RESULTS

Overall, 272 patients were enrolled in pSR1 and 207 patients were enrolled in rSR1. Inclusion criteria, defining complex spinal deformities, and exclusion criteria were identical. Sagittal Cobb measurements were higher in pSR1, although sagittal alignment was similar. Preoperative neurological deficit rates were similar in the groups. Three-column osteotomies were more common in pSR1, particularly vertebral column resection. New neurological deficits were more common in pSR1 (pSR1 17.3% [95% CI 12.6–22.2] and rSR1 9.0% [95% CI 5.0–13.0]; p = 0.01). The majority of deficits in both studies were at the nerve root level, and the distribution of level of injury was similar.

CONCLUSIONS

New neurological deficit rates were nearly twice as high in the prospective study than the retrospective study with identical inclusion criteria. These findings validate concerns regarding retrospective cohort studies and confirm the need for and value of carefully designed prospective, observational cohort studies in ASD.

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Ganesh M. Shankar, Michelle J. Clarke, Tamir Ailon, Laurence D. Rhines, Shreyaskumar R. Patel, Arjun Sahgal, Ilya Laufer, Dean Chou, Mark H. Bilsky, Daniel M. Sciubba, Michael G. Fehlings, Charles G. Fisher, Ziya L. Gokaslan and John H. Shin

OBJECTIVE

Primary osteosarcoma of the spine is a rare osseous neoplasm. While previously reported retrospective studies have demonstrated that overall patient survival is impacted mostly by en bloc resection and chemotherapy, the continued management of residual disease remains to be elucidated. This systematic review was designed to address the role of revision surgery and multimodal adjuvant therapy in cases in which en bloc excision is not initially achieved.

METHODS

A systematic literature search spanning the years 1966 to 2015 was performed on PubMed, Medline, EMBASE, and Web of Science to identify reports describing outcomes of patients who underwent biopsy alone, neurological decompression, or intralesional resection for osteosarcoma of the spine. Studies were reviewed qualitatively, and the clinical course of individual patients was aggregated for quantitative meta-analysis.

RESULTS

A total of 16 studies were identified for inclusion in the systematic review, of which 8 case reports were summarized qualitatively. These studies strongly support the role of chemotherapy for overall survival and moderately support adjuvant radiation therapy for local control. The meta-analysis revealed a statistically significant benefit in overall survival for performing revision tumor debulking (p = 0.01) and also for chemotherapy at relapse (p < 0.01). Adjuvant radiation therapy was associated with longer survival, although this did not reach statistical significance (p = 0.06).

CONCLUSIONS

While the initial therapeutic goal in the management of osteosarcoma of the spine is neoadjuvant chemotherapy followed by en bloc marginal resection, this objective is not always achievable given anatomical constraints and other limitations at the time of initial clinical presentation. This systematic review supports the continued aggressive use of revision surgery and multimodal adjuvant therapy when possible to improve outcomes in patients who initially undergo subtotal debulking of osteosarcoma. A limitation of this systematic review is that lesions amenable to subsequent resection or tumors inherently more sensitive to adjuvants would exaggerate a therapeutic effect of these interventions when studied in a retrospective fashion.

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Roland D. Donk, Michael G. Fehlings, Wim I. M. Verhagen, Hisse Arnts, Hans Groenewoud, André L. M. Verbeek and Ronald H. M. A. Bartels

OBJECTIVE

Although there is increasing recognition of the importance of cervical spinal sagittal balance, there is a lack of consensus as to the optimal method to accurately assess the cervical sagittal alignment. Cervical alignment is important for surgical decision making. Sagittal balance of the cervical spine is generally assessed using one of two methods; namely, measuring the angle between C-2 and C-7, and drawing a line between C-2 and C-7. Here, the best method to assess sagittal alignment of the cervical spine is investigated.

METHODS

Data from 138 patients enrolled in a randomized controlled trial (Procon) were analyzed. Two investigators independently measured the angle between C-2 and C-7 by using Harrison's posterior tangent method, and also estimated the shape of the sagittal curve by using a modified Toyama method. The mean angles of each quantitative assessment of the sagittal alignment were calculated and the results were compared. The interrater reliability for both methods was estimated using Cronbach's alpha.

RESULTS

For both methods the interrater reliability was high: for the posterior tangent method it was 0.907 and for the modified Toyama technique it was 0.984. For a lordotic cervical spine, defined by the modified Toyama method, the mean angle (defined by Harrison's posterior tangent method) was 23.4° ± 9.9° (range 0.4°–52.4°), for a kyphotic cervical spine it was −2.2° ± 9.2° (range −16.1° to 16.9°), and for a straight cervical spine it was 10.5° ± 8.2° (range −11° to 36°).

CONCLUSIONS

An absolute measurement of the angle between C-2 and C-7 does not unequivocally define the sagittal cervical alignment. As can be seen from the minimum and maximum values, even a positive angle between C-2 and C-7 could be present in a kyphotic spine. For this purpose, the modified Toyama method (drawing a line from the posterior inferior part of the vertebral body of C-2 to the posterior upper part of the vertebral body of C-7 without any measurements) is a better tool for a global assessment of cervical sagittal alignment.

Clinical trial registration no.: ISRCTN41681847 (https://www.isrctn.com)

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Kristin J. Redmond, Simon S. Lo, Scott G. Soltys, Yoshiya Yamada, Igor J. Barani, Paul D. Brown, Eric L. Chang, Peter C. Gerszten, Samuel T. Chao, Robert J. Amdur, Antonio A. F. De Salles, Matthias Guckenberger, Bin S. Teh, Jason Sheehan, Charles R. Kersh, Michael G. Fehlings, Moon-Jun Sohn, Ung-Kyu Chang, Samuel Ryu, Iris C. Gibbs and Arjun Sahgal

OBJECTIVE

Although postoperative stereotactic body radiation therapy (SBRT) for spinal metastases is increasingly performed, few guidelines exist for this application. The purpose of this study is to develop consensus guidelines to promote safe and effective treatment for patients with spinal metastases.

METHODS

Fifteen radiation oncologists and 5 neurosurgeons, representing 19 centers in 4 countries and having a collective experience of more than 1300 postoperative spine SBRT cases, completed a 19-question survey about postoperative spine SBRT practice. Responses were defined as follows: 1) consensus: selected by ≥ 75% of respondents; 2) predominant: selected by 50% of respondents or more; and 3) controversial: no single response selected by a majority of respondents.

RESULTS

Consensus treatment indications included: radioresistant primary, 1–2 levels of adjacent disease, and previous radiation therapy. Contraindications included: involvement of more than 3 contiguous vertebral bodies, ASIA Grade A status (complete spinal cord injury without preservation of motor or sensory function), and postoperative Bilsky Grade 3 residual (cord compression without any CSF around the cord). For treatment planning, co-registration of the preoperative MRI and postoperative T1-weighted MRI (with or without gadolinium) and delineation of the cord on the T2-weighted MRI (and/or CT myelogram in cases of significant hardware artifact) were predominant. Consensus GTV (gross tumor volume) was the postoperative residual tumor based on MRI. Predominant CTV (clinical tumor volume) practice was to include the postoperative bed defined as the entire extent of preoperative tumor, the relevant anatomical compartment and any residual disease. Consensus was achieved with respect to not including the surgical hardware and incision in the CTV. PTV (planning tumor volume) expansion was controversial, ranging from 0 to 2 mm. The spinal cord avoidance structure was predominantly the true cord. Circumferential treatment of the epidural space and margin for paraspinal extension was controversial. Prescription doses and spinal cord tolerances based on clinical scenario, neurological compromise, and prior overlapping treatments were controversial, but reasonable ranges are presented. Fifty percent of those surveyed practiced an integrated boost to areas of residual tumor and density override for hardware within the beam path. Acceptable PTV coverage was controversial, but consensus was achieved with respect to compromising coverage to meet cord constraint and fractionation to improve coverage while meeting cord constraint.

CONCLUSIONS

The consensus by spinal radiosurgery experts suggests that postoperative SBRT is indicated for radioresistant primary lesions, disease confined to 1–2 vertebral levels, and/or prior overlapping radiotherapy. The GTV is the postoperative residual tumor, and the CTV is the postoperative bed defined as the entire extent of preoperative tumor and anatomical compartment plus residual disease. Hardware and scar do not need to be included in CTV. While predominant agreement was reached about treatment planning and definition of organs at risk, future investigation will be critical in better understanding areas of controversy, including whether circumferential treatment of the epidural space is necessary, management of paraspinal extension, and the optimal dose fractionation schedules.

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Dean Chou, Mark H. Bilsky, Alessandro Luzzati, Charles G. Fisher, Ziya L. Gokaslan, Laurence D. Rhines, Mark B. Dekutoski, Michael G. Fehlings, Ravi Ghag, Peter Varga, Stefano Boriani, Niccole M. Germscheid, Jeremy J. Reynolds and the AOSpine Knowledge Forum Tumor

OBJECTIVE

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft-tissue sarcomas. Resection is the mainstay of treatment and the most important prognostic factor. However, complete resection of spinal MPNSTs with tumor-free margins is challenging due to the likelihood of residual tumor cells. The objective of this study was to describe whether the type of Enneking resection in the management of spinal MPNSTs had an effect on local recurrence and survival.

METHODS

The AOSpine Knowledge Forum Tumor developed a multicenter database that includes demographic, diagnostic, therapeutic, local recurrence, and survival data on patients with primary spinal column tumors. Patients who had undergone surgery for a primary spinal MPNST were included and were analyzed in 2 groups: 1) those undergoing Enneking appropriate (EA) resections and 2) those undergoing Enneking inappropriate (EI) resections. EA surgery was performed if there was histopathological evidence of an intact tumor pseudocapsule and at least a marginal resection on a vital structure. EI surgery was performed if there was an intentional or inadvertent transgression of the margin.

RESULTS

Between 1993 and 2012, 29 primary spine MPNSTs were identified in 12 (41%) females and 17 (59%) males with a mean age at diagnosis of 40 ± 17 years (range 5–74 years). The median patient follow-up was 1.3 years (range 42 days to 11.2 years). In total, 14 (48%) patients died and 14 (48%) patients suffered a local recurrence, 10 (71%) of whom died. Within 2 years after surgery, the median survival and local recurrence were not achieved. Data about Enneking appropriateness of surgery were available for 27 patients; 9 (33%) underwent an EA procedure and 18 (67%) underwent an EI procedure. Enneking appropriateness did not have a significant influence on local recurrence or survival. Twenty-two patients underwent adjuvant treatment with combined chemo- and radiotherapy (n = 7), chemotherapy alone (n = 3), or radiotherapy alone (n = 12). Adjuvant therapy had no significant influence on recurrence or survival.

CONCLUSIONS

The rates of recurrence and survival were similar for spinal MPNSTs regardless of whether patients had an EA or EI resection or received adjuvant therapy. Other factors such as variability of pathologist interpretation, PET CT correlation, or neurofibromatosis Type 1 status may play a role in patient outcome. Nonetheless, MPNSTs should still be treated as sarcomas until further evidence is known. The authors recommend an individualized approach with careful multidisciplinary decision making, and the patient should be informed about the morbidity of en bloc surgery when considering MPNST resection.

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Nardin Samuel, Lindsay Tetreault, Carlo Santaguida, Anick Nater, Nizar Moayeri, Eric M. Massicotte and Michael G. Fehlings

OBJECTIVE

The objective of this study was to identify clinically relevant predictors of progression-free survival and functional outcomes in patients who underwent surgery for intramedullary spinal cord tumors (ISCTs).

METHODS

An institutional spinal tumor registry and billing records were reviewed to identify adult patients who underwent resection of ISCTs between 1993 and 2014. Extensive data were collected from patient charts and operative notes, including demographic information, extent of resection, tumor pathology, and functional and oncological outcomes. Survival analysis was used to determine important predictors of progression-free survival. Logistic regression analysis was used to evaluate the association between an “optimal” functional outcome on the Frankel or McCormick scale at 1-year follow-up and various clinical and surgical characteristics.

RESULTS

The consecutive case series consisted of 63 patients (50.79% female) who underwent resection of ISCTs. The mean age of patients was 41.92 ± 14.36 years (range 17.60–75.40 years). Complete microsurgical resection, defined as no evidence of tumor on initial postoperative imaging, was achieved in 34 cases (54.84%) of the 62 patients for whom this information was available. On univariate analysis, the most significant predictor of progression-free survival was tumor histology (p = 0.0027). Patients with Grade I/II astrocytomas were more likely to have tumor progression than patients with WHO Grade II ependymomas (HR 8.03, 95% CI 2.07–31.11, p = 0.0026) and myxopapillary ependymomas (HR 8.01, 95% CI 1.44–44.34, p = 0.017). Furthermore, patients who underwent radical or subtotal resection were more likely to have tumor progression than those who underwent complete resection (HR 3.46, 95% CI 1.23–9.73, p = 0.018). Multivariate analysis revealed that tumor pathology was the only significant predictor of tumor progression. On univariate analysis, the most significant predictors of an “optimal” outcome on the Frankel scale were age (OR 0.94, 95% CI 0.89–0.98, p = 0.0062), preoperative Frankel grade (OR 4.84, 95% CI 1.33–17.63, p = 0.017), McCormick score (OR 0.22, 95% CI 0.084–0.57, p = 0.0018), and region of spinal cord (cervical vs conus: OR 0.067, 95% CI 0.012–0.38, p = 0.0023; and thoracic vs conus: OR 0.015: 95% CI 0.001–0.20, p = 0.0013). Age, tumor pathology, and region were also important predictors of 1-year McCormick scores.

CONCLUSIONS

Extent of tumor resection and histopathology are significant predictors of progression-free survival following resection of ISCTs. Important predictors of functional outcomes include tumor histology, region of spinal cord in which the tumor is present, age, and preoperative functional status.