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Nicolas Dea, Charles G. Fisher, Jeremy J. Reynolds, Joseph H. Schwab, Laurence D. Rhines, Ziya L. Gokaslan, Chetan Bettegowda, Arjun Sahgal, Áron Lazáry, Alessandro Luzzati, Stefano Boriani, Alessandro Gasbarrini, Ilya Laufer, Raphaële Charest-Morin, Feng Wei, William Teixeira, Niccole M. Germscheid, Francis J. Hornicek, Thomas F. DeLaney, John H. Shin and the AOSpine Knowledge Forum Tumor

OBJECTIVE

The purpose of this study was to investigate the spectrum of current treatment protocols for managing newly diagnosed chordoma of the mobile spine and sacrum.

METHODS

A survey on the treatment of spinal chordoma was distributed electronically to members of the AOSpine Knowledge Forum Tumor, including neurosurgeons, orthopedic surgeons, and radiation oncologists from North America, South America, Europe, Asia, and Australia. Survey participants were pre-identified clinicians from centers with expertise in the treatment of spinal tumors. The suvey responses were analyzed using descriptive statistics.

RESULTS

Thirty-nine of 43 (91%) participants completed the survey. Most (80%) indicated that they favor en bloc resection without preoperative neoadjuvant radiation therapy (RT) when en bloc resection is feasible with acceptable morbidity. The main area of disagreement was with the role of postoperative RT, where 41% preferred giving RT only if positive margins were achieved and 38% preferred giving RT irrespective of margin status. When en bloc resection would result in significant morbidity, 33% preferred planned intralesional resection followed by RT, and 33% preferred giving neoadjuvant RT prior to surgery. In total, 8 treatment protocols were identified: 3 in which en bloc resection is feasible with acceptable morbidity and 5 in which en bloc resection would result in significant morbidity.

CONCLUSIONS

The results confirm that there is treatment variability across centers worldwide for managing newly diagnosed chordoma of the mobile spine and sacrum. This information will be used to design an international prospective cohort study to determine the most appropriate treatment strategy for patients with spinal chordoma.

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Adetokunbo A. Oyelese, Jared Fridley, David B. Choi, Albert Telfeian and Ziya L. Gokaslan

Upper lumbar (L1–2, L2–3) disc herniations are distinct in their diffuse presenting clinical symptomatology and have poorer outcomes with surgical intervention than those following mid and lower lumbar disc herniations and disc surgery. The authors present the cases of 3 patients with L1–2 disc herniations and significant stenosis of the spinal canal. The surgical approach used here combined the principles of transforaminal percutaneous endoscopic discectomy and the extreme lateral lumbar interbody fusion procedures with intraoperative CT-guided navigational assistance. The approach provides a safe corridor of direct visualization to the ventral thecal sac with minimal bony resection and could, in principle, reduce neurological injury and biomechanical instability, which likely contribute to poor outcomes at this level.

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Hannah M. Carl, A. Karim Ahmed, Nancy Abu-Bonsrah, Rafael De la Garza Ramos, Eric W. Sankey, Zachary Pennington, Ali Bydon, Timothy F. Witham, Jean-Paul Wolinsky, Ziya L. Gokaslan, Justin M. Sacks, C. Rory Goodwin and Daniel M. Sciubba

OBJECTIVE

Resection of metastatic spine tumors can improve patients’ quality of life by addressing pain or neurological compromise. However, resections are often complicated by wound dehiscence, infection, instrumentation failures, and the need for reoperation. Moreover, when reoperations are needed, the most common indication is surgical site infection and wound breakdown. In turn, wound reoperations increase morbidity as well as the length and cost of hospitalization. The aim of this study was to examine perioperative risk factors associated with increased rate of wound reoperations after metastatic spine tumor resection.

METHODS

A retrospective study of patients at a single institution who underwent metastatic spine tumor resection between 2003 and 2013 was conducted. Factors with a p value < 0.200 in a univariate analysis were included in the multivariate model.

RESULTS

A total of 159 patients were included in this study. Karnofsky Performance Scale score > 70, smoking status, hypertension, thromboembolic events, hyperlipidemia, increasing number of vertebral levels, and posterior approach were included in the multivariate analysis. Thromboembolic events (95% CI 1.19–48.5, p = 0.032) and number of levels involved were independently associated with increased wound reoperation rates in the multivariate model. For each additional spinal level involved, the risk for wound reoperations increased by 21% (95% CI 1.03–1.43, p = 0.018).

CONCLUSIONS

Although wound complications and subsequent reoperations are potential risks for all patients with metastatic spine tumor, due to adjuvant radiotherapy and other medical comorbidities, this study identified patients with thromboembolic events or those requiring a larger incision as being at the highest risk. Measures intended to decrease the occurrence of perioperative venous thromboembolism and to improve wound care, especially for long incisions, may decrease wound-related revision surgeries in this vulnerable group of patients.

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Mohamed Macki, Rafael De la Garza-Ramos, Ashley A. Murgatroyd, Kenneth P. Mullinix, Xiaolei Sun, Bryan W. Cunningham, Brandon A. McCutcheon, Mohamad Bydon and Ziya L. Gokaslan

OBJECTIVE

Aggressive sacral tumors often require en bloc resection and lumbopelvic reconstruction. Instrumentation failure and pseudarthrosis remain a clinical concern to be addressed. The objective in this study was to compare the biomechanical stability of 3 distinct techniques for sacral reconstruction in vitro.

METHODS

In a human cadaveric model study, 8 intact human lumbopelvic specimens (L2–pelvis) were tested for flexion-extension range of motion (ROM), lateral bending, and axial rotation with a custom-designed 6-df spine simulator as well as axial compression stiffness with the MTS 858 Bionix Test System. Biomechanical testing followed this sequence: 1) intact spine; 2) sacrectomy (no testing); 3) Model 1 (L3–5 transpedicular instrumentation plus spinal rods anchored to iliac screws); 4) Model 2 (addition of transiliac rod); and 5) Model 3 (removal of transiliac rod; addition of 2 spinal rods and 2 S-2 screws). Range of motion was measured at L4–5, L5–S1/cross-link, L5–right ilium, and L5–left ilium.

RESULTS

Flexion-extension ROM of the intact specimen at L4–5 (6.34° ± 2.57°) was significantly greater than in Model 1 (1.54° ± 0.94°), Model 2 (1.51° ± 1.01°), and Model 3 (0.72° ± 0.62°) (p < 0.001). Flexion-extension at both the L5–right ilium (2.95° ± 1.27°) and the L5–left ilium (2.87° ± 1.40°) for Model 3 was significantly less than the other 3 cohorts at the same level (p = 0.005 and p = 0.012, respectively). Compared with the intact condition, all 3 reconstruction groups statistically significantly decreased lateral bending ROM at all measured points. Axial rotation ROM at L4–5 for Model 1 (2.01° ± 1.39°), Model 2 (2.00° ± 1.52°), and Model 3 (1.15° ± 0.80°) was significantly lower than the intact condition (5.02° ± 2.90°) (p < 0.001). Moreover, axial rotation for the intact condition and Model 3 at L5–right ilium (2.64° ± 1.36° and 2.93° ± 1.68°, respectively) and L5–left ilium (2.58° ± 1.43° and 2.93° ± 1.71°, respectively) was significantly lower than for Model 1 and Model 2 at L5–right ilium (5.14° ± 2.48° and 4.95° ± 2.45°, respectively) (p = 0.036) and L5–left ilium (5.19° ± 2.34° and 4.99° ± 2.31°) (p = 0.022). Last, results of the axial compression testing at all measured points were not statistically different among reconstructions.

CONCLUSIONS

The addition of a transverse bar in Model 2 offered no biomechanical advantage. Although the implementation of 4 iliac screws and 4 rods conferred a definitive kinematic advantage in Model 3, that model was associated with significantly restricted lumbopelvic ROM.

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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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Rachel Sarabia-Estrada, Alejandro Ruiz-Valls, Sagar R. Shah, A. Karim Ahmed, Alvaro A. Ordonez, Fausto J. Rodriguez, Hugo Guerrero-Cazares, Ismael Jimenez-Estrada, Esteban Velarde, Betty Tyler, Yuxin Li, Neil A. Phillips, C. Rory Goodwin, Rory J. Petteys, Sanjay K. Jain, Gary L. Gallia, Ziya L. Gokaslan, Alfredo Quinones-Hinojosa and Daniel M. Sciubba

OBJECTIVE

Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat.

METHODS

Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor–engrafted (n = 11), JHC7 tumor–engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E–based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin.

RESULTS

The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma–engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma–engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor–engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats.

CONCLUSIONS

The authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors’ knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.

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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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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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Benjamin D. Elder, Wataru Ishida, C. Rory Goodwin, Ali Bydon, Ziya L. Gokaslan, Daniel M. Sciubba, Jean-Paul Wolinsky and Timothy F. Witham

OBJECTIVE

With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options.

METHODS

A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed.

RESULTS

Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3–9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5–6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02).

CONCLUSIONS

Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.