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Oluwaseun O. Akinduro, Diogo P. Garcia, Dominique M. O. Higgins, Tito Vivas-Buitrago, Mark Jentoft, David A. Solomon, David J. Daniels, Zach Pennington, Wendy J. Sherman, Mychael Delgardo, Mohamad Bydon, Maziyar A. Kalani, George Zanazzi, Nadejda Tsankova, Bernard R. Bendok, Paul C. McCormick, Daniel M. Sciubba, Sheng-fu Larry Lo, Jennifer L. Clarke, Kingsley Abode-Iyamah, and Alfredo Quiñones-Hinojosa

OBJECTIVE

High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic.

METHODS

The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS).

RESULTS

Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19–76) years were included in the analysis. Eighteen patients had H3 K27M mutation–positive tumors, and 12 had H3 K27M mutation–negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation–positive tumors (p = 0.017).

CONCLUSIONS

Although H3 K27M mutant–positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant–positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant–negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.

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Xuguang Chen, Sheng-Fu L. Lo, Chetan Bettegowda, Daniel M. Ryan II, John M. Gross, Chen Hu, Lawrence Kleinberg, Daniel M. Sciubba, and Kristin J. Redmond

OBJECTIVE

Spinal chordoma is locally aggressive and has a high rate of recurrence, even after en bloc resection. Conventionally fractionated adjuvant radiation leads to suboptimal tumor control, and data regarding hypofractionated regimens are limited. The authors hypothesized that neoadjuvant stereotactic body radiotherapy (SBRT) may overcome its intrinsic radioresistance, improve surgical margins, and allow preservation of critical structures during surgery. The purpose of this study is to review the feasibility and early outcomes of high-dose hypofractionated SBRT, with a focus on neoadjuvant SBRT.

METHODS

Electronic medical records of patients with spinal chordoma treated using image-guided SBRT between 2009 and 2019 at a single institution were retrospectively reviewed.

RESULTS

Twenty-eight patients with 30 discrete lesions (24 in the mobile spine) were included. The median follow-up duration was 20.8 months (range 2.3–126.3 months). The median SBRT dose was 40 Gy (range 15–50 Gy) in 5 fractions (range 1–5 fractions). Seventeen patients (74% of those with newly diagnosed lesions) received neoadjuvant SBRT, of whom 15 (88%) underwent planned en bloc resection, all with negative margins. Two patients (12%) developed surgical wound-related complications after neoadjuvant SBRT and surgery, and 4 (two grade 3 and two grade 2) experienced postoperative complications unrelated to the surgical site. Of the remaining patients with newly diagnosed lesions, 5 received adjuvant SBRT for positive or close surgical margins, and 1 received SBRT alone. Seven recurrent lesions were treated with SBRT alone, including 2 after failure of prior conventional radiation. The 2-year overall survival rate was 92% (95% confidence interval [CI] 71%–98%). Patients with newly diagnosed chordoma had longer median survival (not reached) than those with recurrent lesions (27.7 months, p = 0.006). The 2-year local control rate was 96% (95% CI 74%–99%). Among patients with radiotherapy-naïve lesions, no local recurrence was observed with a biologically effective dose ≥ 140 Gy, maximum dose of the planning target volume (PTV) ≥ 47 Gy, mean dose of the PTV ≥ 39 Gy, or minimum dose to 80% of the PTV ≥ 36 Gy (5-fraction equivalent doses). All acute toxicities from SBRT were grade 1–2, and no myelopathy was observed.

CONCLUSIONS

Neoadjuvant high-dose, hypofractionated SBRT for spinal chordoma is safe and does not increase surgical morbidities. Early outcomes at 2 years are promising, although long-term follow-up is pending.

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Zach Pennington, Jeff Ehresman, Andrew Schilling, James Feghali, Andrew M. Hersh, Bethany Hung, Eleni N. Kalivas, Daniel Lubelski, and Daniel M. Sciubba

OBJECTIVE

Patients with spine tumors are at increased risk for both hemorrhage and venous thromboembolism (VTE). Tranexamic acid (TXA) has been advanced as a potential intervention to reduce intraoperative blood loss in this surgical population, but many fear it is associated with increased VTE risk due to the hypercoagulability noted in malignancy. In this study, the authors aimed to 1) develop a clinical calculator for postoperative VTE risk in the population with spine tumors, and 2) investigate the association of intraoperative TXA use and postoperative VTE.

METHODS

A retrospective data set from a comprehensive cancer center was reviewed for adult patients treated for vertebral column tumors. Data were collected on surgery performed, patient demographics and medical comorbidities, VTE prophylaxis measures, and TXA use. TXA use was classified as high-dose (≥ 20 mg/kg) or low-dose (< 20 mg/kg). The primary study outcome was VTE occurrence prior to discharge. Secondary outcomes were deep venous thrombosis (DVT) or pulmonary embolism (PE). Multivariable logistic regression was used to identify independent risk factors for VTE and the resultant model was deployed as a web-based calculator.

RESULTS

Three hundred fifty patients were included. The mean patient age was 57 years, 53% of patients were male, and 67% of surgeries were performed for spinal metastases. TXA use was not associated with increased VTE (14.3% vs 10.1%, p = 0.37). After multivariable analysis, VTE was independently predicted by lower serum albumin (odds ratio [OR] 0.42 per g/dl, 95% confidence interval [CI] 0.23–0.79, p = 0.007), larger mean corpuscular volume (OR 0.91 per fl, 95% CI 0.84–0.99, p = 0.035), and history of prior VTE (OR 2.60, 95% CI 1.53–4.40, p < 0.001). Longer surgery duration approached significance and was included in the final model. Although TXA was not independently associated with the primary outcome of VTE, high-dose TXA use was associated with increased odds of both DVT and PE. The VTE model showed a fair fit of the data with an area under the curve of 0.77.

CONCLUSIONS

In the present cohort of patients treated for vertebral column tumors, TXA was not associated with increased VTE risk, although high-dose TXA (≥ 20 mg/kg) was associated with increased odds of DVT or PE. Additionally, the web-based clinical calculator of VTE risk presented here may prove useful in counseling patients preoperatively about their individualized VTE risk.

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Wuyang Yang, Jordina Rincon-Torroella, James Feghali, Adham M. Khalafallah, Wataru Ishida, Alexander Perdomo-Pantoja, Alfredo Quiñones-Hinojosa, Michael Lim, Gary L. Gallia, Gregory J. Riggins, William S. Anderson, Sheng-Fu Larry Lo, Daniele Rigamonti, Rafael J. Tamargo, Timothy F. Witham, Ali Bydon, Alan R. Cohen, George I. Jallo, Alban Latremoliere, Mark G. Luciano, Debraj Mukherjee, Alessandro Olivi, Lintao Qu, Ziya L. Gokaslan, Daniel M. Sciubba, Betty Tyler, Henry Brem, and Judy Huang

OBJECTIVE

International research fellows have been historically involved in academic neurosurgery in the United States (US). To date, the contribution of international research fellows has been underreported. Herein, the authors aimed to quantify the academic output of international research fellows in the Department of Neurosurgery at The Johns Hopkins University School of Medicine.

METHODS

Research fellows with Doctor of Medicine (MD), Doctor of Philosophy (PhD), or MD/PhD degrees from a non-US institution who worked in the Hopkins Department of Neurosurgery for at least 6 months over the past decade (2010–2020) were included in this study. Publications produced during fellowship, number of citations, and journal impact factors (IFs) were analyzed using ANOVA. A survey was sent to collect information on personal background, demographics, and academic activities.

RESULTS

Sixty-four international research fellows were included, with 42 (65.6%) having MD degrees, 17 (26.6%) having PhD degrees, and 5 (7.8%) having MD/PhD degrees. During an average 27.9 months of fellowship, 460 publications were produced in 136 unique journals, with 8628 citations and a cumulative journal IF of 1665.73. There was no significant difference in total number of publications, first-author publications, and total citations per person among the different degree holders. Persons holding MD/PhDs had a higher number of citations per publication per person (p = 0.027), whereas those with MDs had higher total IFs per person (p = 0.048). Among the 43 (67.2%) survey responders, 34 (79.1%) had nonimmigrant visas at the start of the fellowship, 16 (37.2%) were self-paid or funded by their country of origin, and 35 (81.4%) had mentored at least one US medical student, nonmedical graduate student, or undergraduate student.

CONCLUSIONS

International research fellows at the authors’ institution have contributed significantly to academic neurosurgery. Although they have faced major challenges like maintaining nonimmigrant visas, negotiating cultural/language differences, and managing self-sustainability, their scientific productivity has been substantial. Additionally, the majority of fellows have provided reciprocal mentorship to US students.

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Andrew Hersh, Robert Young, Zach Pennington, Jeff Ehresman, Andy Ding, Srujan Kopparapu, Ethan Cottrill, Daniel M. Sciubba, and Nicholas Theodore

OBJECTIVE

Currently, no consensus exists as to whether patients who develop infection of the surgical site after undergoing instrumented fusion should have their implants removed at the time of wound debridement. Instrumentation removal may eliminate a potential infection nidus, but removal may also destabilize the patient’s spine. The authors sought to summarize the existing evidence by systematically reviewing published studies that compare outcomes between patients undergoing wound washout and instrumentation removal with outcomes of patients undergoing wound washout alone. The primary objectives were to determine 1) whether instrumentation removal from an infected wound facilitates infection clearance and lowers morbidity, and 2) whether the chronicity of the underlying infection affects the decision to remove instrumentation.

METHODS

PRISMA guidelines were used to review the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov databases to identify studies that compared patients with implants removed and patients with implants retained. Outcomes of interest included mortality, rate of repeat wound washout, and loss of correction.

RESULTS

Fifteen articles were included. Of 878 patients examined in these studies, 292 (33%) had instrumentation removed. Patient populations were highly heterogeneous, and outcome data were limited. Available data suggested that rates of reoperation, pseudarthrosis, and death were higher in patients who underwent instrumentation removal at the time of initial washout. Three studies recommended that instrumentation be uniformly removed at the time of wound washout. Five studies favored retaining the original instrumentation. Six studies favored retention in early infections but removal in late infections.

CONCLUSIONS

The data on this topic remain heterogeneous and low in quality. Retention may be preferred in the setting of early infection, when the risk of underlying spine instability is still high and the risk of mature biofilm formation on the implants is low. However, late infections likely favor instrumentation removal. Higher-quality evidence from large, multicenter, prospective studies is needed to reach generalizable conclusions capable of guiding clinical practice.

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Adham M. Khalafallah, Adrian E. Jimenez, Nathan A. Shlobin, Collin J. Larkin, Debraj Mukherjee, Corinna C. Zygourakis, Sheng-Fu Lo, Daniel M. Sciubba, Ali Bydon, Timothy F. Witham, Nader S. Dahdaleh, and Nicholas Theodore

OBJECTIVE

Although fellowship training is becoming increasingly common in neurosurgery, it is unclear which factors predict an academic career trajectory among spinal neurosurgeons. In this study, the authors sought to identify predictors associated with academic career placement among fellowship-trained neurological spinal surgeons.

METHODS

Demographic data and bibliometric information on neurosurgeons who completed a residency program accredited by the Accreditation Council for Graduate Medical Education between 1983 and 2019 were gathered, and those who completed a spine fellowship were identified. Employment was denoted as academic if the hospital where a neurosurgeon worked was affiliated with a neurosurgical residency program; all other positions were denoted as nonacademic. A logistic regression model was used for multivariate statistical analysis.

RESULTS

A total of 376 fellowship-trained spinal neurosurgeons were identified, of whom 140 (37.2%) held academic positions. The top 5 programs that graduated the most fellows in the cohort were Cleveland Clinic, The Johns Hopkins Hospital, University of Miami, Barrow Neurological Institute, and Northwestern University. On multivariate analysis, increased protected research time during residency (OR 1.03, p = 0.044), a higher h-index during residency (OR 1.12, p < 0.001), completing more than one clinical fellowship (OR 2.16, p = 0.024), and attending any of the top 5 programs that graduated the most fellows (OR 2.01, p = 0.0069) were independently associated with an academic career trajectory.

CONCLUSIONS

Increased protected research time during residency, a higher h-index during residency, completing more than one clinical fellowship, and attending one of the 5 programs graduating the most fellowship-trained neurosurgical spinal surgeons independently predicted an academic career. These results may be useful in identifying and advising trainees interested in academic spine neurosurgery.

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Adham M. Khalafallah, Adrian E. Jimenez, Nathan A. Shlobin, Collin J. Larkin, Debraj Mukherjee, Corinna C. Zygourakis, Sheng-Fu Lo, Daniel M. Sciubba, Ali Bydon, Timothy F. Witham, Nader S. Dahdaleh, and Nicholas Theodore

OBJECTIVE

Although fellowship training is becoming increasingly common in neurosurgery, it is unclear which factors predict an academic career trajectory among spinal neurosurgeons. In this study, the authors sought to identify predictors associated with academic career placement among fellowship-trained neurological spinal surgeons.

METHODS

Demographic data and bibliometric information on neurosurgeons who completed a residency program accredited by the Accreditation Council for Graduate Medical Education between 1983 and 2019 were gathered, and those who completed a spine fellowship were identified. Employment was denoted as academic if the hospital where a neurosurgeon worked was affiliated with a neurosurgical residency program; all other positions were denoted as nonacademic. A logistic regression model was used for multivariate statistical analysis.

RESULTS

A total of 376 fellowship-trained spinal neurosurgeons were identified, of whom 140 (37.2%) held academic positions. The top 5 programs that graduated the most fellows in the cohort were Cleveland Clinic, The Johns Hopkins Hospital, University of Miami, Barrow Neurological Institute, and Northwestern University. On multivariate analysis, increased protected research time during residency (OR 1.03, p = 0.044), a higher h-index during residency (OR 1.12, p < 0.001), completing more than one clinical fellowship (OR 2.16, p = 0.024), and attending any of the top 5 programs that graduated the most fellows (OR 2.01, p = 0.0069) were independently associated with an academic career trajectory.

CONCLUSIONS

Increased protected research time during residency, a higher h-index during residency, completing more than one clinical fellowship, and attending one of the 5 programs graduating the most fellowship-trained neurosurgical spinal surgeons independently predicted an academic career. These results may be useful in identifying and advising trainees interested in academic spine neurosurgery.

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Charlotte Dandurand, Charles G. Fisher, Laurence D. Rhines, Stefano Boriani, Raphaële Charest-Morin, Alessandro Gasbarrini, Alessandro Luzzati, Jeremy J. Reynolds, Feng Wei, Ziya L. Gokaslan, Chetan Bettegowda, Daniel M. Sciubba, Aron Lazary, Norio Kawahara, Michelle J. Clarke, Y. Raja Rampersaud, Alexander C. Disch, Dean Chou, John H. Shin, Francis J. Hornicek, IIya Laufer, Arjun Sahgal, and Nicolas Dea

OBJECTIVE

Oncological resection of primary spine tumors is associated with lower recurrence rates. However, even in the most experienced hands, the execution of a meticulously drafted plan sometimes fails. The objectives of this study were to determine how successful surgical teams are at achieving planned surgical margins and how successful surgeons are in intraoperatively assessing tumor margins. The secondary objective was to identify factors associated with successful execution of planned resection.

METHODS

The Primary Tumor Research and Outcomes Network (PTRON) is a multicenter international prospective registry for the management of primary tumors of the spine. Using this registry, the authors compared 1) the planned surgical margin and 2) the intraoperative assessment of the margin by the surgeon with the postoperative assessment of the margin by the pathologist. Univariate analysis was used to assess whether factors such as histology, size, location, previous radiotherapy, and revision surgery were associated with successful execution of the planned margins.

RESULTS

Three hundred patients were included. The surgical plan was successfully achieved in 224 (74.7%) patients. The surgeon correctly assessed the intraoperative margins, as reported in the final assessment by the pathologist, in 239 (79.7%) patients. On univariate analysis, no factor had a statistically significant influence on successful achievement of planned margins.

CONCLUSIONS

In high-volume cancer centers around the world, planned surgical margins can be achieved in approximately 75% of cases. The morbidity of the proposed intervention must be balanced with the expected success rate in order to optimize patient management and surgical decision-making.

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Rafael De la Garza Ramos, Christine Park, Edwin McCray, Meghan Price, Timothy Y. Wang, Tara Dalton, César Baëta, Melissa M. Erickson, Norah Foster, Zach Pennington, John H. Shin, Daniel M. Sciubba, Khoi D. Than, Isaac O. Karikari, Christopher I. Shaffrey, Muhammad M. Abd-El-Barr, Reza Yassari, and C. Rory Goodwin

OBJECTIVE

In patients with metastatic spinal disease (MSD), interhospital transfer can potentially impact clinical outcomes as the possible benefits of transferring a patient to a higher level of care must be weighed against the negative effects associated with potential delays in treatment. While the association of clinical outcomes and transfer status has been examined in other specialties, the relationship between transfer status, complications, and risk of mortality in patients with MSD has yet to be explored. The purpose of this study was to examine the impact of transfer status on in-hospital mortality and clinical outcomes in patients diagnosed with MSD.

METHODS

The National (Nationwide) Inpatient Sample (NIS) database was retrospectively queried for adult patients diagnosed with vertebral pathological fracture and/or spinal cord compression in the setting of metastatic disease between 2012 and 2014. Demographics, baseline characteristics (e.g., metastatic spinal cord compression [MSCC] and paralysis), comorbidities, type of intervention, and relevant patient outcomes were controlled in a multivariable logistic regression model to analyze the association of transfer status with patient outcomes.

RESULTS

Within the 10,360 patients meeting the inclusion and exclusion criteria, higher rates of MSCC (50.2% vs 35.9%, p < 0.001) and paralysis (17.3% vs 8.4%, p < 0.001) were observed in patients transferred between hospitals compared to those directly admitted. In univariable analysis, a higher percentage of transferred patients underwent surgical intervention (p < 0.001) when compared with directly admitted patients. After controlling for significant covariates and surgical intervention, transferred patients were more likely to develop in-hospital complications (OR 1.34, 95% CI 1.18–1.52, p < 0.001), experience prolonged length of stay (OR 1.33, 95% CI 1.16–1.52, p < 0.001), and have a discharge disposition other than home (OR 1.70, 95% CI 1.46–1.98, p < 0.001), with no significant difference in inpatient mortality rates.

CONCLUSIONS

Patients with MSD who were transferred between hospitals demonstrated more severe clinical presentations and higher rates of inpatient complications compared to directly admitted patients, despite demonstrating no difference in in-hospital mortality rates.

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Zach Pennington, Jeff Ehresman, Aladine A. Elsamadicy, John H. Shin, C. Rory Goodwin, Joseph H. Schwab, and Daniel M. Sciubba

OBJECTIVE

Long-term local control in patients with primary chordoma and sarcoma of the spine and sacrum is increasingly reliant upon en bloc resection with negative margins. At many institutions, adjuvant radiation is recommended; definitive radiation is also recommended for the treatment of unresectable tumors. Because of the high off-target radiation toxicities associated with conventional radiotherapy, there has been growing interest in the use of proton and heavy-ion therapies. The aim of this study was to systematically review the literature regarding these therapies.

METHODS

The PubMed, OVID, Embase, and Web of Science databases were queried for articles describing the use of proton, combined proton/photon, or heavy-ion therapies for adjuvant or definitive radiotherapy in patients with primary sarcoma or chordoma of the mobile spine and sacrum. A qualitative synthesis of the results was performed, focusing on overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS); local control; and postradiation toxicities.

RESULTS

Of 595 unique articles, 64 underwent full-text screening and 38 were included in the final synthesis. All studies were level III or IV evidence with a high risk of bias; there was also significant overlap in the reported populations, with six centers accounting for roughly three-fourths of all reports. Five-year therapy outcomes were as follows: proton-only therapies, OS 67%–82%, PFS 31%–57%, and DFS 52%–62%; metastases occurred in 17%–18% and acute toxicities in 3%–100% of cases; combined proton/photon therapy, local control 62%–85%, OS 78%–87%, PFS 90%, and DFS 61%–72%; metastases occurred in 12%–14% and acute toxicities in 84%–100% of cases; and carbon ion therapy, local control 53%–100%, OS 52%–86%, PFS (only reported for 3 years) 48%–76%, and DFS 50%–53%; metastases occurred in 2%–39% and acute toxicities in 26%–48%. There were no studies directly comparing outcomes between photon and charged-particle therapies or comparing outcomes between radiation and surgical groups.

CONCLUSIONS

The current evidence for charged-particle therapies in the management of sarcomas of the spine and sacrum is limited. Preliminary evidence suggests that with these therapies local control and OS at 5 years are comparable among various charged-particle options and may be similar between those treated with definitive charged-particle therapy and historical surgical cohorts. Further research directly comparing charged-particle and photon-based therapies is necessary.