Publications by authors named "Peter Pal Varga"

45 Publications

A novel three-dimensional volumetric method to measure indirect decompression after percutaneous cement discoplasty.

J Orthop Translat 2021 May 1;28:131-139. Epub 2021 Apr 1.

Department of Spine Surgery, Semmelweis University, Budapest, Hungary.

Purpose: Percutaneous cement discoplasty (PCD) is a minimally invasive surgical option to treat patients who suffer from the consequences of advanced disc degeneration. As the current two-dimensional methods can inappropriately measure the difference in the complex 3D anatomy of the spinal segment, our aim was to develop and apply a volumetric method to measure the geometrical change in the surgically treated segments.

Methods: Prospective clinical and radiological data of 10 patients who underwent single- or multilevel PCD was collected. Pre- and postoperative CT scan-based 3D reconstructions were performed. The injected PMMA (Polymethylmethacrylate) induced lifting of the cranial vertebra and the following volumetric change was measured by subtraction of the geometry of the spinal canal from a pre- and postoperatively predefined cylinder. The associations of the PMMA geometry and the volumetric change of the spinal canal with clinical outcome were determined.

Results: Change in the spinal canal volume (ΔV) due to the surgery proved to be significant (mean ΔV = 2266.5 ± 1172.2 mm, n = 16; p = 0.0004). A significant, positive correlation was found between ΔV, the volume and the surface of the injected PMMA. A strong, significant association between pain intensity (low back and leg pain) and the magnitude of the volumetric increase of the spinal canal was shown (ρ = 0.772, p = 0.009 for LBP and ρ = 0.693, p = 0.026 for LP).

Conclusion: The developed method is accurate, reproducible and applicable for the analysis of any other spinal surgical method. The volume and surface area of the injected PMMA have a predictive power on the extent of the indirect spinal canal decompression. The larger the ΔV the higher clinical benefit was achieved with the PCD procedure.

The Translational Potential Of This Article: The developed method has the potential to be integrated into clinical software's to evaluate the efficacy of different surgical procedures based on indirect decompression effect such as PCD, anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), oblique lumbar interbody fusion (OLIF), extreme lateral interbody fusion (XLIF). The intraoperative use of the method will allow the surgeon to respond if the decompression does not reach the desired level.
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http://dx.doi.org/10.1016/j.jot.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050383PMC
May 2021

Development of a Computer-Aided Design and Finite Element Analysis Combined Method for Affordable Spine Surgical Navigation With 3D-Printed Customized Template.

Front Surg 2020 25;7:583386. Epub 2021 Jan 25.

National Center for Spinal Disorders, Buda Health Center, Budapest, Hungary.

Revision surgery of a previous lumbosacral non-union is highly challenging, especially in case of complications, such as a broken screw at the first sacral level (S1). Here, we propose the implementation of a new method based on the CT scan of a clinical case using 3D reconstruction, combined with finite element analysis (FEA), computer-assisted design (CAD), and 3D-printing technology to provide accurate surgical navigation to aid the surgeon in performing the optimal surgical technique by inserting a pedicle screw at the S1 level. A step-by-step approach was developed and performed as follows: (1) Quantitative CT based patient-specific FE model of the sacrum was created. (2) The CAD model of the pedicle screw was inserted into the sacrum model in a bicortical convergent and a monocortical divergent position, by overcoming the geometrical difficulty caused by the broken screw. (3) Static FEAs (Abaqus, Dassault Systemes) were performed using 500 N tensile load applied to the screw head. (4) A template with two screw guiding structures for the sacrum was designed and manufactured using CAD design and 3D-printing technologies, and investment casting. (5) The proposed surgical technique was performed on the patient-specific physical model created with the FDM printing technology. The patient-specific model was CT scanned and a comparison with the virtual plan was performed to evaluate the template accuracy FEA results proved that the modified bicortical convergent insertion is stiffer (6,617.23 N/mm) compared to monocortical divergent placement (2,989.07 N/mm). The final template was created via investment casting from cobalt-chrome. The template design concept was shown to be accurate (grade A, Gertzbein-Robbins scale) based on the comparison of the simulated surgery using the patient-specific physical model and the 3D virtual surgical plan. Compared to the conventional surgical navigation techniques, the presented method allows the consideration of the patient-specific biomechanical parameters; is more affordable, and the intraoperative X-ray exposure can be reduced. This new patient- and condition-specific approach may be widely used in revision spine surgeries or in challenging primary cases after its further clinical validation.
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http://dx.doi.org/10.3389/fsurg.2020.583386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873739PMC
January 2021

Global Treatment Outcome after Surgical Site Infection in Elective Degenerative Lumbar Spinal Operations.

Surg Infect (Larchmt) 2021 Mar 23;22(2):193-199. Epub 2020 Apr 23.

National Center for Spinal Disorders, Buda Health Center, Budapest, Hungary.

Surgical site infection (SSI) is a serious complication after routine lumbar spinal operations, and its effect on global treatment outcome (GTO) is less reported. The aim of the current study was to measure the impact of SSI on outcome, which was evaluated with patient reported outcome measures (PROMs) and patients' subjective judgment (GTO). A total of 910 patients underwent primary a single- or two-level lumbar decompression or instrumented fusion surgical procedure. Patients completed Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Core Outcome Measurement Index (COMI) at baseline and at two-year follow-up. The rate of improvement in PROMs was measured for the total cohort and the group of patients with SSI. Patients evaluated GTO on a five-point Likert scale. This study was approved by the Scientific and Research Ethics Committee of the Medical Research Council (number: 29970-3/2015/EKU) and the Institutional Review Board. Regardless of the presence of SSI, significant improvement was measured in all PROMs without any difference in the rate of change between the clinical subgroups (non-SSI vs. SSI, dODI: p = 0.370, dCOMI: p = 0.383, dVAS: p = 0.793). In the total cohort, 87.3% of patients reported good outcome (N% = 87.3%). After an SSI, however, more patients (25.7%) reported poor outcome compared with those without the complication (chi-square test: value = 5.66; df = 1; p = 0.017; odds ratio = 2.49). Patients with successfully treated SSI can expect as good objective clinical result as patients without SSI while the subjective treatment outcome can be worse. The GTO could also be improved in complicated cases, however, with more extensive peri-operative patient education and information considering the patients' expectations, too.
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http://dx.doi.org/10.1089/sur.2019.344DOI Listing
March 2021

Correction to: Association of vitamin D receptor gene polymorphisms with disc degeneration.

Eur Spine J 2020 Mar;29(3):648

National Center for Spinal Disorders, Kiralyhago Street 1, Budapest, 1126, Hungary.

Unfortunately, the following reference was missed out in the original publication.
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http://dx.doi.org/10.1007/s00586-019-06284-8DOI Listing
March 2020

Geometrical accuracy evaluation of an affordable 3D printing technology for spine physical models.

J Clin Neurosci 2020 Feb 3;72:438-446. Epub 2020 Jan 3.

National Center for Spinal Disorders, Királyhágó u. 1-3, H-1126 Budapest, Hungary.

Objective: The aim of the study is to develop a workflow to establish geometrical quality criteria for 3D printed anatomical models as a guidance for selecting the most suitable 3D printing technologies available in a clinical environment.

Methods: We defined the 3D geometry of a 25-year-old male patient's L4 vertebra and the geometry was then printed using two technologies, which differ in printing resolution and affordability: Fused Deposition Modelling (FDM) and Digital Light Processing (DLP). In order to measure geometrical accuracy, the 3D scans of two physical models were compared to the virtual input model. To compare surface qualities of these printing technologies we determined surface roughness for two regions of interest. Finally, we present our experience in the clinical application of a physical model in a congenital deformity case.

Results: The analysis of the distribution of the modified Hausdorff distance values along the vertebral surface meshes (99% of values <1 mm) of the 3D printed models provides evidence for high printing accuracy in both printing techniques. Our results demonstrate that the surface qualities, measured by roughness are adequate (~99% of values <0.1 mm) for both physical models. Finally, we implemented the FDM physical model for surgical planning.

Conclusion: We present a workflow capable of determining the quality of 3D printed models and the application of a high quality and affordable 3D printed spine physical model in the pre operative planning. As a result of the visual guidance provided by the physical model, we were able to define the optimal trajectory of the screw insertion during surgery.
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http://dx.doi.org/10.1016/j.jocn.2019.12.027DOI Listing
February 2020

Association of vitamin D receptor gene polymorphisms with disc degeneration.

Eur Spine J 2020 03 25;29(3):596-604. Epub 2019 Nov 25.

National Center for Spinal Disorders, Kiralyhago Street 1, Budapest, 1126, Hungary.

Purpose: Numerous candidate genes and single-nucleotide polymorphisms (SNPs) have been identified in the background of lumbar disc degeneration (LDD). However, in most of these underpowered studies, definitions of LDD are inconsistent; moreover, many of the findings have not been replicated and are contradictory. Our aim was to characterize LDD by well-defined phenotypes and possible endophenotypes and analyse the association between these and candidate vitamin D receptor (VDR) gene polymorphisms on a large (N = 1426) dataset.

Methods: Seven candidate VDR SNPs were genotyped. Individual association, haplotype and gene-gene interaction analyses were performed. All degenerative endophenotypes were significantly associated with one or more candidate VDR gene variants.

Results: Haplotype analyses confirmed the association between the 3'-end VDR variants (BsmI, ApaI, TaqI) and Modic changes as well as the relationship of 5'-end variants (Cdx2, A1012G) with endplate defects. We also found significant interactions between the 3'- and 5'-end regulatory regions and endplate defects. Based on our results, VDR and its gene variants are highly associated with specific degenerative LDD endophenotypes.

Conclusion: Understanding relationships between phenotype and gene variants is crucial for describing the pathways leading to the multifactorial, polygenic degeneration process and LDD-related conditions. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-019-06215-7DOI Listing
March 2020

Attitude of spine surgeons towards the application of 3D technologies - a survey of AOSpine members.

Ideggyogy Sz 2019 Jul;72(7-8):227-235

National Center for Spinal Disorders, Budapest.

Background And Purpose: 3D technologies (3D virtual and physical model, 3D printing, computer aided engineering, finite element analysis based simulations) play an important role in personalized spine surgery. Objective - In collaboration with AOSpine a global, online survey-based study was performed in order to determine the acceptance rate and the factors which stand against the wider spread of 3D technologies.

Methods: A survey containing 21 questions was developed and divided into five pages, every page corresponding to one chapter. Our analysis is based on the responses of 282 spine surgeons from 57 countries. To interpret our results in a global context, we used the Human Development Index of the respondent's countries in comparisons.

Results: Significant difference between the AOSpine regions (p ≤ 0.05) was found, with the highest acceptance in Asia-Pacific region. There was no significant difference in acceptance score according to the field of spine surgery, or the surgical experience in years (p=0.77, and p=0.19). In the case of public practice, we found significantly higher acceptance compared to private and mixed (public and private) surgical practice (p ≤ 0.05). The acceptance of the technology varied based on the respondent's resident country's Human Development Index and was significantly different between "Medium" vs "Very high" (p = 0.0005) and "High" vs "Very high" (p=0.019) category. Significant positive correlation was found between the acceptance score and the HDI score (Spearman test, ρ = 0.37, p = 0.007). The main limitation factor was identified as the lack of information.

Conclusion: There is high interest among spine surgeons towards the incorporation of 3D technologies into the clinical practice. Education, the healthcare system, and the economic environment plays a major role in acceptance. Our results provide the basis of a strategy to promote the application of 3D technologies.
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http://dx.doi.org/10.18071/isz.72.0227DOI Listing
July 2019

Clinical presentation, management and outcomes of sacral metastases: a multicenter, retrospective cohort study.

Ann Transl Med 2019 May;7(10):214

Department of Orthopaedics, Division of Spine, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada.

Background: Sacral metastases are rare and literature regarding their management is sparse. This multicenter, prospective, observational study aimed to determine health related-quality of life (HRQOL) and pain in patients treated for sacral metastases with surgery and/or radiation therapy (RT). The secondary objectives were to describe the adverse event (AE) profile and change in neurologic function in this population.

Methods: Twenty-three patients presenting with symptomatic sacral metastases were identified from the Epidemiology, Process and Outcomes of Spine Oncology (EPOSO) dataset, a prospective multicenter study on spinal metastases. Patients requiring surgery and/or RT between August 2013 and February 2017 were prospectively enrolled. HRQOL, assessed by the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQv2.0), the Short Form-36 version 2 (SF-36v2), and the EuroQol-5Dimension (EQ-5D) was documented at baseline, 6 weeks, 3 and 6 months post-treatment. Pain numeric rating scale (NRS), AEs, lower extremities motor score (ASIA), and bowel and bladder function were also recorded.

Results: Eight patients underwent surgery ± RT and 15 patients underwent RT alone. Mean age was 59.3 (SD 11.7) years and 13 patients were female. At 6 months, 3 (37.5%) surgical patients and 2 (13.3%) RT patients were deceased. There was a trend showing that surgical patients had worse baseline HRQOL and pain. Pain NRS, EQ-5D, SOSGOQv2.0, and the mental component of the SF-36v2 showed improvement, irrespective of treatment (P>0.05). Ten AEs occurred in the surgical cohort, dominated by wound complications (n=3). Bowel and bladder function improved at 6 weeks in both groups.

Conclusions: Surgical treatment and RT are both valid treatment options for symptomatic sacral metastases. Improvement in HRQOL can be expected with an acceptable AE rate.
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http://dx.doi.org/10.21037/atm.2019.04.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595205PMC
May 2019

Indirect foraminal decompression and improvement in the lumbar alignment after percutaneous cement discoplasty.

Eur Spine J 2019 06 20;28(6):1441-1447. Epub 2019 Apr 20.

National Center for Spinal Disorders, Buda Health Center, Királyhágó St. 1-3, Budapest, 1126, Hungary.

Purpose: Percutaneous cement discoplasty (PCD) is a minimally invasive surgical procedure, that can provide a segmental stabilizing and indirect decompression effect in case of severely degenerated discs characterized by vacuum phenomenon. The objective of this study was to evaluate the effects of PCD on spinopelvic radiological parameters and their associations with the clinical outcome.

Methods: Retrospective analysis of prospectively collected dataset of 28 patients (112 lumbar segments) who underwent single- or multilevel PCD was performed. Spinopelvic, intrasegmental and intersegmental parameters were measured on lumbar X-rays pre-, postoperatively and 6 months after the surgery. Correlations between radiological parameters and clinical outcome data were determined.

Results: Sacral slope significantly increased (p < .001), and pelvic tilt (p < .05) was decreased after the PCD procedure. Segmental and total lordosis (p < .05, p < .05) disc and foraminal height showed significantly increase (p < .001, p < .001) after procedure. Pain and disability (ODI) significantly decreased due to PCD. An association was found between postoperative increase in SS and improvement in ODI (r = 0.39, p < .05). The change in low back pain was correlated with segmental scoliosis correction (p < .001). Moderate correlation was detected between the increase in disc height and ODI (p < .05) as well as leg pain (p < .01).

Conclusion: PCD is an effective minimally invasive technique to treat axial pain and disability related to severe lumbar disc degeneration. Our study shows that an improvement in lumbar alignment and a significant indirect foraminal decompression could be achieved with the procedure. These changes can significantly contribute to the pain relief and increase in the patients' functional capacity. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-019-05966-7DOI Listing
June 2019

Prognostic significance of human telomerase reverse transcriptase promoter region mutations C228T and C250T for overall survival in spinal chordomas.

Neuro Oncol 2019 08;21(8):1005-1015

Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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.
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http://dx.doi.org/10.1093/neuonc/noz066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682209PMC
August 2019

Survival, local control, and health-related quality of life in patients with oligometastatic and polymetastatic spinal tumors: A multicenter, international study.

Cancer 2019 03 29;125(5):770-778. Epub 2018 Nov 29.

Research Department, AOSpine International, Davos, Switzerland.

Background: The treatment of oligometastatic (≤5 metastases) spinal disease has trended toward ablative therapies, yet to the authors' knowledge little is known regarding the prognosis of patients presenting with oligometastatic spinal disease and the value of this approach. The objective of the current study was to compare the survival and clinical outcomes of patients with cancer with oligometastatic spinal disease with those of patients with polymetastatic (>5 metastases) disease.

Methods: The current study was an international, multicenter, prospective study. Patients who were admitted to a participating spine center with a diagnosis of spinal metastases and who underwent surgical intervention and/or radiotherapy between August 2013 and May 2017 were included. Data collected included demographics, overall survival, local control, and treatment information including surgical, radiotherapy, and systemic therapy details. Health-related quality of life (HRQOL) measures included the EuroQOL 5 dimensions 3-level questionnaire (EQ-5D-3L), the 36-Item Short Form Health Survey (SF-36v2), and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ).

Results: Of the 393 patients included in the current study, 215 presented with oligometastatic disease and 178 presented with polymetastatic disease. A significant survival advantage of 90.1% versus 77.3% at 3 months and 77.0% versus 65.1% at 6 months from the time of treatment was found for patients presenting with oligometastatic disease compared with those with polymetastatic disease. It is important to note that both groups experienced significant improvements in multiple HRQOL measures at 6 months after treatment, with no differences in these outcome measures noted between the 2 groups.

Conclusions: The treatment of oligometastatic disease appears to offer a significant survival advantage compared with polymetastatic disease, regardless of treatment choice. HRQOL measures were found to improve in both groups, demonstrating a palliative benefit for all treated patients.
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http://dx.doi.org/10.1002/cncr.31870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020734PMC
March 2019

Risk factors of non-specific spinal pain in childhood.

Eur Spine J 2018 05 15;27(5):1119-1126. Epub 2018 Feb 15.

National Center for Spinal Disorders, Kiralyhago u. 1-3, Budapest, 1126, Hungary.

Purpose: Non-specific spinal pain can occur at all ages and current evidence suggests that pediatric non-specific spinal pain is predictive for adult spinal conditions. A 5-year long, prospective cohort study was conducted to identify the lifestyle and environmental factors leading to non-specific spinal pain in childhood.

Materials And Methods: Data were collected from school children aged 7-16 years, who were randomly selected from three different geographic regions in Hungary. The risk factors were measured with a newly developed patient-reported questionnaire (PRQ). The quality of the instrument was assessed by the reliability with the test-retest method. Test (N = 952) and validity (N = 897) datasets were randomly formed. Risk factors were identified with uni- and multivariate logistic regression models and the predictive performance of the final model was evaluated using the receiver operating characteristic (ROC) method.

Results: The final model was built up by seven risk factors for spinal pain for days; age > 12 years, learning or watching TV for more than 2 h/day, uncomfortable school-desk, sleeping problems, general discomfort and positive familiar medical history (χ = 101.07; df = 8; p < 0.001). The probabilistic performance was confirmed with ROC analysis on the test and validation cohorts (AUC = 0.76; 0.71). A simplified risk scoring system showed increasing possibility for non-specific spinal pain depending on the number of the identified risk factors (χ = 65.0; df = 4; p < 0.001).

Conclusion: Seven significant risk factors of non-specific spinal pain in childhood were identified using the new, easy to use and reliable PRQ which makes it possible to stratify the children according to their individual risk. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-018-5516-1DOI Listing
May 2018

[Change of paradigm in the surgical treatment of metastatic diseases of the bone. Part II. Treatment of spinal metastases].

Orv Hetil 2018 Feb;159(8):297-302

Országos Gerincgyógyászati Központ Budapest, Királyhágó u. 1-3., 1126.

The incidence of spinal metastases is constantly growing, but due to the advancements in oncologic treatment methods, the survival and the quality of life of the patients are persistently improving. Choosing the optimal treatment method is essential, and several factors should be considered: type of the primary tumor, segmental stability, the symptoms caused by the metastasis and the general condition of the patient. Using modern radiotherapeutic methods combined with minimally invasive surgical techniques (minimally invasive stabilization, separation surgery) in the majority of patients permits adequate local control with low complication rate. In our review, we describe the state-of-the-art, modern spinal metastasis treatment options based on the recently published evidence. Orv Hetil. 2018; 159(8): 297-302.
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http://dx.doi.org/10.1556/650.2018.30930DOI Listing
February 2018

Psychometric evaluation and adaptation of the Spine Oncology Study Group Outcomes Questionnaire to evaluate health-related quality of life in patients with spinal metastases.

Cancer 2018 04 6;124(8):1828-1838. Epub 2018 Feb 6.

Research Department, AOSpine International, Davos, Switzerland.

Background: The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ) was developed as the first spine oncology-specific health-related quality of life (HRQOL) measure. This study evaluated the psychometric properties and clinical validity of the SOSGOQ in a diverse cohort of patients with spinal metastases.

Methods: An international, multicenter, prospective observational cohort study including patients with spinal metastases who underwent surgery and/or radiotherapy was conducted by the AOSpine Knowledge Forum Tumor. Demographic, tumor, and treatment data were collected. HRQOL was evaluated using the SOSGOQ and Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) at baseline and fixed follow-up times. Construct validity was assessed using multitrait scaling analyses, confirmatory factor analyses, and correlation with the SF-36 and NRS pain score. Test-retest reliability was assessed in a subgroup of patients between 12 weeks after treatment and the retest 4 to 9 days later.

Results: A total of 238 patients were enrolled at 9 centers across North America; 153 of these patients had HRQOL data available at 12 weeks after treatment. Multitrait scaling analyses and confirmatory factor analyses resulted in a refined version of the SOSGOQ with 4 domains and 4 single items. The revised SOSGOQ (SOSGOQ2.0) demonstrated strong correlations with SF-36 and the ability to discriminate between clinically distinct patient groups. Reliability of the SOSGOQ2.0 was demonstrated to be good, with an intraclass correlation coefficient ranging from 0.58 to 0.92 for the different domains.

Conclusions: The SOSGOQ2.0 is a reliable and valid measure with which to evaluate HRQOL in patients with spinal metastases. It is recommended to use the SOSGOQ2.0 together with a generic HRQOL outcome measure to comprehensively assess HRQOL and increase sensitivity and specificity. Cancer 2018;124:1828-38. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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http://dx.doi.org/10.1002/cncr.31240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900572PMC
April 2018

Diagnostic algorithm, prognostic factors and surgical treatment of metastatic cancer diseases of the long bones and spine.

EFORT Open Rev 2017 Sep 1;2(9):372-381. Epub 2017 Sep 1.

National Center for Spinal Disorders, H-1126 Budapest, Királyhágó u.1., Hungary.

Oncological management of skeletal metastases has changed dramatically in the last few decades. A significant number of patients survive for many years with their metastases.Surgeons are more active and the technical repertoire is broader, from plates to intramedullary devices to (tumour) endoprostheses.The philosophy of treatment should be different in the case of a trauma-related fracture and a pathological fracture. A proper algorithm for establishing a diagnosis and evaluation of prognostic factors helps in planning the surgical intervention.The aim of palliative surgery is usually to eliminate pain and to allow the patient to regain his/her mobility as well as to improve the quality of life through minimally invasive techniques using life-long durable devices.In a selected group of patients with an oncologically controlled primary tumour site and a solitary bone metastasis with positive prognostic factors, which meet the criteria for radical excision (approximately 10% to 15% of the cases), a promising three to five years of survival may be achieved, especially in cases of metastases from breast and kidney cancer.Spinal metastases require meticulous evaluation because decisions on treatment mostly depend on the tumour type, segmental stability, the patient's symptoms and general state of health.Advanced radiotherapy combined with minimally invasive surgical techniques (minimally invasive stabilisation and separation surgery) provides durable local control with a low complication rate in a number of patients. Cite this article: 2017;2:372-381.
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http://dx.doi.org/10.1302/2058-5241.2.170006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644421PMC
September 2017

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

Neuro Oncol 2017 03;19(3):405-413

Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.

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.
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http://dx.doi.org/10.1093/neuonc/now156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464366PMC
March 2017

Risk factors for surgical site infection in elective routine degenerative lumbar surgeries.

Spine J 2016 11 9;16(11):1377-1383. Epub 2016 Aug 9.

National Center for Spinal Disorders, Buda Health Center, Budapest, Hungary.

Background Context: Surgical site infection (SSI) is one of the most serious complications of spine surgery. Its predisposing factors, especially in routine surgeries, are less reported. However, a number of patient- and procedure-related risk factors could be avoided or at least determined preoperatively. Moreover, the patient-specific risk for SSI could be estimated before the elective surgery.

Purpose: The aim of the present study was to analyze the preoperatively determinable risk factors for SSI in patients who require elective routine surgery related to lumbar disc degeneration and to build a multivariable model for the individual risk prediction.

Study Design: Analysis of prospectively collected standardized clinical data and the validation of the results on an independent prospective cohort were performed.

Patient Sample: One thousand thirty (N=1,030) patients were included in the study. All subjects underwent primary lumbar single- or two-level decompression, microdiscectomy, or instrumented fusion.

Outcome Measures: Occurrence of an SSI defined according to the current Centers for Disease Control and Prevention guidelines that required surgical or nonsurgical therapy.

Methods: The effect of preoperative patient characteristics, comorbidities, disease history, and invasiveness of the elective surgery on the risk of SSI was determined in uni- and multivariate logistic regression models in the test cohort (N=723). The performance of the final multivariable regression model was assessed by measuring its discriminative ability (c-index) in receiver operating characteristic analysis. Performance of the multivariable risk estimation model was tested on the validation (N=307) cohort.

Results: The prevalence of SSI was 3.5% and 3.9% in the test and in the validation cohorts, respectively. The final multivariable regression model predictive (p=.003) for SSI contained the patient's age, body mass index (BMI), and the presence of 5 comorbidities, such as diabetes, ischemic heart disease, arrhythmia, chronic liver disease, and autoimmune disease as risk factors. The c-index of the model was 0.71, showing good discriminative ability, and it was confirmed by the data of the independent validation cohort (c=0.72).

Conclusions: Predisposing factors for SSI were older age, higher BMI, and the presence of certain comorbidities in the present study. The cumulative number of risk factors significantly associated with the increasing risk for an SSI (p<.0001). Our model needs further validation but it may be used for individual risk assessment and reduction in the future.
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http://dx.doi.org/10.1016/j.spinee.2016.08.018DOI Listing
November 2016

Muscle strength is associated with vitamin D receptor gene variants.

J Orthop Res 2016 11 14;34(11):2031-2037. Epub 2016 Mar 14.

National Center for Spinal Disorders, Buda Health Center, Budapest, Hungary.

Vitamin D receptor (VDR) is an important candidate gene in muscle function. Scientific reports on the effect of its genetic variants on muscle strength are contradictory likely due to the inconsistent study designs. Hand grip strength (HGS) is a highly heritable phenotype of muscle strength but only limited studies are available on its genetic background. Association between VDR polymorphisms and HGS has been poorly investigated and previous reports are conflicting. We studied the effect of VDR gene variants on HGS in a sample of 706 schoolchildren. Genomic DNA was extracted from saliva samples and six candidate single nucleotide polymorphisms (SNPs) across the VDR gene were genotyped with Sequenom MassARRAY technique. HGS was measured with a digital dynamometer in both hands. Single marker and haplotype associations were adjusted for demographic parameters. Three SNPs, rs4516035 (A1012G; p = 0.009), rs1544410 (BsmI; p = 0.010), and rs731236 (TaqI; p = 0.038) and a 3' UTR haploblock constructed by three SNPs (Bsml-Taq1-rs10783215; p < 0.005) showed significantly associations with HGS of the dominant hand. In the non-dominant hand, the effects of the A1012G (p = 0.034) and the 3' UTR haploblock (p < 0.01) on HGS were also significant. Since the promoter SNP (A10112G) and the 3' UTR haplotype were proved to be associated with the expression and the stability of the VDR mRNA in earlier studies, VDR variants can be supposed to have a direct effect on muscle strength. The individual genetic patterns can also explain the inconsistency of the previously published clinical results on the association between vitamin D and muscle function. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2031-2037, 2016.
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http://dx.doi.org/10.1002/jor.23220DOI Listing
November 2016

Surgical Management of Spinal Chondrosarcomas.

Spine (Phila Pa 1976) 2016 Apr;41(8):678-85

*Division of Spine, Department of Orthopaedics, University of British Columbia, and the Combined Neurosurgical and Orthopaedic Spine Program at Vancouver Coastal Health, Vancouver, British Columbia, Canada †Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands ‡Division of Neurosurgery, Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada §Unit of Oncologic and Degenerative Spine Surgery, Rizzoli Institute, Bologna, Italy ¶National Center for Spinal Disorders and Buda Health Center, Budapest, Hungary ||The CORE Institute, Phoenix, AZ **Oncologia Ortopedica e Ricostruttiva del Rachide, Istituto Ortopedico Galeazzi, Milano, Italy ††Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD ‡‡Department of Orthopaedics, Princess Alexandra Hospital, Brisbane, Queensland, Australia §§Spinal Division, Oxford University Hospitals NHS Trust, Oxford, UK ¶¶Division of Neurosurgery and Spine Program, Department of Surgery, University of Toronto and Toronto Western Hospital, Toronto, Ontario, Canada ||||Research Department, AOSpine International, Davos, Switzerland ***Department of Neurosurgery, MD Anderson Cancer Center, The University of Texas, Houston, TX.

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 ± 15.8 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.
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http://dx.doi.org/10.1097/BRS.0000000000001485DOI Listing
April 2016

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

J Neurosurg Spine 2016 Apr 18;24(4):644-51. Epub 2015 Dec 18.

Department of Oncologic and Degenerative Spine Surgery, Rizzoli Orthopaedic Institute, Bologna, Italy.

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.
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http://dx.doi.org/10.3171/2015.7.SPINE15201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818185PMC
April 2016

[MEASURING THE FUNCTIONAL IMPAIRMENT OF THE LUMBAR SPINE].

Ideggyogy Sz 2015 Mar;68(3-4):135-41

Background And Purpose: The purpose of our study was to outline the Hungarian validation process of the Oswestry Disability Index, the Quebec Back Pain Disability Scale, the Roland-Morris Disability Questionnaire and the Core Outcome Measurement Index, as well as to draw up recommendations regarding their future applications.

Methods: The Hungarian versions were created after a cultural and linguistic adaptation. Next to the above-mentioned questionnaires, the questionnaire booklet used for validation also contained the WHOQoL-BREF general quality of life questionnaire and a pain measuring Visual Analog Scale. The data of low-back pain patients were registered twice in two weeks. We determined the internal homogeneity (Cronbach alpha), reproducibility, standard error of measurement and the minimal detectable change of the questionnaires. Patients were assigned into different two subgroups (surgical / non-surgical, with/without affection of nerve roots) and differences between the subgroups were examined with the help of the questionnaires. We determined the physical subscale of the WHOQoL-BREF and the correlation between the pain and the studied questionnaires.

Results: The value of Cronbach alpha was between 0.85 and 0.95. All four questionnaires showed significant differences (p<0.001) between the subgroups. The correlation studies brought strong and significant results (p<0.001, r>0.5) in every case. The values of reproducibility were between 0.93-0.92. The results of standard measurement error: 4.8 (Oswestry), 5.2 (Quebec), 1.6 (Roland-Morris), 0.59 (Core Index). The minimal detectable change was 13; 14; 4, and 2 points, respectively.

Conclusion: The Hungarian versions of all four questionnaires are valid. They can be applied with scientific certainty to measure low back pain patients. From the studied questionnaires, we especially recommend the wide-raging application of the Oswestry Disability Index and the Core Outcome Measurement Index based on their psychometric and application features.
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March 2015

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

Spine (Phila Pa 1976) 2015 May;40(9):656-64

*Division of Neurosurgery, Department of Surgery, University of Toronto and Toronto Western Hospital, Toronto, Ontario, Canada †National Center for Spinal Disorders and Buda Health Center, Budapest, Hungary ‡Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD §Department of Degenerative and Oncological Spine Surgery, Rizzoli Institute, Bologna, Italy ¶Oncologia Ortopedica e Ricostruttiva del Rachide, Istituto Ortopedico Galeazzi, Milano, Italy ‖Department of Neurosurgery, MD Anderson Cancer Center, The University of Texas, Houston, TX **Division of Spine, Department of Orthopaedics, University of British Columbia and Vancouver Coastal Health, Vancouver, British Columbia, Canada ††Department of Neurological Surgery, University of California San Francisco, San Francisco, CA ‡‡Department of Orthopaedics, Princess Alexandra Hospital, Brisbane, Queensland, Australia §§Orthopaedic Surgery, The CORE Institute, Sun City West, AZ ¶¶Center for Spine Studies and Surgery, Queens Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; and ‖‖Department of Orthopaedic Surgery, Kanazawa Medical University, Kahoku-gun, Japan.

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.
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http://dx.doi.org/10.1097/BRS.0000000000000840DOI Listing
May 2015

Cross-cultural adaptation and validation of the Hungarian version of the Core Outcome Measures Index for the back (COMI Back).

Eur Spine J 2016 Jan 9;25(1):257-264. Epub 2015 Jan 9.

National Center for Spinal Disorders, Buda Health Center, Kiralyhago u. 1-3, Budapest, 1126, Hungary.

Purpose: The Core Outcome Measure Index (COMI) is a short, multidimensional outcome instrument developed for the evaluation of patients with spinal conditions. The aim of this study was to produce a cross-culturally adapted and validated Hungarian version of the COMI Back questionnaire.

Methods: A cross-cultural adaptation of the COMI into Hungarian was carried out using established guidelines. Low back pain patients completed a booklet of questionnaires containing the Hungarian versions of COMI, Oswestry Disability Index (ODI) and WHO Quality of Life-BREF assessment (WHOQOL-BREF). The validation of the COMI included assessment of its construct validity, reliability, and responsiveness.

Results: 145 patients participated in the assessment of reliability and 159 surgically treated patients were included in the responsiveness study. Excellent correlation was found between COMI and ODI scores (rho = 0.83, p < 0.01). The COMI showed a very good correlation with the physical subscale of WHOQOL-BREF (rho = -0.75, p < 0.01) and pain (rho = 0.68, p < 0.01). Test-retest analysis showed that Hungarian COMI is a reliable measurement tool (ICC = 0.92) with an acceptable standard error of measurement (SEM = 0.59) and minimum detectable change (MDC = 1.63). Internal responsiveness analysis indicated a large effect size (1.16) for the change in COMI score after lumbar surgery. The area under the ROC curve (AUC) for the COMI score compared with the global outcome of the surgery was 0.87.

Conclusion: The translation and cross-cultural adaptation of the COMI into the Hungarian language was successful, resulting in a reliable and valid measurement tool with good clinimetric properties.
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http://dx.doi.org/10.1007/s00586-014-3750-8DOI Listing
January 2016

Surgical treatment of sacral chordoma: prognostic variables for local recurrence and overall survival.

Eur Spine J 2015 May 23;24(5):1092-101. Epub 2014 Dec 23.

National Center for Spinal Disorders, Kiralyhagó Street 1-3, 1126, Budapest, Hungary,

Purpose: Sacral chordomas (SC) are rare, locally invasive, malignant neoplasms. Despite surgical resection and adjuvant therapies, local recurrence (LR) is common and overall survival (OS) is poor. The objective of this study was to identify prognostic factors that have an impact on the local recurrence-free survival (LRFS) and OS of patients with SC.

Methods: Utilizing the AOSpine Knowledge Forum Tumor multicenter ambispective database, surgically treated SC cases were identified. Cox regression modeling was used to assess the effect of several clinically relevant variables on OS and LRFS.

Results: A total of 167 patients with surgically treated SC were identified. The male/female ratio was 98/69 with a mean age of 57 ± 15 years at the time of surgery. The LR was 35% (n = 57), death occurred in 30% of patients (n = 50) during the study period. The median OS was 6 years post-surgery and LRFS was 4 years. In the univariate analysis, previous tumor surgery at the same site (P = 0.002), intralesional resection (P < 0.001), and larger tumor volume (P = 0.030) were significantly associated with LR. Increasing age (P < 0.001) and a preoperative motor deficit of C or D (P = 0.003) were significantly associated with poor OS, and nerve root sacrifice showed a trend towards significance (P = 0.088). In the multivariate models, previous surgery and intralesional resection were significantly related to LR, while increasing age and motor deficit of C or D were associated with poor OS.

Conclusions: This study identified two predictive variables for LRFS (previous tumor surgery and type of surgical resection) and two for OS (age and impaired motor function) in surgically treated SC patients. Our results indicate that en bloc resection reduces LR but does not influence OS. However, this was likely due to short follow-up (3.2 years).
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http://dx.doi.org/10.1007/s00586-014-3728-6DOI Listing
May 2015

[Primary Spinal Tumor Registry at the National Centre for Spinal Disorders].

Orv Hetil 2014 May;155(19):745-9

Országos Gerincgyógyászati Központ Budapest Királyhágó u. 1-3. 1126.

Primary spinal tumors are rare diseases. Primary spinal tumor registry would be useful to help decision making in this complex field of spine surgery. In this article the authors present the latest findings from the Primary Spinal Tumor Registry at the National Centre for Spinal Disorders, Hungary. The registry is based on a novel database management software, the REDCap electronic data capture system. It contains data of 323 patients treated surgically during an 18-year period. Among the 126 malignant tumors, the most frequent was chordoma (61 cases). In the case of benign tumors schwannoma showed the largest prevalence (45 cases). The authors conclude that due to the rarity of the disease and the complexity of the management, multicenter, prospective registries are required to provide high level of evidence. The structure of the Primary Spinal Tumor Registry in the National Centre for Spinal Disorders in Hungary is optimal for user-friendly, fast and secure data collection providing a prospective database for scientific researches and clinical follow-up.
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http://dx.doi.org/10.1556/OH.2014.29920DOI Listing
May 2014

Primary Spinal Tumor Mortality Score (PSTMS): a novel scoring system for predicting poor survival.

Spine J 2014 Nov 17;14(11):2691-700. Epub 2014 Mar 17.

National Center for Spinal Disorders, Kiralyhagó St 1-3, Budapest 1126, Hungary. Electronic address:

Background Context: Although the surgical and oncological therapies of primary spinal tumors (PSTs) have changed significantly over the last few decades, the prognosis of this rare disease is still poor. The decision-making process in the multidisciplinary management is handicapped by the lack of large-scale population-based prognostic studies.

Purpose: The objective of the present study was to investigate preoperative factors associated with PST mortality and to develop a predictive scoring system of poor survival.

Study Design: This is a large-scale ambispective cohort study.

Patient Sample: The study included 323 consecutive patients with PSTs, treated surgically over an 18-year period at a tertiary care spine referral center for a population of 10 million.

Outcome Measure: Survival was the outcome measure.

Methods: Patients were randomly divided into a training cohort (n=273) and a validation cohort (n=50). In the training cohort, 12 preoperative factors were investigated using Cox proportional hazard models. Based on the mortality-related variables, a simple scoring system of mortality was created, and three groups of patients were identified. Kaplan-Meier and log-rank analyses were used to compare the survival in the three groups. The model performance was assessed by measuring the discriminative ability (c-index) of the model and by applying a pseudo-R(2) goodness-of-fit test (Nagelkerke R(2), RN(2)). Internal validation was performed using bootstrapping in the training cohort and assessing the discrimination and explained variation of the model in the validation cohort.

Results: Patient age, spinal region, tumor grade, spinal pain, motor deficit, and myelopathy/cauda equina syndrome were significantly associated with poor survival in the multivariate analysis (p<.001, RN(2)=0.799). Based on these variables, we developed the Primary Spinal Tumor Mortality Score (PSTMS), where an eight-point scale was divided into three categories (low, medium, and high mortality). The three PSTMS categories were significantly associated with the overall survival (p<.001, RN(2)=0.811, c=0.82). The model performance remained similarly high in the validation cohort (RN(2)=0.831, c=0.81).

Conclusions: The present study identifies six predictive variables for mortality in PSTs. Using these six variables, an easy-to-use scoring system was developed that can be applied to the estimation of postoperative survival in all types of PST patients.
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http://dx.doi.org/10.1016/j.spinee.2014.03.009DOI Listing
November 2014

Reliability of the Spinal Instability Neoplastic Score (SINS) among radiation oncologists: an assessment of instability secondary to spinal metastases.

Radiat Oncol 2014 Mar 4;9:69. Epub 2014 Mar 4.

Division of Spine, Department of Orthopaedics, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.

Background: The Spinal Instability Neoplastic Score (SINS) categorizes tumor related spinal instability. It has the potential to streamline the referral of patients with established or potential spinal instability to a spine surgeon. This study aims to define the inter- and intra-observer reliability and validity of SINS among radiation oncologists.

Methods: Thirty-three radiation oncologists, across ten international sites, rated 30 neoplastic spinal disease cases. For each case, the total SINS (0-18 points), three clinical categories (stable: 0-6 points, potentially unstable: 7-12 points, and unstable: 13-18 points), and a binary scale ('stable': 0-6 points and 'current or possible instability'; surgical consultation recommended: 7-18 points) were recorded. Evaluation was repeated 6-8 weeks later. Inter-observer agreement and intra-observer reproducibility were calculated by means of the kappa statistic and translated into levels of agreement (slight, fair, moderate, substantial, and excellent). Validity was determined by comparing the ratings against a spinal surgeon's consensus standard.

Results: Radiation oncologists demonstrated substantial (κ=0.76) inter-observer and excellent (κ=0.80) intra-observer reliability when using the SINS binary scale ('stable' versus 'current or possible instability'). Validity of the binary scale was also excellent (κ=0.85) compared with the gold standard. None of the unstable cases was rated as stable by the radiation oncologists ensuring all were appropriately recommended for surgical consultation.

Conclusions: Among radiation oncologists SINS is a highly reliable, reproducible, and valid assessment tool to address a key question in tumor related spinal disease: Is the spine 'stable' or is there 'current or possible instability' that warrants surgical assessment?
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http://dx.doi.org/10.1186/1748-717X-9-69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995991PMC
March 2014
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