A Nationwide Study of Stereotactic Radiosurgery in a Newly Diagnosed Spine Metastasis Population.

BACKGROUND: Stereotactic radiosurgery (SRS), a technique that is emerging as a new treatment option, has been reported to be an effective, noninvasive treatment for spine metastasis patients. OBJECTIVE: This nationwide study aimed to understand the current state of SRS for spine metastasis. METHODS: Patients in this study were first diagnosed with a metastatic spine tumor between 1 July and 31 December 2011. One group (the SRS group) received SRS at least once within 1 year of diagnosis and the other (the non-SRS group) did not receive SRS. We analyzed the characteristics, medication, and survival of each group. RESULTS: In 628 new patients, there were no significant differences between groups regarding gender, age, type of health insurance, and comorbidities. There were significant differences with regard to the medical costs (USD 23,276 vs. 18,458; p = 0.001) and the duration of hospital stay (101.3 vs. 86.5 days; p = 0.023). Median survival was significantly longer in the SRS group (p = 0.003). CONCLUSIONS: There was no significant pretreatment baseline demographic difference between the SRS and the non-SRS group. There was a tendency for greater use of medication in the SRS group. Patients with a longer overall survival tended to be those who underwent SRS treatment.

Which one is a valuable surrogate for predicting survival between Tomita and Tokuhashi scores in patients with spinal metastases? A meta-analysis for diagnostic test accuracy and individual participant data analysis.

This study is to estimate the diagnostic accuracy of Tokuhashi and Tomita scores that assures 6-month predicting survival regarded as a standard of surgical treatment. We searched PubMed, EMBASE, European PubMed central, and the Cochrane library for papers about the sensitivities and specificities of the Tokuhashi and/or Tomita scores to estimate predicting survival. Studies with cut-off values of ≥9 for Tokuhashi and ≤7 for Tomita scores based on prior studies were enrolled. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC), and the best cut-off value were calculated via meta-analysis and individual participant data analysis. Finally, 22 studies were enrolled in the meta-analysis, and 1095 patients from 8 studies were included in the individual data analysis. In the meta-analysis, the pooled sensitivity/specificity/DOR for 6-month survival were 57.7 %/76.6 %/4.70 for the Tokuhashi score and 81.8 %/47.8 %/4.93 for Tomita score. The AUC of summary receiver operating characteristic plots was 0.748 for the Tokuhashi score and 0.714 for the Tomita score. Although Tokuhashi score was more accurate than Tomita score slightly, both showed low accuracy to predict 6 months residual survival. Moreover, the best cut-off values of Tokuhashi and Tomita scores were 8 and 6, not 9 and 7, for predicting 6-month survival, respectively. Estimation of 6-month predicting survival to decide surgery in patients with spinal metastasis is quite limited by using Tokuhashi and Tomita scores alone. Tokuhashi and Tomita scores could be incorporated as part of a multidisciplinary approach or perhaps interpreted in the context of a multidisciplinary approach.

Clinical result of stereotactic radiosurgery for spinal metastasis from hepatocellular carcinoma: comparison with conventional radiation therapy.

We investigated the clinical outcome following stereotactic radiosurgery (SRS) for spinal metastasis from hepatocellular carcinoma (HCC) and compared it with that of conventional radiation therapy (cRT). Thirty-nine metastatic spine tumors from 27 HCC patients were treated with SRS from 2002 to 2011. Their medical records and radiological data were retrospectively analyzed. Median tumor volume was 49.7 cc, and a mean marginal dose of 28.7 Gy was delivered to the tumor mass. We analyzed overall survival (OS), local progression-free survival, and the rate of pain control following SRS. Factors relating to clinical outcomes were also investigated. Clinical results following cRT were obtained from 32 patients. The cRT protocol consisted of 30 Gy in 10 fractions or 39 Gy in 13 fractions. OS and local progression-free survival were compared between SRS and cRT. OS was a median of 7 months following SRS. Significant prognostic factors relating to OS included Child-Pugh class and Karnofsky performance scale. Tumor recurrence was noted in nine lesions during follow-up. The median local progression-free survival was 7 months. Previous irradiation was a significant prognostic factor for local recurrence (P = 0.043). The overall pain control rate was 85 % and no factors were found to be significantly correlated with the pain control rate. The median OS was 3 months in the cRT group and 7 months in the SRS group (P = 0.035). The median local progression-free survival was 2.0 months in the cRT group, and 7.0 months in the SRS group, which were significantly different (P = 0.033). SRS showed better local control than cRT in the treatment of HCC spinal metastasis.

Stereotactic radiosurgery compared with external radiation therapy as a primary treatment in spine metastasis from renal cell carcinoma: a multicenter, matched-pair study.

The aim of this multicenter, matched- pair study was to compare the outcome of stereotactic radiosurgery (SRS) with that of external radiation therapy (RT) when used as a primary treatment in spine metastasis from renal cell carcinoma (RCC). From 2005 to 2012, 13 patients underwent SRS as a primary treatment in spine metastasis from RCC. Thirteen patients who underwent RT as the primary treatment of RCC spine metastasis were paired with the SRS patients based on age, number of spine metastasis, time interval from original tumor diagnosis to spine metastasis, Eastern Cooperative Oncology Group status, and year of treatment. The primary outcomes of interest were pain relief and progression free survival. Secondary outcomes were treatment toxicities and need for further treatment. The perioperative VAS score decrease was larger in the SRS group than that in the RT group (P = 0.04). More SRS patients had complete or partial pain relief although the difference was not significant. There was a significant difference in progression free survival between the two groups (P = 0.01). The percentage of patients with toxicities was 38.5 % (5/13) in the SRS group and 53.9 % (7/13) in the RT group, but the difference was not significant. There were 2 SRS patients and 3 RT patients who received further intervention at the index segment. This study showed that, when performed as a primary treatment in spine metastasis from RCC, SRS provides relatively better pain relief and better local control than that obtained from RT.

Treatment outcomes of stereotactic body radiation therapy for primary and metastatic sarcoma of the spine.

PURPOSE: This study evaluated the treatment outcomes of spine stereotactic body radiation therapy (SBRT) in sarcoma patients. MATERIALS AND METHODS: A total of 44 sarcoma patients and 75 spinal lesions (6 primary tumors, 69 metastatic tumors) treated with SBRT were retrospectively reviewed between 2006 and 2017. The median radiation dose was 33 Gy (range, 18-45 Gy) in 3 fractions (range, 1-5) prescribed to the 75% isodose line. RESULTS: The median follow-up duration was 18.2 months. The 1-year local control was 76.4%, and patients treated with single vertebral body were identified as a favorable prognostic factor on multivariate analyses. Progression-free survival at 1 year was 31.9%, with the interval between initial diagnosis and SBRT and extent of disease at the time of treatment being significant prognostic factors. The 1-year overall survival was 80.5%, and PTV and visceral metastases were independently associated with inferior overall survival. CONCLUSION: SBRT for spinal sarcoma is effective in achieving local control, particularly when treating a single vertebral level with a limited extent of disease involvement, resulting in an excellent control rate. The extent of disease at the time of SBRT is significantly correlated with survival outcomes and should be considered when treating spine sarcoma.

Local tumor control after retreatment of spinal metastasis using stereotactic body radiotherapy; comparison with initial treatment group.

BACKGROUND: The aim of this study is to evaluate local control rates after stereotactic body radiotherapy (SBRT) in recurrent spinal metastasis after external beam radiotherapy (EBRT) and new spinal metastatic lesions. MATERIAL AND METHODS: Retrospective review of medical records and radiological data was performed on 54 retreatment and 131 initial SBRT patients. To compare various fractionation schedules, the biologically effective dose (BED) was applied. SBRT dose was calculated with linear-quadratic model and normalized to a 2-Gy equivalent dose (nBED, α/ß =2 Gy for spinal cord, α/ß =10 Gy for tumor). Doses to a point within the spinal cord that received the maximum dose (Pmax) were checked. Local control failure was defined as progression by imaging study. Overall survival, progression free survival, delivered radiation dose to tumor and spinal cord, and spinal cord Pmax nBED were compared in two groups. RESULTS: The mean delivered radiation doses to tumor margin during SBRT were 51.1 Gy2/10 (retreatment) and 50.7 Gy2/10 (initial treatment). Mean survival was 29.6 months (overall)/20.7 months (retreatment)/ 32.4 months (initial treatment). Mean progression free period was 23.9 months (overall)/18.0 months (retreatment)/ 26.0 months (initial treatment). Radiological control rates of retreatment and initial treatment group were 96%/95% at six months, 81%/89% at 12 months and 79%/90% at 24 months. Among 54 retreatment lesions, 13 lesions showed local control failure during follow-up. With regard to spinal cord radiation dose during SBRT, Spinal cord Pmax nBED was 46.2 Gy2/2 (retreatment) and 48.7 Gy2/2 (initial treatment). In retreatment group, total nBED to spinal cord was a mean of 83.4 Gy2/2. There was no case of radiation myelopathy detected. CONCLUSIONS: Retreatment of spinal metastases using SBRT provided effective local control without neurological complications.

Thecal Sac Contouring as a Surrogate for the Cauda Equina and Intracanal Spinal Nerve Roots for Spine Stereotactic Body Radiation Therapy (SBRT): Contour Variability and Recommendations for Safe Practice.

PURPOSE: To present interobserver variability in thecal sac (TS) delineation based on contours generated by 8 radiation oncologists experienced in spine stereotactic body radiation therapy and to propose contouring recommendations to standardize practice. METHODS AND MATERIALS: In the setting of a larger contouring study that reported target volume delineation guidelines specific to sacral metastases, 8 academically based radiation oncologists with dedicated spine stereotactic body radiation therapy programs independently contoured the TS as a surrogate for the cauda equina and intracanal spinal nerve roots. Uniform treatment planning simulation computed tomography datasets fused with T1, T2, and T1 post gadolinium magnetic resonance imaging for each case were distributed to each radiation oncologist. All contours were analyzed and agreement was calculated using both Dice similarity coefficient and simultaneous truth and performance level estimation with kappa statistics. RESULTS: A fair level of simultaneous truth and performance level estimation agreement was observed between practitioners, with a mean kappa agreement of 0.38 (range, 0.210.55) and the mean Dice similarity coefficient (± standard deviation, with range) was 0.43 (0.36 ± 0.1 to -0.53 ±0.1). Recommendations for a reference TS contour, accounting for the variations in practice observed in this study, include contouring the TS to encompass all the intrathecal spinal nerve roots, and caudal to the termination of the TS, the bony canal can be contoured as a surrogate for the extra thecal nerves roots that run within it. CONCLUSIONS: This study shows that even among high-volume practitioners, there is a lack of uniformity when contouring the TS. Further modifications may be required once dosimetric data on nerve tolerance to ablative doses, and pattern of failure analyses of clinical data sets using these recommendations, become available. The contouring recommendations were designed as a guide to enable consistent and safe contouring across general practice.

Radiosurgery using the Cyberknife for benign spinal tumors: Korea Cancer Center Hospital experience.

This study evaluated clinical outcome and safety of radiosurgery using the Cyberknife for treatment of benign spinal tumors. The authors treated 30 benign spinal tumors in 20 patients with the Cyberknife (Accuray, Inc., Sunnyvale, CA, USA) from 2002 to 2008. Among these there were 20 neurogenic tumors, eight hemangioblastomas, and two meningiomas. Four patients with neurofibromatosis (NF) type 2 and four patients with Von Hippel Lindau disease were also included. Radiosurgery was done as primary treatment for 22 lesions, for postoperative residual tumor control for four lesions, and for the remaining four lesions with image-based progression after initial subtotal resection. The distribution of lesions was cervical (18 tumors), thoracic (six), and cauda equina level (six). Follow-up data included imaging studies, clinical findings, and radiotherapy data. Tumor volume ranged from 0.04 to 33.65 cm³ (mean, 4.52 cm³). A 14-33 Gy marginal dose was delivered in 1-5 fractions. The mean follow-up period was 35.6 months (range, 12-84 months). On follow-up, most lesions decreased in size (57%) or remained unchanged (33%). Two lesions initially decreased, then increased later. One lesion increased without response. With regard to clinical aspects, radicular pain and myelopathic pain improved after radiosurgery in most cases (94%). Motor weakness recovered in two out of five patients and recovery of sensory change occurred in four out of ten patients. In two patients, symptoms were aggravated by tumor enlargement and the occurrence of new lesion. Mean spinal cord volumes receiving more than 10 and 8 Gy were 0.40 ± 0.4 and 0.81 ± 0.7 cm³, respectively. Stereotactic radiosurgery (SRS) using the Cyberknife showed the ability to control benign spinal tumors without complication in most cases.

The treatment outcome depending on the extent of resection in skull base and spinal chordomas.

PURPOSE: The authors tried to assess the treatment outcomes depending on the extent of resection in axial chordomas and compare the outcome of two adjunctive therapies (external beam radiation therapy vs. stereotactic radiosurgery) following incomplete tumour resection in terms of local tumour control. PATIENTS AND METHODS: We retrospectively reviewed 30 consecutive patients with chordoma involving skull base, sacrum and mobile spine between 1993 and 2008. Their initial treatments had different extent of resection. Wide resection was performed for 12 (40%), subtotal resection and adjunctive radiotherapy/radiosurgery for 12 (40%), while six patients (20%) were solely treated with radiotherapy/radiosurgery. For these three groups, overall and progression-free survival rate were compared. RESULTS: The overall survival rate was 96% at 5 years and 67% at 10 years. Tumour progression-free survival (PFS) rates were 73% and 43% at 5 and 10 years, respectively. Local tumour progression was seen in 67% in all patients, 58% in wide resection group, 67% in subtotal resection plus radiotherapy/radiosurgery group, and 75% in radiotherapy/radiosurgery group; however, this was not statistically significant (P = 0.69). Neither the extent of resection nor tumour location significantly influenced overall and progression-free survival (P > 0.05). With regard to the type of radiotherapy, tumour progression occurred in all lesions treated with external photon beam radiation therapy (EBRT) but only 38% of lesions treated with stereotactic radiosurgery (SRS) (P = 0.003). CONCLUSIONS: Adjunctive radiotherapy/radiosurgery following subtotal resection showed comparable local control and survival to wide resection. SRS offered superior local tumour control compared to EBRT.

International consensus recommendations for target volume delineation specific to sacral metastases and spinal stereotactic body radiation therapy (SBRT).

BACKGROUND AND PURPOSE: To interrogate inter-observer variability in gross tumour volume (GTV) and clinical target volume (CTV) delineation specific to the treatment of sacral metastases with spinal stereotactic body radiation therapy (SBRT) and develop CTV consensus contouring recommendations. MATERIALS AND METHODS: Nine specialists with spinal SBRT expertise representing 9 international centres independently contoured the GTV and CTV for 10 clinical cases of metastatic disease within the sacrum. Agreement between physicians was calculated with an expectation minimisation algorithm using simultaneous truth and performance level estimation (STAPLE) and with kappa statistics. Optimised confidence level consensus contours were obtained using a voxel-wise maximum likelihood approach and the STAPLE contours for GTV and CTV were based on an 80% confidence level. RESULTS: Mean GTV STAPLE agreement sensitivity and specificity was 0.70 (range, 0.54-0.87) and 1.00, respectively, and 0.55 (range, 0.44-0.64) and 1.00 for the CTV, respectively. Mean GTV and CTV kappa agreement was 0.73 (range, 0.59-0.83) and 0.59 (range, 0.41-0.70), respectively. Optimised confidence level consensus contours were identified by STAPLE analysis. Consensus recommendations for the CTV include treating the entire segment containing the disease in addition to the immediate adjacent bony anatomic segment at risk of microscopic extension. CONCLUSION: Consensus recommendations for CTV target delineation specific to sacral metastases treated with SBRT were established using expert contours. This is a critical first step to achieving standardisation of target delineation practice in the sacrum and will serve as a baseline for meaningful pattern of failure analyses going forward.

A Nationwide Study of Surgery in a Newly Diagnosed Spine Metastasis Population.

OBJECTIVE: The aim of this nationwide study was to analyze the current state of patients with newly diagnosed metastatic spine tumors according to surgical methods. METHODS: Data was extracted from the Korean Health Insurance Review and Assessment Service database. Surgery was categorized into three. METHODS: fusion, decompression, and vertebroplasty. Data included patient age, sex, health insurance type, and co-morbidities. Survival rates of metastatic spine tumor patients according to each surgical method were evaluated. RESULTS: Among 1677 patients who had an operation, 823 patients were treated by fusion, 141 patients underwent decompression, and 713 patients were treated by vertebroplasty. The three most prevalent primary tumor sites were the lung, breast, and liver & biliary. On the other hand, the three most prevalent primary tumor sites of patients who underwent surgery were the lung, liver & biliary, and the prostate. The median survival periods for each surgical method in the metastatic spine tumor patients were 228 days for those who underwent surgery, 249 days for decompression, and 154 days for vertebroplasty. Age, sex, and comorbidities significantly affected survival rate. CONCLUSION: For every primary tumor site, decompression was the least common surgical method during the study period. Although the three surgical methods did not significantly affect the survival period, patients with a poor prognosis tended to undergo vertebroplasty.

Nationwide comparative study of synchronous and metachronous spine metastasis in the adult Korean population.

This nationwide study of the adult Korean population aimed to compare the survival period between synchronous and metachronous group and to determine recent treatment trends in newly diagnosed spine metastasis patients. Data were extracted from the Korean Health Insurance Review and Assessment Service database. Patients in this study were newly diagnosed with metastatic spine tumors between July 1, 2011 and June 31, 2014. The metachronous group was defined when the primary tumor was diagnosed prior to the diagnosis of spine metastasis, otherwise patients were considered to be the part of the synchronous group. The survival period was calculated from the date of first diagnosis of spine metastasis. In a multivariate analysis, patients in the synchronous group survived significantly longer than those in the metachronous group (P < 0.0001). Median overall survival periods were 273.6 days for the metachronous group and 541.4 days for the synchronous group. Conventional radiation therapy (RT) was the most common treatment modality for metastatic spine tumors, whereas surgery combined with RT was a steadily increasing treatment modality during the study period. Synchronous spine metastasis patients survive significantly longer than metachronous patients. Surgery combined with RT is a recently increasing trend among spine metastasis treatments.

Changes in adjacent-level disc pressure and facet joint force after cervical arthroplasty compared with cervical discectomy and fusion.

OBJECT: The authors of previous in vitro investigations have reported an increase in adjacent-level intradiscal pressures (IDPs) and facet joint stresses following cervical spine fusion. This study was performed to compare adjacent-level IDPs and facet force following arthroplasty with the fusion model. METHODS: Eighteen human cadaveric cervical spines were tested in the intact state for different modes of motion (extension, flexion, bending, and rotation) up to 2 Nm. The specimens were then divided into three groups: those involving the ProDisc-C cervical artificial disc, Prestige cervical artificial disc, and cervical fusion. They were load tested after application of instrumentation or surgery at the C6-7 level. During the test, IDPs and facet forces were measured at adjacent levels. RESULTS: In arthroplasty-treated specimens, the IDP showed little difference from that of the intact spine at both proximal and distal levels. In fusion-treated specimens, the IDP increased at the posterior anulus fibrosus on extension and at the anterior anulus fibrosus on flexion at the proximal level. At the distal level, the IDP change was not significant. The facet force changes were minimal in flexion, bending, and rotation modes in both arthroplasty- and fusion-treated spines. Significant changes were noted in the extension mode only. In extension, arthroplasty models exhibited significant increases of facet force at the treated level. In the fusion model the facet forces decreased at the treated segment and increased at the adjacent segment. CONCLUSIONS: The two artificial discs of the semiconstrained systems maintain adjacent-level IDPs near the preoperative values in all modes of motion, but with respect to facet force pressure tended to increase after arthroplasty.

Range of motion change after cervical arthroplasty with ProDisc-C and prestige artificial discs compared with anterior cervical discectomy and fusion.

OBJECT: Range of motion (ROM) changes were evaluated at the surgically treated and adjacent segments in cadaveric specimens treated with two different cervical artificial discs compared with those measured in intact spine and fusion models. METHODS: Eighteen cadaveric human cervical spines were tested in the intact state for the different modes of motion (extension, flexion, lateral bending, and axial rotation) up to 2 Nm. Three groups of specimens (fitted with either the ProDisc-C or Prestige II cervical artificial disc or submitted to anterior cervical discectomy and fusion [ACDF]) were tested after implantation at C6-7 level. The ROM values were measured at treated and adjacent segments, and these values were then compared with those measured in the intact spine. RESULTS: At the surgically treated segment, the ROM increased after arthroplasty compared with the intact spine in extension (54% in the ProDisc-C group, 47% in the Prestige group) and in flexion (27% in the ProDisc-C group, 10% in the Prestige group). In bending and rotation, the postarthroplasty ROMs were greater than those of the intact spine (10% in the ProDisc-C group and 55% in the Prestige group in bending, 17% in the ProDisc-C group and 50% in the Prestige group in rotation). At the adjacent levels the ROMs decreased in all specimens treated with either artificial disc in all modes of motion (< 10%) except for extension at the inferior the level (29% decrease for ProDisc-C implant, 12% decrease for Prestige disc). The ROM for all motion modes in the ACDF-treated spine decreased at the treated level (range 18-44%) but increased at the adjacent levels (range 3-20%). CONCLUSIONS: Both ProDisc-C and Prestige artificial discs were associated with increased ROM at the surgically treated segment compared with the intact spine with or without significance for all modes of testing. In addition, adjacent-level ROM decreased in all modes of motion except extension in specimens fitted with both artificial discs.

Consensus guidelines for postoperative stereotactic body radiation therapy for spinal metastases: results of an international survey.

OBJECTIVE Although postoperative stereotactic body radiation therapy (SBRT) for spinal metastases is increasingly performed, few guidelines exist for this application. The purpose of this study is to develop consensus guidelines to promote safe and effective treatment for patients with spinal metastases. METHODS Fifteen radiation oncologists and 5 neurosurgeons, representing 19 centers in 4 countries and having a collective experience of more than 1300 postoperative spine SBRT cases, completed a 19-question survey about postoperative spine SBRT practice. Responses were defined as follows: 1) consensus: selected by ≥ 75% of respondents; 2) predominant: selected by 50% of respondents or more; and 3) controversial: no single response selected by a majority of respondents. RESULTS Consensus treatment indications included: radioresistant primary, 1-2 levels of adjacent disease, and previous radiation therapy. Contraindications included: involvement of more than 3 contiguous vertebral bodies, ASIA Grade A status (complete spinal cord injury without preservation of motor or sensory function), and postoperative Bilsky Grade 3 residual (cord compression without any CSF around the cord). For treatment planning, co-registration of the preoperative MRI and postoperative T1-weighted MRI (with or without gadolinium) and delineation of the cord on the T2-weighted MRI (and/or CT myelogram in cases of significant hardware artifact) were predominant. Consensus GTV (gross tumor volume) was the postoperative residual tumor based on MRI. Predominant CTV (clinical tumor volume) practice was to include the postoperative bed defined as the entire extent of preoperative tumor, the relevant anatomical compartment and any residual disease. Consensus was achieved with respect to not including the surgical hardware and incision in the CTV. PTV (planning tumor volume) expansion was controversial, ranging from 0 to 2 mm. The spinal cord avoidance structure was predominantly the true cord. Circumferential treatment of the epidural space and margin for paraspinal extension was controversial. Prescription doses and spinal cord tolerances based on clinical scenario, neurological compromise, and prior overlapping treatments were controversial, but reasonable ranges are presented. Fifty percent of those surveyed practiced an integrated boost to areas of residual tumor and density override for hardware within the beam path. Acceptable PTV coverage was controversial, but consensus was achieved with respect to compromising coverage to meet cord constraint and fractionation to improve coverage while meeting cord constraint. CONCLUSIONS The consensus by spinal radiosurgery experts suggests that postoperative SBRT is indicated for radioresistant primary lesions, disease confined to 1-2 vertebral levels, and/or prior overlapping radiotherapy. The GTV is the postoperative residual tumor, and the CTV is the postoperative bed defined as the entire extent of preoperative tumor and anatomical compartment plus residual disease. Hardware and scar do not need to be included in CTV. While predominant agreement was reached about treatment planning and definition of organs at risk, future investigation will be critical in better understanding areas of controversy, including whether circumferential treatment of the epidural space is necessary, management of paraspinal extension, and the optimal dose fractionation schedules.

Biomechanical study of thoracolumbar junction fixation devices with different diameter dual-rod systems.

OBJECT: Advances in the design of a smaller-diameter rod system for use in the thoracolumbar region prompted the authors to undertake this biomechanical study of two different thoracolumbar implants. METHODS: In vitro biomechanical testing was performed using human cadaveric spines. All specimens were loaded to a maximum moment of 5 Nm with 300-N axial preload in six modes of motion. Two types of anterior implants with different rod diameters were applied to intact T10-12 specimens in two groups. The loading was repeated and the range of motion (ROM) was measured. A T-11 corpectomy was then performed and a strain gauge-mounted carbon fiber stackable cage was implanted. The ROM and compression force on the cage were measured, and the mean values were compared between these two groups. With stabilization of the intact spine, ROM decreased least in extension and greatest in bending compared with the intact specimens. After corpectomy and stabilization, ROM increased in extension by 104.89 +/- 53.09% in specimens with a 6.35-mm rod insertion and by 83.81 +/- 16.96% in those with a 5.5-mm rod, respectively; in flexion, ROM decreased by 26.98 +/- 27.43% (6.35 mm) and by 9.59 +/- 15.42% (5.5 mm), respectively; and in bending and rotation, both groups each showed a decrease in ROM. The load sharing of the cage was similar between the two groups (the 6.35-mm compared with 5.5-mm rods): 47.44 and 44.73% (neutral), 49.16 and 39.02% (extension), 61.90 and 56.88% (flexion), respectively. CONCLUSIONS: There were no statistical differences in the ROM and load sharing of the cage when either the 6.35-or 5.5-mm-diameter dual-rod was used.

The Effect of Perioperative Radiation Therapy on Spinal Bone Fusion Following Spine Tumor Surgery.

INTRODUCTION: Perioperative irradiation is often combined with spine tumor surgery. Radiation is known to be detrimental to healing process of bone fusion. We tried to investigate bone fusion rate in spine tumor surgery cases with perioperative radiation therapy (RT) and to analyze significant factors affecting successful bone fusion. METHODS: Study cohort was 33 patients who underwent spinal tumor resection and bone graft surgery combined with perioperative RT. Their medical records and radiological data were analyzed retrospectively. The analyzed factors were surgical approach, location of bone graft (anterior vs. posterior), kind of graft (autologous graft vs. allograft), timing of RT (preoperative vs. postoperative), interval of RT from operation in cases of postoperative RT (within 1 month vs. after 1 month) radiation dose (above 38 Gy vs. below 38 Gy) and type of radiation therapy (conventional RT vs. stereotactic radiosurgery). The bone fusion was determined on computed tomography images. RESULT: Bone fusion was identified in 19 cases (57%). The only significant factors to affect bony fusion was the kind of graft (75% in autograft vs. 41 in allograft, p=0.049). Other factors proved to be insignificant relating to postoperative bone fusion. Regarding time interval of RT and operation in cases of postoperative RT, the time interval was not significant (p=0.101). CONCLUSION: Spinal fusion surgery which was combined with perioperative RT showed relatively low bone fusion rate (57%). For successful bone fusion, the selection of bone graft was the most important.

Establishment and characterization of a chordoma cell line from the tissue of a patient with dedifferentiated-type chordoma.

OBJECTIVE Chordoma is a rare bone tumor of the axial skeleton believed to originate from the remnants of the embryonic notochord. The available tumor cells are characteristically physaliferous and express brachyury, a transcription factor critical for mesoderm specification. Although chordomas are histologically not malignant, treatments remain challenging because they are resistant to radiation therapy and because wide resection is impossible in most cases. Therefore, a better understanding of the biology of chordomas using established cell lines may lead to the advancement of effective treatment strategies. The authors undertook a study to obtain this insight. METHODS Chordoma cells were isolated from the tissue of a patient with dedifferentiated-type chordoma (DTC) that had recurred. Cells were cultured with DMEM/F12 containing 10% fetal bovine serum and antibiotics (penicillin and streptomycin). Cell proliferation rate was measured by MTS assay. Cell-cycle distribution and cell surface expression of proteins were analyzed by fluorescence-activated cell sorting (FACS) analysis. Expression of proteins was analyzed by Western blot and immunocytochemistry. Radiation resistance was measured by clonogenic survival assay. Tumor formation was examined by injection of chordoma cells at hindlimb of nude mice. RESULTS The putative (DTC) cells were polygonal and did not have the conventional physaliferous characteristic seen in the U-CH1 cell line. The DTC cells exhibited similar growth rate and cell-cycle distribution, but they exhibited higher clonogenic activity in soft agar than U-CH1 cells. The DTC cells expressed high levels of platelet-derived growth factor receptor-ß and a low level of brachyury and cytokeratins; they showed higher expression of stemness-related and epithelial to mesenchymal transition-related proteins than the U-CH1 cells. Intriguingly, FACS analysis revealed that DTC cells exhibited marginal surface expression of CD24 and CD44 and high surface expression of CXCR4 in comparison to U-CH1 cells. In addition, blockade of CXCR4 with its antagonist AMD3100 effectively suppressed the growth of both cell lines. The DTC cells were more resistant to paclitaxel, cisplatin, etoposide, and ionizing radiation than the U-CH1 cells. Injection of DTC cells into the hindlimb region of nude mice resulted in the efficient formation of tumors, and the histology of xenograft tumors was very similar to that of the original patient tumor. CONCLUSIONS The use of the established DTC cells along with preestablished cell lines of chordoma may help bring about greater understanding of the mechanisms underlying the chordoma that will lead to therapeutic strategies targeting chordomas.