Study design: We conducted a prospective cohort study of 448 patients with a variety of spinal metastases. Objective. To compare the predictive value of the Tokuhashi scoring system (T12) and its revised edition (T15) for life expectancy both in the entire study group as well as in the various primary tumor subgroups. Summary of background data. In 1990 Tokuhashi and coworkers formulated a one point-addition-type prognostic scoring system with a total sum of 12 points for preoperative prediction of life expectancy as an adjunct in selecting appropriate treatment. Because the site of the primary tumor influences ultimate survival, the scoring system was revised in 2005 to a total sum of 15 points based on the origin of the primary tumor. Methods. This study included 448 patients with vertebral metastases, all of whom underwent surgical treatment during November 1992 to November 2009 at the Aarhus University Hospital. Data was retrieved from the Aarhus Spinal Metastases Algorithm. Scores based on the T12- and T15 scoring systems were calculated prospectively for each patient. All the patients were divided into three survival groups with different life expectancies according to their score points in both scoring systems. Furthermore, we divided all the patients into different groups dictated by the site of their primary tumor. The predictive value of each scoring system, both in the entire group and in each subgroup determined by the original tumour site, was evaluated by the Log-rank-test. The McNemar's test was used to compare the differences in accuracy rates between these two scoring systems. Survival curves were estimated using the Kaplan-Meier methods. Probability value less than 0.05 was considered statistically significant. Result. For the 448 patients with vertebral metastases, both the T12 and T15 scoring systems showed statistically significant predictive value (T12 group p<0.0001, T15 group p<0.0001, Log-rank test). The correlation between predicted survival period and real survival was significantly higher in T15 (p<0.0001, McNemar's test) than in T12. The further analyses by type of metastases showed that the predictive value of T12 and T15 was found in the prostate (p=0.0003), breast (p=0.0385), other tumor group (p<0.001) and lymphoma (p<0.05). Only T12 displayed predictive value in the colon group (p=0.0011). The accuracy rate of prognosis in T15 was significantly higher in those groups with spinal metastases originating from prostate (p=0.0032), breast (p<0.0001) and lung (p=0.0076). Conclusion. Both the T12 and T15 scoring systems have significant preoperative predictive value in terms of predicting the survival period for the entire vertebral metastases patient group as well as in the prostate, breast, lymphoma, and colon tumor groups. The accuracy rate was significantly improved in T15 for the total study group and in the subgroups of prostate, breast, and lung tumor

Introduction. Patients (2.7M in EU) with positive cancer prognosis frequently develop metastases (≈1M) in their remaining lifetime. In 30-70% cases, metastases affect the spine, reducing the strength of the affected vertebrae. Fractures occur in ≈30% patients. Clinicians must choose between leaving the patient exposed to a high fracture risk (with dramatic consequences) and operating to stabilise the spine (exposing patients to unnecessary surgeries). Currently, surgeons rely on their sole experience. This often results in to under- or over-treatment. The standard-of-care are scoring systems (e.g. Spine Instability Neoplastic Score) based on medical images, with little consideration of the spine biomechanics, and of the structure of the vertebrae involved. Such scoring systems fail to provide clear indications in ≈60% patients. Method. The HEU-funded METASTRA project is implemented by biomechanicians, modellers, clinicians, experts in verification, validation, uncertainty quantification and certification from 15 partners across Europe. METASTRA aims to improve the stratification of patients with vertebral metastases evaluating their risk of fracture by developing dedicated reliable computational models based on Explainable Artificial Intelligence (AI) and on personalised Physiology-based biomechanical (VPH) models. Result. The METASTRA-AI model is expected to be able to stratify most patients with limited effort end cost, based on parameters extracted semi-automatically from the medical files and images. The cases which are not reliably stratified through the AI model, are examined through a more detailed and personalised biomechanical VPH model. These METASTRA numerical tools are trained through an unprecedentedly large multicentric retrospective study (2000 cases) and validated against biomechanical ex vivo experiments (120 specimens). Conclusion. The METASTRA decision support system is tested in a multicentric prospective observational study (200 patients). The METASTRA approach is expected to cut down the indeterminate diagnoses from the current 60% down to 20% of cases. METASTRA project funded by the European Union, HEU topic HLTH-2022-12-01, grant 101080135

Vertebral metastases are the most common type of malignant lesions of the spine. Although this tumour is still considered incurable and standard treatments are mainly palliative, the standard approach consists in surgical resection, which results in the formation of bone gaps. Hence, scaffolds, cements and/or implants are needed to fill the bone lacunae. Here, we propose a novel approach to address spinal metastases recurrence, based on the use of anti-tumour metallic-based nanostructured coatings. Moreover, for the first time, a gradient microfluidic approach is proposed for the screening of nanostructured coatings having anti-tumoral effect, to determine the optimal concentration of the metallic compound that permits selective toxicity towards tumoral cells. Coatings are based on Zinc as anti-tumour agent, which had been never explored before for treatment of bone metastases. The customized gradient generating microfluidic chip was designed by Autodesk Inventor and fabricated from a microstructured mould by using replica moulding technique. Microstructured mould were obtained by micro-milling technique. The chip is composed of a system of microfluidic channels generating a gradient of 6 concentrations of drug and a compartment with multiple arrays of cell culture chambers, one for each drug concentration. The device is suitable for dynamic cultures and in-chip biological assays. The formation of a gradient was validated using a methylene blue solution and the cell loading was successful. Preliminary biological data on 3D dynamic cultures of stromal cells (bone-marrow mesenchymal stem cells) and breast carcinoma cells (MDA-MB-231) were performed in a commercial microfluidic device. Results showed that Zn eluates had a selective cytotoxic effect for tumoral cells. Indeed, cell migration and cell replication of treated tumoral cells was inhibited. Moreover, the three-dimensionality of the model strongly affected the efficacy of Zn eluates, as 2D preliminary experiments showed a high cytotoxic effect of Zn also for stromal cells, thus confirming that traditional screening tests on 2D cultured cells usually lead to an overestimation of drug efficacy and toxicity. Based on preliminary data, the customized platform could be considered a major advancement in cancer drug screenings as it also allows the rapid and efficient screening of biomaterials having antitumor effect

Bone metastases radiographically appear as regions with high (i.e. blastic metastases) or low (i.e. lytic metastases) bone mineral density. The clinical assessment of metastatic features is based on computed tomography (CT) but it is still unclear if the actual size of the metastases can be accurately detected from the CT images and if the microstructure in regions surrounding the metastases is altered (Nägele et al., 2004, Calc Tiss Int). This study aims to evaluate (i) the capability of the CT in evaluating the metastases size and (ii) if metastases affect the bone microstructure around them. Ten spine segments consisted of a vertebra with lytic or mixed metastases and an adjacent control (radiologically healthy) were obtained through an ethically approved donation program. The specimens were scanned with a clinical CT (AquilionOne, Toshiba: slice thickness:1mm, in-plane resolution:0.45mm) to assess clinical metastatic features and a micro-CT (VivaCT80, Scanco, isotropic voxel size:0.039mm) to evaluate the detailed microstructure. The volume of the metastases was measured from both CT and micro-CT images (Palanca et al., 2021, Bone) and compared with a linear regression. The microstructural alteration around the metastases was evaluated in the volume of interest (VOI) defined in the micro-CT images as the volume of the vertebral body excluding the metastases. Three 3D microstructural parameters were calculated in the VOI (CTAn, Bruker SkyScan): Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th.), Trabecular Spacing (Tb.Sp.). Medians of each parameter were compared (Kruskal-Wallis, p=0.05). One specimen was excluded as it was not possible to define the size of the metastases in the CT scans. A strong correlation between the volume obtained from the CT and micro-CT images was found (R2=0.91, Slope=0.97, Intercept=2.55, RMSE=5.7%, MaxError=13.12%). The differences in BV/TV, Tb.Th. and Tb.Sp. among vertebrae with lytic and mixed metastases and control vertebrae were not statistically significant (p-value>0.6). Similar median values of BV/TV were found in vertebrae with lytic (13.2±2.4%) and mixed (12.8±9.8%) metastases, and in controls (13.0±10.1%). The median Tb.Th. was 176±18 ∓m, 179±43 ∓m and 167±91 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. The median Tb. Sp. was 846±26 ∓m, 849±286 ∓m and 880±116 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. In conclusion, the size of vertebral metastases can be accurately assess using CT images. The 3D microstructural parameters measured were comparable with those reported in the literature for healthy vertebrae (Nägele et al., 2004, Calc Tiss Int, Sone et al., 2004, Bone) and showed how the microstructure of the bone tissue surrounding the lesion is not altered by the metastases

Purpose of the study: The goal of palliative surgical treatment of vertebral metastases is to avoid, stabilise, or improve neurological disorders and to relieve pain. We propose early treatment for fixation of threatening lesions and extensive release without resection for programmed surgery outside the emergency context. Material and methods: From 2001 to 2005, eighty patients underwent scheduled surgery for threatening or symptomatic lesions. Mean age was 59 years (range 32–82). The primary tumour was: breast (n=35), lung (n=19), kidney (n=8), uterus (n=1), prostate (n=2), ENT (n=3), gastrointestinal (n=5), haematology (n=7). Sixty-six patients presented Frankel B to D neurological involvement. The Tokuhashi score was 8 on average (range 5–9) and the Karnofsky index 57% (range 30–70). Sixty-four patients had visceral metastases. On average 7 levels were instrumented (range 4 to 8). The procedure included laminectomy in all cases. Results: Blood loss was 500 cc (300–2700) and operative time 110″ (65–110). Fifty-nine patients recovered one or more Frankel grade. Six patients (7%) developed a postoperative infection. The actuarial survival at one year was 78%; 95% for patients free of motor neurological involvement and 65% for the others. This difference was significant. Discussion: Spinal metastases should be detected and treated before emergency care is required. At the present time this treatment is well programmed. Fixation without tumour resection enables prolonged survival and allows time for other treatments in a pluridisciplinary management scheme. Several therapeutic options are possible but converge towards improved quality of life. Conclusion: Posterior tumour resection is not useful for palliative surgical management of vertebral metastases. We propose an active approach using a simple well-defined surgical procedure without waiting for development of a neurological emergency

Quantitative assessment of metastatic involvement of the bony spine is important for assessing disease progression and treatment response. Quantification of metastatic involvement is challenging as tumours may appear as osteolytic (bone resorbing), osteoblastic (bone forming) or mixed. This investigation aimed to develop an automated method to accurately segment osteoblastic lesions in a animal model of metastatically involved vertebrae, imaged with micro computed tomography (μCT). Radiomics seeks to apply standardized features extracted from medical images for the purpose of decision-support as well as diagnosis and treatment planning. Here we investigate the application of radiomic-based features for the delineation of osteoblastic vertebral metastases. Osteoblastic lesions affect bone deposition and bone quality, resulting in a change in the texture of bony material physically seen through μCT imaging. We hypothesize that radiomics based features will be sensitive to changes in osteoblastic lesion bone texture and that these changes will be useful for automating segmentation. Osteoblastic metastases were generated via intracardiac injection of human ZR-75-1 breast cancer cells into a preclinical athymic rat model (n=3). Four months post inoculation, ex-vivo μCT images (µCT100, Scanco) were acquired of each rodent spine focused on the metastatically involved third lumbar vertebra (L3) at 7µm/voxel and resampled to 34µm/voxel. The trabecular bone within each vertebra was isolated using an atlas and level-set based segmentation approach previously developed by our group. Pyradiomics, an open source Radiomics library written in python, was used to calculate 3D image features at each voxel location within the vertebral bone. Thresholding of each radiomic feature map was used to isolate the osteoblastic lesions. The utility of radiomic feature-based segmentation of osteoblastic bone tissue was evaluated on randomly selected 2D sagittal and axial slices of the μCT volume. Feature segmentations were compared to ground truth osteoblastic lesion segmentations by calculating the Dice Similarity Coefficient (DSC). Manually defined ground truth osteoblastic tumor segmentations on the μCT slices were informed by histological confirmation of the lesions. The radiomic based features that best segmented osteoblastic tissue while optimizing computational time were derived from the Neighbouring Gray Tone Difference Matrix (NGTDM). Measures of coarseness yielded the best agreement with the manual segmentations (DSC=707%) followed by contrast, strength and complexity (DSC=6513%, 5428%, and 4826%, respectively). This pilot study using a radiomic based approach demonstrates the utility of the NGTDM features for segmentation of vertebral osteoblastic lesions. This investigation looked at the utility of isolated features to segment osteoblastic lesions and found modest performance in isolation. In future work we will explore combining these features using machine learning based classifiers (i.e. decision forests, support vector machines, etc.) to improve segmentation performance

Introduction. The rising incidence of metastatic bone disease (MBD) in the UK poses a significant management problem. Poorly defined levels of service provision have meant that improvements in patient prognosis have been mediocre at best. For that reason the British Orthopaedic Association (BOA) in conjunction with the British Orthopaedic Oncology Society (BOOS) issued guidelines in 2002 on good practice in the management of MBD. Despite the availability of these standards, there is very little robust data available for audit. The aim of this study was to conduct a regional survey of how these guidelines are being used in the management of MBD. Methods. A questionnaire was designed with 9 multiple choice questions representing the most common MBD scenarios. This was posted to 106 Consultant Orthopaedic Surgeons in 12 NHS Trusts in the South East of England. Results. The overall response rate to the questionnaire was 44%. There was considerable variation in the management of solitary femoral diaphyseal lesions, pathological subtrochanteric and intertrochanteric femoral neck fractures and vertebral metastases. Furthermore only 2 out of the 12 Trusts surveyed had a designated MBD lead as per the BOA/BOOS guidelines. Discussion. Our study reflects the variation in the management of MBD throughout the region, which may in turn be linked to poorer clinical outcomes. The results demonstrate the possibility of (i) inappropriate initial treatment, (ii) subsequent late tertiary referral and (iii) poor understanding of the biomechanical basis of orthopaedic implants, with the potential for inappropriate choice of prostheses and high failure rates. Streamlining cancer care will involve establishing regional MBD units within large centres where multidisciplinary services are available. Consequently all surrounding hospitals will need a designated MBD lead that can function as a conduit to this integrated care for selected patients

Historically spine surgeons have been powerless to help most patients with painful vertebral insufficiency fractures. Treatment was supportive, hoping that fractures could heal in situ, and accepting the resulting kyphosis and its consequences. Surgery was the court of last resort in instances of disabling neurologic deficits. The very same deficient skeleton that lead to the clinical issue, was simultaneously the principal limiting factor in surgical undertakings. Complications could be common and substantial. Vertebroplasty was born out necessity in the treatment of ‘inoperable’ vertebral metastases. The technique has become a widely adopted method of managing refractory painful vertebral insufficiency fractures, especially those due to osteoporosis. In skilled hands, vertebroplasty provides a high degree of pain relief and patient satisfaction. The fracture is fixed in situ as the marrow space is embolised with PMMA. Kyphoplasty is a technical evolution that enables active fracture reduction before fixation with PMMA. Much is made about the potential differences between the two treatment methods, but no direct comparative studies are available to allow objective conclusions. In any event, as medical therapies improve the treatment of osteoporosis in general, surgeons now have the opportunity to intervene when painful vertebral fractures are a primary source of functional impairment and life quality

Introduction: The rising incidence of metastatic bone disease (MBD) in the UK poses a significant management problem. Poorly defined levels of service provision have meant that improvements in patient prognosis have been mediocre at best. For that reason the British Orthopaedic Association (BOA) in conjunction with the British Orthopaedic Oncology Society (BOOS) issued guidelines in 2002 on good practice in the management of MBD. Despite the availability of these standards, there is very little robust data available for audit. The aim of this study was to conduct a regional survey of how these guidelines are being used in the management of MBD. Methods: A questionnaire was designed with 9 multiple choice questions representing the most common MBD scenarios. This was posted to 106 Consultant Orthopaedic Surgeons in 12 NHS Trusts in the South East of England. Results: The overall response rate to the questionnaire was 44%. There was considerable variation in the management of solitary femoral diaphyseal lesions, pathological subtrochanteric and intertrochanteric femoral neck fractures and vertebral metastases. Furthermore only 2 out of the 12 Trusts surveyed had a designated MBD lead as per the BOA/BOOS guidelines. Discussion: Our study reflects the variation in the management of MBD throughout the region, which may in turn be linked to poorer clinical outcomes. The results demonstrate the possibility of. inappropriate initial treatment,. subsequent late tertiary referral and. poor understanding of the biomechanical basis of orthopaedic implants, with the potential for inappropriate choice of prostheses and high failure rates. Streamlining cancer care will involve establishing regional MBD units within large centres where multidisciplinary services are available. Consequently all surrounding hospitals will need a designated MBD lead that can function as a conduit to this integrated care for selected patients

Introduction and purpose: The purpose of our study is to make a critical review of our experience and find a method of systematised, objective therapeutic strategy in the treatment of vertebral metastases. Materials and methods: We reviewed 38 cases of vertebral metastasis (1995–2004) from primary tumours: lung 21%, breast 21%, prostate 12%, renal 12%, ovary 8%, tongue 4%, cavum 4%, melanoma 4%, unknown primary tumour 17%. 24 cases were treated surgically in terms of the clinical criterion agreed between oncologist and traumatologist. We reviewed the follow-up of the cases (treatment, complications, mortality) and the subsequent application of the Tokuhashi prognostic index and the Tomita therapy protocol with two objectives: to evaluate our results and assess these two methods as working tools. Results: 74% of the patients had preoperative radiotherapy. The surgical treatment was corporectomy and dorsal decompression (17%), partial corporectomy and dorsal decompression (29%), decompression and dorsal instrumentation (37%) and non-instrumented decompression laminectomy (17%). The mean survival was 17 months. The surgical treatment controlled pain in 87%; there was neurological improvement in 21%, control in 54% and progression in 25%. Conclusions: Our results were not as good as those found in the literature, in which the usefulness of postoperative radiotherapy is emphasised. Preoperative radiotherapy may have made tumour excision more difficult which, together with the delayed decision-making, influenced the loss of efficacy in our cases. We need more prospective studies to validate the Tokuhashi index and the Tomita protocol, which we think are very useful in taking therapy decisions

Introduction. The main symptoms in multiple myeloma are the result of skeletal destruction mainly the vertebral column. The current treatments for multiple myeloma include radiotherapy and chemotherapy but unfortunately it is still incurable. However, the symptoms and quality of life of these patients can be improved by cement augmentation which has gained popularity in the recent years. Aim. To analyse the efficacy and safety of cement augmentation and to assess the survival and outcome of the patients with vertebral fractures secondary to multiple myeloma. Material and Methods. In this retrospective study, we reviewed the data over the last 3 years. Medical records review included correction of vertebral angle (VA), assessment of disability, survival and postoperative improvement in pain and functional status. Results. We reviewed 12 patients with 48 vertebral compression fractures including 9 male and 3 female patients. Mean age was 62.5 years (41–85). 5 patients had single vertebral involvement while 7 had multiple fractures at different levels in thoracolumbar spine. Average length of follow-up was 20.3 months (14–33 months). Based on Modified Tokuhashi score, the expected survival was less than 12 months in 2 patients and more than 12 months in the remaining patients. 11 patients are alive till date with average survival of 26 months (18–42 months) while 1 patient died, 23 months after the initial correction surgery. Prior to correction, the average vertebral angle (VA) was 10.60 (2.30 to 25.20) and after cement augmentation the average VA was 7.00 (1.60–22.80). Mean correction achieved was 3.60. There was no loss of vertebral height in any patient until their latest follow-up. Karnofsky performance score was more than 70 in 5 patients, 50–70 in 6 and less than 50 in 1 patient preoperatively while it improved to more than 70 in all patients postoperatively which indicates improvement in their functional status. All patients reported improvement in their pain level after surgery. No cement leakage or major complication occurred in these patients. Conclusion. Cement augmentation is a safe and effective way of treating the symptoms of multiple myeloma which occur due to vertebral metastases. It results in excellent pain control and improvement in quality of life

Study Design: A retrospective review of case notes and histology reports. Summary of Background Data: Up to 8% of cancer patients develop second malignancies. The vertebral column is frequently involved in metastatic disease and may represent the first manifestation of malignancy in up to 40% of patients. The rate of vertebral metastasis from a second tumour in patients with a known primary is not well known. Objective: We sought to identify the incidence of a second primary in patients referred to our unit with spinal malignancy and a previously diagnosed primary tumour. Subjects: 222 patients underwent definitive surgery for spinal metastatic disease of whom 135 had a prior history of malignancy. Outcome measures: Histological tissue of origin of spinal metastasis in light of previous known malignancy. Results: In 16 patients (11.9%) the vertebral histology differed from the initial primary. The period between first and second malignancies varied widely (19 months – 22 years). Thirteen patients (9.6%) had identifiable tissue origins for the metastasis that was not in keeping with the previous malignancy. Three further patients showed sufficient histological and imunohistochemical differences such that a further tumour of unknown origin and not de-differentiation of the previous tumour was suspected. Three previously unrecognised tumours were diagnosed on biopsy and eight on tissue obtained at definitive surgery. Conclusion: The incidence of second primaries, in particular myeloma, presenting with vertebral metastases is significant and should always be borne in mind when assessing patients and planning treatment. Biopsy should be performed when possible. Comparison needs to be made between the histological features of the previous primary and metastasis

Using serial CT scans, this project aims to develop a clinical research tool that analyzes changes in vertebral density in spines involved with metastatic disease. Tracking of total vertebral body and tumor volume alone was investigated. A program was developed to semi-automate the segmentation of the region of interest followed by image registration to superimpose the segmentation onto spatially aligned serial scans. Based on analysis of a simulated metastatic vertebra, generating a voxel distribution histogram from the vertebral body best quantified density in serial scans. This quantification method may improve clinical decision-making and treatment options for patients with vertebral metastases. To develop a clinical research tool to serially track tumor involvement in vertebrae with metastatic disease by quantifying changes in CT attenuation. Segmentation of the vertebral body and analysis of the voxel distribution within the region provides the most accurate method of quantifying changes in tumor involvement for the metastatic spine. A quantitative method to assess the progression or regression of disease may improve clinical decision–making and treatment options for patients with spinal metastases. The vertebral body segmentation was more accurate at tracking tumor involvement (voxel distribution histogram: 96.8% +/− 0.75% accuracy, mean density error: 4.7% +/− 0.8%) than segmenting the tumor volume alone (voxel distribution histogram: 86.1% +/− 3.6% accuracy, mean density error: 14.1% +/− 4.8%). A program was developed to semi-automatically segment the total vertebral body and tumor volume alone from CT scans of metastatically involved vertebrae. Image registration through user-defined landmarks and surface matching was used to spatially align serial scans, and the initial segmentation was superimposed with the aligned scans. Changes within the segmentation between CT scans were tracked using mean density and a voxel distribution histogram. A cadaveric vertebra with a simulated tumor was scanned at five orientations with 20° offsets to determine the accuracy of the methods. Error primarily resulted from unavoidable re-sampling during alignment of the scans

Photodynamic therapy (PDT) is a promising new treatment for spinal metastases; however, the effects of PDT on bone are largely unknown. This study assessed the impact of PDT on spinal stability in rats at high (non-therapeutic) drug and LASER light doses. Spinal stability was assessed using stereological measures attained from in vitro μCT scans. High doses of PDT were shown to cause a reduction in vertebral density. Postoperative paralysis was also noted in a subset of animals treated. Tumour-involved vertebrae are already mechanically weakened; as such it is essential to establish a safe and efficacious therapeutic window for vertebral PDT. This study assessed the effect of high doses of photodynamic therapy (PDT) on biomechanical stability and bone density of lumbar vertebrae. PDT can cause damage to the vertebral bone and induce paralysis when treatment is applied at very high doses in the rat spine. PDT is a promising new treatment for spinal metastases however, it is important to understand its effect on vertebral bone in order to closely define the therapeutic window for safety and efficacy. Trabecular bone density decreased from L1–L3 in normal, untreated rats. The L2 vertebra when treated with high dose PDT was shown to have decreased bone density as compared to both L1 and L3. As expected, tumour-bearing rats had lower vertebral densities than normals. Rnu/Rnu rats were separated into normal controls, normals treated with PDT and tumour-bearing rats. Rats treated with PDT received an intercardiac injection of 2.5mg/Kg BPD-MA. The drug was activated through administration of 500J (300mA) of a non-thermal 690nm LASER adjacent to the L2 vertebral body. After one week, in vitro μCT scans were taken of L1–L3 and stereological quantities measured. The demonstrated reduction of bone density as quantified one week following treatment is important when considering spinal stability in the potential use of PDT to treat vertebral metastases. We have observed that the therapy can induce paralysis when treatment is applied at high doses in the rat spine. The intermediate and long-term effects of PDT on bone remain unknown and require ongoing study

Purpose. Maintenance of vertebral mechanical stability is of paramount importance to prevent pathologic fractures and resultant neurologic compromise in individuals with spinal metastases. Current non-surgical treatments for vertebral metastases (i.e. chemotherapy, bisphophonates (BP) and radiation) yield variable responses in the tumour and surrounding bone. Photodynamic therapy (PDT) is a novel, minimally-invasive technology that utilizes a drug activated by light at a specific non-thermal wavelength to locally destroy tumour cells. Previously, we observed that PDT can ablate cancer cells within bone and yield short-term (1-week) improvements in vertebral architecture and biomechanical strength, particularly when combined with BP therapy. This study aims to evaluate the effects of PDT in vertebral bone over a longer (6-week) time period, alone and combined with previous BP treatment, to determine if improvements in skeletal architecture and strength are maintained. Method. Fourty healthy rnu/rnu rats were randomly assigned to four treatment groups: (i) untreated control, (ii) BP only, (iii) PDT only and (iv) PDT following BP. BP treatments were administered on day 0 via subcutaneous injection of zoledronic acid. PDT was administered on day 7 via an intravenous injection of BPD-MA photosensitizer. A flat-cut optical fiber was inserted percutaneously adjacent to lumbar vertebra L2. After a 15-minute drug-light interval, 75J of light energy was delivered from a 690nm laser. Six weeks later, animals were euthanized. Structural properties of excised L2 vertebral bodies were quantified through semi-automated analysis of micro-CT images. In of the specimens, mechanical properties were evaluated by loading the L2 vertebral body to failure in axial compression. The remaining L2 vertebrae were analyzed for morphology, osteoid formation and osteoclast activity using histological methods. Results. Combined PDT+BP treatment yielded the largest increases in bone volume fraction (31%), trabecular thickness (45%) and vBMD (37%) and decreases in trabecular number (14%) and separation (26%) compared to untreated controls (n=10, all p<0.05). The cortical shell mass fraction was significantly lower than that of controls (24%) indicating increases in bone structure were primarily due to trabecular changes. Mechanically, PDT+BP treatment demonstrated a trend towards an increase in ultimate force compared to controls (n=5, p=0.176). BP-only and PDT-only treatments demonstrated similar trends to the combined treatment, but with a lower magnitude of effect. Qualitatively, histological analysis suggested more osteoid formation in groups receiving PDT, and a higher proportion of bone in BP-treated groups. Conclusion. PDT has a sustained positive effect on the mechanical and structural integrity of bone, particularly in combination with BP treatment. By ablating tumour tissue and strengthening bone, combined PDT+BP treatment presents as an attractive adjuvant minimally-invasive therapy for spinal metastasis

Vertebroplasty (VP) is currently used to improve spinal stability in patients with vertebral metastases. This study assessed the effects of Laser Induced Thermo Therapy (LITT), a minimally invasive technique used to ablate tumor tissue prior to vertebroplasty. Load-induced canal narrowing (LICN) was measured pre and post-vertebroplasty in twelve paired spinal motion segments with simulated lytic metastases. LICN improved post-vertebroplasty for all specimens treated with LITT. In all specimens, cement location was an important factor in post-vertebroplasty stability. Reduction of the tumor volume pre-vertebroplasty resulted in more reliable defect filling. To investigate the effect of tumor ablation using Laser Induced Thermo Therapy (LITT) prior to vertebroplasty (VP) on cement distribution and vertebral stability. Tumor volume reduction using LITT prior to cement injection improves defect filling and consistently reduces Load Induced Canal Narrowing (LICN). A simple, minimally invasive procedure providing accurate tissue destruction pre-vertebroplasty may result in more reliable cement fill, reduce cement extravasation and improve post-vertebroplasty stability. Following verebroplasty, LICN improved in all specimens treated with LITT and in those VP alone specimens with cement located posterior to the tumor tissue (33%). LITT treated vertebrae exhibited a trend toward reduced posterior wall motion post-vertebroplasty (LICN=29.7±27.1%) versus specimens treated with VP alone (LICN=248.7±253%). In the LITT+VP group, cement was fully contained within the vertebral body while cement extravasation into the canal was noted in 33% of the specimens treated without LITT. Twelve paired cadaveric thoracolumbar spinal motion segments with simulated lytic metastases were randomized for treatment with VP alone or LITT+VP. In the LITT+VP group, a laser fibre inserted through a transpedicular approach was used to ablate the tumor tissue prior to cement injection. The specimens were axially loaded to 800N pre and post-treatment. LICN was used as a measure of vertebral stability. Cement location was assessed post-testing through axial sectioning. Location of cement is an important factor in determining post-VP stability. Vertebroplasty is effective in decreasing LICN if the tumor is ablated or surrounded posteriorly with cement. Funding: USAMRMC DAMD 17–00–1–0693

Purpose: To examine the effect of image resolution and structural model on quantifying architectural differences between healthy and metastatically involved vertebrae. Method: Lumbar vertebrae of healthy(n=6) and meta-statically involved(n=6) rnu/rnu rats were utilized. Osteolytic vertebral metastases were developed via intracardiac injection of human MT1 breast cancer cells. μCT images of the vertebrae were acquired ex vivo at 14μ isotropic spatial resolution. The whole vertebrae were segmented using an automated atlas based demons deformable registration followed by level set curvature evolutions. A subsequent iteration of level set was used to yield a segmentation of the trabecular centrum. The individual trabecular network was further segmented using intensity based thresholding. Architectural parameters were computed from the segmented μCT images: Cortical Bone Volume(CBV), Trabecular Bone Volume(TBV), Trabecular Bone Surface Area and the degree of anisotropy based on Mean Intercept Length(MIL). From this, trabecular Thickness(TbTh), Trabecular Number(TbN) and Trabecular Separation(TbS) were calculated using the Parfitt Model (Parfitt, Bone & Mineral. 1987). TbTh was also calculated separately using the Hilderbrand model (Hilderbrand, J of Microscopy 1997). The degree of anisotropy was determined via Mean Intercept Length (MIL) measured utilizing a binary shift/subtraction approach. The measures of TbTh and MIL were compared for each image at 8.725(high), 17.45(medium) and 34.9(low) μm3 isotropic spatial resolutions. Results: Parfitt’s plate model showed a significant decrease in TBV, TbN and CBV and a significant increase in TbS in the metastatic vertebrae in comparison to the healthy group at the highest resolution. In both Hilderbrand’s and Parfitt’s models at the highest resolution there was no significant difference in TbTh between the healthy and metastatic groups. In both models, TbTh and TbS values rose while TBV and TbN decreased as the resolution was lowered. Significant reductions were observed only in TbTh between the healthy and metastatic vertebrae at the medium and low resolutions. In all cases, the Hildebrand model yielded lower values of TbTh than the Parfitt model. However, achieving robust automated results using the Hildebrand method was limited in the final stage of the segmentation due to sensitivity to small islands of bone. Structural anisotropy remained consistent in all groups at all resolutions, with ~3x greater MIL in the superior/inferior direction. The degree of anisotropy was, however, consistent in both groups suggesting that the metastatic destruction does not have any directional preference. Conclusion: The automated use of Parfitt’s plate model along with the MIL method can be used to yield quantitative analyses demonstrating differences in vertebral microstructure due to metastatic involvement. However the sensitivity of these architectural parameters to resolution motivates the need for high resolution scanning in future preclinical applications

Aims: The purpose is to assess the risk of spinal cord compression in patients with spine metastases using radiological data. Methods: We evaluate 103 patients with the thoraco-lumbar vertebral body metastases Ð 52 with neurological symptoms of spinal cord compression and 51 symptoms free. We measured the statistical relation between spinal cord compression, pathological fracture, angle deformity of the spine and metastasis location. We divide spine into 3 columns and named pediculum as the fourth. We used statistical multiple regression analysis. Results: The risk of spinal cord compression is depended on the location of the metastasis in vertebral body (p< 0,01). We found spinal cord compression symptoms in 25 out of 31 patients in group with pediculum involvement and in 27 out of 72 in group with other locations. It was highly statistically important (p< 0.001). In 45 out of 68 patients with vertebral fractures we found spinal cord compression symptoms (p< 0.01). We did not found statistical correlation between angle deformity and compression symptoms. Conclusions: Compression risk is higher if the metastases are localised in thoraco-lumbar part of spine and if the pediculum is involved. The pathological fracture increases the risk of the compression, too

Introduction: Arterial bleeding following pelvic fractures is widely recognized as an indication for angiography and embolization although controversy persists as to the timing of this procedure in the treatment algorithm. Less well appreciated is its application in similar circumstances following blunt injury to the pelvic arteries and limb injuries. We describe our experience in a variety of haemorrhagic orthopaedic pathologies. Patients and Methods: Angiography was performed in 29 patients- 16 with pelvic fractures, 9 with extremity injuries, and 4 with tumors. Seldinger technique was used for angiographic access, usually from the groin although on occasion extensive local injury required use of the brachial approach. Following the initial diagnostic study the a selective catheter was placed at the target, appropriate embolic material was selected and the source of haemorrhage was closed off. Results: In our experience of pelvic traumatic bleeding (14 associated with fracture, 2 without) embolization was successful in promptly arresting hemorrhage in all but one case of advanced DIC. Mortality was confined to this last case and two others, all of whom were referred for embolization following prolonged hypotension and commenced angiographic intervention with blood pressure unmeasureable or of the order of 30mm systolic. With 9 cases of extremity injury, 1 iatrogenic, 5 penetrating, 2 blunt and one following fracture of the femur, embolization successfully treated the hemorrhage. Finally we present our experience in preventing hemorrhage in 4 cases, 3 of which were vertebral body tumours and 1 pathological fracture of the humerus due to RCC. At surgery following embolization none bled significantly. Conclusions: The present study describes our experience in various orthopedic conditions. Less well recognized is its role in preventing hemorrhage; as a prelude to bloody operations on vertebral body metastases, aneurysmal bone cysts and hemangiomata as well as open reduction and internal fixation of pathological extremity fractures. We conclude that this technique is a valuable addition to the tools available to the orthopedic surgeon and whose application is not necessarily limited to the examples quoted, but should be applied in any case where the direct surgical approach is considered hazardous or ineffective

Objectives

In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians.