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. Methods. A total of 39 patients with non-fractured femoral metastatic lesions who were irradiated for pain were included from three radiotherapy institutes. During follow-up, nine pathological fractures occurred in seven patients. Quantitative CT-based FE models were generated for all patients. Femoral failure load was calculated and compared between the fractured and non-fractured femurs. Due to inter-scanner differences, patients were analyzed separately for the three institutes. In addition, the FE-based predictions were compared with fracture risk assessments by experienced clinicians. Results. In institute 1, median failure load was significantly lower for patients who sustained a fracture than for patients with no fractures. In institutes 2 and 3, the number of patients with a fracture was too low to make a clear distinction. Fracture locations were well predicted by the FE model when compared with post-fracture radiographs. The FE model was more accurate in identifying patients with a high fracture risk compared with experienced clinicians, with a sensitivity of 89% versus 0% to 33% for clinical assessments. Specificity was 79% for the FE models versus 84% to 95% for clinical assessments. Conclusion. FE models can be a valuable tool to improve clinical fracture risk predictions in metastatic bone disease. Future work in a larger patient population should confirm the higher predictive power of FE models compared with current clinical guidelines. Cite this article: F. Eggermont, L. C. Derikx, N. Verdonschot, I. C. M. van der Geest, M. A. A. de Jong, A. Snyers, Y. M. van der Linden, E. Tanck. Can patient-specific finite element models better predict fractures in metastatic bone disease than experienced clinicians? Towards computational modelling in daily clinical practice. Bone Joint Res 2018;7:430–439. DOI: 10.1302/2046-3758.76.BJR-2017-0325.R2

Aims. Surgery is often indicated in patients with metastatic bone disease (MBD) to improve pain and maximize function. Few studies are available which report on clinically meaningful outcomes such as quality of life, function, and pain relief after surgery for MBD. This is the published protocol for the Bone Metastasis Audit — Patient Reported Outcomes (BoMA-PRO) multicentre MBD study. The primary objective is to ascertain patient-reported quality of life at three to 24 months post-surgery for MBD. Methods. This will be a prospective, longitudinal study across six UK orthopaedic centres powered to identify the influence of ten patient variables on quality of life at three months after surgery for MBD. Adult patients managed for bone metastases will be screened by their treating consultant and posted out participant materials. If they opt in to participate, they will receive questionnaire packs at regular intervals from three to 24 months post-surgery and their electronic records will be screened until death or five years from recruitment. The primary outcome is quality of life as measured by the European Organisation for Research and the Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ) C30 questionnaire. The protocol has been approved by the Newcastle & North Tyneside 2 Research Ethics Committee (REC ref 19/NE/0303) and the study is funded by the Royal College of Physicians and Surgeons of Glasgow (RCPSG) and the Association for Cancer Surgery (BASO-ACS). Discussion. This will be the first powered study internationally to investigate patient-reported outcomes after orthopaedic treatment for bone metastases. We will assess quality of life, function, and pain relief at three to 24 months post-surgery and identify which patient variables are significantly associated with a good outcome after MBD treatment. Cite this article: Bone Jt Open 2021;2(2):79–85

Objectives

Guidelines for the management of patients with metastatic bone disease (MBD) have been available to the orthopaedic community for more than a decade, with little improvement in service provision to this increasingly large patient group. Improvements in adjuvant and neo-adjuvant treatments have increased both the number and overall survival of patients living with MBD. As a consequence the incidence of complications of MBD presenting to surgeons has increased and is set to increase further. The British Orthopaedic Oncology Society (BOOS) are to publish more revised detailed guidelines on what represents ‘best practice’ in managing patients with MBD. This article is designed to coincide with and publicise new BOOS guidelines and once again champion the cause of patients with MBD.

Aims. The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype. Methods. The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures. Results. In total, 407,893 unique patients with metastatic bone disease were identified. Of the 14 primary tumours assessed, metastatic bone disease most frequently originated from lung (24.8%), prostatic (19.4%), breast (19.3%), gastrointestinal (9.4%), and urological (6.5%) malignancies. The top five malignant tumours resulting in long bone pathological fracture were renal (5.8%), myeloma (3.4%), female reproductive (3.2%), lung (2.8%), and breast (2.7%). Following treatment of pathological fractures of long bones, 90-day mortality rates were greatest for lung (12.1%), central nervous system (10.5%), lymphoma (10.4%), gastrointestinal (10.1%), and non-renal urinary (10.0%) malignancies. Finally, our study demonstrates improved 90-day and 360-day survival in patients treated for impending pathological fracture compared to completed fracture, as well as significantly lower rates of deep vein thrombosis, pulmonary embolism, urinary tract infection, and blood transfusion. Conclusion. This study defines the contemporary characteristics of primary malignancies resulting in metastatic bone disease. These data should be considered by surgeons when prognosticating patient outcomes during treatment of their metastatic bone disease. Cite this article: Bone Jt Open 2023;4(6):424–431

Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

Advances in cancer therapy have prolonged cancer patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in patients more likely to walk after surgery, longer survival, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data for MBD patients (2009–2016) in order to determine which features are most commonly associated with fracture. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 1146 patients comprising 224 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray. The clinical data includes patient demographics, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. Each of Mirel's criteria has been further subdivided and recorded for each lesion. We have trained a convolutional neural network (CNN) with X-ray images of 1146 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. This model converges on two fully connected deep neural network layers that output the fracture risk. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a test's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Five-fold cross validation testing of our fully trained model revealed accurate classification for 88.2% of patients with metastatic bone disease of the proximal femur. The F1 statistic is 0.87. This represents a 24% error reduction from using Mirel's criteria alone to classify the risk of fracture in this cohort. This is the first reported application of convolutional neural networks, a machine learning algorithm, to an important Orthopaedic problem. Our neural network model was able to achieve impressive accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to validate this algorithm on an external cohort

Advances in cancer therapy have prolonged patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in longer survival, preserved mobility, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The ideal clinical decision support tool will be of the highest sensitivity and specificity, non-invasive, generalizable to all patients, and not a burden on hospital resources or the patient's time. Our research uses novel machine learning techniques to develop a model to fill this considerable gap in the treatment pathway of MBD of the femur. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data of consecutive MBD patients presenting from 2009–2016. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 546 patients comprising 114 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray and clinical data including patient demographics, Mirel's criteria, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. We have trained a convolutional neural network (CNN) with AP X-ray images of 546 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. The model converges on two fully connected deep neural network layers that output the risk of fracture. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections, until overall prediction accuracy is optimized. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across five test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a model's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Our model achieved 88.2% accuracy in predicting fracture risk across five-fold cross validation testing. The F1 statistic is 0.87. This is the first reported application of convolutional neural networks, a machine learning algorithm, to this important Orthopaedic problem. Our neural network model was able to achieve reasonable accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to externally validate this algorithm on an international cohort

Surgical management for acute or impending pathologic fractures in metastatic bone disease (MBD) places patients at high-risk for post-operative venous thromboembolism (VTE). Due to the combination of malignancy, systemic cancer treatment, and surgical treatment, VTE-risk is increased 7-fold in patients with MBD compared to non-cancer patients undergoing the same procedure. The extent and duration of post-operative hypercoagulability in patients with MBD remains unknown and thromboprophylaxis guidelines were developed for non-cancer patients, limiting their applicability to address the elevated VTE-risk in cancer patients. Thrombelastography (TEG) analysis is a point-of-care test that measures clot formation, stabilization, and lysis in whole blood samples. The TEG parameter, maximal amplitude (MA), indicates clot strength and the threshold of ≥65 mm has been used to define hypercoagulability and predict VTE events in non-cancer patients requiring orthopaedic surgery. Therefore, this study aims to quantify the extent and duration of post-operative hypercoagulability in patients with MBD using serial TEG analysis. Consecutive adults (≥18 years) with MBD who required orthopaedic surgery for acute or impending pathologic fractures were enrolled into this single-centre, prospective cohort study. Serial TEG analysis was performed onsite using a TEG®6s haemostasis analyzer (Haemonetics Corporation, Boston, MA) on whole blood samples collected at seven timepoints: pre-operatively; on post-operative day (POD) 1, 3, and 5; and at 2-, 6-, and 12-weeks post-operatively. Hypercoagulability was defined as MA ≥65 mm. Participants received standardized thromboprophylaxis for four weeks and patient-reported compliance with thromboprophylaxis was recorded. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were performed and difference between pre-operative MA values of participants with VTE versus no VTE was evaluated using Student's t-test (p≤0.05). Twenty-one participants (10 female; 47.6%) with a mean age of 70 ± 12 years were enrolled. Nine different primary cancers were identified amongst participants, with breast (23.8%), colorectal (19.0%), and lung cancer (14.3%) most frequently reported. Most participants (57.1%) were hypercoagulable pre-operatively, and nearly half remained hypercoagulable at 6- and 12-weeks post-operatively (47.1 and 46.7%, respectively). VTE occurred in 5 patients (23.8%) and mean MA was 68.1 ± 4.6 mm at the time of diagnosis. Mean pre-operative MA values were significantly higher (p=0.02) in patients who experienced VTE (68.9 ± 3.5 mm) compared to those who did not (62.7 ± 6.5 mm). VTE incidence was highest in the first week post-operatively, during which time four VTE events (80%) occurred. The proportion of patients in a hypercoagulable state increased at three consecutive timepoints, beginning on POD3 (85.0%), increasing on POD5 (87.5%), and peaking at 2-weeks post-operatively (88.9%). Current thromboprophylaxis guidelines do not consider cancer-associated risk factors that contribute to increased VTE incidence and prescription duration may be inadequate to address prolonged post-operative hypercoagulability in patients with MBD. The high rate of VTE events observed and sustained hypercoagulable state indicate that thromboprophylaxis may be prematurely terminated while patients remain at high risk for VTE. Therefore, extending thromboprophylaxis duration beyond 4-weeks post-operatively in patients with MBD warrants further investigation

Due to advances in the assessment and treatment of patients with metastatic bone disease, the survival has improved in recent years. It was the aim of this met-analysis to assess the outcome of patients with metastatic bone disease across Europe. Five major bone tumour treatment centres participated in the met-analyses. Data had been collected prospectively and was retrieved from the databases for the purpose of this study. All patients were referred to the bone tumour centre for assessment and possible surgical treatment. The data of almost 2500 patients were analysed. The average age at diagnosis was 60 years and the male to female ratio was 1:1.07. The overall 5-year survival was 35%, but this was significantly better in metastatic disease of the thyroid and breast as well as multiple myeloma. The number and site of metastases or the presence of a pathological fracture were not prognostic factors in terms of survival. Patients who were female or younger than 50 years of age at time of diagnosis had a better outcome. This registry will be expanded and more information analysed to try and provide useful information about prognostic factors and outcome for patients with meta-static bone disease

The presence of metastatic bone disease (MBD) often necessitates major orthopaedic surgery. Patients will enter surgical care either through emergent or electively scheduled care pathways. Patients in a pain crisis or with an acute fracture are generally admitted via emergent care pathways whereas patients with identified high-risk bone lesions are often booked for urgent yet scheduled elective procedures. The purpose of this study is to compare the post-operative outcomes of patients who present through emergent or electively scheduled care pathways in patients in a Canadian health care system. We have conducted a retrospective, multicenter cohort study of all patients presenting for surgery for MBD of the femur, humerus, tibia or pelvis in southern Alberta between 2006 and 2021. Patients were identified by a search query of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or actual pathologic fracture in the Calgary, South and Central Alberta Zones. Subsequent chart reviews were performed. Emergent surgeries were defined by patients admitted to hospital via urgent care mechanisms and managed via unscheduled surgical bookings (“on call list”). Elective surgeries were defined by patients seen by an orthopaedic surgeon at least once prior to surgery, and booked for a scheduled urgent, yet elective procedure. Outcomes include overall survival from the time of surgery, hospital length of stay, and 30-day hospital readmission rate. We have identified 402 patients to date for inclusion. 273 patients (67.9%) underwent surgery through emergent pathways and 129 patients (32.1%) were treated through urgent, electively scheduled pathways. Lung, prostate, renal cell, and breast cancer were the most common primary malignancies and there was no significant difference in these primaries amongst the groups (p=0.06). Not surprisingly, emergent patients were more likely to be treated for a pathologic fracture (p<0.001) whereas elective patients were more likely to be treated for an impending fracture (p<0.001). Overall survival was significantly shorter in the emergent group (5.0 months, 95%CI: 4.0-6.1) compared to the elective group (14.9 months 95%CI: 10.4-24.6) [p<0.001]. Hospital length of stay was significantly longer in the emergent group (13 days, 95%CI: 12-16 versus 5 days, 95%CI: 5-7 days). There was a significantly greater rate of 30-day hospital readmission in the emergent group (13.3% versus 7.8%) [p=0.01]. Electively managed MBD has multiple benefits including longer post-operative survival, shorter length of hospital stay, and a lower rate of 30-day hospital readmission. These findings from a Canadian healthcare system demonstrate clinical value in providing elective orthopaedic care when possible for patients with MBD. Furthermore, care delivery interventions capable of decreasing the footprint of emergent surgery through enhanced screening or follow-up of patients with MBD has the potential to significantly improve clinical outcomes in this population. This is an ongoing study that will justify refinements to the current surgical care pathways for MBD in order to identify patients prior to emergent presentation. Future directions will evaluate the costs associated with each care delivery method to provide opportunity for health economic efficiencies

Metastatic bone disease resulting in acetabular destruction can provide the orthopaedic surgeon with the difficult challenge of achieving a stable reconstruction of the hip to provide pain relief and restoration of mobility. We review of twenty patients with metastatic disease requiring major acetabular reconstruction presenting to our orthopaedic oncology unit over a five year period was undertaken. This yielded 15 female and 5 male patients with mean age 59 years. The primary lesion was breast (8 cases), renal (3) prostate (2), myeloma (2) and others (5) with a solitary acetabular metastasis in 75% of cases. Eight patients had received radiotherapy to the region pre-operatively. In all cases, diseased bone was macroscopically cleared from the pelvis and reconstruction performed by means of a Harrington procedure with threaded pins passed antegrade from the iliac crest 915 cases) or mesh and screws (5 cases), all reinforced with cement around which a total hip arthroplasty was performed. Mean follow-up was 16 months. Complications were broken pin (1 case), dislocation of femoral prosthesis (1) and deep venous thrombosis (1). Three patients died of their disease at a mean of 12 months from surgery. The remaining 17 patients continue to function at a satisfactory level with no patients having required revision surgery for loosening or deep infection. We believe that surgical reconstruction of the acetabulum is worthwhile and can provide these deserving patients with improvement in quality of life

The aim of the study is to review the results of prophylactic reconstruction of subtrochanteric metastatic bone disease of femur using a Long Gamma Nail. Metastasis in the subtrochanteric region of femur can be challenging to treat not only due to peculiarities in biomechanics and anatomy, but also due to weak and deficient bone stock due to metastasis. Between 1996 and 2002, 28 subtrochanteric metastatic lesions of femur in 25 patients (3 bilateral) were treated with Long Gamma Nail. The outcome measures used in this study were pain relief, postoperative mobilization, and medical and implant related complications rate. There were 16 female and 9 male patients with an average age of 64 years. All patients reported marked pain relief. All but one regained pre-operative mobilization status. There were no intra-operative deaths including 3 bilateral nailings. Significant surgical and implant related complications were seen in 3(12%) patients. Postoperative medical complications were seen in 3 (12%) patients. There were no implant failures and reoperations. At the time of study 14 patients died with an average survival of 9 months and 11 patients were alive with an average survival of 16.5 months. Long Gamma Nail is valuable reconstruction device for the prophylactic treatment of subtrochanteric metastatic bone disease of femur. It is strong, versatile and biomechanically superior to extramedullary devises and compares favourably with other intramedullary devices. In our experience Long Gamma Nail allows immediate unrestricted mobilization with marked pain relief

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

Introduction: Sending intramedullary reamings for histology in patients with metastaic bone disease (MBD) is routinely done in many centres. However, whether the results of these reamings help in the diagnosis of MBD remains unclear. Recent studies have shown that on the basis of biopsy of the metastases alone, only 35% of the primary tumours are detected. British Orthopaedic Oncology Society guidelines recommend further investigations and a bone biopsy if the primary disease is unknown. Aim:The aim of this study was to correlate clinical, radiological and histological findings for patients with metastatic bone disease and assess the diagnostic accuracy of the reamings in MBD. Method: Demographic details, clinical evaluation, radiological findings and the histology results of the bone biopsy or reamings were reviewed retrospectively for all patients admitted in the year 2003 with suspected MBD. Results:Records and x-rays were identified of 50 patients admitted in 2003 with suspected primary or MBD of a long bone and pain or pathological fracture. . 56% were male. Average age was 69.2years (range 10–98years). 6 patients had primary bone tumour and were referred to the tumour specialist. Of the remaining patients with suspected MBD all required fixation and in all cases intramedullary reamings were sent for histology. 18 patients had a known primary tumour of which 8 (44%) had no evidence of malignancy on histology. 22 patients had an unknown primary tumour of which 19 (86%) had no evidence of malignancy on histology. Conclusion: Reamings, are a poor method of diagnosis, even in cases where the primary is known the histology is still less than 50 % accurate in confirming malignancy. Therefore, in patients with MBD the diagnostic accuracy of reamings should be re-evaluated due to the high false negative results

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

The burden of metastatic bone disease (MBD) in our Canadian cancer population continues to increase. MBD has a significant effect on patient morbidity, mortality, and health-related quality of life (HRQOL). There are various technical options used to surgically stabilize MBD lesions, surgical decision-making is variable and largely dependent on anatomic and surgeon-based factors. There is a paucity of research examining how surgical decision-making for MBD can be modified or individualized to improve quality of life (QOL) and functional outcomes, while more accurately aligning with patient-reported goals and expectations. The objective of this study was tosurvey MBD patients, support persons, physicians, and allied health care providers (HCP) with the goal of identifying 1) important contributors to HRQOL, 2) discordance in peri-operative expectations, and 3) perceived measures of success in the surgical management of MBD. This project is a longitudinal patient-engaged research initiative in MBD. A survey was developed based on HRQOL themes in the literature and based on feedback from our patient research partners. Participants were asked to identify 1) important contributors to HRQOL and 2) perceived measures of success relevant to the surgical management of MBD. Participants were asked to rank themes from ‘extremely important’ to ‘not important at all’. Using open-ended questions, participants were asked to identify areas of improvement. Responses from the open-ended questions were analyzed by an experienced qualitative researcher using conventional content analysis. Participant's demographics were calculated using descriptive statistics. Concordance or discordance of perceived measure of success was assessed via a Chi-Square test of independence. All statistical analyses were performed using IBM SPSS® software. Nine patients, seven support persons, 23 orthopaedic surgeons, 11 medical oncologists, 16 radiation oncologists, 16 nurses, and eight physiotherapists completed the survey. Regarding perceived measures of success, increased life expectancy (p Two main themes emerged around the timeliness of surgical care and the coordination of multidisciplinary care from patients and support persons. Patients and support persons expressed a sense of urgency in progressing to surgery/treatment, and frustration at perceived delays in treatment. Within coordination of care, patients and support persons would like clearer communication from the health care team. There is discordance between patient/support person goals compared to physicians/HCP goals in the surgical management of MBD. Surgical decision-making and operative techniques that minimize disease progression and improve survival are important to MBD patients. Timely access to surgery/surgical consultation and improved multidisciplinary communication is important to patients. This data suggests improved peri-operative communication and education is needed for MBD patients. Furthermore, future research evaluating how modern orthopaedic surgical techniques influence survival and disease progression in MBD is highly relevant and important to patients with MBD

The management of pathological fractures due to Metastatic Bone Disease (MBD) and Primary Bone Tumours (PBTs) has implications for the Trauma service due to the extra pressures on staff, service delivery and budgets. We undertook an analysis of a cohort of patients presenting with MBD and PBTs. A retrospective chart review of all cases with MBD and PBTs admitted to a 40-bed Trauma Unit between 2005 and 2009 was conducted. The study looked at frequency, primary pathology, and site of pathology/fracture, time from primary diagnosis to referral, subsequent interventions and others. The results identified 34 patients, 21 females (62%) and 13 males (38%) (mean age: 64.6 years) with MBD or PBTs. Metastases secondary to breast cancer (n=13, 38%) and Myeloma (n=5, 15%) were the most common with the majority being found in the femur (n=22, 65%) and the Humerus (n=6, 18%). The mean time from primary tumour diagnosis to fracture referral was 29.6 months with 27 (79%) patients undergoing definitive surgical management within the unit. The conclusions of the study demonstrate that a wide variety of pathology presented to the unit over a 5 year period. Considerable variation was noted in the time from primary tumour diagnosis to presentation with a fracture. This could be due to improvements in treatments of specific cancers or a lack of understanding of what an Orthopaedic surgeon can offer the cancer patient. No definitive increase in pathological fractures was seen. The consensus opinion is that prompt and appropriate management of pathological fractures in cancer patients is cost effective. Management of these injuries, in a Trauma Unit, represents a small, but significant part of the annual work-load. While no significant trend has been seen, with respect to an increased incidence, it is noted that a proportion of these patients were a number of years from their initial diagnosis. With improvements in the survivorship of cancer patients, close scrutiny will be required to determine whether this ultimately translates into an increased fracture burden

To assess the referral system, clinical notes and radiographs of patients presenting with metastatic disease of long bones in a regional oncology unit.

Thirty questionnaires were sent to oncologists asking about reasons for referral to orthopaedics and use of scoring system to assess risk of pathological fracture.

Ninety three percent of oncologists did not use a reliable scoring system to assess risk of pathological fracture. The majority referred in respect to pain on mobilising and the presence of a lytic lesion. Sixty percent felt an improvement in communication between the departments was required.

The notes and radiographs were reviewed of thirty-seven patients presenting with femoral metastatic lesions to the oncology department.

Sixteen patients had a Mirels score of greater than eight. Four patients were referred for an Orthopaedic opinion. All patients underwent prophylactic fixation. Twelve patients with a score of greater than eight were not referred. Seven of theses patients suffered a pathological fracture within three months.

Five patients had a Mirels score of 8. One patient had prophylactic fixation. No fractures occurred.

Sixteen patients had a Mirels score of less than 8. None of these patients were referred for an orthopaedic opinion. None of these patients had a pathological fracture within three months.

In conclusion, we presently do not offer a multidisciplinary approach to metastatic disease affecting the appendicular skeleton.

The majority of patients’ who score eight or above in the Mirels scoring system are at risk of fracture and do require prophylactic surgery.

In keeping with the BOA guidelines, “Metastatic Bone Disease: A Guide to Good Practice”, we would recommend that the introduction of a multidisciplinary approach and the use of a recognised scoring system is essential to improve patient care.

Breast cancer is the most frequent malignancy in women with an estimation of 2.1 million new diagnoses in 2018. Even though primary tumours are usually efficiently removed by surgery, 20–40% of patients will develop metastases in distant organs. Bone is one of the most frequent site of metastases from advanced breast cancer, accounting from 55 to 58% of all metastases. Currently, none of the therapeutic strategies used to manage breast cancer bone metastasis are really curative. Tailoring a suitable model to study and evaluate the disease pathophysiology and novel advanced therapies is one of the major challenges that will predict more effectively and efficiently the clinical response. Preclinical traditional models have been largely used as they can provide standardization and simplicity, moreover, further advancements have been made with 3D cultures, by spheroids and artificial matrices, patient derived xenografts and microfluidics. Despite these models recapitulate numerous aspects of tumour complexity, they do not completely mimic the clinical native microenvironment. Thus, to fulfil this need, in our study we developed a new, advanced and alternative model of human breast cancer bone metastasis as potential biologic assay for cancer research. The study involved breast cancer bone metastasis samples obtained from three female patients undergoing wide spinal decompression and stabilization through a posterior approach. Samples were cultured in a TubeSpin Bioreactor on a rolling apparatus under hypoxic conditions at time 0 and for up to 40 days and evaluated for viability by the Alamar Blue test, gene expression profile, histology and immunohistochemistry. Results showed the maintenance and preservation, at time 0 and after 40 days of culture, of the tissue viability, biological activity, as well as molecular markers, i.e. several key genes involved in the complex interactions between the tumour cells and bone able to drive cancer progression, cancer aggressiveness and metastasis to bone. A good tis sue morphological and microarchitectural preservation with the presence of lacunar osteolysis, fragmented trabeculae locally surrounded by osteoclast cells and malignant cells and an intense infiltration by tumour cells in bone marrow compartment in all examined samples. Histomorphometrical data on the levels of bone resorption and bone apposition parameters remained constant between T0 and T40 for all analysed patients. Additionally, immunohistochemistry showed homogeneous expression and location of CDH1, CDH2, KRT8, KRT18, Ki67, CASP3, ESR1, CD8 and CD68 between T0 and T40, thus further confirming the invasive behaviour of breast cancer cells and indicating the maintaining of the metastatic microenvironment. The novel tissue culture, set-up in this study, has significant advantages in comparison to the pre-existent 3D models: the tumour environment is the same of the clinical scenario, including all cell types as well as the native extracellular matrix; it can be quickly set-up employing only small samples of breast cancer bone metastasis tissue in a simple, ethically correct and cost-effective manner; it bypasses and/or decreases the necessity to use more complex preclinical model, thus reducing the ethical burden following the guiding principles aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes; it can allow the study of the interactions within the breast cancer bone metastasis tissue over a relatively long period of up to 40 days, preserving the tumour morphology and architecture and allowing also the evaluation of different biological factors, parameters and activities. Therefore, the study provides for the first time the feasibility and rationale for the use of a human-derived advanced alternative model for cancer research and testing of drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses