Impending Pathologic Fractures Research Articles

Intervention for impending pathological fractures at proximal femur is associated with lower mortality rates in patients with intermediate-to-high risk according to the Katagiri-New score

BackgroundProphylactic intervention for impending pathological fractures (IF) is associated with improved survival in patients with long-bone metastasis. However, information regarding whether the tumor burden and/or physical status are associated with survival benefits of intervention for IF is lacking.MethodsThis multicenter retrospective study investigated 121 patients who underwent surgery for 63 impending and 58 complete metastatic fractures of the proximal femur between 2008 and 2023. After matching for age, sex, body mass index, and Katagiri-New score, 42 patients with IF were compared with 42 patients with complete pathological fractures. The 1-year mortality rate was considered the primary outcome, and was compared and stratified by risk based on the Katagiri-New score. The 1-year mortality rate was evaluated according to the surgical method in the subgroup analysis of patients with IF.ResultsThe 1-year mortality rate was significantly lower in patients with IF with intermediate-to-high risk(p = 0.04), whereas no difference was observed in patients with low-to-high risk. IF was associated with a significantly higher rate of home discharge (p < 0.01) and improved post-operative ambulatory function (p = 0.07). The subgroup analysis of patients with IF revealed no difference in the survival rate between nailing and hemiarthroplasty.ConclusionPatients with intermediate-to-high risk IF based on the Katagiri-New score had a lower mortality rate than those who underwent surgery for pathological fractures. A higher rate of home discharge was observed in patients with IF. Based on the Katagiri-New score, survival benefits can be obtained from prophylactic intervention for IF of the proximal femur in patients with intermediate-to high-risk.

CT-based finite element simulating spatial bone damage accumulation predicts metastatic human vertebrae strength and stiffness.

Introduction: Pathologic vertebral fractures are devastating for patients with spinal metastases. However, the mechanical process underlying these fractures is poorly understood, limiting physician's ability to predict which vertebral bodies will fail. Method: Here, we show the development of a damage-based finite element framework producing highly reliable pathologic vertebral strength and stiffness predictions from X-Ray computed tomography (CT) data. We evaluated the performance of specimen-specific material calibration vs. global material calibration across osteosclerotic, osteolytic, and mixed lesion vertebrae that we derived using a machine learning approach. Results: The FE framework using global calibration strongly predicted the pathologic vertebrae stiffness (R 2 = 0.90, p < 0.0001) and strength (R 2 = 0.83, p = 0.0002) despite the remarkable variance in the pathologic bone structure and density. Specimen-specific calibration produced a near-perfect prediction of both stiffness and strength (R 2 = 0.99, p < 0.0001, for both), validating the FE approach. The FE damage-based simulations highlighted the differences in the pattern of spatial damage evolution between osteosclerotic and osteolytic vertebral bodies. Discussion: With failure, the FE simulation suggested a common damage evolution pathway progressing largely localized to the low bone modulus regions within the vertebral volume. Applying this FE approach may allow us to predict the onset and anatomical location of vertebral failure, which is critical for developing image-based diagnostics of impending pathologic vertebral fractures.

Recent Advances in Minimally Invasive Management of Osteolytic Periacetabular Skeletal Metastases.

Painful skeletal osteolytic metastases, impending pathological fractures, and nondisplaced fractures present as a devastating clinical problem in advanced stage cancer patients. Open surgical approaches provide excellent mechanical stabilization but are often associated with high complication rates and slow recovery times. Percutaneous minimally invasive interventions have arisen as a pragmatic and logical treatment option for patients with late-stage cancer in whom open surgery may be contraindicated. These percutaneous interventions minimize soft tissue dissection, allow for the immediate initiation or resumption of chemotherapies, and present with fewer complications. This review provides the most up-to-date technical and conceptual framework for the minimally invasive management of osseous metastases with particular focus on periacetabular lesions. Fundamental topics discussed are as follows: (1) pathogenesis of cancer-induced bone loss and the importance of local cytoreduction to restore bone quality, (2) anatomy and biomechanics of the acetabulum as a weight-bearing zone, (3) overview of ablation options and cement/screw techniques, and (4) combinatorial approaches. Future studies should include additional studies with more long-term follow-up to better assess mechanical durability of minimally invasive interventions. An acetabulum-specific functional and pain scoring framework should be adopted to allow for better cross-study comparison.

MakoTM robotic-arm-assisted total hip and total knee arthroplasty outcomes in an orthopedic oncology setting: A case series

BackgroundThe MAKO Robotic-Arm system is a cutting-edge technology which combines both computed tomography (CT) scanning and three-dimensional planning to determine the ideal size and orientation of implants prior to bone resection. It is typically utilized within a general orthopedic setting for joint replacement procedures, such as total joint arthroplasties. However, its use within orthopedic oncology, which contains a much more compromised patient population and more complex surgical treatment, is not well documented within the literature. Question/purposesTo determine the patient outcomes of those who underwent a total hip arthroplasty (THA) or total knee arthroplasty (TKA) at Morristown Medical Center using the MAKO Robotic-Arm System. Particularly, we aspired to delve into the use of the MAKO in an orthopedic oncology setting for patients with a degenerative hip or knee and a history of cancer or other orthopedic tumor, impending pathological fracture, PVNS, chondromatosis, radiation therapy, or other oncological related conditions. Patients and methodsOur institution monitored twenty-five individuals with unique orthopedic oncology conditions that underwent MAKO robotic-assisted total hip and knee arthroplasty. This was performed between 2020 and 2022 at Morristown Medical Center in New Jersey. During this time period, 52% (13/25) of the operations were performed on knees and 48% (12/25) were performed on hips. Data regarding patient demographics, body mass index (BMI), medications, hemoglobin, hematocrit, comorbidities, American Society of Anesthesiologists (ASA) Class, operative data, the length of stay (LOS), readmission rates due to infection or periprosthetic fractures, and complications were collected retrospectively. All confidence intervals were calculated at the 95% confidence level. ResultsPostoperatively, the average LOS was 3.2 days, and there were no complications after any of the MAKO-assisted joint arthroplasty procedures. Additionally, there were no readmissions at any of our recorded intervals - 1–30, 1–60, 1–90, and 1 year - however one patient presented to the emergency department after falling 4 days post-operatively. X-ray imaging ultimately revealed no periprosthetic fracture or malalignment of the prosthesis. ConclusionsThe utilization of the MAKO Robotic-Arm System for joint arthroplasty procedures (THAs and TKAs) on orthopedic oncology patients yielded exceptional outcomes, with no complications or readmissions directly attributed to the use of this innovative robotic technology. Thus, this newly emerging surgical system holds great promise, potentially revolutionizing the approach for selected orthopedic oncology patients undergoing total joint arthroplasty compared to the traditional manual techniques. It further demonstrates that its use in an orthopedic oncology setting - where the cohort of patients are often compromised, leading to more intricate surgeries with heightened risks - elicits safety and provides optimal outcomes for patients. Nevertheless, its role within the field is evolving, and in the coming years, as it gains further popularity and sees broader application by orthopedic oncology surgeons, its potential will become clearer. To solidify its position, future clinical investigations and prospective research should be conducted to support the preference of the MAKO system over traditional manual techniques. This will help provide the necessary evidence to advocate for its widespread adoption and continued advancements in orthopedic oncology procedures.

Operative Fixation of a Humeral Shaft Periprosthetic Fracture After IlluminOss: A Case Report.

An 82-year-old man sustained a periprosthetic fracture after IlluminOss photodynamic bone stabilization system (PBSS) stabilization for an impending pathologic fracture. Nonoperative management was unsuccessful, and he subsequently underwent operative fixation, which featured lag screw fixation of the spiral distal humeral shaft fracture and osteotomy followed by plate fixation of the pathologic humeral shaft fracture. This is the first article to report this complication with IlluminOss PBSS stabilization and details regarding revision surgery.

Development and Validation of a Convolutional Neural Network Model to Predict a Pathologic Fracture in the Proximal Femur Using Abdomen and Pelvis CT Images of Patients With Advanced Cancer.

Development and Validation of a Convolutional Neural Network Model to Predict a Pathologic Fracture in the Proximal Femur Using Abdomen and Pelvis CT Images of Patients With Advanced Cancer.

Prevalence of primary malignant tumours, rates of pathological fracture, and mortality in the setting of metastatic bone disease.

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. 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. 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. 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.

Chemotherapy May Obviate Prophylactic Femoral Nail Surgery for Multiple Myeloma Patients With High Mirels’ Score Lesions and Impending Pathological Hip Fracture

Bone involvement presents in &gt;80% of patients with multiple myeloma. This causes lytic lesions for which prophylactic surgery is indicated to prevent pathological fractures if the lesion is graded ≥9/12 on Mirels’ score. Although successful, these surgeries have risks and extended recovery periods. We present a case indicating myeloma chemotherapy may obviate prophylactic femoral nailing for high Mirels’ score lesions in the femoral head with impending pathological hip fracture. A 72-year-old woman presented in December 2017 with back pain. A plain X-ray indicated degenerative anterolisthesis in her lumbosacral spine. Serum analysis revealed abnormal protein, globulin, alkaline phosphatase, and albumin levels while protein electrophoresis and serum immunofixation revealed raised immunoglobulin A (IgA) kappa paraprotein and kappa serum free light chains, respectively. Whole-body CT scans showed widespread lytic bone lesions and bone marrow biopsy confirmed infiltration by plasma cells. She was diagnosed with International Staging System (ISS) stage 3 multiple myeloma, which was successfully treated with bortezomib, thalidomide and dexamethasone with regular bisphosphonates that year. She presented again to the hospital in June 2020 with acute back and pelvic pain; Her paraprotein and serum-free light chains had increased significantly from her previous clinic appointment, indicating serological progression. MRI showed a relapse of the myeloma deposits in her right femoral head and spine. The deposit in her femoral head was graded 10/12 on Mirels’ score, which indicated prophylactic femoral nailing. Instead, the patient was treated with daratumumab, bortezomib, and dexamethasone with escalation to monthly zoledronic acid infusions, as it was thought surgery would provide limited cytoreductive effect, preventing chemotherapy for six weeks post-surgery, potentiating pathological hip fracture and disease progression at other sites. This resulted in a complete response, thus reducing the deposits such that the femoral lesion was graded &lt;8 on Mirels’ score, improved her pain, and restored her ability to traverse stairs. She remains in complete response with ongoing daratumumab and denosumab maintenance treatment as of December 2022. Chemotherapy and bisphosphonates substantially reduced the myeloma deposit in the femoral head such that indications of prophylactic surgery were eliminated according to Mirels’ score recommendations. This reduced the risk of pathological hip fracture whilst eliminating surgical complications. Further research should be conducted into the safety and efficacy of this treatment regimen in patients with high Mirels’ score lesions. With this knowledge, consideration can be taken as to whether prophylactic femoral nailing is necessary given strong indications.

Conservative Treatment in Impending Fracture of Solitary Brown Tumor of Tibia: A Case Report and Review of Literature

Background: Brown tumors, also known as osteitis fibrosa cystica, are focal benign bone lesions caused by an increased osteoclastic activity because of high levels of parathyroid hormones. The increase of parathyroid hormones can be primary hyperparathyroidism (HPT) and secondary HPT resulting from renal failure and vitamin D deficiency. Case presentation: A 26-year-old Thai female visited the clinic because of right leg pain and swelling for three weeks. Plain radiography revealed a solitary osteolytic lesion with an impending fracture at the anterior cortex of the right proximal tibia. The patient underwent a core needle biopsy. The initial histopathology report depicted a giant cell lesion. In addition, the patient had elevated serum parathyroid hormones. A parathyroid adenoma was discovered on a further investigation with contrast-enhanced computed tomography of the neck. The immunochemistry and molecular study report were consistent with a brown tumor. The patient underwent parathyroidectomy for her adenoma and was on weight-bearing restrictions for her leg. After three months of follow-up, she could bear weight on her right leg without pain, and radiographic evaluation showed restoration of the tibial cortex. Conclusion: Conservative management has a role in managing brown tumors of the lower extremities with impending pathologic fracture. Rapid diagnosis and removing the primary cause of parathyroid adenoma as soon as possible is a crucial part of the treatment.

Cement leakage during vertebroplasty: comparison between intact and wall disruption in spinal metastases.

Percutaneous vertebroplasty (PVP) is an effective measure for painful metastases or impending pathological fractures of the spine with cement leakages being the most frequent complication. Posterior extrusion of cement into the spinal canal may result in neurological symptoms and deficits. To compare the occurrence of intraspinal canal cement leakage between vertebrae with posterior wall disruption and vertebrae without posterior wall disruption. A single-center retrospective study was conducted of all PVP for spine metastases between June 2020 and November 2021. All leaks were analyzed by a postprocedural computed tomography scan or cone-beam computed tomography. A total of 77 patients with 143 vertebrae treated by PVP were included. Posterior wall disruption was observed in 64 (44.8%) vertebrae while 79 (55.2%) had a complete posterior wall. Spinal canal cement leakage occurred in 36 (25.2%) vertebrae and was comparable in both groups, occurring in 16 (25.0%) vertebrae with posterior wall disruption and 20 (25.3%) vertebrae without posterior wall disruption (P = 1). No risk factors for spinal canal leakage were found in the univariate and multivariate analyses. One spinal leak was symptomatic with intercostal neuralgia. Our results suggest that an incomplete vertebral posterior wall does not increase the rate of spinal canal cement leakage during PVP.

FEMORAL SHAFT-NAIL RADIUS OF CURVATURE DISCREPANCY: PREOPERATIVE ANALYSIS OF FEMORAL SHAFT ANTERIOR RADIUS OF CURVATURE USING IMAGING AND ITS ASSOCIATION WITH ANTERIOR CORTICAL IMPINGEMENT DURING FIXATION OF FEMORAL PATHOLOGY

Long femoral nails for neck of femur fractures and prophylactic fixation have a risk of anterior cortex perforation. Previous studies have demonstrated the radius of curvature (ROC) of a femoral nail influencing the finishing point of a nail and the risk of anterior cortex perforation. This study aims to calculate a patients femoral ROC using preoperative XR and CT and therefore nail finishing position.We conducted a retrospective study review of patients with long femoral cephalomedullary nailing for proximal femur fractures (OTA/AO 31(A) and OTA/AO 32) or impending pathological fractures at a level 1 trauma centre between January 1, 2015 and December 31, 2020 with both full length lateral X-ray and CT imaging. Femoral ROC was calculated on both imaging modalities. Outcomes measured including nail finishing position, anterior cortex encroachment and impingement. The mean femoral ROC was 1026mm on CT and 1244mm on XR. CT femoral ROC strongly correlated with nail finishing point with a spearmans coefficient of 0.77. Additionally, femurs with a ROC &lt;1000mm were associated with a higher risk of anterior encroachment (OR 6.12) and femurs with a ROC &lt;900mm were associated with a higher risk of anterior cortex impingement (OR 6.47).To our knowledge this is the first study to compare a measured femoral ROC to nail finishing position. The use of CT to measure femoral ROC and to a lesser extent XR was able to predict both nail finishing position and risk of anterior cortex encroachment. Preoperative XRs and CTs were able to identify patients with a small femoral ROC. This predicted patients at risk of anterior cortex impingement, anterior cortex encroachment and nail finishing position. We may be able to select femoral nails that resemble the native femoral ROC and mitigate the risk of anterior cortex perforation.

Modification to Mirels scoring system location component improves fracture prediction for metastatic disease of the proximal femur

BackgroundCorrectly identifying patients at risk of femoral fracture due to metastatic bone disease remains a clinical challenge. Mirels criteria remains the most widely referenced method with the advantage of being easily calculated but it suffers from poor specificity. The purpose of this study was to develop and evaluate a modified Mirels scoring system through scoring modification of the original Mirels location component within the proximal femur.MethodsComputational (finite element) experiments were performed to quantify strength reduction in the proximal femur caused by simulated lytic lesions at defined locations. Virtual spherical defects representing lytic lesions were placed at 32 defined locations based on axial (4 axial positions: neck, intertrochanteric, subtrochanteric or diaphyseal) and circumferential (8 circumferential: 45-degree intervals) positions. Finite element meshes were created, material property assignment was based on CT mineral density, and femoral head/greater trochanter loading consistent with stair ascent was applied. The strength of each femur with a simulated lesion divided by the strength of the intact femur was used to calculate the Location-Based Strength Fraction (LBSF). A modified Mirels location score was next defined for each of the 32 lesion locations with an assignment of 1 (LBSF > 75%), 2 (LBSF: 51–75%), and 3 (LBSF: 0–50%).To test the new scoring system, data from 48 patients with metastatic disease to the femur, previously enrolled in a Musculoskeletal Tumor Society (MSTS) cross-sectional study was used. The lesion location was identified for each case based on axial and circumferential location from the CT images and assigned an original (2 or 3) and modified (1,2, or 3) Mirels location score. The total score for each was then calculated. Eight patients had a fracture of the femur and 40 did not over a 4-month follow-up period. Logistic regression and decision curve analysis were used to explore relationships between clinical outcome (Fracture/No Fracture) and the two Mirels scoring methods.ResultsThe location-based strength fraction (LBSF) was lowest for lesions in the subtrochanteric and diaphyseal regions on the lateral side of the femur; lesions in these regions would be at greatest risk of fracture. Neck lesions located at the anterior and antero-medial positions were at the lowest risk of fracture. When grouped, neck lesions had the highest LBSF (83%), followed by intertrochanteric (72%), with subtrochanteric (50%) and diaphyseal lesions (49%) having the lowest LBSF. There was a significant difference (p < 0.0001) in LBSF between each axial location, except subtrochanteric and diaphyseal which were not different from each other (p = 0.96).The area under the receiver operator characteristic (ROC) curve using logistic regression was greatest for modified Mirels Score using site specific location of the lesion (Modified Mirels-ss, AUC = 0.950), followed by a modified Mirels Score using axial location of lesion (Modified Mirels-ax, AUC = 0.941). Both were an improvement over the original Mirels score (AUC = 0.853).Decision curve analysis was used to quantify the relative risks of identifying patients that would fracture (TP, true positives) and those erroneously predicted to fracture (FP, false positives) for the original and modified Mirels scoring systems. The net benefit of the scoring system weighed the benefits (TP) and harms (FP) on the same scale. At a threshold probability of fracture of 10%, use of the modified Mirels scoring reduced the number of false positives by 17–20% compared to Mirels scoring.ConclusionsA modified Mirels scoring system, informed by detailed analysis of the influence of lesion location, improved the ability to predict impending pathological fractures of the proximal femur for patients with metastatic bone disease. Decision curve analysis is a useful tool to weigh costs and benefits concerning fracture risk and could be combined with other patient/clinical factors that contribute to clinical decision making.

Predicting Pathological Fractures at Metastatic Humeral Lesions.

We performed a retrospective electronic chart review of patients with humeral metastases at our institution (2005 to 2021), with 188 patients meeting the inclusion criteria. Sixty-one of the patients developed a fracture during follow-up. The metastatic humeral lesions were scored according to the Mirels rating system and additional radiographic criteria (cortical breach, location within the humerus, number of lesions). The predictive value of each Mirels score cutoff for fracture was assessed using sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and multivariate logistic regression. Survivorship until fracture was analyzed for each Mirels score cutoff using Kaplan-Meier curves and the log-rank test. Significance was set at p < 0.01. There were no significant differences in age, sex, side of the lesion, type of malignancy, and radiation dose between the groups with and without fracture (all p > 0.01). A Mirels score of ≥8 points had the best predictive profile, with sensitivity of 83.6%, specificity of 79.5%, and AUC of 0.82 (95% confidence interval [CI], 0.75 to 0.88, p < 0.01). A logistic regression model also demonstrated that a Mirels score of ≥8 (odds ratio = 5.8, 95% CI = 1.9 to 18.2, p < 0.01) and a cortical breach (odds ratio = 21.0, 95% CI = 5.7 to 77.2, p < 0.01) were significant predictors of pathological fracture. No other radiographic characteristics were found to be significant predictors of fracture. This study indicated that a Mirels score of ≥8 points had the best predictive profile for anticipating fractures at a metastasis in the humerus. This is in contrast to the traditional Mirels definition of an impending pathological fracture that is used for the lower extremity, a score of ≥9. Additionally, the presence of a cortical breach was a significant predictor of fracture risk. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Finite Element Model-Computed Mechanical Behavior of Femurs with Metastatic Disease Varies Between Physiologic and Idealized Loading Simulations.

Femurs affected by metastatic bone disease (MBD) frequently undergo surgery to prevent impending pathologic fractures due to clinician-perceived increases in fracture risk. Finite element (FE) models can provide more objective assessments of fracture risk. However, FE models of femurs with MBD have implemented strain- and strength-based estimates of fracture risk under a wide variety of loading configurations, and "physiologic" loading models typically simulate a single abductor force. Due to these variations, it is currently difficult to interpret mechanical fracture risk results across studies of femoral MBD. Our aims were to evaluate (1) differences in mechanical behavior between idealized loading configurations and those incorporating physiologic muscle forces, and (2) differences in the rankings of mechanical behavior between different loading configurations, in FE simulations to predict fracture risk in femurs with MBD. We evaluated 9 different patient-specific FE loading simulations for a cohort of 54 MBD femurs: strain outcome simulations-physiologic (normal walking [NW], stair ascent [SA], stumbling), and joint contact only (NW contact force, excluding muscle forces); strength outcome simulations-physiologic (NW, SA), joint contact only, offset torsion, and sideways fall. Tensile principal strain and femur strength were compared between simulations using statistical analyses. Tensile principal strain was 26% higher (R 2 = 0.719, P < .001) and femur strength was 4% lower (R 2 = 0.984, P < .001) in simulations excluding physiologic muscle forces. Rankings of the mechanical predictions were correlated between the strain outcome simulations (ρ = 0.723 to 0.990, P < .001), and between strength outcome simulations (ρ = 0.524 to 0.984, P < .001). Overall, simulations incorporating physiologic muscle forces affected local strain outcomes more than global strength outcomes. Absolute values of strain and strength computed using idealized (no muscle forces) and physiologic loading configurations should be used within the appropriate context when interpreting fracture risk in femurs with MBD.

Preoperative coagulation biomarkers associate with survival and pulmonary embolism after surgical treatment of non-spinal skeletal metastases

BackgroundThrombotic complications are synergistic and associated with orthopedic procedures, trauma, and malignancy. Because cancer enhances coagulation activity and vice versa, we assessed preoperative biomarkers for survival and complications after treatment of pathologic fractures in non-spinal skeletal metastases.Patients/methodsOur study population comprised 113 actual or impending pathologic fractures in 100 patients admitted to two referral centers. Laboratory variables were collected retrospectively from patient records and analyzed related to incidence of pulmonary embolism (PE) and mortality (Kaplan-Meier and Cox regression analyses and biomarker quartiles).ResultsPreoperative coagulation variables were high without exceptions. PE occurred in 12 patients at 36 post-operative days at incidence of 11% in the lower and 13% in the upper extremity fractures. Patients with fibrinogen exceeding 5 g/l (log-rank 0.022) developed PE earlier (5 to 15 days postoperatively) than others. Also, mean patient survival with normal fibrinogen range (2–4 g/l) was 34 months, whereas it halved upon elevated fibrinogen (log-rank p = 0.009). Survival in patients with FVIII levels under 326 IU/dl (Q3) was 22 months, but only 7 months if FVIII exceeded 326 IU/dl (log-rank p = 0.002). Combined elevated fibrinogen and FVIII predicted survival: for patients with levels below threshold limits was 22 months versus only 7 months when both variables exceeded the ranges (log-rank p < 0.001). Multivariate analysis to control confounders supported an independent role of fibrinogen and FVIII for survival.ConclusionsOur study has established fibrinogen and FVIII as potential preoperative contributors of survival and complications after treatment of metastatic fractures. These results highlight the need for novel anticoagulation and thromboprophylaxis strategies among these patients.

Machine learning algorithms to estimate 10-Year survival in patients with bone metastases due to prostate cancer: toward a disease-specific survival estimation tool

BackgroundPrognostic indicators, treatments, and survival estimates vary by cancer type. Therefore, disease-specific models are needed to estimate patient survival. Our primary aim was to develop models to estimate survival duration after treatment for skeletal-related events (SREs) (symptomatic bone metastasis, including impending or actual pathologic fractures) in men with metastatic bone disease due to prostate cancer. Such disease-specific models could be added to the PATHFx clinical-decision support tool, which is available worldwide, free of charge. Our secondary aim was to determine disease-specific factors that should be included in an international cancer registry.MethodsWe analyzed records of 438 men with metastatic prostate cancer who sustained SREs that required treatment with radiotherapy or surgery from 1989–2017. We developed and validated 6 models for 1-, 2-, 3-, 4-, 5-, and 10-year survival after treatment. Model performance was evaluated using calibration analysis, Brier scores, area under the receiver operator characteristic curve (AUC), and decision curve analysis to determine the models’ clinical utility. We characterized the magnitude and direction of model features.ResultsThe models exhibited acceptable calibration, accuracy (Brier scores < 0.20), and classification ability (AUCs > 0.73). Decision curve analysis determined that all 6 models were suitable for clinical use. The order of feature importance was distinct for each model. In all models, 3 factors were positively associated with survival duration: younger age at metastasis diagnosis, proximal prostate-specific antigen (PSA) < 10 ng/mL, and slow-rising alkaline phosphatase velocity (APV).ConclusionsWe developed models that estimate survival duration in patients with metastatic bone disease due to prostate cancer. These models require external validation but should meanwhile be included in the PATHFx tool. PSA and APV data should be recorded in an international cancer registry.

Management of Pathologic Fractures around the Knee: Part 1-Distal Femur.

Pathologic fractures secondary to metastatic disease are an increasingly prevalent problem. Such patients require multidisciplinary collaboration to optimize clinical outcomes. An established algorithm for clinical, laboratory, and radiographic work-up will ensure that each patient achieves the best outcome while avoiding catastrophic complications. Metastatic disease to the region of the knee is less commonly encountered than in other regions of the body, but it presents unique difficulties that merit discussion. Part one of this two-part article series will discuss the appropriate work-up of patients with suspected or impending pathologic fracture of the distal femur, highlight biopsy principles, address perioperative nonsurgical treatments that will optimize patient outcomes, and discuss available surgical treatment modalities.

Prophylactic surgical treatment using CT-based rigidity analysis vs. after the fact fracture treatment of pathologic femoral lesions.

Accurate comparison of prophylactic surgical treatment (PST) to after fracture treatment (AF) of patients with femoral metastatic disease requires more accurately identifying patients for impending fracture, such as with CT-based structural rigidity analysis (CTRA). This study compares a more accurately defined PST group (of impending fractures defined by CTRA) to AF for metastatic femoral disease. PST patients were enrolled and treated by the PI in a longitudinal multicenter study of impending pathologic fractures evaluated for accuracy by CTRA. The AF patients were also treated by the senior author and were identified by retrospective chart review. Fifty-five patients were treated surgically for metastatic femoral lesions and were divided into three groups for the purpose of this study: Group I (AF), Group II (PST-high), and Group III (PST-low). Demographic information, comorbidities, and clinical variables of interest were collected by retrospective chart review; cost data was collected by collaboration with our hospital financial personnel (office of the Chief Financial Officer). Survival showed statistically significant differences favoring Group II. Transfusions in Group I were nearly twice those of Groups II and III, but there was no statistically significant (NS) difference between groups. Estimated blood loss (EBL) was generally with NS difference. Similarly, there were NS differences in LOS between groups. Discharge disposition showed statistically significant differences between groups (P=0.012, global). Discharge to home was highest in Group II (76%) and lowest in Group I (27%). Discharge to rehab was lowest in Group II (24%) and highest in Group I (47%). There were no discharges to hospice or morgue in Group II, while both occurred in Group I. Mean direct and total costs were highest in Group I ($18,837 and $31,997, respectively) and lowest in Group II ($16,094 and $27,357) but the differences were NS. This study shows benefits of PST over AF in a group of PST patients more accurately defined to have impending pathologic fractures by CTRA definition.

Does surgical technique influence the burden of lung metastases in patients with pathologic long bone fractures?

BackgroundThe aims of this study are to (1) determine whether fixation of metastatic long bone fractures with an intramedullary nail (IMN) influences the incidence of lung metastasis in comparison to arthroplasty or ORIF (Arthro/ORIF); and (2) assess this relationship in primary tumor types; and (3) to assess survival implications of lung metastasis after surgery.MethodsRetrospective cohort study investigating 184 patients (107 IMN, and 77 Arthro/ORIF) surgically treated for metastatic long bone fractures. Patients were required to have a single surgically treated impending or established pathologic fracture of a long bone, pre-operative lung imaging (lung radiograph or computed tomography) and post-operative lung imaging within 6 months of surgery. Primary cancer types included were breast (n = 70), lung (n = 43), prostate (n = 34), renal cell (n = 37). Statistical analyses were conducted using two-tailed Fisher’s exact tests, and Kaplan-Meier survival analyses.ResultsPatients treated with IMN and Arthro/ORIF developed new or progressive lung metastases following surgery at an incidence of 34 and 26%, respectively. Surgical method did not significantly influence lung metastasis (p = 0.33). Furthermore, an analysis of primary cancer subgroups did not yield any differences between IMN vs Arthro/ORIF. Median survival for the entire cohort was 11 months and 1-year overall survival was 42.7% (95% CI: 35.4–49.8). Regardless of fixation method, the presence of new or progressive lung metastatic disease at follow up imaging study was found to have a negative impact on patient survival (p < 0.001).ConclusionsIn this study, development or progression of metastatic lung disease was not affected by long bone stabilization strategy. IM manipulation of metastatic long bone fractures therefore may not result in a clinically relevant increase in metastatic lung burden. The results of this study also suggest that lung metastasis within 6 months of surgery for metastatic long bone lesions is negatively associated with patient survival.Level of evidenceIII, therapeutic study

Clinical Outcome Differences in the Treatment of Impending Versus Completed Pathological Long-Bone Fractures.

The outcome differences following surgery for an impending versus a completed pathological fracture have not been clearly defined. The purpose of the present study was to assess differences in outcomes following the surgical treatment of impending versus completed pathological fractures in patients with long-bone metastases in terms of (1) 90-day and 1-year survival and (2) intraoperative blood loss, perioperative blood transfusion, anesthesia time, duration of hospitalization, 30-day postoperative systemic complications, and reoperations. We retrospectively performed a matched cohort study utilizing a database of 1,064 patients who had undergone operative treatment for 462 impending and 602 completed metastatic long-bone fractures. After matching on 22 variables, including primary tumor, visceral metastases, and surgical treatment, 270 impending pathological fractures were matched to 270 completed pathological fractures. The primary outcome was assessed with the Cox proportional hazard model. The secondary outcomes were assessed with the McNemar test and the Wilcoxon signed-rank test. The 90-day survival rate did not differ between the groups (HR, 1.13 [95% CI, 0.81 to 1.56]; p = 0.48), but the 1-year survival rate was worse for completed pathological fractures (46% versus 38%) (HR, 1.28 [95% CI, 1.02 to 1.61]; p = 0.03). With regard to secondary outcomes, completed pathological fractures were associated with higher intraoperative estimated blood loss (p = 0.03), a higher rate of perioperative blood transfusions (p = 0.01), longer anesthesia time (p = 0.04), and more reoperations (OR, 2.50 [95% CI, 1.92 to 7.86]; p = 0.03); no differences were found in terms of the rate of 30-day postoperative complications or the duration of hospitalization. Patients undergoing surgery for impending pathological fractures had lower 1-year mortality rates and better secondary outcomes as compared with patients undergoing surgery for completed pathological fractures when accounting for 22 covariates through propensity matching. Patients with an impending pathological fracture appear to benefit from prophylactic stabilization as stabilizing a completed pathological fracture seems to be associated with increased mortality, blood loss, rate of blood transfusions, duration of surgery, and reoperation risk. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.