Estimating Survival in Patients with Operable Skeletal Metastases: An Application of a Bayesian Belief Network

BACKGROUND: Accurate estimations of life expectancy are important in the management of patients with metastatic cancer affecting the extremities, and help set patient, family, and physician expectations. Clinically, the decision whether to operate on patients with skeletal metastases, as well as the choice of surgical procedure, are predicated on an individual patient's estimated survival. Currently, there are no reliable methods for estimating survival in this patient population. Bayesian classification, which includes bayesian belief network (BBN) modeling, is a statistical method that explores conditional, probabilistic relationships between variables to estimate the likelihood of an outcome using observed data. Thus, BBN models are being used with increasing frequency in a variety of diagnoses to codify complex clinical data into prognostic models. The purpose of this study was to determine the feasibility of developing bayesian classifiers to estimate survival in patients undergoing surgery for metastases of the axial and appendicular skeleton. METHODS: We searched an institution-owned patient management database for all patients who underwent surgery for skeletal metastases between 1999 and 2003. We then developed and trained a machine-learned BBN model to estimate survival in months using candidate features based on historical data. Ten-fold cross-validation and receiver operating characteristic (ROC) curve analysis were performed to evaluate the BNN model's accuracy and robustness. RESULTS: A total of 189 consecutive patients were included. First-degree predictors of survival differed between the 3-month and 12-month models. Following cross validation, the area under the ROC curve was 0.85 (95% CI: 0.80-0.93) for 3-month probability of survival and 0.83 (95% CI: 0.77-0.90) for 12-month probability of survival. CONCLUSIONS: A robust, accurate, probabilistic naïve BBN model was successfully developed using observed clinical data to estimate individualized survival in patients with operable skeletal metastases. This method warrants further development and must be externally validated in other patient populations

Surgical treatment of skeletal metastases in proximal tibia: a multicenter case series of 74 patients

Background and purpose - The proximal tibia is a rare site for metastatic bone disease and is a challenging anatomical site to manage due to the proximity to the knee joint and poor soft tissue envelope. We investigated implant survival and complications of different surgical strategies in the treatment of proximal tibia pathological fractures. Patients and methods - The study comprised a 4 medical center, retrospective analysis of 74 patients surgically treated for metastases of the proximal tibia. Patient records were reviewed to identify outcome, incidence, and type of complications as well as contributing factors. Results - Reconstruction techniques comprised cement-augmented osteosynthesis (n = 33), tumor prosthesis (n = 31), and total knee arthroplasty with long cemented stems (n = 10). Overall implant survival was 88% at 6 months and 1 year, and 67% at 3 years. After stratification by technique, the implant survival was 82% and 71% at 1 and 3 years with tumor prosthesis, 100% at 1 and 3 years with total knee arthroplasty, and 91% at 1 year and 47% at 3 years with osteosynthesis. Preoperative radiotherapy decreased implant survival. Complications were observed in 19/74 patients. Treatment complications led to amputation in 5 patients. Interpretation - In this study, the best results were seen with both types of prothesis reconstructions, with good implant survival, when compared with treatment with osteosynthesis. However, patients treated with tumor prosthesis showed an increased incidence of postoperative infection, which resulted in poor implant survival. Osteosynthesis with cement is a good alternative for patients with short expected survival whereas endoprosthetic replacement achieved good medium-term results.Peer reviewe

Sääriluun yläosan metastaattisten murtumien kirurginen hoito

English abstrac

Surgery of non-spinal skeletal metastases in renal cell carcinoma

Background and purpose - Surgery for metastases of renal cell carcinoma has increased in the last decade. It carries a risk of massive blood loss, as tumors are hypervascular and the surgery is often extensive. Preoperative embolization is believed to facilitate surgery. We evaluated the effect of preoperative embolization and resection margin on intraoperative blood loss, operation time, and survival in non-spinal skeletal metastases of renal cell carcinoma. Patients and methods - This retrospective study involved 144 patients, 56 of which were treated preoperatively with embolization. The primary outcome was intraoperative blood loss. We also identified factors affecting operating time and survival. Results - We did not find statistically significant effects on intraoperative blood loss of preoperative embolization of skeletal non-spinal metastases. Pelvic localization and large tumor size increased intraoperative blood loss. Marginal resection compared to intralesional resection, nephrectomy, level of hemoglobin, and solitary metastases were associated with better survival. Interpretation - Tumor size, but not embolization, was an independent factor for intraoperative blood loss. Marginal resection rather than intralesional resection should be the gold standard treatment for skeletal metastases in non-spinal renal cell carcinoma, especially in the case of a solitary lesion, as this improved the overall survival.Peer reviewe

Metastatic bone disease

Aim: To evaluate epidemiology, prognosis and diagnostics in metastatic bone disease and identify risk factors for failure after operation for pathologic fracture. Patients: The study was based on patients treated for skeletal metastases, myeloma or lymphoma between 1986 and 1998 at the Oncology Service, Department of Orthopedics, Karolinska Hospital and on patients diagnosed with symptomatic skeletal metastases 1989-1994 in the Stockholm Region. Epidemiology: 641 breast cancer patients were diagnosed with symptomatic skeletal metastases 1989-1994. Based upon 1100 new primary breast cancer cases yearly, the overall risk of developing symptomatic skeletal metastases was 10-15%. One out of 5 patients with skeletal metastases required surgical treatment for skeletal complications. Prognosis: The survival rate after surgical treatment for skeletal complications was 0.3 at 1 year and 0.008 at 3 years. Multivariate analysis based on 619 patients showed that complete pathologic fracture and soft tissue metastases were negative prognostic variables for 1-year survival after operation. Solitary skeletal metastasis, breast, prostate, kidney cancer, myeloma and lymphoma were positive variables. Immunohistochemistry was used to analyze ER, PgR, MIB and p53 in 43 primary breast carcinomas and their skeletal metastases. PgR and p53 may provide prognostic information after pathologic fracture and not only at diagnosis of the primary tumor. Diagnosis: Fine Needle Aspiration Biopsy ((FNAB) was assessed in 110 patients for diagnostic accuracy and to which extent information about primary site of the metastatic carcinoma could be gained. There were 80 patients with metastatic carcinoma, 14 with lymphoma, and 16 with myeloma. FNAB offered correct diagnosis in 9 of 10 patients an also provided guidance in the search for the primary lesions. Hence, 27 of 30 myeloma or lymphomas were diagnosed by FNAB and in half of the patients with metastatic carcinoma the site of the primary tumor could be ascertained. For patients with a suspected skeletal metastasis the search for the primary tumor may preferably start with FNAB. Surgical treatment: Risk factors for failure after operation for pathologic fractures were identified in 192 patients treated for 228 metastatic lesions of the long bones. 26 out of 22 procedures (11 %) lead to failures necessitating reoperation. Long survival after surgery was the most important risk factor for failure of the reconstruction. Kidney cancer was the primary tumor associated with the highest rate of reoperations. Reconstructions based on prosthetic a opposed to osteosynthetic devices appeared safer. There was a tendency for a high reoperation rate in hospitals with few treated patients. Conclusion: To decrease the risk of reoperation, it is important to identify patients with a long expected survival. In patients with a good prognosis, wide resection and reconstruction as applied in primary malignant bone tumors should be considered

Predicting survival of patients with spinal metastatic disease using PathFX 3.0 : a validation study of 668 patients in Sweden

Introduction: PathFx is a computer-based prediction model for estimating survival of patients with bone metastasis. The model has been validated in several studies, but this is the first validation using exclusively patients with spinal metastases. Material and Methods: 668 patients (67% male, median age 67 years) presenting with spinal metastases at two university hospitals in Sweden 1991-2014 were included. Of those, the majority (82%, n=551) underwent surgery. Data on all patients was analyzed with PathFX version 3.0, generating a probability of survival at 1, 3, 6, 12, 18 and 24 months. The predictions were compared to real survival data and the precision in estimation was evaluated with Receiver-Operating Characteristic curve (ROC) analysis where the Area Under Curve (AUC) was calculated. Brier score and decision curve analyses were also assessed. Results: The AUC for 1-, 3-, 6- and 12 months survival predictions were 0.64 (95% CI 0.5-0.71), 0.71 (95% CI 0.67-0.75), 0.70 (95% CI 0.66-0.77) and 0.74 (95% CI 0.70-0.78). For 18- and 24 months survival the AUC were 0.74 (95% CI 0.69-0.78) and 0.76 (95% CI 0.72-0.81). The Brier scores were all 0.23 or lower depending on the estimated survival time. Conclusion: PathFX 3.0 is a reliable tool for predicting survival in patients with spinal metastatic disease. As the PathFX computer model can be updated to reflect advancements in oncology, we suggest this type of model, rather than rigid point-based scoring systems, to be used for estimating survival in patients with metastatic spinal disease in the future