Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients.

Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over the past three decades and are particularly low for patients with metastatic disease. We conducted a multi-institutional genome-wide association study (GWAS) to identify germline genetic variants associated with overall survival in 632 patients with osteosarcoma, including 523 patients of European ancestry and 109 from Brazil. We conducted a time-to-event analysis and estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models, with and without adjustment for metastatic disease. The results were combined across the European and Brazilian case sets using a random-effects meta-analysis. The strongest association after meta-analysis was for rs3765555 at 9p24.1, which was inversely associated with overall survival (HR = 1.76; 95% CI 1.41-2.18, p = 4.84 × 10-7 ). After imputation across this region, the combined analysis identified two SNPs that reached genome-wide significance. The strongest single association was with rs55933544 (HR = 1.9; 95% CI 1.5-2.4; p = 1.3 × 10-8 ), which localizes to the GLDC gene, adjacent to the IL33 gene and was consistent across both the European and Brazilian case sets. Using publicly available data, the risk allele was associated with lower expression of IL33 and low expression of IL33 was associated with poor survival in an independent set of patients with osteosarcoma. In conclusion, we have identified the GLDC/IL33 locus on chromosome 9p24.1 as associated with overall survival in patients with osteosarcoma. Further studies are needed to confirm this association and shed light on the biological underpinnings of this susceptibility locus.

Salvage of the proximal femur following pathological fractures involving benign bone tumors.

BACKGROUND AND OBJECTIVES: To describe the surgical treatment of patients with a pathologic fracture through a benign tumor of the proximal femur to determine if there is a difference in local recurrence, complications or functional outcome compared to patients with tumors in the same location without pathologic fractures. METHODS: From 1989-2010, of 97 patients, 29 presented with a pathologic fracture (PF) through a proximal femoral benign bone tumor and 68 presented without a pathologic fracture (NPF). Outcomes of the two groups were compared in terms of surgical management, postoperative complications, local recurrence and functional scores. RESULTS: Fibrous dysplasia, giant cell tumor of bone and chondroblastoma were the most common subtypes. Most patients were managed with joint preservation in both PF (86.2%) and NPF (98.5%) groups (P = 0.03). Local recurrence risk was similar for patients in the PF (10.3%) and NPF (8.8%) groups. Mean follow-up was 105.7 months (P = 0.8). Functional outcome scores were high in both groups and not statistically significantly different. CONCLUSIONS: The majority of pathologic fractures through a benign bone tumor of the proximal femur can be successfully treated with curettage, burring, bone grafting and internal fixation without increasing the risk of local recurrence or negatively impacting functional outcome.