Physeal breach as a potential predictor of pulmonary metastasis in paediatric osteosarcoma.
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BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescents, and pulmonary metastasis remains the leading cause of death. In skeletally immature patients, the avascular physis is considered a barrier to local tumour spread, but its relationship to lung metastasis has not been quantified. METHODS: We conducted a single-centre, retrospective cohort study of 32 paediatric OS patients. Tumour-physis relationships were evaluated before and after chemotherapy using standard local staging and chest CT. The primary outcome was pulmonary metastasis at last follow-up, analysed with multivariable logistic regression including age, sex, tumour size, location, laterality, and physeal breach. A complementary orthotopic tibial xenograft model was established by injecting 143B cells into nude mice, creating physeal-breach and non-breach groups. Vascular endothelial growth factor (VEGF) immunohistochemistry (IHC) assessed angiogenic activity at the tumour-physis interface. RESULTS: Pulmonary metastases were present in 22% at diagnosis and in 50% (16/32) by last follow-up. Physeal breach was the only independent predictor of metastasis (odds ratio 59.89; 95% CI 3.34-1073.95; p=0.006). In the xenograft model, pulmonary metastases developed in all physeal-breach mice and in none of the non-breach group. VEGF IHC showed increased angiogenic activity in breach-associated tumours. CONCLUSION: Physeal breach identifies a biologically aggressive subset of paediatric OS with high metastatic potential. Because breach status is readily appreciable on routine imaging, it may serve as a practical biomarker to refine risk stratification, predict pulmonary metastasis and guide evaluation of anti-angiogenic strategies.