Physeal breach as a potential predictor of pulmonary metastasis in paediatric osteosarcoma

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.

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.

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.

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.