Management of pediatric bone sarcomas

Pediatric bone sarcomas - principally osteosarcoma (OS) and Ewing sarcoma (ES) - remain curable for many with localized disease, but outcomes for metastatic or relapsed cases have stagnated. We synthesize recent clinically relevant developments that inform diagnosis, risk stratification, local control, systemic therapy, and survivorship in children and adolescents.

Standard frontline therapy has not changed in decades for OS and ES. Maturing evidence for new technologies such as circulating tumor DNA (ctDNA) raises questions of how to validate and incorporate these tools into treatment regimens to improve outcomes for children with bone sarcomas. In OS, the debate between a minimally invasive approach to pulmonary metastasectomy over open thoracotomy remains; attempts to address this debate are underway. Improving survival continues to pose a great challenge. Adding tyrosine kinase inhibition to chemotherapy is the current strategy to improve upfront therapy, while a more radical approach of frequently changing drug combinations in the upfront setting, in an attempt to evade resistance, is also being tested in OS and ES. While the rEEcur trial attempted to compare chemotherapeutic regimens for relapsed ES, better understanding of the underlying biological nature of OS and ES are necessary for development of novel treatment strategies. Long-term survivorship care remains a global focus for various national consortia.

Although the activity of single-agent checkpoint inhibitors remains disappointing in pediatric bone tumors, rational tyrosine kinase inhibitor-chemotherapy combinations, improved biologic risk stratification (ctDNA; MYC in OS; STAG2 in ES), recycling chemotherapeutic agents, and standardized local-control frameworks are being developed to reshape care. Near-term priorities include biomarker-anchored upfront trials and supportive-care measures that preserve cure while reducing late effects. Clinical trials provide access to potentially paradigm-shifting therapeutic strategies.