Osteosarcoma
ICD-10 C41.9 · ICD-11 2B51

Treatment of High-Grade Osteosarcoma in Patients Under 40 Years Without Methotrexate Intolerance

This first-line protocol applies to patients with high-grade osteosarcoma who are under 40 years of age and have no intolerance to high-dose methotrexate. Multi-agent combination chemotherapy is the recommended standard approach for this population.

Clinical Scenario

High-grade osteosarcoma in a patient under 40 years with no contraindication to high-dose methotrexate. This age profile and treatment tolerance determines eligibility for the most widely used first-line regimen for potentially resectable tumours.

Treatment Approach

Curative treatment involves a course of neoadjuvant combination chemotherapy — built around a high-dose methotrexate-containing regimen — followed by surgical resection, then further adjuvant chemotherapy. The total treatment course typically spans several months.

The complete regimen, full agent selection, sequencing, and additional clinical considerations are detailed in the structured protocol.

Treatment Goal

The primary pathological target after neoadjuvant chemotherapy is a high histological necrosis rate — a recognised prognostic indicator that also informs surgical planning.

Instant Access to Structured Evidence-Based Regimens

References

The most widespread regimen is multi-agent therapy with MAP (high-dose methotrexate (HDMTX), doxorubicin and cisplatin) and is recommended for UK patients with potentially resectable tumours up to 40 years of age.

Curative treatment for high-grade osteosarcoma comprises neoadjuvant chemotherapy, surgical resection and adjuvant chemotherapy, typically taking 6–9 months.

The aim of surgery is complete tumour removal, preserving function where possible.

If there is a good histological necrosis rate (> 90%) after chemotherapy, a closer surgical margin can be considered safe. Histological response to induction therapy is a robust prognostic indicator.

DOI: 10.1038/s41416-024-02868-4

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