What is the recommended treatment plan for a patient with aggressive bone cancer similar to osteosarcoma?

Treatment of ABC-Like Osteosarcoma

For aggressive bone cancer similar to osteosarcoma, the standard treatment is neoadjuvant chemotherapy with MAP (high-dose methotrexate, cisplatin, and doxorubicin), followed by wide surgical excision with negative margins, and then adjuvant chemotherapy tailored to histologic response. 1, 2

Initial Treatment Algorithm

Neoadjuvant Chemotherapy (Category 1)

• Begin with MAP regimen (high-dose methotrexate, cisplatin, and doxorubicin) for 2-4 cycles before surgery 1, 2
• Alternative regimens include doxorubicin and cisplatin alone, or combinations with ifosfamide and etoposide 1
• For patients >40 years, high-dose methotrexate may be challenging; doxorubicin, cisplatin, and potentially ifosfamide combinations are alternatives 1
• Chemotherapy should include appropriate growth factor support 1

Surgical Resection

• Wide excision with negative margins is the primary goal after neoadjuvant chemotherapy 1
• Limb-salvage surgery is achievable in approximately 83-90% of cases without compromising survival compared to amputation 1, 3, 4
• Complete surgical resection of all tumor sites is essential for survival 1
• Areas of suspected close margins should be marked on the surgical specimen 1

Adjuvant Chemotherapy Based on Histologic Response

Good Responders (>90% Tumor Necrosis)

• Continue with the same chemotherapy regimen (MAP) for several additional cycles 1, 2
• 5-year disease-free survival is 67.9% and overall survival is 78.4% in good responders 1
• 8-year event-free survival reaches 81% and overall survival 87% 1
• For patients <30 years with completely resected localized disease, consider adding mifamurtide (L-MTP-PE), which improved 10-year overall survival 1, 5

Poor Responders (<90% Tumor Necrosis)

• Consider changing to a different chemotherapy regimen, though evidence for improved outcomes is limited 1, 2
• Options include adding ifosfamide and etoposide to the original regimen 1, 3
• 5-year disease-free survival is 51.3% and overall survival is 63.7% in poor responders 1
• Attempts to improve outcomes by modifying regimens have been largely unsuccessful 1, 2

Critical Caveats and Pitfalls

Avoid These Common Errors

• Do not use preserved methotrexate formulations for high-dose therapy—only preservative-free formulations are safe 6
• Do not perform internal fixation for pathological fractures, as this disseminates tumor; use external splintage instead 1
• Pathological fracture does not necessarily require amputation if neoadjuvant chemotherapy allows fracture hematoma contraction 1

Unresectable Disease

• If tumor remains unresectable after preoperative chemotherapy, use radiotherapy followed by adjuvant chemotherapy 1
• Modern RT techniques including proton beam therapy and IMRT should be considered, especially in pediatric/young adult patients 1

Surveillance Protocol

Structured follow-up schedule 1:

• Every 3 months for years 1-2
• Every 4 months for year 3
• Every 6 months for years 4-5
• Yearly thereafter

At each visit include 1:

• Complete physical examination
• Chest imaging (plain radiograph; CT if abnormal)
• Plain film of the extremity
• Functional reassessment
• Consider bone scan (Category 2B) 1

Special Considerations for Metastatic Disease

Metastatic at Presentation

• Outcomes are significantly worse: 2-year event-free survival is only 21% versus 75% for localized disease 1, 7
• Complete surgical resection of all metastatic sites is the most important prognostic factor, with 48% long-term survival versus 5% without complete resection 1, 7
• Use same MAP chemotherapy regimen followed by metastasectomy when feasible 1, 7
• Patients with 1-2 metastatic lesions have 78% 2-year disease-free survival versus 28% for ≥3 lesions 1, 7

Relapsed Disease

• Approximately 30-40% of patients with localized disease will relapse 1
• Complete surgical resection remains critical; repeated thoracotomies may be warranted for recurrent pulmonary metastases 1, 7
• Second-line options include ifosfamide and etoposide, gemcitabine and docetaxel, or multi-targeted tyrosine kinase inhibitors (cabozantinib, regorafenib, lenvatinib) 1

Important Distinction

If this is truly an aneurysmal bone cyst (ABC) rather than osteosarcoma, treatment is entirely different—ABCs are benign lesions not requiring chemotherapy 8. Confirm the diagnosis with biopsy and multidisciplinary review before initiating aggressive multimodal therapy.