What are the treatment options for round cell tumors?

Treatment Options for Round Cell Tumors

Round cell tumors require immediate multiagent chemotherapy as the cornerstone of treatment, combined with definitive local control through surgery and/or radiation therapy, with specific regimens determined by molecular genetic classification. 1, 2

Immediate Diagnostic Requirements Before Treatment

• Obtain core needle biopsy at a specialized sarcoma center to secure tissue for histology, immunohistochemistry (CD99/MIC2, desmin, myogenin, cytokeratin panels), and molecular genetic testing (FISH or RT-PCR) to identify specific translocations 2
• Complete staging workup must include chest CT, MRI of primary site with contrast, whole body FDG-PET/CT, and bone marrow biopsy and aspirate before any definitive treatment 2
• Molecular classification is mandatory as it determines both prognosis and treatment strategy—do not proceed with treatment until genetic testing confirms the specific fusion type 3, 2

Treatment by Molecular Subtype

Ewing Sarcoma (EWSR1-FLI1 fusion, 85% of cases)

• Start VDC/IE chemotherapy immediately after diagnosis: vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide, which demonstrates superiority over VIDE regimens 2
• Administer multiagent chemotherapy for at least 9 weeks prior to local therapy 2
• Local control requires surgery, radiotherapy, or both to treat all structures involved in pre-chemotherapy volume 2
• For high-risk localized disease after VIDE chemotherapy, consolidation with melphalan-based high-dose chemotherapy with autologous stem cell transplant (HDT/ASCT) conveys event-free survival and overall survival benefit over standard chemotherapy consolidation 1
• Limb-sparing surgery should be pursued when feasible, but amputation may be necessary 3

EWSR1 Non-ETS Fusions (e.g., EWSR1-NFATC2)

• Follow bone sarcoma protocols with neoadjuvant chemotherapy and wide surgical excision, as these are high-grade tumors with metastatic rates of at least 50% 3
• These tumors have poorer response to conventional Ewing sarcoma chemotherapy regimens and unfavorable prognosis compared to classic Ewing sarcoma 3, 2
• Radiation therapy is indicated for tumors where complete surgical resection is not possible, for positive margins after surgery, or for palliation in metastatic disease 3

CIC-Rearranged Sarcomas (CIC-DUX4 fusion)

• Treat with Ewing sarcoma protocols despite distinct biology: multiagent chemotherapy for at least 9 weeks prior to local therapy 2
• These tumors have poorer response to conventional Ewing sarcoma chemotherapy and unfavorable prognosis 3, 2
• Local control with surgery, radiotherapy, or both is required 2

BCOR-Altered Sarcomas (BCOR-CCNB3 fusion)

• Treat with Ewing sarcoma protocols: multiagent chemotherapy for at least 9 weeks prior to local therapy 2
• These occur mainly in bone and predominantly affect pediatric patients 3, 2
• Local control with surgery, radiotherapy, or both is required 2

Rhabdomyosarcoma

• No proven survival benefit of HDT/ASCT in primary localized, metastatic, or relapsed disease 1
• Standard multiagent chemotherapy remains the treatment approach 1

Metastatic and Relapsed Disease

Relapsed Ewing Sarcoma

• Second-line chemotherapy options include: topotecan/cyclophosphamide, irinotecan/temozolomide, or high-dose ifosfamide 2
• Multi-targeted tyrosine kinase inhibitors (pazopanib, cabozantinib, regorafenib) show single-agent activity 2
• Selected patients with relapsed Ewing sarcoma should be considered for HDT/ASCT, particularly those demonstrating treatment response before HDT and patients under age 14 1
• Clinical trial enrollment is strongly prioritized for relapsed disease 2
• Median overall survival is approximately one year 2

Metastatic Disease at Diagnosis

• Survival benefits of HDT/ASCT are not confirmed for Ewing sarcoma patients with metastatic disease at initial diagnosis 1
• Standard multiagent chemotherapy with local control remains the approach 1, 2

Critical Treatment Pitfalls

• Never perform biopsy outside a specialized sarcoma center—tissue plane contamination can compromise outcomes 3, 2
• Do not treat based on histology alone—molecular genetic testing is mandatory as treatment response varies significantly between different fusion partners 3, 2
• Do not delay chemotherapy initiation—systemic therapy should start immediately after diagnosis for Ewing sarcoma 2
• Recognize that CIC-rearranged and BCOR-altered sarcomas require Ewing protocols but have worse prognosis than classic Ewing sarcoma 3, 2

Surveillance Requirements

• Regular imaging surveillance is necessary due to high metastatic risk (≥50%) 3
• Lung metastases are common and require specific monitoring 3
• Prolonged surveillance is required as some round cell tumors can recur years later 1