What is the treatment for round cell carcinoma?

Treatment of Round Cell Carcinoma

For round cell sarcomas including Ewing sarcoma, BCOR-altered, and CIC-rearranged tumors, systemic chemotherapy combined with local control (surgery and/or radiotherapy) is the standard treatment approach, with VDC/IE being the preferred regimen for localized Ewing sarcoma. 1

Primary Systemic Treatment

• Multiagent chemotherapy is the cornerstone of treatment and should be initiated for at least 9 weeks, with longer duration considered for metastatic disease. 1
• VDC/IE (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide) is the category 1 preferred regimen for localized Ewing sarcoma, as it has demonstrated superiority over VIDE. 1
• For other round cell sarcomas (BCOR-altered and CIC-rearranged tumors), Ewing sarcoma protocols are commonly used, though optimal therapy is not definitively established. 1
• Appropriate growth factor support should accompany chemotherapy. 1

Local Control Therapy

After primary chemotherapy, disease should be restaged with imaging (chest CT, contrast-enhanced MRI of primary site, and FDG-PET/CT or bone scan). 1

For patients with stable or improved disease, local control options include: 1

• Wide surgical excision (preferred when feasible with acceptable morbidity)
• Definitive radiotherapy with chemotherapy (for anatomically challenging locations)
• Amputation (in selected cases)

Surgery Considerations

• When treating with curative intent, all structures involved in the pre-chemotherapy volume should be addressed with surgery, radiotherapy, or both. 1
• Wide excision with negative margins is optimal. 1
• Adjuvant chemotherapy following surgery is recommended for all patients regardless of surgical margins, with duration between 28-49 weeks depending on regimen. 1
• Postoperative radiotherapy should be added for patients with positive or very close surgical margins. 1

Radiotherapy Considerations

• Radiotherapy can be delivered pre-operatively, post-operatively, or as definitive treatment. 1
• Definitive RT is appropriate for tumors in anatomically challenging locations not amenable to wide resection. 1
• Tumor size and RT dose are predictive of local control rates. 1

Metastatic Disease Management

• Local control therapy improves outcomes even in primary metastatic disease. 1
• For widely metastatic disease, palliative therapies may be considered. 1
• For metastatic disease amenable to local therapy, wide excision or definitive RT with adjuvant chemotherapy is recommended. 1

Relapsed Disease

• Several molecularly targeted agents show promise, with multi-targeted tyrosine kinase inhibitors (pazopanib, cabozantinib, regorafenib) demonstrating single-agent activity. 1
• High-dose chemotherapy followed by autologous stem cell rescue may be considered as consolidation in selected patients with minimal residual disease, though this remains controversial. 1
• Enrollment in clinical trials is strongly recommended for all patients with relapsed disease. 1

Special Considerations for Subtypes

BCOR-altered Sarcoma

• Outcomes are comparable to Ewing sarcoma when treated with similar protocols. 1

CIC-rearranged Sarcoma

• Survival is poor irrespective of chemotherapy regimen used. 1
• Soft tissue sarcoma regimens (doxorubicin and ifosfamide) show similar outcomes to Ewing protocols for localized disease. 1
• No treatment at relapse has been found beneficial; clinical trial enrollment is essential. 1

Critical Pitfalls to Avoid

• Do not delay local control therapy after chemotherapy response, as this may compromise outcomes. 1
• Do not omit postoperative radiotherapy when margins are positive or close, as this significantly impacts local control. 1
• Do not use inadequate chemotherapy duration—ensure 28-49 weeks of total treatment. 1
• For CIC-rearranged tumors, recognize the poor prognosis and prioritize clinical trial enrollment rather than standard protocols. 1