What is the treatment for Ewing's sarcoma?

Treatment of Ewing's Sarcoma

The optimal treatment for Ewing's sarcoma requires a multidisciplinary approach combining intensive chemotherapy, local therapy (preferably surgery), and consolidation chemotherapy, which has significantly improved 5-year survival rates from less than 10% to approximately 60%. 1, 2

Diagnosis and Initial Evaluation

• Patients with radiological findings suggesting bone sarcoma should be referred without prior biopsy to a specialized center with bone sarcoma expertise 1
• Ewing's sarcoma is often associated with a large soft tissue component and can be diagnosed via needle biopsy or open surgical biopsy 1
• Immunohistochemical detection of MIC2 gene expression and identification of characteristic translocations (most commonly t(11;22)(q24;q12)) by cytogenetics or PCR are diagnostic (present in >90% of cases) 1
• Before treatment initiation, comprehensive staging should include:
  • Complete radiological evaluation of the affected bone 1
  • CT scan for pulmonary metastases 1
  • Bone scintigraphy for bone metastases 1
  • Bone marrow aspirates for microscopic examination 1
  • Consideration of sperm banking 1

Treatment Protocol for Localized Disease

Chemotherapy

• Combination chemotherapy is the backbone of treatment 1, 2
• Standard regimen includes:
  • Doxorubicin, vincristine, ifosfamide, etoposide, dactinomycin, and cyclophosphamide 1
  • Total of 12-15 cycles over 8-12 months 1, 2
  • Treatment divided into:
    • Induction chemotherapy (3-6 cycles) 1
    • Local therapy 1
    • Consolidation chemotherapy (8-10 cycles) 1, 2
• Recent evidence suggests at least 12 cycles of chemotherapy is associated with improved event-free and overall survival 3

Local Therapy

• Surgery is the preferred treatment for local control despite Ewing's sarcoma being radiosensitive 1, 2
• A wide surgical margin should be attempted whenever possible 1
• Radiotherapy should be given to patients with:
  • Marginal or intralesional surgery 1
  • Inoperable tumors 1, 2
• Radiation doses:
  • 40-45 Gy for microscopic residual disease 1
  • 50-60 Gy for macroscopic disease 1
• A hyperfractionated regimen may be considered for optimal integration with chemotherapy 1

Treatment for Metastatic Disease

• Patients with metastatic disease at diagnosis should receive the same standardized chemotherapy as those with localized disease 1
• For patients with lung metastases who achieve complete remission, total lung irradiation should be considered 1
• Thoracotomy should be evaluated for patients with limited residual macroscopic disease 1
• Supplemental irradiation of bone metastases is usually indicated 1
• Prognosis varies by metastatic site:
  • Lung metastases alone: 30% 5-year survival 1
  • Skeletal metastases: 10% 5-year survival 1

Recurrent Disease

• With the possible exception of patients with limited relapse after a long disease-free interval, patients relapsing systemically or locally should be considered to be in a palliative situation 1

Prognostic Factors

• Adverse prognostic factors include:
  • Metastatic disease at diagnosis 1
  • Pelvic localization 1, 2
  • Tumor diameter >8-10 cm 1
  • Age >15 years 1
  • Elevated serum lactate dehydrogenase 1
  • Poor histological response to preoperative chemotherapy 1
  • Radiotherapy as the only local treatment 1

Follow-up Recommendations

• 3-month intervals until 3 years after the end of treatment 1
• 6-month intervals until 5 years 1
• 8-12 month intervals until at least 10 years 1
• Extended follow-up is recommended due to:
  • Risk of late relapse 1
  • Long-term toxicity concerns 1
  • 5% risk of second cancers (particularly acute myelogenous leukemia and secondary sarcoma in radiation fields) 1

Treatment Considerations and Pitfalls

• Timing of chemotherapy cycles is important - minimizing delays is associated with improved overall survival 3
• Approximately 20% of patients have detectable metastases at diagnosis, most commonly in lungs and/or bone/bone marrow 1
• Current 5-year overall survival rates:
  • Localized disease: 65-75% 4
  • Metastatic disease: <30% (except isolated pulmonary metastasis: ~50%) 4
• Aggressive surgical resection with adjuvant chemoradiotherapy should be considered even for challenging locations like head and neck 5