What is the treatment for Ewing's sarcoma?

Treatment of Ewing's Sarcoma

The optimal treatment for Ewing's sarcoma consists of a multidisciplinary approach combining intensive chemotherapy (induction and consolidation) with local therapy (preferably surgery when feasible), which has increased 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
• Diagnosis is confirmed by needle biopsy or open surgical biopsy, with immunohistochemical detection of MIC2 gene expression and molecular detection of EWS gene translocations (most commonly t(11;22)(q24;q12)) 1
• Before treatment initiation, comprehensive staging should include:
  • Complete radiological evaluation of the affected bone 1
  • CT scan of chest to evaluate pulmonary metastases 1
  • Bone scintigraphy to investigate bone metastases 1
  • Bone marrow aspirates for microscopic examination 1
  • Consideration of sperm banking for male patients 1

Treatment Protocol for Localized Disease

Chemotherapy

• Combination chemotherapy forms the backbone of treatment with 12-15 courses over 8-12 months 1, 2
• Standard chemotherapy drugs include:
  • Doxorubicin
  • Vincristine
  • Ifosfamide
  • Etoposide
  • Dactinomycin
  • Cyclophosphamide 1, 2
• Treatment is divided into:
  • Induction chemotherapy (3-6 courses)
  • Local therapy
  • Consolidation chemotherapy (8-10 courses) 1, 2

Local Therapy

• Surgery is the preferred treatment for local control despite Ewing's sarcoma being radiosensitive 1
• A wide surgical margin should be attempted whenever possible 1, 2
• Radiotherapy should be given in the following situations:
  • Patients with marginal or intralesional surgery
  • Patients with inoperable tumors
  • Radiation doses: 40-45 Gy for microscopic residual disease and 50-60 Gy for macroscopic disease 1
  • Hyperfractionated regimens 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 in the lungs 1
• Supplemental irradiation of bone metastases is usually indicated 1
• Prognosis varies by metastatic site:
  • Lung metastases alone: 30% 5-year survival
  • Skeletal metastases: 10% 5-year survival 1

Recurrent Disease

• With the exception of patients with limited relapse after a long disease-free interval, patients with systemic or local relapse should be considered to be in a palliative situation 1
• Current 5-year overall survival for recurrent disease remains poor 3, 4

Prognostic Factors

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

Follow-up Recommendations

• 3-month intervals until 3 years after treatment completion 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 (5-15 years)
  • Long-term toxicity to heart, kidneys, and lungs
  • 5% risk of second cancers (particularly acute myelogenous leukemia and secondary sarcoma in radiation fields) 1

Treatment Outcomes

• Current 5-year overall survival for localized disease: 65-75% 3, 5
• Survival rates by location:
  • Extremity tumors (non-metastatic): 72-95% 6, 5
  • Axial and proximal tumors: 65-79% 6, 7
• Combined multimodal treatment for head and neck Ewing's sarcoma has shown 5-year overall survival of 87% 7

Important Considerations and Pitfalls

• Approximately 20% of patients have detectable metastases at diagnosis, most commonly in lungs and/or bone/bone marrow 1, 2
• Patients should be treated in specialized centers due to the rarity and complexity of managing Ewing's sarcoma 1
• Aggressive chemotherapy prior to local therapy can significantly reduce tumor size and allow pathologically-eroded bone to heal before radiation therapy 6
• While shorter, more intensive chemotherapy protocols (like MSKCC P6) have shown comparable outcomes to longer regimens, the standard remains 8-12 months of therapy 5, 4