A 16-year-old girl presents to the orthopedic clinic with a 4-month history of pain in the left tibia and a palpable mass over the anterior shin. She reports constitutional symptoms including low-grade fever and fatigue. Radiographs show a mixed lytic-sclerotic lesion in the diaphysis with an aggressive periosteal reaction. MRI confirms a large intramedullary tumor with extensive soft tissue component. Biopsy reveals small round blue cells with high mitotic activity. Immunohistochemistry is positive for CD99 and FLI1. What is the most appropriate next step in management?

Explanation

## Management Strategy for Ewing Sarcoma **Key Point:** Modern multimodal therapy for Ewing sarcoma uses **neoadjuvant chemotherapy first**, followed by definitive surgery, then adjuvant chemotherapy. This approach has dramatically improved survival from <10% (surgery alone) to ~70% with complete protocols. ### Rationale for Neoadjuvant Approach **High-Yield:** Neoadjuvant chemotherapy: 1. Reduces tumor volume and soft tissue extension, facilitating limb-sparing surgery 2. Allows assessment of chemotherapy response (prognostic indicator) 3. Treats micrometastases present at diagnosis (~20% have occult pulmonary disease) 4. Enables surgical planning with better margins ### Standard Chemotherapy Regimen **Mnemonic: VAC-IE** — **V**incristine, **A**driamycin (doxorubicin), **C**yclophosphamide, **I**fosfamide, **E**toposide - **Induction phase:** Vincristine, doxorubicin, cyclophosphamide (VAC) alternating with ifosfamide and etoposide (IE) - **Duration:** 12–14 weeks of neoadjuvant therapy - **Goal:** Achieve >90% tumor necrosis on surgical specimen (good prognostic sign) ### Treatment Timeline ```mermaid flowchart TD A[Diagnosis: Ewing Sarcoma]:::outcome --> B[Staging: CT chest, bone scan/PET]:::action B --> C[Neoadjuvant Chemotherapy VAC-IE]:::action C --> D{Response Assessment}:::decision D -->|Good response| E[Surgical Resection with wide margins]:::action D -->|Poor response| F[Consider intensification or alternative approach]:::action E --> G[Adjuvant Chemotherapy]:::action G --> H[Long-term follow-up]:::outcome F --> H ``` **Clinical Pearl:** Surgical timing is critical — resection is typically performed **after 10–12 weeks of neoadjuvant chemotherapy**, allowing tumor shrinkage and assessment of response. ### Why Limb-Sparing Surgery Is Preferred - Modern neoadjuvant chemotherapy enables **limb-sparing resection in >90% of cases** - Amputation is reserved for: - Tumors with vascular invasion making resection impossible - Pathologic fracture with tumor extension - Neurovascular compromise - Patient/family preference **Warning:** Early amputation without chemotherapy is outdated and reduces survival significantly. ### Prognostic Factors | Factor | Favorable | Unfavorable | |--------|-----------|-------------| | **Tumor size** | <8 cm | >8 cm | | **Location** | Distal femur, proximal tibia | Pelvis, proximal femur | | **Metastases** | None | Pulmonary or skeletal | | **Chemotherapy response** | >90% necrosis | <90% necrosis | | **Age** | <15 years | >15 years | ### Survival Outcomes - **Localized disease with multimodal therapy:** ~70% 5-year survival - **Metastatic disease:** ~25–30% 5-year survival - **Pulmonary metastases:** Aggressive chemotherapy + pulmonary resection can improve outcomes [cite:Robbins 10e Ch 26; Tuli's Orthopedics 7e Ch 15]