Ewing’s sarcoma

Ewing's Saecoma - Powerpoint Presentation

1. Dr . Manish Shrestha Orthopaedic Surgery

2. Dr. James Ewing Ewing’s Sarcoma

3. Introduction Named after James Ewing who identified it in 1921. Was originally termed as diffuse endothelioma or endothelial myeloma . Currently- part of peripheral primitive neuroectodermal tumors as it shares common cytogenetic translocation of chromosome 11 & 22.

4. Introduction Ewings sarcoma is a round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%.

5. Ewings sarcoma family of tumors: Ewing’s sarcoma Extraosseous Ewing’s sarcoma Peripheral PNET Askin’s tumor.

6. Prevalance Second most frequent bone sarcoma after osteosarcoma in patients younger than 20 years. 2% of cancer in childhood. Caucasians are more frequently affected than asians , africans and african-americans rarely affected. Common age- 10 – 20 years. M>F - (M:F = 1.4 : 1)

7. Sites Long bones diaphysis involvement is common. Ribs – frequently manifests with pneumonia or pleural effusion.

8. SPREAD Generally spread through bloodstream Direct extension into adjacent bone or soft tissue. Micromets is common in all patients.

9. Approximately 50% of patients who present with metastases have pulmonary involvement. 25% - bony metastases. 20% - bone marrow involvement. Liver and lymph node metastases are rare.

10. staging No specific staging system for Ewings sarcoma The AJCC staging systems for bone or soft-tissue sarcomas may be used.

11. Pathology Poorly differentiated tumor Unknown origin. Thought to be of neural crest progenitor cell origin.

12. Gross whitish-gray soft tissue mass arises in the marrow spaces of the affected bone. Necrotic and hemorrhagic areas are frequent. Periosteum elevated and is often perforated. Almost always a large soft tissue mass extending well beyond the bony boundaries. Not encapsulated and invades the surrounding muscle.

13. Gross & Microscopy

14. Microscopic Compact sheets of small polyhedral cells with pale cytoplasm and ill-defined boundaries. Nuclei- uniform, round or oval, and contains scattered areas of chromatin. Cytoplasm is scant Presence of glycogen in the cell

15. Occasional rosette or pseudorosette formation may be present. Must be distinguished from neuroblastoma , non-Hodgkin lymphoma and rhabdomyosarcoma .

16. Cytogenetics 80 to 90 % patient s with Ewing sarcoma have a translocation of chromosomes 11 and 22 or chromosomes 21 and 22.

17. Clinical features Local pain and swelling of affected area. Tender local mass is invariably present. Stiffness – common in involvement of long bone. Limp

18. Weight loss Fever Anemia Occasionally presents with pathological fractures. Other symptoms depend on the site of the lesion .

19. Investigations - Radiographic findings X-RAY Characteristic but not pathognomonic Permeative lesion with mottled rarefaction of the medullary cavity and invasion through the overlying cortex, reflecting rapid bone destructon . Periosteal new bone formation- laminated “ onion peel ”.

20. Moth eaten lesion Lytic or mixed lytic -sclerotic areas Codman’s triangle

21. Radiographic findings resemble Osteomyelitis Osteosarcoma Histiocytosis Wilms tumor Lymphoma Metastatic neuroblastoma

22. MRI is useful to determine the extent of the lesion within the bone and adjacent soft tissue. Dynamic MRI have made it possible to use to access the response to chemotherapy . CT – to search for metastatic disease in the chest.

23. Bone scan - to search for other areas of bone involvement. RT-PCR – most definitive test by demonstration of chromosomal translocation t(11;22)

24. Diagnosis is usually made from histologic study of tissue sections by open or needle biopsy. And it is best to avoid making a cortical defect in a long bone , because if radiation is chosen for local control, the chances of pathologic fracture are greater. Frozen section biopsy , to ensure adequate tissue is obtained for histologic studies.

25. The histologic differential diagnosis – Neuroblastoma Rhabdomyosarcoma Malignant lymphoma Small cell osteosarcoma Wilms tumor Desmoplastic small cell tumor.

26. Laboratory tests CBC Alkaline phosphatase LDH

27. prognosis With the advent of adjuvant chemotherapy and proper local control , the outlook has been considerably better approximately 70 % 5-year event free survival rates Large Central Lesion (esp., Pelvis) – worse outcome than those with distant tumors.

28. Prognostic factors Unfavourable factors Distant metastasis Older than 15 years Size larger than 8cm. Central lesions( pelvis or spine). Poor response to chemotherapy

29. Favourable prognosis Distal extremity <8 cm in greatest diameter or <20o ml estimated volume. Localized Absence of radiographically identifiable soft tissue extension.

30. Fever , weight loss, anemia and elevated WBC, ESR, LDH indicate more extensive disease and a poor prognosis.

31. Treatment Multidisciplinary approach Includes chemotherapy, surgery, radiation therapy. Depends on – Where in the body the tumor started. Where the tumor has spread. The size of the tumor. The result of the treatment.

32. CHEMOTHERAPY With Intensive chemotherapy reported long-term survival rate is 60-70%. Can be given before surgery( neoadjuvant ) or after( adjuvant ) . Current drugs Doxorubicin(DXR), Cyclophsophamide (CPA), Vincristine (VCR) Actinomycin -D (ACT) Ifosfamide (IFM) Etoposide (VP16)

33. VACD-IE regimen – the standard therapy for localized ewings sarcoma . 10 year event-free survival is around 50%.- first line therapy Second line therapy- Cyclophosphamide and topotecan Temozolomide and irinotecan Ifosafamide and etoposide Ifosfamide , etoposide and carboplatin Docetaxel and gemcitabine

34. Preoperative 4 to 6 cycles of multiagent chemotherapy is indicated Decrease in tumor size Decrease in LDH level Tumor necrosis Efficacy of limb salvage surgery Facilitates disease free survival

35. Postoperatively, additional cycles of the same regimen is given. Total 48 weeks. Chemotherapy in every 2 weeks demonstrated improvement in event free survival than chemotherapy in every 3 weeks.

36. RADIATION THERAPY Effectively controls local disease , when combined with chemotherapy. Usual dose- 55.8 to 60 Gy . Adequate dosages result in local control in 53 to 86 %. Studies shows no difference in local control with 2cm margin compared to whole bone irradiation.

37. Definitive radiation therapy: Where resection is impossible Where only intra- lesional resection is achievable Patient refusin g surgery Patient with poor surgical risk.

38. Problems with radiotherapy In younger children with lower extremity primary tumors, irradiation of growth plates can lead to limb length inequality . Fracture - if bone is irradiated. Late occurence of a secondary malignancy in the involved bone.

39. Surgical treatment Resection of tumor. Best done after induction chemotherapy, which often decreases the size of the soft tissue mass. To avoid secondary malignancies. Margins and histologic necrosis in the resected specimen are examined.

40. If margin is positive postoperative radiation is advised but the dose is lower than before . Amputaion – in bulky tumors that do not respond to chemotherapy and irradiation.

41. Metastatic ewing sarcoma Worse prognosis. Survival rates – approximately 25% at 5 years. Addition of ifosfamide and etoposide to vincristine , doxurubicin , cyclophosphamide and actinomycin D would improve outcome.

42. New Treatment Chemotherapy with stem cell transplant Targeted therapy- monoclonal antibody therapy

43. surveillance Physical examination, chest x-ray: Every 2-3 months Increase interval after 24 months Annually after 5 years CBC Bone scan

44. Relapse Early- less than 2 years: Change chemotherapy Late – more than 2 years: Continue the previously used CT.

45. Summary Second most common primary malignant bone tumors in children. Common Age group – 10-20 years (M>F) Commonly involves diaphysis of long bone. Presents with local swelling and tenderness. Metastasis is usually present at the time of presentation. Diagnosis is confirmed by histopathological studies or cytogenetic studies. Treatment modalities includes Neoadjuvant therapy followed by local control of the tumor with surgery/radiotherapy and maintainence with adjuvant chemotherapy. 5-year event free survival has incresed from 10% to 70% with the advent of multi- chemotheraputic agents.

46. Thank you