Bone sarcoma
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Comprehensive overview of bone sarcoma: staging, diagnosis, risk stratification and treatment

Comprehensive overview of bone sarcoma: staging, diagnosis, risk stratification and treatment

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  • 1. Bone sarcoma Ahmed ZeeneldinAssociate Professor of Medical Oncology
  • 2. GTNM Staging BS, 2010• T1: <= 8 cm• T2: > 8 cm• T3: Discontinuous tumors in the primary bone site• No T4 like ovaries• N1: regional LN (RARE) T1 T2 T3 N1 M1a/b• M1a: lung mets LG, GX IA IB IB IVB IVA/IVB• M1b: non-lung distant mets HG IIA IIB III IVB IVA/IVB• Low grade: G1, 2• High grade: G3,4• Grade cannot be assessed: GX
  • 3. Surgical Staging system 1980• T1: intracompartmental• T2: extracompartmental T1 T2 N1 M1• N1: regional LN (RARE) LG IA IB III III• M1: distant mets HG IIA IIB III III• Low grade: G1, 2• High grade: G3,4
  • 4. Incidence• Rare: 0.2% of all cancers• Often curable• Common forms: – Osteosarcoma (35%), OS – Chondrosarcoma (30%), CS – Ewing’s sarcoma (16%), ES – Malignant fibrous histiocytoma (MFH) and fibrosarcoma (FS) (<1%) – Others hemangioendothelioma (HET) and hemangiopericytoma (HPC), and chordoma: very rare
  • 5. CS OS ES MFH HET Chor HPC domaage Middle age Children Children Older adults Young adults Young adultsOrigin Cartilage bone ? Fibrous T vascular notochord
  • 6. Multidisciplinary Team• Core group – Bone pathologist – Musculoskeletal radiologist – Orthopaedic oncologist – Medical/pediatric oncologist – Radiation oncologist• Specialists critical in certain cases – Thoracic surgeon – Plastic surgeon – Interventional radiologist – Physiatrist – Vascular surgeon – Additional surgical subspecialties
  • 7. Workup
  • 8. Workup• Radiology: – Primary site: • Plain film, MRI and or CT, bone scan – Exclude mets and other lesions: • Chest x-ray or CT • Bone scan, PET• Lab: – CBC, LDH, Alk Phos, Ca – Biopsy: Core needle or surgical (better at treating center)
  • 9. Chondrosarcoma (CS)
  • 10. CS• Produce cartilage matrix without bone• Occur at any age, but more common in older adults• Types: – Conventional CS: 85% • 1ry or central: from normal bone • 2ry or peripheral: from preexisting lesion – Other types CS: 10-15% • Clear cell • Dedifferentiated • Myxoid and mesenchymal
  • 11. CS treatment
  • 12. Chemotherapy in CS• Not sensitive to chemo especially conventional• Dedifferentiated and mesenchymal are more sensitive – Dedifferentiated: treat as OS (cisplatin doxo) – Mesenchymal: treat as ES (VACD, VAIA, EVIAI)
  • 13. Ewing’s sarcoma (ES)
  • 14. ES• adolescents and young adults• All ES are undifferentiated• Common sites: femur, pelvic bones, and the bones of chest wall, but any bone can be affected• Diaphysis is the commonest area• Symptoms: – Pain and swelling – Constitutional: fever, weight loss, and fatigue
  • 15. XrayOn imaging, thebone appearsmottled.Periostealreaction isclassic and it isreferred to as“onion skin
  • 16. Ewing Sarcoma Family of tumors ESFT• Ewing’s sarcoma,• extraosseous Ewing’s sarcoma• Askin’s tumor,• Primitive neuroectodermal tumor (PNET),• PNET of bone
  • 17. ES genetics- fusion of EWSgene on chr 22qWITHETS gene family(FLI1) on chr 11- Found in 85%of ES
  • 18. ES IHCstrong expression of cell-surfaceglycoprotein MIC2 (CD99)
  • 19. Prognostic factors• Good – Distal site – Absence of mets – Normal LDH• Risk stratification: – High risk: mets, high disease volume (< 100 ml) – Low/standard risk: no mets, low disease vol(> 100 ml)
  • 20. Treatment of ES
  • 21. Treatment of non-progressive disease
  • 22. Chemotherapy in ES• Drugs • Metastatic: – V: vincreistine – VDC – A: dactinomycin – Others – C: cyclophosphamide • Nonmetastatic : more – D (A): doxorubicin intensive – I: fosfamide – Include etoposide – E: etoposide – Alternating cycles• Regimens – VAC vs VACD (IESSI-II) – VACD vs VACD/IE – VAIA vs VACA – VAIA vs EVAIA
  • 23. VAC vs VACD VAC (IESS-I) VACD (IESS-II)RFS 24 60%OS Bettertoxicity More
  • 24. VACD vs VACD/IE
  • 25. VACD vs VACDlIENon-metastatic disease Metastatic disease VACD VACD/IE P VACD VACD/IE PN ~200 ~200 N ~120 ~1205- y EFS 55% 70% 0.005 5- y EFS 22% 22% 0.815-y OS 61 72% 0.01 5-y OS 34% 35% 0.43
  • 26. Figure 1. Event-free Survival According to Study Group Figure 2. Event-free Survival According to Study Groupand the Presence or Absence of Metastatic Disease. and Tumor Site among Patients without Metastases
  • 27. VACD vs VAIA vs EVAIA
  • 28. VACA vs VAIA vs EVAIAStandard risk (localized, low volume < 100 ml) High-risk (metastatic, high volume > 100 ml)VAIA = VAID, VACA= VACD VAIA = VAID VAIAà VAIAà P EVAIA VAIA P VAIA VACAN 79 76 N 252 2423- y EFS 74% 73% NS 3- y EFS 52% 47% NS3-y OS 86 90% NS 3-y OS 62 59 NSToxicity Less more
  • 29. Relapsed or Refractory ES• Good Prognostic factors: – Time to Rec => 2years – Local recurrence treatable by surgery and intensive chemo – Lug only mets – Non-elevated LDH
  • 30. Treatment of relapsed or refractory ES• Relapse => 2years: – the same initial therapy can be used• Relapse < 2 years: – Cyclophosphamide and topotecan – Temozolomide and irinotecan – Ifosfamide and etoposide – Ifosfamide, carboplatin and etoposide – Docetaxel and gemcitabine
  • 31. Osteosarcoma (OS)
  • 32. OS• Commonest bone malig in children and young adults• Sites of max bone growth (distal femur and prox tibia)• Types:• Classic: 80%
  • 33. Prognostic factors• Tumor site (distal vs prox)• Tumor size (small vs large)• Metastases (no vs yes)• Metastatic site (lung vs non-lung)• Number of lung mets (few/resectable vs many/iresectable)• Response to chemotherapy ( good vs poor)• Resection (R0 vs R1)• LDH (normal vs elevated)
  • 34. OS plain x ray• Plain radiographs show cortical destruction and irregular reactive bone formation
  • 35. Workup in OS• Imaging: – For 1ry: • Plain radiograph • MRI (BEST) and or CT • Bone scan – For 2ry: • CT chest, bone scan• Lab: LDH, ALP
  • 36. Treatment• Surgery (limb sparing or amputation) AND• Adjuvant or neoadjuvant chemotherapy
  • 37. Chemotherapy regimens• First line (adj/neoadj/primary) – Cisplatin and doxorubicin – MAP (High-dose methotrexate, cisplatin and doxorubicin) – Doxorubicin, cisplatin, ifosfamide and high-dose methotrexate – Ifosfamide and etoposide – Ifosfamide, cisplatin and epirubicin• Second line (relapsed and refractory) – Docetaxel and gemcitabine – Cyclophosphamide and etoposide – Cyclophosphamide and topotecan – Gemcitabine Ifosfamide and etoposide – Ifosfamide, carboplatin and etoposide – High-dose methotrexate, etoposide and ifosfamide• Third line – Resection – RT – Samarium
  • 38. Treatment of OS
  • 39. Adjuvant CT better than observation
  • 40. As in the historical experience,50% of the patients suffered relapse within six months of diagnosis, andoverall, more than 80% developed recurrent disease.Fewer than 20% of patients treated only with surgery of the primary tumor can be expected to survive free of recurrent disease.Thus adjuvant chemotherapy should be recommended to all patients with high-grade osteosarcoma of the extremity
  • 41. Short equal to long CT regimens in operable OS Short LongDrugs Doxorubicin 25 mg/m2 D1–3 preoperatively ( 7wks) cisplatin 100 mg/m2 D1 vincristine, high-dose methotrexate, preoperatively (9wks) and doxorubicin; postoperatively (9 wks) postoperatively (37 wks) bleomycin, cyclophosph, dactinomycin, vincristine, methotrexate, doxorubicin, cisplatinCycles/weeks 6 cycles (18 wks) 44 weeks
  • 42. ResultsPFS the same OS the same
  • 43. Two drugs Multiagent (Cis-Adria)Treatment 94% 51%completionTOXICITY Similar similar> 90% tumor 29% 29%necrosis
  • 44. Ifosfamide/etoposide in met OS
  • 45. Adding ifosfamide to cisplatin Epirubicin in non-met OS
  • 46. Indirect comparison Cisplatin – Cisplatin – adriamycin epirubicin – ifosfamide APx3 àS àAPx3 PEI x 3 àS àPEI x 3Treatment 94% 84%complateionComplete R 26%Good R 29% 37%5-y DFS 42%5-y OS 48%
  • 47. AP vs PEI
  • 48. Neoadj CT
  • 49. High dose CT and SCT• Investigational• High risk metastatic and relapsed• TRM 3%• 3-y DFS: 12%• 3-y OS: 21%
  • 50. Good response (>90% necrosis) to Neoadj chemo is agood prognostic factor