Bone sarcoma      Ahmed ZeeneldinAssociate Professor of Medical          Oncology
GTNM Staging BS, 2010• T1: <= 8 cm• T2: > 8 cm• T3: Discontinuous tumors in the primary bone site• No T4 like ovaries• N1:...
Surgical Staging system 1980• T1: intracompartmental• T2: extracompartmental                                T1    T2    N1...
Incidence• Rare: 0.2% of all cancers• Often curable• Common forms:   – Osteosarcoma (35%), OS   – Chondrosarcoma (30%), CS...
CS             OS             ES             MFH         HET        Chor                                                  ...
Multidisciplinary Team• Core group   –   Bone pathologist   –   Musculoskeletal radiologist   –   Orthopaedic oncologist  ...
Workup
Workup• Radiology:  – Primary site:     • Plain film, MRI and or CT, bone scan  – Exclude mets and other lesions:     • Ch...
Chondrosarcoma (CS)
CS• Produce cartilage matrix without bone• Occur at any age, but more common in older  adults• Types:  – Conventional CS: ...
CS treatment
Chemotherapy in CS• Not sensitive to chemo especially  conventional• Dedifferentiated and mesenchymal are more  sensitive ...
Ewing’s sarcoma (ES)
ES• adolescents and young adults• All ES are undifferentiated• Common sites: femur, pelvic bones, and the  bones of chest ...
XrayOn imaging, thebone appearsmottled.Periostealreaction isclassic and it isreferred to as“onion skin
Ewing Sarcoma Family of tumors                 ESFT•   Ewing’s sarcoma,•   extraosseous Ewing’s sarcoma•   Askin’s tumor,•...
ES genetics- fusion of EWSgene on chr 22qWITHETS gene family(FLI1) on chr 11- Found in 85%of ES
ES IHCstrong expression of cell-surfaceglycoprotein MIC2 (CD99)
Prognostic factors• Good   – Distal site   – Absence of mets   – Normal LDH• Risk stratification:   – High risk: mets, hig...
Treatment of ES
Treatment of non-progressive disease
Chemotherapy in ES• Drugs                        • Metastatic:  –   V: vincreistine             – VDC  –   A: dactinomycin...
VAC vs VACD           VAC (IESS-I)   VACD (IESS-II)RFS        24             60%OS                        Bettertoxicity  ...
VACD vs VACD/IE
VACD vs VACDlIENon-metastatic disease            Metastatic disease           VACD   VACD/IE P                   VACD   VA...
Figure 1. Event-free Survival According to Study Group   Figure 2. Event-free Survival According to Study Groupand the Pre...
VACD vs VAIA vs EVAIA
VACA vs VAIA vs EVAIAStandard risk (localized, low volume < 100 ml)   High-risk (metastatic, high volume > 100 ml)VAIA = V...
Relapsed or Refractory ES• Good Prognostic factors:  – Time to Rec => 2years  – Local recurrence treatable by surgery and ...
Treatment of relapsed or refractory ES• Relapse => 2years:  – the same initial therapy can be used• Relapse < 2 years:  – ...
Osteosarcoma (OS)
OS• Commonest bone malig in children and young  adults• Sites of max bone growth (distal femur and  prox tibia)• Types:• C...
Prognostic factors• Tumor site (distal vs prox)• Tumor size (small vs large)• Metastases (no vs yes)• Metastatic site (lun...
OS plain x ray• Plain radiographs show  cortical destruction and  irregular reactive bone  formation
Workup in OS• Imaging:  – For 1ry:     • Plain radiograph     • MRI (BEST) and or CT     • Bone scan  – For 2ry:     • CT ...
Treatment• Surgery (limb sparing or amputation) AND• Adjuvant or neoadjuvant chemotherapy
Chemotherapy regimens•   First line (adj/neoadj/primary)     –   Cisplatin and doxorubicin     –   MAP (High-dose methotre...
Treatment of OS
Adjuvant CT better than observation
As in the historical experience,50% of the patients suffered relapse within six months of diagnosis, andoverall, more than...
Short equal to long CT regimens in operable OS               Short                       LongDrugs          Doxorubicin 25...
ResultsPFS the same       OS the same
Two drugs Multiagent             (Cis-Adria)Treatment    94%       51%completionTOXICITY     Similar   similar> 90% tumor ...
Ifosfamide/etoposide in met OS
Adding ifosfamide to cisplatin  Epirubicin in non-met OS
Indirect comparison               Cisplatin –     Cisplatin –               adriamycin      epirubicin –                  ...
AP vs PEI
Neoadj CT
High dose CT and SCT•   Investigational•   High risk metastatic and relapsed•   TRM 3%•   3-y DFS: 12%•   3-y OS: 21%
Good response (>90% necrosis) to Neoadj chemo is agood prognostic factor
Bone sarcoma
Bone sarcoma
Bone sarcoma
Bone sarcoma
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Bone sarcoma

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

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Bone sarcoma

  1. 1. Bone sarcoma Ahmed ZeeneldinAssociate Professor of Medical Oncology
  2. 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. 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. 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. 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. 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. 7. Workup
  8. 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. 9. Chondrosarcoma (CS)
  10. 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. 11. CS treatment
  12. 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. 13. Ewing’s sarcoma (ES)
  14. 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. 15. XrayOn imaging, thebone appearsmottled.Periostealreaction isclassic and it isreferred to as“onion skin
  16. 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. 17. ES genetics- fusion of EWSgene on chr 22qWITHETS gene family(FLI1) on chr 11- Found in 85%of ES
  18. 18. ES IHCstrong expression of cell-surfaceglycoprotein MIC2 (CD99)
  19. 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. 20. Treatment of ES
  21. 21. Treatment of non-progressive disease
  22. 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. 23. VAC vs VACD VAC (IESS-I) VACD (IESS-II)RFS 24 60%OS Bettertoxicity More
  24. 24. VACD vs VACD/IE
  25. 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. 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. 27. VACD vs VAIA vs EVAIA
  28. 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. 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. 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. 31. Osteosarcoma (OS)
  32. 32. OS• Commonest bone malig in children and young adults• Sites of max bone growth (distal femur and prox tibia)• Types:• Classic: 80%
  33. 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. 34. OS plain x ray• Plain radiographs show cortical destruction and irregular reactive bone formation
  35. 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. 36. Treatment• Surgery (limb sparing or amputation) AND• Adjuvant or neoadjuvant chemotherapy
  37. 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. 38. Treatment of OS
  39. 39. Adjuvant CT better than observation
  40. 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. 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. 42. ResultsPFS the same OS the same
  43. 43. Two drugs Multiagent (Cis-Adria)Treatment 94% 51%completionTOXICITY Similar similar> 90% tumor 29% 29%necrosis
  44. 44. Ifosfamide/etoposide in met OS
  45. 45. Adding ifosfamide to cisplatin Epirubicin in non-met OS
  46. 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. 47. AP vs PEI
  48. 48. Neoadj CT
  49. 49. High dose CT and SCT• Investigational• High risk metastatic and relapsed• TRM 3%• 3-y DFS: 12%• 3-y OS: 21%
  50. 50. Good response (>90% necrosis) to Neoadj chemo is agood prognostic factor

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