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Management of OSTEOSARCOMA

Management of OSTEOSARCOMA. Carlos Rodriguez-Galindo, MD. Cancer in Children. “More” Common. Common. “Less” Common. Clinical Presentation Extremity bone pain Progressive swelling Distal Femur Proximal tibia Proximal humerus Fever uncommon (vs. Ewing sarcoma). Diagnostic work-up

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Management of OSTEOSARCOMA

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  1. Management of OSTEOSARCOMA Carlos Rodriguez-Galindo, MD

  2. Cancer in Children “More” Common Common “Less” Common

  3. Clinical Presentation Extremity bone pain Progressive swelling Distal Femur Proximal tibia Proximal humerus Fever uncommon (vs. Ewing sarcoma)

  4. Diagnostic work-up Diagnostic imaging XR extremity (MRI) XR chest (CT) Laboratory CBC Chemistries (AP, LDH) Biopsy Needle vs. open Site of biopsy important if LSP planned

  5. MRI T1 W STIR

  6. Bone Tumors in Children

  7. OSTEOSARCOMA Systemic Chemotherapy: Adriamycin Cisplatin/Carboplatin Methotrexate Ifosfamide Local Control: Surgery NO radiation therapy EWING’S SARCOMA Systemic Chemotherapy: Adriamycin Ifosfamide, cyclophos. Etoposide Vincristine Local Control: Surgery Radiation therapy Bone TumorsTreatment

  8. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets

  9. Treatment of Localized Osteosarcoma

  10. Overall and Event-free Survival of Patients with Metastatic OSSt Jude Studies OS-86 and OS-91 5-year estimates S: 24.1% ± 7.4% EFS: 6.9% ± 3.8% Survival (n=29) Event-free Survival (n=29)

  11. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets

  12. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma

  13. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery

  14. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery Modification of Post Surgery CT

  15. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery Modification of Post Surgery CT New Approaches Treatment of OS in Developing Countries

  16. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery Modification of Post Surgery CT New Approaches Treatment of OS in Developing Countries

  17. MTX or no MTX? Jaffe et al NEJM 1974

  18. MTX or no MTX? Jaffe et al NEJM 1974

  19. OsteosarcomaMethotrexate or not Methotrexate?

  20. OsteosarcomaMethotrexate or not Methotrexate?

  21. Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: Prognostic Factors and Impact on Survival Petrilli et al. J Clin Oncol 2006;24:1161 OS and EFS for patients with non-metastatic extremity tumors

  22. OS-99 for Localized Osteosarcoma S U R G IFO CBP IFO CBP IFO CBP IFO DOX IFO CBP CBP DOX IFO DOX DOX 0 3 6 9 12 14 17 20 23 Eval Eval IFO 2.65 g/m2 x 3d DOX 25 mg/m2 x 2-3 d. CBP AUC 8 END OF THERAPY IFO CBP CBP DOX IFO DOX CBP DOX 26 29 32 35 38 Eval Eval

  23. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery Modification of Post Surgery CT New Approaches Treatment of OS in Developing Countries

  24. Overall and Event-free Survival of Patients with Metastatic OSSt Jude Studies OS-86 and OS-91 5-year estimates S: 24.1% ± 7.4% EFS: 6.9% ± 3.8% Survival (n=29) Event-free Survival (n=29)

  25. Metastatic Osteosarcoma

  26. POG 9450 - PFS and survival for all patients Goorin, A. M. et al. J Clin Oncol; 20:426-433 2002

  27. Factors Prognostic of Survival in Patients with Pulmonary Metastases Only St. Jude Studies OS-86, OS-91

  28. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery Modification of Post Surgery CT New Approaches Treatment of OS in Developing Countries

  29. LOCAL CONTROL Radical surgery is critical Amputation Limb salvage procedures Limb salvage should not take priority! LIVE  LIMB Upfront vs. delayed (after induction) Limb salvage State of the art team Local recurrence rates should remain < 5-10%

  30. Survival of Patients with Local recurrence of Osteosarcoma: 5-year Post Relapse Survival19.2 % ± 7.7% Rodriguez-Galindo et al. Cancer 2004; 100:1928

  31. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery Modification of Post Surgery CT New Approaches Treatment of OS in Developing Countries

  32. Osteosarcoma -“T-10” Histologic Response as a Prognostic Factor • Modification of postoperative therapy? • Upfront Surgery? • Intensification of preoperative therapy? No Impact in Outcome

  33. The Big Question (still) Modification of Postoperative Chemotherapy for Poor Responders

  34. The Big Question (still) Modification of Postoperative Chemotherapy for Poor Responders

  35. A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-operative Chemotherapy R A N D O M I Z E MAP GR SURGERY MAPIfn REGISTER MAP R A N D O M I Z E MAP POOR MAPIE

  36. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery Modification of Post Surgery CT New Approaches Treatment of OS in Developing Countries

  37. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets MTX or no MTX? Metastatic Osteosarcoma Timing of Surgery Type of Surgery Modification of Post Surgery CT New Approaches Treatment of OS in Developing Countries

  38. Osteosarcoma in Developing Countries Challenges Delayed diagnosis  Increased tumor burden Large tumors Metastatic disease Drug availability Suboptimal imaging techniques Limited surgical options Poor supportive treatment Complexity of therapy Pain management Physical therapy High abandonment rates

  39. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets

  40. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets AMPUTATION

  41. Treatment of Osteosarcoma S U R G E R Y Tumor Induction Chemotherapy Methotrexate Adriamycin Platinum (CDDP) Continuation Chemotherapy Same Agents Mets AMPUTATION ABANDONMENT 30-40%?

  42. Treatment of Osteosarcoma S U R G E R Y Chemotherapy Methotrexate? Adriamycin Platinum (CDDP) Surgery of mets Preoperative chemotherapy Symptom management Preparation for amputation

  43. OsteosarcomaMethotrexate or not Methotrexate?

  44. Treatment of Osteosarcoma with CDDP/DOX

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