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Overview of Systemic Px in MS malignancies

Overview of Systemic Px in MS malignancies. งานประชุมวิชาการคณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่น 2009 ผศ . พญ . เอื้อมแข สุขประเสริฐ ภาควิชาอายุรศาสตร์ คณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่น. Primary bone tumors - Osteosarcoma : Role of systemic Px. Secondary bone tumors - Metastatic bone lesion

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Overview of Systemic Px in MS malignancies

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  1. Overview of Systemic Px in MS malignancies งานประชุมวิชาการคณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่น 2009 ผศ.พญ.เอื้อมแข สุขประเสริฐ ภาควิชาอายุรศาสตร์ คณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่น

  2. Primary bone tumors - Osteosarcoma : Role of systemic Px Secondary bone tumors - Metastatic bone lesion : Where is the 10 and how to manage ? Bone tumors

  3. OsteosarcomaESMO Clinical Recommendations for diag, treatment and follow • Standard staging in localized tumors 1. CT scan chest 2. Bone scan 3. Routine CBC, Chemistry (Cr,Electrolytes, Mg, ALP and LDH) 4. Sperm banking should be considered ESMO guideline. Annals Oncol 2007.

  4. Treatment Modalities • Surgery: local control • Radiation: local control (positive margin) • Multidrug chemotherapy: systemic control

  5. Treatment plan • Concept 1. Chemotherapy has significantly  5-yr survival rate for pt with localized tumors from 20% to 60% *** CT is a “must” 2. Surgery is a “must” too ! - Retrospective study, all of the patients who were not surgically treated had disease progression and died within 40 months after 1st recurrence ESMO guideline. Annals Oncol 2007.

  6. Multidrug Chemotherapiesin Osteosarcoma First-line chemotherapy High-dose Methotrexate (HD-MTX): 8-12 gm/m2 Adriamycin: 60-90 mg/m2 Cisplatin: 100-120 mg/m2 Ifosfamide: 8-15 gm/m2 Salvage chemotherapy Ifosfamide 8-15 gm/m2 alone or combination with Etoposide 100 mg/m2/day x 5 days

  7. Neo-adjuvant CT Adjuvant CT Systemic Chemotherapy in Osteosarcoma

  8. T-10: Surgery + Adjuvant Chemotherapy Surgery + Chemo Surgery + Chemo Surgery Surgery Eilber F. et al. JCO 1987; 5:21

  9. Active agents: Methotrexate (HD) Doxorubicin Cisplatin Ifosfamide Etoposide

  10. Role of Neo-adjuvant CT in Osteosarcoma • Improve DFS and OS (compare to adjuvant CT) • Allow limb sparing surgery • In vitro chemosensitivity

  11. POG 8651 Goorin, AM. et al. J Clin Oncol; 21:1574-1580 2003

  12. POG8651 Survival (P = 0.8) EFS (P = 0.6) Neoadjuvant per se did not improve outcome and survival Goorin, AM. et al. J Clin Oncol; 21:1574-1580 2003

  13. POG 8651 5-yr Survival(P = 0.896) 5-yr EFS(P = 0.027) But patients who respond with neoadjuvant improve EFS Goorin, AM. et al. J Clin Oncol; 21:1574-1580 2003

  14. What is the best “regimen” ? • How many drugs ? • How much ?

  15. Cisplatin/Doxo Cisplatin/Doxo Multidrug T10-like Multidrug T10-like Souhami et al, The Lancet 1997; 350:911-917

  16. Souhami et al. Lancet Cisplatin/Doxo q 2wks *  Dose intensity does not improve the outcome ! Lewis, I. J. et al. J. Natl. Cancer Inst. 2007 99:112-128

  17. MAP regimen Current standard Rx program encourage by EURAMOS (European and American Osteosarcoma Study Group) • Children’s Oncology Group (COG) • Cooperative Osteosarcoma Study Group (COSS) • European Osteosarcoma Intergroup (EOI) • Scandinavian Sarcoma Group (SSG)

  18. Change Rx for poor responder Salvage population did worse

  19. Biologic Response Modifier & Targeted Therapy in Osteosarcoma Liposome encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE, Mifamurtide, Junovan®) Interferon- Pegylated Interferon- Anti-HER2 antibody Expression of HER2/erb2 correlate with poor survival IGF-1R monoclonal antibody

  20. Patient who not fit for limb-sparing surgery - Pathological fracture : Surgery then adjuvant CT Patient who arepotentially for limb sparing surgery :Chemo (Cis/A or Cis/A/HDMX in fit < 35 yr) 2-3 cycles : Surgery : Chemo same regimen until finish totally of 6 cycles Conclusion for localized osteosarcoma All patients need full staging: CT chest and Bone scan

  21. Bone metastasis of unknown primary

  22. Cancer of Unknown Primary(CUP)

  23. Concepts • First rule - Try to establish definite“tissue diagnosis” - LN biopsy - liver biopsy - bone biopsy - sputum cytology, FNA • Second rule - search forpossible “primary” siteof involvement - huge liver mass = possible liver 10 -huge pulmonary mass = possible lung 10

  24. Concepts • Third rule - Try to understand several clinicopathological features that help identify patient with“responsive tumors” - Germ cell tumors (especially EGCT) - Lymphoma - Breast cancer, ovarian cancer - Prostate cancer

  25. 11 Months 15 Months Knowledge of Primary Site Improves Survival1 • Cancers with favorable treatments2: • Germ cell carcinomas • Ovarian cancer • Breast cancer • Cervical squamous cancer • Neuroendocrine cancers • Prostate cancer 1 Abbruzzese et al, JCO, Vol 13, No 8 (August), 19952 Pavlidis et al, Eur. J. Cancer, 39, 1990-2005, 2003

  26. All male with blastic metastasis All male with bone met with histology of adeno CA PSA both in serum and IHC stain in tissue should be performed Px as prostate in case of rising PSA 3. Men with suspected prostate CA metastasis TREATMENTFAVORABLE SUBSETS

  27. Non-hematologic (> 60% up) - Lung cancer (20%) - Breast CA (20%) - Prostate CA (20%) - Unknown (10%) - RCC (5%) - Colorectal (5%) Hematologic ( 20-30%) - MM - Lymphoma What (where) is primary malignancy ?

  28. Hx & PE - fever - bone pain - anemia - hepatospenomegaly - lymphadenopathy Investigations - ALP ( in MM) - CBC (rouleaux) - Bun/Cr - Globulin - Urine bence jone - Film skull - Ca Bone metastasis : Approach1. Suspected hematologic malignancy : MM

  29. Bone metastasis : Approach1. Suspected non-hematologic malignancy • Hx & PE - Cough, dyspnea, tightness - GI symptoms - Abdominal mass - Supraclavicular LN - Breast exam - Hematuria • Investigations - ALP ( ) - CXR - PSA (all men) - Mammo (women) - CT chest & abdomen

  30. Take home messages for bone metastasis of unknown primary • 1. All men : PSA • 2. All women : breast PE, mammogram • 3. All patient : CXR, ALP, Ca, CBC - Normal ALP  Rouleaux, Globulin, Cr, Urine bence -  ALP : solid tumors : if PSA normal, breast and CXR no clue CT chest and whole abdomen

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