Transcript ภาพนิ่ง 1
Overview of Systemic Px in MS malignancies งานประชุ มวิชาการคณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่ น 2009 ผศ.พญ.เอือ้ มแข สุ ขประเสริฐ ภาควิชาอายุรศาสตร์ คณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่ น Bone tumors Primary bone tumors - Osteosarcoma : Role of systemic Px Secondary bone tumors - Metastatic bone lesion : Where is the 10 and how to manage ? Osteosarcoma ESMO 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. Treatment Modalities Surgery: local control Radiation: local control (positive margin) Multidrug chemotherapy: systemic control 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. Multidrug Chemotherapies in 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 Systemic Chemotherapy in Osteosarcoma Neo-adjuvant CT Adjuvant CT Benefit Disadvantage Benefit Disadvantage OS, DFS Delay surgery OS, DFS No organ preserve No delay surg No measurable lesion Limb-sparing In vitro sense T-10: Surgery + Adjuvant Chemotherapy Surgery + Chemo Surgery + Chemo Surgery Surgery Eilber F. et al. JCO 1987; 5:21 Active agents: Methotrexate (HD) Doxorubicin Cisplatin Ifosfamide Etoposide Role of Neo-adjuvant CT in Osteosarcoma Improve DFS and OS (compare to adjuvant CT) Allow limb sparing surgery In vitro chemosensitivity POG 8651 Goorin, AM. et al. J Clin Oncol; 21:1574-1580 2003 POG 8651 EFS (P = 0.6) Survival (P = 0.8) Neoadjuvant per se did not improve outcome and survival Goorin, AM. et al. J Clin Oncol; 21:1574-1580 2003 POG 8651 5-yr EFS (P = 0.027) 5-yr Survival (P = 0.896) But patients who respond with neoadjuvant improve EFS Goorin, AM. et al. J Clin Oncol; 21:1574-1580 2003 What is the best “regimen” ? How many drugs ? How much ? Cisplatin/Doxo Cisplatin/Doxo Multidrug T10-like Multidrug T10-like Souhami et al, The Lancet 1997; 350:911-917 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 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) Change Rx for poor responder Salvage population did worse 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 Conclusion for localized osteosarcoma All patients need full staging : CT chest and Bone scan Patient who not fit for limbsparing surgery - Pathological fracture : Surgery then adjuvant CT Patient who are potentially 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 Bone metastasis of unknown primary Cancer of Unknown Primary (CUP) Concepts First rule - Try to establish definite “tissue diagnosis” - LN biopsy - liver biopsy - bone biopsy - sputum cytology, FNA Second rule - search for possible “primary” site of involvement - huge liver mass = possible liver 10 - huge pulmonary mass = possible lung 10 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 Knowledge of Primary Site Improves Survival1 Cancers with favorable treatments2: 11 15 Months Months 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 TREATMENT FAVORABLE SUBSETS 3. Men with suspected prostate CA metastasis 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 What (where) is primary malignancy ? Non-hematologic (> 60% up) - Lung cancer (20%) - Breast CA (20%) - Prostate CA (20%) - Unknown (10%) - RCC (5%) - Colorectal (5%) Hematologic ( 20-30%) - MM - Lymphoma Bone metastasis : Approach 1. Suspected hematologic malignancy : MM 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 : Approach 1. 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 Take home messages for bone metastasis of unknown primary 1. All men 2. All women 3. All patient - Normal ALP - ALP : PSA : breast PE, mammogram : CXR, ALP, Ca, CBC Rouleaux, Globulin, Cr, Urine bence : solid tumors : if PSA normal, breast and CXR no clue CT chest and whole abdomen