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

3 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.

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 Chemotherapies in Osteosarcoma
First-line chemotherapy High-dose Methotrexate (HD-MTX): 8-12 gm/m2 Adriamycin: mg/m2 Cisplatin: 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 Systemic Chemotherapy in Osteosarcoma
Neo-adjuvant CT Adjuvant CT Benefit Disadvantage  OS, DFS Delay surgery Limb-sparing In vitro sense Benefit Disadvantage  OS, DFS No organ preserve No delay surg No measurable lesion

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:

12 Neoadjuvant per se did not improve outcome and survival
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:

13 But patients who respond with neoadjuvant improve EFS
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:

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:

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

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18 Current standard Rx program encourage by EURAMOS
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)

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20 Change Rx for poor responder
Salvage population did worse

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22 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

23 Conclusion for localized osteosarcoma
All patients need full staging : CT chest and Bone scan Patient who not fit for limb-sparing 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

24 Bone metastasis of unknown primary

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26 Cancer of Unknown Primary (CUP)

27 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

28 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

29 Knowledge of Primary Site Improves Survival1
15 Months 11 Months 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), Pavlidis et al, Eur. J. Cancer, 39, , 2003

30 3. Men with suspected prostate CA metastasis
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

31 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

32 Bone metastasis : Approach 1. Suspected hematologic malignancy : MM
Investigations - ALP ( in MM) - CBC (rouleaux) - Bun/Cr - Globulin - Urine bence jone - Film skull - Ca Hx & PE - fever - bone pain - anemia - hepatospenomegaly - lymphadenopathy

33 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

34 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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