Bone tumors n Primary bone tumors Osteosarcoma Role

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

Osteosarcoma ESMO Clinical Recommendations for diag, treatment and follow n 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 n Surgery: local control n Radiation: local control (positive margin) n Multidrug chemotherapy: systemic control

Treatment plan n 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 1 st recurrence ESMO guideline. Annals Oncol 2007.

Multidrug Chemotherapies in Osteosarcoma n First-line chemotherapy n n n High-dose Methotrexate (HD-MTX): 8 -12 gm/m 2 Adriamycin: 60 -90 mg/m 2 Cisplatin: 100 -120 mg/m 2 Ifosfamide: 8 -15 gm/m 2 Salvage chemotherapy n n Ifosfamide 8 -15 gm/m 2 alone or combination with Etoposide 100 mg/m 2/day x 5 days

Systemic Chemotherapy in Osteosarcoma Neo-adjuvant CT Adjuvant CT 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 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) n Allow limb sparing surgery n In vitro chemosensitivity n

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 ? n How much ? n

Cisplatin/Doxo Multidrug T 10 -like Souhami et al, The Lancet 1997; 350: 911 -917

Souhami et al. Lancet Cisplatin/Doxo q 2 wks * 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) n n 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 n n Liposome encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE, Mifamurtide, Junovan (® Interferon- n Pegylated Interferon- Anti-HER 2 antibody n Expression of HER 2/erb 2 correlate with poor survival IGF-1 R monoclonal antibody

Conclusion for localized osteosarcoma All patients need full staging : CT chest and Bone scan n Patient who not fit for limbsparing surgery - Pathological fracture : Surgery then adjuvant CT n 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 n First rule n - 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 n 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 Survival 1 Cancers with favorable treatments 2: 11 15 Months 4 Germ cell carcinomas 4 Ovarian cancer 4 Breast cancer 4 Cervical squamous cancer 4 Neuroendocrine cancers 4 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 n n 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 ? n Non-hematologic (> 60% up) - Lung cancer (20%) - Breast CA (20%) - Prostate CA (20%) - Unknown (10%) - RCC (5%) - Colorectal (5%) n Hematologic ( 20 -30%) - MM - Lymphoma

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

Bone metastasis : Approach 1. Suspected non-hematologic malignancy n Hx & PE - Cough, dyspnea, tightness - GI symptoms - Abdominal mass - Supraclavicular LN - Breast exam - Hematuria n Investigations - ALP ( ) - CXR - PSA (all men) - Mammo (women) - CT chest & abdomen

Take home messages for bone metastasis of unknown primary n n n 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