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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