Management of OSTEOSARCOMA

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Management of OSTEOSARCOMA
Carlos Rodriguez-Galindo, MD
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Cancer in Children
More Common
Common
Less Common
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Clinical Presentation Extremity bone
pain Progressive swelling Distal
Femur Proximal tibia Proximal humerus Fever
uncommon (vs. Ewing sarcoma)
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Diagnostic work-up Diagnostic imaging XR
extremity (MRI) XR chest (CT) Laboratory CBC C
hemistries (AP, LDH) Biopsy Needle vs.
open Site of biopsy important if LSP planned
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MRI
T1 W
STIR
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Bone Tumors in Children
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Bone TumorsTreatment

• OSTEOSARCOMA
• Systemic Chemotherapy
• Adriamycin
• Cisplatin/Carboplatin
• Methotrexate
• Ifosfamide
• Local Control
• Surgery
• NO radiation therapy

• EWINGS SARCOMA
• Systemic Chemotherapy
• Adriamycin
• Ifosfamide, cyclophos.
• Etoposide
• Vincristine
• Local Control
• Surgery
• Radiation therapy

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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
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Treatment of Localized Osteosarcoma
Study (Year report) No. of pts Chemotherapy Event-free survival Survival
INT 0133 POG-9351 CCG-7921 (2001) 577 CDDP/Doxo/HDMTX CDDP/Doxo/HDMTXMTP CDDP/Doxo/HDMTXIfos CDDP/Doxo/HDMTXIfosMTP 5-yr EFS 64 5-yr EFS 63 5-yr EFS 56 5-yr EFS 72
POG-8651 (2003) 55 45 CDDP/Doxo/HDMTX Surgery week 0 vs. Surgery week 10 5-yr EFS 69 5-yr EFS 61 5-yr S 79 5-yr S 76
St. Jude OS-91 (2001) 47 Carbo/Ifos/Doxo/HDMTX 5-yr EFS 66 5-yr S 73
T12 (1998) 73 HDMTX/BCD/CDDP/Doxo HDMTX/BCD/CDDP/Doxo (more intensive preop chemo) Both regimens 5-yr EFS 73 5-yr EFS 78 5-yr EFS 76
COSS 86 (1998) 171 CDDP/Doxo/HDMTX?Ifos iv CDDP vs. ia CDDP 10-yr EFS 66 10-yr S 72
IOR/OS-4 (2001) 133 HDMTX/CDDP/Doxo/Ifos 5-yr EFS 56 5-yr S 71
SSG VIII (2003) 113 HDMTX/Doxo/CDDP 5-yr EFS 61 5-yr S 74
EOI (2003) 250 254 CDDP/doxo q 3 weeks vs. CDDP/doxoG-CSF q 2 weeks 3-yr PFS 41 3-yr PFS 46 3-yr S 64 3-yr S 67
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Overall and Event-free Survival of Patients with
Metastatic OSSt Jude Studies OS-86 and OS-91
5-year estimates S 24.1 7.4 EFS 6.9 3.8
Survival (n29)
Event-free Survival (n29)
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
MTX or no MTX? Metastatic Osteosarcoma
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
MTX or no MTX? Metastatic Osteosarcoma
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
Modification of Post Surgery CT
MTX or no MTX? Metastatic Osteosarcoma
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
Modification of Post Surgery CT
MTX or no MTX? Metastatic Osteosarcoma
New Approaches Treatment of OS in Developing
Countries
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
Modification of Post Surgery CT
MTX or no MTX? Metastatic Osteosarcoma
New Approaches Treatment of OS in Developing
Countries
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MTX or no MTX?
Jaffe et al NEJM 1974
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MTX or no MTX?
Jaffe et al NEJM 1974
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OsteosarcomaMethotrexate or not Methotrexate?
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OsteosarcomaMethotrexate or not Methotrexate?
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Results of the Brazilian Osteosarcoma
Treatment Group Studies III and IV Prognostic
Factors and Impact on Survival Petrilli et al. J
Clin Oncol 2006241161
OS and EFS for patients with non-metastatic
extremity tumors
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OS-99 for Localized Osteosarcoma
S U R G
IFO CBP
IFO CBP
IFO CBP
IFO DOX
IFO CBP
CBP DOX
IFO DOX
DOX
0 3 6 9 12 14 17 20 23
Eval
Eval
IFO 2.65 g/m2 x 3d DOX 25 mg/m2 x 2-3 d. CBP AUC 8
END OF THERAPY
IFO CBP
CBP DOX
IFO DOX
CBP DOX
26 29 32 35 38
Eval
Eval
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
Modification of Post Surgery CT
MTX or no MTX? Metastatic Osteosarcoma
New Approaches Treatment of OS in Developing
Countries
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Overall and Event-free Survival of Patients with
Metastatic OSSt Jude Studies OS-86 and OS-91
5-year estimates S 24.1 7.4 EFS 6.9 3.8
Survival (n29)
Event-free Survival (n29)
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Metastatic Osteosarcoma
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POG 9450 - PFS and survival for all patients
Goorin, A. M. et al. J Clin Oncol 20426-433 2002
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Factors Prognostic of Survival in Patients with
Pulmonary Metastases Only
St. Jude Studies OS-86, OS-91
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
Modification of Post Surgery CT
MTX or no MTX? Metastatic Osteosarcoma
New Approaches Treatment of OS in Developing
Countries
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LOCAL CONTROL Radical surgery is
critical Amputation Limb salvage
procedures Limb salvage should not take
priority! LIVE ? LIMB Upfront vs. delayed
(after induction) Limb salvage State of the art
team Local recurrence rates should remain lt
5-10
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Survival of Patients with Local recurrence of
Osteosarcoma 5-year Post Relapse Survival19.2
7.7
Rodriguez-Galindo et al. Cancer 2004 1001928
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
Modification of Post Surgery CT
MTX or no MTX? Metastatic Osteosarcoma
New Approaches Treatment of OS in Developing
Countries
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Osteosarcoma -T-10 Histologic Response as a
Prognostic Factor

• Modification of postoperative therapy?
• Upfront Surgery?
• Intensification of preoperative therapy?

No Impact in Outcome
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The Big Question (still) Modification of
Postoperative Chemotherapy for Poor Responders
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The Big Question (still) Modification of
Postoperative Chemotherapy for Poor Responders
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A Randomized Trial of the European and American
Osteosarcoma Study Group to Optimize Treatment
Strategies for Resectable Osteosarcoma Based on
Histological Response to Pre-operative
Chemotherapy


R A N D O M I
Z E
MAP
GR
SURGERY
MAPIfn
REGISTER
MAP
R A N D O M
I Z E


MAP
POOR
MAPIE
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
Modification of Post Surgery CT
MTX or no MTX? Metastatic Osteosarcoma
New Approaches Treatment of OS in Developing
Countries
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
Timing of Surgery Type of Surgery
Modification of Post Surgery CT
MTX or no MTX? Metastatic Osteosarcoma
New Approaches Treatment of OS in Developing
Countries
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Osteosarcoma in Developing Countries Challenges
Delayed diagnosis ? Increased tumor burden Large
tumors Metastatic disease Drug
availability Suboptimal imaging
techniques Limited surgical options Poor
supportive treatment Complexity of therapy Pain
management Physical therapy High abandonment
rates
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
AMPUTATION
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Treatment of Osteosarcoma
S U R G E R Y
Tumor
Induction Chemotherapy Methotrexate Adriamycin Pla
tinum (CDDP)
Continuation Chemotherapy Same Agents
Mets
AMPUTATION
ABANDONMENT 30-40?
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Treatment of Osteosarcoma
S U R G E R Y
Chemotherapy Methotrexate? Adriamycin Platinum
(CDDP)
Surgery of mets
Preoperative chemotherapy Symptom
management Preparation for amputation
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OsteosarcomaMethotrexate or not Methotrexate?
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Treatment of Osteosarcoma with CDDP/DOX
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Transfer of Complex Frontline Anticancer Therapy
to a Developing Country The St. Jude
Osteosarcoma Experience in Chile
Rivera GK et al. Pediatr Blood Cancer 2008501143
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AHOPCA OSTEOSARCOMA 2000
CDDP 75 mg/m2 x 2 d Doxorubicin 75 mg/m2 x 1 d
X 4 cycles
Ifosfamide 3 g/m2 x 3 d Etoposide 150 mg/m2 x 3 d
X 4 cycles
PI Dr. Fulgencio Baez PI Dr. Roberta
Ortiz Nicaragua
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AHOPCA 2000 Preliminary Results
Overall Survival, Abandonment as Event
PI Dr. Fulgencio Baez PI Dr. Roberta Ortiz
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AHOPCA 2000 Preliminary Results
Overall Survival, Abandonment Censored
PI Dr. Fulgencio Baez PI Dr. Roberta Ortiz
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Barriers
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Barriers
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Barriers
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Barriers
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AHOPCA OSTEOSARCOMA 2008
Early Amputation Maintenance chemotherapy
PI Dr. Fulgencio Baez PI Dr. Roberta
Ortiz Nicaragua
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Treatment of Osteosarcoma
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Treatment of Osteosarcoma
Multidisciplinary Team Approach
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Treatment of Osteosarcoma
Multidisciplinary Team Approach
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Treatment of Osteosarcoma in Developing Countries
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Discussion Osteosarcoma burden Late
diagnosis? Advanced disease Treatment Best
chemotherapeutic options Amputation
when? Abandonment? Outcomes