soft tissue sarcoma an overview & update mohamed abdulla (m.d.) ass. prof. clinical oncology...
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Soft Tissue SarcomaAn Overview & Update
Mohamed Abdulla (M.D.)Ass. Prof. Clinical Oncology
Kasr El-Aini School of MedicineCairo University
April, 2007
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1% of all human cancers. 50 histological subtypes. Small peak of incidence in early childhood
“embryonal rhabdomyosarcoma”. Increased frequency with age. Limbs, Abdominal Cavity &
Retroperitoneum, Thoracic then Head & Neck Region.
Prevalence & Problems:
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Mesenchymal Cell of Origin
Bone
Muscle
Fat Cartilage
Tendon
Ligament
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Molecular Data are More Important than Site of Origin in Determining Prognosis & Treatment
Options
Soft Tissue Sarcomas
AberranciesCell Regulatory Pathway
Karyotype Abnormalities
Rb p53 Simple Complex
High Grade Lesion
Aggressive Behavior
Poor Survival
Aggressive Behavior
Tumor TypeRegardless
Cell of Origin? Aneuploidy
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Sarcomas with Complex Karyotype Abnormalities:1) Fibrosarcoma.2) Leiomyosarcoma.3) Osteosarcoma.4) Chondrosarcoma.5) Liposarcoma.6) Rhabdomyosarcoma.7) Malignant Schwannoma &
Neurofibrosarcoma.8) Angiosarcoma.
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Evaluation of The 1ry Lesion:1) Plain
Radiography.Low Cost.
Informative.
Benign, Aggressive or Malignant Lesion.
Calcification in Soft Tissue Extension
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Evaluation of The 1ry Lesion:2. MRI:
3. Spiral CT-Scan:
Tissue of Origin.
Location & Extent.
Relationship to Surroundings.
Define Further Steps of Locoregional Management.
Better for Chest & Abdominal Lesions.
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1. CT-Scan of The Chest.2. FDG-PET Scan.3. Isotopic Bone Scan.4. Bone Marrow Examination.5. Others.
Evaluation of The Systemic Extent:
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Biopsy:
1. FNAC.2. True Cut Biopsy.3. Excisional Biopsy.4. Incisional Biopsy.
Adequate Amount of Tissues.
Not to Compromise Oncologic Safety.
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Surgical Aspects:
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5-Yr Survival
Stage %
I 86
II 72
III 52
IV 10-20
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Improvement of Disease Specific Survival
“DSS”Proper Surgery
Radiation TherapySystemic Therapy
Improvement in Local Control
Eradication of Micrometastases
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The Use of Radiation Therapy:
High Grade Lesions.Intermediate Grade with Positive Margins.Recurrent Tumors.Low Grade Lesions.Retroperitoneal Disease.
External Beam RTh or Brachytherapy.Optimal Timing.Dose to Be Delivered.
Advanced Technology
Local Recurrence
10%
Amputation Rate 5%
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Systemic Therapy:
75% of All Patients with Localized Extremity STS will not Relapse After Local
Treatment.
No Need For Further Therapy
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High Risk Patients:
Large Tumors > 5 cm.High Grade Lesions.Deep Lesions to Investing Fascia.Recurrent Tumors at Presentations.Leiomyosarcoma & PNST.Locations other than Extremities.??Positive Margins.??
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Doxorubicin Experience:The Lancet Sarcoma Meta-analysis; 1997:
10% in DFS (p < 0.05)4% in OAS (p > 0.05)7% in OAS with Extremities Disease (p < 0.05)
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Ifosfamide Experience:
Italian Cooperative Trial; 2001 UCLA, JCO; 2001
DFS Advantage.
Insignificant Impact OAS.
Improvement is Restricted to HIGH RISK PATIENTS.
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Adjuvant Chemotherapy:
Superiority of Doxorubicin Based Regimens only in Terms of DFS.(Mayo Clinic; 1984 & EORTC; 1994).
Sarcoma Meta-Analysis Collaboration: 1997
1. 27% reduction in risk of LR.2. Distant Recurrence Free Survival.3. Marginal Improvement in OS
EORTC Adjuvant Trial (High Dose Therapy with Growth Factor Support).
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Neo-adjuvant + Surgery vs Surgery:No Survival Advantage.(Gortzak et al, Eur J Cancer; 2001)
Neo-adjuvant vs Adjuvant:No Superiority(DeLaney et al, Int J Oncol Biol Phys; 2003).
Neo-Adjuvant Chemotherapy:
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Adjuvant Treatment:
Neo-Adjuvant:
Yes
Not Yet
To Treat or Not??
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Metastatic & Unresectable Disease:
Doxorubicin/Ifosfamide with Dose Escalation.Gemcitabine & Combinations.Paclitaxel in Angiosarcoma.Bortezomib.9-Nitrocampothecin.Imatinib Mesylate. Liposomal Doxorubicin.
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Gemcitabine & Combinations.
Single Agent Activity: 18% (2-13 months).Protracted Infusion : (Median Survival 13 ms).Gem/Docetaxel: 35% in all Types
50% in Leiomyosarcoma.Gem/Venoralbine.
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Paclitaxel in Angiosarcoma: MSKCC
Phase II.80%5 months.
Liposomal Doxorubicin vs Doxorubicin: EORTC
Phase II.10% & 9%4 months.