Soft Tissue SarcomaAn Overview & Update
Mohamed Abdulla (M.D.)Ass. Prof. Clinical Oncology
Kasr El-Aini School of MedicineCairo University
April, 2007
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:
Mesenchymal Cell of Origin
Bone
Muscle
Fat Cartilage
Tendon
Ligament
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
Sarcomas with Complex Karyotype Abnormalities:1) Fibrosarcoma.2) Leiomyosarcoma.3) Osteosarcoma.4) Chondrosarcoma.5) Liposarcoma.6) Rhabdomyosarcoma.7) Malignant Schwannoma &
Neurofibrosarcoma.8) Angiosarcoma.
Evaluation of The 1ry Lesion:1) Plain
Radiography.Low Cost.
Informative.
Benign, Aggressive or Malignant Lesion.
Calcification in Soft Tissue Extension
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.
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:
Biopsy:
1. FNAC.2. True Cut Biopsy.3. Excisional Biopsy.4. Incisional Biopsy.
Adequate Amount of Tissues.
Not to Compromise Oncologic Safety.
Surgical Aspects:
5-Yr Survival
Stage %
I 86
II 72
III 52
IV 10-20
Improvement of Disease Specific Survival
“DSS”Proper Surgery
Radiation TherapySystemic Therapy
Improvement in Local Control
Eradication of Micrometastases
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%
Systemic Therapy:
75% of All Patients with Localized Extremity STS will not Relapse After Local
Treatment.
No Need For Further Therapy
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.??
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)
Ifosfamide Experience:
Italian Cooperative Trial; 2001 UCLA, JCO; 2001
DFS Advantage.
Insignificant Impact OAS.
Improvement is Restricted to HIGH RISK PATIENTS.
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).
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:
Adjuvant Treatment:
Neo-Adjuvant:
Yes
Not Yet
To Treat or Not??
Metastatic & Unresectable Disease:
Doxorubicin/Ifosfamide with Dose Escalation.Gemcitabine & Combinations.Paclitaxel in Angiosarcoma.Bortezomib.9-Nitrocampothecin.Imatinib Mesylate. Liposomal Doxorubicin.
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.
Paclitaxel in Angiosarcoma: MSKCC
Phase II.80%5 months.
Liposomal Doxorubicin vs Doxorubicin: EORTC
Phase II.10% & 9%4 months.