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.