Soft Tissue Sarcoma

Presley Regional Trauma Center

Department of Surgery

University of Tennessee Health Science Center

Memphis, Tennessee

• Collective term for an unusual and diverse

group of malignancies that arise from cells

of the embryonic mesoderm

• Account for 1% of adult and 15% of

pediatric tumors

• Comprise more than 50 distinct histologic

subtypes

Soft Tissue Sarcoma

• May occur anywhere in the body

• 43% - extremities

• 15% - RP

• 10% - trunk

• 19% - viscera

• 13% - other

Soft Tissue Sarcoma

• Unclear and controversial

• Genetic factors

• Chemical exposure

• Lymphedema

Etiology

• Chromosomal abnormalities

- Translocations

- Point mutations

- Deletions

• Regulatory genes

- p53

- RB1

Etiology

• Ionizing radiation

- Often do not become clinically apparent until

long after inciting exposure

- Osteosarcoma

- Malignant fibrous histiocytoma

• Chemical carcinogenesis

- Thorotrast

- Vinyl chloride

- Arsenic

Etiology

Pathologic Classification

• Categorized on the basis of the tissue type

from which it is believed to originate

• Subtypes may be defined by

histochemistry, flow cytometry, EM, tissue

culture and cytogenetic analysis

• Useful in determining which therapy is

best – not part of staging system

STS

• Best indicator of biologic aggressiveness

and metastatic potential

• Defined by tumor’s cellularity, nuclear

atypia, degree of necrosis and mitotic

activity

• AJCC staging system integrates tumor

grade, size, depth of tissue invasion,

degree of nodal involvement and mets

Grade

Clinical Evaluation

• Asymptomatic mass

• Painless and large

• Often noticed because of h/o recent

trauma to the area

• 38% are > 10 cm

Presentation

• Distant mets vary with tumor histology and

site of primary

• Extremity lung

• Abdominal and RP liver

• Few go to regional LN (2.6%)

Presentation

Management

• Foundation of treatment

• Amputation was once considered the only

option for cure

• Rosenberg et al (1982)

• Amputation is usually reserved for

extremity sarcomas that involve major

vessels, nerves or bones

Surgical Therapy

• Rosenberg et al (1982)

- 43 patients with extremity sarcoma

- Amputation – (n = 16)

- Limb-sparing surgery + radiation – (n = 27)

- All received adjuvant chemotherapy

- 5-year local recurrence slightly higher in LSS

- 5-year survival nearly identical

NCI

• Adequate resection involves excising a

margin of normal tissue along with any

areas through which biopsies have been

performed

• Compartmental resection or resection of

entire muscle groups provides no benefit

over WLE

• 1 to 2 cm margin should be the goal

Surgical Therapy

• Regional lymphadenectomy is not usually

indicated

• Tumor is in proximity to a LN basin

• Tumor is one of the following subtypes

- Rhabdomyosarcoma

- Epithelioid sarcoma

- Clear cell sarcoma

- Synovial sarcoma

- Vascular sarcoma

Surgical Therapy

Sarcoma Type Incidence of Nodal Metastases (%)

Rhabdosarcoma 11 - 36

Epithelioid Sarcoma 17 - 80

Clear Cell Sarcoma 25 - 50

Synovial Sarcoma 2 - 17

Vascular Sarcoma 11 - 40

• Dramatically changed the surgical

treatment of sarcomas

• Provides local control

• Brachytherapy

• Post-, pre-operative external beam

Radiation Therapy

• MSKCC

- 164 pts with extremity or superficial trunk

sarcoma

- Resection ± brachytherapy

- 76 month median f/u

- Local control rate better in BT group

- No difference in 5-year disease-specific

survival

Brachytherapy

• NCI

- 91 pts with high-grade STS

- Resection ± radiation

- All pts received adjuvant chemotherapy

- One local recurrence with radiation vs 8 with

no radiation

- No difference in overall survival

External Beam

• Canada

- 190 pts

- Closed because of wound complications

- Pre-op = 35% vs 17% with post-op

- No difference in local control

- Significant difference in overall survival that

slightly favored the pre-op group

Pre- vs Post-op External Beam

• Post-op chemo has been studied in multiple

prospective, randomized trials but small

sample sizes and differences among them

have made it difficult to interpret the data

• Sarcoma Meta-analysis Collaboration

• Post-op adjuvant chemotherapy is best

employed in the context of appropriate

clinical trials

Chemotherapy

• Allows delivery of agents through native

vasculature

• Permits assessment of effectiveness of tx

by pathologic analysis

• May facilitate tx of micromets

• May downstage tumors – making them

more amenable to resection

Pre-op Chemotherapy

• MD Anderson

- Retrospective, 46 pts extremity sarcomas

- Overall tumor response rate was 40%

- Significant improvement in both disease-free

and overall survival

• MSKCC

- Prospective, 29 pts

- Large, high-grade extremity sarcomas

- No benefit

Conflicting Data

• Given the lack of sufficient evidence for any

survival benefit, pre-op chemotherapy may

be considered in attempting to preserve

limb function but otherwise its use should

be limited to clinical trials

Conclusion

• Most interesting and exciting advances

• The characterization and targeting of the

tyrosine kinase receptor = c-kit

• GIST

Targeted Therapeutics

• Reserved for patients in whom LSS is not

possible

• Cannulate the arterial and venous supply

and apply a proximal tourniquet

• Bypass machine maintains mild

hyperthermia, oxygenation and circulates

chemotherapeutic agents in the limb

Isolated Limb Perfusion

• Extremity - local recurrence = 8 to 20%

• RP - local recurrence = 38 to 50%

• Salvage surgery is an option

• Radiation for those who did not receive it

previously

Recurrent STS

Metastatic Disease

• Lung mets present in 20% of pts with trunk

or extremity

• Resection may be attempted if pt is

medically fit, no extrathoracic disease is

present and the primary tumor is

controlled

• 3-year survival ranges from 23 to 54%

Resectable

• Distant mets may develop in as many as

50% of cases

• For the vast majority, only available

treatment option is systemic

chemotherapy

• Doxorubicin

Unresectable