Soft Tissue Sarcoma Presley Regional Trauma Center Department of - - PowerPoint PPT Presentation

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

• f 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
• ption 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

• ver 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
• r 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