Resection for Thoracic Metastases From Sarcoma

Sarcoma metastasizes to the lungs in 20% to 40% of patients and in most cases does not involve any other organ. Systemic chemotherapy is of unproven benefit for stage IV sarcoma. Retrospective studies have shown 5-year survival rates of 21% to 38% with wedge resection of metastatic pulmonary nodules, and up to 30% to 40% of patients survive an additional 5 years with repeated metastasectomy. In this article, we provide an extensive review of patient selection criteria and surgical approaches, as well as of controversies regarding resection for metastatic sarcoma.

Introduction

Sarcomas may arise from nearly any embryonic mesodermal tissue and constitute approximately 1% of all newly diagnosed malignancies annually. Through hematogenous dissemination, rates of metastatic disease to the lungs have been reported to be as high as 20% for osteogenic sarcoma[1] and 40% for soft-tissue sarcoma,[2] and pulmonary metastases are present in most patients who die from sarcomatous malignancies. Furthermore, the pulmonary bed often is the only site of distant disease.[1-3] Sarcomas are the second most common cause of pulmonary metastatic disease, following colorectal cancer. The youthful demographic most often affected by sarcoma warrants an aggressive approach to metastases.

The Pathophysiology of Pulmonary Metastases

Tumor progression from the primary site to clinically detectable pulmonary metastases involves multiple complex steps, including vascular invasion, survival without an extracellular matrix (anoikis), immune system evasion, extravasation into the target organ, dormancy followed by proliferation, and angiogenesis.[4] This pathway applies to all solid tumors, yet certain solid tumors preferentially metastasize to specific organs. Attempts to characterize this phenomenon date back to Paget in the late 19th century, with his proposal of a “seed” and “soil” theory. Paget theorized that certain elements within the tumor cell (seed) have an affinity for elements in the target organ (soil). This was challenged by Ewing in the early 20th century, who maintained that target organ anatomic variables were more critical.[4] Ewing postulated that the frequency of lung metastases was related to the vast capillary system that could snare tumor cells, and the high oxygen tension that could support their growth. Although both theories are likely relevant to the lung as a primary site of metastases, more recent data evaluating pulmonary and tumor chemokine production and receptors have suggested that the “seed” and “soil” theory may have a more significant impact on the development of pulmonary metastases. Specifically, a primary chemokine produced by the lungs is CXCL12, and its cognate receptor is CXCR4. In both breast cancer and melanoma, the overexpression of the receptor CXCR4 has been associated with a dramatic increase in the rate of pulmonary metastases.[5,6] CXCR4 overexpression has also been demonstrated in soft-tissue sarcoma and seems to correlate with the targeting of metastases to lung and bone.[7] Blocking this chemokine-receptor interaction represents a potentially clinically useful intervention for preventing metastases, but it likely would have little to no impact on existing lung lesions.

Therapeutic Interventions for Thoracic Metastases From Sarcoma

FIGURE 1

Overall Actuarial Survival After Lung Metastasectomy: Complete Resection Vs Incomplete ResectionFIGURE 2

Survival of Four Prognostic Groups of Patients With Lung Metastases

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