Metastatic Sarcomas (bone, soft tissue, and retroperitoneal)
Sarcoma Program
Approximately 80% of patients with extremity and trunk soft tissue sarcomas who have distant disease will have isolated pulmonary metastases. The detection of pulmonary metastatic disease is accomplished by either plain film radiographs or CT scanning of the thorax. CT scans have a greater sensitivity in detecting small (3 to 10) mm pulmonary nodules than plain film radiographs, which has led many clinicians to use CT rather than plain films when evaluating for pulmonary metastases. On the other hand, this greater sensitivity to small nodules means that many subcentimeter benign nodules are identified on CT scans, especially in older patients. Proving these nodules to be benign can be difficult, and their detection often leads to concern for metastasis for patient and physician alike.
Because of the strong predilection for sarcoma to metastasize to the lungs and only to the lungs, resection of even multiple pulmonary metastases (metastasectomies) has been shown in multiple reports to be associated with prolonged relapse-free survival in a small but significant percentage of patients (probably at least 25%).
Reported survival rates following complete resection of pulmonary metastases (sometimes with repeated thoracotomies) range from 25% to 39% at five years. From published reports to date an aggressive approach to resection of pulmonary metastases is warranted.
The role of chemotherapy in the treatment of unresectable metastatic disease has been extensively reviewed. Doxorubicin, ifosfamide and dacarbazine have all been shown to have significant single agent activity in the treatment of metastatic soft tissue sarcomas. While published reports of various combinations of available drugs have been suggested them to be superior to single agent therapy, to date there is little evidence from prospective randomized trials to support that contention.
The influence of drug dose intensity has been studied in numerous retrospective and prospective evaluations. There is considerable evidence to support the contention that the two most active drugs, doxorubicin and ifosfamide, yield better results in terms of response rates and time to progression if given at high doses.
Clinical trials remain a highly appropriate option for patients with metastatic soft tissue sarcomas of all histologic subtypes. Novel approaches to clinical trials design are also worthy of exploration, given the multiple potential interactions of drug type, dose and schedule with histologic subtype and prior treatment status.