Treatment approaches in soft tissue sarcomas--putting our best foot forward.

Treatment approaches to adult soft tissue sarcomas of the extremity have changed dramatically over the last 15 years. While radical surgery (often amputation) was once considered to be the treatment of choice, “limb-sparing” surgery combined with radiation therapy has been shown more recently to yield cornparable local control rates (8595%) while preserving limb function. Wide local excision in which the tumor is removed en bloc with a margin of normal surrounding tissue is the recommended surgical procedure for extremity sarcomas, realizing that a pseudocapsule with infiltrating tumor often immediately surrounds a soft tissue sarcoma. Treatment approaches which integrate limb-sparing surgery and radiation therapy include preoperative, postoperative and intra-operative irradiation or combinations thereof. To date, no clinical trial has compared these different combined modality approaches with respect to 1:reatment results and functional outcome. Instead, variouis recent randomized prospective trials have attempted to define the role of adjuvant chemotherapy in this patient group. The role of adjuvant chemotherapy in the postoperative setting remains unresolved. While approximately 60% of non-visceral soft tissue sarcomas occur in the extremities, most of these sarcomas occur in the proximal extremity, particularly in the thigh. Soft tissue sarcomas of the distal extremity, especially arising in the hand or foot, are quite uncommon. Given the functional complexity of the hand and foot, the treatment issues of how best to establish local control and maintain function are particularly noteworthy. Until recently, it was assumed that the high doses of radiation (55-65 Gy) required to control even microscopic disease of sarcoma would result in such poor function over time that amputation was stllll considered the treatment of choice. This assumption is wrong for a majority of patients with sarcomas arising in the hand and foot based on data from three recent series ( 10, 12, 13), as well as data from the UCLA group. In the July issue of the journal, Selch and colleagues from UCLA report on a small group of 20 patients with foot sarcomas treated over a 14-year period. With a median follow-up of 3 years, local control was achieved in 17 of 20 patients and most patients ( 14 pt) maintained good to excellent function. Actuarial overall and diseasefree survival at 3 years was 83% and 63%, respectively. These results are similar to the above cited studies although the UCLA treatment approach is quite different and deserves further comment. A majority ( 16 pts) of this patient group received sequential preoperative chemotherapy (usually Adriamycin given by continuous intraarterial infusion over 3 days) and unconventional fractionated radiation therapy (using 3.5 Gy fractions to 17.5, 28, or 35 Gy). I have some difficulty understanding the clinical rationale of this approach, particularly in 9 of the 16 patients who had gross tumor excision prior to entry in the study. My first concern deals with the use of Adriamycin. While Adriamycin is the most active single agent in soft tissue sarcomas (response rate of 15-35% in metastatic patients (4)), pharmacokinetic data to support its use by direct intra-arterial infusion are less convincing. In general, regional (e.g. intra-arterial) drug delivery is designed to improve selectivity of a drug as a cytotoxic and/or radiosensitizing agent. Clearly, some drugs have more favorable pharmacokinetics for regional delivery than others. The ratio of total body clearance (CL& of a drug to its regional exchange rate is the principal determinant of therapeutic advantage for regional drug delivery (5). Drugs with a high total body clearance and/or site of delivery with low exchange rates (such as with intrathecal [IT] or intra-