Preoperative isolated limb infusion of Doxorubicin and external irradiation for limb-threatening soft tissue sarcomas

At present, limb-sparing surgery is the most appropriate and acceptable treatment option for soft tissue sarcomas of the extremities. To increase the number of limb-sparing resections in the treatment of locally advanced soft tissue sarcomas of the extremities, preoperative radiotherapy and/or chemotherapy are often used. Isolated limb perfusion of cytostatic agents is an effective alternative option but technically complex. Isolated limb infusion, essentially a low-flow isolated limb perfusion without oxygenation via a percutaneous catheter, had been developed as a simple alternative.

The objective of this study was to achieve limb-sparing surgery in patients with locally advanced soft tissue sarcomas of the extremities that would otherwise have required an amputation or a functionally mutilating surgery by performing preoperative isolated limb infusion with doxorubicin and external beam irradiation to obtain local control and make limb-sparing surgery feasible.

A total of 40 patients with locally advanced soft tissue sarcomas of the extremities were evaluated between 2002 and 2005. Tumors were located in the lower limb in 28 patients (70%) and in the upper limb in 12 patients (30%). All of these patients were felt to be unresectable and were referred because amputation was considered the only available treatment option. They underwent preoperative isolated limb infusion with doxorubicin (0.7 and 1.4 mg/kg for the upper and lower limbs, respectively). Preoperative external beam radiotherapy started within 3-7 days after isolated limb infusion was administered. The total dose was 35 Gy in ten fractions. After 3-7 weeks, surgery was performed aiming at limb preservation.

Tumor response was seen in 85% of patients, rendering these large sarcomas resectable in most cases. The mean values of pretreatment tumor volume and post-treatment volume were 2797 cm(3) and 1781 cm(3), respectively, with a significant p value of 0.0001. Histologic response was seen in 80% of patients. At a median followup of 15 months (range = 5-35), limb salvage was achieved in 82.5%. Procedure-related complications were limited and easily managed.

Isolated limb infusion with doxorubicin is a simple and safe method of regional chemotherapy. The addition of preoperative external beam irradiation helped to increase the rate of limb salvage in patients with large and/or high-grade soft tissue sarcomas of the extremities.