Neoadjuvant Treatment of Locally Advanced Soft Tissue Sarcoma of the Extremities to Avoid Amputation. Isolated Limb Perfusion is a Valid Option

Abstract

The goals of treatment for soft tissue sarcoma (STS) of the extremities are local tumor control, preservation of limb function and reduction of the risk of distant metastasis. The standard treatment for STS of the limbs is wide local excision with histologically negative margins and, in the majority of cases, adjuvant radiotherapy. In the case of locally advanced tumors, this might not be feasible, especially when the tumor is located at the periphery of the limb, or tumor infiltration, encasement or fixation of motor nerves, major vessels or bones has occurred, in which case, amputation may be necessary. The aim of neoadjuvant treatment is to minimize the need for amputation or surgery that leads to major functional impairment with an acceptable level of toxicity and without a negative impact on survival. This is a comprehensive review of the various neoadjuvant treatment strategies applied in an attempt to salvage the limb and to preserve its function in patients with locally advanced STS. Systemic chemotherapy with regional hyperthermia and isolated limb infusion (ILI) are promising. Novel treatment option such as, isolated limb perfusion (ILP) with tumor necrosis factor-α (TNF-α) and melphalan appears to be the most effective neoadjuvant treatment modality for these cases. ILP provides the highest likelihood of local tumor eradication with preservation of the limb and its function for patients with limb-threatening locally advanced STS. Approximately one quarter of the patients experience complete pathological response and half of the patients a partial response, together resulting in limb salvage in three quarters of the patients. Because of the high pathological response rates, the high limb salvage rate, the improved surgical margins after ILP with TNF-α and melphalan, and its low toxicity, the indications for performing this treatment should be evaluated for primary and recurrent tumors when infiltration, encasement and/or fixation of motor nerves, major vessels, or bones are present. When ILP is indicated, the limited availability of the technique, which is provided at present by only one center in Greece, should not be a reason to withhold from a patient the opportunity of salvage of the limb and its function.