Feasibility and Efficacy of External Beam Radiotherapy after Hyperthermic Isolated Limb Perfusion with TNF-α and Melphalan for Limb-saving Treatment in Locally Advanced Extremity Soft-tissue Sarcoma

Purpose: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and melphalan is associated with a dramatic antitumor effect in locally advanced extremity soft-tissue sarcomas (STS). The aim of this study was to demonstrate the feasibility and efficacy of adjuvant radiotherapy after HILP with TNF-α, IFN-γ, and melphalan and delayed surgical resection. Methods and Materials: Between 1991 and 1995, 34 patients—16 males and 18 females, median age 50 (range 18–80) years—underwent HILP for locally advanced extremity STS. Resection of the residual tumor mass was performed in most patients after 6–8 weeks. Fifteen patients with histopathological viable tumor after resection received adjuvent 60–70 Gy external beam radiotherapy (EBRT) (44%, HILP + EBRT group). Nineteen patients received HILP without adjuvent EBRT (56%, HILP-only group). Five patients in the HILP-only group had also distant metastases (15%) and received HILP as a palliative treatment. Treatment morbidity, local recurrences, and regional and distant metastases were scored. Results: During a median follow-up of 34 months (range 8–54), limb salvage was achieved in 29 patients (85%): 14 patients after HILP + EBRT and 15 patients after HILP only. None of the patients from the HILP + EBRT group developed local recurrences; however, five patients from the HILP-only did (26%) ( p < 0.05). Regional metastases were observed in one patient from the HILP + EBRT group (7%) and in two patients from the HILP-only group who were treated with curative intent (14%). Distant metastases occurred in four patients after HILP + EBRT (27%) and in four patients after HILP only with curative intent (29%). The mean morbidity (subjective, objective, medical management, and analytical evaluation) score in both groups was, respectively, 0.33 for skin and subcutaneous tissue and for muscle and soft tissue, 0.34 (HILP + EBRT group) and 0.33 (HILP-only group). Conclusion: Adjuvent EBRT after HILP with TNF-α, IFN-γ, and melphalan and delayed tumor resection of locally advanced extremity STS is feasible and may increase local tumor control without increasing treatment morbidity.