A Prospective Multicenter Trial for Limb Sparing With Mild Hyperthermic ILP with Low Dose TNF Alfa and Melphalan in the Treatment of Locally Advanced Soft Tissue Sarcoma of the Extremities

Background: Soft tissue sarcomas (STS) are malignant neoplasms where survival rate of patients depends on the grade, depth of the lesion, and tumor size, and not on the aggressiveness of initial surgical treatment; therefore amputation of the limb has not shown to increase survival rate when compared to limb-sparing surgery. Isolated limb perfusion (ILP) is an effective method for limb sparing surgery and cancer control. The purpose of this study is to present the results obtained the patients that underwent ILP with melphalan and TNF-alpha due to a locally advanced soft tissue sarcoma of the extremity that would otherwise merit amputation. It represents the experience garnered from multiple cancer centers around the country. Materials and Methods: A prospective analysis was performed of TNF-ILP procedures on 139 patients with locally advanced STS of the extremity, from January 2010 to March 2018. All patients considered for the ILP procedure had a histopathologically confirmed diagnosis and were candidates to amputation according to the evaluation by their oncologists in their cancer treatment centre. The final response was evaluated between 8 and 12 weeks after ILP. Local toxicity was assessed using the Wieberdink scale. Technique Standardization: In order to ensure the technique used for the trial was applied as homogeneously as possible in the eight cancer treatment centers involved, receiving theoretical and practical training at NCI Mexico. Statistical Analysis: Descriptive statistical analysis was performed on the data obtained. Time to local recurrence, disease-free interval, and overall survival rate were defined by the time between the ILP procedure and either local or systemic recurrence, or death of the patient, respectively. The Kaplan-Meier estimator (Logrank) was used. Results: 139 TNF-ILP were done in 137 patients (66 male – 71 female). Median of age was 41.6 years and median follow up of 42 months was reached. Most patients had stage III tumors (86.7%), lower extremity (73.3%), and femoral perfusion was the most common (42%). The major histology was synovial sarcoma and lyposarcoma. Eight patients was perfunded with recurrent agressive fibromatosis with no other option than amputation. The global response rate was 77.8%, 18 patients with complete response included. The limb sparing succes rate was 82%. The Overall survival for 12, 24, 36 and 48 months was 78%, 58%, 49% and 46% respectively.Ten patients will develop a local recurrent disease treated with amputation. The subsequent limb sparing success rate dropped to 78%. Conclusions: This Prospective multicenter trial of ILP with mild hyperthermia for locally advanced soft tissue sarcoma diagnosed histologically, who underwent to TNF-ILP, and the application of training program reveals that TNF-ILP is a high effective treatment, and can be done safe in major centers of Mexico.