Clinical responses and outcome of 110 consecutive isolated limb perfusion (ILP) with TNF-α and melphalan (M) for locally advanced soft tissue sarcomas (LASTS) of extremities at the Institut Gustave Roussy

Abstract

10587 Background: ILP with TNF-α and M allows limb preservation in 80% of patients (pts) with LASTS. The exact mechanisms through which TNF-α and M are mediated have to be established. The aim of this analysis was to identify subgroups of pts who benefit more from ILP than others. Methods: Between 2000 and 2005, 110 pts with LASTS were treated with ILP in our institution. Systemic and perfusate blood samples and urines were collected before, during and day 1 and 2 after ILP. Paraffin-embedded material (PEM) of the tumor was collected before and/or after ILP at the time of the resection two months later. Results: The sex ratio was 58 M/52F and median age was 45 years (range 8–81). Location/median size was 37%/50mm and 63%/80mm for upper and lower limbs, respectively. Eighty- four per cent of tumors were high grade STS. The objective response rate was 70 %. Histologic necrosis was ≥ 90% in 32 pts (33%). A limb salvage procedure was obtained in 82% of pts. Half of pts had a pre ILP systemic chemotherapy (CT). After ILP, 48 pts received radiation therapy (RT), 3 pts a systemic CT and 6 both. Out of the 101 pts without distant metastases before ILP, a relapse occurred in 40 pts: local relapse (LR) in 18 (median time of relapse: 12 months), distant in 30 (median time: 10 months), both in 10 pts and 2 pts died without recurrence. A good correlation was found between absence of LR and RT after ILP (11% pts with RT and 45% without RT had a LR (p=0.0005). The 2 yr PFS and OS were 51% and 79%, respectively. Collection of material (serum, plasma, peripheral blood mononuclear cells and urines) were stored for 53 pts. Pre and post ILP PEM were obtained in 63 pts and pre or ILP PEM in 50 other pts. The outcome of pts (OS or PFS) was subsequently analyzed according to each investigated biologic factor. Conclusions: High response rate was observed in TNF-α+M-based ILP. Post-ILP RT improved local tumor control. We will take advantage of the material collected and we will investigate the putative determinants associated with the treatment efficacy considering to better understand such factors and to improve response to treatment (Conticanet program). Final analysis will be presented at the meeting. No significant financial relationships to disclose.