A feasibility study of circulating melanoma cells in the perioperative context of hyperthermic isolated limb perfusion (HILP) in 20 patients

Introduction Hyperthermic Iota solated Limb Perfusion using melphalan and TNF alpha (TM-HILP) is a regional chemotherapy method for advanced melanoma. Purpose To explore the feasibility of the study of Circulating Melanoma Cells (CMCs) in the context of acute physiological changes induced by TM-HILP and their association with oncological outcomes. Methods The study included 20 patients undergoing TM-HILP for unresectable in-transit melanoma of the limbs, stage III(B/C/D). CMCs in the peripheral blood were analyzed at 5-time points from the preoperative day until day 7 from surgery using the following biomarkers: MITF, Tyrosinase mRNA, Melan-A and S100b, through quantitative RT-PCR. Results No CMCs according to Tyrosinase and Melan-A biomarkers were found in any sample. Friedman test showed significant alterations perioperatively for MITF (p < .001) and S100b (p = .001). Pairwise tests showed a significant increase of MITF levels on postoperative day 7 compared with postoperative day 1, intraoperative and preoperative levels (p < .05). Pairwise tests for S100b showed a significant difference between intraoperative sample and postoperative day 7 (p < .0001). Patients who experienced a complete response to TM-HILP (n = 12) had higher mean levels of MITF and the difference was significant at the time point immediately after the operation (0.29 +/- 0.27 vs. 0.06 +/- 0.06, p = .014) and on postoperative day 1 (1.48 +/- 2.24 vs. 0.41 +/- 0.65, p = .046). There was no association of MITF or S100b levels with 4-year disease specific survival. Conclusion TM-HILP is associated with increased levels of CMCs, but there was no association of this increase with survival. Patients with complete response to HILP demonstrate higher values of MITF shortly after the operation.

Automated summary

TM-HILP is associated with increased levels of CMCs, but this increase is not related to patient survival. Patients who experience a complete response to TM-HILP demonstrate higher levels of MITF shortly after the operation.