A Novel Multi-Mode Thermal Therapy for Colorectal Cancer Liver Metastasis: A Pilot Study.

Wentao Li,Lichao Xu,Guangzhi Wang,Ping Liu,Lisa X Xu,Yue Lou,Kangwei Zhang

doi:10.3390/biomedicines10020280

Abstract

A novel multi-mode thermal therapy was developed for local tumor ablation and the systemic stimulation of anti-tumor immunity, consisting of a rapid liquid nitrogen freezing, and followed by the radiofrequency heating of target tumor tissue. This pilot study aimed to compare the therapeutic effects of the new therapy with conventional radiofrequency ablation (RFA) on patients with colorectal cancer liver metastasis (CRCLM). From August 2016 to September 2019, thirty-one patients with CRCLM received either multi-mode thermal therapy (n = 17) or RFA (n = 14). Triphasic contrast-enhanced magnetic resonance imaging (MRI), routine blood tests, and peripheral blood immune responses were evaluated before the treatment and in 1, 3, 6, and 12 months after. Local tumor response and progression-free survival (PFS) were assessed using the Kaplan-Meier method, and pre- and post-treatment immune cell counts were analyzed using Mann-Whitney U and Wilcoxon tests. A significantly longer PFS was observed in the multi-mode thermal therapy group in comparison to that of the conventional RFA group (median, 11.4 versus 3.4 months, p = 0.022). It was found that multi-mode therapy induced the functional maturation of dendritic cells, promoted CD4+ T cell-mediated antitumor responses, and decreased regulatory T cells, contributing to better therapeutic efficacy in CRCLM patients.

Highlights

This multi-mode approach involves the precise control of a hybrid thermal process characterized by a rapid liquid nitrogen cooling followed by a rapid radiofrequency heating
While the tumor center was completely coagulated by high temperatures, a peripheral tumor zone was created, in which tumor cells and vasculature were completely broken under sub-lethal temperatures to allow the maximal release of tumor-associated molecules and antigens in situ
It is seen that most of the enrolled patients suffered from disease progression who had undergone at least two lines of systemic chemotherapy

Summary

Introduction

The control of metastatic tumors is a long-sought goal in cancer therapy. Accumulating evidence has shown that the induction of tumor-specific adaptive immunity is essential for the long-term control of cancer. To enhance the stimulation of systemic antitumor immunity, a novel multi-mode thermal therapy was developed in our previous studies [6,7]. This multi-mode approach involves the precise control of a hybrid thermal process characterized by a rapid liquid nitrogen cooling followed by a rapid radiofrequency heating. Through this procedure, while the tumor center was completely coagulated by high temperatures, a peripheral tumor zone was created, in which tumor cells and vasculature were completely broken under sub-lethal temperatures to allow the maximal release of tumor-associated molecules and antigens in situ

Methods

Results

Conclusion