Phase II/III Study of Radiofrequency Ablation Combined with Cytokine-Induced Killer Cells Treating Colorectal Liver Metastases

Abstract

Purpose: This phase II/III, non-randomized clinical trial aimed to determine the efficacy and safety of the combination of radiofrequency ablation (RFA) and cytokine-induced killer (CIK) cells transfusion for patients with colorectal liver metastases (CRLMs). Experimental Design: A total of 60 eligible patients with CRLMs were enrolled and divided into Group A (RFA alone, n = 30) and Group B (RFA plus CIK, n = 30), and following enzyme-linked immunosorbent spot assay was performed in 8 patients with CEA > 50 ng/mL pre-RFA and 7 days post-RFA and CIK treatment, respectively. Results: The median progression-free survival (PFS) times of Group A and Group B were 18.5 months and 23 months, respectively (P = 0.0336). The 3-year progression-free rates were 13.3% in Group A and 20.3% in Group B, respectively. The median overall survival time was 43 months in Group A, and not reached in Group B. The 3-year survival rates were 64.6% in Group A and 81.0% in Group B, respectively (P = 0.1187). Among the 8 patients with CEA > 50ng/mL, 6 had increase of circulating CEA-specific T cells after RFA (P = 0.010). After CIK cell therapy, the number of CEA-specific T cells increased in all the 8 patients comparing with that pre-treatment (P = 0.001) and in 7 patients comparing with that post-RFA (P = 0.028). Conclusions: We firstly confirm that the combination of RFA and CIK cells boosts CEA-specific T cell response and shows to be an efficacious and safe treatment modality for patients with CRLMs.

Chemotherapy combined with dendritic cell vaccine and cytokine-induced killer cells in the treatment of colorectal carcinoma: a meta-analysis

“…CIK cell-based immunotherapy is effective for metastatic CRC, as demonstrated by improved OS and progression-free survival rates. 16 , 52 Moreover, researchers have demonstrated that the infusion of DC vaccine and CIK cells can induce a strong immune response with a positive response of delayed-type hypersensitivity (DTH) in cancer patients, such as those with advanced renal cell carcinoma, hepatocellular carcinoma, and pancreatic cancer. 45 , 50 …”

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer

“…The use of autologous and allogeneic CIK cells in combination with curative therapy has thus far yielded mixed responses. For the treatment of 60 patients with colorectal liver metastases, autologous CIK cell transfer 1 week following RFA showed higher median PFS (23 vs 18.5 months), 3‐year progression‐free rates (20.3% vs 13.3%), and 3‐year survival rates (81.0% vs 64.6%) relative to the control group not receiving CIK cell transfer 71 . In a phase 3 clinical trial for the treatment of hepatocellular carcinoma (HCC), autologous CIK cell transfer after liver resection did not improve disease‐free survival (DFS) or OS, but prolonged the median time in therapeutic range (TTR) in a total of 200 patients (13.6 vs 7.8 months) 72 .…”

Immunotherapy in colorectal cancer: for the select few or all?

“…Radiofrequency ablation (RFA) is an established treatment for CRC liver metastases, and by heating the tissue, RFA induces coagulation necrosis, leading to a strong inflammatory response (59). One study has investigated the efficacy and safety of the combination of RFA and cytokineinduced killer (CIK) cell transfusion for patients with CRC liver metastases (60). Compared to RFA alone, the median PFS is 23 months with the combination versus 18.5 months with RFA alone.…”