Clearance of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection or Liver Transplantation.

Víctor Amado,Clara Linares,Manuel Rodríguez-Perálvarez,María Lola Espejo-Cruz,Marina Sánchez-Frías,Rubén Ciria,Rafael Alejandre,José Luis Montero,Sandra González-Rubio,Gustavo Ferrín,Javier Zamora,Manuel De La Mata,Gema García-Jurado

doi:10.3390/cancers13102476

Abstract

In patients with hepatocellular carcinoma (HCC), a complete clearance of circulating tumor cells (CTCs) early after liver transplantation (LT) or surgical resection (LR) could prevent tumor recurrence. prospective pilot study including patients with HCC who underwent LR or LT from September 2017 to May 2020. Enumeration of CTCs was performed in peripheral blood samples (7 mL) using the Isoflux® system (Fluxion Biosciences) immediately before surgery, at post-operative day 5 and at day 30. A clinically relevant number of CTCs was defined as >30 CTCs/sample. 41 HCC patients were included (mean age 58.7 ± 6.3; 82.9% male). LR was performed in 10 patients (24.4%) and 31 patients (75.6%) underwent LT. The main etiology of liver disease was chronic hepatitis C (31.7%). Patients undergoing LR and LT were similar in terms of preoperative CTC count (p = 0.99), but clearance of CTCs within the first month was more pronounced in the LT group. Clusters of CTCs at baseline were associated with incomplete clearance of CTCs at day 30 (54.2% vs. 11.8%, p = 0.005), which in turn impacted negatively on survival (p = 0.038). Incomplete clearance of CTCs after surgery could be a surrogate marker of HCC aggressiveness.

Highlights

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of cancer-related death worldwide [1]
Liver resection (LR) was performed in 10 patients (24.4%) and 31 patients (75.6%) underwent liver transplantation (LT)
We evaluated the clearance of circulating tumor cells (CTCs) separately in immunocompetent patients, who underwent LR, and in immunocompromised individuals, who received a LT and immunosuppressive drugs immediately thereafter

Summary

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of cancer-related death worldwide [1]. Liver resection (LR) and liver transplantation (LT) are the first-line therapeutic options in selected patients with tumors confined to the liver [2]. LT is the only therapeutic option able to cure both HCC and the underlying liver cirrhosis, with 5-year survival rates above 70% in patients within Milan criteria [3]. Tumor recurrence may occur in up to 15% of patients after LT and it is associated with a poor prognosis [3]. In patients with hepatocellular carcinoma (HCC), a complete clearance of circulating tumor cells (CTCs) early after liver transplantation (LT) or surgical resection (LR) could prevent tumor recurrence. Clusters of CTCs at baseline were associated with incomplete clearance of CTCs at day 30 (54.2% vs 11.8%, p = 0.005), which in turn impacted negatively on survival (p = 0.038). Conclusion: Incomplete clearance of CTCs after surgery could be a surrogate marker of HCC aggressiveness

Methods

Results

Conclusion