Cytokine Change in Hepatocellular Carcinoma Treated by Thermal Ablation

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with aggressive tumor behavior. Radiofrequency ablation (RFA) or microwave ablation (MWA) is an effective curative treatment for early stage HCC. This thermal ablation of liver tumor induces host immune response with changes in serum concentration of various cytokines. It is not clear whether this host immune response correlates with tumor recurrence and long-term patient survival. Objective: This prospective study is to investigate the change of cytokines' level following RFA or MWA for HCC and its clinical correlation with tumor recurrence and patients' long-term survival data. Hypothesis: Thermal ablation of HCC creates tumor antigen source for the generation of antitumor immunity and enhances host immune responses. The resulting inflammation and changes in cytokines may augment tumor cell death by increasing neutrophil infiltration and oxidative burst mechanisms. On the other hand, there may be negative effects via the production of growth factors, which could stimulate tumor cell growth within the sub-lethal margin. Therefore, the ultimate clinical consequences would be significantly affected by these immune responses. Study design: This is a prospective study on the measurement of changes of serum cytokines in patients with HCC undergone RFA or MWA using the commercially available kit (MILLIPEX, Human cytokine/chemokine magnetic bead panel - Immunology Multiplex Assay ), which measure 10 cytokines, including IL-1β, IL-6, IL-10, IL-12 (p40), IL-12 (p70), TNF-α, CXCL8, CXCL9, CXCL10, CCL2, CCL5. Statistical correlation will be performed between the cytokine change and long-term patients' clinical outcome using the prospectively collected database. Subjects: Patients with HCC undergone RFA or MWA in the Department of Surgery, The Chinese University of Hong Kong will be recruited. Exclusion criteria were evidence of extrahepatic metastasis, patients receiving combined hepatectomy and other local ablative therapy and patients with decompensated liver function that preclude local ablative treatment. Intervention: RFA or MWA will be performed for patients with HCC. The serum samples of all consecutive recruited patients will be collected prospectively during the intervention. The measurement of cytokines level will be performed in the Laboratory of Department of Chemical Pathology, The Chinese University of Hong Kong under the standard protocol. Main outcome measures: Primary outcome measure is early intrahepatic tumor recurrence within one year after thermal ablation. Secondary outcome measures are other tumor recurrence pattern (late intrahepatic recurrence and extrahepatic metastasis), overall survival and recurrence-free survival. Data analysis: All data will be prospectively collected by a research assistant and computerized in a database. Statistical analysis will be performed by Chi-square test or Fisher's exact test, where appropriate, to compare discrete variables and Mann-Whitney U test to compare continuous variables. Cumulative survival will be computed by the Kaplan-Meier method and compared by Log-rank test. Multivariable analysis using logistic regression model will be done to identify the independent prognostic factors affecting early tumor recurrence. Expected results: Understanding the relationship between the cytokines change during thermal ablation and post-treatment tumor recurrence helps to identify high risk patients for the possible adjuvant therapy in future study.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Consecutive patients with HCC undergoing RFA or MWA will be recruited into this study provided the following criteria are fulfilled.

  1. HCC of maximal diameter \< 8cm, and/or
  2. Multiple tumor nodules \< 5, and/or
  3. Normal liver (serum total bilirubin level \< 50 umol/L and serum albumin \> 30 g/L) and renal function (serum creatinine level \<120 mmol/L)
  4. Child-Pugh class A or B

Exclusion Criteria:

1. Evidence of extrahepatic metastasis
2. Patients receiving combined hepatectomy and other local ablative therapy
3. Patients with decompensated liver function that preclude local ablative treatment.
4. Patients with previous treatment for HCC (TACE, radiofrequency ablation, high intensity focus ultrasound or systemic chemotherapy)
5. Patients with inadequate serum sample for cytokine analysis