Petra Prins

Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Tumor immune infiltration is a prognostic marker for relapse in patients with colorectal cancer. The Immunoscore methodology was extended to patients with hepatocellular carcinoma. The Immunoscore could predict the risk of postsurgical relapse and duration of relapse-free survival. Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3+) and cytotoxic (CD8+) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3+ and CD8+ cells and clinical outcome. High densities of both CD3+ and CD8+ T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3+ and CD8+ cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6–21.8] for CD3+ and 3.9 (95% CI, 1.1–14.1) for CD8+. Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419–30. ©2016 AACR.

Systemic therapy for advanced hepatocellular carcinoma: an update

Advanced hepatocellular carcinoma (HCC) is a deadly disease with few systemic therapeutic options. Sorafenib is the only agent to be FDA approved for the first-line treatment of patients with HCC. This drug increases overall survival (OS) by 3 months compared with placebo (10.7 months with sorafenib vs. 7.7 months with placebo). More recently, the RESORCE trial demonstrated efficacy of regorafenib in the second-line treatment of HCC: OS was increased from 7.8 months with placebo to 10.6 months with regorafenib after patients experienced disease progression on sorafenib. However, there is still an unmet need for effective systemic therapy of patients with advanced HCC. Numerous genetic pathways have been studied along with drugs to target these pathways but, thus far, drugs targeting cell proliferation, metastasis, angiogenesis, and metabolite use have been studied with minimal success. HCC can be divided into two subclasses: proliferative and non-proliferative, each dependent on separate pathways. HCC can be caused by alcoholic cirrhosis, hepatitis C virus (HCV), and hepatitis B virus (HBV); however no etiology-specific therapies have been demonstrated. Immunotherapy is currently being assessed in clinical trials and is demonstrating some efficacy. More research is needed to determine the most essential pathways to target in the war against this deadly cancer.

Diverse clinical outcome and predictors for clinical outcome in patients with HCC treated with TACE.

442 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the second leading cause of cancer-related death, worldwide. This reflects the challenges facing HCC treatment. Methods: Patients (pts) with HCC receiving TACE treatment (n = 96) were examined retrospectively for clinical outcome and its possible predictors. The number of TACE treatments and the time elapsed between each treatment were assessed and correlated with overall survival (OS) using the log rank test of Kaplan Meier curves. T-stage, level of differentiation, vascular invasion, and Child Pugh score at the time of HCC diagnosis were compared among pts who received different numbers of TACE treatments (Kaplan-Meier survival analysis, ANOVA and student T test). Results: TACE treated pts had a median OS of 46 month (mo) and progression free survival of 12 mo (difference in time between the date of first progression and the date of diagnosis). Pts received 1-2 (n = 52), 3-4 (n = 28), or 5-6 (n = 16) TACE treatments. We ...