[Show abstract][Hide abstract] ABSTRACT: The promigratory molecule L1CAM is overexpressed in various tumors, often representing an unfavorable prognostic marker. Recently, we identified L1CAM expression in pancreatic ductal adenocarcinoma (PDAC) cells accounting for chemoresistance and increased cell migration. Thus, the present study aims at further elucidating the role of L1CAM in a larger cohort of PDAC specimens including precursor lesions and metastasis. L1CAM expression was determined by immunohistochemistry in tissues of 123 patients including tissues of 110 primary PDACs, 15 lymph node metastases and 14 liver metastases. The immunohistochemical analyses revealed L1CAM expression in 92.7% of primary PDACs, 80% of lymph node metastases and 100% of liver metastases. Furthermore, we have investigated PDAC precursors, pancreatic intraepithelial neoplasia (PanIN) lesions, revealing a significant increase of L1CAM expression with the PanIN grade (6.4 and 6.8% in PanIN 1A and B, 35% in PanIN 2 and 20% in PanIN 3). The elevated expression of L1CAM already found in PanINs points to a role of L1CAM quite early in tumorigenesis of PDAC. Furthermore, its broad expression in primary tumors as well as in metastases of PDAC patients provide a rationale to further explore the value of L1CAM as a therapeutic target in the treatment of this highly malignant tumor.
[Show abstract][Hide abstract] ABSTRACT: Disease progression of hepatocellular cancer (HCC) in patients eligible for liver transplantation (LTx) occurs in up to 50% of patients, resulting in withdrawal from the LTx waiting list. Transarterial chemoembolization (TACE) is used as bridging therapy with highly variable response rates. The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer.
The HeiLivCa study is a double-blinded, controlled, prospective, randomized multi-centre phase III trial. Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid. Patients in study arm B will be treated with transarterial chemoembolization plus placebo. A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled. An interim patients' analysis will be performed after 60 events. Evaluation of time-to-progression as primary endpoint (TTP) will be performed at 120 events. Secondary endpoints are number of patients reaching LTx, disease control rates, OS, progression free survival, quality of live, toxicity and safety.
As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities. This study is designed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx.