Research Article: Treatment algorithm based on the multivariate survival analyses in patients with advanced hepatocellular carcinoma treated with trans-arterial chemoembolization

Date Published: February 7, 2017

Publisher: Public Library of Science

Author(s): Hasmukh J. Prajapati, Hyun S. Kim, Chien-Wei Su.


To develop the treatment algorithm from multivariate survival analyses (MVA) in patients with Barcelona clinic liver cancer (BCLC) C (advanced) Hepatocellular carcinoma (HCC) patients treated with Trans-arterial Chemoembolization (TACE).

Consecutive unresectable and non-tranplantable patients with advanced HCC, who received DEB TACE were studied. A total of 238 patients (mean age, 62.4yrs) was included in the study. Survivals were analyzed according to different parameters from the time of the 1st DEB TACE. Kaplan Meier and Cox Proportional Hazard model were used for survival analysis. The SS was constructed from MVA and named BCLC C HCC Prognostic (BCHP) staging system (SS).

Overall median survival (OS) was 16.2 months. In HCC patients with venous thrombosis (VT) of large vein [main portal vein (PV), right or left PV, hepatic vein, inferior vena cava] (22.7%) versus small vein (segmental/subsegmental PV) (9.7%) versus no VT had OSs of 6.4 months versus 20 months versus 22.8 months respectively (p<0.001). On MVA, the significant independent prognostic factors (PFs) of survival were CP class, eastern cooperative oncology group (ECOG) performance status (PS), single HCC<5 cm, site of VT, metastases, serum creatinine and serum alpha-feto protein. Based on these PFs, the BCHP staging system was constructed. The OSs of stages I, II and III were 28.4 months, 11.8 months and 2.4 months accordingly (p<0.001). The treatment plan was proposed according to the different stages. On MVA of patients with advanced HCC treated with TACE, significant independent prognostic factors (PFs) of survival were CP class, ECOG PS, single HCC<5 cm or others, site of VT, metastases, serum creatinine and serum alpha-feto protein. New BCHP SS was proposed based on MVA data to identify the suitable advanced HCC patients for TACE treatments.

Partial Text

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, accounts for the sixth most common malignancy worldwide [1] and the third most common cause of cancer-related death globally behind only lung and stomach cancers [2]. Because most patients present with advanced disease, curative surgical resection is an option for less than 20% of the patients [3] and their available treatment options are different locoregional therapies. Among these unresectable HCC patients, the patients with advanced stage HCC have limited treatment options [4–6]. Barcelona-Clinic Liver Cancer (BCLC) staging treatment algorithm of HCC is widely used in Western countries. According to the BCLC treatment algorithm, the sorafenib has been the proposed care for the HCC patients with BCLC C stage [6]. However, several doxorubicin drug eluting beads trans-arterial chemoembolization (DEB TACE) studies have also shown survival benefits in patients with advanced stage HCC [7, 8]. The two recent prospective studies of DEB TACE with sorafenib have shown promising efficacy in patients with advanced stage HCC [9, 10]. As most HCC patients present with advanced disease, it is important to identify the independent variables of improved survival after TACE and to identify the BCLC C (advanced stage) HCC patients who can get maximum benefit from TACE. This information can be very useful to select the TACE therapy for the correct patient with advanced stage HCC.

This is a single institution prospective study with the patient’s written consent, approved by the Emory University Hospital Institutional Review Board (IRB) and is Health Insurance Portability and Accountability Act (HIPAA) compliant. The consents were recorded electronically and procedure was approved by the IRB.

As compared to other cancers, the treatment options and prognosis of the HCC not only depend on the morphology of the tumor but also on the extent on impaired liver function. There is also heterogeneity in different viral and metabolic conditions at the root of the HCC. Identification and appropriate quantification of the relevant prognostic factors are very crucial to leading the development of the staging systems. This study investigated the multiple imaging, clinical and serum examination variables and the BCHP staging system was proposed based on the MVA.




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