This analysis was reported according to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines.16As a prelude to the main study, the specificity of the HAP score for patients undergoing TACE was examined in 3,556 patients with early HCC who underwent resection and in 967 patients with advanced HCC who received sorafenib within clinical trials.17, 18In the main study, the reported TACE cohort19 was expanded by collecting further cases in which the response to TACE according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST)20, 21 was recorded. This analysis has involved only patients who were classified by the local investigator as undergoing TACE as their primary and first treatment. Patients whose TACE was used as a bridge to transplantation or other potentially curative treatment options were excluded, as were patients with extrahepatic metastasis. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the appropriate institutional review committee.
All participating centers had specific expertise in the management of HCC and the practice of TACE. There were 19 centers representing 11 different countries, including a reported multicenter cohort22, 23 that comprised patients from London (United Kingdom), Osaka (Japan), Seoul (Korea), and Novara (Italy) (Tables 1 and 2). Most centers used “conventional” TACE, although several moved to drug‐eluting bead (DEB)–based TACE after 2008. In all centers, patients were followed up by computed tomography (CT) or magnetic resonance imaging scans once every 3 months after stable disease (SD) had been attained.
Baseline variables available in all the centers were age, sex, cause (hepatitis C virus [HCV], hepatitis B virus [HBV], alcohol, or “other”), tumor number (solitary or multiple), tumor size (centimeters), VI, Child‐Pugh grade, albumin (grams per liter), bilirubin (micromoles per liter), and AFP (nanograms per milliliter). The approach to TACE (DEB‐based or lipiodol‐based methods) was not proscribed, although no case received transarterial radioembolization.
The “other” cause comprised mainly patients with nonalcoholic fatty liver disease (NAFLD), other types of chronic liver disease, and more than one cause. The first TACE procedure was undertaken within 6 weeks of diagnosis, and laboratory data were recorded during that period.
VI (including portal vein, hepatic vein, and inferior vena cava involvement) was assessed in the portal phase of CT and supplemented where appropriate by arterial portography and classified as “present” or “absent.” Response assessments according to mRECIST20, 21 were made within the 6 to 9 weeks following the first TACE treatment. mRECIST response was categorized as complete response (CR), partial response (PR), SD, and progressive disease (PD). mRECIST data were available in eight of the 17 cohorts (2,688 patients). This analysis did not take into account further TACE treatments undertaken after the first one. Liver function was assessed by the Child‐Pugh grade (as graded by the local investigator) and the albumin‐bilirubin (ALBI) score, the latter being graded according to the published cut‐off points.24 Grades 1, 2, and 3 refer to good, intermediate, and poor liver function, respectively. Data on treatment of hepatitis C with direct‐acting antivirals (DAAs) were not collected, but an estimate of the number who might have received this therapy was gained by assessing the date of TACE treatment, assuming there were only a very limited number who would receive DAAs before January 2012.
After generation of the models, as described below, they were externally validated in independent data sets from China and Germany, representing “Eastern” and “Western” cohorts respectively. External validation and calibration were undertaken using methods described by Royston and Altman.25, 26
Free full text: Click here