Transarterial Embolization Alone Versus Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma

Developed in Japan in the 1980s, TACE became the most frequent treatment for unresectable hepatocellular carcinoma (HCC) in patients with preserved hepatic function after 2002, when two radiochemotherapies (RCTs) showed survival benefits for HCC patients who underwent conventional Lipiodol-based TACE (cTACE). Nowadays, nearly half of HCC patients undergo this procedure during their clinical history. In the last ten years, cTACE has been challenged by an alternative procedure, drug-eluting beads-TACE (DEB-TACE), after the introduction of calibrated embolizing microspheres loaded with a chemotherapeutic agent. DEB-TACE is considered to be less toxic and better standardized than cTACE, with reported no differences in patient survival. Since 2006, DEB-TACE has become the standard in many centers worldwide. Though, the need of adding doxorubicin to small beads embolization alone (TAE) remains unsettled. Though cTACE/DEB-TACE and TAE have been compared in several RCTs, no study demonstrated a clear survival benefit associated with the former. Our study aims to compare first-line DEB-TACE and TAE on a random sample of HCC with the hypothesis that the addition of drug to embolization with small size beads is not associated with a survival benefit when compared to embolization alone performed with tiny calibrated microspheres. HCC is considered a chemo-resistant tumor and to date there is no clear evidence of benefits in associating anticancer agents to TAE. On the other hand, the optimal size of embolic agents has still to be defined. A comparative evaluation of TACE and TAE is essential for two additional reasons: a) it is still unclear whether side effects following embolization procedures are related to the embolization itself, to drug addition or both; b) DEB-TACE procedure is more expensive than TAE and, given the current attention on cancer-related health care cost control, identification of opportunities for cost savings in HCC treatments of an increasingly common cancer would be valuable.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

\- First level eligibility criteria include

1. HCC diagnosis according to the AASLD criteria \[26\];
2. patients ≥18 years;
3. HCC unsuitable for curative treatment or had failed/recurred after resection/ablation diagnosed according to the AASLD criteria;
4. no previous treatment in target lesions (prior treatments including resection on non-target lesions will be accepted);
5. Child-Pugh class A or B (max score 7);
6. ECOG Performance Status (PS) \<2;
7. target lesion measurable according to mRECIST.

Second level eligibility criteria include:

1. The modified hepatoma arterial-embolization prognostic score (m-HAP-II), based on bilirubin, albumin, serum alpha fetoprotein, tumor number and tumor size, divides patients in 4 classes (A, B, C, D) with different survivals and is useful for prognosis stratification. The first selection criteria will be m-HAP-II classes B or C fulfilment.
2. The UNOS/TNM stage: only patients with T1, T2, T3 and T4 tumors will be included.

   These two main criteria will be used for stratification of patients prior to randomization in order to obtain identical prevalence of m-HAP-II classes B/C and of UNOS/TNM stages from T1 to T4a
3. obtaining of the informed consent.

Exclusion Criteria:

1. infiltrative HCC;
2. neoplastic branch or main portal vein invasion;
3. equivocal hepatic lesion;
4. advanced liver disease (bilirubin levels \>2.5 mg dl-1, albumin \<30 g l-1, platelets \<50 x 109/L, INR \>1.5);
5. ascites and/or F3 oesophageal varices;
6. other tumors in the previous 5 years;
7. technical contraindications to arteriography or TACE.

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