Transarterial therapies for hepatocellular carcinoma (HCC): A long way towards standardization
Authors: Emmanuel A. Tsochatzis, Tim Meyer, James O’Beirne, Andrew K. Burroughs
Journal: Journal of Hepatology (2012)

Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial designJournal of HepatologyVol. 56Issue 6PreviewTransarterial chemoembolisation (TACE) improves survival of properly selected patients with hepatocellular carcinoma (HCC). Drug eluting beads (DEB) provide a calibrated and homogenous procedure while increasing efficacy. Outcome data applying this technology is lacking, and this is instrumental for clinical decision-making and for trial design. We evaluated the survival of HCC patients treated with DEB-TACE following a strict selection (preserved liver function, absence of symptoms, extrahepatic spread or vascular invasion). Full-Text PDF Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinomaJournal of HepatologyVol. 56Issue 6PreviewTransarterial chemoembolization (TACE) is an important palliative treatment for unresectable hepatocellular carcinoma (HCC), but TACE-induced ischemic injury can upregulate angiogenic factors and is associated with poor prognosis. The aim of this study was to evaluate the safety and efficacy of concurrent conventional TACE and sorafenib in patients with unresectable HCC. Full-Text PDF Reply to: “Transarterial therapies for hepatocellular carcinoma (HCC): A long way towards standardization”Journal of HepatologyVol. 58Issue 1PreviewChemoembolization is an important treatment for hepatocellular carcinoma (HCC) and has been shown to improve survival compared with best supportive care in two randomized controlled trials [1,2]. It is also the current standard of care for intermediate HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system [3]. The commonly used method of “conventional” transcatheter arterial chemoembolization involves intra-arterial infusion of lipiodol mixed with anticancer drugs such as doxorubicin into the feeding artery of the HCC. Full-Text PDF Open Access We read with interest the articles by Burrel [[1]Burrel M. Reig M. Forner A. Barrufet M. de Lope C.R. Tremosini S. et al.Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design.J Hepatol. 2012; 56: 1330-1335Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar] and Park [[2]Park J.W. Koh Y.H. Kim H.B. Kim H.Y. An S. Choi J.I. et al.Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma.J Hepatol. 2012; 56: 1336-1342Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar] on transarterial chemoembolization (TACE) in HCC. They demonstrate the lack of standardization of this technique, which has led others to question its overall efficacy [[3]Oliveri R.S. Wetterslev J. Gluud C. Transarterial (chemo) embolisation for unresectable hepatocellular carcinoma.Cochrane Database Syst Rev. 2011; : CD004787PubMed Google Scholar], but also provide the basis for important clarifications. Burrel et al. [[1]Burrel M. Reig M. Forner A. Barrufet M. de Lope C.R. Tremosini S. et al.Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design.J Hepatol. 2012; 56: 1330-1335Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar] used the newer DEB-BEADs, at a size of 300–700 μm, to ensure controlled delivery of chemotherapy to the tumor cells over a period of several days. DEB-BEADs decrease the rate of chemotherapy-induced side effects but do not improve survival [[4]Lammer J. Malagari K. Vogl T. Pilleul F. Denys A. Watkinson A. et al.Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.Cardiovasc Intervent Radiol. 2010; 33: 41-52Crossref PubMed Scopus (1149) Google Scholar]. They used a highly selected cohort of patients, 40% of whom were staged as BCLC-A and they concluded that median survival was 48.6 months after a median follow-up of 24.5 months. This indeed is a mathematical paradox, as actual follow-up was much less than supposed survival; at the time of the projected median survival, less than 15 patients were still at risk of death according to the Kaplan–Meier curve and 35 had died, i.e., there was no adequate follow-up for at least 50% of the cohort and indeed 54/69 patients still alive did not have the median survival follow-up. Therefore, their statement and conclusion need to be revisited as they are based on projected and not actual data, in a highly selected group of patients. Furthermore, the size of the embolizing agent may not be optimal, as it does not allow super-selective occlusion of smaller tumor feeding arteries. For instance, polyvinyl alcohol particles can be as small as 45–150 μm [[5]Tsochatzis E.A. Germani G. Burroughs A.K. Transarterial chemoembolization, transarterial chemotherapy, and intra-arterial chemotherapy for hepatocellular carcinoma treatment.Semin Oncol. 2010; 37: 89-93Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar]. The study by Park et al. [[2]Park J.W. Koh Y.H. Kim H.B. Kim H.Y. An S. Choi J.I. et al.Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma.J Hepatol. 2012; 56: 1336-1342Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar] is a more pragmatic one, including patients with more advanced disease and a few with BCLC-C stage who would not be normally suitable for TACE [[6]European Association for the Study of the Liver; European Organization for Research and Treatment of Cancer, EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012;56:908–943.Google Scholar]. Unfortunately, the suboptimal gelfoam was used as the embolizing agent and therefore the maximal therapeutic effect was probably not reached. As we had previously pointed out, gelfoam only temporarily occludes the tumor vessels and the effect does not seem to last for more than 14 days [[7]Marelli L. Stigliano R. Triantos C. Senzolo M. Cholongitas E. Davies N. et al.Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies.Cardiovasc Intervent Radiol. 2007; 30: 6-25Crossref PubMed Scopus (687) Google Scholar]. This important detail, among others, was not taken into account in the recent Cochrane meta-analysis [[3]Oliveri R.S. Wetterslev J. Gluud C. Transarterial (chemo) embolisation for unresectable hepatocellular carcinoma.Cochrane Database Syst Rev. 2011; : CD004787PubMed Google Scholar]. Despite important advances in the field, transarterial therapies in HCC still suffer from a lack of standardization in the selection of patients, the embolizing agent used, the size of the embolizing particles, the choice of the chemotherapeutic agent, the interval between therapeutic sessions and agreement on stopping rules [[7]Marelli L. Stigliano R. Triantos C. Senzolo M. Cholongitas E. Davies N. et al.Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies.Cardiovasc Intervent Radiol. 2007; 30: 6-25Crossref PubMed Scopus (687) Google Scholar]. Even the addition of chemotherapy has not been proven to be superior to embolization alone in randomized controlled trials [[8]Tsochatzis E.A. Meyer T. Burroughs A.K. Hepatocellular carcinoma.N Engl J Med. 2012; 366: 92-93Crossref PubMed Scopus (18) Google Scholar]. Ideally, embolization should be done with small and permanently occluding particles, to ensure more selective occlusion of small feeding tumour arteries and fewer side effects. This is an advantage of PVA particles, whose size is smaller than that of DEB-BEADS. Clearly randomized controlled trials are needed in order to establish the optimal transarterial technique, as the choice of the embolizing agent and its size could potentially make a difference. In the interim, reporting of actual and not projected data of survival is cardinal for balanced conclusions and information given to health providers and patients. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.