Management and prognosis of hepatocellular carcinoma (HCC) patients depends on tumor status, general health, and recent liver functional reserve (Okuda, Ohtsuki et al. 1985, Llovet, Bustamante et al. 1999, Marrero, Fontana et al. 2005, Cabibbo, Enea et al. 2010). Curative treatments, such as resection, liver transplantation, or local ablation, are generally restricted to limited tumor mass (Bruix and Sherman 2005, Llovet, Schwartz et al. 2005). Transarterial chemoembolization (TACE) is currently considered the first line-therapy for intermediate-stage HCC patients (Llovet and Bruix 2003, Llovet, Di Bisceglie et al. 2008, Bruix and Sherman 2011), aiming for local tumor control (Arii, Yamaoka et al. 2000, Ikai, Arii et al. 2004, Takayasu, Arii et al. 2006, Lee, Huo et al. 2012). Apart from its use in the palliative setting for intermediate and advanced tumor stages, TACE is applied as bridging treatment to liver transplantation (LT) in order to control local tumor growth and maintain the patient’s tumor load (Majno, Adam et al. 1997, Decaens, Roudot-Thoraval et al. 2005, Porrett, Peterman et al. 2006, Bruix and Sherman 2011, Kollmann, Selzner et al. 2017). The aim of TACE is to induce tumor necrosis of medium local application of high-dose chemotherapy and additional hypoxia (through vascular occlusion) (Zangos, Eichler et al. 2007).
The efficacy of general TACE procedures has already been evaluated several times in patients with purely palliative therapy indications (Biselli et al. 2005; Llovet and Bruix 2003; Takayasu et al. 2006). However, the benefits of TACE as bridging therapy for liver transplantation have been studied to a much lesser extent, with unambiguous results (Decaens et al. 2005; Fujiki et al. 2011; Holowko et al. 2015; Majno et al. 1997; Porrett et al. 2006). Currently, different variants of TACE are in use. These include conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE), and TACE with degradable starch microspheres (DSM-TACE). In cTACE, a mixture of the chemotherapeutic agent and an embolizing material is usually administered at the beginning of TACE procedure, after which a single dose of the embolisate is administered until the blood flow in the artery supplying the tumor ceases (Gruber-Rouh, Schmitt et al. 2018). The cTACE procedure is carried out with different chemotherapy and embolising materials depending on the clinic and the scheme used (Lencioni and Llovet 2010). The most commonly used embolizing material is Lipiodol (Vogl and Gruber-Rouh 2019). It plays a central role in cTACE as it is simultaneously used as a carrier substance for the chemotherapy drug, as an X-ray contrast agent for marking the tumor and as an embolizing material (Liapi and Geschwind 2011). The most widely used chemotherapeutic drug for cTACE worldwide is doxorubicin (Lencioni, Petruzzi et al. 2013) — although agents such as epirubicin, mitomycin, cisplatin, and miriplanin are also used (Vogl and Gruber-Rouh 2019). The different application of cTACE, with regard to the technique and the therapy plan, limits the comparability of cTACE (Lencioni, Petruzzi et al. 2013). The DEB-TACE procedure describes the intraarterial application of beads loaded with chemotherapeutically active substances in order to achieve a continuous release of these substances in (Vogl and Gruber-Rouh 2019). These beads are available in different sizes and, in contrast to cTACE, lead to a longer dwell of the chemotherapeutic agent in the tumor, with at the same time less systemic effects (Poon, Tso et al. 2007, Varela, Real et al. 2007, Vogl and Gruber-Rouh 2019). This is due to the lack of a time gap between the application of the chemotherapeutic agent and the embolisate as the beads act simultaneously as both thereby making an additional application of embolizing substances unnecessary. DC Beads® (non-biodegradable, polyvinyl alcohol-laden microspheres loaded with doxorubicin) are used most commonly for performing DEB-TACE procedures (Song and Kim 2017). Due to the lower plasma concentration of the chemotherapeutic agent in a DEB-TACE, significantly fewer drug-related adverse reactions could already be observed compared to cTACE (Varela, Real et al. 2007, Lencioni, de Baere et al. 2012). Nevertheless, the superiority of DEB-TACE over cTACE continues to be questioned due to insufficient randomized controlled studies (Facciorusso 2018). The most modern variant of TACE uses more biodegradable particles (degradable starch microspheres = DSM), such as EmboCept® S particles (Caine, Carugo et al. 2017). As DSM-TACE is a recent development, it has been the topic of a few studies, some of which found both a favourable secondary level profile and a sufficient effectiveness of biodegradable particles in TACE (Kirchhoff, Bleck et al. 2007, Orlacchio, Chegai et al. 2015, Schicho, Pereira et al. 2017). However, data comparing the efficacy of the different TACE methods used in the bridging to transplant with those used in the palliative collective are rare. Here, we retrospectively assessed and compared the clinical safety and efficiency of the TACE variants used for bridging to transplant and in palliative procedures in HCC patients.
Although the results of sorafenib therapy in combination with other therapies, such as TACE, were positive in various meta-analyses (time-to-progress (TTP)), they were less so for overall survival (Zeng, Lv et al. 2016, Li, Zhao et al. 2018, Wang, Zhao et al. 2018). As a multikinase inhibitor, sorafenib interferes with the proliferation mechanism of tumor cells and their angiogenesis while increasing apoptosis (Chang, Adnane et al. 2007). However, due to its systemic application, as opposed to the local application within the framework of a TACE, side effects such as diarrhea, nausea, vomiting, and the hand-foot-skin syndrome ensue (Li, Gao et al. 2015).