Multicentre prospective study of drug-eluting bead chemoembolisation safety using tightly calibrated small microspheres in non-resectable hepatocellular carcinoma
Introduction
In randomised studies, drug-eluting bead transarterial chemoembolisation (DEB-TACE) for the treatment of hepatocellular carcinoma (HCC) has not achieved better overall survival (OS) than conventional chemoembolisation (cTACE) [[1], [2], [3]]. Nonetheless, DEB-TACE has several proven advantages such as the delivery of higher concentrations of the chemotherapy drug in the tumour, lower systemic toxicity, a need for fewer sessions, controlled and sustained release of the drug, greater efficacy in advanced-stage or large tumours, and better standardisation of the procedure itself [[4], [5], [6]].
There is no consensus on the optimal size of the microparticles for DEB-TACE treatment [7]. Animal studies have shown that small microspheres penetrate deeper and more homogenously into tumours, causing more intense ischaemia and achieving a higher intratumoural concentration of the chemotherapy [8,9]. This would imply a better objective local response. The DEBs most commonly used in current clinical practice are 100–300 μm; DEBs sized ≤100 μm are used less often, as they are considered potentially more dangerous [10].
Biliary toxicity of DEB-TACE attributed to the ischaemic injury of the peribiliary plexus, associated with local doxorubicin toxicity, has been a particular source of concern. It has been suggested that this type of toxicity may be more intense when small microspheres are used, thus placing limits on their use [11]. Several uncontrolled retrospective studies have reported significantly higher rates of biliary complications with DEB-TACE than with cTACE [12,13]. In this context, the question of the most suitable microsphere size for use in DEB-TACE remains unanswered.
The objective of this multicentre prospective study was to assess whether DEB-TACE using small microspheres (100 μm) is associated with a higher rate of complications compared with cTACE and with DEB-TACE using bigger microspheres.
Section snippets
Study design and endpoints
This was a multicentre prospective study to assess the safety and tolerability of DEB-TACE of non-resectable HCC, using 100-μm doxorubicin-loaded microspheres (Embozene Tandem™, CeloNova BioSciences, Boston Scientific, San Antonio, TX, USA). Institutional Review Board approval was obtained at all the participating institutions. All patients provided written informed consent.
The safety of selective DEB-TACE with tightly calibrated 100-μm microspheres loaded with 50 mg of doxorubicin per
DEB-TACE procedures
The results are summarised in Fig. 1. A total of 214 DEB-TACE procedures (a mean of 1.64 per patient) were performed, with 46.5 % of the patients undergoing two DEB-TACE procedures and 12.9 %, 3.8 %, and 0.7 % undergoing three, four, and six procedures, respectively. Catheterisation was super-selective in 60.8 % of the procedures and selective in 39.2 %. The endpoint of stasis was achieved in 89.2 % of cases. Doxorubicin dose, based on the volume of microspheres infused, was 50 mg in 24, 75 mg
Discussion
Since the Precision V study, many researchers have attempted to optimise the DEB-TACE procedure [1]. The size and characteristics of the DEB is a key issue. Doxorubicin disseminates a maximum of 150 μm from the surface of the microsphere, and the density of microspheres inside the tumour should be as high as possible [22]. Animal studies have confirmed that small DEBs achieve deeper intra-tumour penetration and more uniform intra-tumour coverage, improving doxorubicin distribution and tumour
CRediT authorship contribution statement
Jose Urbano: Conceptualization, Methodology, Investigation, Data curation, Validation, Writing - original draft, Writing - review & editing, Supervision, Project administration. J. Javier Echevarria-Uraga: Investigation, Data curation, Validation, Writing - original draft, Writing - review & editing. J. Jose Ciampi-Dopazo: Investigation, Data curation, Validation, Writing - original draft, Writing - review & editing. Juan A. Sánchez-Corral: Investigation, Data curation. Jorge Cobos Alonso:
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
Authors thanks Dr. Lucia Llanos-Jiménez, epidemiologist, for her kind and efficient support in the approval processes of the national drug agency, regionals IRBs and clinical trials gov documents.
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2023, European Journal of Oncology NursingReduced nontarget embolization and increased targeted delivery with a reflux-control microcatheter in a swine model
2021, Diagnostic and Interventional ImagingCitation Excerpt :Such iatrogenesis include inadvertent ischemia of non-targeted tissues, toxicity linked to the drug delivery in the healthy tissues in case drug eluting beads administration or toxicity due to the beta emissions during transarterial radioembolization procedures [10,13–18]. Lung, stomach, pancreas, gallbladder, duodenum, diaphragm, and spleen are the most affected organs by NTE after transcatheter arterial chemoembolization (TACE) [19–25]. Less recurrent but nevertheless dangerous complications include the damages related to transcatheter procedures including uterine fibroid embolization, prostate artery embolization, which affects the rectum, bladder, and penis, and finally bronchial artery embolization for hemoptysis [26–36].
Radiopaque beads loaded with doxorubicin in the treatment of patients with hepatocellular carcinoma: A retrospective, multi-center study
2020, Cancer Treatment and Research CommunicationsCitation Excerpt :The treatment paradigm studied resulted in a 6.8% rate of CTCAE Grade 3 hepatic toxicity, with no other CTCAE Grade 3 or higher AEs occurring. The ORR and DCR in our group are comparable to those found in other studies utilizing drug-loadable microspheres for TACE (Fig 3) [8–10,26–28]. Outcomes of the current study are compared with results from other newer embolics, all measuring 150 microns or less (Table 4).