Application and evaluation of drug-eluting beads in interventional therapy of liver metastasis in colorectal cancer
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ABSTRACT:
DISEASE(S): Liver Metastasis In Coloretcal Cancer
PROVIDER: 2679092 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:PurposeTo develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo.Materials and methodsAn ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model.ResultsLipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology.ConclusionsA simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.
| S-EPMC6663477 | biostudies-literature
Project description:There are currently two methods widely used in clinical practice to perform transarterial chemoembolization (TACE). One is based on mixing an aqueous drug with an iodized oil (Lipiodol) and creating an emulsion that is delivered intraarterially, followed by embolization with a particulate agent. The other is based on a one-step TACE using Drug-eluting Beads (DEBs) loaded with drug. It is not recommended to mix Lipiodol with DEBs due to incompatibility. For the first time, novel DEB: Lipiodol: doxorubicin (Dox) emulsions are identified using lyophilized polyvinyl alcohol (PVA) hydrogels (non-iodinated or iodinated) DEBs.Methods15 DEB emulsions (50mg Dox) were assessed for stability and deliverability in vitro and in vivo in a swine model. Dox release from selected formulations was measured in vitro using a vascular flow model and in vivo in a VX2 rabbit tumor model.ResultsBoth DEB formats were shown to be able to form emulsions, however only Iodinated DEBs consistently met defined handling criteria. Those based on the non-iodinated DEB achieved >99%+ Dox loading in <5 minutes but were generally less stable. Those prepared using iodinated DEBs, which are more hydrophobic, were able to form stable Pickering-like emulsions (separation time ≥ 20 minutes) and demonstrated handling, administration and imaging observations more akin to Lipiodol™ TACE emulsions in both embolization models. Controlled Dox release and hence beneficial in vivo pharmacokinetics associated with DEB-TACE were maintained.ConclusionsThis study demonstrates that it is possible to formulate novel DEB emulsions suitable for TACE that combine positive elements of both Lipiodol™ based and DEB-TACE procedures.
| S-EPMC6735388 | biostudies-literature
Project description:Chemoembolization with drug-eluting beads is a type of locoregional therapy currently being used for the treatment of hepatocellular carcinoma and metastatic disease to the liver. This treatment has proven effectiveness in controlling tumor growth, extending survival time, and improving quality of life. Chemoembolization with drug-eluting beads have been shown to be safe, but like any other invasive procedure, can have associated complications. The authors present a case of intrahepatic biloma formation occurring as a result of treatment with drug-eluting beads.
| S-EPMC3193327 | biostudies-other
Project description:Trans arterial chemoembolization using Irinotecan Drug-eluting Beads before liver surgery for patients with primarily unresectable colorectal liver metastasis
| 2379485 | ecrin-mdr-crc
Project description:ObjectiveTo determine the feasibility of using radiopaque (RO) beads as direct tumour surrogates for image-guided radiotherapy (IGRT) in patients with liver tumours after transarterial chemoembolisation (TACE).MethodsA novel vandetanib-eluting RO bead was delivered via TACE as part of a first-in-human clinical trial in patients with either hepatocellular carcinoma or liver metastases from colorectal cancer. Following TACE, patients underwent simulated radiotherapy imaging with four-dimensional computed tomography (4D-CT) and cone-beam CT (CBCT) imaging. RO beads were contoured using automated thresholding, and feasibility of matching between the simulated radiotherapy planning dataset (AVE-IP image from 4D data) and CBCT scans assessed. Additional kV, MV, helical CT and CBCT images of RO beads were obtained using an in-house phantom. Stability of RO bead position was assessed by comparing 4D-CT imaging to CT scans taken 6-20 days following TACE.ResultsEight patients were treated and 4D-CT and CBCT images acquired. RO beads were visible on 4D-CT and CBCT images in all cases and matching successfully performed. Differences in centre of mass of RO beads between CBCT and simulated radiotherapy planning scans (AVE-IP dataset) were 2.0 mm mediolaterally, 1.7 mm anteroposteriorally and 3.5 mm craniocaudally. RO beads in the phantom were visible on all imaging modalities assessed. RO bead position remained stable up to 29 days post TACE.ConclusionRO beads are visible on IGRT imaging modalities, showing minimal artefact. They can be used for on-set matching with CBCT and remain stable over time.Advances in knowledgeThe role of RO beads as fiducial markers for stereotactic liver radiotherapy is feasible and warrants further exploration as a combination therapy approach.
| S-EPMC8822567 | biostudies-literature
Project description:Transarterial chemoembolization has proven benefit in the treatment of unresectable hepatocellular carcinoma (HCC). Commonly reported symptoms following chemoembolization with or without drug-eluting beads include abdominal pain, nausea, and low-grade fever, which typically limited resolve within a few days. A recent study comparing traditional chemoembolization versus chemoembolization with drug-eluting beads demonstrated similar survival between the two techniques, but improved tolerability when the drug-eluting beads were used. This case report describes a patient with unresectable HCC undergoing chemoembolization with drug-eluting beads. The postprocedure course was complicated by interstitial pneumonitis secondary to shunting of the drug-eluting beads containing doxorubicin to both lungs via tumor vasculature. This case highlights the relationship between the number and size of the tumors to be treated, arteriovenous shunting within the liver/tumors, and the size of the embolization particles.
| S-EPMC3193323 | biostudies-other
Project description:Nontarget embolization is a relatively common cause of post-chemoembolization complications. Clinical presentation following nontarget embolization varies from minimal to fatal, and oftentimes relates to the vascular distribution embolized rather than the amount or type of embolic agent. Post-chemoembolization pancreatitis is an uncommon complication, but one that is known to occur. The following manuscript presents a case of post-chemoembolization pancreatitis, and suggests methods to decrease this complication as well as treatment once the complication occurs.
| S-EPMC4346048 | biostudies-other
Project description:PURPOSE:To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70-150 ?m or 100-300 ?m) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug). MATERIALS AND METHODS:Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of "imageable" DEBs was investigated ex vivo with micro-computed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining. RESULTS:MicroCT demonstrated that 70-150-?m DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (?300 ?m) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70-150-?m DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours. CONCLUSIONS:Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine.
| S-EPMC3360470 | biostudies-literature
Project description:Interventions: experimental group:detoxification and dispersal herbs combined with TACE ;control group:placebo (herb) combined with TACE
Primary outcome(s): PFS
Study Design: Parallel
| 2686364 | ecrin-mdr-crc
Project description:ObjectivesOur study sought to compare the overall survival in patients with hepatocellular carcinoma (HCC) and portal venous thrombosis (PVT), treated with either conventional trans-arterial chemoembolization (cTACE) or drug-eluting beads (DEB) TACE.MethodsThis retrospective analysis included a total of 133 patients, treated without cross-over and compared head-to-head by means or propensity score weighting. Mortality was compared using survival analysis upon propensity score weighting. Adverse events and liver toxicity grade ≥3 were recorded and reported for each TACE. In order to compare with historical sorafenib studies, a sub-group analysis was performed and included patients who fulfilled the SHARP inclusion criteria.ResultsThe median overall survival (MOS) of the entire cohort was 4.53 months (95 % CI, 3.63-6.03). MOS was similar across treatment arms, no significant difference between cTACE (N = 95) and DEB-TACE (N = 38) was observed (MOS of 5.0 vs. 3.33 months, respectively; p = 0.157). The most common adverse events after cTACE and DEB- TACE, respectively, were as follows: post-embolization syndrome [N = 57 (30.0 %) and N = 38 (61.3 %)], diarrhea [N = 3 (1.6 %) and N = 3 (4.8 %)], and encephalopathy [N = 11 (5.8 %) and N = 2 (3.2 %)].ConclusionOur retrospective study could not reveal a difference in toxicity and efficiency between cTACE and DEB-TACE for treatment of advanced stage HCC with PVT.Key points• Conventional TACE (cTACE) and drug-eluting-beads TACE (DEB-TACE) demonstrated equal safety profiles. • Survival rates after TACE are similar to patients treated with sorafenib. • Child-Pugh class and tumor burden are reliable predictors of survival.
| S-EPMC5470590 | biostudies-literature