Drug-eluting Bead Transarterial Chemoembolization Research Articles

Drug-eluting beads transarterial chemoembolization by CalliSpheres is effective and well tolerated in treating intrahepatic cholangiocarcinoma patients: A preliminary result from CTILC study.

This study aimed to investigate the efficacy and safety of drug-eluting beads (DEB) transarterial chemoembolization (TACE) treatment in Chinese intrahepatic cholangiocarcinoma (ICC) patients.37 ICC patients underwent DEB-TACE treatment in CTILC study (registered on clinicaltrials.gov with registry No. NCT03317483) were included in this present study. Treatment response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was calculated from the time of DEB-TACE operation until the date of death from any causes. Liver function change and adverse events (AEs) were recorded during and after DEB-TACE operation.3 (8.1%) patients achieved complete response (CR) and 22 (59.5%) patients achieved partial response (PR), with objective response rate (ORR) of 67.6%. After DEB-TACE treatment, mean OS was 376 days (95%CI: 341–412 days). Multivariate logistic regression analysis revealed that Bilobar disease (P = .040, OR: 0.105, 95% CI: 0.012–0.898) and portal vein invasion (P = .038, OR: 0.104, 95% CI: 0.012–0.881) could independently predict less possibility of ORR. Patients with ALB abnormal, TP abnormal, ALT abnormal and AST abnormal were increased at 1-week post DEB-TACE treatment (P = .034, P = .001, P < .001, P = .006, respectively), while returned to the levels at baseline after 1 to 3 months (all P > .050). Besides, most of the AEs were mild including pain, fever, vomiting, and nausea in this study.DEB-TACE was effective and well tolerated in treating ICC patients, and bilobar disease as well as portal vein invasion were independently correlated with less probability of ORR achievement.

Initial experience of drug-eluting bead transarterial chemoembolization with CalliSpheres® microspheres in treating liver metastases patients.

BackgroundTo evaluate the treatment efficacy, survival, safety profiles and factors affecting the clinical outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) in liver metastases patients.MethodsA total of 39 liver metastases patients underwent DEB-TACE treatment with the novel CalliSpheres® microspheres were retrospectively enrolled. Patients’ demographic information, tumor characteristics, history of treatment, laboratory indexes, and treatment procedures were recorded, meanwhile, patients’ treatment response survival and adverse events were also evaluated.ResultsThe rate of complete response, partial response, stable disease and progressive disease of total treated cycles were 1.6%, 34.4%, 54.7% and 9.4%, respectively, and 5.0%, 26.7%, 57.8% and 10.6% of total treated nodules, respectively. Regarding survival, the median progression-free survival (PFS) was 15.3 months (95% CI: 9.7–20.8 months) and the median overall survival was 28.7 months (95% CI: 20.3–37.0 months). Cox’s proportional hazard model regression analyses disclosed that previous liver resection was correlated with worse PFS, while combined targeted therapy and disease control rate after the first DEB-TACE were correlated with longer PFS. For safety profiles, biochemical indexes showed that patients’ liver function was deteriorated at 1 week after DEB-TACE, but was mainly recovered at 1 month after DEB-TACE.ConclusionsDEB-TACE is an efficient and safe treatment choice for liver metastases, moreover, strict screening of indications for resection and combined therapy with targeted therapy might improve the efficacy of DEB-TACE.

Doxorubicin-loaded polyphosphate glass microspheres for transarterial chemoembolization.

The standard of care for intermediate stage hepatocellular carcinoma is transarterial chemoembolization (TACE). Drug-eluting bead TACE (DEB-TACE) has emerged as a leading form of TACE, as it uses highly calibrated microspheres to deliver consistent embolization and controlled drug release to the tumor microenvironment. We report here on doxorubicin (DOX)-loaded polyphosphate glass microspheres (PGM) as a novel resorbable, radiopaque, preloaded DEB-TACE platform. Coacervate composed of polyphosphate chains complexed with Ba2+ , Ca2+ , and Cu2+ can be loaded with DOX prior to PGM synthesis, with PGM production achieved using a water-in-oil emulsion technique at room temperature yielding highly spherical particles in clinically relevant size fractions. In vitro, DOX release was found to be linear, pH dependent, and in accordance with Type II non-Fickian transport. PGM degradation was characterized by an initial burst release of degradation products over 7 days, followed by a plateau in mass loss at approximately 75% over a period of several weeks. in vitro studies indicate that PGM degradation products, namely Cu2+ , are cytotoxic and may interact with eluted DOX to impair its pharmacological activity. With additional compositional considerations, this approach may prove promising for DEB-TACE applications.

3:27 PM Abstract No. 301 Drug-eluting beads transcatheter arterial chemoembolization is effective and well-tolerated in hepatocellular carcinoma patients with portal vein tumor thrombus

The aim of this study was to investigate the efficacy and safety of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) and prognostic factors in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). 58 HCC patients with PVTT who received DEB-TACE treatment were included in this retrospective study, and the baseline characteristics were recorded. Treatment response was assessed at 4-6 weeks post treatment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST), Overall survival (OS) was calculated using the Kaplan–Meier method, and adverse events (AEs) were also recorded. Univariate and multivariate Cox regression analyses were used to evaluate the relevant clinical variables in predicting OS. The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh stage (HR = 2.279; 95% CI, 1.042–4.985, P = 0.039) and tumor burden (P = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. As to AEs, they were mainly transient elevated liver enzymes and postembolization syndrome, all of which were not severe. DEB-TACE is effective and well-tolerated in HCC patients with PVTT. The higher Child-Pugh stage and tumor burden are independent predictors for poorer OS.

Abstract No. 535 Drug-eluting bead transarterial chemoembolization versus conventional transarterial chemoembolization in colorectal liver metastasis: efficacy and safety and prognostic factors

To evaluate the efficacy, safety and prognostic factors of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) in the treatment of colorectal liver metastasis (CRLM). This study retrospectively analyzed 75 patients with CRLM who received DEB-TACE treatment (36 cases) or cTACE treatment (39 cases) between January 2016 and December 2017. Local control, survival outcome and complications were compared between the two groups. Univariate and multivariate analyses of prognostic factors affecting progression-free survival (PFS) and total survival (OS) were performed. The median duration of follow-up in the two groups was 10.49 months (range, 0.5-22). The median PFS and OS in DEB-TACE group were 10.0 months and 13.0 months, respectively, and in the cTACE group were 6.0 months and 8.5 months (P = 0.009 and 0.008). The 3-, 6- and 12-month survival rates in DEB-TACE group were 100.0%, 94.4%, and 55.6%, respectively. The survival rates in the cTACE group were 92.3%, 71.8%, and 35.9%, respectively. There was no statistically significant difference in the 3-month survival rate (P = 0.083), but significant statistical difference in the 6-month and 12-month survival rates (P = 0.008 and 0.030). Univariate and multivariate survival analyses showed that different treatment methods, tumor size and tumor number were important prognostic factors for PFS and OS. DEB-TACE has advantages over cTACE in prolonging PFS and OS in CRLM patients. Different treatment methods, tumor number and tumor size are important prognostic factors affecting PFS and OS. However, further randomized, multicenter and prospective trials are still needed to confirm the results of this study.Tabled 1Local tumor control and survival of two treatment cohorts.ParameterDEB-TACE (N=36)cTACE (N=39)Z, χ2or t valuePmRECIST (%)Z = 8.8160.032 CR16.7 (6/36)12.8 (5/39) PR41.7 (15/36)15.4 (6/39) SD25.0 (9/36)30.8 (12/39) PD16.7 (6/36)41.0 (16/39)Response rate (%)83.3 (30/36)59.0 (23/39)χ2 = 5.5390.025PFS (months)χ2 = 6.8970.009 Median10.06.0 IQR6.0-14.02.0-10.0OS (months)χ2 = 7.1280.008 Median13.08.5 IQR9.0-16.05.0-12.5OS rate (%) 3 months100.0 (36/36)92.3 (36/39)t = 1.7800.083 6 months94.4 (34/36)71.8 (28/39)t = 2.7410.008 12 months55.6 (20/36)35.9 (14/39)t = 2.2140.030 Open table in a new tab

3:00 PM Abstract No. 146 ■ FEATURED ABSTRACT Efficacy and safety of bronchial arterial infusion chemotherapy plus drug-eluting bead transarterial chemoembolization in treating advanced lung cancer patients: a pilot study

3:00 PM Abstract No. 146 ■ FEATURED ABSTRACT Efficacy and safety of bronchial arterial infusion chemotherapy plus drug-eluting bead transarterial chemoembolization in treating advanced lung cancer patients: a pilot study

Abstract No. 391 Frailty is predictive of complications after transarterial chemoembolization

To determine the association between frailty, 30-day complications and 1-year mortality following conventional and drug-eluting bead transarterial chemoembolization. A retrospective analysis was performed on a cohort of 125 adult patients with previously untreated hepatocellular carcinoma who underwent first time conventional TACE (cTACE) or drug-eluting beads (DEB-TACE) at our institution between 2014 and 2015. Liver function parameters, tumor stage, and all components of the Modified Frailty Index (mFI) were used to determine frailty status for each patient. Severe adverse events (SAEs) that occurred within 30 days of TACE were classified according to NCI-CTCAE v5.0. The primary outcomes were SAEs (grade 3 or above) and 1-year mortality. Univariate analysis was performed on conventional predictors of mortality and postoperative complications after TACE. Covariates were then incorporated into a multivariate model based on a statistically significant univariate relationship. Univariate logistic regression demonstrated that frailty and the use of cTACE over DEB-TACE predicted SAEs at 30 days (P <0.03, P <0.01 respectively). Subsequent multivariate analysis showed that frailty independently predicted 30-day severe AEs (P <0.02). Specifically, a 1-unit increase in mFI conferred a 60% increase in the risk of having a postoperative SAE. While higher MELD, BCLC and Child Pugh Class were predictive of higher mortality, there was no significant association between frailty and 1-year mortality in this dataset. Increasing frailty is an independent predictor of SAEs but not 1-year mortality following TACE.

4:12 PM Abstract No. 306 Survival benefits of drug-eluting bead transarterial chemoembolization in Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma patients

4:12 PM Abstract No. 306 Survival benefits of drug-eluting bead transarterial chemoembolization in Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma patients

Abstract No. 551 Effectiveness of drug-eluting bead transarterial chemoembolization and transarterial radioembolization for patients with large hepatocellular carcinoma

To evaluate the clinical outcomes of drug-eluting bead transarterial chemoembolization (DEB–TACE) and transarterial radioembolization (TARE) for patients with BCLC intermediate stage large hepatocellular carcinoma (HCC). A retrospective analysis of patients who underwent DEB–TACE or TARE for BCLC intermediate stage large HCC (> 5 cm) was conducted at a single academic medical center from January 2016 to December 2018. Mann–Whitney test and Fisher’s exact test were used to compare groups. Kaplan-Meier and Cox regression were performed to assess overall survival (OS) and time to progression (TTP). During a median follow-up period of 11.2 months (range, 1.3-56.7 months), 17 and 27 patients were treated with DEB–TACE and TARE, respectively. Both groups had similar background variables. Objective tumor response rate was higher for TARE (81.5%) than for DEB–TACE (41.2%; P < 0.05). The median TTP of DEB–TACE and TARE was 9 months and 10.5 months (P = 0.96), respectively. The 1-, 2-, and 3-year OS were 71.4%, 35.7%, and 35.7% for DEB–TACE and 80.7%, 60.5%, and 60.5% for TARE (P = 0.4). There were more patients succeeded to obtain downstaging within Milan criteria for TARE (25.9%) than for DEB–TACE (17.7%; P = 0.72). With regression analysis, the tumor size was an independent prognostic factor for OS (P < 0.01) and TTP (P < 0.05). Compared to DEB–TACE, TARE has better tumor response rate for intermediate stage large HCC. However, there is no significant difference in tumor downstaging rate, TTP and OS between these techniques.

Nivolumab (NIVO) and drug eluting bead transarterial chemoembolization (deb-TACE): Preliminary results from a phase I study of patients (pts) with liver limited hepatocellular carcinoma (HCC).

525 Background: Regional therapies in HCC impact the immune microenvironment and may augment the effects of immune checkpoint inhibitors. Methods: This is a multicenter phase 1 study of NIVO and deb-TACE in unresectable HCC pts (BCLC Stage B) and Child Pugh A cirrhosis (NCT03143270). The primary objective is to assess safety. Secondary objectives include response rate by RECIST v1.1, progression-free and overall survival by Kaplan-Meier methodology, and blood/tumor immune correlates. A 3 + 3 design sequentially evaluates 3 cohorts of differing schedules of NIVO relative to deb-TACE. Deb-TACE (75mg of doxorubicin) is administered on Day 0. NIVO is dosed at 240mg IV every 14 days for 1 year (Cohort 1: NIVO begins day +14 after deb-TACE; Cohort 2, interrupted NIVO dosing begins at Day -28 but is held on the Day 0 then restarted on Day +14; Cohort 3, continuous NIVO dosing begins on Day -28 without interruption). Results: As of July 2019, 9 pts have been treated [median 65 years (range: 54-76), male (89%), viral (44%;1 HBV, 3 HCV), non-viral (56%;2 EtOH, 1 NASH, 2 unknown), prior resection (44%), prior regional therapy (44%), 3 pts in each cohort]. No cases of treatment related liver failure, dose-limiting toxicity, or Grade 5 adverse events (AEs) were observed. Grade ≥3 AEs possibly related to nivolumab, deb-TACE, or both included: transaminase elevation (1 pt: day 1 post TACE resolved in 7 days without treatment; 2 pts: ≥30 days post TACE resolved with steroids between 20-41 days), post-embolization syndrome (1 pt: resolved in 5 days), asymptomatic lipase increase (1 pt: resolved in 14 days), post-procedural groin hematoma (1 pt: resolved in 2 days). All 9 pts were evaluable for efficacy: 2 (22%) confirmed PR and 7 (78%) SD. 4/9 pts remain on study with SD or better—2 pts continue &gt; 18 months post embolization with durable PRs. 12 months OS rate was 71%. Ongoing correlates will be presented at a separate meeting. Conclusions: Nivolumab given at various times relative to deb-TACE appears safe and tolerable. Cohort 3 continues to accrue to provide a better estimate of safety and antitumor activity of the combination. Clinical trial information: NCT03143270.

Imaging response predictors following drug eluting beads chemoembolization in the neoadjuvant liver transplant treatment of hepatocellular carcinoma.

BACKGROUNDDrug-eluting bead transarterial chemoembolization (DEB-TACE) is an endovascular treatment to release chemotherapeutic agents within a target lesion, minimizing systemic exposure and adverse effects to chemotherapeutics. Therefore, identifying which patient characteristics may predict imaging response to DEB-TACE can improve treatment results while selecting the best candidates. Predictors of the response after DEB-TACE still have not been fully elucidated. This is the first prospective study performed with standardized DEB-TACE technique that aim to identify predictors of radiological response, assessing patients clinical and laboratory characteristics, diagnostic imaging and intraprocedure data of the hepatocellular carcinoma treated in the neoadjuvant context for liver transplantation.AIMTo identify pre- and intraoperative clinical and imaging predictors of the radiological response of drug-eluting bead transarterial chemoembolization (DEB-TACE) for the neoadjuvant treatment of hepatocellular carcinoma (HCC).METHODSThis is prospective, cohort study, performed in a single transplant center, from 2011 to 2014. Consecutive patients with HCC considered for liver transplant who underwent DEB-TACE in the first session for downstaging or bridging purposes were recruited. Pre and post-chemoembolization imaging studies were performed by computed tomography or magnetic resonance. The radiological response of each individual HCC was evaluated by objective response using mRECIST and the percentage of necrosis.RESULTSTwo hundred patients with 380 HCCs were examined. Analysis of the objective response (nodule-based analysis) demonstrated that HCC with pseudocapsules had a 2.01 times greater chance of being responders than those without pseudocapsules (P = 0.01), and the addition of every 1mg of chemoembolic agent increased the chance of therapeutic response in 4% (P < 0.001). Analysis of the percentage of necrosis through multiple linear regression revealed that the addition of each 1mg of the chemoembolic agent caused an average increase of 0.65% (P < 0.001) in necrosis in the treated lesion, whereas the hepatocellular carcinoma with pseudocapsules presented 18.27% (P < 0.001) increased necrosis compared to those without pseudocapsules.CONCLUSIONThe presence of a pseudocapsule and the addition of the amount of chemoembolic agent increases the chance of an objective response in hepatocellular carcinoma and increases the percentage of tumor necrosis following drug-eluting bead chemoembolization in the neoadjuvant treatment, prior to liver transplantation.

Efficacy and safety of drug-eluting bead-transcatheter arterial chemoembolization using 100-300 μm versus 300-500 μm CalliSpheres microspheres in patients with advanced-stage hepatocellular carcinoma.

To evaluate the efficacy and safety of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) using 100-300 μm versus 300-500 μm CalliSpheres microspheres (CSMs) for treating multiple hepatocellular carcinoma (HCC) with the largest nodule measuring between 5 and 10 cm. Eighty-one advanced-stage HCC patients treated by DEB-TACE between January 2017 and March 2020 were retrospectively analyzed. There were 48 patients in the 100-300 μm group and 33 patients in the 300-500 μm group. Treatment response, liver function tests, and complications were compared between the two groups. At 6 months, the response rates in the 100-300 μm group were higher than those in the 300-500 μm group (P < 0.05). Disease control rates in the 100-300 μm group were higher than those in the 300-500 μm group at 1, 3, and 6 months (P < 0.05). Progression-free survival (PFS) and overall survival (OS) were longer in the 100-300 μm group (P < 0.05). Visual analog score points were higher in the 300-500 μm group (P < 0.05). There were no significant differences in complications between the two groups. The use of small-diameter CSMs in multiple HCC with the largest nodule size of 5-10 cm provides better treatment response and longer PFS and OS for treating advanced-stage HCC.

Drug-eluting beads transarterial chemoembolization with CalliSpheres microspheres for treatment of unresectable intrahepatic cholangiocarcinoma.

Objective: This study aimed to evaluate the efficacy and safety of doxorubicin-loaded drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres (CSM) in treating unresectable intrahepatic cholangiocarcinoma (ICC).Methods: 88 unresectable ICC patients who received DEB-TACE treatment with CSM were retrospectively enrolled in this study. Information about treatment response, survival and adverse events were collected. The Kaplan-Meier curve was used to evaluate progression-free survival (PFS) and overall survival (OS), and factors affecting OS were determined by Cox's proportional hazards regression model.Results: Tumor response of the whole sample of 88 patients was partial response (PR) in 58 (65.9%) patients, stable disease (SD) in 19 (21.6%) and progressive disease (PD) in 11 (12.5%) at one month after therapy, with no complete responses (CR). The median PFS and OS were 3.0 months and 9.0 months respectively. Cox's proportional hazards regression analysis disclosed that subsequent treatment was an independent favorable prognostic factor, while cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastasis were the three prognostic factors associated with poor survival in ICC patients. Besides, common adverse events included nausea/vomiting, abdominal pain and transient elevation of liver transaminase in patients treated by DEB-TACE with CSM.Conclusion: DEB-TACE with CSM is safe and well-tolerated for unresectable ICC patients, with a low complication rate and a relative benefit in terms of survival. Subsequent treatments including systemic/loco-regional treatments is an independent favorable prognostic factor, but cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastases are the three prognostic factors associated with poor survival.

Comparison of transcatheter arterial chemoembolization combined with radiofrequency ablation or microwave ablation for the treatment of unresectable hepatocellular carcinoma: a systemic review and meta-analysis

Background Transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), and microwave ablation (MWA) are regarded as effective therapies for treating unresectable hepatocellular carcinoma (HCC). We conducted this study to compare the efficiency and safety of TACE combined with RFA (TR group) or MWA (TM group). Method PubMed, the Cochrane Library, Ovid Medline, Web of Science, Scopus, Embase, ScienceDirect, and Google Scholar were searched. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rates, and complications. Result Eight cohort studies and one randomized controlled trial were included. The TM group had better OS (Hazard ratio [HR]: 1.55; 95% confidence interval [CI]: 1.09–2.21, p = 0.01) and a better 2- and 3-year OS rate, 24-month PFS rate (Risk ratio [RR]: 0.67; 95% CI: 0.46–0.96, p = 0.03), and complete response rate (RR: 0.87; 95% CI: 0.79–0.96, p = 0.003) than the TR group. Furthermore, the TM and TR groups did not show significant differences in PFS, the disease control rate or complications. The advantage of TM was mainly reflected in younger patients (50–60 years old) compared with patients aged 60–70 years, as well as in patients with larger tumors (≥3 cm) compared with patients with tumors <3 cm. Moreover, patients treated with conventional TACE (cTACE) in the TM group showed longer OS, while patients treated with drug-eluting bead transarterial chemoembolization (DEB-TACE) in the TR group showed a higher overall response rate. Conclusion TM seems to be a more effective therapy than TR for unresectable HCC, with better survival and similar safety.

Superselective arterial embolization with drug-loaded microspheres for the treatment of unresectable breast cancer.

To investigate the short-term efficacy and safety of drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) using CalliSpheres® microspheres in the treatment of unresectable locally advanced breast cancer (LABC). DEB-TACE using CSM was performed in 15 patients with LABC after failure of medical treatment. The efficacy was evaluated based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The postoperative adverse reactions and complications were analyzed. The changes of white blood cell (WBC) count, creatine kinase isoenzyme-MB (CK-MB), B-type natriuretic peptide (BNP), and carbohydrate antigen15-3 (CA15-3) before and after treatment were compared by using Wilcoxon signed-rank test. The surgeries were successful in all patients. The subjects were followed up for 2-60 months (median: 10 months). According to the mRECIST, no patient achieved complete remission (CR) 1, 3, and 5 months after surgery, and partial response (PR) was achieved in 9, 11, and 11 cases; also, there were 6, 4, and 2 stable disease (SD) cases, and 0, 0, and 2 progressive disease (PD) cases. The postoperative WBC count, CK-MB level, and BNP level were not significantly different from those before surgery, whereas the CA15-3 level significantly decreased. The main postoperative adverse reactions were pain, fever, and gastrointestinal reactions. No severe adverse reactions were observed. DEB-TACE with CalliSpheres® microspheres is a safe and feasible treatment for LABC. However, more multi-center studies with larger sample sizes are still warranted.

Conventional versus drug-eluting beads chemoembolization for infiltrative hepatocellular carcinoma: a comparison of efficacy and safety

BackgroundTo compare the efficacy and safety between conventional transarterial chemoembolization (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with infiltrative hepatocellular carcinoma (iHCC).MethodsA total of 89 iHCC patients who were treated with either cTACE (n = 33) or DEB-TACE (n = 56) between April 2013 and September 2017 were included in this retrospective study. Patients with the situations that might have a poor outcome were defined as advanced disease including Child-Pugh class B, bilobar lesions, tumor size greater than 10 cm, ECOG 1–2, tumor burden of 50–70%, and the presence of ascites, arterioportal shunt (APS), and portal venous tumor thrombus (PVTT). The tumor response was measured 1-month and 3-month after the procedure. Progression-free survival (PFS) was calculated. Toxicity was graded by Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The differences in tumor response, PFS, and toxicity were compared between the DEB-TACE group and cTACE group.ResultsAt 1-month and 3-month after the procedure, the objective response rate (ORR) in the overall study population was similar in DEB-TACE group and cTACE group. The disease control rate (DCR), at 1-month after the procedure, was significantly higher in the patients treated with DEB-TACE relative to those treated with cTACE (P = 0.034), while after 3 months, the difference did not differ between two groups. DEB-TACE showed a higher DCR than cTACE in patients with tumor size greater than 10 cm (P = 0.036) or associated with APS (P = 0.030) at 1-month after the procedure, while after 3 months, the difference was only noted in patients with APS (P = 0.036). The median PFS in DEB-TACE group was 96 days, while in cTACE group was 94 days, and there was no difference in PFS between two groups (P = 0.831). In the side effect analysis, abdominal pain (P = 0.034) and fever (P = 0.009) were more frequently present in the cTACE group than DEB-TACE group, but there was no difference in high grade liver toxicity between the two groups.ConclusionsCompared to cTACE, DEB-TACE offers slightly better DCR and tolerability for iHCC patients, particularly in patients associated with APS and large tumor size. However, DEB-TACE does not provide higher PFS than cTACE.

Transarterial chemoembolization for hepatocellular carcinoma: quality of life, tumour response, safety and survival comparing two types of drug-eluting beads.

To compare two different types of drug-eluting microspheres with regard to impact on HRQoL after first TACE, tumour response, peri-procedural complications, adverse events and 1-year survival in patients suffering from unresectable hepatocellular carcinoma (HCC). HRQoL was prospectively assessed with validated questionnaires (EORTC QLQ-C30 and -HCC18) before and 2weeks after treatment with their first drug-eluting beads (DEB-)TACE with either acrylamido-polyvinylalcohol-AMPS hydrogel microspheres (groupDCB; 20 patients) or polyvinyl alcohol-co-acrylic acid microspheres (groupHS; 16 patients). Baseline characteristics, peri-procedural complications, treatment-related adverse events and 1-year survival were compared between both types of microspheres. Treatment response and objective response rates (ORR) were analysed using established tumour response criteria. Subgroup analysis for pooled groups with small (groupSMALL; 21 patients) versus large particles (groupLARGE; 15 patients) was performed. At baseline, there were no significant differences between the treated microsphere groups. No significant differences were found in absolute HRQoL changes after first DEB-TACE between the different types of microspheres. Response rates and survival were comparable between the investigated microsphere groups. For groupSMALL, we found a significant difference in post-interventional deterioration of physical function (- 19.4%) compared to groupLARGE (- 8%; p = 0.025). Tumour response and ORR according to mRECIST were significantly higher in groupSMALL (p = 0.008; p = 0.009). DEB-TACE is generally well tolerated and effective, with comparable changes in HRQoL for both types of drug-eluting microspheres. Tumour response is better with small microspheres. A relevant deterioration of physical function underlines that an aggressive TACE using small beads should be well deliberated.

In vitro evaluation of doxorubicin-eluting porous titania microspheres for transcatheter arterial chemoembolization

ABSTRACTPreparing drug-eluting beads (DEBs) from radiopaque materials such as titania (TiO2) can meet clinical need for directly visualizing DEBs during drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE). Porous anatase-type TiO2 microspheres with mean volume diameters of approximately 30 µm were obtained when silica nanoparticles (SiNPs) were introduced into the TiO2 matrix by a sol–gel process involving a water-in-oil emulsion, and the SiNPs were then dissolved by subsequent treatment with NaOH solution. Of special note, microspheres prepared using SiNPs of approximately 20 – 25 nm in diameter had a high specific surface area of ~120 m2·g−1 and a high doxorubicin (DOX)-adsorption capacity of ~150 mg·mL−1, and they gradually released ~10% of the adsorbed DOX within 5 days. The DOX-loaded microspheres were non-cytotoxic, moreover, and exerted anticancer effects on HeLa cells. We propose that the present TiO2 microspheres are potentially useful as novel radiopaque embolic materials for DEB-TACE.

Quantification of Functional MR Predicts Early Response in Post-doxorubicin Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma.

The purpose of this study was to assess the value of functional MRI (fMRI) of post-doxorubicin drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) as an early imaging biomarker of response to therapy. This prospective analysis included 21 consecutive patients undergoing fMRI before and after DEB-TACE at a single medical center from January 2013 to December 2014. Functional MRI, including relative changes in apparent diffusion coefficient (ADC) and choline levels measured at hydrogen-1 magnetic resonance spectroscopy (MRS) of treated lesions, was recorded at baseline before DEB-TACE, and at 1, 2, and 4weeks after DEB-TACE therapy. Assessment of tumor response was based on dynamic contrast-enhanced computer tomography imaging response according to modified response evaluation criteria in solid tumors. At post-therapy, 76% (n = 16) of patients demonstrated objective tumor response, 10% (n = 2) had stable disease, and 3 (14%) had progressive disease. Stable disease and progressive disease were designated as non-response. At week 2, the mean change in ADC value of responsive tumors was 0.35 ± 0.24mm2/s, which was greater than that of non-response tumors (mean 0.01 ± 0.13 × 10-3mm2/s) (P = 0.006). Significant differences were found in mean choline/water ratio between responsive (7.8 ± 4.9 × 10-3) and non-responsive (17.2 ± 4.9 × 10-3) tumors (P = 0.005). Composite scores of choline/water ratio and relative change of ADC showed significantly better diagnostic accuracy in non-responsive tumors than responsive tumors (area under the curve = 1.0; P < 0.001). Combined DWI and MRS may be used as an early imaging biomarker of therapy response in HCC patients after chemoembolization therapy.

Long-term outcomes of hepatocellular carcinoma that underwent chemoembolization for bridging or downstaging.

BACKGROUNDProspective study of 200 patients with hepatocellular carcinoma (HCC) that underwent liver transplant (LT) after drug-eluting beads transarterial chemoembolization (DEB-TACE) for downstaging versus bridging. Overall survival and tumor recurrence rates were calculated, eligibility for LT, time on the waiting list and radiological response were compared. After TACE, only patients within Milan Criteria (MC) were transplanted. More patients underwent LT in bridging group. Five-year post-transplant overall survival, recurrence-free survival has no difference between the groups. Complete response was observed more frequently in bridging group. Patients in DS group can achieve post-transplant survival and HCC recurrence-free probability, at five years, just like patients within MC in patients undergoing DEB-TACE.AIMTo determine long-term outcomes of patients with HCC that underwent LT after DEB-TACE for downstaging vs bridging.METHODSProspective cohort study of 200 patients included from April 2011 through June 2014. Bridging group included patients within MC. Downstaging group (out of MC) was divided in 5 subgroups (G1 to G5). Total tumor diameter was ≤ 8 cm for G1, 2, 3, 4 (n = 42) and was > 8 cm for G5 (n = 22). Downstaging (n = 64) and bridging (n = 136) populations were not significantly different. Overall survival and tumor recurrence rates were calculated by the Kaplan-Meier method. Additionally, eligibility for LT, time on the waiting list until LT and radiological response were compared.RESULTSAfter TACE, only patients within MC were transplanted. More patients underwent LT in bridging group 65.9% (P = 0.001). Downstaging population presented: higher number of nodules 2.81 (P = 0.001); larger total tumor diameter 8.09 (P = 0.001); multifocal HCC 78% (P = 0.001); more post-transplantation recurrence 25% (P = 0.02). Patients with maximal tumor diameter up to 7.05 cm were more likely to receive LT (P = 0.005). Median time on the waiting list was significantly longer in downstaging group 10.6 mo (P = 0.028). Five-year post-transplant overall survival was 73.5% in downstaging and 72.3% bridging groups (P = 0.31), and recurrence-free survival was 62.1% in downstaging and 74.8% bridging groups (P = 0.93). Radiological response: complete response was observed more frequently in bridging group (P = 0.004).CONCLUSIONTumors initially exceeding the MC down-staged after DEB-TACE, can achieve post-transplant survival and HCC recurrence-free probability, at five years, just like patients within MC in patients undergoing DEB-TACE.