Drug-eluting Embolic Chemoembolization Research Articles

Combination of Bronchial Arterial Infusion Chemotherapy plus Drug-Eluting Embolic Transarterial Chemoembolization for Treatment of Advanced Lung Cancer—A Retrospective Analysis of 23 Patients

PurposeTo determine the efficacy and safety of the combination of bronchial arterial infusion (BAI) chemotherapy and transarterial chemoembolization with the use of drug-eluting embolic (DEE) particles in the treatment of unresectable advanced lung cancer. Materials and MethodsA retrospective review was performed of 23 patients with unresectable lung cancer (stage III/IV) who received BAI chemotherapy and DEE chemoembolization. Treatment response was assessed by enhanced CT and evaluated on the basis of Response Evaluation Criteria In Solid Tumors at 30 d after the last combination treatment. Patients were followed up until death or March 15, 2020, whichever was first. Overall survival (OS) was estimated by Kaplan–Meier analysis, and factors associated with OS were evaluated by Cox proportional-hazards test. ResultsComplete response, partial response, stable disease, and progressive disease were seen in 2, 16, 5, and 0 patients at 30 d after the last combination treatment, respectively; therefore, the overall response rate was 78.3% and the disease control rate was 100%. Preprocedure symptoms (hemoptysis in 7 patients and dyspnea in 10) resolved in all cases after combination therapy. Nineteen patients died during follow-up, and 4 survived. Median OS was 15.6 mo (95% confidence interval, 10.1–21.1 mo). On univariate analysis and multivariate analysis, tumor/node/metastasis staging was an independent risk factor for prognosis. There were no serious adverse events during the procedures. ConclusionsThe combination of BAI chemotherapy plus DEE chemoembolization appears to be a promising method for treatment of advanced lung cancer.

Idarubicin-Loaded ONCOZENE Drug-Eluting Bead Chemoembolization in a Rabbit Liver Tumor Model: Investigating Safety, Therapeutic Efficacy, and Effects on Tumor Microenvironment

PurposeTo investigate toxicity, efficacy, and microenvironmental effects of idarubicin-loaded 40-μm and 100-μm drug-eluting embolic (DEE) transarterial chemoembolization in a rabbit liver tumor model. Materials and MethodsTwelve male New Zealand White rabbits with orthotopically implanted VX2 liver tumors were assigned to DEE chemoembolization with 40-μm (n = 5) or 100-μm (n = 4) ONCOZENE microspheres or no treatment (control; n = 3). At 24–72 hours postprocedurally, multiparametric magnetic resonance (MR) imaging including dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI), and biosensor imaging of redundant deviation in shifts (BIRDS) was performed to assess extracellular pH (pHe), followed by immediate euthanasia. Laboratory parameters and histopathologic ex vivo analysis included fluorescence confocal microscopy and immunohistochemistry. ResultsDCE MR imaging demonstrated a similar degree of devascularization of embolized tumors for both microsphere sizes (mean arterial enhancement, 8% ± 12 vs 36% ± 51 in controls; P = .07). Similarly, DWI showed postprocedural increases in diffusion across the entire lesion (apparent diffusion coefficient, 1.89 × 10−3 mm2/s ± 0.18 vs 2.34 × 10−3 mm2/s ± 0.18 in liver; P = .002). BIRDS demonstrated profound tumor acidosis at baseline (mean pHe, 6.79 ± 0.08 in tumor vs 7.13 ± 0.08 in liver; P = .02) and after chemoembolization (6.8 ± 0.06 in tumor vs 7.1 ± 0.04 in liver; P = .007). Laboratory and ex vivo analyses showed central tumor core penetration and greater increase in liver enzymes for 40-μm vs 100-μm microspheres. Inhibition of cell proliferation, intratumoral hypoxia, and limited idarubicin elution were equally observed with both sphere sizes. ConclusionsNoninvasive multiparametric MR imaging visualized chemoembolic effects in tumor and tumor microenvironment following DEE chemoembolization. Devascularization, increased hypoxia, coagulative necrosis, tumor acidosis, and limited idarubicin elution suggest ischemia as the predominant therapeutic mechanism. Substantial size-dependent differences indicate greater toxicity with the smaller microsphere diameter.

Comparison of Opioid Medication Use after Conventional Chemoembolization versus Drug-Eluting Embolic Chemoembolization

PurposeTo assess the use of opioid analgesics and/or antiemetic drugs for pain and nausea following selective chemoembolization with doxorubicin-based conventional (c)-transarterial chemoembolization versus drug-eluting embolic (DEE)-transarterial chemoembolization for hepatocellular carcinoma (HCC). Materials and MethodsFrom October 2014 to 2016, 283 patients underwent 393 selective chemoembolization procedures including 188 patients (48%) who underwent c-transarterial chemoembolization and 205 (52%) who underwent DEE-transarterial chemoembolization. Medical records for all patients were retrospectively reviewed. Administration of postprocedural opioid and/or antiemetic agents were collated. Time of administration was stratified as phase 1 recovery (0–6 hours) and observation (6–24 hours). Logistic regression model was used to investigate the relationship of transarterial chemoembolization type and use of intravenous and/or oral analgesic and antiemetic medications while controlling for other clinical variables. ResultsMore patients treated with DEE-transarterial chemoembolization required intravenous analgesia in the observation (6–24 hours) phase (18.5%) than those treated with c-transarterial chemoembolization (10.6%; P = .033). Similar results were noted for oral analgesic agents (50.2% vs. 31.4%, respectively; P < .001) and antiemetics (17.1% vs. 7.5%, respectively; P = .006) during the observation period. Multivariate regression models identified DEE-transarterial chemoembolization as an independent predictor for oral analgesia (odds ratio [OR], 1.84; P = .011), for intravenous and oral analgesia in opioid-naïve patients (OR, 2.46; P = .029) and for antiemetics (OR, 2.56; P = .011). ConclusionsCompared to c-transarterial chemoembolization, DEE-transarterial chemoembolization required greater amounts of opioid analgesic and antiemetic agents 6–24 hours after the procedure. Surgical data indicate that a persistent opioid habit can develop even after minor surgeries, therefore, caution should be exercised, and a regimen of nonopiate pain medications should be considered to reduce postprocedural pain after transarterial chemoembolization.

The development of early ascites is associated with shorter overall survival in patients with hepatocellular carcinoma treated with drug-eluting embolic chemoembolization

BackgroundA single-centre cohort study was performed to identify the independent factors associated with the overall survival (OS) of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization with drug-eluting beads (DEB-TACE).MethodsA total of 216 HCC patients who underwent DEB-TACE from October 2008 to October 2015 at a tertiary hospital were consecutively recruited. The analysis of prognostic factors associated with overall survival after DEB-TACE, stressing the role of post-TACE events, was performed.ResultsThe objective response (OR) rate (Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria) to the first DEB-TACE (DEB-TACE-1) was 70.3%; the median OS from DEB-TACE-1 was 27 months (95% confidence interval (CI), 24–30). In the multivariate analysis, tumor size, AFP < 100 ng/mL and serum alkaline phosphatase were independent factors for survival following DEB-TACE-1. The most important clinical event associated with poor survival was the development of early ascites after DEB-TACE-1 (median OS, 17 months), which was closely related to the history of ascites, albumin and hemoglobin but not to tumour load or to response to therapy.ConclusionsEarly ascites post-DEB-TACE is associated with the survival of patients despite adequate liver function and the use of a supra-selective technical approach. History of ascites, albumin and hemoglobin are major determinants of the development of early ascites post-DEB-TACE.

Transarterial Chemoembolization in a Woodchuck Model of Hepatocellular Carcinoma

PurposeTo assess the feasibility of transarterial chemoembolization with drug-eluting embolic (DEE) microspheres in a woodchuck model of hepatocellular carcinoma (HCC). Materials and MethodsNine woodchucks were studied: 4 normal animals and 5 animals infected with woodchuck hepatitis virus in which HCC had developed. Three animals with HCC underwent multidetector CT. A 3-F sheath was introduced into the femoral artery, and the hepatic arteries were selectively catheterized with 2.0–2.4-F microcatheters. Normal animals underwent diagnostic angiography and bland embolization. Animals with HCC underwent DEE transarterial chemoembolization with 70–150-μm radiopaque microspheres loaded with 37.5 mg doxorubicin per milliliter. Cone-beam CT and multidetector CT were performed. Following euthanasia, explanted livers underwent micro-CT, histopathologic examination, and fluorescence imaging of doxorubicin. ResultsThe tumors were hypervascular and supplied by large-caliber tortuous vessels, with arteriovenous shunts present in 2 animals. There was heterogeneous enhancement on multidetector CT with areas of necrosis. Six tumors were identified. The most common location was the right medial lobe (n = 3). Mean tumor volume was 30.7 cm3 ± 12.3. DEE chemoembolization of tumors was achieved. Excluding the 2 animals with arteriovenous shunts, the mean volume of DEE microspheres injected was 0.49 mL ± 0.17. Fluorescence imaging showed diffusion of doxorubicin from the DEE microspheres into the tumor. ConclusionsWoodchuck HCC shares imaging appearances and biologic characteristics with human HCC. Selective catheterization and DEE chemoembolization may similarly be performed. Woodchucks may be used to model interventional therapies and possibly characterize radiologic–pathologic correlations.

A Predictive Model for Postembolization Syndrome after Transarterial Hepatic Chemoembolization of Hepatocellular Carcinoma.

Purpose To develop and validate a predictive model for postembolization syndrome (PES) following transarterial hepatic chemoembolization (TACE) for hepatocellular carcinoma. Materials and Methods In this single-center, retrospective study, 370 patients underwent 513 TACE procedures between October 2014 and September 2016. Seventy percent of the patients were randomly assigned to a training data set and the remaining 30% were assigned to a testing data set. Variables included demographic, laboratory, clinical, and procedural details. PES was defined as pain and/or nausea beyond 6 hours after TACE that required intravenous medication for symptom control. The predictive model was developed by using conditional inference trees and Lasso regression. Results Demographics, laboratory data, performance, tumor characteristics, and procedural details were statistically similar for the training and testing data sets. Overall, 83 of 370 patients (22.4%) after 107 of 513 TACE procedures (20.8%) met the predefined criteria. Factors identified at univariable analysis included large tumor burden (P = .004), drug-eluting embolic TACE (P = .03), doxorubicin dose (P = .003), history of PES (P < .001) and chronic pain (P < .001), of which history of PES, tumor burden, and drug-eluting embolic TACE were identified as the strongest predictors by the multivariable analysis and were used to develop the predictive model. When applied to the testing data set, the model demonstrated an area under the curve of 0.62, sensitivity of 79% (22 of 28), specificity of 44.2% (53 of 120), and a negative predictive value of 90% (53 of 59). Conclusion The model identified history of postembolization syndrome, tumor burden, and drug-eluting embolic chemoembolization as predictors of protracted recovery because of postembolization syndrome. © RSNA, 2018.

ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma.

Treatment outcome for hepatocellular carcinoma (HCC) is related to tumor burden and liver function. Grading systems assessing liver function need validation in different clinical settings. To evaluate drug-eluting embolic transarterial chemoembolization (DEE-TACE) in Child-Pugh A HCC with respect to albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (P-ALBI) grade. Forty-nine patients with Child-Pugh class A, diagnosed with HCC and allocated to DEE-TACE treatment, were retrospectively analyzed regarding tumor and treatment characteristics, radiological response (mRECIST) one month post treatment, overall survival (OS), and adverse events (AEs; CTCAE, grades ≥3) with respect to ALBI and P-ALBI grade. There were 21 ALBI 1 patients, 29 P-ALBI 1 patients, and 19 patients were both ALBI and P-ALBI 1. Objective response rate was 74% with no statistically significant difference for ALBI (1 vs. 2; P = 0.08), or P-ALBI (1 vs. 2; P = 0.49). OS was 14.8 months (range = 1.7-62.0; ALBI 1 vs. 2: P = 0.08; P-ALBI 1 vs. 2: P = 0.003). OS in responders with ALBI 1 and 2 was 28.9 vs.10.2 months ( P = 0.02), and P-ALBI 1 and 2 was 26.7 vs. 8.6 months ( P < 0.001). In multivariate analyses, both ALBI 2 (HR = 2.4, P = 0.02) and P-ALBI 2 (HR = 3.3, P < 0.01) were negative prognostic factors for survival. There were 15 AEs in 13 patients, with hepatic failure only occurring in ALBI 2 and P-ALBI 2 patients. P-ALBI grade 1 and 2 differentiated survival in Child-Pugh A patients treated with DEE-TACE. Both grading systems can differentiate survival in patients responding to treatment.

Baseline Apparent Diffusion Coefficient as a Predictor of Response to Liver-Directed Therapies in Hepatocellular Carcinoma.

Predicting outcomes in patients with hepatocellular carcinoma (HCC) who undergo locoregional therapies remains a substantial clinical challenge. The purpose of this study was to investigate pre-procedure diffusion weighted magnetic resonance imaging (DW-MRI) as an imaging biomarker for tumoral response to therapy for patients with HCC undergoing drug eluting embolic (DEE) chemoembolization and radioembolization. A retrospective review of HCC patients who underwent DEE chemoembolization or radioembolization was performed. Of the 58 patients who comprised the study population, 32 underwent DEE chemoembolization and 26 underwent radioembolization. There was no significant difference in median apparent diffusion coefficient (ADC) values across the two treatment groups (1.01 × 10−3 mm2/s, P = 0.25). The immediate objective response (OR) rate was 71% (40/56). Tumors with high ADC values were found to have a higher probability of OR within 90 days (odds ratio 4.4, P = 0.03). Moreover, index lesion specific progression free survival (PFS) was greater for high ADC tumors, independent of conventional predictors of treatment response (hazard ratio 0.44, P = 0.01). Low ADC was associated with poorer PFS (P = 0.02). Pre-procedure ADC < 1.01 × 10−3 mm2/s is an independent predictor of poorer immediate OR and index lesion specific PFS in patients with HCC undergoing DEE chemoembolization or radioembolization.

Doxorubicin Drug-Eluting Embolic Chemoembolization of Hepatocellular Carcinoma: Study of Midterm Doxorubicin Delivery in Resected Liver Specimens

This study evaluated the midterm delivery of doxorubicin in liver specimens from patients (N = 4) with hepatocellular carcinoma treated with drug-eluting embolic (DEE) transarterial chemoembolization. The patients had surgical resection 57, 79, 80 and 105 days after doxorubicin DEE chemoembolization. Doxorubicin concentrations inside embolic particles and in surrounding tissues were assessed by infrared microspectroscopy and microspectrofluorimetry, respectively. Embolic particles still contained doxorubicin and provided sustained drug delivery within targeted tissues 80 days after chemoembolization. Doxorubicin was undetectable after 105 days. In addition, aggregation of embolic particles inside vessel lumina was associated with slower doxorubicin elution and higher tissue concentrations when the number of aggregated embolic particles increased.

Abstract No. 177 - Comparing overall survival in patients with hepatocellular carcinoma treated with drug eluting embolic chemoembolization with or without portal vein thrombus

Abstract No. 177 - Comparing overall survival in patients with hepatocellular carcinoma treated with drug eluting embolic chemoembolization with or without portal vein thrombus

Korean Multicenter Registry of Transcatheter Arterial Chemoembolization with Drug-Eluting Embolic Agents for Nodular Hepatocellular Carcinomas: Six-Month Outcome Analysis

PurposeTo assess the efficacy and safety of transcatheter arterial chemoembolization with drug-eluting embolic (DEE) agents for nodular hepatocellular carcinoma (HCC). Materials and MethodsThe study design was a prospective multicenter registry-based, single-arm clinical trial that included 152 patients. One hundred three (67.8%) had a Child–Pugh class/score of A5, 114 (75.0%) had a performance status of 0, and 77 (50.7%) had Barcelona Clinic Liver Cancer (BCLC) stage A disease. The DEE chemoembolization procedures were performed with DC Bead particles loaded with doxorubicin solution. The primary endpoint of the study was 6-month tumor response assessed per modified Response Evaluation Criteria In Solid Tumors. Secondary endpoints were treatment safety and overall survival. ResultsAt 1-month posttreatment assessment, complete response (CR) and objective response (OR; ie, CR or partial response) rates were 40.1% and 91.4%, respectively. At 6-month assessment, 121 patients remained for analysis, and CR and OR rates were 43.0% and 55.4%, respectively. The cumulative progression-free survival (PFS) rate at 6 months was 65.0%. Child–Pugh score, tumor multiplicity, and tumor size were independent predictors of PFS (P = .020, P = .029, and P = .001, respectively). There was no 30-day mortality. The overall 6-month survival rate was 97.4%. There were no grade 4 adverse events or laboratory changes. Serious adverse events were reported in 7.2% of patients, and persistent deterioration of liver function was observed in 3.9%. Prominent biliary injury was demonstrated in 19.7% of patients. No liver abscess was observed. ConclusionsDEE chemoembolization for nodular HCC had an acceptable safety profile and acceptable 6-month tumor response and survival rates.

Safety and Efficacy of Doxorubicin Drug-Eluting Embolic Chemoembolization of Hepatocellular Carcinoma Supplied by Extrahepatic Collateral Arteries

PurposeTo assess safety and efficacy of doxorubicin drug-eluting embolic (DEE) transarterial chemoembolization of hepatocellular carcinoma (HCC) by extrahepatic collateral arteries. Materials and MethodsRecords of 177 patients with HCC who underwent 338 consecutive DEE chemoembolization procedures from 2011 to 2014 were retrospectively reviewed. A subgroup of 16 patients (13 men, 3 women, median age 66 y) underwent 24 procedures for 17 HCCs via extrahepatic arteries and was included in the study. Median tumor size was 3.1 cm (range, 1.0–10.3 cm). Extrahepatic collaterals included right inferior phrenic (19 procedures; 12 patients), adrenal (4 procedures; 3 patients), and cystic arteries (2 procedures; 2 patients). Radiographic response was assessed by Modified Response Evaluation Criteria in Solid Tumors criteria. Complications were defined by National Cancer Institute Common Terminology Criteria for Adverse Events. ResultsDEE chemoembolization achieved stable disease in 6 (35.3%), partial response in 6 (35.3%), and complete response in 4 (23.5%) HCCs. Disease progression was ultimately observed in 8 tumors (47.1%), with mean time to progression of 8.3 months after chemoembolization (range, 2–13 mo). Three minor and 5 major complications occurred in 8 patients; 2 minor complications were rash in vascular distribution after right inferior phrenic artery DEE chemoembolization. The 5 major complications were transient hepatotoxicity that resolved within 4–80 days; 1 was accompanied by pleural effusion requiring hospitalization. A mean 13.4 months after DEE chemoembolization, 67% of transplant candidates proceeded to liver transplant. ConclusionsDEE transarterial chemoembolization via extrahepatic collaterals was effective and facilitated bridging to transplant. It was generally well tolerated; transient hepatotoxicity was the most common major complication.

Role of Locoregional Therapy and Predictors for Dropout in Patients with Hepatocellular Carcinoma Listed for Liver Transplantation

PurposeTo identify factors associated with removal from the liver transplantation waitlist because of death, deterioration of condition, or exceeding Milan criteria in patients with hepatocellular carcinoma (HCC), with emphasis on the role of locoregional therapy (LRT), defined as percutaneous thermal ablation and drug-eluting embolic chemoembolization, as bridge therapy. Materials and MethodsAll patients listed for liver transplant at a single institution with exception points for HCC during 2004–2012 were evaluated. The most common cause of cirrhosis was hepatitis C (68%; 121/177). Seventy-one percent (125/177) of patients underwent liver transplantation, and 83% (147/177) underwent at least 1 LRT procedure. Of the 52 patients who did not undergo liver transplantation, 31 (60%) of livers were removed because of progression of HCC. ResultsThe likelihood of transplant was higher for patients who received LRT (odds ratio [OR], 2.9; confidence interval [CI], 2.2–7.2) and lower for patients with multifocal tumors (OR, 0.25; CI, 0.12–0.52) and with larger tumors (OR, 0.94; CI, 0.90–0.98). Time on the waitlist (OR, 0.99; CI, 0.99–1.0) was not found to correlate with removal. LRT increased the likelihood of liver transplantation, specifically for patients with prolonged wait times. Patients who demonstrated complete response (CR) to LRT on the first follow-up imaging study were more likely to undergo liver transplantation. ConclusionsLRT increased the likelihood of a patient with HCC achieving liver transplant, particularly in patients facing prolonged waiting times. CR after LRT significantly increased the likelihood of liver transplantation.

A Single-Center Retrospective Comparison of Doxorubicin-Loaded HepaSphere Transarterial Chemoembolization with Conventional Transarterial Chemoembolization for Patients with Unresectable Hepatocellular Carcinoma

PurposeTo compare doxorubicin-loaded HepaSphere transarterial chemoembolization versus conventional transarterial chemoembolization in terms of survival, time to recurrence, acute reversible hepatotoxicity, postembolization syndrome, and chemoembolization-related mortality and morbidity. Materials and MethodsOne hundred twenty-six patients (103 men, 23 women; mean age, 64.3 y) with unresectable hepatocellular carcinoma (HCC) who underwent conventional chemoembolization between January 2007 and March 2011 or drug-eluting embolic (DEE) chemoembolization (after the protocol change) between March 2011 and October 2014 were included in a retrospective analysis. Primary outcome measures were survival and time to recurrence. Secondary outcome measures were frequency of recurrence, technical success, acute reversible hepatotoxicity, postembolization syndrome, and chemoembolization-related mortality and morbidity. ResultsThe technical success rate was 97.1%. There were no significant differences between the conventional and DEE chemoembolization groups with regard to mean survival duration (39.0 vs 37.4 mo), recurrence (32.9% vs 39.6%), postembolization syndrome (90% vs 89%), and chemoembolization-related mortality (5.5% vs 1.9%) and morbidity (9.6% vs 9.4%; P > .05). The time to recurrence was shorter in DEE chemoembolization–treated patients than in conventional chemoembolization–treated patients (5.0 vs 11.5 mo; P = .006), and acute reversible hepatotoxicity occurred more frequently after conventional chemoembolization (P = .019). ConclusionsConventional chemoembolization and DEE chemoembolization were safe and effective interventions for unresectable HCC. DEE chemoembolization was not better than conventional chemoembolization in terms of survival and was associated with a shorter time to recurrence. Acute reversible hepatotoxicity occurred more frequently after conventional chemoembolization.