Transarterial Chemoembolization for the Palliation of Painful Bone Metastases Refractory to First-Line Radiotherapy

PurposeTo compare the efficacy and safety of transarterial chemoembolization for the palliation of radiotherapy (RT)-failure bone metastases (BMs) with those of re-radiotherapy (Re-RT) in achieving pain relief.Materials and MethodsFifty consecutive patients with RT-failure BMs who had undergone Re-RT (23 patients) and transarterial chemoembolization (27 patients) were retrospectively analyzed. The primary endpoint was clinical response, and the secondary endpoints were objective response and adverse events. Pain assessment was performed using the numerical rating scale, and tumor response was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Pain relief was defined as lack of pain with no analgesic usage (complete pain response) or a decrease in pain score by ≥3 points with analgesic usage (partial pain response).ResultsThe pain relief rates in the Re-RT and transarterial chemoembolization groups were 57% and 92%, respectively (P = .006). The median pain relief duration was 2 and 3 months in the Re-RT and transarterial chemoembolization groups, respectively (P = .002). The 6-month pain-free survival rates were 30% and 51% in the Re-RT and transarterial chemoembolization groups, respectively (P = .08). The median tumor reduction rates were –4% and 9% in the Re-RT and transarterial chemoembolization groups, respectively (P < .001). The objective response rates were 0% and 11% in the Re-RT and transarterial chemoembolization groups, respectively (P = .29). No serious adverse events or complications were observed.ConclusionsTransarterial chemoembolization achieved a superior response rate and longer duration of palliation in symptomatic RT-failure BMs.     

Transarterial Chemoembolization Followed by Radiofrequency Ablation for Hepatocellular Carcinoma: Impact of the Time Interval between the Two Treatments on Outcome

PurposeTo compare the efficacy of radiofrequency (RF) ablation after transarterial chemoembolization within or beyond 30 days for medium-large or multiple recurrent hepatocellular carcinomas (HCCs).Materials and MethodsIn this single-center retrospective study conducted from 2007 through 2015, 135 patients with a single recurrent HCC (>3 cm) or multiple (2–5 tumors) recurrent HCCs underwent transarterial chemoembolization plus RF ablation. A total of 62 patients underwent RF ablation after transarterial chemoembolization within 30 days (sequential group) and 73 patients underwent RF ablation after transarterial chemoembolization beyond 30 days (delayed group). Outcomes of interests included overall survival (OS), progression-free survival (PFS), and complete response (CR) rate.ResultsThe median OS and PFS were 49.8 and 38.0 months for sequential group, and 31.0 and 11.6 months for the delayed group. The sequential group experienced significantly better OS (hazard ratio [HR]: 0.517; P = .002) and PFS (HR, 0.621; P = .021). Among patients with multiple tumors or a single tumor >5 cm, the sequential group still had significantly longer OS (P = .022; P = .018, respectively) and PFS (P = 0.042; P = .036, respectively) than the delayed group, although no significant differences were observed among patients with solitary 3- to 5-cm tumors (P = .138; P = .803, respectively). The sequential group had a significantly better CR rate than the delayed group (85.4% vs. 68.5%, respectively; P = .035). Significant predictors of OS and PFS included maximum tumor size, number of tumors, and time interval between transarterial chemoembolization and RF ablation.ConclusionsTransarterial chemoembolization plus sequential RF ablation within 30 days was more effective for recurrent HCCs than transarterial chemoembolization plus delayed RF ablation. The time interval within 30 days is required for treating large or multiple HCCs but may not be necessary for solitary medium-sized HCC.     

Hepatic Hilar and Celiac Plexus Nerve Blocks as Analgesia for Doxorubicin-Eluting Microsphere Chemoembolization Procedures for Hepatocellular Carcinoma: A Nonblinded Randomized Clinical Trial

PurposeTo investigate whether hepatic hilar and celiac plexus nerve blocks provide safe and effective analgesia to patients undergoing doxorubicin-eluting embolics transarterial chemoembolization (DEE-TACE) for hepatocellular carcinoma.Materials and MethodsIn this prospective, randomized trial, 92 patients undergoing DEE-TACE for hepatocellular carcinoma were enrolled. The control group received standard intraprocedural local anesthetic, intra-arterial lidocaine, and intravenous analgesia; the study group underwent additional hepatic hilar and celiac plexus nerve blocks. Intra-arterial lidocaine, intravenous and oral narcotic and antiemetic requirements after the procedure, pain, patient satisfaction, adverse events, and hospital stay were compared.ResultsThe nerve block group reported less pain during and after the procedure at days 1 and 7 (P < .001), although differences resolved by week 2. The control group received more intra-arterial lidocaine (P < .001) and required approximately double the amount of narcotic analgesia during and after the procedure, extending to 3 weeks after the procedure (P < .001), as well as less antiemetics (P < .001). No differences in adverse events, hospital stay, and overall patient satisfaction were noted.ConclusionsHepatic hilar and celiac plexus nerve blocks before procedures can result in lower pain during and after procedures in patients undergoing DEE-TACE. Furthermore, nerve blocks result in lower opioid consumption and opioid-related complications for 3 weeks following procedures.     

Chronic Hepatotoxicity in Patients with Metastatic Neuroendocrine Tumor: Transarterial Chemoembolization versus Transarterial Radioembolization

PurposeTo compare the manifestations of chronic liver injury following transarterial chemoembolization with those of transarterial radioembolization (TARE) in patients with neuroendocrine tumor (NET).Materials and MethodsThis study consisted of an Institutional Review Board-approved single-institution retrospective analysis of NET patients who received transarterial chemoembolization from 2006 to 2016 and TARE from 2005 to 2014 and survived at least 1 year from the initial treatment. Patients receiving only transarterial chemoembolization (n = 63) or TARE (n = 28) were evaluated for the presence or absence of durable hepatic toxicities occurring at least 6 months after initial treatment. The definitions and grades of liver injury were adapted from Common Terminology Criteria for Adverse Events version 4.0 and were characterized by the presence of laboratory or clinical toxicities of Grade 3 or above.ResultsChronic hepatic toxicity occurred in 14 of 63 transarterial chemoembolization patients (22%) with a total of 26 Grade 3-4 events, in whom elevation of bilirubin was the most common toxicity, compared to 8 of 28 TARE patients (29%) with a total of 16 Grade 3-4 and 2 Grade 5 events, in whom ascites were the most frequent toxicity. There were more laboratory toxicities in the transarterial chemoembolization group (65% vs 38%, P = .11) and fewer Grade 4–5 injuries (6% vs 27% of patients, P = .06). There was also a significantly higher number of patients who experienced intrahepatic progression of disease in the transarterial chemoembolization cohort than in the TARE patients (75% vs 43%, respectively; P = .005).ConclusionsDelayed hepatotoxicity from transarterial chemoembolization and TARE occurred in 22% and 29% of patients, respectively, from 6 months to several years following treatment. Transarterial chemoembolization-related toxicities on average were less severe and manifested primarily as laboratory derangements, compared to TARE toxicities which consisted of clinical hepatic decompensation.     

Integrated Liver Inflammatory Score Predicts the Therapeutic Outcome of Patients with Hepatocellular Carcinoma after Transarterial Chemoembolization

PurposeTo evaluate the performance of the integrated liver inflammatory score (ILIS) in predicting survival in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization, and to compare ILIS to other prognostic scoring systems and inflammatory indices.Materials and MethodsThis study included 192 patients with unresectable HCC who underwent transarterial chemoembolization from 3 medical centers. The potential risk factors of the patients’ overall survival (OS) were determined by multivariate Cox regression analysis. The predictive performances of ILIS in 1-, 2-, 3-, 4-, and 5-year survival were evaluated using receiver operating characteristic curves. The discriminatory power in the OS of ILIS and the other known scoring systems or inflammatory indices was determined by C-statistic.ResultsMultivariate regression analysis showed that high ILIS (P = .047), low lymphocyte count (P = .034), beyond up-to-seven criteria (P = .021), and nonresponse to the first transarterial chemoembolization session (P = .039) were risk factors for poor prognosis after transarterial chemoembolization. The predictive performances of ILIS for 1-, 2-, 3-, 4-, and 5-year survival were good, with area under the curve values of 0.627, 0.631, 0.621, 0.577, and 0.681, respectively. ILIS outperformed other standard scoring systems and inflammatory indices in predicting OS, with a C-statistic of 0.625.ConclusionsILIS is a powerful prognostic index for predicting the survival of patients with HCC after transarterial chemoembolization, which suggests that ILIS before treatment should be considered during the patient evaluation process.     

Use of a Glass Membrane Pumping Emulsification Device Improves Systemic and Tumor Pharmacokinetics in Rabbit VX2 Liver Tumor in Transarterial Chemoembolization

PurposeTo evaluate the phamacokinetics of epirubicin in conventional transarterial chemoembolization using a developed pumping emulsification device with a microporous glass membrane in VX2 rabbits.Materials and MethodsEpirubicin solution (10 mg/mL) was mixed with ethiodized oil (1:2 ratio) using the device or 3-way stopcock. Forty-eight rabbits with VX2 liver tumor implanted 2 weeks prior to transarterial chemoembolization were divided into 2 groups: a device group (n = 24) and a 3-way-stopcock group (n = 24). Next, 0.5 mL of emulsion was injected into the hepatic artery, followed by embolization using 100–300-μm microspheres. The serum epirubicin concentrations (immediately after, 5 minutes after, and 10 minutes after) and the tumor epirubicin concentrations (20 minutes after and 48 hours after) were measured after transarterial chemoembolization. Histopathologic evaluation was performed with a fluorescence microscope.ResultsThe area under the curve and maximum concentrations of epirubicin in plasma were 0.45 ± 0.18 μg min/mL and 0.13 ± 0.06 μg/mL, respectively, in the device group and 0.71 ± 0.45 μg min/mL and 0.22 ± 0.17 μg/mL, respectively, in the 3-way-stopcock group (P = .013 and P = .021, respectively). The mean epirubicin concentrations in VX2 tumors at 48 hours in the device group and the 3-way-stopcock group were 13.7 ± 6.71 and 7.72 ± 3.26 μg/g tissue, respectively (P = .013). The tumor necrosis ratios at 48 hours were 62 ± 11% in the device group and 51 ± 13% in the 3-way-stopcock group (P = .039).ConclusionsConventional transarterial chemoembolization using the pumping emulsification device significantly improved the pharmacokinetics of epirubicin compared to the current standard technique using a 3-way stopcock.     

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.     

Thermal Ablation and Transarterial Chemoembolization are Characterized by Changing Dynamics of Circulating MicroRNAs

PurposeTo determine whether the levels of circulating microRNAs (miRNAs) are altered in patients undergoing thermal ablation and chemoembolization and whether these changes are predictive of a clinical outcome.Material and MethodsThis prospective study consisted of 43 patients diagnosed with hepatocellular carcinoma (n = 15) and intrahepatic colorectal cancer metastases (n = 28) treated with thermal ablation (n = 23; radiofrequency [n = 6] or microwave [n = 19]), chemoembolization using drug-eluting embolics (n = 18), or both (n = 2). Four blood samples (immediately before the intervention and 60–90 minutes, 24 hours, and 7 days after the intervention) were taken to measure the plasma concentrations of miRNAs related to hypoxia (miR-21 and miR-210), liver injury (miR-122), epithelial–mesenchymal transition (miR-200a), and apoptosis (miR-34a) using miRNA-specific TaqMan assays and quantitative real-time polymerase chain reaction. Tumor burden and treatment response at 3 months were evaluated using the modified response evaluation criteria in solid tumors. The miRNA results were compared with clinical outcomes (Mann-Whitney U test, Wilcoxon matched-pair test).ResultsDynamic changes in the circulating miRNA levels were observed following both the interventions. For thermal ablation, significant increases in miR-21, miR-210, miR-122, miR-200a, and miR-34a concentrations peaked 60–90 minutes after the intervention (P < .01). However, for transarterial chemoembolization, maximum increases in the miRNA concentrations were observed at 24 hours after the intervention for miR-21, miR-210, miR-122, miR-200a, and miR-34a (P < .05). The increased concentrations of the circulating miRNAs were followed by a subsequent decline to baseline by 7 days. For the thermal ablation (but not chemoembolization) patients, elevations in the miR-210 and miR-200a levels were associated with early progressive disease at 3 months (P = .040 and P = .012, respectively).ConclusionsIncreased but dynamic levels of circulating miRNAs are present following interventional oncologic procedures and may prove useful as biomarkers for the monitoring of clinical outcomes.     

γ-Glutamyltranspeptidase as a Prognostic Biomarker in Advanced Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

PurposeTo evaluate the prognostic value of pretreatment serum γ-glutamyltransferase (GGT) level in patients with advanced hepatocellular carcinoma (HCC) receiving transarterial chemoembolization.Materials and MethodsThis retrospective study included 140 patients (123 male, 17 female; mean age, 56.9 y ± 12.0; range, 22.0–82.0 y) with Barcelona Clinic Liver Cancer class C HCC who received first-line conventional chemoembolization between December 2013 and March 2018. Patients were divided into low and high GGT groups based on a cutoff value calculated with a receiver operating characteristic curve. Overall survival (OS) was compared between groups by log-rank test. Univariate and multivariate survival analyses were performed.ResultsThe optimal cutoff values of GGT were 119.5 U/L in men and 175.0 U/L in women. The 6-, 9-, and 12-mo OS rates were 81.7%, 72.4%, and 62.9%, respectively, for patients in the low GGT group (n = 44) and 58.8%, 35.7%, and 28.8%, respectively, for patients in the high GGT group (n = 96; P < .001). Multivariable Cox regression analysis identified high pretreatment serum GGT level (hazard ratio [HR], 2.71; 95% confidence interval [CI], 1.67–4.40; P < .001), multiple tumors (HR, 3.05; 95% CI, 1.23–7.53; P = .02), and performance of target treatment (ie, sorafenib; HR, 0.41; 95% CI, 0.24–0.72; P = .002) or ablation (HR, 0.35; 95% CI, 0.18–0.66; P = .001) as independent prognostic factors for OS.ConclusionsPretreatment serum GGT level was an independent prognostic factor for OS in patients with advanced HCC treated with chemoembolization, suggesting that GGT is a useful prognostic biomarker for advanced HCC.     

Transarterial Radioembolization versus Transarterial Chemoembolization Plus Percutaneous Ablation for Unresectable,Solitary Hepatocellular Carcinoma of ≥3 cm: A Propensity Score–Matched Study

PurposeTo compare the safety and effectiveness of transarterial radioembolization (TARE) and transarterial chemoembolization with drug-eluting embolic agents combined with percutaneous ablation (transarterial chemoembolization [TACE] + ablation) in the treatment of treatment-naïve, unresectable, solitary hepatocellular carcinoma (HCC) of ≥3 cm.Materials and MethodsTwenty-nine patients with treatment-naïve, unresectable, solitary HCC of ≥3 cm received combined TACE + ablation, and 40 patients received TARE at a single institution. Local tumor response, tumor progression-free survival (PFS), overall survival, need for reintervention, bridge to transplant, and major complications were compared. Clinical variables and outcomes were compared before and after propensity score matching (PSM).ResultsBefore PSM, patients who underwent TARE had a larger tumor size (3.7 vs 5.5 cm; P = .0005) and were older (61.5 vs 69.3 years; P = .0014). After PSM, there was no difference in baseline characteristics between the 2 groups, with the mean tumor sizes measuring 3.9 and 4.1 cm in the TACE + ablation and TARE cohorts, respectively. After PSM (n = 19 in each group), no statistically significant difference was observed in local radiological response (disease control rates, 100% vs 94.7%; P = .31), survival (subdistribution hazard ratio [SHR], 0.71; 95% confidence interval [CI], 0.28–1.80; P = .469), PFS (SHR, 0.61; 95% CI, 0.21–1.71; P = .342), bridge to transplant (21.1% vs 31.6%, P = .46), and major adverse event rates (15.8% vs 10.5%, P = .63) between the 2 groups. The mean total number of locoregional interventions was higher in the TACE + ablation cohort (1.9 vs 1.3 sessions, P = .02), with an earlier median reintervention trend (SHR, 0.61; 95% CI, 0.20–1.32; P = .167).ConclusionsThe present study showed that TARE and the combination of TACE and ablation are comparable in safety and effectiveness for treating treatment-naïve, unresectable, solitary HCC of ≥3 cm.     

Comparison of Drug-Eluting Embolics versus Conventional Transarterial Chemoembolization for the Treatment of Patients with Unresectable Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

PurposeTo compare the cost-effectiveness of using doxorubicin-loaded drug-eluting embolic (DEE) transarterial chemoembolization versus that of using conventional transarterial chemoembolization for patients with unresectable hepatocellular carcinoma (HCC).Materials and MethodsA decision-analysis model was constructed over the lifespan of a payer’s perspective. The model simulated the clinical course, including periprocedural complications, additional transarterial chemoembolization or other treatments (ablation, radioembolization, or systemic treatment), palliative care, and death, of patients with unresectable HCC. All clinical parameters were derived from the literature. Base case calculations, probabilistic sensitivity analyses, and multiple two-way sensitivity analyses were performed.ResultsIn the base case calculations for patients with a median age of 67 years (range for conventional transarterial chemoembolization: 28–88 years, range for DEE-transarterial chemoembolization: 16–93 years), conventional transarterial chemoembolization yielded a health benefit of 2.11 quality-adjusted life years (QALY) at a cost of $125,324, whereas DEE-transarterial chemoembolization yielded 1.71 QALY for $144,816. In 10,000 Monte Carlo simulations, conventional transarterial chemoembolization continued to be a more cost-effective strategy. conventional transarterial chemoembolization was cost-effective when the complication risks for both the procedures were simultaneously varied from 0% to 30%. DEE-transarterial chemoembolization became cost-effective if the conventional transarterial chemoembolization mortality exceeded that of DEE-transarterial chemoembolization by 17% in absolute values. The two-way sensitivity analyses demonstrated that conventional transarterial chemoembolization was cost-effective until the risk of disease progression was >0.4% of that for DEE-transarterial chemoembolization in absolute values. Our analysis showed that DEE-transarterial chemoembolization would be more cost-effective if it offered >2.5% higher overall survival benefit than conventional transarterial chemoembolization in absolute values.ConclusionsCompared with DEE-transarterial chemoembolization, conventional transarterial chemoembolization yielded a higher number of QALY at a lower cost, making it the more cost-effective of the 2 modalities.     

Neutrophil/Lymphocyte Ratio Predicts Increased Risk of Immediate Progressive Disease following Chemoembolization of Hepatocellular Carcinoma

PurposeTo demonstrate that patients with hepatocellular carcinoma (HCC) and elevated baseline neutrophil/lymphocyte ratio (NLR) have a significantly greater risk of progressive disease following initial transarterial chemoembolization.Materials and MethodsA total of 190 HCC patients (149 male/41 female) treated with transarterial chemoembolization between July 2013 and July 2017 were reviewed. Mean patient age was 62. Child-Pugh grades were 132 A, 61 B, and 4 C. Tracked criteria included etiology of cirrhosis, tumor number, Barcelona Clinic Liver Cancer score, diameter of the largest 2 tumors, and presence of portal vein thrombosis. Complete blood count with differential before the procedure was used for NLR calculation. Follow-up imaging was performed 2 months after treatment. The modified response evaluation criteria in solid tumors were used to assess response. The association between baseline NLR and tumor response (ordinal modified response evaluation criteria in solid tumors categories) on 2-month follow-up imaging was evaluated using the proportional odds logistic regression model.ResultsA total of 194 patients (76.6%) patients had a preprocedural NLR <3.5, and 59 (23%) patients had a preprocedural NLR ≥3.5. There was a statistically significant association between baseline NLR and immediate progression on 2-month follow-up imaging (mean NLR 4.10, 2.76, 2.72, and 2.48 for progressive and stable disease and partial and complete response, respectively; odds ratio 2.1, P = .04). NLR (P = .021) and tumor multiplicity (P = .011) predicted progressive disease at 2-month imaging.ConclusionsElevated baseline NLR is associated with higher rates of HCC tumor progression at 2-month follow-up imaging after transarterial chemoembolization.     

Pain,Nausea, and Hospital Admission after Uterine Fibroid Embolization: A Comparison of 2 Protocols

Uterine fibroid embolization (UFE) procedures performed from 2013 to 2019 were reviewed. Seventy-two patients were treated with a standard protocol consisting of sedation, ketorolac, ondansetron, and overnight parenteral analgesics and antiemetics. Ninety-six patients were treated with a new protocol, which added transdermal scopolamine, lorazepam, and intravenous acetaminophen. Outpatient uterine fibroid embolization (OP-UFE) not requiring hospitalization was successful in 81.4% and 2.7% of patients treated with the new and old protocols, respectively (odds ratio [OR], 141.4; P < .0001). Procedural fentanyl doses were lower with the new protocol than with the old one (mean, 148 vs 186 mcg; P = .0016). In the new protocol subset, patients were 1.01 times more likely to fail OP-UFE for every microgram increase in procedural fentanyl (OR, 0.99, P = .009), and those presenting with pain were less likely to succeed with OP-UFE than those with bleeding or bulk symptoms (OR, 0.31, P = .04). In conclusion, decreasing the opioid dose while increasing the antiemetic and nonopioid analgesic medications improves the chances of same day discharge after UFE.     

Clinical Significance of the Initial and Best Responses after Chemoembolization in the Treatment of Intermediate-Stage Hepatocellular Carcinoma with Preserved Liver Function

PurposeTo evaluate the clinical implications of initial and best responses during repeated transarterial chemoembolization procedures for hepatocellular carcinoma (HCC).Materials and MethodsThis study included 726 patients who received a diagnosis of intermediate-stage HCC with Child-Pugh class A liver function between 2007 and 2016, and who were treated with transarterial chemoembolization as the first-line treatment. Evaluation of treatment response was based on the modified response evaluation criteria in solid tumors. Overall survival (OS) was compared between response categories after implementation of landmark analysis.ResultsOf the 726 patients, an objective response (complete response [CR] or partial response [PR]) was observed as the initial response in 78.1% of patients. Regarding the best response during the transarterial chemoembolization series, 87.2% of patients were overall responders. The median OS of initial responders (n = 483) was not significantly different from that of subsequent responders at the 1-year landmark (stable disease [SD] after first transarterial chemoembolization but CR or PR after repeated transarterial chemoembolization; n = 61; 46.2 vs 40.1 months, respectively; P = .145). Likewise, the median OS of initial CR patients (n = 326) was not significantly different from that of the subsequent CR group (n = 126) at the 1-year landmark (PR or SD after first transarterial chemoembolization but CR after repeated transarterial chemoembolization; 53.4 vs 46.3 months, respectively; P = .455). Multivariate Cox analyses showed that the objective responses, the initial responses (hazard ratio [HR], 0.638; P = .001), and the best responses (HR, 0.304; P < .001) had the significant prognostic significance for OS.ConclusionsBoth the initial and best responses during repeated transarterial chemoembolization were significantly associated with OS in patients with intermediate-stage HCC and preserved liver function.     

Survival of Patients with Colorectal Liver Metastases after Transarterial Chemoembolization Using Irinotecan-Eluting Microspheres: A Single-Center Retrospective Analysis Comparing RECIST 1.1 and Choi Criteria

PurposeTo evaluate the factors that affected overall survival and hepatic progression–free survival using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Choi criteria in patients with colorectal liver metastases treated with transarterial chemoembolization (TACE) using irinotecan-eluting microspheres (IEMs) who failed at least 1 line of systemic chemotherapy.Materials and MethodsA single-institution retrospective analysis was performed including patients with unresectable liver metastases from a colorectal primary malignancy and treated with IEM-TACE. Radiologic hepatic progression–free survival was measured using the RECIST 1.1 and Choi criteria.ResultsThe median patient age was 61.5 years, with 80 (67%) men. A total of 328 IEM-TACE procedures were performed during the study period. One hundred eighteen patients who failed at least 1 line of systemic chemotherapy before TACE demonstrated a median overall survival of 12.7 months. Overall survival was higher in patients who had previous primary resection (P < .05), prior ablation (P < .05), or completed the scheduled TACE treatments (P < .05) but was adversely affected by the presence of extrahepatic disease (P < .05) and larger preprocedural tumor burden (P < .01). Prior systemic chemotherapy lines (P = .98) and microsphere size (P = .34) did not affect survival. Partial radiologic response to treatment using the Choi criteria (n = 28, P < .01) correlated significantly with survival, a correlation not seen with the RECIST 1.1 measurements (n = 5, P = .13).ConclusionsA partial response to treatment of unresectable colorectal liver metastases treated by TACE with IEMs measured using the Choi criteria correlated significantly with improved survival, while RECIST 1.1 measurements did not.     

Diffusion-Weighted MR Imaging of Primary and Secondary Lung Cancer: Predictive Value for Response to Transpulmonary Chemoembolization and Transarterial Chemoperfusion

PurposeTo examine predictive value of apparent diffusion coefficient (ADC) in diffusion-weighted imaging (DWI) for response of patients with primary and secondary lung neoplasms undergoing transpulmonary chemoembolization (TPCE) and transarterial chemoperfusion (TACP) treatment.Materials and MethodsThirty-one patients (mean age ± SD 64 ± 12.4 y) with 42 lung target lesions (13 primary and 29 secondary) underwent DWI and subsequent ADC analysis on a 1.5T MR imaging scanner before and 30.3 days ± 6.4 after first session of TPCE or TACP. After 3.1 treatment sessions ± 1.4 performed in 2- to 4-week intervals, morphologic response was analyzed by comparing tumor diameter and volume before and after treatment on unenhanced T1-weighted MR images. On a per-lesion basis, response was classified according to Response Evaluation Criteria In Solid Tumors.ResultsThreshold ADC increase of 20.7% indicated volume response with 88% sensitivity and 78% specificity (area under the curve [AUC] = 0.84). Differences between ADC changes in volume response groups were significant (P = .002). AUC for volume response predicted by ADC before treatment was 0.77. Median ADC before treatment and mean ADC change were 1.09 × 10⁻³ mm²/second and 0.36 × 10⁻³ mm²/second ± 0.23, 1.45 × 10⁻³ mm²/second and 0.14 × 10⁻³ mm²/second ± 0.16, and 1.30 × 10⁻³ mm²/second and 0.06 × 10⁻³ mm²/second ± 0.19 in partial response, stable disease, and progressive disease groups. In primary lung cancer lesions, strong negative correlation of ADC change with change in diameter (ρ = −.87, P < .001) and volume (ρ = −.66, P = .016) was found. In metastases, respective correlation coefficients were ρ = −.18 (P = .356) and ρ = −.35 (P = .061).ConclusionsADC quantification shows considerable diagnostic value for predicting response and monitoring TPCE and TACP treatment of patients with primary and secondary lung neoplasms.     

Long-term Outcomes of Patients with Hepatocellular Carcinoma Who Underwent Microwave Ablation after Downstaging with Transarterial Chemoembolization to Barcelona Clinic Liver Cancer Stage A

PurposeTo compare the clinical results of microwave ablation (MWA) between patients downstaged to Barcelona Clinic Liver Cancer (BCLC) Stage A with transarterial chemoembolization (TACE) and those initially classified as BCLC Stage A.Materials and MethodsFrom January 2012 to May 2017, 1,087 patients were reviewed retrospectively using propensity score matching (1:1): 86 patients underwent MWA as a curative treatment after downstaging to BCLC Stage A by TACE (downstaging group) and 86 patients initially classified as BCLC Stage A underwent MWA (control group). The overall survival (OS) and disease-free survival (DFS) between the 2 groups were compared.ResultsThe 1-, 3-, and 5-year OS rates were 95.3%, 79.1%, and 58.1%, respectively, in the downstaging group and 93.0%, 81.4%, and 61.6%, respectively, in the control group (hazard ratio [HR], 0.75; 95% CI, 0.50–1.13; P = .162). The 1-, 3-, and 5-year DFS rates were 80.2%, 50.0%, and 24.4%, respectively, in the downstaging group and 77.9%, 52.3%, and 27.9%, respectively, in the control group (HR, 1.08; 95% CI, 0.76–1.53; P = .678). No significant differences were found in OS and DFS.ConclusionsThe long-term prognosis in patients with HCC who underwent MWA after downstaging to BCLC Stage A using TACE was similar to that in patients with initial BCLC Stage A.     

Intra-Arterial Therapy for Unresectable Colorectal Liver Metastases: A Meta-Analysis

PurposeTo evaluate the efficacy of hepatic arterial infusion (HAI), conventional transarterial chemoembolization, drug-eluting embolic transarterial chemoembolization (DEE-TACE), transarterial radioembolization, and their combinations with systemic chemotherapy (SCT) for unresectable colorectal liver metastases.MethodsA search was conducted on Embase, Scopus, PubMed, and Web of Science for prospective nonrandomized studies and randomized controlled trials (RCTs) from inception to June 20, 2020. Survival data of patients were recovered from original Kaplan-Meier curves by exploiting a graphical reconstructive algorithm. One-stage meta-analyses were conducted for the median overall survival (OS), survival rates (SRs), and restricted mean survival time (RMST), whereas two-stage meta-analyses of proportions were conducted to determine response rates (RRs) and conversion to resection rates (CRRs).ResultsA total of 71 prospective nonrandomized studies and 21 RCTs were identified, comprising 6,695 patients. Among patients treated beyond the first-line, DEE-TACE + SCT (n = 152) had the best survival outcomes of median OS of 26.5 (95% confidence interval [CI], 22.5–29.1) months and a 3-year RMST of 23.6 (95% CI, 21.8–25.5) months. Upon further stratification by publication year, DEE-TACE + SCT appeared to consistently have the highest pooled SRs at 1 year (81.9%) and 2 years (66.1%) in recent publications (2015–2020). DEE-TACE + SCT and HAI + SCT had the highest pooled RRs of 56.7% (I² = 0.90) and 62.6% (I² = 0.87) and pooled CRRs of 35.5% (I² = 0.00) and 30.3% (I² = 0.80), respectively.ConclusionsAlbeit significant heterogeneity, the paucity of high-quality evidence, and the noncomparative nature of all analyses, the overall evidence suggests that patients treated with DEE-TACE + SCT have the best oncological outcomes and greatest potential to be converted for resection.     

Six-Year Evaluation of Same-Day Discharge following Conventional Transarterial Chemoembolization of Hepatocellular Carcinoma

PurposeTo evaluate whether same-day discharge increased the incidence of 30-day readmission (30dR) after conventional transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at a single institution.Materials and MethodsIn this retrospective study, 253 patients with HCC underwent 521 transarterial chemoembolization procedures between 2013 and 2020. TACE was performed with 50-mg doxorubicin/10-mg mitomycin C/5–10-mL ethiodized oil/particles. Patients not requiring intravenous pain medications were discharged after a 3-hour observation, and 30dR was tracked. The primary objective was to determine the incidence of 30dR in same-day discharge patients versus patients admitted for observation using the chi-square test. Secondary objectives assessed factors associated with overnight admission and factors predictive of 30dR using generalized estimated equation calculations and logistic regression.ResultsIn the cohort, 24 readmissions occurred within 30 days (4.6%). Same-day discharge was completed after 331 TACE procedures with sixteen 30dRs (4.8%). Patients admitted overnight were readmitted 8 times after 190 TACE procedures (4.2%). This difference was not statistically significant (P = .4). Factors predicting overnight admission included female sex (58/190 [30.5%] vs 58/331 [17.5%], P < .001) and tumor size of ≥3.8 cm (104/190 [55%] vs 85/190 [45%]). Factors predicting 30dR included female sex (10/116 [8.6%] vs 14/405 [0.2%]) and younger age (median [interquartile range], 63 years [55–65 years] vs 65 years [59–71 years]). At regression, factors predictive of 30dR were Child-Pugh Class B/C (odds ratio [OR], 2.1; P = .04) and female sex (OR, 2.9; P = .004).ConclusionsSame-day discharge after conventional TACE is a safe and effective strategy with 30dR rate of <5%, similar to overnight observation.     

Sodium Cholate Bile Acid-Stabilized Ferumoxytol-Doxorubicin-Lipiodol Emulsion for Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma

PurposeTo develop bile acid-stabilized multimodal magnetic resonance (MR) imaging and computed tomography (CT)-visible doxorubicin eluting lipiodol emulsion for transarterial chemoembolization of hepatocellular carcinoma (HCC).Materials and MethodsFerumoxytol, a US Food and Drug Administration-approved iron oxide nanoparticle visible under MR imaging was electrostatically complexed with doxorubicin (DOX). An amphiphilic bile acid, sodium cholate (SC), was used to form a stable dispersion of ferumoxytol-DOX complex in lipiodol emulsion. Properties of the fabricated emulsion were characterized in various component ratios. Release kinetics of DOX were evaluated for the chemoembolization applications. Finally, in vivo multimodal MR imaging/CT imaging properties and potential therapeutic effects upon intra-arterial (IA) infusion bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion were evaluated in orthotopic McA-Rh7777 HCC rat models.ResultsDOX complexed with ferumoxytol through electrostatic interaction. Amphiphilic SC bile acid at the interface between the aqueous ferumoxytol-DOX complexes and lipiodol enabled a sustained DOX release (17.2 ± 1.6% at 24 hours) at an optimized component ratio. In McA Rh7777 rat HCC model, IA-infused emulsion showed a significant contrast around tumor in both T2-weighted MR imaging and CT images (P = .044). Hematoxylin and eosin and Prussian blue staining confirmed the local deposition of IA-infused SC bile acid-stabilized emulsion in the tumor. The deposited emulsion induced significant increases in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) stain-positive cancer cell apoptosis compared to those in a group treated with the nonstabilized emulsion.ConclusionsSC bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion demonstrated sustained drug release and multimodal MR imaging/CT imaging capabilities. The new lipiodol-based formulation may enhance the therapeutic efficacy of chemoembolization in HCC.