Spectral CT Imaging–Based Quantification of Iodized Oil Retention following Chemoembolization: Phantom and Animal Studies

PurposeTo evaluate accuracy of iodine quantification using spectral CT and the potential of quantitative iodized oil analysis as an imaging biomarker of chemoembolization.Materials and MethodsA phantom of an artificial liver with 6 artificial tumors containing different amounts of iodized oil (0–8 vol%) was scanned by spectral CT, and iodized oil density (mg/mL) and Hounsfield unit (HU) values were measured. In addition, VX2 hepatoma was induced in 23 rabbits. After chemoembolization using iodized oil chemoemulsion, the rabbits were scanned by spectral CT. The accumulation of iodized oil in the tumor was quantified in terms of iodized oil density and HUs, and the performances in predicting a pathologic complete response (CR) were evaluated by receiver operating characteristic curve analyses.ResultsThe mean difference between true iodine densities and spectral image–based measurements was 0.5 mg/mL. Mean HU values were highly correlated with mean iodine density (r² = 1.000, P < .001). In the animal study, a pathologic CR was observed in 17 of 23 rabbits (73.9%). The range of area under the curve values of iodine and HU measurements was 0.863–0.882. A tumoral iodine density of 3.57 mg/mL, which corresponds to 0.7 vol% iodized oil in the tumor, predicted a pathologic CR with a sensitivity of 70.6% and a specificity of 100.0%.ConclusionsSpectral CT imaging has a potential to predict tumor responses after chemoembolization by quantitatively assessing iodized oil in targets.     

Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma with Intra-atrial Tumor Extension: Imaging Response and Oncologic Outcomes

To evaluate outcomes in patients with right atrial (RA) hepatocellular carcinoma extension treated with transarterial chemoembolization. Eight patients were retrospectively reviewed. Follow-up visits occurred at 4–6 weeks; transarterial chemoembolization was repeated if residual tumor persisted. After transarterial chemoembolization, RA tumor volume reduction was 86% ± 19; α-fetoprotein level showed a reduction of 95%. From RA tumor diagnosis, 3-, 6-, and 12-month overall survival was 100% ± 0, 100% ± 0, and 67% ± 29, respectively. In patients with hepatocellular carcinoma invading the right atrium, transarterial chemoembolization alone or in combination with systemic therapy yields an improved imaging response and may be associated with improved survival.     

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.     

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.     

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.     

Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma

PurposeTo investigate the safety of replacing doxorubicin with tirapazamine in conventional transarterial chemoembolization (TACE) in an Asian population with hepatocellular carcinoma (HCC), and to determine the optimal tirapazamine dose for phase II studies.Materials and MethodsThis was a phase I, 3 + 3 dose-escalation study for patients with unresectable early- and intermediate-stage HCC who received 5, 10, or 20 mg/m² of intra-arterial (IA) tirapazamine followed by ethiodized oil/gelatin sponge-based embolization. Key eligibilities included HCCs no more than 10 cm in diameter, prior embolization allowed, Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of 5–7, and platelet count of ≥60,000 μL. Dose-limiting toxicity (DLT) was defined as any grade 3 nonhematological or grade 4 hematological toxicity, with the exception of transient elevation of aminotransferase levels after the procedure.ResultsSeventeen patients were enrolled, 59% of whom had progression from a prior HCC therapy and 35% of whom had progression or recurrence after TACE. All patients tolerated the tirapazamine TACE well without any DLT or serious adverse event. Using the modified Response Evaluation Criteria in Solid Tumors, the complete response (CR) rate was 47%, and the CR + partial response rate was 65%. The median duration of response was not reached. The median time to progression was 12.6 months (95% confidence interval, 5.1–not reached). The median overall survival was 29.3 months. The selected phase II dose was set at a fixed dose of 35 mg of IA tirapazamine.ConclusionsIA tirapazamine with transarterial embolization was well tolerated and showed promising efficacy signals in intermediate-stage HCC, justifying pursuit of a phase II study.     

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.     

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.     

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.     

Robot-Assisted Transarterial Chemoembolization of Hepatocellular Carcinoma Using a Coaxial Microcatheter Driving Controller-Responder Robot System: Clinical Pilot Study

PurposeTo evaluate the feasibility and safety of robot-assisted transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) using a new coaxial microcatheter driving controller-responder robot (CRR) system.Materials and MethodsA single-center prospective pilot study approved by the institutional review board was conducted using this CRR developed after analyzing 20 cases of conventional TACE procedures from May to October 2021. The study included 10 patients with HCCs: 5 (median age, 72 years; range, 64–73 years) underwent robot-assisted TACE, and 5 (median age, 57 years; range, 44–76 years) underwent conventional TACE for comparison. The feasibility and safety of robot-assisted TACE were evaluated by assessing the technical success, procedure time, adverse event rate, radiation dose, and early tumor response.ResultsThe entire TACE procedure was divided into 30 steps, of which 8 could be robotized. In robot-assisted TACE, technical success was achieved in 4 (80%) of 5 patients. No procedure-related adverse event was observed. The median procedure time was 56 minutes. At the 1-month follow-up, 3 of the 4 patients showed a complete or partial response after robot-assisted TACE. The median radiation doses for the operator and patients were 0.4 and 2,167.5 μSv in robot-assisted TACE and 53.2 and 2,989.7 μSv in conventional TACE, respectively.ConclusionsRobot-assisted TACE using a new CRR system was feasible and safe for the treatment of HCC and could remarkably decrease radiation exposure for the operators.     

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.     

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.     

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.     

Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model

PurposeTo investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model.Materials and MethodsVX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry.ResultsThe median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 μg/mL (interquartile range [IQR], 7.42–33.5 μg/mL), and its maximal plasma concentration (C_max) was 0.164 μg/mL (IQR, 0.0798–0.528 μg/mL). The intratumoral concentration and C_max of doxorubicin were similar between the groups: 4.08 μg/mL (IQR, 3.18–4.79 μg/mL) and 0.677 μg/mL (IQR, 0.315–1.23 μg/mL), respectively, in the DOX-TACE group and 1.68 μg/mL (IQR, 0.795–4.08 μg/mL) and 0.298 μg/mL (IQR, 0.241–0.64 μg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups.ConclusionsThe addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.     

Correlation of Serum Chemokine Ligand 14 with Barcelona Clinic Liver Cancer Stage,Lymphocyte Profile,and Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma

PurposeTo investigate the clinical relevance of serum chemokine ligand 14 (sCCL14) in patients with hepatocellular carcinoma (HCC) and the effect of transarterial chemoembolization (TACE) on the expression level of sCCL14 and the immune microenvironment.Materials and MethodsIn this prospective single-center observational study, 52 patients with HCC were recruited from January 2019 to December 2021, their clinical data and blood samples were collected, and the relationship between sCCL14 and progression-free survival (PFS) and TACE treatment response was analyzed.ResultsAmong the 52 patients with HCC (Barcelona Clinic Liver Cancer [BCLC] Stage A, 25.0%; BCLC Stage B, 44.2%; and BCLC Stage C, 30.8%), patients with BCLC Stage C HCC had significantly lower sCCL14 levels than those of patients with BCLC Stages A and B HCC (P = .001). sCCL14 levels were significantly higher in the first week after treatment than before TACE treatment (P = .024). Baseline sCCL14 levels in patients who showed complete response after TACE treatment were significantly higher than those in other groups, and lower baseline sCCL14 values were associated with shorter PFS times. Multivariate Cox regression analysis showed that sCCL14 level (hazard ratio, 1.855; 95% CI, 1.039–3.311; P = .037) was an independent prognostic factor of PFS. sCCL14 levels negatively correlated with the proportion of B lymphocytes and regulatory T cells in circulating blood and positively correlated with the absolute T-lymphocyte count.ConclusionssCCL14 may be a predictive biomarker of TACE effectiveness. Further studies are needed to validate and outline the role of combination immunotherapy.     

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.     

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.     

Pathologic Response of Hepatocellular Carcinoma Treated with Yttrium-90 Glass Microsphere Radiation Segmentectomy Prior to Liver Transplantation: A Validation Study

PurposeTo evaluate the pathologic outcomes of hepatocellular carcinoma (HCC) treated with Yttrium-90 radiation segmentectomy using glass microspheres prior to liver transplantation and explore parameters associated with pathologic necrosis.Materials and MethodsA single-institution retrospective analysis of HCC patients who received radiation segmentectomy prior to liver transplantation from November 2016 to May 2020 was performed. Patients were included if the treatment angiosome encompassed the entire tumor and could be correlated with available gross pathology. Archived histology slides were reviewed for percentage of pathologic necrosis. Thirty-three patients with 37 tumors were evaluated. The median tumor size was 2.3 cm (range, 1–6.7 cm).ResultsAll tumors received a single treatment. The median time from radiation segmentectomy to transplantation was 206 days (range, 58–550 days). Objective response per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was 92% (complete response, 76%; partial response, 16%). A total of 68% (n = 25) of tumors demonstrated ≥99% pathologic necrosis. Complete pathologic necrosis was present in 53% and 75% of tumors treated with >190 Gy (n = 18) and >500 Gy (n = 8) single-compartment Medical Internal Radiation Dose, respectively. Complete response per mRECIST, posttreatment angiosome T1 hypointensity, dose >190 Gy, microsphere specific activity >297 Bq, and a longer time between treatment and transplant were associated with ≥99% tumor necrosis (P < .05). No posttransplant tumor recurrences occurred within a median follow-up of 604 days (range, 138–1,223 days).ConclusionsRadiation segmentectomy can serve as an ablative modality for the treatment of HCC prior to liver transplant.     

Radiofrequency Ablation versus Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma Awaiting Liver Transplant: An Analysis of the Scientific Registry of Transplant Recipients

PurposeTo evaluate differences in waitlist mortality and dropout in liver transplant candidates with hepatocellular carcinoma (HCC) who undergo radiofrequency (RF) ablation versus transarterial chemoembolization (TACE).Material and MethodsFrom 2004 to 2013, 11,824 patients with HCC in the Scientific Registry of Transplant Recipients who underwent RF ablation or TACE were included and followed until December 31, 2019, or 5 years, whichever came first, and were stratified by the Milan criteria. Competing risk and Cox regression analyses to compare waitlist mortality and dropout were performed using adjusted hazard ratios (asHRs, with RF ablation group as reference). Regression models were adjusted for age, race, sex, calculated Model for End-Stage Liver Disease score, tumor size, and number.ResultsThere was no difference in waitlist mortality and dropout for patients outside the Milan criteria (n = 1,226) who underwent TACE (19.2%) or RF ablation (19.0%) (asHR, 0.91; 95% CI, 0.79–1.03). There was also no difference for patients inside the Milan criteria (n = 10,598) in waitlist mortality/dropout (TACE 13.4% vs RF ablation 12.9%) (asHR, 1.29; 95% CI, 0.79–2.09). A subgroup analysis within the Milan criteria demonstrated no difference between TACE and RF ablation treatments in patients with a single tumor of ≤3 cm (asHR, 0.92; 95% CI, 0.77–1.10), with a single tumor of >3 cm (asHR, 1.03; 95% CI, 0.79–1.34), or with >1 tumor (asHR, 0.89; 95% CI, 0.72–1.09).ConclusionsUsing the national registry data, no difference was found in waitlist mortality and dropout for transplant candidates with HCC who received TACE versus RF ablation.     

Prediction of Response of Hepatocellular Carcinoma to Radioembolization: Machine Learning Using Preprocedural Clinical Factors and MR Imaging Radiomics

PurposeTo create and evaluate the ability of machine learning–based models with clinicoradiomic features to predict radiologic response after transarterial radioembolization (TARE).Materials and Methods82 treatment-naïve patients (65 responders and 17 nonresponders; median age: 65 years; interquartile range: 11) who underwent selective TARE were included. Treatment responses were evaluated using the European Association for the Study of the Liver criteria at 3-month follow-up. Laboratory, clinical, and procedural information were collected. Radiomic features were extracted from pretreatment contrast-enhanced T1-weighted magnetic resonance images obtained within 3 months before TARE. Feature selection consisted of intraclass correlation, followed by Pearson correlation analysis and finally, sequential feature selection algorithm. Support vector machine, logistic regression, random forest, and LightGBM models were created with both clinicoradiomic features and clinical features alone. Performance metrics were calculated with a nested 5-fold cross-validation technique. The performances of the models were compared by Wilcoxon signed-rank and Friedman tests.ResultsIn total, 1,128 features were extracted. The feature selection process resulted in 12 features (8 radiomic and 4 clinical features) being included in the final analysis. The area under the receiver operating characteristic curve values from the support vector machine, logistic regression, random forest, and LightGBM models were 0.94, 0.94, 0.88, and 0.92 with clinicoradiomic features and 0.82, 0.83, 0.82, and 0.83 with clinical features alone, respectively. All models exhibited significantly higher performances when radiomic features were included (P = .028, .028, .043, and .028, respectively).ConclusionsBased on clinical and imaging-based information before treatment, machine learning–based clinicoradiomic models demonstrated potential to predict response to TARE.