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.     

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.     

Sintilimab plus Bronchial Arterial Infusion Chemotherapy/Drug-Eluting Embolic Chemoembolization for Advanced Non–Small Cell Lung Cancer: A Preliminary Study of 10 Patients

PurposeTo evaluate the short-term efficacy and safety of immunotherapy with sintilimab combined with bronchial arterial infusion (BAI) chemotherapy/drug-eluting embolic (DEE) bronchial arterial chemoembolization (BACE) for advanced non–small cell lung cancer (NSCLC).Materials and MethodsTen patients with advanced NSCLC were treated with sintilimab plus BAI/DEE-BACE between December 2019 and November 2020 and retrospectively evaluated. The Response Evaluation Criteria in Solid Tumors version 1.1 was applied to evaluate the treatment response. The local tumor control duration, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier analysis.ResultsAt 30 days after the last multimodal treatment, complete response, partial response, and stable disease were recorded in 1 (10%), 7 (70%), and 2 (20%) patients, respectively, for an objective response rate of 80% and a disease control rate of 100%. No patient experienced progressive disease. The median duration of local tumor control was 8.0 months (95% CI, 6.2–9.7 months). The median PFS and OS were 11.0 months (95% CI, 6.9–15.1 months) and 8.0 months (95% CI, 5.5–10.5 months), respectively. Two cases of Grade III adverse events related to medications were reported.ConclusionsSintilimab combined with BAI/DEE-BACE for patients with advanced NSCLC appears to be safe and feasible. Compared with previous studies on BAI/DEE-BACE, the addition of immunotherapy may improve survival.     

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.     

Transarterial Chemoembolization Using 100-μm Drug-Eluting Microspheres in Patients with Hepatocellular Carcinoma: A Prospective Study and Midterm Follow-up

PurposeThe purpose of this study was to assess the safety and efficacy of drug-eluting embolic (DEE) transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients who are ineligible for curative treatment, using doxorubicin-loaded Tandem (Varian Medical) microspheres.Materials and MethodsBetween October 2015 and December 2017, 98 patients with unresectable HCC (69 males, 29 females; mean age, 60.5 ± 10.0 years of age; and American Joint Committee on Cancer [AJCC] stage ≦T3a) treated with DEE transarterial chemoembolization using 100-μm doxorubicin-loaded microspheres were enrolled prospectively. All studies were reviewed and approved by the Institutional Review Board of Chang Gung Memorial Hospital. Dynamic contrast-enhanced computed tomography or magnetic resonance imaging 1 month after treatment was used for tumor response assessment according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Outcomes included overall survival (OS), progression-free survival (PFS), and downstaging profile.ResultsMedian follow-up was 21.2 months. At follow-up examinations at 0.5-, 1-, 1.5- and 2.5-year follow-up, OS rates were 93.8%, 89.5%, 79.4%, and 77.0%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were noted in 50 (51.0%), 23 (23.5%), 18 (18.4%), and 7 (7.1%) patients, respectively, with 93.9% disease control rate and 74.5% objective response rate. Mean OS was 28.7 months, and mean PFS was 19.6 months. Number of nodules >3, bilobar disease, larger tumor, and higher AJCC stage correlated with worse CR. No serious adverse events occurred after DEE transarterial chemoembolization. Successful downstage rate was 73.3% (22 of 30) and number of nodules predicting successful downstaging was 7 nodules (cutoff).ConclusionsTandem DEE transarterial chemoembolization provides safe and effective treatment for HCC and a bridge or downstage therapy for liver transplantation.     

Survival Analysis Using Albumin-Bilirubin (ALBI) Grade for Patients Treated with Drug-Eluting Embolic Transarterial Chemoembolization for Hepatocellular Carcinoma

PurposeThe albumin-bilirubin (ALBI) grade has been established as an improved predictor of survival in patients with hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization and yttrium-90 radioembolization. The purpose of the study was to investigate the utility of ALBI grade in prognosticating outcomes in patients with HCC treated with drug-eluting embolic (DEE) transarterial chemoembolization (TACE).Materials and MethodsA single-center retrospective review was performed to compare the efficacy of ALBI grade and Child-Pugh (CP) classification in predicting the survival of patients with HCC receiving DEE-TACE. A total of 303 patients with HCC were identified who had received DEE-TACE without concomitant locoregional therapy within 30 days. Survival analysis was performed using Kaplan-Meier methods and censored for curative therapy. Survival curves were stratified based on the ALBI grade, CP class, Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group performance status, and presence of ascites. The discriminatory ability of survival curves was calculated by C-Index.ResultsKaplan-Meier survival curves stratified by the ALBI grade produced distinct, nonoverlapping curves (P < .001), showing greater discriminatory ability than the CP classification (C-index = 0.568 and 0.545, respectively). The substratification of the BCLC stage by the ALBI grade yielded greater discriminatory ability than the substratification by the CP classification (C-index = 0.573 and 0.565, respectively). For patients with BCLC stage B, the substratification by the ALBI grade yielded distinct curves, whereas the substratification by the CP classification did not (P = .011 and P = .379, respectively).ConclusionsALBI grade showed improved discriminatory ability compared with CP classification in differentiating overall survival among patients with HCC receiving DEE-TACE. Furthermore, ALBI grade was effective in substratifying survival among patients categorized as CP class A and patients with BCLC stage B, whereas CP classification was not effective.     

Image-Guided Ablation of Recurrent or Unresectable Intrahepatic Cholangiocarcinoma

PurposeTo assess the safety and effectiveness of image-guided ablation of recurrent or unresectable intrahepatic cholangiocarcinoma (ICC).Materials and MethodsIn this retrospective study, 25 patients (14 women; age, 36–84 years) underwent 37 image-guided liver tumor ablation procedures to treat 47 ICCs (May 2004 to January 2022). At initial diagnosis, 20 patients had Stage 1 or 2 disease and 5 had Stage 3 or 4 disease. Before ablation, 19 (76.0%) of the 25 patients had progressed through prior treatments, including resection (n = 11), chemotherapy (n = 11), transarterial embolization (n = 3), or radiotherapy (n = 1); 6 (24.0%) of the 25 patients were treatment naïve. Ablation modality selection was based on patient and tumor characteristics and operator preference. Primary outcomes included local progression–free survival (LPFS) and overall survival (OS) after ablation. Statistical analysis included Kaplan-Meier (KM) survival analyses and Cox proportional hazards models.ResultsThe mean ablated tumor size was 2.0 cm ± 1.2 (range, 0.5–5.0 cm). The 1-, 2-, and 5-year LPFS rates were 84.0% (95% CI, 72.9–96.8), 73.0% (95% CI, 59.0–90.4), and 59.5% (95% CI, 41.6–85.1), respectively. The 1-, 2-, and 5-year secondary LPFS rates were 89.5% (95% CI, 80.2–99.9), 81.9% (95% CI, 69.4–96.6), and 75.6% (95% CI, 60.2–94.9). The 1-, 2-, and 5-year LPFS rates for tumors ≤2 cm in size were all 95.8% (95% CI, 88.2–100.0). The 1-, 2-, and 5-year OS rates were 78.5% (95% CI, 63.5–97.2), 68.4% (95% CI, 51.3–91.1), and 43.5% (95% CI, 23.5–80.5). Larger tumor size was associated with decreased time to local progression (hazard ratio, 1.93; P = .012).ConclusionsPercutaneous ablation provided favorable intermediate to long-term disease control for patients with recurrent or inoperable cholangiocarcinoma.     

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.     

Ablation Therapy for Advanced Stage Non-Small Cell Lung Cancer: A National Cancer Database Study

PurposeTo compare overall survival (OS) of ablation with no treatment for patients with advanced stage non-small cell lung cancer.MethodsPatients with clinical stage IIIB (T_1–4N₃M₀, T₄N₂M₀) and stage IV (T_1–4N_0–3M₁) non-small cell lung cancer, in accordance with the American Joint Committee on Cancer, 7th edition, who did not receive treatment or who received ablation as their sole primary treatment besides chemotherapy from 2004 to 2014, were identified from the National Cancer Data Base. OS was estimated using the Kaplan-Meier method and evaluated by log-rank test, univariate and multivariate Cox proportional hazard regression, and propensity score-matched analysis. Relative survival analyses comparing age- and sex-matched United States populations were performed.ResultsA total of 140,819 patients were included. The 1-, 2-, 3- and 5-year survival rates relative to age- and sex-matched United States population were 28%, 18%, 12%, and 10%, respectively, for ablation (n = 249); and 30%, 15%, 9%, and 5%, respectively for no treatment (n = 140,570). Propensity score matching resulted in 249 patients in the ablation group versus 498 patients in the no-treatment group. After matching, ablation was associated with longer OS than that in the no-treatment group (median, 5.9 vs 4.7 months, respectively; hazard ratio, 0.844; 95% confidence interval, 0.719–0.990; P = .037). These results persisted in patients with an initial tumor size of ≤3 cm.ConclusionsPreliminary results suggest ablation may be associated with longer OS in patients with late-stage non-small cell lung cancer than survival in those who received no treatment.     

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.     

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 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.     

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.     

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.     

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.     

Polyethylene Glycol Drug-Eluting Embolic Microspheres Loaded with Doxorubicin for the Treatment of Hepatocellular Carcinoma: Feasibility,Safety, and Pharmacokinetic Study

PurposePolyethylene glycol drug-eluting microspheres (PEG-DEMs) can be loaded to elute doxorubicin. The current study evaluated the pharmacokinetic profile and safety of PEG-DEMs in the treatment of patients with hepatocellular carcinoma (HCC).Materials and methodsThe current prospective, multicenter, dose-escalation study enrolled 25 patients (68% men) with early or intermediate stage HCC and a performance status of 0. Patients in Cohort I were assigned to receive target doxorubicin doses of 75, 100, or 150 mg. Analyses were performed on the basis of the specific dose of doxorubicin that the patients received because some patients received less than the assigned dose. Patients in Cohort II received the maximum safe tested dose. Adverse events were classified according to the Common Terminology Criteria for Adverse Events version 4.03. The tumor response was evaluated every 3 months according to the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors.ResultsThe maximum tested safe dose of doxorubicin was 150 mg. For the groups that received ≤75, 75–100, and 101–150 mg of doxorubicin, the peak plasma concentrations were 286.7 ng/mL ± 220.1, 157.1 ng/mL ± 94.6, and 245.4 ng/mL ± 142.8, respectively; the areas under the curves calculated from 0 to 24 h were 421.7 (ng × h)/mL ± 221.2, 288.1 (ng × h)/mL ± 100.9, and 608.3 (ng × h)/mL ± 319.3, respectively, with almost complete clearance at 24 h. There was no death within 30 d. The best objective response rate was 81%, and the disease control rate was 91%. The median overall survival was 27.2 months (95% confidence interval [CI], 17.5 months to not evaluated [n.e.]); the median progression-free survival was 9.8 months (95% CI, 5.5 months to n.e.).ConclusionsPEG-DEMs demonstrated a favorable safety profile with low systemic concentration of doxorubicin, and promising efficacy.     

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.     

Feasibility and Safety of CT-Guided High-Dose-Rate Brachytherapy Combined with Transarterial Chemoembolization Using Irinotecan-Loaded Microspheres for the Treatment of Large,Unresectable Colorectal Liver Metastases

PurposeTo evaluate feasibility and safety of combined irinotecan chemoembolization and CT-guided high-dose-rate brachytherapy (HDRBT) in patients with unresectable colorectal liver metastases > 3 cm in diameter.Materials and MethodsThis prospective study included 23 patients (age, 70 y ± 11.3; 16 men) with 47 liver metastases (size, 62 mm ± 18.7). Catheter-related adverse events were reported per Society of Interventional Radiology classification, and treatment toxicities were reported per Common Terminology Criteria for Adverse Events. Liver-related blood values were analyzed by Wilcoxon test, with P < .05 as significant. Time to local tumor progression, progression-free survival (PFS), and overall survival (OS) were estimated by Kaplan–Meier method.ResultsNo catheter-related major or minor complications were recorded. Significant differences vs baseline levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT; both P < .001), γ-glutamyltransferase (GGT; P = .013), and hemoglobin (P = .014) were recorded. After therapy, 11 of 23 patients (47.8%) presented with new grade I/II toxicities (bilirubin, n = 3 [13%]; AST, n = 16 [70%]; ALT, n = 18 [78%]; ALP, n = 12 [52%] and hemoglobin, n = 15 [65%]). Moreover, grade III/IV toxicities developed in 10 (43.5%; 1 grade IV): AST, n = 6 (26%), grade III, n = 5; grade IV, n = 1; ALT, n = 3 (13%); GGT, n = 7 (30%); and hemoglobin, n = 1 (4%). However, all new toxicities resolved within 3 months after therapy without additional treatment. Median local tumor control, PFS, and OS were 6, 4, and 8 months, respectively.ConclusionsCombined irinotecan chemoembolization and CT-guided HDRBT is safe and shows a low incidence of toxicities, which were self-resolving.