Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis

Background/Aims@#Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. @*Methods@#This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). @*Results@#In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28–0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0–56.7%, whereas that of the TKI group was 12.3–15.0%. @*Conclusions@#For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.

Transarterial chemoembolization for hepatocellular carcinoma: 2023 Expert consensus-based practical recommendations of the Korean Liver Cancer Association

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Prospective Multi-Center Korean Registry of Transcatheter Arterial Chemoembolization with Drug-Eluting Embolics for Nodular Hepatocellular Carcinoma: A Two-Year Outcome Analysis

Objective@#To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). @*Materials and Methods@#This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and perlesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. @*Results@#The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). @*Conclusion@#DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.

LI-RADS Version 2018 Treatment Response Algorithm: Diagnostic Performance after Transarterial Radioembolization for Hepatocellular Carcinoma

Objective@#To assess the diagnostic performance of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 treatment response algorithm (TRA) for the evaluation of hepatocellular carcinoma (HCC) treated with transarterial radioembolization. @*Materials and Methods@#This retrospective study included patients who underwent transarterial radioembolization for HCC followed by hepatic surgery between January 2011 and December 2019. The resected lesions were determined to have either complete (100%) or incomplete (< 100%) necrosis based on histopathology. Three radiologists independently reviewed the CT or MR images of pre- and post-treatment lesions and assigned categories based on the LI-RADS version 2018 and the TRA, respectively. Diagnostic performances of LI-RADS treatment response (LR-TR) viable and nonviable categories were assessed for each reader, using histopathology from hepatic surgeries as a reference standard. Inter-reader agreements were evaluated using Fleiss κ. @*Results@#A total of 27 patients (mean age ± standard deviation, 55.9 ± 9.1 years; 24 male) with 34 lesions (15 with complete necrosis and 19 with incomplete necrosis on histopathology) were included. To predict complete necrosis, the LR-TR nonviable category had a sensitivity of 73.3–80.0% and a specificity of 78.9–89.5%. For predicting incomplete necrosis, the LR-TR viable category had a sensitivity of 73.7–79.0% and a specificity of 93.3–100%. Five (14.7%) of 34 treated lesions were categorized as LR-TR equivocal by consensus, with two of the five lesions demonstrating incomplete necrosis. Interreader agreement for the LR-TR category was 0.81 (95% confidence interval: 0.66–0.96). @*Conclusion@#The LI-RADS version 2018 TRA can be used to predict the histopathologic viability of HCCs treated with transarterial radioembolization.

Prospective Multi-Center Korean Registry of Transcatheter Arterial Chemoembolization with Drug-Eluting Embolics for Nodular Hepatocellular Carcinoma: A Two-Year Outcome Analysis

Objective@#To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). @*Materials and Methods@#This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and perlesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. @*Results@#The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). @*Conclusion@#DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.

LI-RADS Version 2018 Treatment Response Algorithm: Diagnostic Performance after Transarterial Radioembolization for Hepatocellular Carcinoma

Objective@#To assess the diagnostic performance of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 treatment response algorithm (TRA) for the evaluation of hepatocellular carcinoma (HCC) treated with transarterial radioembolization. @*Materials and Methods@#This retrospective study included patients who underwent transarterial radioembolization for HCC followed by hepatic surgery between January 2011 and December 2019. The resected lesions were determined to have either complete (100%) or incomplete (< 100%) necrosis based on histopathology. Three radiologists independently reviewed the CT or MR images of pre- and post-treatment lesions and assigned categories based on the LI-RADS version 2018 and the TRA, respectively. Diagnostic performances of LI-RADS treatment response (LR-TR) viable and nonviable categories were assessed for each reader, using histopathology from hepatic surgeries as a reference standard. Inter-reader agreements were evaluated using Fleiss κ. @*Results@#A total of 27 patients (mean age ± standard deviation, 55.9 ± 9.1 years; 24 male) with 34 lesions (15 with complete necrosis and 19 with incomplete necrosis on histopathology) were included. To predict complete necrosis, the LR-TR nonviable category had a sensitivity of 73.3–80.0% and a specificity of 78.9–89.5%. For predicting incomplete necrosis, the LR-TR viable category had a sensitivity of 73.7–79.0% and a specificity of 93.3–100%. Five (14.7%) of 34 treated lesions were categorized as LR-TR equivocal by consensus, with two of the five lesions demonstrating incomplete necrosis. Interreader agreement for the LR-TR category was 0.81 (95% confidence interval: 0.66–0.96). @*Conclusion@#The LI-RADS version 2018 TRA can be used to predict the histopathologic viability of HCCs treated with transarterial radioembolization.

Evaluation of Early Response to Treatment of Hepatocellular Carcinoma with Yttrium-90 Radioembolization Using Quantitative Computed Tomography Analysis

OBJECTIVE: To identify an imaging predictor for the assessment of early treatment response to yttrium-90 transarterial radioembolization (TARE) in patients with hepatocellular carcinoma (HCC), using a quantitative assessment of dynamic computed tomography (CT) images. MATERIALS AND METHODS: Dynamic contrast-enhanced CT was obtained pre- and 4 weeks post-TARE in 44 patients (34 men, 10 women; mean age, 60 years) with HCC. Computer software was developed for measuring the percentage increase in the combined delayed-enhancing area and necrotic area (pD + N) and the percentage increase in the necrotic area (pNI) in the tumor-containing segments pre- and post-TARE. Local progression-free survival (PFS) was compared between patient groups using Cox regression and Kaplan-Meier analyses. RESULTS: Post-TARE HCC with pD + N ≥ 35.5% showed significantly longer PFS than those with pD + N < 35.5% (p = 0.001). The local tumor progression hazard ratio was 17.3 (p = 0.009) for pD + N < 35.5% versus pD + N ≥ 35.5% groups. HCCs with a high pNI tended to have longer PFS, although this difference did not reach statistical significance. CONCLUSION: HCCs with a larger pD + N are less likely to develop local progression after TARE.

Imaging Evaluation Following ⁹⁰Y Radioembolization of Liver Tumors: What Radiologists Should Know

Radioembolization using beta-emitting yttrium-90 microspheres is being increasingly used for the treatment of primary and metastatic liver cancers. It is a form of intra-arterial brachytherapy which delivers intense radiation to liver tumors with little embolic effect; this mode of action results in unique post-treatment imaging findings. It is important to understand these imaging findings to avoid misinterpretation of tumor response and to determine further management of the disease. Herein, we discuss the current concepts for assessing tumor response, common post-treatment imaging features, and associated complications following radioembolization.

Angled Cool-Tip Electrode for Radiofrequency Ablation of Small Superficial Subcapsular Tumors in the Liver: A Feasibility Study

OBJECTIVE: To evaluate the feasibility of angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular liver tumors abutting abdominal wall, in order to traverse normal liver parenchyma, and thereby, obtain favorable configuration of ablation margin. MATERIALS AND METHODS: In this study, we retrospectively analyzed 15 small superficial subcapsular liver tumors abutting abdominal wall in 15 patients, treated with radiofrequency ablation from March 2013 to June 2015 using a cool-tip electrode manually modified to create 25-35° angle at the junction between exposed and insulated segments. The tumors were hepatocellular carcinoma (n = 13) and metastases (n = 2: cholangiocellular carcinoma and rectosigmoid cancer), with maximum diameter of 10-26 mm (mean, 15.68 ± 5.29 mm). Under ultrasonographic guidance, the electrode tip was advanced to the depth of the tumors' epicenter about 1 cm from the margin. The tip was re-directed to penetrate the tumor for radiofrequency ablation. Minimal ablation margin was measured at immediate post-treatment CT. Radiological images and medical records were evaluated for success rate, length of minimal ablation margin and complications. RESULTS: Technical success rate of obtaining complete necrosis of the tumors was 100%, with no procedure-related complication. Minimal ablation margin ranged from 3-12 mm (mean, 7.07 ± 2.23 mm). CT/MRI follow-up at 21-1022 days (mean, 519.47 ± 304.51 days) revealed no local recurrence, but distant recurrence in 9 patients. CONCLUSION: Using an angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors abutting abdominal wall may be a feasible technique for obtaining adequate ablation margin and lower complication rate.

Plug-Assisted Retrograde Transvenous Obliteration for the Treatment of Gastric Variceal Hemorrhage

OBJECTIVE: To evaluate the feasibility, safety, and clinical outcomes of plug-assisted retrograde transvenous obliteration (PARTO) to treat gastric variceal hemorrhage in patients with portal hypertension. MATERIALS AND METHODS: From May 2012 to June 2014, 19 patients (11 men and 8 women, median age; 61, with history of gastric variceal hemorrhage; 17, active bleeding; 2) who underwent PARTO using a vascular plug and a gelfoam pledget were retrospectively analyzed. Clinical and laboratory data were examined to evaluate primary (technical and clinical success, complications) and secondary (worsening of esophageal varix [EV], change in liver function) end points. Median follow-up duration was 11 months, from 6.5 to 18 months. The Wilcoxon signed-rank test was used to compare laboratory data before and after the procedure. RESULTS: Technical success (complete occlusion of the efferent shunt and complete filling of gastric varix [GV] with a gelfoam slurry) was achieved in 18 of 19 (94.7%) patients. The embolic materials could not reach the GV in 1 patient who had endoscopic glue injection before our procedure. The clinical success rate (no recurrence of gastric variceal bleeding) was the same because the technically failed patient showed recurrent bleeding later. Acute complications included fever (n = 2), fever and hypotension (n = 2; one diagnosed adrenal insufficiency), and transient microscopic hematuria (n = 3). Ten patients underwent follow-up endoscopy; all exhibited GV improvement, except 2 without endoscopic change. Five patients exhibited aggravated EV, and 2 of them had a bleeding event. Laboratory findings were significantly improved after PARTO. CONCLUSION: PARTO is technically feasible, safe, and effective for gastric variceal hemorrhage in patients with portal hypertension.

Hepatocellular Carcinomas Smaller Than 4 cm Supplied by the Intercostal Artery: Can We Predict Which Intercostal Artery Supplies the Tumor?

OBJECTIVE: To predict which intercostal artery supplies a tumor by examining the spatial relationship between hepatocellular carcinoma (HCC) and the intercostal artery feeding the tumor on transverse computed tomography (CT) images. MATERIALS AND METHODS: Between January 2000 and September 2009, 46 intercostal arteries supplying HCCs smaller than 4 cm were noted in 44 patients, and CT scans and angiograms of these patients were retrospectively reviewed. The intercostal artery feeding the tumor was marked on the CT scan showing the center of the tumor. In addition, its spatial relationship with the tumor center was examined. The angle of the tumor location was measured on the transverse CT scan in the clockwise direction from the sagittal line on the virtual circle centered in the right hemithorax. Correlations between the angle of the tumor location and the level of the tumor-feeding intercostal artery were assessed with the Spearman rank coefficient. RESULTS: Of 46 intercostal arteries feeding HCC, 39 (85%) were the first ones observed from the tumor center in a counterclockwise direction on the transverse CT image containing the tumor center. The level of the tumor-feeding intercostal artery was significantly correlated with the angle of the tumor, as the posteriorly located tumor tends to be supplied by lower intercostal arteries, while the laterally located tumor by upper intercostal arteries (Spearman coefficient = -0.537; p < 0.001). CONCLUSION: We can predict the tumor feeder with an accuracy of 85% as the first intercostal artery encountered from the tumor center in a counterclockwise direction on a transverse CT image.

The Correlation Between the GFR and the Renal Dimensions in Glomerulopathy Patients: Comparison of 2D and 3D Ultrasound

PURPOSE: We wanted to determine the correlation between the renal length as measured on two dimensional (2D) ultrasonography (US) and the renal parenchymal volume as measured with a new three-dimensional (3D) volume probe ultrasound system. We also wanted to determine the correlation between the renal length or renal parenchymal volume and the glomerular filtration rate (GFR) in patients with glomerulopathy. MATERIALS AND METHODS: From July 2007 to December 2007, 26 patients who were pathologically confirmed to have glomerulopathy by biopsy were enrolled. Renal length was measured with 2D US and the renal parenchymal volume was measured with 3D US just prior to biopsy. The GFR was obtained from the electronic medical records. Pearson's correlation coefficients were used to analyze the correlation between the renal length and the renal parenchymal volume, the correlation between the renal length and the GFR and the correlation between the renal parenchymal volume and the GFR. RESULTS: The renal length and the renal parenchymal volume showed strong positive correlation (r = 0.850, p = 0.0001). The correlation coefficient between the renal length and the GFR was 0.623 (p = 0.0007) and the correlation coefficient between the renal volume and the GFR was 0.590 (p = 0.0015). Both the renal length and renal parenchymal volume showed apparently positive correlations with the GFR in glomerulopathy patients. CONCLUSION: The renal length showed strong positive correlations with the renal parenchymal volume. Both the renal length and the renal parenchymal volume showed apparently positive correlations with the GFR in glomerulopathy patients. In glomerulopathy patients, the renal dimensions measured by ultrasound can reflect the status of the GFR, and the measurement of the 2D renal length could be sufficient for follow up. Further studies are needed to evaluate the role of 3D US for assessing patients with renal disease.