- Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma. - Background: There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. - brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT).. - 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT. - Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p’ s ≤ 0.001). - Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR CI p <. - In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3.. - Keywords: Hepatocellular carcinoma, Portal vein branch tumor thrombosis, Brachytherapy, Iodine-125 seeds. - The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. - If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. - Full list of author information is available at the end of the article. - Hepatocellular carcinoma (HCC) is the sixth most com- mon cancer and the third most prevalent cause of cancer-related death worldwide [1]. - Recently, stent placement plus brachy- therapy with iodine-125 seeds has been reported in the treatment of HCC with main portal vein tumor thrombus, with a median OS of 9.3 months [7]. - PVTT was confirmed by the enhancement of an expanding intraluminal mass in the portal vein on the arterial phase, and a low-attenuation intraluminal filling defect on the portal phase of contrast-enhanced computed tomography (CT) or. - Vp2, presence of a tumor thrombus in the second-order branches. - Vp3, presence of a tumor thrombus in the first-order branches. - The exclusion cri- teria were (a) previous treatment for the tumor, includ- ing surgery, radiotherapy, TACE, molecular targeting therapy, and immunotherapy, and (b) Vp4, presence of a tumor thrombus in the main trunk of the portal vein.. - Some patients rejected iodine-125 im- plantation. - Patients in the TACE-iodine-125 group received combined treatments of iodine-125 seed implantation and TACE. - patients in the TACE group were treated with TACE alone. - This clinical study was approved by the Ethics Committee of the First Hospital of China Medical University, and written informed consent was obtained from all patients before the procedures.. - Hepatic arteriography was conducted to detect feeding arteries of the HCC and existence of arterioportal shunts (APS). - If APS was confirmed, the location, severity and direction of the vessels was identified through further ar- teriography, then super selection was performed with a microcatheter (Progreat, Terumo, Japan) advancing into the feeding artery of APS. - Lastly, a micro- catheter was inserted into the feeding arteries of the HCC to deliver 40 mg epirubicin (Pharmorubicin, Pfizer, USA) mixed with 4–20 mL (mean mL) iodized oil (Youliying, Hengrui, China) under fluoroscopic guid- ance. - Brachytherapy was performed for the TACE- Iodine-125 group 1–2 weeks after the administration of. - Preprocedural contrast-enhanced images were imported into the treatment planning system (Beijing University of Aeronautics and Astronautics, China) to evaluate the number and locations of seeds and access paths of the needles. - CT examin- ation was performed immediately after the procedures, and the images were input to the treatment planning system again to verify the doses of the implantations.. - Follow-up was conducted for all patients, with contrast- enhanced CT or MRI 1 month after completion of the initial treatments, and follow-up intervals of 2 – 3 months. - Classic RILD was defined as anic- teric hepatomegaly and ascites with more than double the upper limit of the normal level of alkaline phosphate (AKP). - nonclassic RILD was defined as ≥ grade 3 hepatic toxicities, with more than 3 times the upper limit of the normal level of blood bilirubin or more than 5 times the upper limit of the normal levels of ALT or AST [13]. - 1 a Contrast-enhanced CT of two 1-cm diameter tumor thrombi floating in the right segment of the portal vein. - c The needle (white arrow) was placed in the distal thrombus. - PVBTT re- sponse was evaluated between baseline and best re- sponse by a modified standard: the product of the largest perpendicular diameters of the tumor thrombus was calculated and compared to the initial value [15].. - The response of the PVBTT was defined as complete re- sponse (CR), complete disappearance of the PVBTT;. - partial response (PR), ≥50% decrease in the value. - Progression-free survival (PFS) was defined as the period from the day of the procedure until radiologic confirm- ation of tumor progression or death. - PVBTT PFS was calculated separately according to the progressive disease of the tumor thrombus. - For analyses of the base- line characteristics, continuous variables are presented as the mean ± SD and were compared by Student’s t-test or Mann-Whitney U test. - 0.1 in the univariate analyses were en- tered into the multivariate analyses. - Backward elimin- ation Cox regression was applied to select the risk factors in the multivariate analyses. - Among the 69 patients included in the study, 34 were in the TACE-iodine-125 group, and 35 were in the TACE group. - The mean age of the entire cohort was years. - The baseline characteristics of the TACE-iodine- 125 group and the TACE group were not significantly different except for a slightly higher AFP value in the TACE-only patients (p = 0.032) (Table 1). - An average of 15 iodine-125 seeds were implanted in the patients in the combined treatment group. - The duration of the proced- ure was 10–20 min (mean min). - All the iodine-125 brachytherapy and TACE procedures were technically successful.. - Grades 1 and 2 post-chemoembolization syn- drome (fever, vomiting, and abdominal pain) occurred in 27 patients (79.4%) in the TACE-iodine-125 group and 30 patients (85.7%) in the TACE group (p = 0.49). - Tumor responses of the intrahepatic tumor and PVBTT are given in Table 3. - The ORR and DCR for PVBTT were significantly higher in the TACE-iodine- 125 group than in the TACE group (58.9% vs. - Similarly, the DCR for intra- hepatic tumor was significantly greater in the TACE- iodine-125 group than in the TACE group (73.5% vs.. - The patients in the TACE-iodine-125 group had a significantly longer median PFS for PVBTT than did those in the TACE group (9 vs. - In addition, the median PFS for intrahepatic tumors was significantly longer in the TACE-iodine-125 group than in the TACE group (5 vs. - The median OS was 13 months in the CR + PR group and 7 months in the SD + PD group (HR CI p <. - 0.1 in the univariate. - The multivariate Cox proportional hazard model revealed that treatment modality (TACE- iodine − 125 vs. - Treatment with TACE-iodine-125 provided a better OS in the subgroups of male, ECOG = 0, type of Vp1 + Vp2, single tumor, size. - 400 ng/mL, compared OS of the sub- groups of female, ECOG = 1 + 2, type of VP3, multiple tumors, size ≤5 cm, and AFP ≤ 400 ng/mL. - The median OS for PVBTT types was further analyzed: In the Vp1 + Table 1 Baseline characteristics of the patients. - Variable TACE-Iodine-125 ( n = 34. - Vp2 subgroup, the median OS was significantly longer in the TACE-iodine-125 group than in the TACE-alone group (13 vs. - 7.5 months, HR CI p = 0.017], whereas in the Vp3 subgroup, the median OS was not significantly different for the two treatment modalities (8 vs. - Our study revealed that combined treatment of TACE and implantation iodine-125 seeds had a better tumor re- sponse and significant survival benefit over TACE alone in the patients with PVBTT. - In the subgroup analysis,. - Our study has thus demonstrated, with correlation analysis, that effective treatment of PVBTT could improve intrahepatic tumor Table 3 Intrahepatic tumor and PVBTT responses in the two groups. - 2 PVBTT response rate in the TACE-Iodine-125 group (blue bars) and the TACE group (yellow bars). - The PVBTT response rate is presented as change in the product of perpendicular diameters of the tumor thrombosis from baseline. - The me- dian OS was better in the patients whose PVBTT responded (CR + PR, 13 months) rather than in the pa- tients without response (SD + PD, 7 months). - Therefore, control of the PVTT is as important as treatment of intrahepatic tumors for patients with advanced HCC.. - The survival benefit of local brachytherapy of PVBTT in the Vp3 subgroup was not statistically significant, with a median survival time of 8 vs. - CT guidance was used in most previous studies of iodine-125 treatment of PVTT [21, 22]. - Unlike with CT guidance, the direction of the needle can be adjusted precisely in real time with ultrasound, thereby substantially reducing operation time and complications. - The ultrasound guiding ap- proach has disadvantages, however, as the images it ac- quires cannot be imported into the treatment planning system immediately to verify effective distribution after seed implantation, and examination of the lesion is sometimes affected by gastrointestinal and lung gas.. - 3 Scatter plot of the PVBTT and intrahepatic tumor response rate in the entire cohort. - c Comparison of the OS curves. - 400 into baseline characteristics in the last 5 years . - One of the reasons for the lack of detection was hepatatrophy caused by cirrhosis, which may affect liver function and survival. - Multicenter randomized controlled trials with a large cohort of patients treated with brachytherapy and immune checkpoint inhibitors may be warranted in the future.. - HCC: Hepatocellular carcinoma. - PVBTT: Portal vein-branch tumor thrombus. - PVTT: Portal vein tumor thrombus. - The threshold value was 3 times the upper limit of the normal level (20 μ mol/L). - The threshold value was 2 times the upper limit of the normal level (125 U/L). - The threshold value was 5 times the upper limit of the normal level (50 U/L). - The threshold value was 5 times the upper limit of the normal level (40 U/L).. - DH conceived of the project, collected cases and wrote the paper. - All the authors gave the final approval of the manuscript.. - The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.. - This clinical study was approved by the Ethics Committee of the First Hospital of China Medical University and was carried out in accordance with. - Hepatocellular carcinoma with portal vein tumor involvement: best management strategies. - https://doi.org/10.1055/s . - Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. - Surgical treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus. - Multidisciplinary treatments for hepatocellular carcinoma with major portal vein tumor thrombus. - https://doi.org/10.1007/s . - chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis. - Hepatic resection or transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus. - https://doi.org/10.1 007/s x.. - Hepatic resection versus transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus. - Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus. - Treatment of hepatocellular carcinoma with tumor Thrombus with the use of Iodine-125 seed Strand implantation and Transarterial chemoembolization: a propensity-score analysis
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