BACKGROUND:While partial splenic artery embolization (PSE) has been effectively employed in treating portal hypertension, cirrhosis, and idiopathic thrombocytopenia, its combination with hepatic artery infusion chemotherapy (HAIC) for the management of chemotherapy-induced hypersplenism (CIH) has not been previously explored. This retrospective study aims to provide clinical insights into this potential therapeutic approach. MATERIALS AND METHODS:We conducted a retrospective analysis involving patients with colorectal cancer liver metastases (CRLM) who received PSE in conjunction with HAIC (utilizing the FOLFOX regimen) to manage thrombocytopenia due to hypersplenism. Tumor response assessment followed the response evaluation criteria in solid tumors, while adverse reactions were categorized using the Common Terminology Criteria for Adverse Events (version 5.0). The primary objective was to attain a platelet (PLT) count of 100 × 10 9 /L, with secondary objectives encompassing evaluation of adverse events related to the combined therapy and its efficacy against liver metastases. RESULTS:From January 2018 to May 2023, 20 patients with CRLM and CIH were consecutively enrolled in this investigation, each undergoing PSE and HAIC. In total, PSE was performed 25 times. Median pre- and post-PSE PLT counts were 51 × 10 9 /L and 116 × 10 9 /L, respectively, with 80% of participants reaching the primary endpoint of a PLT count of ≥100 × 10 9 /L. Abdominal pain emerged as the most frequent postoperative complication, affecting 11 patients (44%). The objective response rate stood at 25%, while the disease-control rate was reported at 80%. The median progression-free survival was measured at 3.9 months, with a median overall survival of 13.8 months. CONCLUSION:The combination of PSE and HAIC (FOLFOX regimen) represents a safe and effective strategy for managing CIH and CRLM, demonstrating favorable outcomes in PLT count restoration and disease control.

53 Background: Liver metastases are the main cause of death in colorectal cancer (CRC), yet only ~20% of patients qualify for surgery. For unresectable colorectal liver metastases (CRCLM), hepatic arterial infusion chemotherapy (HAIC) and drug-eluting bead transarterial chemoembolization (DEB-TACE) are common treatments. This study assesses the efficacy and safety of combining DEB-TACE with HAIC using FOLFOX or FOLFIRI. Methods: This retrospective study included 221 CRCLM patients treated at Peking University Cancer Hospital from 2018 to 2023. Of these, 182 received DEB-TACE with HAIC-FOLFOX and 39 with HAIC-FOLFIRI. Propensity score matching (PSM) minimized selection bias. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), hepatic PFS (hPFS), objective response rate (ORR), disease control rate (DCR), and treatment-related safety. Results: Propensity matching resulted in 38 pairs, achieving comparable baseline between DEB-TACE-HAIC-FOLFOX and DEB-TACE-HAIC-FOLFIRI cohorts. Of these pairs, 45 were male and 31 were female. Around 65.8% patients were younger than 65 years. The original locations of CRC in 67.1% of patients were on the left side. The middle to high grades of tumor were dominant (88.2%). Notably, 56.6% of patients harbored mutations in KRAS, NRAS or BRAF and extrahepatic metastasis occurred in 78.9% patients. Additionally, 75% patients were refractory to second line systemic therapy. Median hepatic progression-free survival (hPFS), progression-free survival (PFS), and overall survival (OS) were all slightly better in the matched DEB-TACE-HAIC-FOLFOX cohort, but not statistically significant (median hPFS: 8.6 vs. 5.8 months, P=0.206; median PFS: 6.4 vs. 4 months, P=0.062; median OS: 11.8 vs. 10.8 months, P=0.249). The objective response rate (ORR) was 36.8% in the DEB-TACE-HAIC-FOLFOX group and 39.5% in the DEB-TACE-HAIC-FOLFIRI group, with disease control rates (DCR) of 71.1% and 76.3%, respectively. These patients received 224 DEB-TACE plus HAIC treatments. There were no treatment-related deaths. Serious adverse events were comparable between the two groups, except for elevated transaminase. However, transaminase elevation was actually due to drug-eluting beads difference during DEB-TACE. With the further analysis of drug-eluting beads’ effect on adverse events, transaminase elevation, nausea, vomiting and pain occurred much frequently with DCB drug-eluting bead than HepaSphere drug-eluting bead; these differences were statistically significant. Conclusions: The combination of DEB-TACE with FOLFOX or FOLFIRI HAIC shows promising efficacy and tolerable safety for unresectable CRCLM. The FOLFIRI-based regimen is a viable alternative, especially for oxaliplatin-intolerant patients.

Background: Gastric cancer (GC) is the fifth most common cancer and the fourth leading cause of cancer-related mortality worldwide. The liver is the primary metastatic site, and the prognosis of gastric cancer with liver metastasis (GCLM) remains poor. While transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are used for liver cancer, their roles in GCLM remain underexplored. Objectives: This study aimed to evaluate the efficacy and safety of drug-eluting bead TACE (DEB-TACE) combined with HAIC in patients with unresectable GCLM. Design: This was a retrospective, single-center cohort study. Methods: We retrospectively analyzed 62 patients with GCLM treated at Peking University Cancer Hospital between July 2018 and June 2023. Patients underwent 135 sessions using either HepaSphere beads plus HAIC-FOLFOX (HEPA-HAIC, n = 33) or DC bead plus HAIC-FOLFOX (DCB-HAIC, n = 29). The primary endpoint was median overall survival (mOS); secondary endpoints included median hepatic progression-free survival (mhPFS), median progression-free survival (mPFS), tumor response, and safety. Results: Among the patients (53 male, 9 female), 75.8% had intestinal-type cancer. Over 95% underwent prior treatments. The mOS was 10.7 months in both groups. The HEPA-HAIC cohort achieved longer mhPFS (8.6 vs 7.6 months) and mPFS (5.7 vs 4.4 months), though not statistically significant. Objective response rate and disease control rate were similar (30.3%/75.8% vs 31.0%/75.9%). Propensity score matching confirmed these findings. Univariate Cox regression suggested primary tumor location and carcinoembryonic antigen were prognostic for hPFS and OS, respectively. No treatment-related deaths occurred. Common adverse events (AEs) were transaminase elevation and pain. Nausea, vomiting, and severe pain were significantly less frequent with HEPA-HAIC (5.6% vs 31.7%, p = 0.001; 4.2% vs 31.7%, p < 0.001; 8.3% vs 22.2%, p = 0.01). Conclusion: DEB-TACE plus HAIC was feasible and demonstrated intrahepatic disease control with acceptable tolerability in unresectable GCLM; HEPA-HAIC showed a favorable safety profile.

Background:Chemotherapy combined with immune checkpoint inhibitor have prolonged survival of patients with advanced biliary tract cancers (BTCs), and the previous studies showed the synergistic anti-tumor effect of chemotherapy, anti-angiogenesis therapy, and immunotherapy. Hepatic arterial infusion chemotherapy (HAIC) achieved a higher tumor response and survival benefit in previous phase II studies for advanced BTCs. Thus, we conducted this phase II trial to evaluate the efficacy and safety of HAIC combined with bevacizumab and toripalimab for advanced BTCs. Methods:Treatment-naïve participants with advanced BTCs were recruited for this phase II trial. Combination therapy, comprising HAIC with bevacizumab (300 mg, day 1), oxaliplatin (40 mg/m2, 2 h, days 1-3), and 5-fluorouracil (800 mg/m2, 22 h, days 1-3) plus intravenous toripalimab (240 mg, day 1 before HAIC), was repeated every 4 weeks for a maximum of six consecutive cycles. Intravenous toripalimab (240 mg) and bevacizumab (300 mg) were administered every 4 weeks as maintenance treatment. The primary endpoint was objective response rate (ORR) according to Immune-Modified Response Evaluation Criteria in Solid Tumors criteria, and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Olink proximity extension assay with a Target 96 Immuno-Oncology panel was exploratory investigated. Results:Between July 2020 and January 2022, 32 participants were enrolled. The ORR was 84.38%, and the disease control rate was 96.88%. Median PFS and OS were 13.20 months [95% confidence interval (CI): 8.93-17.47] and 19.0 months (95% CI: 12.22-25.78), respectively. Grade 3 or higher adverse events (AEs) were observed in 10 participants (31.25%), and the most frequent grade 3 or higher AEs were elevated ALT/AST (4/32, 12.50%), elevated total bilirubin (3/32, 9.38%), and neutropenia (3/32, 9.38%). In exploratory analysis, Child-Pugh B [hazard ratio (HR): 22.65, 95% CI: 3.66-140.08, P=0.001] and high level of macrophage metalloproteinase-12 (HR: 5.99, 95% CI: 1.60-22.37, P=0.008) were indicated as the risk factors related to worse PFS. Conclusions:HAIC combined with bevacizumab and toripalimab may serve as an improved first-line treatment for advanced BTCs, which require a randomized control trial for verification. Trial Registration:This trial is registered at ClinicalTrail.gov (NCT04217954).

Aim: To analyze the risk factors for oxaliplatin (OXA)-induced severe hypersensitivity reactions and identify the recurrence rate of the reactions after an OXA rechallenge in patients treated with hepatic arterial infusion chemotherapy (HAIC). Methods: Among the 2251 patients treated with HAIC (OXA), 84 patients with gastrointestinal cancer who displayed hypersensitivity reactions between May 2013 and May 2022 were included in this study. Among the 84 patients, 23 (27.4%) developed severe anaphylactic reactions (grade III/IV), and 61 (72.6%) developed grade I/II reactions. We explored the risk factors for severe OXA-induced hypersensitivity reactions. Twenty-seven patients with grade I/II reactions underwent retreatment (HAIC with OXA), and the recurrence rate of the hypersensitivity reactions was determined. A multivariate logistic regression model was used to analyze the risk factors for OXA-induced hypersensitivity reaction. Results: In the study, multivariate analysis indicated that the dose of OXA (odds ratio [OR] 3.077, 95 % confidence interval [CI] 1.106-8.558, p = 0.031) was an independent risk factor for OXA-induced severe hypersensitivity reactions. Twenty-seven patients with non-severe hypersensitivity reactions underwent retreatment HAIC with OXA and 14 (51.9 %) experienced HSR recurrence, including 2 (7.4 %) who experienced hypersensitivity shock. Conclusions: The administration of OXA doses is a risk factor for OXA-induced severe hypersensitivity reactions in patients treated with HAIC (OXA). Rechallenging HAIC with OXA appears to be associated with a higher recurrence rate of the HSR.

e16164 Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) is established as a safe and effective treatment for advanced hepatocellular carcinoma (HCC). Recent advancements in molecular targeted agents and immunotherapy have led to exploration of combining DEB-TACE with tyrosine kinase inhibitors (TKIs) or immunotherapy. However, real-world evaluations of DEB-TACE in combination with TKIs or immunotherapy are limited. This study aimed to assess the efficacy and safety of DEB-TACE alone, DEB-TACE with TKIs, and DEB-TACE with TKIs and immunotherapy. Methods: This study retrospectively enrolled 124 patients with unresectable HCC treated at Peking University Cancer Hospital from April 2018 to April 2023. Patients were divided into three groups: DEB-TACE alone (DTACE, 45 patients), DEB-TACE plus TKI (DTACE+TKI, 51 patients), and DEB-TACE plus TKI and immunotherapy (DTACE+TKI+IM, 28 patients). Propensity score matching (PSM) was used to compare efficacy and safety between DTACE and DTACE+TKI. Primary endpoints were progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), assessed by RECIST Version 1.1. Adverse events were graded according to CTCAE version 5.0. Results: Among the patients, 99 were male and 25 were female, with 88.7% in BCLC-B or C stage. Before enrollment, 50.8% had received other treatments. In the DTACE+TKI+IM group, mPFS and mOS were higher compared to DTACE or DTACE+TKI alone (mPFS: 15.2 vs 9.2 for DTACE, 8.7 for DTACE+TKI; mOS: 32.3 vs 25.0 for DTACE, 20.9 for DTACE+TKI), though not statistically significant. ORR and DCR were 31.3% and 86.7% in DTACE, 35.3% and 84.3% in DTACE+TKI, and 39.3% and 96.4% in DTACE+TKI+IM, respectively. PSM analysis for DTACE and DTACE+TKI showed slightly better mPFS and mOS in DTACE+TKI (mPFS: 9.5 vs 9.2 months; mOS: 26.2 vs 19.4 months). No treatment-related deaths occurred, and serious adverse events (AEs) were comparable among the groups, with pain being the most common. AE. Notably, the frequency and severity of pain were closely related to the type of drug-eluting beads used, with the incidence of severe pain significantly lower in the HepaSphere DEB-TACE group compared to the CalliSphere or DCB group (0% versus 12.4% versus 19.7%, respectively; p < 0.001). Conclusions: DEB-TACE has been demonstrated as a safe, feasible, and efficacious treatment option for patients with unresectable HCC. There is a notable trend towards prolonged progression-free survival (PFS) and overall survival (OS) when DEB-TACE is combined with TKIs and immunotherapy. Moreover, HepaSphere DEB-TACE shows a lower incidence of severe pain compared to other types of drug-eluting beads, further highlighting its potential advantages in managing HCC.

BACKGROUND AND AIM:Transarterial chemoembolization combined with hepatic arterial infusion chemotherapy (TACE-HAIC) has shown encouraging efficacy in the treatment of unresectable hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict overall survival (OS) of patients with unresectable HCC treated with TACE-HAIC. METHODS:A total of 591 patients with unresectable HCC treated with TACE-HAIC between May 2009 and September 2020 were enrolled. These patients were randomly divided into training and validation cohorts. The independent prognostic factors were identified with Cox proportional hazards model. The model's discriminative ability and accuracy were validated using concordance index (C-index), calibration plots, the area under the time-dependent receiver operating characteristic curve (AUC) and decision curve analyses (DCAs). RESULTS:The median OS was 15.6 months. A nomogram was established based on these factors, including tumor size, vein invasion, extrahepatic metastasis, tumor number, alpha fetoprotein (AFP), and albumin-bilirubin (ALBI), to predict OS for patients with unresectable HCC treated with TACE-HAIC. The C-index of the nomogram were 0.717 in the training cohort and 0.724 in validation cohort. The calibration plots demonstrated good agreement between the predicted outcomes and the actual observations. The AUC values were better than those of three conventional staging systems. The results of DCA indicated that the nomogram may have clinical usefulness. The patients in the low-risk group had a longer OS than those in intermediate-risk and high-risk groups (P<0.001). CONCLUSION:A prognostic nomogram was developed and validated to assist clinicians in accurately predicting the OS of patients with unresectable HCC after TACE-HAIC.

Purpose: Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity for hepatocellular carcinoma (HCC). Several studies have compared HAIC and Transarterial chemoembolization (TACE). However, comparisons between TACE plus HAIC and HAIC are rarely reported. Here, we evaluated the performance of HepaSphere DEB-TACE combined with HAIC (HepaHAIC) compared to HAIC in patients with advanced HCC. Patients and Methods: In this retrospective study, we enrolled 167 patients diagnosed with advanced HCC and treated at Peking University Cancer Hospital from May 2018 to May 2022. The cohort comprised 74 patients who received HepaSphere DEB-TACE combined with HAICFOLFOX (Hepa-HAIC) and 93 patients who received HAIC-FOLFOX. Over 60% of patients received prior treatments. To avoid selection bias, propensity score matching was applied to the efficacy and safety analyses. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoints include objective response rate (ORR), disease control rate (DCR), and safety. Results: Propensity-matching yielded 48 pairs, and group baselines were almost equal after matching. Median PFS and median OS were both higher in the matched Hepa-HAIC cohort (median PFS: 8.9 vs 5.8 months, p = 0.035; median OS: 22.4 vs 9.5 months, p = 0.027), which was consistent with pre-matching analysis. The ORR in the Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; the DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Grade 3-4 ALT elevation was more frequent in the Hepa-HAIC group (33.3% vs 8.3%, p = 0.003), while vomiting was more frequent in the HAIC group (29.2% vs 12.5%, p = 0.084). Conclusion: The Hepa-HAIC group is superior to the HAIC group in metrics of PFS, OS, ORR, and DCR, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with a comparable safety profile in advanced HCC.

Background The prognosis of hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT) is dismal after standard treatment with sorafenib. Hepatic arterial infusion chemotherapy (HAIC) has been suggested for patients with HCC and major PVTT. Purpose To compare the efficacy and safety of sorafenib plus 3cir-OFF HAIC versus sorafenib alone for advanced HCC with major PVTT. Materials and Methods This phase II trial recruited systemic treatment-naïve patients with HCC and major PVTT (portal vein invasion grade Vp3 [first branch] and Vp4 [main trunk]) between June 2017 and November 2019. Patients were randomly assigned (1:1 ratio) to receive sorafenib (400 mg twice daily) plus 3cir-OFF HAIC (35 mg/m2 oxaliplatin [hours 0-2] followed by 600 mg/m2 5-fluorouracil [hours 2-24], days 1-3) with a standardized percutaneous port catheter system or sorafenib alone (400 mg twice daily) every 4 weeks. The primary end point was overall survival (OS). The secondary end points were objective response rate, progression-free survival (PFS), and safety. OS and PFS were assessed using the Kaplan-Meier method and log-rank test. Results The intent-to-treat population included 64 patients, with 32 in each group. The median OS was 16.3 months (95% CI: 0.0, 35.5) with sorafenib plus HAIC and 6.5 months (95% CI: 4.4, 8.6) with sorafenib alone (hazard ratio [HR] = 0.28; 95% CI: 0.15, 0.53; P < .001). A higher objective response rate (41% [n = 13] vs 3% [n = 1], P < .001) and a longer median PFS (9.0 months vs 2.5 months; HR = 0.26; 95% CI: 0.15, 0.47; P < .001) were observed in the sorafenib plus HAIC group. Grade 3 or 4 adverse events were more frequent in the sorafenib plus HAIC group, including diarrhea (n = 7 [22%] vs n = 5 [16%]), hand-foot syndrome (n = 6 [19%] vs n = 2 [6%]), and thrombocytopenia (n = 7 [22%] vs n = 0). Conclusion Sorafenib plus 3cir-OFF hepatic arterial infusion chemotherapy may be a promising treatment in patients with hepatocellular carcinoma and major portal vein tumor thrombosis because of the improved survival and an acceptable safety profile. Clinical trial registration no. NCT03009461 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chung in this issue.

Abstract Background Hepatic arterial infusion chemotherapy delivers the drug directly to the liver. We aim to explore the benefits and tolerability of Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal liver metastasis refractory to standard systemic chemotherapy. Methods This study analyzed 47 patients treated with hepatic arterial infusion chemotherapy plus regorafenib after standard systemic oxaliplatin and/or irinotecan in combination with bevacizumab or cetuximab between Jan 2017 and Jun 2020. Regorafenib was given for only 3 weeks in a 4-week cycle. Results Among 47 patients, 32 (68%) were males. The median age was 61 (29–75). With a median follow-up of 22.2 months (3.7–50.7 months). Before Hepatic arterial infusion chemotherapy administration in combination with regorafenib, 34 (72.3%) patients previously received ≥ 2 prior lines of systemic therapy and 37 (78.7%)patients previously received targeted biological treatment (anti-VEGF or anti-EGFR, or both). The initial doses of regorafenib were 40 mg/d (n = 1, 2.13%), 80 mg/d (n = 11, 23.43%), 120 mg/d (n = 2, 4.26%), and 160 mg/d (n = 23, 48.94%), while for 24.6% (n = 14) dose was unknown. Median Overall Survival was 22.2 months. Median Progression-Free Survival was 10.8 (95% CI: 9.0–13.7) months. Common Adverse Events were hand-foot skin reaction (12.77%), fatigue (6.38%), vomiting (6.38%), and decreased appetite (6.38%). Only 2 patients discontinued regorafenib due to Adverse Events. Conclusions Regorafenib combined with Hepatic arterial infusion was effective and tolerable in patients with liver predominant metastasis of colorectal cancer. Hence, this therapy can be considered as an alternative for second- or subsequent lines of therapy in patients refractory to standard systemic chemotherapy.

Background The association of contrast-enhanced MRI (CE-MRI) and the overall survival (OS) of biliary tract cancers (BTC) is ambiguous. Thus, the aim of this study is to evaluate the value of signal enhancement ratio (SER) and its early change in CE-MRI as biomarkers of survival after hepatic arterial infusion chemotherapy (HAIC) in BTC. Results One hundred and two BTC patients treated via HAIC with 3cir-OFF regimen between January 2011 and June 2020 were enrolled in this retrospective study. The median progression-free survival (PFS) and OS were 9.8 months [range 1.5–83.3 months, 95% confidence interval (CI) 7.789–11.811] and 14.2 months (range 1.8–83.3 months, 95% CI: 11.106–17.294), respectively. The cutoff value of SER before HAIC (SER 0 ) was 1.04, and both median PFS and OS in the SER 0 ≥ 1.04 group were longer than in the SER 0 < 1.04 group (median PFS: 10.5 vs. 8.5 months, p = 0.027; median OS: 23.9 vs. 12.3 months, p < 0.001). The median OS in the ΔSER > 0 group was longer than in the ΔSER < 0 group (17.3 versus 12.8 months, p = 0.029 (ΔSER means the change of SER after two cycles of HAIC). Multivariate analysis showed SER 0 ( p = 0.029) and HAIC treatment cycle ( p = 0.002) were independent predictors of longer survival. Conclusions SER in CE-MRI before HAIC (SER 0 ) is a potential biomarker for the prediction of survival after HAIC in advanced BTC.

OBJECTIVE:This study aimed to introduce and evaluate a new embolization technique for the right gastric artery (RGA) during percutaneous implantation of a port-catheter system for hepatic arterial infusion chemotherapy (HAIC).METHODS:From January 2013 to January 2017, 159 patients with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system. In 86 of these patients (56 men; aged 28-88 years; mean: 60.6 ​± ​12.0 years), in whom the RGA was obvious on arteriography, embolization of RGA was attempted using microcoils to protect the gastric mucosa during HAIC. In the first phase (first three years), antegrade embolization of the RGA using a 2.7 Fr microcatheter was performed in 55 patients. In the second phase (next two years), embolization of the RGA was attempted by combining antegrade embolization and retrograde embolization through the left gastric artery (LGA) in 31 patients. The success rates and the incidence of acute gastroduodenal mucosal toxicity (AGMT) in these two groups were compared.RESULTS:The total success rate of the RGA embolization was 70.9%. The success rate was 83.9% in 31 patients who underwent combined antegrade and retrograde embolization, which was significantly higher than that of antegrade embolization alone (63.6%) performed in 55 patients (p ​= ​0.047). No complications related to embolization of RGA were documented. The incidence of AGMT was 29.1% (16/55) in patients in the first phase, which was significantly higher than that in the patients in the second phase (9.7%, 3/31) (p ​= ​0.037).CONCLUSION:A combination of retrograde embolization via LGA could increase the success rates of RGA embolization and reduce the incidence of AGMT after HAIC.

Aim: We investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKIs) for advanced hepatocellular carcinoma (HCC). Method: This retrospective study included HCC patients treated with HAIC, TKIs and anti-PD-1 antibodies between May 2019 and November 2020 in our hospital. Primary end points were progression-free survival and safety. Results: Twenty-seven advanced HCC patients were analyzed. The median follow-up was 12.9 months (range: 4.0-24.0 months) and the median progression-free survival was 10.6 months. The objective response rate and disease control rate were 63.0 and 92.6%, respectively. No treatment-related deaths occurred. Conclusion: In patients with advanced HCC, treatment with HAIC, anti-PD-1 antibodies and oral TKIs was effective and safe. Lay abstract Some tyrosine kinase inhibitors (TKIs) that inhibit tumor vessel growth, such as sorafenib and lenvatinib, have been recommended as first-line treatment for advanced hepatocellular carcinoma (HCC). In hepatic artery infusion chemotherapy, chemotherapeutic drugs can be delivered via a microcatheter to the tumor-supplying artery to increase the local drug concentration, leading to higher local disease control rates and less toxicity than systemic chemotherapy. The combination of anti-PD-1 immunotherapy plus TKIs was shown in a previous study to be a safe and effective treatment for advanced HCC. This study explored the safety and effectiveness of hepatic artery infusion chemotherapy, TKIs and an anti-PD-1 antibody for the treatment of advanced HCC and found that combination therapy is effective, with good tolerability.

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Background. Survival of patients with portal vein tumor thrombosis (PVTT) is extremely poor; transarterial chemoembolization (TACE) is a treatment for patients with HCC and PVTT. Some studies showed that hepatic arterial infusion chemotherapy (HAIC) might improve the survival of HCC with PVTT. There were few researches of combining TACE with HAIC for patients with HCC and PVTT. Aim. This study was aimed at comparing overall survival (OS) and progression-free survival (PFS) following treatment with conventional transarterial chemoembolization plus hepatic arterial infusion chemotherapy (cTACE-HAIC) or conventional transarterial chemoembolization (cTACE) alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). Methods. From January 2011 to December 2016, 155 patients with HCC and PVTT who received cTACE-HAIC (cTACE-HAIC group) (n=86) or cTACE alone (cTACE group) (n=69) were retrospectively evaluated. Propensity score matching (PSM) reduced the confounding bias and yielded 60 matched patient pairs. The tumors’ responses were evaluated using the modified response evaluation criteria in solid tumors (mRECIST). OS and PFS of groups were compared using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models. Results. The median follow-up duration was 93 months (range: 1–93 months). The cTACE-HAIC group’s OS (9.0 months) and PFS (6.0 months) were significantly longer than the cTACE group’s OS (5.0 months) and PFS (2.0 months) (p=0.018 and p=0.045, respectively) in the matched cohort. Multivariate analyses showed that cTACE-HAIC was independently associated with OS (hazard ratio (HR) 0.602, p=0.010) and PFS (HR 0.66, p=0.038). The matched groups did not differ regarding grade 3 or 4 adverse events. Conclusion. cTACE-HAIC was superior to cTACE alone regarding OS and PFS in patients with HCC and PVTT. Treatment-associated toxicities were generally well tolerated.

Purpose: To evaluate the prognostic value of pretreatment serum g-glutamyltransferase (GGT) level in patients with advanced hepatocellular carcinoma (HCC) receiving transarterial chemoembolization. Materials and Methods: This 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. Results: The 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. Conclusions: Pretreatment 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.

To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) to transarterial chemoembolization/embolization (TACE/TAE) for the treatment of advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT). Forty-six patients with advanced HCC with major PVTT who underwent HAIC or TACE/TAE between April 2013 and April 2017 were included. In the HAIC group (n = 22), oxaliplatin (35–40 mg/m2 for 2 h) and 5-fluorouracil (600–800 mg/m2 for 22 h) on days 1–3 every 4 weeks were administered for a maximum of six serial courses. In the TACE/TAE group (n = 24), an emulsion of epirubicin (40–60 mg) and lipiodol was administered followed by particles (cTACE), or particles alone embolization (TAE). Overall survival (OS), tumor response according to mRECIST, progression-free survival (PFS), and adverse events were investigated. Median OS was 20.8 months in the HAIC group versus 4.0 months in the TACE/TAE group (P < 0.001; hazard ratio [HR], 0.17). The HAIC group showed higher tumor response rates than the TACE/TAE group (59.1% [13/22] vs. 22.7% [5/22]; P = 0.014) and a longer median PFS (9.6 vs. 1.5 months; P < 0.001; HR, 0.09). The Child–Pugh class (P = 0.007) and treatment method (P = 0.002) were independent risk factors of survival. The most frequent grade 3 or worse treatment-related adverse events were liver dysfunction (2 [9.1%] vs. 5 [20.8%]), hematological abnormalities (1 [4.5%] vs. 2 [8.3%]), and fever (1 [4.5%] vs. 4 [16.7%]). One treatment-related death due to acute liver failure occurred 3 days after TACE treatment. HAIC may significantly improve OS and provide better tumor control with mild side effects and preserved liver function in patients with advanced HCC with major PVTT compared to TACE/TAE treatment.

BACKGROUND There is little evidence of combining sorafenib with hepatic arterial infusion chemotherapy (HAIC) after transarterial chemoembolization (TACE) for intermediate and advanced hepatocellular carcinoma (HCC). It is important to identify that patients with intermediate and advanced HCC are most likely to benefit from this combination therapy. AIM To investigate the safety and clinical outcomes of sorafenib combined with HAIC with folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) after TACE for intermediate and advanced HCC. METHODS This prospective phase II study enrolled patients with intermediate and advanced HCC who underwent treatment with sorafenib combined with TACE-HAIC. All patients initially received the standard 400 mg dose of sorafenib twice daily before TACE-HAIC. Participants at our institute with intermediate and advanced HCC underwent routine TACE. Then, the catheter used for embolization was kept in place in the hepatic artery, and oxaliplatin was intra-arterially administered for 6 h, followed by 5-FU for 18 h, and folinic acid was intravenously administered for 2 h. The primary endpoints were safety, as evaluated by the Common Terminology and Criteria for Adverse Events version 4.0, and 12-mo progression-free survival (PFS), as analyzed by the Kaplan-Meier method. As secondary endpoints, the objective response rate (ORR) was evaluated by the modified Response Evaluation Criteria for Solid Tumors, and survival time [overall survival (OS)] was analyzed by the Kaplan-Meier method. RESULTS Sixty-six participants at our institute with intermediate and advanced HCC were enrolled in this prospective study (mean age, 53.3 ± 11.7 years). Approximately 56.1% of participants had Barcelona Clinic Liver Cancer (BCLC) stage C disease, and 43.9% had BCLC stage B disease. The ORR was 42.4%. The disease control rate was 87.9%. The grade 3-4 toxicities consisted of thrombocytopenia (4.5%), neutropenia (3.0%), and elevated aspartate aminotransferase (12.2%). Hand-foot skin reaction was also observed (40.9%). The median PFS was 13.1 mo (13.5 mo in the BCLC stage B participants and 9.4 mo in the BCLC stage C participants). The 6-mo, 12-mo, and 24-mo PFS rates were 75.0%, 54.7%, and 30.0%, respectively. The median OS was 21.8 mo. CONCLUSION Sorafenib combined with HAIC (FOLFOX) after TACE may be a feasible treatment choice for intermediate and advanced HCC because this treatment met the prespecified endpoint of a 6-mo PFS rate exceeding 50% and had good patient tolerance. Prospective randomized controlled trials are needed to confirm the effect of this combination therapy.