NLCECA score: a serum inflammatory-tumor biomarker score to predict survival of advanced perihilar cholangiocarcinoma after hepatic arterial infusion chemotherapy.

Prognostic features in advanced perihilar cholangiocarcinoma (pCCA) patients who received first-line hepatic arterial infusion chemotherapy (HAIC) are unknown. The purpose of our study was to develop an applicable score based on serum inflammatory-tumor biomarkers to predict the survival of advanced pCCA patients who received first-line HAIC. In total, 106 advanced pCCA patients were enrolled as the training cohort. The optimal cutoff values of baseline variables were defined by the receiver operating characteristic method or according to previous publications. According to the results of Cox regression analysis, baseline neutrophil-to-lymphocyte ratio (NLR) > 3.19, carcinoembryonic antigen (CEA) > 10 ng/mL, and carbohydrate antigen 19-9 (CA19-9) > 200 U/mL were identified as independent survival predictors, which were used to develop the NLCECA score (NLR, CEA, and CA19-9). When including the NLCECA score in the multivariate analysis, the NLCECA score was the only independent predictor of survival. The risk of survival decreased by 111.9% for each 1-point increase in the NLCECA score. Additionally, the NLCECA score could also predict survival in another 33 patients in the validation cohort (P < 0.001). In summary, the NLCECA score is a potential biomarker system for predicting the survival of advanced pCCA patients who received first-line HAIC.

Techniques and status of hepatic arterial infusion chemotherapy for primary hepatobiliary cancers.

Primary hepatobiliary cancers (PHCs), which mainly include hepatocellular carcinoma (HCC) and biliary tract cancers (BTCs), are mostly diagnosed in the advanced stage and are not candidates for curative surgery or ablation, resulting in a dismal prognosis. Targeted therapies with or without programmed death receptor 1 (PD-1)/PD-L1 inhibitors have been incorporated into first-line treatments for advanced HCC. Systemic chemotherapy is still the mainstay treatment for advanced BTCs, and combining it with PD-1/PD-L1 inhibitors has resulted in prolonged patient survival. Intra-arterial therapies, including trans-arterial chemoembolization, selective internal radiation therapy, and hepatic arterial infusion chemotherapy (HAIC), have been explored and used for advanced hepatobiliary cancers for many years with positive results, particularly when combined with systemic treatments. Recently, an increasing number of phase II/III trials have demonstrated the efficacy and safety of HAIC for the treatment of advanced HCC with portal vein tumor thrombosis and/or a large tumor burden, for the neoadjuvant and adjuvant treatment of HCC with high-risk factors, and for treating advanced intrahepatic and perihilar cholangiocarcinoma. However, the techniques and regimens used for HAIC are diverse and differ greatly between various regions and centers worldwide. This review focuses on these diverse techniques and regimens, as well as the updated evidence on HAIC regarding the treatment of PHCs.

Different interventional time of hepatic arterial infusion with PD-1 inhibitor for advanced biliary tract cancer: a multicenter retrospective study.

This study investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with PD-1 immunotherapy for advanced biliary tract cancer (BTC) and evaluated the optimal timing of HAIC. A total of 36 unresectable BTC patients treated with HAIC and PD-1 inhibitors between September 2019 and July 2021 were included in this study. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) were investigated. Overall, 52.8% patients with advanced BTC were in stage IV, 23 patients who progressed after receiving PD-1 inhibitor had undergone HAIC, and 23 patients have received 2 or more lines of therapy. The median OS was 8.8 months (range: 4.0-24.0 months), and the median PFS was 3.7 months. The objective response rate and disease control rate were 11.5% and 76.9%, respectively. In the subgroup analysis, patients who treated with HAIC early without progression after immunotherapy were associated with a trend toward better OS (median 13.0 vs. 7.6 months; P = 0.004) and PFS (median 7.9 vs. 3.6 months; P = 0.09) compared to with HAIC with progression after PD-1 treatment. No treatment-related deaths occurred. A total of 44.4% of the patients experienced grade 3 or 4 AEs. We conclude that the combination of HAIC and PD-1 inhibitors is safe and effective. Early HAIC combined with immunotherapy can effectively prolong the overall survival of patients with advanced BTC.

Signal enhancement ratio of CE-MRI: a potential biomarker of survival after hepatic arterial infusion chemotherapy in biliary tract cancers.

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 (SER0) was 1.04, and both median PFS and OS in the SER0 ≥ 1.04 group were longer than in the SER0 < 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 SER0 (p = 0.029) and HAIC treatment cycle (p = 0.002) were independent predictors of longer survival. CONCLUSIONS: SER in CE-MRI before HAIC (SER0) is a potential biomarker for the prediction of survival after HAIC in advanced BTC.

Sorafenib Plus Hepatic Arterial Infusion Chemotherapy versus Sorafenib for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis: A Randomized Trial.

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.

Retrograde embolization technique of the right gastric artery during the implantation of port-catheter system for hepatic arterial infusion chemotherapy.

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 â€‹± â€‹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 â€‹= â€‹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 â€‹= â€‹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.

Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Gallbladder Cancer.

PURPOSE: The aim of this study was to assess the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil for patients with advanced gallbladder cancer (GBC). MATERIALS AND METHODS: Twenty-six patients with advanced GBC, who underwent HAIC with oxaliplatin and 5-fluorouracil from January 2012 to July 2019, were enrolled in this retrospective study. The HAIC regimen consisted of infusions of oxaliplatin at 40 mg/m2 for 2 h, followed by 5-fluorouracil at 800 mg/m2 for 22 h on days 1-3 every 3-4 weeks. A maximum of six cycles of HAIC were applied for tumor control patients followed by maintenance with oral capecitabine or S-1. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were investigated. RESULTS: Six of the 26 patients (23.1%) had failed systemic chemotherapy, 8/26 (30.8%) patients had failed various local therapies, and 9/26 (34.6%) patients had contraindications to systemic chemotherapy. The median OS was 13.5 months, and the median PFS was 10.0 months. The overall response rate was 69.2% (18/26), and disease control rate was 92.3% (24/26). Carcinoembryonic antigen (CEA) ≥ 10 U/ml (p = 0.003) and carbohydrate antigen 19-9 (CA19-9) ≥ 200 U/ml (p = 0.000) were independent risk factors for decreased survival. The most frequent Grade 3 or 4 treatment-related adverse event was liver dysfunction (4, 15.4%). CONCLUSION: HAIC with oxaliplatin and 5-fluorouracil is an acceptable and well-tolerated treatment for advanced gallbladder cancer even for patients in whom systemic chemotherapy had failed or is contraindicated. LEVEL OF EVIDENCE: Level 2, Observation Study with Dramatic Effect.

Hepatic Arterial Infusion Chemotherapy Using Oxaliplatin Plus 5-Fluorouracil Versus Transarterial Chemoembolization/Embolization for the Treatment of Advanced Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis.

PURPOSE: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.