Efficacy and Safety of Chemoradiation Therapy Using One- Shot Cisplatin via Hepatic Arterial Infusion for Advanced Hepatocellular Carcinoma with Major Macrovascular Invasion: a Single-arm Retrospective Cohort Study

Abstract Background: Patients with hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) who receive systemic chemotherapy have a poor prognosis. This study aimed to determine if one-shot cisplatin (CDDP) chemotherapy via hepatic arterial infusion (HAI) combined with radiation therapy (RT) prior to systemic chemotherapy could improve the outcomes of these patients. Methods: This study consisted of 32 HCC patients with the following eligibility criteria: (i) portal vein invasion 3/4 and/or hepatic vein invasion 2/3; (ii) received one-shot CDDP via HAI; (iii) received RT for MVI, (iv) a Child-Pugh score ≤7; and (v) an Eastern Clinical Oncology Group Performance Status score of 0 or 1. To determine the therapeutic effect, we collect the information of patients’ characteristics and took contrast-enhanced computed tomography at the start of the therapy and every 2 to 4 months after the therapy initiated. We evaluated the overall response of the tumor and tumor thrombosis according to modified Response Evaluation Criteria in Solid Tumors. We assessed the patient’s data statistically by the Mann-Whitney U-test, fisher’s exact test, and evaluated overall survival and progress-free survival by log-ranked test, and analyzed the predictive factors by as appropriate. Results: The overall response rate at the first evaluation performed a median of 1.4 weeks after HAI was 16% of the main intrahepatic tumor and 59% of the MVI. The best responses were the same as those of the first-time responses. The duration of median survival was 8.6 months, and for progression-free survival of the main intrahepatic tumor was 3.2 months. The predictive factor of overall survival was the relative tumor volume in the liver and the first therapeutic response of MVI. There were no severe adverse events or radiation-induced hepatic complications. Conclusions: One-shot CDDP via HAI and RT were well tolerated and showed immediate and favorable control of MVI. Thus, this combination shows potential as a bridging therapy to systemic chemotherapy.

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Hepatic Arterial Infusion Chemotherapy of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Sorafenib as Initial Treatment for Advanced Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.619461 ◽

2021 ◽

Vol 11 ◽

Author(s):

Run-Bin Liang ◽

Yang Zhao ◽

Min-Ke He ◽

Dong-Sheng Wen ◽

Xiao-Yun Bu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Survival Benefit ◽

Hepatic Arterial Infusion ◽

Progression Free Survival ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Free Survival ◽

Arterial Infusion Chemotherapy ◽

Infusion Chemotherapy

PurposeOur previous study showed that hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) plus sorafenib provided a significant survival benefit over sorafenib for advanced hepatocellular carcinoma. However, it is unclear whether the survival benefit should be attributed to the synergism between HAIC and sorafenib or just HAIC alone. We aim to compare HAIC using FOLFOX plus sorafenib with HAIC alone in patients with advanced hepatocellular carcinoma.Materials and MethodsThis was a retrospective study including 225 eligible patients treated with HAIC using FOLFOX (HAIC alone group, n=126, oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil bolus 400 mg/m² and 2400 mg/m² for 46 hours, every 3 weeks) alone or HAIC plus sorafenib (soraHAIC group, n=99, sorafenib 400 mg twice daily). Survival curves were calculated by the Kaplan-Meier method, and propensity-score matching was used to reduce bias.ResultsThe soraHAIC group showed a longer overall survival (12.9 [95% CI, 10.4-15.4] vs. 10.5 [95% CI, 9.5-11.5] months, HR=0.71 [95% CI, 0.53-0.96]; P=0.025), a better progression free survival (7.0 [95% CI, 5.3-8.8] vs. 5.3 [95% CI, 3.5-7.1] months, HR=0.76 [95% CI, 0.58-0.99]; P=0.046), and a higher disease control rate (RECIST 1.1: 74.8% vs. 61.1%, P=0.030) than the HAIC alone group. In multivariate analysis, soraHAIC was an independent favor factor for survival. In terms of the grade 3/4 adverse event, hand–foot skin reaction was more frequent in the soraHAIC group than the HAIC alone group. In the propensity-score matched cohorts (93 pairs), the overall survival, the progression free survival and disease control rates in the soraHAIC group were also better than those in the HAIC group (P<0.05).ConclusionHAIC plus sorafenib may improve overall survival and progression free survival compared with HAIC alone as initial treatment for advanced hepatocellular carcinoma.

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Chemotherapy for advanced hepatocellular carcinoma: systemic chemotherapy or hepatic arterial infusion chemotherapy?

Journal of Gastroenterology ◽

10.1007/s00535-004-1330-0 ◽

2004 ◽

Vol 39 (4) ◽

pp. 404-406 ◽

Cited By ~ 1

Author(s):

Tatsuya Yamashita

Keyword(s):

Hepatocellular Carcinoma ◽

Systemic Chemotherapy ◽

Hepatic Arterial Infusion ◽

Hepatic Arterial Infusion Chemotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Arterial Infusion Chemotherapy ◽

Infusion Chemotherapy

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Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211002720 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110027

Author(s):

Min-Ke He ◽

Run-Bin Liang ◽

Yang Zhao ◽

Yu-Jie Xu ◽

Huan-Wei Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Hepatic Arterial Infusion ◽

Progression Free Survival ◽

Complete Response ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Free Survival ◽

Infusion Chemotherapy ◽

Modified Recist

Background: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma, but prognosis is still unsatisfactory. Recently, hepatic arterial infusion chemotherapy (HAIC), and immune checkpoint inhibitors showed promising results for advanced hepatocellular carcinoma. Considering different anti-malignancy mechanisms, combining these three treatments may improve outcomes. This study aimed to compare the efficacy and safety of lenvatinib, toripalimab, plus HAIC versus lenvatinib for advanced hepatocellular carcinoma. Methods: This was a retrospective study including patients treated with lenvatinib [8 mg (⩽60 kg) or 12 mg (>60 kg) once daily] or lenvatinib, toripalimab plus HAIC [LeToHAIC group, lenvatinib 0–1 week prior to initial HAIC, 240 mg toripalimab 0–1 day prior to every HAIC cycle, and HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 h, every 3 weeks)]. Progression-free survival, overall survival, objective response rate, and treatment-related adverse events were compared. Results: From February 2019 to August 2019, 157 patients were included in this study: 71 in the LeToHAIC group and 86 in the lenvatinib group. The LeToHAIC group showed longer progression-free survival (11.1 versus 5.1 months, p < 0.001), longer overall survival (not reached versus 11 months, p < 0.001), and a higher objective response rate (RECIST: 59.2% versus 9.3%, p < 0.001; modified RECIST: 67.6% versus 16.3%, p < 0.001) than the lenvatinib group. In addition, 14.1% and 21.1% of patients in the LeToHAIC group achieved complete response of all lesions and complete response of the intrahepatic target lesions per modified RECIST criteria, respectively. Grade 3/4 treatment-related adverse events that were more frequent in the LeToHAIC group than in the lenvatinib group included neutropenia (8.5% versus 1.2%), thrombocytopenia (5.6% versus 0), and nausea (5.6% versus 0). Conclusions: Lenvatinib, toripalimab, plus HAIC had acceptable toxic effects and might improve survival compared with lenvatinib alone in advanced hepatocellular carcinoma.

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Clinical Benefits of Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma

Applied Sciences ◽

10.3390/app11041882 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1882

Author(s):

Takahiro Yamasaki ◽

Issei Saeki ◽

Yurika Kotoh-Yamauchi ◽

Ryo Sasaki ◽

Norikazu Tanabe ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Vascular Invasion ◽

Hepatic Arterial Infusion ◽

Hepatic Arterial Infusion Chemotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Arterial Infusion Chemotherapy ◽

Infusion Chemotherapy ◽

Recent Success ◽

Clinical Benefits

Recent success of systemic therapeutic agents, including combination immunotherapy, could promote a change in the treatment strategy in patients with advanced hepatocellular carcinoma (HCC). Although hepatic arterial infusion chemotherapy (HAIC) is a treatment option for advanced HCC in Japan, it is not recommended by other guidelines. We discuss the clinical benefits of HAIC compared to sorafenib. The clinical benefits of HAIC are as follows: (1) even a patient with Child–Pugh B HCC (7 or 8 points) is a candidate for HAIC (2) Child–Pugh scores barely decline with the use of HAIC compared with sorafenib (3) HAIC is highly effective in patients with vascular invasion compared with sorafenib; and (4) survival in patients receiving HAIC may not be associated with skeletal muscle volume. In contrast, the disadvantages are problems related with the reservoir system. HAIC has clinical benefits in a subpopulation of patients without extrahepatic metastasis with Child–Pugh A HCC and vascular invasion (especially primary branch invasion or main portal vein invasion) or with Child–Pugh B HCC.

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