Influence of Sorafenib on Host Immunity in Patients with Liver Cirrhosis With Advanced Hepatocellular Carcinoma Stratified by Etiology

Nagai, Hidenari; Mukozu, Takanori; Kobayashi, Kojiro F.; Amaki, Makoto; Yoshimine, Naoyuki; Ogino, Yu; Matsui, Daigo; Daido, Yasuko; Matsukiyo, Yasushi; Matsui, Teppei; Wakui, Noritaka; Momiyama, Koichi; Shinohara, Mie; Higai, Koji; Igarashi, Yoshinori

doi:10.21873/anticanres.13333

Cited by 7 publications

(4 citation statements)

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“…This indicated that treatment response was a prognostic factor in the HAIC alone group but not in the concurrent RT group, of which the initial- or after-RT liver function status may have been the key risk factor of OS. The median OS of the 140 HAIC alone patients in our study was 17 months for CP-A and 7.8 months for CP-B patients ( p < 0.001); considering these results together with Nagai et al’s 33 series of patients treated with HAIC plus sorafenib (10.3 vs 7.7 months) and Abouchaleh et al’s 18 series of patients treated with SIR (13.3 vs 6.9 months) 18 indicates that aggressive treatments of any sort should be cautioned against for Child-Pugh B HCC patients.…”

Section: Discussionsupporting

confidence: 79%

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy

Chiang,

Liang,

Chang

et al. 2023

Journal of the Chinese Medical Association

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Background: Hepatocellular carcinoma (HCC) with major portal vein invasion (MPVI) presents very poor outcomes. Hepatic artery infusion chemotherapy (HAIC) and radiation therapy (RT) have both been found to be effective for advanced HCC. In this retrospective study, we compared the therapeutic outcomes of our “new HAIC regimen with and without concurrent RT, before and after propensity score matching (PSM) in treating HCC patients with MPVI. Methods: 140 patients with MPVI received HAIC alone and 35 patients underwent concurrent HAIC and RT during a 16-year period. The left subclavian artery was adopted as the entry site for a temporary catheter placement for a 5-day chemoinfusion. The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was adopted to assess the objective response rate (ORR). The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS) between the two groups. Univariate and multivariate analyses by Cox’s regression model were used to assess hazard ratios. Results: Of the 140 patients with Child-Pugh A liver function, the median OS was 17.0 months. In the initial cohort, higher ORR and PFS were found in the concurrent RT group than in the HAIC alone group (80% vs 66.4% and 9 vs 8 months, respectively) but shorter OS (10.5 vs 14.5 months, p=0.039) were observed. After PSM, the OS was 10 and 15 months (p=0.012), respectively. Multivariable Cox regression analysis revealed that the significant factors for adjusting hazard ratios for OS were Child-Pugh classification, AFP level, and hepatic vein invasion. Conclusion: HAIC is an effective treatment for advanced HCC patients with MPVI. Concurrent HAIC and full dose RT was associated with worse clinical outcomes.

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Section: Discussionsupporting

confidence: 79%

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy

Chiang,

Liang,

Chang

et al. 2023

Journal of the Chinese Medical Association

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“…We previously reported that treatment with sorafenib caused a decrease in peripheral blood Th2 cells and Treg cells in patients with CLD and advanced HCC, a change that might induce Th1 dominance [ 5 ]. We also reported that sorafenib might prevent evasion of the host immune system by tumor cells in patients with advanced HCC and HCV-related CLD; however, this did not appear to occur in patients with CLD of other etiologies [ 10 ]. The VEGF family includes VEGFA, VEGFB, VEGFC, VEGFD, VEGFE, and placental growth factor with three receptors: VEGFR1, VEGFR2, and VEGFR3 with associated co-receptors neutrophillin 1 and 2 [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Lenvatinib Might Induce Activation of Host Immunity in Patients with Hepatocellular Carcinoma

et al. 2022

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Introduction: Atezolizumab, an immune checkpoint inhibitor, plus bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), is an approved first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Immune checkpoint inhibitors are more effective in patients with HCC when administered with anti-VEGF drugs; however, these drugs affect host immunity. Lenvatinib is an anti-VEGF agent used to treat HCC; therefore, this study evaluated the effect of treatment of HCC with lenvatinib on host immunity in patients with chronic liver disease (CLD). Methods: We studied adult Japanese patients with CLD and unresectable HCC treated with lenvatinib at our hospital. Lenvatinib was administered for 4 weeks (8 mg/day for bodyweight < 60 kg; 12 mg/day for bodyweight > 60 kg). Blood samples were collected at baseline and at four weeks of treatment and examined for immune-related changes. Results: Forty-three patients were enrolled in this study. We found a significant increase T helper (Th) 1 cells following 4 weeks of lenvatinib treatment, although there were no significantly difference in Th2 cells and regulatory T cells. We also found a significant increase serum levels of TNF-alpha, soluble TNF-alpha receptor I, and endothelial growth factor following 4 weeks of lenvatinib treatment. Furthermore, an increase in Th1 cells and serum levels of TNF-alpha were found in patients with partial response. Conclusion: Lenvatinib might induce Th1 dominant host immunity in patients with CLD and unresectable HCC treatment who showed a partial response. These changes in host immunity may be a biomarker in HCC patients treated with lenvatinib.

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“…It is well known that HBV infection is the most important carcinogenic factor for HCC in China [ 27 ]. The influence of SOR on host immunity in HCC stratifies by etiology [ 28 ], and a high HBV load and antiviral therapy affect the survival of patients treated with SOR [ 29 ]. So, it is necessary to explore the effect of HBV infection on prognostic significance of miR-122.…”

Section: Discussionmentioning

confidence: 99%

High HBV Load Weakens Predictive Effect of Serum miR-122 on Response to Sorafenib in Hepatocellular Carcinoma Patients

Zhang

Wang

et al. 2021

Journal of Oncology

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Background. MiR-122 is a liver-specific microRNA. The aim of the study was to explore the association of serum miR-122 with response to sorafenib in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) patients and to further reveal the effect of the virus load on such potential relationship. Methods. A total of 588 patients with HCC were retrospectively included. All of them were diagnosed with HBV-related locally advanced HCC and were treated with sorafenib. Therapeutic and prognostic information and other information were collected from medical records. Stored blood specimens that were obtained before sorafenib treatment were adopted to detect miR-122. Results. The patients were divided into high-level group and low-level group according to the median of serum miR-122 level, and each group contained 294 patients. During the first 24 weeks after sorafenib treatment, the patients in the high-level group had more opportunities to experience progression-free survival (PFS) and overall survival (OS) than those in the low-level group (HR: 2.47, 95%CI: 1.24∼4.88; HR: 1.20, 95%CI: 1.09∼1.32). In the subgroup analysis, the relationship between serum miR-122 level and overall survival still existed in the patients with relatively lower HBV load (HR: 1.22, 95%CI: 1.09∼1.36), but not in the patients with higher HBV load (HR: 1.12, 95%CI: 0.93∼1.35). Conclusion. Higher serum level of miR-122 at baseline was associated with a better response to sorafenib in HBV-related locally advanced HCC patients, and relatively high HBV load weakened such predictive effect mentioned above.

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Influence of Sorafenib on Host Immunity in Patients with Liver Cirrhosis With Advanced Hepatocellular Carcinoma Stratified by Etiology

Cited by 7 publications

References 0 publications

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy

Lenvatinib Might Induce Activation of Host Immunity in Patients with Hepatocellular Carcinoma

High HBV Load Weakens Predictive Effect of Serum miR-122 on Response to Sorafenib in Hepatocellular Carcinoma Patients

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