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      Outcomes of Patients with Child-Pugh B and Unresectable Hepatocellular Carcinoma Undergoing First-Line Systemic Treatment with Sorafenib, Lenvatinib, or Atezolizumab Plus Bevacizumab

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          Abstract

          Introduction: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. Methods: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. Results: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function ( p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. Conclusion: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.

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          Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma

          The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.
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            Sorafenib in advanced hepatocellular carcinoma.

            No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.) 2008 Massachusetts Medical Society
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              Cancer statistics for the year 2020: An overview

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                Author and article information

                Journal
                OCL
                Oncology
                10.1159/issn.0030-2414
                Oncology
                Oncology
                S. Karger AG
                0030-2414
                1423-0232
                2024
                March 2024
                20 September 2023
                : 102
                : 3
                : 239-251
                Affiliations
                [a ]Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Higashihiroshima, Japan
                [b ]Research Center for Hepatology and Gastroenterology, Hiroshima University, Higashihiroshima, Japan
                [c ]Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan
                [d ]Department of Gastroenterology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan
                [e ]Department of Gastroenterology, Chugoku Rosai Hospital, Hiroshima, Japan
                [f ]Department of Gastroenterology, JA Hiroshima General Hospital, Hiroshima, Japan
                [g ]Department of Gastroenterology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan
                [h ]Department of Gastroenterology, National Hospital Organization Higashihiroshima Medical Center, Hiroshima, Japan
                [i ]Department of Gastroenterology, Hiroshima Memorial Hospital, Hiroshima, Japan
                [j ]Department of Gastroenterology, Hiroshima Prefectural Hospital, Hiroshima, Japan
                Author notes
                *Tomokazu Kawaoka, kawaokatomo@hiroshima-u.ac.jp
                Article
                533859 Oncology 2024;102:239–251
                10.1159/000533859
                37729889
                befbe1b4-fac6-4382-bed6-2486ea23f0a5
                © 2023 S. Karger AG, Basel
                History
                : 12 April 2023
                : 31 July 2023
                Page count
                Figures: 7, Tables: 5, Pages: 13
                Funding
                We did not receive any funding.
                Categories
                Clinical Study

                Medicine
                Sorafenib,Hepatocellular carcinoma,Child-Pugh B,Atezolizumab plus bevacizumab,Lenvatinib
                Medicine
                Sorafenib, Hepatocellular carcinoma, Child-Pugh B, Atezolizumab plus bevacizumab, Lenvatinib

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