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      Prognostic factors and survival prediction in hepatocellular carcinoma: development and validation of a novel nomogram based on the SEER database

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          Abstract

          Background

          Current staging systems for hepatocellular carcinoma (HCC) still have limitations in clinical practice. Our study aimed to explore the prognostic factors and develop a new nomogram to predict the cancer-specific survival (CSS) for patients with HCC.

          Methods

          A total of 6,166 HCC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly grouped into the training cohort (70%) and validation cohort (30%). Multivariate Cox analysis was used to identify prognostics factors for CSS of patients, then we incorporated these variables and presented a new nomogram to predict 2- and 5-year CSS. The performance of the nomogram was assessed with respect to its calibration, concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), and decision curve analysis (DCA).

          Results

          Multivariate Cox analysis revealed that American Joint Committee on Cancer (AJCC) stage, race, grade, surgery, chemotherapy, radiation, tumor size, bone metastasis (BM), and alpha-fetoprotein (AFP) were independently associated with CSS. The prediction nomogram which contained these predictors showed good performance, with a C-index of 0.802 [95% confidence interval (CI), 0.792–0.812] in the training cohort and 0.801 (95% CI, 0.787–0.815) in the validation cohort. The calibration curves demonstrated good agreement between the actual observation and the nomogram prediction. Furthermore, the nomogram showed improved discriminative capacity (AUC, 0.873 and 0.875 for 2- and 5-year CSS in validation set) compared to the 7 th tumor-node-metastasis (TNM) staging system (AUC, 0.735 and 0.717). The DCA also indicated good application of the nomogram.

          Conclusions

          This study presents a novel nomogram that incorporates the important prognostic factors of HCC, which can be conveniently used to accurately predict the 2- and 5-year CSS of patients with HCC, thus assisting individualized clinical decision making.

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          Most cited references39

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          EASL Clinical Practice Guidelines: Management of 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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              Hepatocellular carcinoma

              Hepatocellular carcinoma appears frequently in patients with cirrhosis. Surveillance by biannual ultrasound is recommended for such patients because it allows diagnosis at an early stage, when effective therapies are feasible. The best candidates for resection are patients with a solitary tumour and preserved liver function. Liver transplantation benefits patients who are not good candidates for surgical resection, and the best candidates are those within Milan criteria (solitary tumour ≤5 cm or up to three nodules ≤3 cm). Image-guided ablation is the most frequently used therapeutic strategy, but its efficacy is limited by the size of the tumour and its localisation. Chemoembolisation has survival benefit in asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread. Finally, sorafenib, lenvatinib, which is non-inferior to sorafenib, and regorafenib increase survival and are the standard treatments in advanced hepatocellular carcinoma. This Seminar summarises the scientific evidence that supports the current recommendations for clinical practice, and discusses the areas in which more research is needed.
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                Author and article information

                Journal
                J Gastrointest Oncol
                J Gastrointest Oncol
                JGO
                Journal of Gastrointestinal Oncology
                AME Publishing Company
                2078-6891
                2219-679X
                21 July 2023
                31 August 2023
                : 14
                : 4
                : 1817-1829
                Affiliations
                [1 ]deptDepartment of Infectious Disease , The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , Wenzhou, China;
                [2 ]deptThe Second Clinical Medical College , Wenzhou Medical University , Wenzhou, China;
                [3 ]deptDepartment of Gastroenterology , The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , Wenzhou, China;
                [4 ]Department of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de la Arrixaca , deptIMIB-Arrixaca , Murcia, Spain;
                [5 ]Hepatology Unit, University Croix-Rousse Hospital, Hospices Civils de Lyon , Lyon, France;
                [6 ]deptDepartment of Gastrointestinal Surgery , The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , Wenzhou, China
                Author notes
                [#]

                These authors contributed equally to this work.

                Contributions: (I) Conception and design: S Huang, Z Zhu; (II) Administrative support: G Lu, L Li; (III) Provision of study materials or patients: S Huang, G Lu; (IV) Collection and assembly of data: Y Ruan, F Zhang, Y Xu; (V) Data analysis and interpretation: S Huang, L Jin, L Li; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Guangrong Lu, MD. Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou 325027, China. Email: luguangrong1987@ 123456163.com ; Liyi Li, MD. Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou 325027, China. Email: liliyi@ 123456wmu.edu.cn .
                [^]

                ORCID: 0000-0003-1938-9442.

                Article
                jgo-14-04-1817
                10.21037/jgo-23-427
                10502553
                37720431
                0e13b066-020a-4f09-b831-2fdedefe619a
                2023 Journal of Gastrointestinal Oncology. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 18 May 2023
                : 14 July 2023
                Funding
                Funded by: the Zhejiang Medical and Health Plan
                Award ID: No. 2023KY910
                Funded by: Wenzhou Science and Technology Project
                Award ID: No. Y20210920
                Categories
                Original Article

                hepatocellular carcinoma (hcc),prognostic factors,cancer-specific survival (css),nomogram

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