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      Fibrinogen/Albumin Ratio as a Promising Marker for Predicting Survival in Pancreatic Neuroendocrine Neoplasms

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          Abstract

          Background

          The fibrinogen/albumin ratio (FAR) has been widely reported to be a possible biomarker for predicting prognosis in several types of tumors, but the prognostic value of the FAR in pancreatic neuroendocrine neoplasms (Pan-NENs) has not been systematically studied.

          Patients and Methods

          In total, 324 patients with Pan-NENs were recruited. The patients were divided into 2 subgroups according to the FAR cutoff value, and clinicopathological characteristics of the 2 subgroups were compared. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The prognostic value of the FAR was analyzed in univariate and multivariate analyses.

          Results

          The optimal cutoff value for the FAR was calculated to be 0.08 for OS. The patients with a FAR ≥0.08 had higher proportions of nonfunctioning tumors, Pan-NECs, grade 3 tumors, and stage IV tumors than those with a FAR <0.08. In the univariate analysis, a FAR ≥ 0.08 was associated with poor OS (hazard ratio (HR) = 2.37, P < 0.001) and PFS (HR = 2.37, P < 0.001). In the multivariate analysis, a FAR ≥0.08 was an independent risk factor for poor OS (HR = 4.70, P < 0.001) and PFS (HR = 1.80, P = 0.006).

          Conclusion

          The pretreatment FAR, which includes fibrinogen and albumin, was a feasible and predictive biomarker for prognosis in patients with Pan-NENs. An elevated FAR, based on a cutoff value of 0.08, was an independent risk factor for poor OS and PFS.

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          One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States.

          James C Yao, Manal Hassan, Alexandria Phan … (2008)
          PURPOSE Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology of and prognostic factors for NETs, because a thorough examination of neither had previously been performed. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program registries were searched to identify NET cases from 1973 to 2004. Associated population data were used for incidence and prevalence analyses. Results We identified 35,618 patients with NETs. We observed a significant increase in the reported annual age-adjusted incidence of NETs from 1973 (1.09/100,000) to 2004 (5.25/100,000). Using the SEER 9 registry data, we estimated the 29-year limited-duration prevalence of NETs on January 1, 2004, to be 9,263. Also, the estimated 29-year limited-duration prevalence in the United States on that date was 103,312 cases (35/100,000). The most common primary tumor site varied by race, with the lung being the most common in white patients, and the rectum being the most common in Asian/Pacific Islander, American Indian/Alaskan Native, and African American patients. Additionally, survival duration varied by histologic grade. In multivariate analysis of patients with well-differentiated to moderately differentiated NETs, disease stage, primary tumor site, histologic grade, sex, race, age, and year of diagnosis were predictors of outcome (P < .001). CONCLUSION We observed increased reported incidence of NETs and increased survival durations over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristic of these tumors.
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            A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal

            Guido Rindi, David Klimstra, Behnoush Abedi-Ardekani … (2018)
            The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.
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              Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial.

              Tom Thuren, Paul Ridker, … (2012)
              To test formally the inflammatory hypothesis of atherothrombosis, an agent is needed that reduces inflammatory biomarkers such as C-reactive protein, interleukin-6, and fibrinogen but that does not have major effects on lipid pathways associated with disease progression. We conducted a double-blind, multinational phase IIb trial of 556 men and women with well-controlled diabetes mellitus and high cardiovascular risk who were randomly allocated to subcutaneous placebo or to subcutaneous canakinumab at doses of 5, 15, 50, or 150 mg monthly and followed over 4 months. Compared with placebo, canakinumab had modest but nonsignificant effects on the change in hemoglobin A1c, glucose, and insulin levels. No effects were seen for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol, although triglyceride levels increased ≈10% in the 50-mg (P=0.02) and 150-mg (P=0.03) groups. By contrast, the median reductions in C-reactive protein at 4 months were 36.4%, 53.0%, 64.6%, and 58.7% for the 5-, 15-, 50-, and 150-mg canakinumab doses, respectively, compared with 4.7% for placebo (all P values ≤0.02). Similarly, the median reductions in interleukin-6 at 4 months across the canakinumab dose range tested were 23.9%, 32.5%, 47.9%, and 44.5%, respectively, compared with 2.9% for placebo (all P≤0.008), and the median reductions in fibrinogen at 4 months were 4.9%, 11.7%, 18.5%, and 14.8%, respectively, compared with 0.4% for placebo (all P values ≤0.0001). Effects were observed in women and men. Clinical adverse events were similar in the canakinumab and placebo groups. Canakinumab, a human monoclonal antibody that neutralizes interleukin-1β, significantly reduces inflammation without major effect on low-density lipoprotein cholesterol or high-density lipoprotein cholesterol. These phase II trial data support the use of canakinumab as a potential therapeutic method to test directly the inflammatory hypothesis of atherosclerosis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Manag Res
                Journal ID (iso-abbrev): Cancer Manag Res
                Journal ID (publisher-id): cmar
                Journal ID (pmc): cancmanres
                Title: Cancer Management and Research
                Publisher: Dove
                ISSN (Electronic): 1179-1322
                Publication date (Electronic): 08 January 2021
                Publication date Collection: 2021
                Volume: 13
                Pages: 107-115
                Affiliations
                [1 ]Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center , Shanghai, People’s Republic of China
                [2 ]Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, People’s Republic of China
                [3 ]Shanghai Pancreatic Cancer Institute , Shanghai, People’s Republic of China
                [4 ]Pancreatic Cancer Institute, Fudan University , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Chen Liu; Xianjun Yu Shanghai Pancreatic Cancer Institute , 270 Dong an Road, Shanghai200032, People’s Republic of ChinaTel/Fax +86-21-6403-1446 Email liuchen@fudanpci.org; yuxianjun@fudanpci.org
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: 275173
                DOI: 10.2147/CMAR.S275173
                PMC ID: 7802789
                PubMed ID: 33447083
                SO-VID: ae473916-6ee4-4074-a315-0f8853b53a5e
                Copyright © © 2021 Deng et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 03 August 2020
                Date accepted : 10 December 2020
                Page count
                Figures: 4, Tables: 7, References: 37, Pages: 9
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: pancreatic neuroendocrine neoplasms,survival,fibrinogen/albumin ratio
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: pancreatic neuroendocrine neoplasms, survival, fibrinogen/albumin ratio

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