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      Establishment of inflammation biomarkers-based nomograms to predict prognosis of advanced colorectal cancer patients based on real world data

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          Abstract

          Purpose

          To establish three novel prognostic nomograms with inflammatory factors for advanced colorectal cancer (ACRC), right-sided colon cancer (RSCC) and left-sided colorectal cancer (LSCRC) according to real world data.

          Materials and methods

          ACRC patients receiving medicine therapy from January 1 st, 2005 to September 31 th, 2015 in Sun Yat-sen University Cancer Center were enrolled. Inflammatory indicators such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA 19–9), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were analyzed for establishing nomograms predicting overall survival (OS). Concordance index (C-index) determined predictive accuracy and discriminative ability.

          Results

          Our study selected 807 ACRC patients, 29.6% RSCC and 70.4% LSCRC. Median OS was 23.36 months. Patients at lower level of NLR, PLR, CEA, CA 19–9, LDH and CRP showed longer OS ( P < 0.001). For all patients, pathological grade ( P = 0.018), treatments ( P = 0.042), sidedness ( P = 0.003), NLR ( P < 0.001), CA 19–9 ( P < 0.001), LDH ( P < 0.001) and CRP ( P = 0.0012) contributed to OS independently. For RSCC, pathological grade ( P = 0.022), CA 19–9 ( P < 0.001), LDH ( P < 0.001) and CRP ( P = 0.001) were significantly related with OS. For LSCRC patients, treatments (cetuximab vs chemotherapy: P = 0.008; bevacizumab vs chemotherapy: P = 0.166), NLR ( P < 0.001), CA 19–9 ( P = 0.030) and LDH ( P < 0.001) were independent factors for OS. Final models showed acceptable internal validity with C-indexes of 0.687, 0.697 and 0.667 in all, RSCC and LSCRC patients.

          Conclusions

          Inflammatory factors enrolled in the proposed nomograms showed accurately individualized prognostic prediction, and prognostic factors for RSCC and LSCRC were different.

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          Most cited references22

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          Development and Validation of a Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Colorectal Cancer.

          To develop and validate a radiomics nomogram for preoperative prediction of lymph node (LN) metastasis in patients with colorectal cancer (CRC).
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            Nomogram predicting long-term survival after d2 gastrectomy for gastric cancer.

            The aim of this study was to combine clinicopathologic variables associated with overall survival after gastric resection with D2 lymphadenectomy (D2 gastrectomy) for gastric cancer into a prediction nomogram. We retrospectively analyzed 7,954 patients who underwent D2 gastrectomy for gastric cancer at Seoul National University Hospital (SNUH) in Seoul, Korea. Two thirds of the patients were randomly assigned to the training set (n = 5,300), and one third were assigned to the validation set (n = 2,654). Multivariate analysis by Cox proportional hazards regression was performed using the training set, and the nomogram was constructed. Discrimination and calibration were performed using the SNUH validation set. Additional external validation was performed using the data set (n = 2,500) from Cancer Institute Ariake Hospital (CIAH) in Tokyo, Japan. The multivariate Cox model identified age at diagnosis, sex, location, depth of invasion, number of metastatic lymph nodes, and number of examined lymph nodes as covariates associated with survival. In the SNUH validation set, the nomogram exhibited superior discrimination power compared with the seventh American Joint Committee on Cancer TNM classification (Harrell's C-index, 0.78 v 0.69, respectively; P < .001). Calibration of the nomogram predicted survival corresponding closely with the actual survival. In the CIAH validation set, discrimination was good (C-index, 0.79), and the predicted survival was within a 10% margin of ideal nomogram. We developed a nomogram predicting 5- and 10-year overall survival after D2 gastrectomy for gastric cancer. Validation using the SNUH and CIAH data sets revealed good discrimination and calibration, suggesting good clinical utility. The nomogram improved individualized predictions of survival.
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              Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma.

              Few published studies have addressed individual patient risk after R0 resection for gastric cancer. We developed and internally validated a nomogram that combines these factors to predict the probability of 5-year gastric cancer-specific survival on the basis of 1,039 patients treated at a single institution. Nomogram predictor variables included age, sex, primary site (distal one-third, middle one-third, gastroesophageal junction, and proximal one-third), Lauren histotype (diffuse, intestinal, mixed), number of positive lymph nodes resected, number of negative lymph nodes resected, and depth of invasion. Death as a result of gastric cancer was the predicted end point. The concordance index was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. Gastric cancer-specific survival at 5 years was 50%. A nomogram was constructed on the basis of a Cox regression model. The bootstrap-corrected concordance index was 0.80. When compared with the predictive ability of American Joint Committee on Cancer stage, the nomogram discrimination was superior (P <.001). Nomogram calibration appeared to be excellent. A nomogram was developed to predict 5-year disease-specific survival after R0 resection for gastric cancer. This tool should be useful for patient counseling, follow-up scheduling, and clinical trial eligibility determination.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Project administration
                Role: Project administration
                Role: Data curation
                Role: MethodologyRole: Project administration
                Role: Investigation
                Role: Formal analysisRole: Methodology
                Role: ConceptualizationRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 December 2018
                2018
                : 13
                : 12
                : e0208547
                Affiliations
                [1 ] VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
                [2 ] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
                [3 ] Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China
                [4 ] Department of Orthopedics, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
                University of Nebraska Medical Center, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interest exists.

                Author information
                http://orcid.org/0000-0003-1197-1147
                Article
                PONE-D-18-24415
                10.1371/journal.pone.0208547
                6279229
                30513126
                23b9b613-cad5-4133-af42-631c5ea1b39f
                © 2018 Guo et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 August 2018
                : 18 November 2018
                Page count
                Figures: 7, Tables: 2, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003453, Natural Science Foundation of Guangdong Province;
                Award ID: 2017A030313685
                Award Recipient :
                Funded by: Guangdong Provincial Traditional Chinese Medicine Bureau of scientific research projects
                Award ID: 20171069
                Award Recipient :
                This work was funded by Natural Science Foundation of Guangdong Province (grant number No. 2017A030313685, 2017), and Guangdong Provincial Traditional Chinese Medicine Bureau of scientific research projects (grant number No. 20171069, 2017).
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Colorectal Cancer
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Biology and Life Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Immunology
                Immune Response
                Inflammation
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                Custom metadata
                Our data cannot be shared publicly because our institutional ethics committee requires clinical data confidentiality for our data containing potentially sensitive patient information. Our institution requires us to upload the raw data onto the research data deposit (RDD) to keep the possible traceability for the research data in the future. RDD are highly confidential on the deposited datasets, which would not be reached by any third party and not used for any scientific purposes. However, RDD can provide the support for the inspection of raw data under the following conditions: a) Successful application for inspection from the administration or governmental offices; b) Successful application for inspection by chief-editor(s) of a scientific journal wherein the authenticity of the research is doubted by public and or the Journal readers/editors. And the authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform ( www.researchdata.org.cn), with the approval RDD number as RDDA2018000867. Anonymized data are only available from the Sun Yat-sen University Cancer Center Data Access / Ethics Committee for researchers who meet the criteria for access to confidential data. You can contact our Ethics Committee via Tel (+86-20-87343009) and RDD department via Tel (+86-20-8734355).

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