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      Development and Validation of a Nomogram for Predicting Survival in Patients with Advanced Pancreatic Ductal Adenocarcinoma

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          Abstract

          This study aimed to develop and validate an effective prognostic nomogram for advanced PDAC patients. We conducted a prospective multicenter cohort study involving 1,526 advanced PDAC patients from three participating hospitals in China between January 1, 2004 and December 31, 2013. Two thirds of the patients were randomly assigned to the training set (n = 1,017), and one third were assigned to the validation set (n = 509). Multivariate cox regression analysis was performed to identify significant prognostic factors for overall survival to develop the nomogram. Internal and external validation using C-index and calibration curve were conducted in the training set and validation set respectively. As results, seven independent prognostic factors were identified: age, tumor stage, tumor size, ALT (alanine aminotransferase), ALB (albumin), CA 19-9, HBV infection status, and these factors were entered into the nomogram. The proposed nomogram showed favorable discrimination and calibration both in the training set and validation set. The C-indexes of the training set and validation set were 0.720 and 0.696 respectively, which were both significantly higher than that of the staging system (C-index = 0.613, P < 0.001). In conclusion, the proposed nomogram may be served as an effective tool for prognostic evaluation of advanced PDAC.

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          Cancer statistics in China, 2015.

          Wanqing Chen, Rongshou Zheng, Peter D Baade … (2016)
          With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population-based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.
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            FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.

            Thierry Conroy, Françoise Desseigne, Marc Ychou … (2011)
            Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer. We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).
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              How to build and interpret a nomogram for cancer prognosis.

              Alexia Iasonos, Deborah Schrag, Ganesh Raj … (2008)
              Nomograms are widely used for cancer prognosis, primarily because of their ability to reduce statistical predictive models into a single numerical estimate of the probability of an event, such as death or recurrence, that is tailored to the profile of an individual patient. User-friendly graphical interfaces for generating these estimates facilitate the use of nomograms during clinical encounters to inform clinical decision making. However, the statistical underpinnings of these models require careful scrutiny, and the degree of uncertainty surrounding the point estimates requires attention. This guide provides a nonstatistical audience with a methodological approach for building, interpreting, and using nomograms to estimate cancer prognosis or other health outcomes.
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                Author and article information

                Contributors
                Jin-Ming Yu: jmy@fudan.edu.cn
                Qi-Wen Chen: cqwly@hotmail.com
                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 14 September 2017
                Publication date PMC-release: 14 September 2017
                Publication date Collection: 2017
                Volume: 7
                Electronic Location Identifier: 11524
                Affiliations
                [1 ]ISNI 0000 0001 0125 2443, GRID grid.8547.e, Institute of Clinical Epidemiology, , Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, ; 200032 Shanghai, China
                [2 ]ISNI 0000 0001 0125 2443, GRID grid.8547.e, Department of Integrative Oncology, Shanghai Cancer Center, , Fudan University, ; Shanghai, 200032 China
                [3 ]ISNI 0000 0004 0619 8943, GRID grid.11841.3d, Department of Oncology, Shanghai Medical College, Fudan University, ; 200032 Shanghai, China
                [4 ]ISNI 0000 0004 0369 1660, GRID grid.73113.37, Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, , Second Military Medical University, ; 200433 Shanghai, China
                [5 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Integrative Medicine of Shanghai Ruijin Hospital, , Shanghai Jiao Tong University School of Medicine, ; 200025 Shanghai, China
                Article
                Publisher ID: 11227
                DOI: 10.1038/s41598-017-11227-8
                PMC ID: 5599641
                PubMed ID: 28912447
                SO-VID: 4dfb9216-e0cc-4d01-b6bd-33e49dab8315
                Copyright © © The Author(s) 2017
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 25 May 2017
                Date accepted : 21 August 2017
                Categories
                Subject: Article
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                issue-copyright-statement © The Author(s) 2017

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