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      Development and validation of a nomogram for predicting cancer-specific survival in patients with Wilms' tumor

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          Abstract

          Purpose: The objective of this study was to develop and validate a nomogram for predicting the cancer-specific survival (CSS) in patients with Wilms' tumor (WT).

          Methods: Patients with WT diagnosed between 2002 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were divided randomly into training and validation cohorts in this study. Multivariate Cox regression analysis was used to screen variables. A Cox proportional-hazards regression model and a nomogram were constructed based on variables that significantly affected the CSS in the training cohort. The nomogram for distinguishing and predicting the CSS was evaluated using the concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC), and calibration plots.

          Results: In total, 1631 patients from the SEER database were enrolled, with 1141 categorized into the training cohort and 490 into the validation cohort. All significant variables associated with CSS—age, the number of examined lymph nodes, SEER stage, and tumor size—were included in the nomogram. The C-index values of the nomogram in the training and validation cohorts were 0.746 and 0.703, respectively. The 3-, 5-, and 10-year AUCs were 0.755, 0.749, and 0.724, respectively, in the training cohort, and 0.718, 0.707, and 0.718 in the validation cohort. The calibration plots indicated the nomogram could accurately predict the 3-, 5-, and 10-year CSS.

          Conclusions: We have developed and validated the first nomogram for predicting the survival of WT patients. The nomogram is a reliable tool for distinguishing and predicting the CSS in patients with WT. Information provided by the nomogram may help to improve the clinical practices related to WT.

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          Most cited references16

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            Wilms' tumor.

            Wilms' tumor accounts for nearly 6% of all pediatric cancers and more than 95% of all kidney tumors in children. Fortunately, survival for patients with Wilms' tumor is generally excellent. This review will outline the results of prior clinical trials that have led to this excellent outcome and how information gleaned from these trials has led to the development of the current series of clinical trials for the management of children with Wilms' tumor. Tumor stage and histologic subtype have long been recognized as important prognostic factors in Wilms' tumor. More recent evidence suggests that, in certain instances, patient age, tumor size, response to therapy, and genetic abnormalities, specifically the loss of genetic material on chromosomes 1p and 16q, provide additional prognostic information. These factors have, therefore, been incorporated into a new risk stratification system that is currently being used to assign patients with Wilms' tumor to specific protocol-based therapies. Survival for patients with Wilms' tumor when considered as a whole, once less than 30%, is currently greater than 90%, with this dramatic improvement being due, in part, to the systematic manner in which the approach to therapy has evolved. Further refinement in therapy is being undertaken, with the current trials aiming to maintain the excellent survival for children being treated for Wilms' tumor, while minimizing therapy-related toxicity.
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              Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.

              Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2019
                28 August 2019
                : 10
                : 21
                : 5299-5305
                Affiliations
                [1 ]Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
                [2 ]School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
                [3 ]Department of Pharmacy, The Affiliated Children Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
                [4 ]Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
                [5 ]Department of Genetics, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China
                [6 ]Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
                Author notes
                ✉ Corresponding author: Jun Lyu, Email: lujun2006@ 123456xjtu.edu.cn , Tel: +86-29-85323614; No. 277 Yanta West Road, Xi'an, 710061, China.

                *These authors contributed equally to the article.

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

                Article
                jcav10p5299
                10.7150/jca.32741
                6775601
                31602280
                e68d3377-d527-40b4-89e3-a7499d03c383
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 2 January 2019
                : 25 June 2019
                Categories
                Research Paper

                Oncology & Radiotherapy
                wilms' tumor,nomogram,predict,survival
                Oncology & Radiotherapy
                wilms' tumor, nomogram, predict, survival

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