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      Malignancy Risk Stratification Prediction of Amorphous Calcifications Based on Clinical and Mammographic Features

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          Abstract

          Purpose

          To explore the potential factors influencing the malignancy risk of amorphous calcifications and establish a predictive nomogram for malignancy risk stratification.

          Patients and Methods

          Consecutive mammograms from January 2013 to December 2018 were retrospectively reviewed. Traditional clinical features were recorded, and mammographic features were estimated according to the 5th BI-RADS. Included calcifications were randomly divided into the training and validation cohorts. A nomogram was developed to graphically predict the risk of malignancy (risk) based on stepwise multivariate logistic regression analysis. The discrimination and calibration performance of the model were assessed in both the training and validation cohorts.

          Results

          Finally, 1018 amorphous calcifications with final pathological results in 907 women were identified with a malignancy rate of 28.4% (95% CI: 25.7%, 31.3%). The malignancy rates of subgroups divided by the distribution of calcifications, quantity of calcifications, age, menopausal status and family history of cancer were significantly different. There were 712 cases and 306 cases in the training and validation cohorts. The prediction nomogram was finally developed based on four risk factors, including age and distribution, maximum diameter and quantity of calcifications. The AUC of the nomogram was 0.799 (95% CI: 0.761, 0.836) in the training cohort and 0.795 (95% CI: 0.738, 0.852) in the validation cohort.

          Conclusion

          On mammography, the distribution, maximum diameter and quantity of calcifications are independent predictors of malignant amorphous calcifications and can be easily obtained in the clinic. The nomogram developed in this study for individualized malignancy risk stratification of amorphous calcifications shows good discrimination performance.

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          Most cited references26

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          Cancer statistics, 2020

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.
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            How to build and interpret a nomogram for cancer prognosis.

            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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              Radiomics Signature: A Potential Biomarker for the Prediction of Disease-Free Survival in Early-Stage (I or II) Non-Small Cell Lung Cancer.

              Purpose To develop a radiomics signature to estimate disease-free survival (DFS) in patients with early-stage (stage I-II) non-small cell lung cancer (NSCLC) and assess its incremental value to the traditional staging system and clinical-pathologic risk factors for individual DFS estimation. Materials and Methods Ethical approval by the institutional review board was obtained for this retrospective analysis, and the need to obtain informed consent was waived. This study consisted of 282 consecutive patients with stage IA-IIB NSCLC. A radiomics signature was generated by using the least absolute shrinkage and selection operator, or LASSO, Cox regression model. Association between the radiomics signature and DFS was explored. Further validation of the radiomics signature as an independent biomarker was performed by using multivariate Cox regression. A radiomics nomogram with the radiomics signature incorporated was constructed to demonstrate the incremental value of the radiomics signature to the traditional staging system and other clinical-pathologic risk factors for individualized DFS estimation, which was then assessed with respect to calibration, discrimination, reclassification, and clinical usefulness. Results The radiomics signature was significantly associated with DFS, independent of clinical-pathologic risk factors. Incorporating the radiomics signature into the radiomics-based nomogram resulted in better performance (P < .0001) for the estimation of DFS (C-index: 0.72; 95% confidence interval [CI]: 0.71, 0.73) than with the clinical-pathologic nomogram (C-index: 0.691; 95% CI: 0.68, 0.70), as well as a better calibration and improved accuracy of the classification of survival outcomes (net reclassification improvement: 0.182; 95% CI: 0.02, 0.31; P = .02). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinical-pathologic nomogram. Conclusion The radiomics signature is an independent biomarker for the estimation of DFS in patients with early-stage NSCLC. Combination of the radiomics signature, traditional staging system, and other clinical-pathologic risk factors performed better for individualized DFS estimation in patients with early-stage NSCLC, which might enable a step forward precise medicine. (©) RSNA, 2016 Online supplemental material is available for this article.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                cmar
                cancmanres
                Cancer Management and Research
                Dove
                1179-1322
                12 January 2021
                2021
                : 13
                : 235-245
                Affiliations
                [1 ]Shanghai Institute of Medical Imaging , Shanghai, People’s Republic of China
                [2 ]Department of Radiology, Fudan University Shanghai Cancer Center , Shanghai, People’s Republic of China
                [3 ]Department of Oncology, Fudan University Shanghai Cancer Center , Shanghai, People’s Republic of China
                [4 ]Department of Pathology, Fudan University Shanghai Cancer Center , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Weijun Peng; Chao You Fudan University Shanghai Cancer Center , No. 270, Dongan Road, Xuhui District, Shanghai200032, People’s Republic of ChinaTel +86-15026544096; +86-21-64175590Fax +86-21-64174774 Email cjr.pengweijun@vip.163.com: youchao8888@aliyun.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-9420-1919
                Article
                286269
                10.2147/CMAR.S286269
                7811441
                33469367
                24216f6e-2868-4398-9125-af85238cf433
                © 2021 Shen et al.

                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
                : 13 October 2020
                : 17 December 2020
                Page count
                Figures: 5, Tables: 6, References: 27, Pages: 11
                Funding
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Funded by: National Natural Science Foundation of China, Youth Science Fund Project;
                Funded by: Shanghai “Rising Stars of Medical Talent” Youth Development Program, Medical Imaging Practitioner Program;
                Funded by: Shanghai Municipal Health Planning Commission Youth Project;
                This work was supported by the National Natural Science Foundation of China, Youth Science Fund Project(no.81901703), Natural Science and Technology Major Project (no.2020ZX09201-013) and the National Natural Science Foundation of China (no. 61731008). This project has also been funded by Shanghai “Rising Stars of Medical Talent” Youth Development Program, Medical Imaging Practitioner Program (no. SHWRS (2020)_087) and Shanghai Municipal Health Planning Commission Youth Project (no. 20184Y0010).
                Categories
                Original Research

                Oncology & Radiotherapy
                breast cancer,mammography,calcifications,malignancy risk stratification,nomogram

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