{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T20:51:00Z","timestamp":1773348660142,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002579"],"award-info":[{"award-number":["82002579"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M663519"],"award-info":[{"award-number":["2019M663519"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2020YFS0262"],"award-info":[{"award-number":["2020YFS0262"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["2019HXBH044"],"award-info":[{"award-number":["2019HXBH044"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Backgroud<\/jats:title><jats:p>Tumor grade is the determinant of the biological aggressiveness of pancreatic neuroendocrine tumors (PNETs) and the best current tool to help establish individualized therapeutic strategies. A noninvasive way to accurately predict the histology grade of PNETs preoperatively is urgently needed and extremely limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The models training and the construction of the radiomic signature were carried out separately in three-phase (plain, arterial, and venous) CT. Mann\u2013Whitney <jats:italic>U<\/jats:italic> test and least absolute shrinkage and selection operator (LASSO) were applied for feature preselection and radiomic signature construction. SVM-linear models were trained by incorporating the radiomic signature with clinical characteristics. An optimal model was then chosen to build a nomogram.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 139 PNETs (including 83 in the training set and 56 in the independent validation set) were included in the present study. We build a model based on an eight-feature radiomic signature (group 1) to stratify PNET patients into grades 1 and 2\/3 groups with an AUC of 0.911 (95% confidence intervals (CI), 0.908\u20130.914) and 0.837 (95% CI, 0.827\u20130.847) in the training and validation cohorts, respectively. The nomogram combining the radiomic signature of plain-phase CT with T stage and dilated main pancreatic duct (MPD)\/bile duct (BD) (group 2) showed the best performance (training set: AUC\u00a0=\u00a00.919, 95% CI\u00a0=\u00a00.916\u20130.922; validation set: AUC\u00a0=\u00a00.875, 95% CI\u00a0=\u00a00.867\u20130.883).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our developed nomogram that integrates radiomic signature with clinical characteristics could be useful in predicting grades 1 and 2\/3 PNETs preoperatively with powerful capability.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2022.843376","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T07:10:46Z","timestamp":1648710646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Development and Validation of a Novel Radiomics-Based Nomogram With Machine Learning to Preoperatively Predict Histologic Grade in Pancreatic Neuroendocrine Tumors"],"prefix":"10.3389","volume":"12","author":[{"given":"Xing","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Jun","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Lu","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing-Quan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Jie","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Qing","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neng-Wen","family":"Ke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu-Bao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031575","article-title":"Non-Islet Origin of Pancreatic Islet Cell Tumors","volume":"89","author":"Vortmeyer","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djs208","article-title":"TNM Staging of Neoplasms of the Endocrine Pancreas: Results From a Large International Cohort Study","volume":"104","author":"Rindi","year":"2012","journal-title":"J Natl Cancer Institute"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17599","article-title":"A Nation-Wide Retrospective Epidemiological Study of Gastroenteropancreatic Neuroendocrine Neoplasms in China","volume":"8","author":"Fan","year":"2017","journal-title":"Oncotarget"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0589","article-title":"Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States","volume":"3","author":"Dasari","year":"2017","journal-title":"JAMA Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21493","article-title":"Gastroenteropancreatic Neuroendocrine Tumors","volume":"68","author":"Cives","year":"2018","journal-title":"CA: Cancer J Clin"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31821a0696","article-title":"Effect of Tumor Heterogeneity on the Assessment of Ki67 Labeling Index in Well-Differentiated Neuroendocrine Tumors Metastatic to the Liver: Implications for Prognostic Stratification","volume":"35","author":"Yang","year":"2011","journal-title":"Am J Surg Pathol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2013.3376","article-title":"Pattern and Clinical Predictors of Lymph Node Involvement in Nonfunctioning Pancreatic Neuroendocrine Tumors (NF-PanNETs)","volume":"148","author":"Partelli","year":"2013","journal-title":"JAMA Surg"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000003579","article-title":"Multi-Institutional Development and External Validation of a Nomogram to Predict Recurrence After Curative Resection of Pancreatic Neuroendocrine Tumors","volume":"274","author":"Pulvirenti","year":"2019","journal-title":"Ann Surg"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/ans.16072","article-title":"Predicting Survival in Non-Functional Pancreatic Neuroendocrine Tumours","volume":"90","author":"Tan","year":"2020","journal-title":"ANZ J Surg"},{"key":"B10","volume-title":"WHO Classifcation of Tumours of the Digestive System","author":"Bosman","year":"2010"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1159\/000495774","article-title":"Patterns of Recurrence After Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where","volume":"108","author":"Marchegiani","year":"2019","journal-title":"Neuroendocrinology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/jso.26158","article-title":"Clinical Relevance of Performing Endoscopic Ultrasound-Guided Fine-Needle Biopsy for Pancreatic Neuroendocrine Tumors Less Than 2\u2009Cm","volume":"122","author":"Heidsma","year":"2020","journal-title":"J Surg Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2020.12.015","article-title":"Comparison Between EUS-Guided Fine-Needle Aspiration Cytology and EUS-Guided Fine-Needle Biopsy Histology for the Evaluation of Pancreatic Neuroendocrine Tumors","volume":"21","author":"Crin\u00f2","year":"2021","journal-title":"Pancreatol Off J Int Assoc Pancreatol (IAP) [et al]"},{"key":"B14","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s13550-019-0585-7","article-title":"Prediction of the Aggressiveness of Non-Functional Pancreatic Neuroendocrine Tumors Based on the Dual-Tracer PET\/Ct","volume":"9","author":"Majala","year":"2019","journal-title":"EJNMMI Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-014-3532-z","article-title":"Neuroendocrine Neoplasms of the Pancreas at Dynamic Enhanced CT: Comparison Between Grade 3 Neuroendocrine Carcinoma and Grade 1\/2 Neuroendocrine Tumour","volume":"25","author":"Kim","year":"2015","journal-title":"Eur Radiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1177\/0284185113494982","article-title":"The Value of Gadoxetic Acid-Enhanced and Diffusion-Weighted MRI for Prediction of Grading of Pancreatic Neuroendocrine Tumors","volume":"55","author":"Jang","year":"2014","journal-title":"Acta radiologica (Stockholm Sweden 1987)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-016-4539-4","article-title":"Prediction of Pancreatic Neuroendocrine Tumour Grade With MR Imaging Features: Added Value of Diffusion-Weighted Imaging","volume":"27","author":"Lotfalizadeh","year":"2017","journal-title":"Eur Radiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.141","article-title":"Radiomics: The Bridge Between Medical Imaging and Personalized Medicine","volume":"14","author":"Lambin","year":"2017","journal-title":"Nat Rev Clin Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4006","DOI":"10.1038\/ncomms5644","article-title":"Decoding Tumour Phenotype by Noninvasive Imaging Using a Quantitative Radiomics Approach","volume":"5","author":"Aerts","year":"2014","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1038","article-title":"Radiomics Analysis for Evaluation of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer","volume":"23","author":"Liu","year":"2017","journal-title":"Clin Cancer Res an Off J Am Assoc Cancer Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.9128","article-title":"Development and Validation of a Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Colorectal Cancer","volume":"34","author":"Huang","year":"2016","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2018.04.013","article-title":"CT-Based Radiomic Model Predicts High Grade of Clear Cell Renal Cell Carcinoma","volume":"103","author":"Ding","year":"2018","journal-title":"Eur J Radiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2018.01.020","article-title":"CT-Based Radiomics Signature to Discriminate High-Grade From Low-Grade Colorectal Adenocarcinoma","volume":"25","author":"Huang","year":"2018","journal-title":"Acad Radiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s11548-012-0681-x","article-title":"Measures of Angular Spread and Entropy for the Detection of Architectural Distortion in Prior Mammograms","volume":"8","author":"Banik","year":"2013","journal-title":"Int J Comput Assist Radiol Surg"},{"key":"B25","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.cmpb.2008.08.005","article-title":"MaZda\u2013a Software Package for Image Texture Analysis","volume":"94","author":"Szczypinski","year":"2009","journal-title":"Comput Methods Programs BioMed"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1118\/1.4747526","article-title":"Ultrasound GLCM Texture Analysis of Radiation-Induced Parotid-Gland Injury in Head-and-Neck Cancer Radiotherapy: An In Vivo Study of Late Toxicity","volume":"39","author":"Yang","year":"2012","journal-title":"Med Phys"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.4377","article-title":"One Hundred Years After \u201cCarcinoid\u201d: Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United States","volume":"26","author":"Yao","year":"2008","journal-title":"J Clin Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002362","article-title":"Clinical Implications of the 2016 International Study Group on Pancreatic Surgery Definition and Grading of Postoperative Pancreatic Fistula on 775 Consecutive Pancreatic Resections","volume":"268","author":"Pulvirenti","year":"2018","journal-title":"Ann Surg"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200609","article-title":"DAXX\/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors","volume":"331","author":"Jiao","year":"2011","journal-title":"Sci (New York NY)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature21063","article-title":"Whole-Genome Landscape of Pancreatic Neuroendocrine Tumours","volume":"543","author":"Scarpa","year":"2017","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2020.01.002","article-title":"CT-Radiomic Approach to Predict G1\/2 Nonfunctional Pancreatic Neuroendocrine Tumor","volume":"27","author":"Zhao","year":"2020","journal-title":"Acad Radiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21552","article-title":"Artificial Intelligence in Cancer Imaging: Clinical Challenges and Applications","volume":"69","author":"Bi","year":"2019","journal-title":"CA: Cancer J Clin"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1109\/CVPR.2019.00866","article-title":"Metric Learning for Image Registration","volume":"2019","author":"Niethammer","year":"2019","journal-title":"Proc IEEE Comput Soc Conf Comput Vision Pattern Recognition"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/mp.15199","article-title":"Radiomics Analysis Combining Unsupervised Learning and Handcrafted Features: A Multiple-Disease Study","volume":"48","author":"Wan","year":"2021","journal-title":"Med Phys"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1305","article-title":"A Combined Nomogram Model to Preoperatively Predict Histologic Grade in Pancreatic Neuroendocrine Tumors","volume":"25","author":"Liang","year":"2019","journal-title":"Clin Cancer Res an Off J Am Assoc Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.521831","article-title":"Application of Radiomics Analysis Based on CT Combined With Machine Learning in Diagnostic of Pancreatic Neuroendocrine Tumors Patient's Pathological Grades","volume":"10","author":"Zhang","year":"2020","journal-title":"Front Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.843376\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T07:11:03Z","timestamp":1648710663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.843376\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,31]]},"references-count":36,"alternative-id":["10.3389\/fonc.2022.843376"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.843376","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,31]]},"article-number":"843376"}}