Oncotarget

Research Papers:

Combining radiomic features with a miRNA classifier may improve prediction of malignant pathology for pancreatic intraductal papillary mucinous neoplasms

Jennifer B. Permuth _, Jung Choi, Yoganand Balarunathan, Jongphil Kim, Dung-Tsa Chen, Lu Chen, Sonia Orcutt, Matthew P. Doepker, Kenneth Gage, Geoffrey Zhang, Kujtim Latifi, Sarah Hoffe, Kun Jiang, Domenico Coppola, Barbara A. Centeno, Anthony Magliocco, Qian Li, Jose Trevino, Nipun Merchant, Robert Gillies, Mokenge Malafa and on behalf of the Florida Pancreas Collaborative

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Oncotarget. 2016; 7:85785-85797. https://doi.org/10.18632/oncotarget.11768

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Abstract

Jennifer B. Permuth1,2 , Jung Choi3, Yoganand Balarunathan4, Jongphil Kim5, Dung-Tsa Chen5, Lu Chen5, Sonia Orcutt2, Matthew P. Doepker11, Kenneth Gage3, Geoffrey Zhang4,6, Kujtim Latifi4,6, Sarah Hoffe2,6, Kun Jiang7, Domenico Coppola7, Barbara A. Centeno7, Anthony Magliocco7, Qian Li4,8, Jose Trevino9, Nipun Merchant10, Robert Gillies4 and Mokenge Malafa2 on behalf of the Florida Pancreas Collaborative

1 Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

2 Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

3 Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

4 Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

5 Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

6 Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

7 Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

8 Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

9 Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, Florida, USA

10 Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida, USA

11 Department of Clinical Surgery/Surgical Oncology, Palmetto Health/USC School of Medicine, Columbia, South Carolina, USA

Correspondence to:

Jennifer B. Permuth, email:

Keywords: radiomics, miRNA, risk stratification, pre-malignant lesions, pancreas

Received: July 06, 2016 Accepted: July 14, 2016 Published: August 31, 2016

Abstract

Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cancer precursors incidentally discovered by cross-sectional imaging. Consensus guidelines for IPMN management rely on standard radiologic features to predict pathology, but they lack accuracy. Using a retrospective cohort of 38 surgically-resected, pathologically-confirmed IPMNs (20 benign; 18 malignant) with preoperative computed tomography (CT) images and matched plasma-based ‘miRNA genomic classifier (MGC)’ data, we determined whether quantitative ‘radiomic’ CT features (+/- the MGC) can more accurately predict IPMN pathology than standard radiologic features ‘high-risk’ or ‘worrisome’ for malignancy. Logistic regression, principal component analyses, and cross-validation were used to examine associations. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were estimated. The MGC, ‘high-risk,’ and ‘worrisome’ radiologic features had area under the receiver operating characteristic curve (AUC) values of 0.83, 0.84, and 0.54, respectively. Fourteen radiomic features differentiated malignant from benign IPMNs (p<0.05) and collectively had an AUC=0.77. Combining radiomic features with the MGC revealed an AUC=0.92 and superior sensitivity (83%), specificity (89%), PPV (88%), and NPV (85%) than other models. Evaluation of uncertainty by 10-fold cross-validation retained an AUC>0.80 (0.87 (95% CI:0.84-0.89)). This proof-of-concept study suggests a noninvasive radiogenomic approach may more accurately predict IPMN pathology than ‘worrisome’ radiologic features considered in consensus guidelines.


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