Program Official

Principal Investigator

Jennifer B.
Permuth
Awardee Organization

H. Lee Moffitt Cancer Ctr & Res Inst
United States

Fiscal Year
2023
Activity Code
R37
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Using Radiogenomics to Noninvasively Predict the Malignant Potential of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Uncover Hidden Biology

Approximately 700,000 pancreatic cysts are incidentally detected by imaging each year. Up to 70% of these radiologically-detected cysts are intraductal papillary mucinous neoplasms (IPMNs), bona fide precursor lesions to pancreatic cancer, the only solid malignancy with a 5-year relative survival rate in the single digits. Once detected, existing imaging modalities and molecular markers cannot reliably distinguish low/moderate grade (benign) IPMNs that merit surveillance from high-grade/invasive (malignant) IPMNs that warrant surgical resection, posing a great clinical challenge. Based on preliminary data generated by our group, we hypothesize that unexplored categories of quantitative ‘radiomic’ features extracted from preoperative computed tomography (CT) scans will have added diagnostic value in predicting malignant IPMN pathology, compared to standard radiologic features. We further hypothesize that a liquid biopsy that measures microRNAs circulating in blood plasma (a miRNA genomic classifier (MGC)) that we have developed may help to further enhance diagnostic accuracy. The goals of this proposal are to 1) Evaluate the diagnostic performance of novel radiomic CT features in predicting IPMN pathology, compared to standard radiologic features, using data and specimens from a retrospective series (Aim 1a) and a prospective multi-institutional series of IPMN cases (Aim 1b); 2) Generate prototype clinical decision-making models (nomograms) that take into account radiomic data, the MGC, and other clinical characteristics (Aim 2); and 3) Evaluate the relationship between radiomic features and biological processes that underlie IPMN tumor development and/or progression. By leveraging interdisciplinary expertise and largely existing data unique to our institutions, our long-term goal is to discover a combined quantitative imaging and biomarker approach that is noninvasive and has added value in predicting IPMN pathology beyond that provided by standard radiologic characteristics. This line of translational research has potential to foster clinically actionable information that could be used to rapidly and cost-effectively personalize care for individuals with IPMNs and ultimately reduce the burden of pancreatic cancer as a major health problem.

Publications

  • Jeong D, Morse B, Polk SL, Chen DT, Li J, Hodul P, Centeno BA, Costello J, Jiang K, Machado S, El Naqa I, Farah PT, Huynh T, Raghunand N, Mok S, Dam A, Malafa M, Qayyum A, Fleming JB, Permuth JB. Pancreatic Cyst Size Measurement on Magnetic Resonance Imaging Compared to Pathology. Cancers. 2024 Jan 1;16. (1). PMID: 38201633
  • Polk SL, Choi JW, McGettigan MJ, Rose T, Ahmed A, Kim J, Jiang K, Balagurunathan Y, Qi J, Farah PT, Rathi A, Permuth JB, Jeong D. Multiphase computed tomography radiomics of pancreatic intraductal papillary mucinous neoplasms to predict malignancy. World journal of gastroenterology. 2020 Jun 28;26(24):3458-3471. PMID: 32655269
  • Park MA, Zaw T, Yoder SJ, Gomez M, Genilo-Delgado M, Basinski T, Katende E, Dam A, Mok SRS, Monteiro A, Mohammadi A, Jeong DK, Jiang K, Centeno BA, Hodul P, Malafa M, Fleming J, Chen DT, Mo Q, Teer JK, Permuth JB. A pilot study to evaluate tissue- and plasma-based DNA driver mutations in a cohort of patients with pancreatic intraductal papillary mucinous neoplasms. G3 (Bethesda, Md.). 2023 Feb 9;13. (2). PMID: 36454217
  • Beato F, Reverón D, Dezsi KB, Ortiz A, Johnson JO, Chen DT, Ali K, Yoder SJ, Jeong D, Malafa M, Hodul P, Jiang K, Centeno BA, Abdalah MA, Balasi JA, Tassielli AF, Sarcar B, Teer JK, DeNicola GM, Permuth JB, Fleming JB. Establishing a living biobank of patient-derived organoids of intraductal papillary mucinous neoplasms of the pancreas. Laboratory investigation; a journal of technical methods and pathology. 2021 Feb;101(2):204-217. Epub 2020 Oct 9. PMID: 33037322
  • Permuth JB, Powers BD, Hodul PJ, Florida Pancreas Collaborative. A Path Forward for Understanding and Addressing Multifaceted Pancreatic Cancer Disparities. Gastroenterology. 2022 Jul;163(1):51-53. Epub 2022 May 2. PMID: 35513007
  • Huynh T, Ali K, Vyas S, Dezsi K, Strickland D, Basinski T, Chen DT, Jiang K, Centeno B, Malafa M, Klapman JB, Hodul PJ, Jeong D, Permuth JB. Comparison of imaging modalities for measuring the diameter of intraductal papillary mucinous neoplasms of the pancreas. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2020 Apr;20(3):448-453. Epub 2020 Feb 21. PMID: 32113936
  • Markovitz M, Jiang K, Kim D, Rose T, Permuth JB, Jeong D. Pancreatic colloid adenocarcinoma arising from intraductal papillary mucinous neoplasm: Radiologic-pathologic correlation with cinematic rendering. Acta radiologica open. 2023 Feb 14;12(2):20584601231157046. doi: 10.1177/20584601231157046. eCollection 2023 Feb. PMID: 36817179
  • Permuth JB, Mesa T, Williams SL, Cardentey Y, Zhang D, Pawlak EA, Li J, Cameron ME, Ali KN, Jeong D, Yoder SJ, Chen DT, Trevino JG, Merchant N, Malafa M. A pilot study to troubleshoot quality control metrics when assessing circulating miRNA expression data reproducibility across study sites. Cancer biomarkers : section A of Disease markers. 2022;33(4):467-478. PMID: 35491771
  • Barnholtz-Sloan JS, Rollison DE, Basu A, Borowsky AD, Bui A, DiGiovanna J, Garcia-Closas M, Genkinger JM, Gerke T, Induni M, Lacey JV Jr, Mirel L, Permuth JB, Saltz J, Shenkman EA, Ulrich CM, Zheng WJ, Nadaf S, Kibbe WA. Cancer Informatics for Cancer Centers (CI4CC): Building a Community Focused on Sharing Ideas and Best Practices to Improve Cancer Care and Patient Outcomes. JCO clinical cancer informatics. 2020 Feb;4:108-116. PMID: 32078367

Clinical Trials

Study Name Clinical Trial ID
Using Radiogenomics to Predict Malignant Potential of Intraductal Papillary Mucinous Neoplasms of the Pancreas NCT04275557