Imaging-Based Subtypes of Pancreatic Ductal Adenocarcinoma Exhibit Differential Growth and Metabolic Patterns in the Pre-Diagnostic Period: Implications for Early Detection

Mohamed Zaid, Dalia Elganainy, Prashant Dogra, Annie Dai, Lauren Widmann, Pearl Fernandes, Zhihui Wang, Maria J. Pelaez, Javier R. Ramirez, Aatur D. Singhi, Anil K. Dasyam, Randall E. Brand, Walter G. Park, Syed Rahmanuddin, Michael H. Rosenthal, Brian M. Wolpin, Natalia Khalaf, Ajay Goel, Daniel D. Von Hoff, Eric P. TammAnirban Maitra, Vittorio Cristini, Eugene J. Koay

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Previously, we characterized subtypes of pancreatic ductal adenocarcinoma (PDAC) on computed-tomography (CT) scans, whereby conspicuous (high delta) PDAC tumors are more likely to have aggressive biology and poorer clinical outcomes compared to inconspicuous (low delta) tumors. Here, we hypothesized that these imaging-based subtypes would exhibit different growth-rates and distinctive metabolic effects in the period prior to PDAC diagnosis.

Materials and methods: Retrospectively, we evaluated 55 patients who developed PDAC as a second primary cancer and underwent serial pre-diagnostic (T0) and diagnostic (T1) CT-scans. We scored the PDAC tumors into high and low delta on T1 and, serially, obtained the biaxial measurements of the pancreatic lesions (T0-T1). We used the Gompertz-function to model the growth-kinetics and estimate the tumor growth-rate constant (α) which was used for tumor binary classification, followed by cross-validation of the classifier accuracy. We used maximum-likelihood estimation to estimate initiation-time from a single cell (10 -6 mm 3) to a 10 mm 3 tumor mass. Finally, we serially quantified the subcutaneous-abdominal-fat (SAF), visceral-abdominal-fat (VAF), and muscles volumes (cm 3) on CT-scans, and recorded the change in blood glucose (BG) levels. T-test, likelihood-ratio, Cox proportional-hazards, and Kaplan-Meier were used for statistical analysis and p-value <0.05 was considered significant.

Results: Compared to high delta tumors, low delta tumors had significantly slower average growth-rate constants (0.024 month -1 vs. 0.088 month -1, p<0.0001) and longer average initiation-times (14 years vs. 5 years, p<0.0001). α demonstrated high accuracy (area under the curve (AUC)=0.85) in classifying the tumors into high and low delta, with an optimal cut-off of 0.034 month -1. Leave-one-out-cross-validation showed 80% accuracy in predicting the delta-class (AUC=0.84). High delta tumors exhibited accelerated SAF, VAF, and muscle wasting (p <0.001), and BG disturbance (p<0.01) compared to low delta tumors. Patients with low delta tumors had better PDAC-specific progression-free survival (log-rank, p<0.0001), earlier stage tumors (p=0.005), and higher likelihood to receive resection after PDAC diagnosis (p=0.008), compared to those with high delta tumors.

Conclusion: Imaging-based subtypes of PDAC exhibit distinct growth, metabolic, and clinical profiles during the pre-diagnostic period. Our results suggest that heterogeneous disease biology may be an important consideration in early detection strategies for PDAC.

Original languageEnglish (US)
Article number596931
JournalFrontiers in Oncology
StatePublished - Dec 2 2020


  • computed tomography
  • early detection
  • mathematical modeling
  • pancreatic cancer
  • tumor metabolism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Imaging-Based Subtypes of Pancreatic Ductal Adenocarcinoma Exhibit Differential Growth and Metabolic Patterns in the Pre-Diagnostic Period: Implications for Early Detection'. Together they form a unique fingerprint.

Cite this