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CT radiomics associations with genotype and stromal content in pancreatic ductal adenocarcinoma

  • Marc A. Attiyeh
  • Jayasree Chakraborty
  • Caitlin A. McIntyre
  • Rajya Kappagantula
  • Yuting Chou
  • Gokce Askan
  • Kenneth Seier
  • Mithat Gonen
  • Olca Basturk
  • Vinod P. Balachandran
  • T. Peter Kingham
  • Michael I. D’Angelica
  • Jeffrey A. Drebin
  • William R. Jarnagin
  • Peter J. Allen
  • Christine A. Iacobuzio-Donahue
  • Amber L. Simpson
  • Richard K. DoEmail author
Pancreas
  • 55 Downloads

Abstract

Purpose

The aim of this study was to investigate the relationship between CT imaging phenotypes and genetic and biological characteristics in pancreatic ductal adenocarcinoma (PDAC).

Methods

In this retrospective study, consecutive patients between April 2015 and June 2016 who underwent PDAC resection were included if previously consented to a targeted sequencing protocol. Mutation status of known PDAC driver genes (KRAS, TP53, CDKN2A, and SMAD4) in the primary tumor was determined by targeted DNA sequencing and results were validated by immunohistochemistry (IHC). Radiomic features of the tumor were extracted from the preoperative CT scan and used to predict genotype and stromal content.

Results

The cohort for analysis consisted of 35 patients. Genomic and IHC analysis revealed alterations in KRAS in 34 (97%) patients, and changes in expression of CDKN2A in 29 (83%), SMAD4 in 16 (46%), and in TP53 in 29 (83%) patients. Models created from radiomic features demonstrated associations with SMAD4 status and the number of genes altered. The number of genes altered was the only significant predictor of overall survival (p = 0.016). By linear regression analysis, a prediction model for stromal content achieved an R2 value of 0.731 with a root mean square error of 19.5.

Conclusions

In this study, we demonstrate that in PDAC SMAD4 status and tumor stromal content can be predicted using radiomic analysis of preoperative CT imaging. These data show an association between resectable PDAC imaging features and underlying tumor biology and their potential for future precision medicine.

Keywords

Pancreatic neoplasm Computational biology Survival Radiogenomics Genomics 

Notes

Acknowledgements

This research was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748, the David M. Rubenstein Center for Pancreatic Research, and Cycle for Survival.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

261_2019_2112_MOESM1_ESM.pdf (112 kb)
Supplementary material 1 (PDF 111 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Marc A. Attiyeh
    • 1
  • Jayasree Chakraborty
    • 1
  • Caitlin A. McIntyre
    • 1
  • Rajya Kappagantula
    • 2
  • Yuting Chou
    • 1
  • Gokce Askan
    • 2
  • Kenneth Seier
    • 3
  • Mithat Gonen
    • 3
  • Olca Basturk
    • 2
  • Vinod P. Balachandran
    • 1
  • T. Peter Kingham
    • 1
  • Michael I. D’Angelica
    • 1
  • Jeffrey A. Drebin
    • 1
  • William R. Jarnagin
    • 1
  • Peter J. Allen
    • 1
  • Christine A. Iacobuzio-Donahue
    • 2
  • Amber L. Simpson
    • 1
  • Richard K. Do
    • 4
    Email author
  1. 1.Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Pathology, Human Oncology and Pathogenesis ProgramMemorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkUSA
  4. 4.Department of RadiologyMemorial Sloan Kettering Cancer CenterNew YorkUSA

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