Extracellular volume fraction determined by equilibrium contrast-enhanced dual-energy CT as a prognostic factor in patients with stage IV pancreatic ductal adenocarcinoma

  • Yoshihiko FukukuraEmail author
  • Yuichi Kumagae
  • Ryutaro Higashi
  • Hiroto Hakamada
  • Masatoyo Nakajo
  • Kosei Maemura
  • Shiho Arima
  • Takashi Yoshiura
Computed Tomography



To evaluate the feasibility of equilibrium contrast-enhanced dual-energy CT (DECT), as compared with single-energy CT (SECT) and to calculate extracellular volume (ECV) fraction to predict the survival outcomes of pancreatic ductal adenocarcinoma (PDAC) patients with distant metastases (stage IV) treated with chemotherapy.


The study cohort included a total of 66 patients with stage IV PDAC who underwent DECT before systemic chemotherapy between July 2014 and March 2017. Unenhanced and 120-kVp equivalent images during the equilibrium phase were used to calculate tumor SECT-derived ECV fractions, and iodine density images were obtained from equilibrium-phase DECT for DECT-derived ECV fractions. Correlations between SECT- and DECT-derived ECV fractions were identified using the Pearson correlation coefficient and Bland–Altman analysis. The effects of clinical prognostic factors and tumor SECT- and DECT-derived ECV fractions on progression-free survival (PFS) and overall survival (OS) were assessed by univariate and multivariate analyses using Cox proportional hazards models.


The correlation between SECT- and DECT-derived ECV fractions was strong (r = 0.965; p < 0.001). The Bland–Altman plot between SECT- and DECT-derived ECV fractions showed a small bias (− 3.4%). Increasing tumor SECT- and DECT-derived ECV fractions were associated with a positive effect on PFS (SECT, p = 0.002; DECT, p = 0.007) and OS (DECT, p = 0.014; DECT, p = 0.015). Only tumor DECT-derived ECV fraction was an independent predictor of PFS (p = 0.018) and OS (p = 0.022) in patients with stage IV PDAC treated with chemotherapy on multivariate analysis.


The ECV fraction determined by equilibrium contrast-enhanced DECT can potentially predict the survival of patients with stage IV PDAC treated with chemotherapy.

Key Points

• Extracellular volume fraction of stage IV pancreatic ductal adenocarcinoma determined by dual-energy CT was strongly correlated to that with single-energy CT (r = 0.965, p < 0.001).

• Tumor extracellular volume fraction was an independent predictor of progression-free survival (p = 0.018) and overall survival (p = 0.022).

• Extracellular volume fraction determined by dual-energy CT could be a useful imaging biomarker to predict the survival of patients with stage IV pancreatic ductal adenocarcinoma treated with chemotherapy.


Pancreatic ductal carcinoma Multidetector computed tomography Contrast media Extracellular space Treatment outcome 



Carbohydrate antigen


Carcinoembryonic antigen


Confidence interval


CT dose index volume


Dual-energy CT


Dose-length product


Extracellular volume


Intraclass correlation coefficient


Iodine density image


Overall survival


Pancreatic ductal adenocarcinoma


Progression-free survival


Regions of interest


Single-energy CT


Union for International Cancer Control


Funding Information

The authors state that this work has not received any funding.

Compliance with ethical standards


The scientific guarantor of this publication is Yoshihiko Fukukura, MD, PhD, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University.

Conflict of interest

The authors declare that they have no competing interests.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived by the institutional review board.

Ethical approval

Institutional review board approval was obtained.


• retrospective

• diagnostic or prognostic study

• performed at one institution


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Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  1. 1.Department of Radiology, Graduate School of Medical and Dental SciencesKagoshima UniversityKagoshima CityJapan
  2. 2.Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental SciencesKagoshima UniversityKagoshima CityJapan
  3. 3.Department of Digestive and Lifestyle Diseases, Graduate School of Medical and Dental SciencesKagoshima UniversityKagoshima CityJapan

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