European Radiology

, Volume 29, Issue 1, pp 353–361 | Cite as

Extracellular volume fraction determined by equilibrium contrast-enhanced multidetector computed tomography as a prognostic factor in unresectable pancreatic adenocarcinoma treated with chemotherapy

  • Yoshihiko FukukuraEmail author
  • Yuichi Kumagae
  • Ryutaro Higashi
  • Hiroto Hakamada
  • Koji Takumi
  • Kosei Maemura
  • Michiyo Higashi
  • Kiyohisa Kamimura
  • Masanori Nakajo
  • Takashi Yoshiura



To assess whether extracellular volume (ECV) fraction with equilibrium contrast-enhanced multidetector computed tomography (MDCT) predicts outcomes for unresectable pancreatic adenocarcinoma patients treated with chemotherapy


Sixty-seven patients (42 men, 25 women; mean age, 67.5 years; range, 45–83 years) with histologically confirmed surgically unresectable pancreatic adenocarcinoma underwent contrast-enhanced MDCT before systemic chemotherapy. Tumour contrast enhancement (CE) and ECV fraction were calculated using region-of-interest measurement within the pancreatic adenocarcinoma and aorta on unenhanced and equilibrium phase-enhanced CT. The effect on survival variables including age, sex, tumour location, tumour size, TNM stage, carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), tumour CE and tumour ECV fraction was determined on univariate and multivariate analyses using Cox proportional hazards regression model.


Median overall survival was 10.5 months. On univariate analysis, elevated serum CA19-9 (hazard ratio (HR), 1.00; p = 0.006) and CEA (HR, 1.02; p = 0.011) levels were found to be associated with a negative effect on overall survival. Increasing tumour CE (HR, 0.98; p < 0.001) and ECV fraction (HR, 0.97; p = 0.001) were associated with a positive effect. Multivariate analysis revealed that only tumour ECV fraction was an independent predictor of overall survival (HR, 0.97; p = 0.012).


ECV fraction with equilibrium contrast-enhanced MDCT could be a useful imaging biomarker for predicting patient survival after chemotherapy for unresectable pancreatic adenocarcinoma.

Key Points

• Tumour aggressiveness and response to therapy are influenced by the extravascular extracellular space.

• Extracellular volume (ECV) fraction can be quantified with equilibrium contrast-enhanced CT.

• Patients with higher tumour ECV fraction had better prognosis after chemotherapy.


Pancreas cancer Multidetector computed tomography Contrast media Extracellular space Treatment outcome 



Carbohydrate antigen


Contrast enhancement


Carcinoembryonic antigen


Extracellular volume


18F-Fluorodeoxyglucose positron emission tomography


Intraclass correlation coefficient


Multidetector computed tomography


Regions of interest


International Union Against Cancer



We thank Dr. Chihaya Koriyama for help with statistical analysis.


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.

Conflict of interest

The authors of this article declare no relationships with any companies whose products or services may be related to the subject matter of the article.

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 2018

Authors and Affiliations

  • Yoshihiko Fukukura
    • 1
    Email author
  • Yuichi Kumagae
    • 1
  • Ryutaro Higashi
    • 1
  • Hiroto Hakamada
    • 1
  • Koji Takumi
    • 1
  • Kosei Maemura
    • 2
  • Michiyo Higashi
    • 3
  • Kiyohisa Kamimura
    • 1
  • Masanori Nakajo
    • 1
  • Takashi Yoshiura
    • 1
  1. 1.Department of Radiology, Graduate School of Medical and Dental SciencesKagoshima UniversityKagoshima CityJapan
  2. 2.Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental SciencesKagoshima UniversityKagoshima CityJapan
  3. 3.Human Pathology, Graduate School of Medical and Dental SciencesKagoshima UniversityKagoshima CityJapan

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