Personalised radioembolization improves outcomes in refractory intra-hepatic cholangiocarcinoma: a multicenter study

  • Hugo LevillainEmail author
  • Ivan Duran Derijckere
  • Lieveke Ameye
  • Thomas Guiot
  • Arthur Braat
  • Carsten Meyer
  • Bruno Vanderlinden
  • Nick Reynaert
  • Alain Hendlisz
  • Marnix Lam
  • Christophe M. Deroose
  • Hojjat Ahmadzadehfar
  • Patrick Flamen
Original Article
Part of the following topical collections:
  1. Oncology – Digestive tract



Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients’ characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome.


This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin 90Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline 18F-FDG-PET/CT. 99mTc-MAA tumor to liver uptake ratio (TLRMAA) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox’s proportional hazards model.


Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29–5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14–4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50–5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05–3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31–5.22, p < 0.001). The presence of lymph node metastasis as well as a TLRMAA < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08–5.11, p = 0.008 and HR = 2.92, 95%CI:1.01–8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23–5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09–4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy).


Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed.


Intra-hepatic cholangiocarcinoma Radioembolization SIRT Yttrium-90 Resin microspheres 



This academic work was supported and sponsored by the Jules Bordet Institute. Part of the results was presented at the 2019 SNMMI–annual congress of the Society of Nuclear Medicine and Molecular Imaging as an oral presentation during the GI – Colorectal, liver, esophageal session (OP- 216).


This work was not supported by a grant.

Compliance with ethical standards

Conflict of interest

PF, AH, HA and CD played an advisory role and received honoraria from Sirtex.

ML is a consultant for BTG, Sirtex, Quirem and Terumo. He receives research support from BTG, Quirem and Terumo. The department of Radiology and Nuclear Medicine of the UMC Utrecht receives royalties from Quirem.

BV played an advisory role and received honoraria from Dosisoft.

The first author and all other co-authors have no conflicts of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Jules Bordet Institute Ethics Committee (CE2575) and Ethics Committees of all other participating centres. For this type of study formal consent is not required.

This article does not contain any studies with animals performed by any of the authors.

Supplementary material

259_2019_4427_MOESM1_ESM.xlsx (14 kb)
Supplementary material 1 18F-FDG-PET/CT and 99mTc-SPECT/CT patient based analysis (XLSX 14 kb)
259_2019_4427_MOESM2_ESM.pdf (332 kb)
Supplementary material 2 Correlation matrix of the 20 continuous variables (PDF 332 kb)
259_2019_4427_MOESM3_ESM.xlsx (16 kb)
Supplementary material 3 Comparison between patients treated with the BSA method and patients treated with the partition-model (XLSX 16 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hugo Levillain
    • 1
    Email author
  • Ivan Duran Derijckere
    • 1
  • Lieveke Ameye
    • 2
  • Thomas Guiot
    • 3
  • Arthur Braat
    • 4
  • Carsten Meyer
    • 5
  • Bruno Vanderlinden
    • 3
  • Nick Reynaert
    • 3
  • Alain Hendlisz
    • 6
  • Marnix Lam
    • 4
  • Christophe M. Deroose
    • 7
  • Hojjat Ahmadzadehfar
    • 8
  • Patrick Flamen
    • 1
  1. 1.Nuclear Medicine Department, Jules Bordet InstituteUniversité Libre de BruxellesBrusselsBelgium
  2. 2.Data Center Department, Jules Bordet InstituteUniversité Libre de BruxellesBrusselsBelgium
  3. 3.Medical Physics Department, Jules Bordet InstituteUniversité Libre de BruxellesBrusselsBelgium
  4. 4.Radiology and Nuclear Medicine DepartmentUniversity Medical Center UtrechtUtrechtThe Netherlands
  5. 5.Radiology DepartmentUniversity Hospital BonnBonnGermany
  6. 6.Digestive Oncology Department, Jules Bordet InstituteUniversité Libre de BruxellesBrusselsBelgium
  7. 7.Department of Imaging and PathologyNuclear Medicine, University Hospitals Leuven and Nuclear Medicine and Molecular ImagingLeuvenBelgium
  8. 8.Nuclear Medicine DepartmentUniversity Hospital BonnBonnGermany

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