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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusion

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.

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Acknowledgments

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).

Funding

This work was not supported by a grant.

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Authors and Affiliations

  1. Nuclear Medicine Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium

    Hugo Levillain, Ivan Duran Derijckere & Patrick Flamen

  2. Data Center Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium

    Lieveke Ameye

  3. Medical Physics Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium

    Thomas Guiot, Bruno Vanderlinden & Nick Reynaert

  4. Radiology and Nuclear Medicine Department, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands

    Arthur Braat & Marnix Lam

  5. Radiology Department, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Carsten Meyer

  6. Digestive Oncology Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium

    Alain Hendlisz

  7. Department of Imaging and Pathology, Nuclear Medicine, University Hospitals Leuven and Nuclear Medicine and Molecular Imaging, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

    Christophe M. Deroose

  8. Nuclear Medicine Department, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Hojjat Ahmadzadehfar

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  1. Hugo Levillain
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Corresponding author

Correspondence to Hugo Levillain.

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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.

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This article is part of the Topical Collection on Oncology - Digestive Tract.

Electronic supplementary material

Supplementary material 1

18F-FDG-PET/CT and 99mTc-SPECT/CT patient based analysis (XLSX 14 kb)

Supplementary material 2

Correlation matrix of the 20 continuous variables (PDF 332 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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Levillain, H., Duran Derijckere, I., Ameye, L. et al. Personalised radioembolization improves outcomes in refractory intra-hepatic cholangiocarcinoma: a multicenter study. Eur J Nucl Med Mol Imaging 46, 2270–2279 (2019). https://doi.org/10.1007/s00259-019-04427-z

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