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Radioablation by Image-Guided (HDR) Brachytherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma: A Randomized Phase II Trial

  • Clinical Investigation
  • Interventional Oncology
  • Published:
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Abstract

Background and Aims

The aim of this single-center, open-label phase II study was to assess the efficacy of image-guided high-dose-rate (HDR) brachytherapy (iBT) compared with conventional transarterial embolization (cTACE) in unresectable hepatocellular carcinoma.

Methods

Seventy-seven patients were treated after randomization to iBT or cTACE, as single or repeated interventions. Crossover was allowed if clinically indicated. The primary endpoint was time to untreatable progression (TTUP). Eligibility criteria included a Child–Pugh score of ≤ 8 points, absence of portal vein thrombosis (PVT) at the affected liver lobe, and ≤ 4 lesions. Survival was analyzed by using the Cox proportional hazard model with stratification for Barcelona Clinic Liver Cancer (BCLC) stages.

Results

Twenty patients were classified as BCLC-A (iBT/cTACE 8/12), 35 as BCLC-B (16/19), and 22 as BCLC-C (13/9). The 1-, 2-, and 3-year TTUP probabilities for iBT compared with cTACE were 67.5% versus 55.2%, 56.0% versus 27.4%, and 29.5% versus 11.0%, respectively, with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval 0.27–0.89; p = 0.019). The 1-, 2-, and 3-year TTPs for iBT versus cTACE were 56.0% versus 28.2%, 23.9% versus 6.3%, and 15.9% versus 6.3%, respectively, with an adjusted HR of 0.49 (0.29–0.85; p = 0.011). The 1-, 2-, and 3-year OS rates were 78.4% versus 67.7%, 62.0% versus 47.3%, and 36.7% versus 27.0%, respectively, with an adjusted HR of 0.62 (0.33–1.16; p = 0.136).

Conclusions

This explorative phase II trial showed a superior outcome of iBT compared with cTACE in hepatocellular carcinoma and supports proceeding to a phase III trial.

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Abbreviations

AASL:

American Association for the Study of the Liver

BCLC:

Barcelona Clinic Liver Cancer (staging system)

CI:

Confidence interval

CLIP:

Cancer of the Liver Italian Program

CT:

Computed tomography

cTACE:

Conventional transarterial chemoembolization

CTCAE:

Common Terminology Criteria for Adverse Events

DEB-TACE:

Drug-eluting beads transarterial chemoembolization

EASL:

European Association for the Study of the Liver

HCC:

Hepatocellular carcinoma

HDR:

High dose rate

HR:

Hazard ratio

iBT:

Interstitial brachytherapy

OS:

Overall survival

PVT:

Portal vein thrombosis

RFA:

Radiofrequency ablation

SBRT:

Stereotactic body radiotherapy

TTP:

Time to progression

TTUP:

Time to untreatable progression

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Funding

This study was funded exclusively by the University of Magdeburg.

Author information

Authors and Affiliations

  1. Department of Radiology and Nuclear Medicine, University of Magdeburg, Leipziger Str.44, 39120, Magdeburg, Germany

    Konrad Mohnike, Robert Damm & Maciej Pech

  2. Department of Radiology, Charité, Berlin, Germany

    Ingo G. Steffen

  3. Department of Radiology, Luwig-Maximilians-University Munich, Munich, Germany

    Max Seidensticker, Ricarda Seidensticker, Tina Streitparth, Gero Wieners & Jens Ricke

  4. Department of Radiotherapy, University of Magdeburg, Magdeburg, Germany

    Peter Hass

  5. Nils-Stensen-Hospital, Osnabrueck, Germany

    Kerstin Schütte

  6. Department of Surgery, University of Magdeburg, Magdeburg, Germany

    Jörg Arend

  7. Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK

    Jan Bornschein

  8. Department of Radiology, University Hospital of Cologne, Cologne, Germany

    Christian Wybranski

  9. DRK-Hospital Berlin-Koepenick, Berlin, Germany

    Patrick Stübs

  10. Department of Gastroenterology, Hepatology and Infectiology, University of Magdeburg, Magdeburg, Germany

    Peter Malfertheiner

  11. Diagnostisch Therapeutisches Zentrum am Frankfurter Tor, Berlin, Germany

    Konrad Mohnike & Nils Peters

  12. Deutsche Akademie für Mikrotherapie e.V., Magdeburg, Germany

    Konrad Mohnike, Max Seidensticker, Ricarda Seidensticker, Maciej Pech & Jens Ricke

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  1. Konrad Mohnike
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Corresponding author

Correspondence to Konrad Mohnike.

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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 and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed Consent

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

Consent for Publication

Consent for publication was obtained for every individual person’s data included in the study.

Financial Support

This work was funded exclusively by the University of Magdeburg.

Ethical Considerations

The study was conducted in accordance with the protocol, the ethical principles that have their origin in the Declaration of Helsinki, and ICH-GCP. The study protocol and all study-related documentation were approved by all relevant authorities (Ethics Committee of the Medical Faculty, University of Magdeburg, 44/06).

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Mohnike, K., Steffen, I.G., Seidensticker, M. et al. Radioablation by Image-Guided (HDR) Brachytherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma: A Randomized Phase II Trial. Cardiovasc Intervent Radiol 42, 239–249 (2019). https://doi.org/10.1007/s00270-018-2127-5

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  • DOI: https://doi.org/10.1007/s00270-018-2127-5

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