European Radiology

, Volume 29, Issue 4, pp 1882–1892 | Cite as

Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: European multicentre study on safety, short-term effects and survival

  • Steffen Marquardt
  • Martha M. Kirstein
  • Roland Brüning
  • Martin Zeile
  • Pier Francesco Ferrucci
  • Warner Prevoo
  • Boris Radeleff
  • Hervé Trillaud
  • Lambros Tselikas
  • Emilio Vicente
  • Philipp Wiggermann
  • Michael P. Manns
  • Arndt Vogel
  • Frank K. WackerEmail author



Cholangiocarcinoma is the second most common primary liver tumour with a poor overall prognosis. Percutaneous hepatic perfusion (PHP) is a directed therapy for primary and secondary liver malignancies, and its efficacy and safety have been shown in different entities. The purpose of this study was to prove the safety and efficacy of PHP in patients with unresectable intrahepatic cholangiocarcinoma (iCCA).

Patients and methods

We retrospectively reviewed data from 15 patients with unresectable iCCA treated with PHP in nine different hospitals throughout Europe. Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumours (RECIST1.1). Overall survival (OS), progression-free survival (PFS) and hepatic PFS (hPFS) were analysed using the Kaplan-Meier estimation. Adverse events (AEs) and toxicity were evaluated.


Fifteen patients were treated with 26 PHPs. ORR was 20%, disease control was achieved in 53% after the first PHP. Median OS was 26.9 months from initial diagnosis and 7.6 months from first PHP. Median PFS and hPFS were 122 and 131 days, respectively. Patients with liver-only disease had a significantly longer median OS compared to patients with locoregional lymph node metastases (12.9 vs. 4.8 months, respectively; p < 0.01). Haematological toxicity was common, but manageable. No AEs of grade 3 or 4 occurred during the procedures.


PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with iCCA, especially in non-metastatic disease.

Key Points

• Percutaneous hepatic perfusion (PHP) offers an additional locoregional therapy strategy for the treatment of unresectable primary or secondary intrahepatic malignancies.

• PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with intrahepatic cholangiocarcinoma (iCCA), especially in non-metastatic disease.

• Side effects seem to be tolerable and comparable to other systemic or local treatment strategies.


Percutaneous hepatic perfusion Cholangiocarcinoma Liver neoplasms Chemosaturation 



Activated clotting time


Adverse events


Alkaline phosphatase


Aspartate aminotransferase


Best alternative care




Intrahepatic cholangiocarcinoma


Complete response


C-reactive protein


Computed tomography


Common terminology criteria for adverse events


Eastern Cooperative Oncology Group


Granulocyte-colony stimulating factor


Hepatic arterial infusion


Hepatocellular carcinoma




International normalized ratio


Liver function test


Magnetic resonance imaging


Ocular melanoma


Overall response rate


Overall survival


Progressive disease


Progression-free survival


Hepatic progression-free survival


Percutaneous hepatic perfusion


Platelet count


Partial response


Response evaluation criteria in solid tumours


Radiofrequency ablation


Stable disease


Transarterial chemoembolisation


Transarterial radioembolisation


Upper limit of normal



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

Compliance with ethical standards


The scientific guarantor of this publication is Frank K. Wacker.

Conflict of interest

Steffen Marquardt reports a travel grant and lecture fees from Delcath Systems, Inc. during the conduct of the study.

Martha M. Kirstein has no conflicts of interest related to the subject matter of the article.

She received honoraria and travel grants from Shire, Novartis, Ipsen and Roche outside the submitted work.

Roland Brüning has no conflicts of interest related to the subject matter of the article or outside the submitted work.

Martin Zeile reports consulting and proctoring fees from Delcath systems, Inc.

He reports consulting fees for Boston Scientific, Inc. outside the submitted work.

Pier Francesco Ferrucci has no conflicts of interest related to the subject matter of the article or outside the submitted work.

Warner Prevoo reports proctoring fees from Delcath systems, Inc.

Boris Radeleff has no conflicts of interest related to the subject matter of the article or outside the submitted work.

Hervé Trillaud has no conflicts of interest related to the subject matter of the article or outside the submitted work.

Lambros Tselikas has no conflicts of interest related to the subject matter of the article.

He reports proctoring/speaking fees for Cook Medical, BTG, GE Healthcare, Sirtex Medical, AMGEN and Pfizer.

Emilio Vicente has no conflicts of interest related to the subject matter of the article or outside the submitted work.

Philipp Wiggermann takes part in "FOCUS Trial in Hepatic Dominant Ocular Melanoma - A Randomized, Controlled, Phase 3 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Melphalan/HDS Treatment in Patients With Hepatic-Dominant Ocular Melanoma".

He has no conflicts of interest outside the submitted work.

Michael P. Manns has no conflicts of interest related to the subject matter of the article or outside the submitted work.

Arndt Vogel reports personal fees and travel grants from Delcath Systems, Inc. He reports personal fees from Roche, Bayer, Lilly, Incyte, BMS, MSD and Amgen outside the submitted work.

Frank K. Wacker reports a grant and personal/proctoring fees from Delcath Systems, Inc. during the conduct of the study. He reports grants from Siemens Healthineers, Promedicus Ltd., BMBF, Forschungscampus STIMULATE, DFG, Rebirth-Cluster of Excellence and personal fees from Novartis Pharma GmbH outside the submitted work.

After data collection of the current study, Hannover Medical School participated in the Phase 2 Clinical Trials in Hepatocellular Carcinoma (HCC) and Intrahepatic Cholangiocarcinoma (ICC) (NCT 02415036).

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Only three of the patients were included in a retrospective single-centre study: "Safety and efficacy of chemosaturation in patients with primary and secondary liver tumors", published in Journal of Research and Clinical Oncology, including 29 patients with different primary and secondary liver malignancies.

In our current study only patients with intrahepatic cholangiocarcinoma across nine different hospitals in Europe were included.


• Retrospective

• Diagnostic/prognostic study

• Multicentre study


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Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Steffen Marquardt
    • 1
  • Martha M. Kirstein
    • 2
  • Roland Brüning
    • 3
  • Martin Zeile
    • 3
  • Pier Francesco Ferrucci
    • 4
  • Warner Prevoo
    • 5
  • Boris Radeleff
    • 6
  • Hervé Trillaud
    • 7
  • Lambros Tselikas
    • 8
  • Emilio Vicente
    • 9
  • Philipp Wiggermann
    • 10
  • Michael P. Manns
    • 2
  • Arndt Vogel
    • 2
  • Frank K. Wacker
    • 1
    Email author
  1. 1.Department of Diagnostic and Interventional RadiologyHannover Medical SchoolHannoverGermany
  2. 2.Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany
  3. 3.Department of Radiology and NeuroradiologyAsklepios Klinik BarmbekHamburgGermany
  4. 4.Melanoma Medical Treatment UnitEuropean Institute of OncologyMilanItaly
  5. 5.Department of RadiologyNetherlands Cancer InstituteAmsterdamThe Netherlands
  6. 6.Department of Diagnostic and Interventional RadiologyHeidelberg University HospitalHeidelbergGermany
  7. 7.Department of RadiologyBordeaux University Hospital CenterBordeauxFrance
  8. 8.Department of RadiologyGustave Roussy Cancer CampusParisFrance
  9. 9.General Surgery DepartmentHM University Sanchinarro HospitalMadridSpain
  10. 10.Department of RadiologyUniversity Hospital RegensburgRegensburgGermany

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