Biocompatibles Satellite Symposium at GEST 2011
Review of Treatment Algorithms and
Procedural Standards for DC Bead in HCC
Professor Riccardo Lencioni
Director, Diagnostic Imaging and Intervention
Department of Hepatology and Liver Transplantation
Pisa University Hospital and School of Medicine, Pisa, Italy
Llovet JM, DiBisceglie A, Lencioni R, et al.
EASL-EORTC
Clinical Practice Guideline:
Hepatocellular Carcinoma
Journal of Hepatology, 2011 - European Journal of Cancer, 2011
Treatment of Hepatocellular Carcinoma (HCC):
The BCLC Staging System
HCC
Stage A–C
PST 0–2, Child–Pugh A–B
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
Portal pressure/
bilirubin
Increased
Resection
Advanced stage (C) End stage (D)
Portal invasion,
N1, M1, PST 1–2
3 nodules ≤ 3 cm
1 HCC
Normal
Intermediate stage (B)
Multinodular,
PST 0
Stage D
PST > 2, Child–Pugh C
Associated diseases
No
Liver transplantation
Curative treatments (30%)
5-year survival 40–70%
Yes
Ablation
TACE
Sorafenib
Palliative treatments (50%)
Median survival 11–20 months
Symptomatic
treatment (20%)
Survival < 3 months
adapted from Llovet JM, DiBisceglie A, Lencioni R, et al. (in press)
Clinical Management of Hepatocellular Carcinoma:
Building Multidisciplinary Consensus
• Compared with conventional TACE, drug eluting bead has a standardized
methodology, is more reproducible, and offers improved response and a
significantly better safety profile.
Cancer Treat Rev 2011;37:212-220
Drug eluting bead vs conventional TACE:
A randomized trial (“PRECISION V”)
Lammer J et al. Cardiovasc Intervent Radiol 2010;33:41-52
DEBDOX: drug-related adverse events and liver
toxicity are significantly reduced
300
AST Units/L
250
200
p=0.001
150
100
p=0.001
50
0
DC Bead
cTACE
ALT Units/L
200
150
100
p<0.001
50
0
Drug-related adverse events
Liver toxicity (AST – ALT levels)
Lammer J et al. Cardiovasc Intervent Radiol 2010;33:41-52
DEBDOX versus conventional Lipiodol TACE:
Tumor response
85
80
80 -
77
75
70
70 -
p=0.11
60
60 -
52
50 -
44
35
40 -
27
Lo
LLovet
Reyes
Poon
Varela
Grosso
10 -
Song
20 -
Malagari
30 -
0
Drug-eluting beads
Precision V
cTACE
Lencioni R. Personal Communication
Tailoring Transcatheter Treatment with DC Bead
to the Individual Patient / Tumor Characteristics
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
• Consensus Meeting during the ECIO 2010 in Florence
• The panel:








Thierry De Baere / Institut Gustav-Roussy, Paris, France
James G. Caridi / University of Florida, USA
Jean-Francois H. Geschwind / Johns Hopkins University, USA
Riccardo Lencioni / University of Pisa, Italy
Katerina Malagari / University of Athens, Greece
Robert C. Martin / University of Louisville, USA
Elizabeth O’Grady / University Hospital Aintree, UK
Thomas J. Vogl / Universty of Frankfurt, Germany
• Independent reviewers:
 Martha Burrel and Maria Isabel Real, Liver Unit, Barcelona, Spain
 Johannes Lammer, University of Vienna, Austria
 Anthony Watkinson, Royan Devon and Exeter University Hospital, UK
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Pre-Treatment Imaging
 Obtaining a triple-phase CT or MRI of the liver is
mandatory to integrate clinical and laboratory data
to evaluate the indication to transcatheter treatment
of HCC with DC Bead in each individual patient by
the local multidisciplinary liver tumor board.
 Additional imaging examinations to rule out
extrahepatic disease should be performed as
appropriate.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Peri-Procedure Medication

Pain medication should be given according to
standard hospital protocol.

Antibiotic prophylaxis and gastric protection
should be administered at the physician's
discretion.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Loading Dose of Doxorubicin

Each vial of DC Bead (2 ml of beads) should be
loaded with 50-75 mg doxorubicin (loading dose,
25-37.5 mg doxorubicin / ml of beads).
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Planned Dose:
Single / Small HCC

Each treatment:
- 1 vial
- up to 75 mg doxo
Planned Dose:
Large / Multiple HCC

Each treatment:
- 2 vials
- up to 150 mg doxo
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Bilobar Tumors

In bilobar tumors, both hepatic lobes should be
treated in separate treatment sessions 2-4 weeks
apart, in the absence of complications requiring a
longer time interval between the two sessions.

Obtaining confirmation that the liver enzymes have
returned to baseline before performing the second
treatment session is recommended.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Very Large Tumors

In very large tumors, even if unilobar, the same
approach including two sessions should be
followed.

Indication to treatment with DC Bead in patients
with tumor replacing more than 50% of the liver
should be carefully evaluated: adequate
interventional and clinical expertise is required to
manage patients with such advanced disease.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Choice of DC Bead Size

Use of 100-300μm beads is recommended for a
standard procedure.

However, individual patient and tumor
characteristics, particularly the identification of
arterio-venous shunting, should be taken into
account when the safety of the treatment and the
choice of DC Bead size are determined.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Choice of DC Bead Size

In the case of significant arterio-portal or hepatic
venous shunting, embolization of the shunt with
gelfoam pledgets is recommended before
proceeding with DC Bead treatment.

Confirmation that the shunt is no longer present
must be obtained before the DC Bead can be safely
administered.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
DC Bead Dilution

Mix loaded DC Bead with a non-ionic contrast
medium.

At least 5-10 ml of non-ionic contrast should be
used per 1 ml of DC Bead (i.e., 10-20 ml are required
to dilute one vial of DC Bead) prior to injection).
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Catheter Positioning

A superselective (i.e., segmental or subsegmental)
approach should be used whenever possible by
using a microcatheter.

Use of C-arm rotational angiography with a flatpanel detector system (cone-beam CT) is
recommended, if available, to improve the accuracy
in identifying tumor-feeding arteries and to confirm
adequate targeting and saturation of the tumor(s).
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Segmental / Subsegmental
approach
Lobar approach
Place the microcatheter into
the segmental or
subsegmental vessel feeding
the tumor as distally as
possible but avoiding
wedging the catheter to avoid
reflux along the catheter
shaft. Flow within the artery
must be preserved.
Place the catheter as selectively
as possible in the right or left
hepatic artery. Pay attention to
identifying the origin of the
cystic artery as well as other
arteries supplying flow to extrahepatic organs. If identified,
these vessels must be either
embolized using coils or
avoided by placing the catheter
tip well beyond the origin of
these vessels.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Injection of the DC Bead

The injection must be very slow: an injection rate of
1 ml of the contrast agent - DC Bead suspension
per minute is recommended.

Care should be taken to avoid sedimentation of the
beads in the syringe by rotating the syringes or
using a 3-way stopcock to gently suspend the
beads in the solution.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Embolization Endpoint

Injection should be continued until “near stasis” is
observed in the artery directly feeding the tumor
(i.e., the contrast the contrast column should clear
within 2-5 heart beats). At that point, injection
should be stopped – regardless of the amount of
beads that have been actually administered – to
avoid reflux of embolic material.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Embolization Endpoint

Once the embolisation endpoint has been achieved,
no additional embolic material should be injected.

If the “near stasis” endpoint is not obtained after
injection of the scheduled volume of beads, no
additional embolization should be performed. This
patient is likely to benefit from a second course
after imaging follow-up.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Post-Treatment Management
 Obtaining a triple-phase CT or MRI of the liver 2-4
weeks after the procedure is recommended to
assess the outcome of the first treatment and to
plan further action.
 Treatment response should be assessed according
to modified RECIST (mRECIST) for HCC. *
* Lencioni R, Llovet JM, Semin Liver Dis 2010;30:52-60
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Post-Treatment Management

Residual viable tumor (partial response, stable
disease, progression): further treatment with DC
Bead can be scheduled after 4-8 weeks in the
absence of contraindications.

Complete response: imaging follow-up should be
scheduled every 2-3 months.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Treatment Discontinuation

Treatment with DC Bead should be discontinued in
patients presenting with untreatable progression. *
* Lencioni R et al. ASCO 2010
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Untreatable Progression (1)

Failure to achieve objective response in the
targeted tumor after at least two DC Bead
treatments. The emergence of new intrahepatic
tumor foci remote from the treated territory,
although clearly represents tumor progression
according to modified RECIST for HCC, does not
contraindicate further treatment with DC Bead.
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
Untreatable Progression (2)

Clinical or functional deterioration. Treatment
should be discontinued in patients showing clinical
progression to ECOG performance status > 2 or
evolution to sustained hepatic decompensation (not
merely after therapy).
DC Bead in HCC: Development of Procedural
Standards and Technical Recommendations
General Statement
 The Interventional Radiologists is the only qualified
physician to decide how to approach the unique
combination of patients and tumor characteristics
that he is facing at the time of the procedure.