Trial Information

Multicenter Registry of Chemoembolization Using Drug-eluting Bead in Patients With Unresectable Hepatocellular Carcinoma

Comparison Between Drug-Eluting Bead vs conventional TACE.

Drug-eluting bead group : TACE using DC bead loading Doxorubicin. Conventional TACE group :
TACE using Doxorubicin/Lipiodol emulsion and gelatin sponge/PVA particle.

cTACE group was chosen by concurrent matched patients (age, sex, tumor stage, and Child-Pugh
class are matched)

5.7 Technically considerable aspects of DC bead TACE group

1. Planned dose of doxorubicin. Each vial of DC Bead (2 ml of beads) should be loaded with
70-75 mg doxorubicin (loading dose, 35-37.5 mg doxorubicin / ml of beads).

- Early-stage HCC. As a general rule, each single treatment should include a planned
dose of up to 75 mg doxorubicin loaded into one vial of DC Bead.

- Medium-sized (less than 8cm) / multinodular HCC. As a general rule, each single
treatment should include a planned dose of up to 150 mg doxorubicin loaded into
two vials of DC Bead.

- In large tumors (more than 8cm), even if unilobar, the separate treatment
including two sessions 2-4 weeks apart is recommended.

- 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
did return to baseline before performing the second treatment session is
recommended.

2. 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.

- In the case of significant arterio-portal or hepatic venous shunting, embolization
of the shunt with gelfoam pledgets is recommended before proceeding with DEBDOX.
Confirmation that the shunt is no longer present must be obtained before DEBDOX
can safely be performed. But, this study excludes the patients with arterio-portal
or hepatic venous shunts.

- In large tumors, hepatic arterial flow does not reach 'near stasis' after
injection of 2 vial of 100-300 μm DC beads. The recommendation is following: 2
vials of the 100-300 μm DC beads is best and then repeat 2 weeks later if the
patient is doing well clinically.

3. 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.

4. Catheter positioning. A superselective (i.e., segmental or subsegmental) approach
should be used whenever possible by using a microcatheter. Use of 3D / MPR obtained
from C-arm rotational angiography with a flat-panel detector system (cone-beam CT) is
recommended, if available, to improve the accuracy in identifying tumor-feeding
arteries. Such imaging allows for accurate targeting of the tumor. In addition, repeat
cone beam CT should be performed after successful delivery of the DC Bead to confirm
adequate targeting and saturation of the tumor(s).

- Segmental / subsegmental approach. Place the microcatheter into the segmental /
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.

- Lobar approach. 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 extra-hepatic organs such as the right
gastric artery, para-esophageal or omental vessels among others. If identified,
these vessels must be either embolized using coils or avoided by placing the
catheter tip well beyond the origin of these vessels. In addition, forward flow
into the desired vessel must be maintained as inadvertent administration of even a
few DC Beads into these extra-hepatic vessels could have dire consequences.

5. Injection. The injection must be very slow. An injection rate of 1 ml of the contrast
agent - DC Bead suspension per minute is recommended. Thus, it takes 10-20 minutes to
infusion 1 vial of DC bead. 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.

6. Embolisation 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. 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.

7. extrahepatic collateral vessels. In principle, DC bead is used for collateral arterial
circulation (inferior phrenic artery, internal mammary artery, intercostal artery), but
doctors can do bland embolization (PVC particle, gelatin sponge) based on their
judgement.

8. Repeated treatment. In principle, treatment with the same method is repeated for every
2 - 3 months as tumor progression is observed. But, even if tumor progression is not
observed, the treatment can be repeated for tumor repression. If there is no tumor
left, contrast enhancement CT or MRI can be performed for every 2- 3 months as follow
up.

5.8. Dose in study Dose of DC bead, anti cancer agent for TACE dose is decided by tumor
size. So, this study just set up the maximum dose.

Drug-eluting bead group DC bead : 2 bottles DC bead absorbs 70-75mg per bottle. Doxorubicin
loading to DC bead needs to be done 1.5 hours before using. The size of DC bead is 100-300
micrometer, and it can be used up to 2 bottles.