1. Traitement
du
CHC
inopérable
:
le
scenario
de
Hong
Kong
Treatment
of
Inoperable
Hepatocellular
Carcinoma:
the
Hong
Kong
Scenario
Philip
CH
KWOK
Queen
Elizabeth
Hospital
Hong
Kong
SAR,
CHINA

2. HCC
in
Hong
Kong
• Worldwide
750000
new
cases
HCC
diagnosed
in
2008
• High
prevalence
in
HK
:
chronic
hepa;;s
B
infec;on
• Worldwide:
6th
most
prevalent
cancer,
3rd
cause
of
cancer
death
• 3rd
leading
cause
of
cancer
death
in
HK
– 4th
commonest
cancer
in
men
– 7th
commonest
cancer
in
women

3. Cura;ve
treatment
for
HCC
• HK
has
high
standard
and
advanced
skill
of
surgical
resec;on
• Play
a
leading
role
in
HCC
research
• Include:
– Surgical
resec;on
– Transplanta;on
– Local
abla;on
with
various
means

4. Treatment
for
Inoperable
HCC
• HCC
is
a
combina;on
of
2
diseases
:
cancer
+
liver
cirrhosis
(mostly)
• Successful
cura;ve
treatment
1. remove
the
tumor
+
some
surrounding
noncancerous
;ssue
2. +
Enough
and
func;oning
residual
liver
;ssue
to
sustain
life

5. Treatment
for
Inoperable
HCC
• Inoperability
due
to:
– Too
much
tumor
;ssue,
either
in
one
lobes,
or
in
both
lobes,
or
outside
the
liver
– Inadequate
func;oning
liver
;ssue
leT
behind
aTer
tumor
resec;on/
abla;on

6. Tools
for
inoperable
HCC
•
•
•
•
Transarterial
chemoemboliza;on
(TACE)
Transarterial
radioemboliza;on
(TARE
or
RE)
External
radiotherapy
Target
therapy
(Sorafenib)

7. Tools
for
Unresectable
HCC
• Unresectable
≠
Inoperable
• Tools
for
unresectable
tumors:
– Radiofrequency
abla;on
(RFA)
– Microwave
abla;on
(MWA)
– Percutaneous
alcohol
injec;on
(PEI)
– Cryoabla;on

8. More
Aggressive
way:
RFA,
ar;ficial
ascites

9. More
Aggressive
way:
RFA,
transpleural
with
ar;ficial
pneumothorax

10. More
Aggressive
way:
RFA,
transpleural
with
ar;ficial
pneumothorax

11. More
Aggressive
way:
RFA,
blood
flow
control,
percutaneous
or
open
Pringle
manoeuvre

12. Percutaneous
Alcohol
Injec;on
(PEI)
PEI:
S'll
has
a
role
for
tumors
near
cri'cal
loca'ons
or
vital
structures
,
where
thermal
abla'on
is
dangerous
or
ineffec've

13. Do
we
have
a
Guideline
to
follow?
• Currently
no
local
consensus,
we
will
have
one
very
soon
• Commonly
quoted
:
– Barcelona
Clinic
Liver
Cancer
(BCLC)
staging
system
and
management
– Asian
Pacific
Associa;on
for
the
Study
of
the
Liver
(APASL)

14. BCLC
staging

15. BCLC
staging
• There
are
more
treatment
modali;es
available
than
men;oned
in
the
“guideline”
• Not
up-­‐to-­‐date

16. APASL
Guidelines
for
HCC
Management

17. APASL
guideline
• More
closely
reflect
the
local
prac;ce

18. China
An;-­‐cancer
Society

19. China
An;-­‐cancer
Society
• In
2009

20. J-­‐HCC
Guidelines

21. J-­‐HCC
Guidelines
• Different
prac;ce
in
Japan

22. Hong
Kong
Guideline
on
Treatment
of
HCC
• Consensus
Mee;ng
in
2013
• Will
come
out
soon
• A
group
of
local
specialists
led
by
Prof
Ronnie
TP
POON
– Surgeons
– Oncologists
– Interven;onal
Radiologists
– Hepatologists

23. Treatment
aim
• For
inoperable
HCC,
the
treatment
aim
is
mainly
pallia;ve

24. HCC
Treatment
• Pallia;ve
– Transarterial
chemoemboliza;on
(TACE)
• lipiodol
+
chemotherapeu;c
agent(s)
• Drug
elu;ng
beads
– Transarterial
radioemboliza;on
(TARE)
• Ymrium-­‐90

25. Conven;onal
TACE
• The
commonest
treatment
for
inoperable
HCC
in
Hong
Kong
• About
500
TACE
per
year
in
a
single
ins;tute
• The
standard
treatment
in
most
centers
for
inoperable
HCC
• Emulsion
of
lipiodol
+
single/
mul;ple
chemotherapeu;c
agents
• Oily
emulsion
can
reach
500
um
• Effect
proven
by
mul;ple
studies
and
2
RCT
(Llovet,
Lo)

26. Conven;onal
TACE
• TACE
given
once
every
2
months
or
3
months
• Usually
through
the
hepa;c
artery
• Also
possible
through
other
extrahepa;c
arteries
• Assess
the
response
aTer
every
TACE

27. TACE
Defect
of
lipiodol
reten.on

28. TACE,
inferior
phrenic
artery

29. TACE

30. Conven;onal
TACE
• Stop
TACE
–
when
the
tumor(s)
do
not
respond,
either
there
is
inadequate
uptake,
or
the
tumor(s)
enlarge
– When
the
liver
func;on
gets
worse
aTer
TACE
– When
the
supplying
artery
is
occluded
– When
there
are
other
complica;ons
of
TACE,
e.g.
biliary
necrosis

31. TACE
–
induced
biliary
Injury
• ATer
6
sessions
of
TACE

32. Conven;onal
TACE
• TACE
can
be
cura;ve,
though
it
is
oTen
considered
a
pallia;ve
treatment
• So,
stop
TACE
also
when
– THE
DISEASE
IS
CURED!
• This
is
oTen
the
situa;on
when
–
TACE
is
performed
superselec;vely
– TACE
is
performed
for
a
small
lesion
inapproachable
by
other
local
abla;ve
treatment
e.g.
RFA
for
a
lesion
near
another
organ
(gall
bladder)

33. Conven;onal
TACE
• Variants:
– Superselec;ve
TACE
with
microcatheter
• Overflow
of
emulsion
to
portal
venules
– (Balloon
occluded
TACE
)
• Not
yet
available
locally

34. Superselec;ve
TACE
with
overflow
to
portal
venules
• Matsui
O.
• Superselec;ve
TACE
with
microcatheter
• Lipiodol
flows
to
the
portal
venules
through
peribiliary
plexus
• Enhances
treatment
effect

35. Superselec;ve
TACE
with
overflow
to
portal
venules
• The
3-­‐year
local
recurrence
rate
for
grade
0,
1,
2:
74%,
42%,
19%

36. Balloon-­‐occluded
TACE

37. B-­‐TACE
• 3Fr
microballoon
catheter
• Reduce
the
arterial
stump
pressure
• Increase
lipiodol
emulsion
accumula;on
inside
the
tumor

38. Conven;onal
TACE
• Side
effects
are
common
• Related
to
early
systemic
release
of
chemo
agents
– Nausea,
vomi;ng,
alopecia,
renal
impairment,
marrow
suppression,
etc.
• Liver
parenchymal
damage
– Liver
func;on
impairment,
liver
failure,
liver
abscess,
biliary
duct
injury
and
biloma

39. Drug
elu;ng
beads-­‐TACE/DEB-­‐
TACE
• Replace
lipiodol
with
microspheres
(100-­‐300um)
• Slow
release
of
drugs
• Enhances
local
therapeu;c
efficacy
• Less
systemic
side
effects

40. DEB-­‐TACE
– Two
randomized
controlled
trials
showed
bemer
control
of
disease
progression
but
– no
sta;s;cal
significant
in
survival
rate
due
to
short
follow-­‐up
period
and
small
sample
size

41. DEB-­‐TACE
– PRECISION
V
study
recruited
217
pa;ent
showed
that
DEB
had
a
disease
control
rate
of
63.4%
and
conven;onal
TACE
had
a
disease
control
rate
of
51.9%
(P=0.11).
– Pa;ent
with
Child-­‐Pugh
B,
ECOG
1,
bilobar
disease,
and
recurrent
disease
showed
a
significant
increase
in
objec;ve
response
(P=0.038)
compared
to
cTACE.
– DC
Bead
was
associated
with
improved
tolerability,
with
a
significant
reduc;on
in
serious
liver
toxicity
(P=0.001)
and
a
significant
lower
rate
of
doxorubicin-­‐
related
side
effects
(P=0.0001).

42. DEB
5-­‐yr
survival
Malagari
K,
et
al.
(CVIR
2012)
173
pa;ents,
Child
A,
B
Mean
lesion
diameter
7.6
+/-­‐
2.1cm
Mean
overall
survival
was
43.8
months
(range
1.2–64.8)
• Overall
survival
at
1,
2,
3,
4,
and
5
years
was
93.6,
83.8,
62,
41.04,
and
22.5
%,
•
•
•
•

43. Malagari
K,
et
al
CVIR
2012

44. DEB-­‐TACE
• Used
more
frequently
in
private
hospitals
than
public
hospitals
due
to
the
high
costs

45. TARE
• Transarterial
Radioemboliza;on
• Ymrium-­‐90
is
beta
emitng
• On
resin
or
glass
beads
(20-­‐60um)
• 2mm
range
bachytherapy
• Half
life
64
hours
• Usually
perform
once

46. TARE
• Can
be
performed
in
3
public
hospitals
and
2
private
hospitals
in
Hong
Kong
– Exper;se
required
– Great
demand
on
several
special;es
working
together
as
a
team
– Currently
Hospital
Authority
only
approved
and
reimbursed
its
use
in
HCC
>
8cm
diameter,
or
there
is
portal
vein
invasion

47. TARE
• In
Western
countries,
TARE
is
used
mainly
for
liver
dominant
colorectal
metastases
• Not
in
HK
public
hospitals

48. TARE
• large-­‐scale
phase
II
studies
show,
when
compared
with
cTACE,
–
less
side
effects,
bemer
tolerance,
– bemer
response
rate
and
longer
;me
to
disease
progression
• No
definite
survival
benefit
when
compared
with
cTACE
• Maybe
related
to
its
use
in
moderate
to
advanced
disease

49. TARE
• Benefit
in
HCC
with
portal
vein
invasion
• Kulik
LM,
et
al.
(Hepatology
2008)
• PR:
42.2%
(WHO);
70%
(EASL)

50. TARE
Salem
and
Lewandowski.
Clin
Gastroenterol
and
Hepatol
2013

51. TACE
+
RFA
• In
HB
cirrhosis,
there
may
be
lots
of
nodules
• HCC
focus
seen
in
CT
or
MR,
but
not
seen
under
ultrasound
• Perform
TACE
once,
then
RFA
under
CT
guidance

52. TACE
+
RFA
S7
lesion
seen
in
MR
Selec;ve
TACE
to
RHA
once

53. TACE
+
RFA
CT
guided
RFA
with
mul;planar
recon
CT
post
RFA
1
month

54. LR
therapies
+
others
• cTACE
+
RFA
has
bemer
response
rate,
bemer
1-­‐year
and
3-­‐year
survival
than
either
monotherapy
• Metaanalysis
of
6
papers
– Ni
JY
et
al.
(J
Cancer
Res
Clin
Oncol
2013)

55. cTACE
+
RFA
• TACE
plus
PRFA
had
significantly
bemer
effec;veness
on
1-­‐
and
3-­‐year
overall
survival
rate
– odds
ra;o
[OR]
1-­‐year
=
4.61,
95
%
confidence
interval
[95
%
CI]
2.26–9.42,
P
<
0.0001
– OR
3-­‐year
=
2.79,
95
%
CI
1.69–
4.61,
P
<
0.0001
• and
3-­‐year
recurrence-­‐free
survival
rate
– [OR]
3-­‐year
=
3.00,
[95
%
CI]
1.75–5.13,
P
<
0.0001
• 1-­‐year
recurrence-­‐free
survival
rate:
no
significant
difference

56. Locoregional
therapies
+
Sorafenib
• cTACE
or
DEB-­‐TACE
+
Sorafenib
(kinases
inhibitor)
– Inves;ga;onal
– Timing
and
dose
of
Sorafenib
needed
to
be
determined
with
clinical
studies

57. Image
guided
Radiotherapy
for
HCC
• Previously
overlooked
because
of
fatal
liver
toxicity
at
doses
lower
than
therapeu;c
doses
• Recently,
precise
delivery
of
focused
high-­‐
dose
on
targeted
volume
of
the
liver
– 3D
conformal
RT
– Intensity
modulated
RT
(IMRT)
– Stereotac;c
body
RT
(SBRT)
– Image
guided
RT
(IGRT)
– Proton
therapy

58. IGRT
and
BCLC
stages
• Stage
A:
nonsurgical
cura;ve
therapy.
• Stage
B:
can
be
combined
with
other
treatments
such
as
TACE.
• Stage
C:
prolong
the
survival
;me
in
selected
pa;ents
with
locally
advanced
HCC
associated
with
portal
vein
invasion
but
not
distant
metastasis.
• Stage
D:
pallia;on.
Lee
IJ
et
al.
Gut
Liver
2012

60. Thanks