Transcript Joint Hospital Grand Round

Joint Hospital Grand Round
20th May 2006
Catherine Choi
United Christian Hospital
Radio-Frequency Ablation
of Liver Metastasis
from Colorectal Carcinoma
Liver Metastasis from
colorectal carcinoma
• most common site of
metastasis from colorectal
cancer
• more than 50% patient would
develop colorectal metastasis
at diagnosis and subsequently
Colorectal liver metastases
Natural history of colorectal liver
metastases
“ The natural history of untreated cancer is the standard against
which the effectiveness of any treatment should be measured…..”
Wagner JS Ann Surg 1984
Patients with unresected liver metastases
median survival 15 - 21 months
Survival
Extent of liver involvement
Median
( month )
3yr
5 yr
21%
3%
21
Multiple but unilateral
6%
0%
15
Widespread or bilobal
4%
2%
Solitary metastasis
Wagner JS Ann Surg 1984
Wood CB Clin Oncol 1976
Colorectal liver metastases
Surgical resection for liver
metastases
•
already well accepted as the standard treatment for colorectal liver metastases
•
survival after liver resection for solitary liver metastasis
Author
Hughes KS
Surgery 1988
No of
patients
Actuarial 5-year
survivals
Median survival
509
37%
-
(months)
Rosen CB
Ann Surg 1992
185
30%
Scheele J
World J Surg
180
36%
45
Am J Surg 1997
77
47%
54
240
47%
1995
Taylor M
Fong Y
J Clin Oncol 1997
• Overall 5-year survival 25 – 39%
Fong Y. et al (1997) J Clin Oncol 15: 938-997
Radio Frequency Ablation
Current Indication
Colorectal liver metastases
• Limited but inoperable liver disease
• Extent or distribution permits ablation
but not resection
• In-operable due to co-morbidity
• In-operable due to inadequate residual
functioning normal liver
• In combination with resection
• Downstage by chemotherapy, can be
ablated but is in-operable
Radio Frequency Ablation
Limitation
•
Colorectal liver metastases
Size



5 – 7 cm ablation zone
max diameter of tumor 5 cm ( with allowance for 1 cm resection margin )
overlapping technique Gerald D Dodd III, AJR Oct 2001
•
Number of tumors

5 or fewer ( rule of fives ) Poston GJ J Clin Oncol Mar 2005

maximum number not known

Risk  high failure rate with increased number

Laparotomy allowed more lesions to be ablated than percutaneous
approach
•
Location

adjacent to major vessel < 3 mm diameter
 higher recurrence rate

risk of thermal damage to bile duct

risk of thermal damage to hollow viscus
•
avoid with laparoscopic or laparotomy
Colorectal liver metastases
Role of Radio Frequency Ablation
in colorectal liver metastases
As primary treatment modality
• resectable disease (curability)
• unresectable disease (additional benefit
over modern chemotherapy)
Colorectal liver metastases
RFA as primary treatment in
resectable disease
•
•
Results compared with hepatic resection
No randomized control study
•
French study started



Poston GJ Journal of Clin Oncoloy Mar 2005
prospectively compared RFA vs surgical resection
ethical issue
slow recruitment
Existing evidence
• case series
• for unresectable colorectal liver metastasis only
• excluded from surgery for

location precluded clear resection margin
vessels or portas )



poor co-morbid
inadequate liver reserve
reluctant for resection
( near major
RFA as primary treatment in
resectable disease
Colorectal liver metastases
Tito Livraghi
Percutaneous Radiofrequency ablation of liver metastases in Potential
candidate for Resection - The “Test-of-Time” approach
Cancer June 2003

88 patients with 134 colorectal liver metastases







80% received chemotherapy
median follow-up 28 months (18-75 mths)
complete ablation achieved in 53 / 88 (60% ) only
16 / 53 ( 30%) tumor-free
37 / 53 ( 70% ) developed new lesions




< 3 lesions
≦4 cm max diameter ; mean diameter 2.1 cm ( 0.6 – 4 )
26 intrahepatic ( repeated RFA ; 7 tumor free )
4 extrahepatic
7 both intrahepatic + extrahepatic
Overall



23 / 88 ( 26% ) tumor-free with RFA
7 / 88 ( 8% ) tumor-free with additional hepatic resection (20 out of
35 with partial necrosis underwnet hepatectomy)
34% disease free in the study
Colorectal liver metastases
RFA as primary treatment in resectable disease
Case control series compared with resection
Oshowo
et al
Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases
British Journal of Surgery 2003
•
•
45 solitary colorectal liver metastases
25 percutaneous RF ablation

•
resection contraindicated for
•
near major vessels (9 )
•
co-morbidity ( 9 )
•
stable extrahepatic disease ( 7 )
20 liver resections in same period
Colorectal liver metastases
RFA as primary treatment in resectable disease
Major Case series
Survival rate (%)
Study
year
No of patient
1 year
3 year
5 year
median survival
( months)
Solbiati
1997
29
94
-
-
-
Lencioni
1998
29
93
-
-
-
Gillams
2000
69
90
34
-
-
Solbiati
2001
117
93
46
-
36
Solbiati
2003
166
96
45
22
Oshowo
2003
25
100
52
-
37
Abdalla
2004
57
92
37
-
-
Lencioni
2004
423
86
47
24
-
Gillams
2004
167
71
21
14
22
Berber
2004
135
-
-
-
28.9
Reference data from surgical series
•Overall 5 years survival in liver resection series 25 – 39%
•5 year survival of small solitary colorectal liver metastasis 50% ( Nuzzo et al Hepato-gstroenterology
1997 )
Colorectal liver metastases
RFA as primary treatment in resectable disease
Problems
•
heterogeneous data
•
inclusion of various metastatic tumors in large series
•
various mode of approach for RFA
•
different instruments used and difficult algorithm
•
lapsed over long period with improvement in electrode
design
•
report of survival data incomplete / lacking
•
presence of extrahepatic disease group in treated
patient cohort

Conclusion of radio frequency ablation better / as
effective as surgery is impossible from present data
Colorectal liver metastases
RFA as primary treatment in resectable disease
Local Recurrence
Surgical resection DeMatteo et al J Gastrointest Surg 2000
• compromised margin ( < 1 cm tumor free resection margin )

2% for anatomic resection

16% for wedge resection
•
Curle
y
Series
de Baere
Siperstein
AJR 2000
Ann
Surg
1999
Solbiati
Bowles
Bleicher
Elias
Ann Surg
Oncol 2000
Radiology
2001
Arch Surg
2001
Ann Surg
Oncol 2003
J Surg Oncol
2005
No of patient
123
68
66
117
76
153
63
No of RFA
169
121
250
170
329
447
154
% colorectal met
50
85
35
100
51
39
100
Percutaneous
25
69
0
100
57
52
0
Surgery
75
31
0
0
34
33
100
0
0
100
0
8
15
0
15
14
13.9
6 - 59
15
11
27.7
1.8%
9%
12%
39%
9%
21%
7.1%
Route of RFA
Laparoscopic
mean FU
( months )
RFA site
local recurrence
Colorectal liver metastases
Meta-analysis
•
•
•
•
on local recurrence
95 independent RFA series
minimal follow-up 6 months / mean follow-up 12 months
Pooled 5224 treated liver tumors ( primary and secondary tumors )
647 local recurrence
 12.4%
•
favorable factors to reduce local recurrence
 small tumor < 3 cm diameter
 surgical ( laparotomy / laparoscopic ) approach
•
local recurrence rate similar for HCC and colorectal metastases
•
Drawback


follow-up duration too short
local recurrence up to 18 months
underestimates local recurrence rate
Stefaan Mulier et at Ann Surg Aug 2005
RFA
Adjunct to hepatectomy
as primary treatment in
unresectable colorectal liver
metastases
Classical criteria for
unresectability

presence of extrahepatic metastases

resection margin < 10 mm

large number of metastatic tumors

inadequate residual liver volume
RFA
in unresectable colorectal
liver metastases
Colorectal liver metastases
Systemic chemotherapy with modern regimen


2 yr survival 22 – 27%
median survival 14 – 21 months
Question
 Any additional survival benefit with RFA over modern
systemic chemotherapy ?
 existing data



•

Yes
3yr survival 21 – 52%
5 yr survival 14 – 22%
median survival 22 – 37 months
EORTC trial
40004 )
RFA series
( European Organization for Research and Treatment of Cancer intergroup study
Chemotherapy vs Chemotherapy + local ablation
•
•
•
•
primary end point – overall survival
open in Europe in late 2003
sample size 400 patients
recruited about 70 patients in > 12 months period
Colorectal liver metastases
Role of Radio Frequency Ablation
in colorectal liver metastases
As treatment option in intrahepatic
recurrence after hepatectomy
RFA in intrahepatic recurrence
Intrahepatic recurrence after
Hepatectomy
•
with successful completed liver resection for
colorectal liver metastases
intraheaptic recurrence
43%
extrahepatic recurrence
60%
Topal B et al
European Journal of Surgical Oncology 2003
RFA in intrahepatic recurrence
• F/62
• Carcinoma of sigmoid colon
• Laparoscopic sigmoid colectomy in August 2004
• pathology - pT3N0
• No postoperative chemotherapy
• Liver metastases detected in Jan 2005
• with posterior sectionectomy + non-anatomical resection in Feb 2005
• Chemotherapy after liver resection
• (5-FU + Irinotecan)
• new intrahepatic liver metastases after
completion of chemotherapy
2 cm diameter in
segment 8
Intrahepatic recurrence after
hepatectomy
RFA in intrahepatic recurrence
Choice of treatment
• Re-hepatectomy
•
•
•
•
technically challenging
related mortality 2% in specialized centre
morbidity 25 – 30%
•
advantage of finding of extrahepatic disease 10 – 20%
Wanebo HJ et al Surgery 1996
Neeleman N et al British Journal of Surgery 1996
Local ablative therapy
Our choice
• Percutaneous RFA
• target USG – difficult to demonstrated with trans-abdominal USG
• adjacency of large bowel
RFA in intrahepatic recurrence
Final procedure
Open radiofrequency ablation with large bowel displaced
contrast CT follow-up
1 month after Open RFA
1
3
2
4
RFA in intrahepatic recurrence
RFA
as
re-treatment option
in
intrahepatic recurrence
•
•
Evidence in literature difficult to find
Case series admix with other liver metastatic tumors
Author
n
% colorectal
Previous
hepatectomy
% of sample
Solbiati L
Radiology 2001
117
100
24
20.5
Poon R
Ann Surg 2004
100
15%
41
41
Gillans AR
Eur Radio 2004
167
100
26
16
Berber E
J Clin Oncol 2005
135
100
19
14
• assessment of survival difficult
• only implication
 RFA being taken as re-treatment option for intrahepatic
recurrence after hepatectomy
RFA in intrahepatic recurrence
Dominique Elias et al
British Journal of Surgery 2002
•
47 patients with liver-only recurrence after
hepatectomy
27 colorectal liver metastases
5 HCC
15 neuroendocrine, cholangiocarcinoma, gastric carcinoma,
sarcoma…etc
• mean age 59.4 yr (13 – 85 )
• mean number of metastases 1.4
• mean diameter 2.1 cm ( 9 – 35 )
(1–3)
per patient
•
mean follow-up 14.4 months
•
•
1 operative mortality
3 postoperative complications ( abscess ; bleeding )
•
local recurrence 9% ablated lesion
( 5.5 – 40 )
Retrospective comparison with case series from
same centre
Percutaneous RFA after
hepatectomy
Re-hepatectomy
Survival
No of
patients
1 year
2 year
47
88%
55%
46
84%
60%
Conclusion
Radio frequency ablation of colorectal liver metastases
•
as primary treatment of resectable liver metastases


•
as treatment of unresectable liver metastases


•
data not enough to support routine usage
high local recurrence rate
published series supported
pending EORTC trial for better answer
as primary treatment in intrahepatic recurrence after
hepatectomy


preliminary data support
allow repeated treatments with acceptable mortality / morbidity
Thank You