joint hospital grand round 20 th may 2006 catherine choi united christian hospital

Joint Hospital Grand Round

20th May 2006

Catherine Choi

United Christian Hospital

Radio-Frequency Ablation of 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

Liver Metastasis from colorectal carcinoma

Patients with unresected liver metastases median survival 15 - 21 months

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

Wood CB Clin Oncol 1976

SurvivalMedian ( month )

Extent of liver involvement 3yr 5 yr

Solitary metastasis 21% 3% 21

Multiple but unilateral 6% 0% 15

Widespread or bilobal 4% 2%

Wagner JS Ann Surg 1984

Natural history of 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 No of patientsActuarial 5-year

survivalsMedian survival

(months)

Hughes KS Surgery 1988 509 37% -

Rosen CB Ann Surg 1992 185 30%

Scheele J World J Surg 1995 180 36% 45

Taylor M Am J Surg 1997 77 47% 54

Fong Y J Clin Oncol 1997 240 47%

• Overall 5-year survival 25 – 39%Fong Y. et al (1997) J Clin Oncol 15: 938-997


Radio Frequency AblationCurrent Indication


• 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 AblationLimitation

• 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


Role of Radio Frequency Ablation in colorectal liver metastases


As As primary treatment modalityprimary treatment modality• resectable disease (curability)• unresectable disease (additional benefit over

modern chemotherapy)

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 ( near major vessels or portas )

poor co-morbid inadequate liver reserve reluctant for resection


Tito Livraghi Percutaneous Radiofrequency ablation of liver metastases in Potential candid

ate for Resection - The “Test-of-Time” approachCancer June 2003

88 patients with 134 colorectal liver metastases < 3 lesions ≦4 cm max diameter ; mean diameter 2.1 cm ( 0.6 – 4 )

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

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


RFA as primary treatment in resectable disease

RFA as primary treatment in resectable diseaseCase control series compared with resection

Oshowo et al Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastasesBritish 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


RFA as primary treatment in resectable diseaseMajor Case series

Survival rate (%)median survival (

months)Study year No of patient 1 year 3 year 5 year

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 )

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


RFA as primary treatment in resectable diseaseLocal 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

Series

CurleyAnn Surg

1999

de BaereAJR 2000

SipersteinAnn Surg Oncol

2000

Solbiati Radiology

2001

BowlesArch Surg

2001

BleicherAnn Surg

Oncol 2003

EliasJ 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

Route of RFA

Percutaneous 25 69 0 100 57 52 0

Surgery 75 31 0 0 34 33 100

Laparoscopic 0 0 100 0 8 15 0

mean FU ( months ) 15 14 13.9 6 - 59 15 11 27.7

RFA site local recurrence

1.8% 9% 12% 39% 9% 21% 7.1%


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 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

Adjunct to hepatectomy

RFA in unresectable 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 ( European Organization for Research and Treatment of Cancer intergroup study 40004 )

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


RFA series

Role of Radio Frequency Ablation in colorectal liver metastases


As As treatment option in intrahepatic treatment option in intrahepatic recurrencerecurrence after hepatectomy after hepatectomy

Intrahepatic recurrence after Hepatectomy

• with successful completed liver resection for colorectal liver metastases

Topal B et al European Journal of Surgical Oncology 2003

RFA in intrahepatic recurrence

intraheaptic recurrence 43%

extrahepatic recurrence 60%

• 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


Choice of treatment• Re-hepatectomy

• technically challenging• related mortality 2% in specialized centre• morbidity 25 – 30%

• advantage of finding of extrahepatic disease 10 – 20%

• Local ablative therapy

Wanebo HJ et al Surgery 1996

Neeleman N et al British Journal of Surgery 1996

RFA in intrahepatic recurrenceIntrahepatic recurrence after

hepatectomy

Our choice

• Percutaneous RFA• target USG – difficult to demonstrated with trans-abdominal USG

• adjacency of large bowel

Final procedure

Open radiofrequency ablation with large bowel displaced

contrast CT follow-up 1 month after Open RFA


13

24

RFA as re-treatment option in intrahepatic recurrence

• Evidence in literature difficult to find• Case series admix with other liver metastatic tumors

Author n % colorectalPrevious

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


Dominique Elias et alBritish Journal of Surgery 2002

• 47 patients with liver-only recurrence after hepatectomy27 colorectal liver metastases5 HCC15 neuroendocrine, cholangiocarcinoma, gastric carcinoma, sarcoma…etc

• mean age 59.4 yr (13 – 85 )• mean number of metastases 1.4 ( 1 – 3 ) per patient• mean diameter 2.1 cm ( 9 – 35 )

• mean follow-up 14.4 months ( 5.5 – 40 )

• 1 operative mortality• 3 postoperative complications ( abscess ; bleeding )

• local recurrence 9% ablated lesion

Retrospective comparison with case series from same centre Survival

No of patients

1 year 2 year

Percutaneous RFA after hepatectomy 47 88% 55%

Re-hepatectomy 46 84% 60%


ConclusionRadio frequency ablation of colorectal liver metastases

• as primary treatment of resectable liver metastases data not enough to support routine usage high local recurrence rate

• as treatment of unresectable liver metastases 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

joint hospital grand round 20 th may 2006 catherine choi united christian hospital

Documents

liver resection

colorectal metastasis

colorectal carcinoma

colorectal cancer

operable slide

hepatic resection

resection downstage

modern chemotherapy