Joint Hospital Grand Round

1. Joint Hospital Grand Round 20th May 2006 Catherine Choi United Christian Hospital

2. Radio-Frequency Ablation of Liver Metastasis from Colorectal Carcinoma

3. 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

4. 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…..” Patients with unresected liver metastases median survival 15 - 21 months Wagner JS Ann Surg 1984 Wagner JS Ann Surg 1984 Wood CB Clin Oncol 1976

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

6. Colorectal liver metastases 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

7. Colorectal liver metastases 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

8. Colorectal liver metastases Role of Radio Frequency Ablationin colorectal liver metastases As primary treatment modality • resectable disease (curability) • unresectable disease (additional benefit over modern chemotherapy)

9. Colorectal liver metastases RFAas 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

10. Colorectal liver metastases RFA as primary treatment in resectable disease Tito Livraghi PercutaneousRadiofrequency ablation of liver metastases in Potential candidate for Resection - The “Test-of-Time” approach Cancer 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

11. 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

12. Colorectal liver metastases RFA as primary treatment in resectable diseaseMajor Case series • 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 )

13. Colorectal liver metastases RFA as primary treatment in resectable diseaseProblems • 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 • Conclusionof radio frequency ablation better / as effective as surgery is impossible from present data

14. 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

15. Colorectal liver metastases Meta-analysison 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

16. Adjunct to hepatectomy 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 livervolume

17. Colorectal liver metastases 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 • recruitedabout 70 patients in > 12 months period RFA series

18. Colorectal liver metastases Role of Radio Frequency Ablationin colorectal liver metastases As treatment option in intrahepatic recurrence after hepatectomy

19. RFA in intrahepatic recurrence Intrahepatic recurrence after Hepatectomy • with successful completed liver resection for colorectal liver metastases Topal B et al European Journal of Surgical Oncology 2003

20. 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

21. RFA in intrahepatic recurrence Intrahepatic recurrence after hepatectomy 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 alSurgery 1996 Neeleman N et alBritish Journal of Surgery 1996 • Our choice • Percutaneous RFA • target USG – difficult to demonstrated with trans-abdominal USG • adjacency of large bowel

22. 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

23. 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 • assessment of survival difficult • only implication • RFA being taken as re-treatment option for intrahepatic recurrence after hepatectomy

24. 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 ( 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

25. Conclusion Radio 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

26. Thank You