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Cardiovasc Intervent Radiol (2010) 33:11–17 Quality Improvement Guidelines for RadiofrequencyAblation of Liver Tumours Laura Crocetti • Thierry de Baere •Riccardo Lencioni Received: 5 October 2009 / Accepted: 5 October 2009 / Published online: 19 November 2009Ó Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2009 The development of image-guided percutane- ous techniques for local tumour ablation has been one ofthe major advances in the treatment of liver malignancies.
Among these methods, radiofrequency ablation (RFA) iscurrently established as the primary ablative modality at This is the region ablated beyond the borders of the tumour most institutions. RFA is accepted as the best therapeutic to achieve complete tumour destruction. Ideally, it should choice for patients with early-stage hepatocellular carci- noma (HCC) when liver transplantation or surgical resec-tion are not suitable options [, ]. In addition, RFA isconsidered a viable alternate to surgery (1) for inoperable patients with limited hepatic metastatic disease, especiallyfrom colorectal cancer, and (2) for patients deemed ineli- This is the nonenhancing area, including the tumour and the gible for surgical resection because of extent and location ablative margin, on contrast-enhanced imaging modalities.
of the disease or concurrent medical conditions []. Theseguidelines were written to be used in quality-improvement programs to assess RFA of HCC and liver metastases. Themost important processes of care are (1) patient selection, Complications can be stratified on the basis of outcome by (2) performing the procedure, and (3) monitoring the using the society of interventional radiology (SIR) standard patient. The outcome measures or indicators for these table. Major complications result in admission to a hospital processes are indications, success rates, and complication for therapy (for outpatient procedures), an unplanned increase in the level of care, prolonged hospitalization,permanent adverse sequelae, or death. Minor complicationsresult in no sequelae, and they may require nominal ther-apy or a short hospital stay for observation (generallyovernight). Major and minor complications and side effectsshould be reported on the basis of the number of ablationsessions on a per-session basis.
L. Crocetti (&) Á R. LencioniDivision of Diagnostic Imaging and Intervention, Department of Hepatology, Liver Transplants, and InfectiousDiseases, University of Pisa, Pisa, Italye-mail: One or multiple electrodes are inserted directly into thetumour to deliver RF energy current. Electrodes can be monopolar or bipolar, and they can have different designs Department of Interventional Radiology, Institut deCance´rologie Gustave Roussy, Villejuif, France (multitined expandable, internally cooled, perfused).
L. Crocetti et al.: Guidelines for RFA of Liver Tumours Monopolar Electrode This has a single active electrode applicator, with current dissipated at one or severalreturn grounding pads.
This is considered when treatment of the tumour was per- Bipolar Electrode This consists in two electrode formed according to protocol and complete tumour coverage applicators or in a single array containing both the is assessed either during or immediately after the procedure.
Multitined Expandable Electrode This has multiple electrode tines that expand from a larger needle cannula.
Internally Cooled Electrode This electrode has an This is the transient ([30–90 min) zone of increased ech- internal lumen that is perfused by saline without ogenicity seen at US within and surrounding a tumour coming into direct contact with patient body tissue.
Perfused Electrode The tip of the electrode has smallapertures that allow the fluid (usually saline) to come incontact with the tissue.
RFA is the therapy of choice in very early and early This is convective cooling by adjacent blood vessels, usu- HCC according to the Barcelona Clinic Liver Cancer ally C3 mm, when ablated tissues are heated. It can nega- (BCLC) classification (Table ) when patients are not tively affect the results of RFA because it can potentially candidates for either liver resection or transplantation.
remove heat before complete tumour ablation is achieved.
Patients are required to have a single tumour smaller oras many as three nodules \3 cm each, no evidence of vascular invasion or extrahepatic spread, performancestatus test of 0, and liver cirrhosis in Child-Pugh class A This is the instillation of liquid (dextrose 5%, sterile water) or gas (air, carbon dioxide) between the area of ablation andthe structure vulnerable to heating damage (usually the RFA is generally indicated for nonsurgical patients with This is the presence of residual unablated tumour, which is colorectal cancer oligometastases isolated to the liver.
seen as peripheral irregular enhancement at imaging. It Selected patients with limited hepatic and pulmonary often grows in a scattered, nodular, or eccentric pattern.
colorectal metastatic disease, however, may qualify forpercutaneous treatment if extrahepatic disease is deemed curable. In patients with hepatic metastases from otherprimary cancers, promising initial results have been This is the appearance at follow-up of foci of untreated reported in the treatment of breast and endocrine tumours.
disease in tumours that were previously considered to becompletely ablated.
The number of lesions should not be considered an abso-lute contraindication to RFA if successful treatment of all This is the time from inclusion in the study to death.
metastatic deposits can be accomplished. Nevertheless, Patients who are alive at the end of follow-up are censored.
most centres preferentially treat patients with B5 lesions.
This is coagulation induction from all electromagnetic The target tumour should not exceed 3 cm at its longest energy sources with frequencies \30 MHz. For tumour axis to achieve best rates of complete ablation using most ablation purposes, the frequency is usually in the range of L. Crocetti et al.: Guidelines for RFA of Liver Tumours PS 0, Child-Pugh A to B, single HCC or 3 HCCs \3 cm PS 0, Child-Pugh A to B, multinodular HCC PS 1 to 2, Child-Pugh A to B, portal neoplastic invasion, includes understanding liver anatomy, liver tumour diag-nosis, and radiologic and non radiologic treatment options.
Pretreatment imaging must carefully define the location ofeach lesion with respect to surrounding structures as follows: Lesions located on the surface of the liver can beconsidered for RFA, although their treatment requires Targeting of the lesion can be performed with ultrasound, adequate expertise and may be associated with a higher computed tomography (CT), or magnetic resonance imaging (MRI). The guidance system is chosen largely on Thermal ablation of superficial lesions that are adjacent to the basis of tumour visibility, operator preference, and any part of the gastrointestinal tract must be avoided local availability of dedicated equipment, such as CT because of the risk of thermal injury of the gastric or bowel fluoroscopy or open MRI systems. The transient hyper- wall. The colon appears to be at greater risk than the echoic zone that is seen on ultrasound within and sur- stomach or small bowel for thermally mediated perfora- rounding a tumour during and immediately after RFA can tion. Gastric complications are rare, most likely owing to be used as an approximate guide to the extent of tumour the relatively greater wall thickness of the stomach or the destruction. It is not sufficient to evaluate immediate rarity of surgical adhesions along the gastrohepatic treatment effectiveness, and follow-up imaging is manda- ligament. Mobility of the small bowel may also provide tory. MRI currently is the only imaging modality with the bowel with greater protection compared with the validated techniques for real-time temperature monitoring.
relatively fixed colon. The use of special techniques, suchas intraperitoneal injection of dextrose to displace thebowel, can be considered in such instances.
Treatment of lesions adjacent to the hepatic hilumincreases the risk of thermal injury of the biliary tract.
Thermal ablation is usually performed with the patient This tumour location represents a relative contraindi- under intravenous sedation or general anaesthesia with cation to RFA. In experienced hands, thermal ablation standard cardiac, pressure, and oxygen monitoring. Amer- of tumours located near the gallbladder has been shown ican Society of Anesthesiologists (ASA) score (Appendix) to be feasible, although associated in most cases with can be used to assess patient physical status before RFA.
self-limited iatrogenic cholecystitis.
Patients with BASA III score can be treated.
Thermal ablation of lesions adjacent to hepatic vesselsis possible because flowing blood usually protects thevascular wall from thermal injury. In this case, however, the risk of incomplete treatment of the neoplastic tissueclose to the vessel may increase due to heat loss by Contrast-enhanced CT or MRI are recognized as the stan- dard modalities with which to assess treatment outcome. CTand MRI results obtained 4–6 weeks after treatment showsuccessful ablation as a nonenhancing area with or without a peripheral enhancing rim. The enhancing rim that may beobserved along the periphery of the ablation zone appears to Before treatment, all patients with liver tumours who are be a relatively concentric, symmetric, and uniform process considered for RFA should undergo a thorough clinical in an area with smooth inner margins. This transient finding evaluation by a multidisciplinary team, including an represents a benign physiologic response to thermal injury interventional radiologist, a hepatologist, an oncologist, a (reactive hyperemia initially and fibrosis and giant cell surgeon, and an anesthesiologist. The core of physiological reaction subsequently). Benign periablational enhance- knowledge required for the interventional radiologist ment must be differentiated from irregular peripheral L. Crocetti et al.: Guidelines for RFA of Liver Tumours enhancement due to residual tumour that occurs at the approximately 90% in tumours [3 cm Histological treatment margin. Compared with benign periablational data from explanted liver specimens in patients who have enhancement, residual unablated tumour often grows in undergone RFA showed that tumour size and presence of scattered, nodular, or eccentric patterns. Contrast-enhanced large (B3 mm) abutting vessels significantly affect local ultrasound can be performed after the end of the procedure treatment effect. Complete tumour necrosis was patholog- and may allow initial evaluation of treatment effects.
ically shown in 83% of tumours \3 cm and 88% of Later follow-up imaging studies should be aimed at tumours located in a nonperivascular space Compari- detecting local tumour progression, development of new son with percutaneous ethanol injection (PEI) in five ran- hepatic lesions, or emergence of extrahepatic disease. A domized trials showed that RFA has a higher local recommended follow-up protocol includes CT or MRI anticancer effect than PEI, thus leading to better local studies at 3, 6, 9, and 12 months after treatment and at control of the disease (Table Consequently there is no 6-month intervals thereafter for the next 3 years.
room per PEI in HCC amenable to RFA.
Five randomized trials compared RFA with PEI for local Contraindications for RFA are as follows: ablation of early-stage HCC (Table The two Europeantrials failed to show a statistically significant difference in tumour located \1 cm from the main biliary duct (due overall survival between patients who received RFA to risk of delayed stenosis of the main biliary tract); compared with those receiving PEI ]. However, sur- vival advantages were identified in three Asian studies anterior exophytic location of the tumour (due to the These data were recently pooled in two indepen- dent meta-analysis, and the survival benefit of patients with small HCCs who received RFA was confirmed [ untreatable/unmanageable coagulopathy.
]. Therefore, RFA is the preferred percutaneous treat-ment for patients with early-stage HCC on the basis ofmore consistent local tumour control and better survival Recently, the long-term survival outcomes of RFA- treated patients were reported (Table ) –Inpatients who underwent RFA, survival depended on the RFA yields satisfactory local tumour control in treating severity of underlying cirrhosis and tumour stage. Patients small HCCs, with a complete ablation rate on imaging of in Child-Pugh class A with early stage HCC had a 5-year L. Crocetti et al.: Guidelines for RFA of Liver Tumours long-term survival outcomes ofpatients with early-stage HCC Child-Pugh A, 1 HCC \ 5 cm or 3 HCCs \ 3 cm Child-Pugh B, 1 HCC \ 5 cm or 3 HCCs \ 3 cm Child-Pugh A, 1 HCC \ 5 cm or 3 HCCs \ 3 cm Child-Pugh B, 1 HCC \ 5 cm or 3 HCCs \ 3 cm recurrent tumour after previoustreatment including resection, Child-Pugh A, 1 HCC \ 5 cm or 3 HCCs \ 3 cm survival rate of 61 to 77%, whereas patients with a single Table 4 Studies reporting long-term survival outcomes of patients tumour B2 cm had a 5-year survival rate of 68%.
with colorectal hepatic metastases who underwent percutaneous RFA Clinical Results: Colorectal Cancer Liver Metastases Many studies have investigated the use of RFA in the treatment of limited colorectal cancer hepatic metastatic disease in patients who were excluded from surgery. Two early studies reported rates of complete response that did not exceed 60–70% [Subsequently, owing to the advances in RFA technique and probably to the treatmentof smaller tumours, reported rates of successful localtumour control after RFA treatment increased substantially.
analysis of a randomized controlled trial comparing che- In two series, RFA allowed eradication of 91% of 100 motherapy plus RFA versus chemotherapy alone in colo- metastases and 97% of 74 metastases, respectively [ Recently, data on long-term survival of nonsurgical patientswith hepatic colorectal metastases who underwent RFA Early major complications associated with RFA occur in have been reported (Table ) –In particular, in three 2.2–3.1% of patients and include intraperitoneal bleeding, series including patients with B5, each B5 cm, the 5-year liver abscess, intestinal perforation, pneumothorax and survival rate ranged 24–44% at 5 years [When haemothorax, bile duct stenosis, and tumour seeding RFA was performed in patients with small (\4 cm) solitary (0.5%); the procedure mortality rate is 0.1–0.5% (Table hepatic colorectal metastases, a 40% 5-year survival rate The minor complication rate ranges from 5% to 8.9%. The was demonstrated ]. These figures are substantially most common causes of death are sepsis, hepatic failure, higher than those obtained with any chemotherapy regi- colon perforation, and portal vein thrombosis, whereas the mens and provide indirect evidence that RFA therapy most common complications are intraperitoneal bleeding, improves survival in patients with limited hepatic meta- hepatic abscess, bile duct injury, hepatic decompensation, static disease. This conclusion is supported by the interim and grounding pad burns. Minor complications and side L. Crocetti et al.: Guidelines for RFA of Liver Tumours 5. Lin SM, Lin CJ, Lin CC et al (2004) Radiofrequency ablation Table 5 Reported and acceptable rate of major complications improves prognosis compared with ethanol injection for hepato- cellular carcinoma B4 cm. Gastroenterology 127:1714–1723 6. Shiina S, Teratani T, Obi S et al (2005) A randomized controlled trial of radiofrequency ablation versus ethanol injection for small hepatocellular carcinoma. Gastroenterology 129:122–130 7. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC (2005) Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less.
8. Brunello F, Veltri A, Carucci P et al (2008) Radiofrequency ablation versus ethanol injection for early hepatocellular carci- noma: A randomized controlled trial. Scand J Gastroenterol 9. Lu DS, Yu NC, Raman SS et al (2005) Radiofrequency ablation of hepatocellular carcinoma: treatment success as defined byhistologic examination of the explanted liver. Radiology effects are usually transient and self-limiting []. An uncommon late complication of RFA can be tumour 10. Orlando A, Leandro G, Olivo M, Andriulli A, Cottone M (2009) seeding along the needle track. In patients with HCC, Radiofrequency thermal ablation vs. percutaneous ethanol tumour seeding occurred in 8 (0.5%) of 1,610 cases in a injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials. Am J Gastroenterol multicentre survey ] and in 1 (0.5%) of 187 cases in a single-institution series [Lesions with subcapsular 11. Cho YK, Kim JK, Kim MY, Rhim H, Han JK (2009) Systematic location and an invasive tumoural pattern, as shown by a review of randomized trials for hepatocellular carcinoma treated poor differentiation degree, seem to be at higher risk for with percutaneous ablation therapies. Hepatology 49:453–459 12. Lencioni R, Cioni D, Crocetti L et al (2005) Early-stage hepa- tocellular carcinoma in cirrhosis: long-term results of percuta-neous image-guided radiofrequency ablation. Radiology 234:961–967 Appendix A: American Society of Anesthesiologists 13. Tateishi R, Shiina S, Teratani T et al (2005) Percutaneous radiofrequency ablation for hepatocellular carcinoma. Cancer (ASA) Physical Status Classification System 14. Cabassa P, Donato F, Simeone F et al (2006) Radiofrequency ablation of hepatocellular carcinoma: long-term experience with expandable needle electrodes. Am J Roentgenol 185(Sup-pl):S316–S321 15. Choi D, Lim HK, Rhim H et al (2007) Percutaneous radiofre- Patient with severe systemic disease that is a constant quency ablation for early-stage hepatocellular carcinoma as a first- line treatment: long-term results and prognostic factors in a Moribund patient who is not expected to survive large single-institution series. Eur Radiol 17:684–692 16. Takahashi S, Kudo M, Chung H et al (2007) Initial treatment response is essential to improve survival in patients with hepa- tocellular carcinoma who underwent curative radiofrequency ablation therapy. Oncology 72(Suppl):S98–S103 17. Hiraoka A, Horiike N, Yamashita Y et al (2008) Efficacy of radiofrequency ablation therapy compared to surgical resection in164 patients in Japan with single hepatocellular carcinoma smaller than 3 cm, along with report of complications. Hepato-gastroenterology 55:2171–2174 1. Bruix J, Sherman M, Llovet JM et al (2001) EASL panel of 18. Lencioni R, Goletti O, Armillotta N et al (1998) Radio-frequency experts on HCC. Clinical management of hepatocellular carci- thermal ablation of liver metastases with a cooled-tip electrode noma. Conclusions of the Barcelona-2000 EASL Conference.
needle: results of a pilot clinical trial. Eur Radiol 8:1205–1211 European Association for the Study of the Liver. J Hepatol 19. Solbiati L, Goldberg SN, Ierace T et al (1997) Hepatic metasta- ses: percutaneous radio-frequency ablation with cooled-tip elec- 2. Bruix J, Sherman M (2005) Management of hepatocellular car- 20. De Baere T, Elias D, Dromain C et al (2000) Radiofrequency 3. Stang A, Fischbach R, Teichmann W, Bokemeyer C, Braumann ablation of 100 hepatic metastases with a mean follow-up of more D (2009) A systematic review on the clinical benefit and role of than 1 year. Am J Roentgenol 175:1619–1625 radiofrequency ablation as treatment of colorectal liver metasta- 21. Helmberger T, Holzknecht N, Schopf U et al (2001) Radiofre- quency ablation of liver metastases. Technique and initial results.
4. Lencioni R, Allgaier HP, Cioni D et al (2003) Small hepatocel- lular carcinoma in cirrhosis: randomized comparison of radio- 22. Solbiati L, Livraghi T, Goldberg SN et al (2001) Percutaneous frequency thermal ablation versus percutaneous ethanol injection.
radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. Radiology 221:159–166 L. Crocetti et al.: Guidelines for RFA of Liver Tumours 23. Lencioni R, Crocetti L, Cioni D et al (2004) Percutaneous 29. Gillams AR, Lees WR (2008) Five-year survival following radiofrequency ablation of hepatic colorectal metastases. Tech- radiofrequency ablation of small, solitary, hepatic colorectal nique, indications, results, and new promises. Invest Radiol metastases. J Vasc Interv Radiol 19:712–717 30. Ruers T, van Coevorden F, Pierie J et al (2008) Radiofrequency 24. Gillams AR, Lees WR (2004) Radio-frequency ablation of ablation combined with chemotherapy for unresectable colorectal colorectal liver metastases in 167 patients. Eur Radiol 14:2261– liver metastases: interim results of a randomised phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC).
25. Machi J, Oishi AJ, Sumida K et al (2006) Long-term outcome of radiofrequency ablation for unresectable liver metastases from 31. Livraghi T, Solbiati L, Meloni MF et al (2003) Treatment of focal colorectal cancer: evaluation of prognostic factors and effec- liver tumors with percutaneous radio-frequency ablation: com- tiveness in first- and second-line management. Cancer J 12:318– plications encountered in a multicentre study. Radiology 26:441– 26. Jackobs TF, Hoffmann RT, Trumm C et al (2006) Radiofre- 32. De Baere T, Risse O, Kuoch V et al (2003) Adverse events during quency ablation of colorectal liver metastases: mid-term results in radiofrequency treatment of 582 hepatic tumors. Am J Roentge- 27. Sorensen SM, Mortensen FV, Nielsen DT (2007) Radiofrequency 33. Bleicher RJ, Allegra DP, Nora DT et al (2003) Radiofrequency ablation of colorectal liver metastases: long-term survival. Acta ablation in 447 complex unresectable liver tumors: lessons 28. Veltri A, Sacchetto P, Tosetti I, Pagano E, Fava C, Gandini G 34. Llovet JM, Vilana R, Bru C et al (2001) Barcelona Clinic Liver (2008) Radiofrequency ablation of colorectal liver metastases: Cancer (BCLC) Group. Increased risk of tumor seeding after small size favorably predicts technique effectiveness and sur- percutaneous radiofrequency ablation for single hepatocellular vival. Cardiovasc Intervent Radiol 31:948–956



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