간암연구회 June 28, 2008 Local Ablation for Small HCCs 성균관의대 삼성서울병원 소화기영상의학과 최동일
간세포암종 진료 가이드라인 대한간암연구회 일차 판단 이차 판단 이차 검사 삼차 판단 치료 방침 방침 ** 간세포암종 D1 간암 병기 Child-Pugh 등급 -수술가 능 D2 선택검사 ICG 검사 역동적 조영증강 MRI 뼈스캔 흉부 CT 혈관조영술/ 리피오돌 CT * PET 용적측정 D2 -절제가능 -절제불가능 잔존간기능 부 족 간절제술(I) 경동맥화학색전술(III) 국소치료술(III) ± 간이식 간이식(II) 경동맥화학색전술(II) 국소치료술(II) 방사선치료 증세치료 +- 기타 실험적치료 -수술불가능 간기능 저하 동반된 전신질환 수행능력 저하 수술거부 광범위 또는 다발성 종양 주혈관 종양 혈 전 간외전이 경동맥화학색전술(II-III 국소치료술(III) 방사선치료(III) 전신적 항암화학요법(II 증세치료 +- 전이병소 절제술, 혈관성형 및 간 절제술 ± 기타 실험적 치료 간세포암종이 명확하지 않은 경우 간조직검사
Ethanol Microwave Laser Cryoablation
RF ablation > Ethanol ablation Better local tumor control and long-term survivals 3 recent prospective randomized studies 1. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma cinoma < 4 cm. Gastroenterology 2004; 127:1714-1723. 1723. 2. Shiina S, Teratani T, Obi S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular ellular carcinoma. Gastroenterology 2005; 129:122-130 130 3. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous eous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut 2005; 54:1151-1156 1156
간세포암종 진료 가이드라인 대한간암연구회 1. 적응증 Child-Pugh A, B 이면서 단발성: 종양 장경 4 cm 이하 다발성: 3개 이하이며 장경 3 cm 이하 2. 상대적 비적응증 간기능 Child-Pugh C 교정 후 혈소판 6만/mm 3 이하, 프로트롬빈시간 60% 이하 직경 3 mm 이상의 간내 혈관이나 주요 장기와 인접한 종양 외장성 종양 종양 장경 5 cm 이상, 개수 5 개 이상 3. 절대적 비적응증 영상 유도가 불가능한 경우/ 협조가 되지 않는 환자/ 조절되지 않은 전신적 세균성 감염/ 조절되지 않은 간성 혼수와 응고장애
Applicator(Electrode) Radiofrequency current (200-1200kHz) Dispersive electrode (Ground Pad) Generator
~ 100 C RF currents Ionic agitation Frictional heat Coagulation necrosis
Equipment RITA Medical Systems Temperature based treatment Typical treatment times: 20 45 minutes Multi tine, deployed electrode
Boston Scientific Impedance based feedback system Typical treatment times: 20 45 minutes Deployed, multiple wire array No temperature monitor
Fully automatic operation Typical treatment times 12 minutes Monitors and responds to impedance Monitors temperature Timed treatment cycle Cool-tip tip System
Perfusion electrode Infusion of saline into tissue large coagulation necrosis Electrical/thermal conductivity Convective cooling of electrode tip Virtual liquid electrode ( surface area of electrode )
1. Planning Tumor analysis by US(>> CT, MRI) 2. Targeting Placement of an electrode 3. Monitoring Hyperechoic zone of ablation on US 4. Controlling Repositioning electrode Controlling thermal parameter Percutaneous approach Local/ conscious sedation < 1 hour treatment 3 month follow-up CT 5. Assessment of Tx.. response Asseeement of post RFA imaging studies
RFA for HCC Pre Needle insertion Sta 5 min 10 min (stop) 15 m
고주파 열치료의 역할 근치목적 TACE의 보완 수술의 보완 Pre-RFA Imme 4-mo. 16-mo Recur 2nd RFA 64-mo.
Evaluation of Therapeutic Response US CT MRI
Safety margin Technical Success (0.5-1cm peripheral margin of normal hepatic tissue surrounds tumor) Ablative margin Index tumor Before Immediate 1-month after RFA
Residual Unablated Tumor Immediate 1-month
US After RFA
Residual Unablated Tumor PDUS Before Immed. Choi & Lim et al. Radiology 2000;217 CE-PDUS
Local tumor progression and new HCC 7-month F/U After TACE
Before RFA After RFA Choi & Lim et al. JUM 2003;22
Helpful in guiding the residual tumor portion during the additional RF ablation for residual tumor. Choi D & Lim HK. Korean J Rad 2004; 5:
Imaging strategy after RFA at SMC Immediate CT (within 1 hours) 1 month F/U CT All patients Baseline study Gd-enhanced liver MRI in allergic patients Follow-up Every 3 months Every 6 months for the patients without local tumor progression longer than 3 years
Local Tumor Control of RFA for HCCs Year Author No. of tumors FU (m) Local tumor progression (%) Complete Tx rate(%) 2005 Lencioni 240 24 10.0 90 2005 Tateishi 306 27 2.4 97.6 2006 Chen 374 NA 12.1 88.9 2007 Choi 674 26 10.9 87.9 ~ 10% ~ 90%
Long-term Survival of RFA for HCCs Year Author No. of Pts Overall survival rates (%) 1yr 3yr 5yr 2005 Lencioni 206 97 67 41 2005 Tateishi 319 95 78 54 2006 Chen 256 83 67 41 2007 Choi 570 95 69 58 ~ 90% ~ 70% ~ 50%
Prognostic factors for Survival Year Author Prognostic factors 2005 Lencioni Child class,, Tumor multiplicity 2005 Tateishi Child class, AFP,, Tumor size 2007 Choi Child class, AFP,, Age
Local tumor progression - Large tumor > Small tumor, p=0.001 (log rank test) 0.5 0.4 0.3 Larger (> 2 cm) All Small 0.2 0.1 8.1% 10.9% 11.8% 0 0 1 2 3
Results LONG-TERM SURVIVAL 570 pts. Follow-up period: 2-82 months (median 26 Ms) 1 95.2% Overall survival Cumulative rate 0.8 0.6 0.4 0.2 60.9% 69.5% 26.5% Event-free survival 58.0% 21.0% 0 1 2 3 4 5 Yr Choi D, Lim HK, et al. Eur Rad,, 2007;17:684.
Overall Survival Child A > Child B, p<0.001 (stepwise Cox hazard model) 1 0.8 0.6 0.4 Child A All 0.2 Child B 0 0 1 2 3 4 5 Yr
Two Korean reports Retrospective study: 55 RFA vs. 93 resection Resection = RFA (single HCC < 4 cm, 3-year) 3 Hong SN, Choi M et al. J Clin Gastroenterol 2005:39;247 Retrospective study: 99 RFA vs. 61 resection Resection = RFA (HCC < 5 cm, 3-year) 3 조창민 등. 대한간학회지 2005:11;59
HCC < 5 cm Prospective randomized controlled trial 90 RFA vs. 90 resection (HCC < 5 cm) Tx. No. of Pts Overall survival rates (%) Dis.-free survival rates (%) 2yr 4yr 2yr 4yr RFA 90 82 68 69 46 Surg. 90 82 64 77 52 P-value >0.05 >0.05 Chen MS, et al. Ann Surg.. 2006;243:321
HCC < 3 cm Retrospective study: 79 RFA vs. 79 resection Resection > RFA (3-year) However, Resection = RFA in HCC < 3 cm Vivarelli M, et al. Ann Surg (2004) 240:102 Retrospective study: 109 RFA vs. 91 resection Resection > RFA (HCC < 6 cm, 5-year) 5 However, in selected pts (Child B, multiple HCCs, or HCC < 3 cm), Resection = RFA Guglielmi A, et al. J Gastrointest Surg (2008) 12:192
Retrospective study: 64 ablation vs. 85 resection HCC < 4 cm HCC < 2 cm Resection > ablation, 10-year survival However, in HCC < 2 cm, Resection = ablation Higher vascular invasion in HCC > 2 cm Wakai T, et al. World J Gastroenterol 2006;12:546 218 RFA for single, operable HCC < 2 cm 5-year survival, 68.5% Livraghi T, et al. HEPATOLOGY, 2008;47:82
Expanded role of RFA in treating HCC Combination with TACE - Medium-sized HCC (3-6 6 cm) - multiple tumors > 4 Combination with hepatectomy - bilobar tumors Recurrent tumors after surgery
Combined Therapy with TACE and RFA Before Immed. 32 months In > 3 cm, TACE-RFA > TACE alone or RFA alone Cheng BQ, et al. JAMA 2008;299:1669-
Combined Therapy with TACE and RFA Before 1-month
Bilobar HCCs Rt. Lobectomy + RFA 1-month 4-months Before Choi D, Lim HK, et al. Ann Surg Oncol 2007; 14:3510
Concurrent Resection and intraop. RFA 1 Survival rates 0.8 0.6 0.4 0.2 87% Smaller Resected Tumor All Larger (> 5 cm) 80% 55% 0 0 1 2 3 4 5 Time after combination therapy (yrs) p=0.004
59-year old man Recurrent HCC after hepatectomy Before OP Recurrent HCC (one year later) 1 m after RFA - complete 1 o effectiveness 30 m after RFA Choi D, Lim HK, et al. Ann Surg Oncol 2007; 14:2319
Percutaneous RFA for Recurrent HCC after hepatectomy 1 0.8 94% 66% Overall Survival 0.6 0.4 0.2 Small All Larger (> 5 cm) 52% 0 0 1 2 3 4 5 Years Overall Survival Resected tumor size p=0.005
Long-term Results at SMC (2007) HCCs No. of Pts Overall survival rates (%) 1yr 3yr 5yr Percut.. RFA for HCCs as the first-line Treatment 1 570 95 69 58 Percut.. RFA for recur. HCC after hepatectomy 2 102 94 66 52 Combined intraop.. RFA + hepatectomy for multifocal HCCs 3 53 87 80 55 1 Choi D, Lim HK, et al. Eur Rad,, 2007;17:684. 2 Choi D, Lim HK, et al. Ann Surg Oncol 2007; 14:2319 3 Choi D, Lim HK, et al. Ann Surg Oncol 2007; 14:3510
Author Rate of complication year No Cx.. rate Curley SA 1999 169/123 2.4 Curley SA 2000 149/110 12.7 Ma K 2001 114 9.6 Mulier S 2002 3670 8.9 Rhim H 2003 1550/1154 2.43 de Baere T 2003 582/312 10.6 Livraghi T 2003 3554/2320 5.0-,, 2.5 Curley SA 2004 1225/608 9.5 Buscarini E 2004 166 32.5-,, 6.5 Rhim H 2004 400/312 3.6-,, 6.0
Complication at SMC- 1st Line Tx 674 HCCs ( < 5 cm) in 570 patients No mortality Total Intraperi.. hemorrhage 9 0 Biloma 9 1 Liver abscess 6 3 Liver infarction 5 4 Cancer seeding 2 2 Pneumothorax 2 0 Hempthorax 1 0 Acute cholecystitis 1 1 Major Cx. 35 (6.1%) 11 (1.9%) Choi & Lim et al. Eur Radiology 2007
Intraperitoneal (and intraepatic) hemorrhage Before Immed. CT Tx.: transfusion
Liver Abscess 75/M, Hepaticojejunostomy due to biliary stricture following left hepatectomy for HCC Before RFA 3 days after RFA Choi D, Lim HK, et al. AJR 2005; 184:1860-
Tumor seeding along the tract Before 1 month 16 months
Lung injury - Pneumothorax
Diaphragm injury - hemopericardium
Pseudoaneurysm - Hepatic artery injury
Bile duct injury Biloma
Bowel injury Courtesy of Asan Medical Center
HCC Abutting Stomach: Laparoscopy guided RFA Before RFA 1 month after RFA 8 months after RFA
RF Ablation: 안전하고도 효과적인 간암의 비수술적 치료법 4cm, 3개3 이하 간세포암. 좋은 적응증! (2cm( 이하땐 수술과 견줄만) 대개 경피적, 초음파 유도하, 국소마취하 시술 근치적 또는 TACE나 Surgery에 보조적으로 사용 국소재발율 10%, 완전치료율 90%, 합병증 2%, 5년5 생존율 50% Non invasive Tx의 보편화전까지 주요 국소치료법