457의학강좌-배시현

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1 Continuing Education Column Up to date Information for Hepatocellular Carcinoma Treatment Si Hyun Bae, MD Department of Internal Medicine, The Catholic University of Korea College of Medicine E mail : baesh@catholic.ac.kr J Korean Med Assoc 2008; 51(5): Abstract Despite therapeutic advances, the overall survival of patients with hepatocellular carcinoma (HCC) has not been significantly improved in the last two decades. In the majority of the cases, there is underlying cirrhosis, therefore the prognosis of HCC depends not only on tumor stage but also on liver function. Patients at an early stage are those who present with an asymptomatic single HCC with a maximum diameter of 5 cm or up to three nodules each less than 3 cm. They will be benefitted by curative therapies, including resection, liver transplantation (LT), and percutaneous ablation, such as destroying tumor cells via the injection of chemical substances, radiation, or heating or cooling. Patients exceeding these limits, but who are free of cancer related symptoms and vascular invasion or extrahepatic spread may be benefitted by palliation with chemoembolization and hepatic arterial infusion chemotherapy. Recently, other treatments were developed under investigation treatments arising from technical advances in ablation and radiation. New promising image guided therapies are continuously emerging and minimize hepatic toxicity and ultimately improve quality of life and survival of patients with HCC. The 3 dimensional conformal RT, tomotherapy, stereotatic radiosurgery, high intensity focused ultrasound, and proton beam radiotherapy will provide the opportunity for curative treatment of HCC, while avoiding critical normal tissue. New drugs, such as tyrosine kinase inhibitors and antiangiogenic agents, are currently being tested in the setting of clinical trials. These new approaches may help to address the enormous need for expanded treatment options for patients with HCC. In the future, patients with HCC will be best treated by a multidisciplinary team approach, utilizing a combination of techniques to improve the patient survival. Keywords : Hepatocellular carcinoma; Surgery; Liver transplantation; Chemotherapy; Radiotherapy; Targeted therapy 457

2 Bae SH Figure 1. Surgical resection of hepatocellular carcinoma. 458

3 Up to date Information for HCC Treatment Table 1. Survival rate of patients with HCC treated by hepatic resection Actual survival (%) Reference Size N 1 yr 3 yr 5 yr early HCC overt HCC 2cm Fong (5) < 5cm Llovet (6) no portal HT, normal bilirubin Ari (7) Stage I < 2cm 1, Stage II HCC 2~5cm 2, < 2cm ~5cm 1, Table 2. Survival rate after liver transplantation in patients with HCC who meet Milan criteria Reference Actual survival (%) N 1 yr 3 yr 5 yr 1. Cadaveric liver transplantation Mazzaferro (9) * Bismuth (10) Llovet (6) Jonas (11) Gonzalez Uriate (12) Adam (13) Hayashi (14) Living donor liver transplantation * Four year survival Gondolesi (15) Todo (16)

4 Bae SH A B C D Figure 2. Transcatheter arterial chemoembolization. (A) CT shows 5cm sized hypodense nodular mass in the angle of right hepatic lobe. (B) Schematic figure of hepatic arterial embolization. (C) Arteriogram shows a hypervascular mass with prominent feeding artery in the right hepatic lobe. (D) After TACE, CT shows a complete retention of lipiodol within the mass in the right hepatic lobe. 460

5 Up to date Information for HCC Treatment Table 3. Survival rate of patients with HCC treated by PEIT Reference Selection Actual Survival (%) criteria N 1 yr 3 yr 5 yr Livraghi (25) Child A, single 3cm Child A, 5cm Sakamoto (26) single, < 2cm Arii (7) Stage I, < 2cm ~5cm Stage II, < 2cm ~5cm Omata (27) 2cm nodules 3cm Table 4. Survival rate of patients with HCC treated by RFA Reference Selection Actual Survival (%) criteria N 1 yr 3 yr 5 yr Rossi (30) single < 3cm Buscarini (31) single 3.5cm Omata (27) single < 5cm or 3 nodules < 3cm * Tateishi (32) cm ~5cm * Four year survial Table 5. Randomized controlled trials comparing PEIT and RFA as treatment for HCC (29) Refernce Complete 2 year local Survival Rate (%) response rate recurrence rate 2 yr 3 yr Lencioni (34) (single < 5cm, 3 nodules < 3cm, Child Pugh A/B) Shiina (36) (3 nodules < 3cm, Child Pugh A/B) PEIT (n=50) PEIT (n=114) 82% 100% 38% 11% RFA (n=52) RFA (n=118) 95% 100% 4% 2%

6 Bae SH Figure 3. Photograph during the Ethanol Injection. The echogenicity of targeted mass is increased after injection of ethanol. 462

7 Up to date Information for HCC Treatment A B Figure 4. Radiofrequency ablation. (A) Pre treatment sonogram shows a hypoechoic mass in the right lobe of liver. (B) The echogenicity of the tumor is increased by micro bubbles immediately after ablation. 463

8 Bae SH Table 6. Anti tumor effect, hepatic function and viral clearance in treatment modalities for HCC Anti tumor effect Hepatic function Removal of carcinogenic liver Viral clearance Surgery 100% Some No, even aggravate TACE 40~ 80% No No PEI or RFA 80% No No Transplantation 100% Yes Yes, in HBV Table 7. Treatment response of systemic chemotherapy for HCC Reference Chlebowski (38) Chemotherapeutic agents Doxorubicin Response rate 11 Falkson (39) Doxorubicin+5 FU+methy CCNU 15 Melia (40) VP Falkson (41) Cisplatin 17 Okada Patt (42) Cisplatin, Mitosantrone+5 FU 5 FU+interferon

9 Up to date Information for HCC Treatment A B C Figure 5. Implantation of arterial chemoport subcutaneously above the right inguinal area. (A) Hepatic arteriogram after catheterization at hepatic proper artery. (B) Right gastroduodenal artery was embolized with multiple microcoils. (C) Chemoport was inserted in the right inguinal area. 465

10 Bae SH Table 8. Treatment response and survival rate of hepatic arterial infusion chemotherapy Reference Treatment method Actual survival Ando (57) HAIC: Cisplatin (10mg/hr, 5 days) + 5 FU (250mg/hr, 5 days), CR/PR 44% n=p mean survival 14Mo 3yr survival 40% Ando (58) HAIC: Cisplatin 7mg/m FU 170mg/m 2, n=48 45% 31% Sumie (59) HAIC: Cisplatin 10mg/m 2 +5 FU 250mg/m 2 (5 days) n=16 4CR/PR 56% CR/PR 24% TACE: adriamycin 30mg + lipiodol + gelfoam, n=21, monthly 81% 56% 76% 33% Cheong (54) Conservative 0% Systemic chemotherapy: 5 FU + doxorubicin + MMC 4% HAIC: Cisplatin 10mg/m FU 250mg/m 2 (5 days) 21% Jang (55) HAIC: Epi 50mg/m 2 + Cisplatin 60mg/m 2 +5 FU 200mg/m 2, n=30 CR/PR 17% CR/PR 0% TACL: adriamycin 50mg + lipiodol + gelfoam, n=22 57% 17% 37% 0% Sim (61) HAIC: Cisplatin 80mg/m 2 (1 day), n=67 CR/PR 20% CR/PR 19% Jang (60) HAIC: Cisplatin 60mg/m 2 (1 day), + 5 FU 200mg/m 2 (3 days), n=36 HAIC: Epi 50mg/m 2 + Cisplatin 60mg/m FU 200mg/m 2, n=80 CR/PR 17% CR/PR 0% conservative, n=23 30% 13.4% 0% TACE; transarterial chemoembolization, HAIC; hepatic arterial chemoinfusion, portal vein tumor thrombi, TACL; transarterial chemolipiodolization, CR; completer response, PR; partial response, MMC; mitomycin C 466

11 Up to date Information for HCC Treatment Figure 6. 3 dimensional conformal radiation threapy. 467

12 Bae SH Figure 7. Stereotactic radiosurgery (CyberKnife) and therapeutic planning. Figure 8. Radiotherapy planning in Helical tomotherapy. 468

13 Up to date Information for HCC Treatment Heat Therapeutic transduer Probe Figure 9. High Intensiy Focused Ultrasound (HIFU). 469

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