Up-to-date Information for Hepatocellular Carcinoma Treatment

Article information

J Korean Med Assoc. 2008;51(5):457-474
Publication date (electronic) : 2008 January 10
doi : https://doi.org/10.5124/jkma.2008.51.5.457
Department of Internal Medicine, The Catholic University of Korea College of Medicine E-mail: baesh@catholic.ac.kr

Abstract

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 5cm or up to three nodules each less than 3cm. 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 anti-angiogenic 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.

Figure 1.

Surgical resection of hepatocellular carcinoma.

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.

Figure 3.

Photograph during the Ethanol Injection. The echogenicity of targeted mass is increased after injection of ethanol.

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.

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.

Figure 6.

3-dimensional conformal radiation threapy.

Figure 7.

Stereotactic radiosurgery (CyberKnife) and therapeutic planning.

Figure 8.

Radiotherapy planning in Helical tomotherapy.

Figure 9.

High Intensiy Focused Ultrasound (HIFU).

Survival rate of patients with HCC treated by hepatic resection

Survival rate after liver transplantation in patients with HCC who meet Milan criteria

Survival rate of patients with HCC treated by PEIT

Survival rate of patients with HCC treated by RFA

Randomized controlled trials comparing PEIT and RFA as treatment for HCC (29)

Anti-tumor effect, hepatic function and viral clearance in treatment modalities for HCC

Treatment response of systemic chemotherapy for HCC

Treatment response and survival rate of hepatic arterial infusion chemotherapy

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Article information Continued

Figure 1.

Surgical resection of hepatocellular carcinoma.

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.

Figure 3.

Photograph during the Ethanol Injection. The echogenicity of targeted mass is increased after injection of ethanol.

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.

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.

Figure 6.

3-dimensional conformal radiation threapy.

Figure 7.

Stereotactic radiosurgery (CyberKnife) and therapeutic planning.

Figure 8.

Radiotherapy planning in Helical tomotherapy.

Figure 9.

High Intensiy Focused Ultrasound (HIFU).

Table 1.

Survival rate of patients with HCC treated by hepatic resection

      Actuual survivval (%)
Reference Size N 1 yr 3 yr 5 yr
  early HCC   15 100 93
  overt HCC ≤ 2cm 52 92 54
Fong (5) < 5cm 38 86 66 59
Llovet (6)   77 85 61 51
  no portal HT, normmal bilirubin 35 91 87 74
Ari (7)
     Stage I < 2cm 1 1,318 96 88 72
  2∼5cm 2 2,722 95 58
     Stage II HCC < 2cm 502 92 55
  2∼5cm 1 1,548 95 58

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) 48 84   74*
 Bismuth (10) 45 82   72
 Llovet (6) 79 86   75
 Jonas (11) 120 90   71
 Gonzalez-Uriate (12) 64 87   73
 Adam (13) 195 80   61
 Hayashi (14) 45   74
2. Living donor liver transplantation
 Gondolesi (15) 15   86  
 Todo (16) 137   79  
*

Four-year survival

Table 3.

Survival rate of patients with HCC treated by PEIT

Reference Selection criteria N Actual Survival (%)
1 yr 3 yr 5 yr
Livraghi (25) Child A, single ≤3cm 169 99 86 48
  Child A, ≤5cm 293 98 47
Sakamoto (26) single, <2cm 88 71
Arii (7) Stage I, <2cm 767 96 54
     2∼5cm 587 95 38
  Stage II, <2cm 426 92 33
     2∼5cm 483 87 28
Omata (27) ≤2cm 144 85 70
  3 nodules ≤3cm 250 80 65

Table 4.

Survival rate of patients with HCC treated by RFA

Reference Selection criteria N Actual Survival (%)
1 yr 3 yr 5 yr
Rossi (30) single <3cm 39 94 58 40
Buscarini (31) single ≤3.5cm 88 89 62 33
Omata (27) single <5cm or        
  3 nodules <3cm 434 95 78 68*
Tateishi (32)   319 94 77 54
  ≤2cm 87 100 91 84
  2.1∼5cm 215 93 74 45
*

Four?year survial

Table 5.

Randomized controlled trials comparing PEIT and RFA as treatment for HCC (29)

Refernce Complete response rate 2 year local recurrence rate Survival Rate (%)
2 yr 3 yr
Lencioni (34)
  (single < 5cm, 3 nodules < 3cm, Child-Pugh A/B)
  PEIT (n=50) 82% 38% 88 73
  RFA (n=52) 95% 4% 96 71
Shiina (36)
  (3 nodules < 3cm, Child-Pugh A/B)
  PEIT (n=114) 100% 11% 82 63
  RFA (n=118) 100% 2% 90 80

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 Chemotherapeutic agents Response rate (%)
Chlebowski (38) Doxorubicin 11
Falkson (39) Doxorubicin+5 – FU+methy – CCNU 15
Melia (40) VP – 16 18
Falkson (41) Cisplatin 17
Okada Cisplatin, Mitosantrone+5-FU 33
Patt (42) 5- FU+interferon 18

Table 8.

Treatment response and survival rate of hepatic arterial infusion chemotherapy

Reference Treatment method Actual survival
1yr 2yr
Ando (57) HAIC: Cisplatin (10mg/hr, 5 days) + 5-FU (250mg/hr, 5 days), n=p CR/PR 44%
mean survival 14Mo
3yr survival 40%
Ando (58) HAIC: Cisplatin 7mg/m2 + 5-FU 170mg/m2, n=48 45% 31%
Sumie (59) HAIC: Cisplatin 10mg/m2+5-FU 250mg/m2 (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/m2 + 5-FU 250mg/m2 (5 days) 21%  
Jang (55) HAIC: Epi 50mg/m2 + Cisplatin 60mg/m2+5-FU 200mg/m2, n=30 CR/PR 17% CR/PR 0%
  TACL: adriamycin 50mg + lipiodol + gelfoam, n=22 57% 17%
    37% 0%
Sim (61) HAIC: Cisplatin 80mg/m2 (1 day), n=67 CR/PR 20% CR/PR 19%
  HAIC: Cisplatin 60mg/m2 (1 day), + 5-FU 200mg/m2 (3 days), n=36    
Jang (60) HAIC: Epi 50mg/m2 + Cisplatin 60mg/m2 + 5-FU 200mg/m2, 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 chemoli-piodolization, CR; completer response, PR; partial response, MMC; mitomycin-C