Transcript HCV Structure and Genome

Staging Strategy and Treatment for
Patients With HCC
HCC
PST 0-2, Child-Pugh A-B
PST 0, Child-Pugh A
Very early stage
Single < 2 cm
Early stage
Single or 3 nodules
≤ 3 cm, PST 0
Single
Resection
Advanced stage
Portal invasion,
N1, M1, PST 1-2
Terminal
stage
3 nodules ≤ 3 cm
Portal pressure/bilirubin
Increased
Normal
Intermediate stage
Multinodular, PST 0
PST > 2,
Child-Pugh C
No
Liver transplant
Curative treatments
Associated
diseases
Yes
RFA/PEI
TACE
Sorafenib
Palliative treatments
Symptomatic
Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and
future prospects.Semin Liver Dis. 2010;30(1):61-74
BCLC Staging and Treatment Strategy
HCC
Okuda 1-2, PS 0-2, Child-Pugh A-B
PS 0, Child-Pugh A
Very early stage (0)
Early stage (A)
Intermediate
Single < 2 cm
Single or 3 nodules
stage (B)
<
3
cm,
PS
0
Carcinoma in situ
Multinodular, PS 0
Single
Resection
Advanced stage (C) Terminal
Portal invasion,
stage (D)
N1, M1, PS 1-2
3 nodules ≤ 3 cm
Portal pressure/bilirubin
Increased
Normal
Okuda 3, PS > 2,
Child-Pugh C
Associated
diseases
No
Liver transplantation
Yes
RFA/PEI
Curative treatments (30%); 5-yr survival: 40%-70%
TACE
Sorafenib
RCTs (50%); 3-yr survival: 10%-40%
Symptomatic
(20%); survival <
3 mos
Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National
Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.
BCLC Staging System
HCC
Stage 0
PS 0, Child-Pugh A
Stage A-C
Stage D
Okuda 1-2, PS 0-2, Child-Pugh A-B
Very early stage (0)
Early stage (A)
Intermediate
Single < 2 cm
Single or 3 nodules
stage (B)
<
3
cm,
PS
0
Carcinoma in situ
Multinodular, PS 0
Okuda 3, PS > 2,
Child-Pugh C
Advanced stage (C) Terminal
Portal invasion,
stage (D)
N1, M1, PS 1-2
Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National
Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.
Liver Transplantation for HCC:
Milan Criteria (Stage 1 and 2)
Single tumor, not > 5 cm
Up to 3 tumors, none > 3 cm
+
Absence of macroscopic vascular invasion,
absence of extrahepatic spread
• 5-yr survival with transplantation: ~ 70%
• 5-yr recurrent rates: < 15%
Mazzaferro V, et al. N Engl J Med. 1996;334:693-699.
Llovet JM. J Gastroenterol Hepatol. 2002;17(suppl 3):S428-S433.
Candidates for RFA/PEI
• Includes individuals who are not candidates
for surgery
• Radiofrequency ablation generally preferred
over percutaneous ethanol injection
– Necrotic effect more predictable across tumor
sizes
– Meta-analyses suggest survival benefit with
radiofrequency ablation vs percutaneous ethanol
injection
Bruix J, et al. AASLD HCC guidelines. July 2010.
BCLC Staging and Treatment Strategy
HCC
Okuda 1-2, PS 0-2, Child-Pugh A-B
PS 0, Child-Pugh A
Very early stage (0)
Early stage (A)
Intermediate
Single < 2 cm
Single or 3 nodules
stage (B)
<
3
cm,
PS
0
Carcinoma in situ
Multinodular, PS 0
Single
Resection
Advanced stage (C) Terminal
Portal invasion,
stage (D)
N1, M1, PS 1-2
3 nodules ≤ 3 cm
Portal pressure/bilirubin
Increased
Normal
Okuda 3, PS > 2,
Child-Pugh C
Unresectable HCC
Associated
diseases
No
Liver transplantation
Yes
RFA/PEI
Curative treatments (30%); 5-yr survival: 40%-70%
TACE
Sorafenib
RCTs (50%); 3-yr survival: 10%-40%
Symptomatic
(20%); survival <
3 mos
Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National
Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.
Arterial Embolization for HCC
Meta-analysis of 6 RCTs (2-Yr Survival)
Random Effects Model,
OR (95% CI)
Author, Journal Yr
Patients, n 0.01
Lin, Gastroenterology 1988
63
GETCH, NEJM 1995
96
Bruix, Hepatology 1998
80
Pelletier, J Hepatol 1998
73
Lo, Hepatology 2002
79
Llovet, Lancet 2002
112
Overall
503
Median survival: ~ 20 mos
Llovet JM, et al. Hepatology. 2003;37:429-442.
0.1
0.5 1
2
10
100
Z = -2.3
P = .017
Favors Treatment
Favors Control
Contraindications to TACE
• Extrahepatic tumor spread
• Lack of portal blood flow
– Portal vein thrombosis, portosystemic
anastomoses or hepatofugal flow
• Advanced liver disease (Child-Pugh Class B or
C)
• Clinical symptoms of end-stage cancer
Bruix J, et al. AASLD HCC guidelines. July 2010.
BCLC Staging and Treatment Strategy
HCC
Okuda 1-2, PS 0-2, Child-Pugh A-B
PS 0, Child-Pugh A
Very early stage (0)
Early stage (A)
Intermediate
Single < 2 cm
Single or 3 nodules
stage (B)
<
3
cm,
PS
0
Carcinoma in situ
Multinodular, PS 0
Single
Resection
Advanced stage (C) Terminal
Portal invasion,
stage (D)
N1, M1, PS 1-2
3 nodules ≤ 3 cm
Portal pressure/bilirubin
Increased
Normal
Okuda 3, PS > 2,
Child-Pugh C
Associated
diseases
No
Liver transplantation
Yes
RFA/PEI
Curative treatments (30%); 5-yr survival: 40%-70%
TACE
Sorafenib
RCTs (50%); 3-yr survival: 10%-40%
Symptomatic
(20%); survival <
3 mos
Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National
Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.