HCC Guidelines and recommendation
2013
Diagnostic algorithm
New mass/nodule
Ø < 1cm
Ø ≥1cm
US 3 months
TC/RM/CEUS*
Increase (Ø ≥ 1 cm)
No
Typical feature
(wash in/wash out)
Yes
No
US 3 months
(for 12 months)
Yes
Alternative imaging
technique
Increase (Ø ≥ 1 cm)
Yes
No
Atypical feature
US 6 months
Biopsy
Inconclusive
Typical feature
Other diagnosis
HCC
US, Ultrasound; MRI, Magnetic resonance imaging; CT, computed tomography; CEUS, contrast-enhanced ultrasonography *Since magnetic resonance imaging (MRI) or computed tomography (CT)
would be performed for hepatocellular carcinoma staging after detection of a nodule by ultrasonography, the most cost-effective approach is to prescribe in first line MRI or CT and to resort to
contrast-enhanced ultrasonography (CEUS) in case of inconclusive diagnosis at MRI and/or CT .
Position paper AISF DLD 2013 45(2013) 712-723
Diagnostic algorithm
Mass/nodule on US
<1cm
1-2cm
>2cm
Repeat US at 4 mo
4-phase CT/Dynamic
Contrast enhanced MRI
4-phase CT or Dynamic
Contrast enhanced MRI
1 or 2 positive techniques*:
HCC radiological Hallmarks**
1 positive technique:
HCC radiological Hallmarks**
Growing/Changing
Character
Stable
Investigate
according to size
Yes
HCC
No
Biopsy
Yes
HCC
No
Biopsy
Inconclusive
Diagnostic algorithm and recall policy.*One imaging technique only recommended in centers of excellence with high-end radiological equipment.**HCC radiological hallmark: arterial
hypervascularity and venous/late phase washout
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943
Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf
Treatment algorithm – AISF guidelines
HCC not amenable to curative treatments
No portal/hepatic vein invasion
(except segmental or subsegmental
portal branches))
Child Pugh class A or B7
Performance Status ≤1
1st treatment
(cTACE or DEB-TACE)
Liver failure or
severe adverse events*
MRI or CT** at 1 month
Complete response
No
Resolution
Palliation
Yes
No complete response
2nd treatment
(cTACE or DEB-TACE)
MRI or CT every 3 months
Desease recurrence
MRI or CT** at 1 month
Partial response
Desease progression
or stable desease
Newly developed HCC
Consider another course of cTACE or DEBTACE (and/or ablation techniques)
* : each TACE; ** : with cTACE, MRI is preferred to CT *** : Response must be assessed by modified RECIST criteria
Position paper AISF DLD 2013 45(2013) 712-723
sorafenib
Systemic therapies – AISF guidelines
Position paper AISF DLD 2013 45(2013) 712-723
Treatment algorithm – NCCN guidelines
Clinical presentation
• Inadequate
hepatic reserve
• Tumor location
Unresectable
Extensive liver
disease
Treatment
Evaluate whether
patient is a candidate
for transplant (See
UNOS criteria under
Surgical Assessment
HCC-5)
Transplant
candidate
• Refer to liver
transplant center
• Consider brige
therapy as
indicated
Not a transplant
candidate
Options:
Surveillance
• Imaging every 3–6 months for 2
years, then every 6-12 months
• AFP, if initially elevated, every 3-6
months for 2 years, then every 6-12
months
• See relevant pathway (HCC-2
through HCC-7) if disease recurs
• Sorafenib
(Child–Pugh Class A [category 1] or B)
• Chemotherapy ± RT only in the context of a clinical trial
 Systemic chemotherapy
 Intra-arterial chemotherapy
• Clinical trial
• Locoregional therapy
• RT (conformal or stereotactic) (category 2B)
• Supportive care
Options:
• Sorafenib
Inoperable by perfomance
status or comorbidity, local
disease or local disease with
minimal extrahepatic disease
only
•
•
•
•
(Child–Pugh Class A [category 1] or B)
Clinical trial
Locoregional therapy
RT (conformal or stereotactic) (category 2B)
Supportive care
Options:
Metastatic
disease or
Extensive
liver burden
• Sorafenib
(Child–Pugh Class A [category 1] or B)
• Supportive care
• Clinical trial
NCCN Clinical Practice Guidelines in Oncology. Hepatobiliary Cancer. V2.2013; Available from: www.nccn.org Accessed on 09-May 2013.
Treatment algorithm - APASL guidelines
HCC
Confined to the liver
Main portal vein patent
Extrahepatic metastasis
Main portal vein tumor thrombus
Resectable
Yes
Child–Pugh A/B
Sorafenib or systemic therapy trial
No
Resection/RFA Solitary tumor < 5 cm < 3
tumors < 3 cm
(for < 3 cm
No venous invasion
HCC)
Child–Pugh A
Local
ablation
Child–Pugh B
Child–Pugh C
Child–Pugh C
Transplantation
APASL recommendations on HCC, Omata M, et al. Hepatol Int. 2010;4:439–474
Tumor > 5 cm
> 3 tumors
Invasion of hepatic / portal vein branches
Child–Pugh A/B
TACE
Child–Pugh C
Supportive care
Consensus-based treatment algorithm - JSH
HCC
No
EXTRAHEPATIC
SPREAD
LIVER fUNCTION
Yes
Child-Pugh A/B
VASCULAR
INVASION
Child-Pugh C Child-Pugh B/C
No
Single
NUMBER
Hypovascular
Early HCC*3
SIZE
≥4
1-3
≤3 cm
TREATMENT
•Intensive
follow up
•Ablation
Yes
•Resection
•Ablation
>3 cm
Resection
TACE
•TACE+
Ablation*4
•TACE*5
•HAIC*5
•Resection*6
•Ablation*6
Sorafenib*5
(TACE refractory,child-pugh A)
Kudo et al. Dig Dis 2011;29:339–364
No
Within Milan*7
criteria
or age ≤65
•HAIC (Vp3,4)*8
•Sorafenib (vp3,4)*8
•TACE (Vp1,2)*9
•Resection(Vp1,2)*9
Child-Pugh A
Yes
*1, *2
Exceeding Milan
criteria
or age >65
•Transplantation
•TACE/ablation
for Child-Pugh C
Patient *10
Palliative care
Sorafenib
Treatment algorithm - AASLD guidelines
HCC
Stage 0
PS 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Stage A–C
PS 0–2, Child–Pugh A–B
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PS 0
Portal pressure/
bilirubin
Increased
Resection
Advanced stage (C)
Portal invasion,
N1, M1, PS 1–2
End stage (D)
3 nodules ≤ 3 cm
1 HCC
Normal
Intermediate stage (B)
Multinodular,
PS 0
Stage D
PS > 2, Child–Pugh C
Associated diseases
No
Liver transplantation
Curative treatments
Yes
RFA
TACE
Sorafenib
Palliative treatments
PS, performance status; TACE, transarterial chemoembolization.
Adapted from Bruix J, Sherman M. HEPATOLOGY, Vol. 53, No. 3, 2011.
Available on: http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/HCCUpdate2010.pdf
Symptomatic
treatment
Treatment algorithm – EASL, EORTC guidelines
HCC
Stage 0
PS 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Stage A–C
PS 0–2, Child–Pugh A–B
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PS 0
Portal pressure/
bilirubin
Increased
Resection
Advanced stage (C)
Portal invasion,
N1, M1, PS 1–2
End stage (D)
3 nodules ≤ 3 cm
1 HCC
Normal
Intermediate stage (B)
Multinodular,
PS 0
Stage D
PS > 2, Child–Pugh C
Associated diseases
No
Liver transplantation
Curative treatments (30%)
5-year survival (40–70%)
Yes
PEI/RFA
TACE
Sorafenib
Target: 20%
Target: 40%
OS: 20 mo (45-14) OS: 11 mo (6-14)
PS, performance status; TACE, transarterial chemoembolization; BSC, Best Supportive Care
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943
Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf.
BSC
Target: 10%
OS: <3 mo
Systemic therapies – EASL, EORTC guidelines
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943
Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf.
Levels of evidence
and grade of recommendation
Levels of
evidence
(NCI)
Sorafenib
1
Chemoembolization
RF (<5 cm),
RF/PEI (<2 cm)
Adjuvant therapy after resection
Resection
LDLT
OLT-Milan
Internal radiation Y90
2
OLT-extended
Neoadjuvant therapy in waiting list
Downstaging
3
External/palliative radiotherapy
C
B
2 (weak)
A
C
B
A
1 (strong)
Grade of recommendation
(GRADE)
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943
Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf
Trial design strategies and
control groups
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943
Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf
Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711