Transcript Advanced stage HCC Management

HCC Guidelines and recommendation
2012
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
Diagnostic algorithm
New mass/nodule
Ø < 1cm
Ø ≥1cm
US 3 months
TC/RM/CEUS
Growing Ø
NO
Typical feature
(wash in/wash out)
Sì
Sì
NO
US 3 months
(for 12 months)
Growing Ø
Other contrast
enhanced technique
Sì
NO
Atypical feature
US 6 months
Biopsy
No diagnosis
Typical feature
Other diagnosis
HCC
Raccomandazioni AISF per la gestione integrata del paziente con Epatocarcinoma; published on www.webaisf.org
Available on: http://www.webaisf.org/media/16110/raccomandazioni-aisf-per-hcc.pdf Accessed on 30-March 2012
US, Ultrasound
Clinical presentation
• Inadequate
hepatic reserve
• Tumor location
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:
• 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
Unresectable
Extensive liver
disease
Surveillance
•
•
•
•
•
(Child–Pugh Class A [category 1] or B)
Chemotherapy + RT only in the context of a clinical trial
Locoregional therapy
RT (conformal or stereotactic) (category 2B)
Supportive care
Systemic or intra-arterial chemotherapy in clinical trial
Options:
• Sorafenib
Inoperable by perfomance
status or comorbidity, local
disease or local disease with
minimal extrahepatic disease
only
Metastatic
disease
•
•
•
•
(Child–Pugh Class A [category 1] or B)
Clinical trial
Locoregional therapy
RT (conformal or stereotactic) (category 2B)
Supportive care
• Sorafenib
(Child–Pugh Class A [category 1] or B)
• Supportive care
• Clinical trial
NCCN Clinical Practice Guidelines in Oncology. Hepatobiliary Cancer. V2.2012; Available from: www.nccn.org Accessed on 30-March 2012
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
Tumor > 5 cm
> 3 tumors
Invasion of hepatic / portal vein branches
Child–Pugh A/B
TACE
Child–Pugh C
Supportive care
APASL recommendations on HCC, Omata M, et al. Hepatol Int. 2010;4:439–474
Consensus-based treatment algorithm for HCC
proposed by 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
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
Sorafenib*5
(TACE refractory,child-pugh A)
Kudo et al. Dig Dis 2011;29:339–364
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
Symptomatic
treatment
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
HCC 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
Levels of evidence
and grade of raccomandation
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
Algorithm for resection in HCC patients
Cirrhotic: patient
eligible for liver
resection
MELD score
9 - 10
<9
>10
Serum sodium level
≥ 140 mEq/L
Major
hepatectomy
(up to 4
segment)
Segmentectomy or
bisegmentectomy
< 140 mEq/L
Segmentectomy or
limited resection
Raccomandazioni AISF per la gestione integrata del paziente con Epatocarcinoma; published on www.webaisf.org
Available on: http://www.webaisf.org/media/16110/raccomandazioni-aisf-per-hcc.pdf Accessed on 30-March 2012
Risk of
IPLF>15% in
all types of
hepatectomy
Treatment algorithm for the repetition of TACE in
intermediate stage HCC patients
TACE candidate
No portal vein thrombosis (accepted segmental thrombosis)
No extra-epatic spread; Child Pugh A or B7
cTACE or DEB-TACE
CR ***
Liver deterioration,
major complication*
MRI or CT **
(at 1 month)
No
cTACE or DEB-TACE
Resolution
BSC
MRI or CT
Every 3 months
MRI or CT **
(at 1 month)
Relapse***
Sì
Progression Disease (PD) ***
or Stable Disease(SD) ***
PR ***
New nodule
Consider other treatment
(cTACE or DEB-TACE)
Growth of target
nodule or SD***
Consider
SORAFENIB
* : each TACE; ** : with cTACE, MRI is preferred to CT
*** : Response must be assessed by modified RECIST criteria [CR: Complete Response; PR: Partial Response; SD: Stable Disease; PD: Progression Disease].
Raccomandazioni AISF per la gestione integrata del paziente con Epatocarcinoma; published on www.webaisf.org
Available on: http://www.webaisf.org/media/16110/raccomandazioni-aisf-per-hcc.pdf Accessed on 30-March 2012
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