il carcinoma epatocellulare
TRANSCRIPT
IL CARCINOMA EPATOCELLULARE
Paolo Caraceni
III Workshop Nazionale
Terapie Innovative delle Epatiti Virali Croniche
Firenze, 14-15 Gennaio 2013
Patients with hepatocellular carcinoma (HCC) should be managed with a
multidisciplinary approach framed in a network where all the diagnostic techniques
and therapeutic resources are available in order to provide the optimal level of care.
Given this assumption as the pre-requisite to adequately approach all patients with
known or suspected HCC, the following recommendations of the Italian Association for
the Study of the Liver (AISF) aim at providing:
1. homogeneous and efficacious diagnostic and staging work-up
2. the best treatment choice tailored to patient status and tumor stage at diagnosis.
Position Paper AISF
The Multidisciplinary Approach to HCC
Dig Liv Dis, 2013 in press
• Surveillance
• Recall procedures
• Staging
• Treatments - Surgical
- Ablation techniques
- Transcatheter arterial techniques
- Systemic
- Adjuvant
- Combined
Position Paper
The Multidisciplinary Approach to HCC
Adjuvant therapy after resection
OLT-extended
Neoadjuvant therapy in waiting list
LDLT
Downstaging
Internal radiation Y90
Resection
Levels of
evidence
(NCI)
Grade of recommendation
(GRADE)
1
2
3
2 (weak) 1 (strong)
RF (<5 cm),
RF/PEI (<2 cm)
Chemoembolization
External/palliative radiotherapy
Sorafenib
A C B A C B
OLT-Milan
Levels of evidence and grade of recommendation
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
Patients candidates to surveillance
• Cirrhotic patients, Child-Pugh class A and B (2b,B)
• Cirrhotic patients, Child-Pugh class C awaiting liver transplantation (5,D)
• Non cirrhotic patients with chronic hepatitis B or inactive hepatitis B carriers with
viremia > 2000 UI/ml (3b,B for Western patients; 1b, A for Oriental patients)
• Non cirrhotic patients with chronic hepatitis C and liver fibrosis ≥ F3 Metavir (o ≥10
Kpa at transient elastography [Fibroscan®]) (5,D for Western patients; 3b,B for
Oriental patients
• Patients with chronic HCV and HBV hepatitis successfully treated (negative viremia),
but corresponding in any of the previous categories at risk prior to starting antiviral
treatment (5,D)
Surveillance is recommended for all the above patients if they do not have
contraindications to radical or effective palliative treatments.
Baseline HBV-DNA level and
risk of HCC in chronic hepatitis B
<10˙000 c/mL
1˙000˙000 c/mL
>1˙000˙000 c/mL
100˙000 c/mL
At entry:
- HBeAg neg.
- Normal ALT
- No cirrhosis
HBV-DNA (c/mL) Annual incidence of HCC (%)
<10,000 0.11
10,000-99,9999 0.29
100,0000-999,9999 0.96
≥1 Million 1.15
HCC risk in non-cirrhotic populations
Masuzaki et al., Hepatology 2009
Liver stiffness
(kPa)
Hazard Ratio Annual incidence
of HCC (%)
≤10 1 0.1
10.1 - 15 16.7 2.9
15.1 – 20 20.9 5.0
20.1 – 25 25.6 8.3
>25 45.5 14.4
Cirrhosis: 15-17 kPa
Prospective study with elastography (Fibroscan) 866 patients anti-HCV+
Patients at risk of HCC development should be enrolled in surveillance programs for early
tumor detection (1a-A). Candidates to liver transplantation should be screened regardless of the
Child-Pugh class, in order to detect tumors exceeding conventional criteria and modify priority
in the waiting list (5-D).
Surveillance should be based on periodic liver ultrasound (2a-B) performed by an experienced
operator (5-D). In the presence of conditions clearly limiting the accuracy of ultrasound, CT scan
or MRI may be proposed as supplementary imaging techniques (5-D). In patients awaiting liver
transplantation and presenting a coarse liver echo-pattern, surveillance should be carried out
with CT or MRI (5-D).
The measurement of alpha-fetoprotein is not indicated as a surveillance tool as its use, alone or in
combination with ultrasound, does not improve the cost/efficacy ratio of surveillance (2b-B).
A surveillance interval of 6 months is recommended (2a-B). Shortening the interval to 3 months,
even in patients at higher risk of developing HCC (5-D), is not associated with any prognostic
improvement and may worsen the cost/efficacy ratio of surveillance (1b-A).
Position Paper
The Multidisciplinary Approach to HCC
* One imaging technique only recommended in centers of excellence with high-end radiological equipment.
** HCC radiological hallmark: arterial hypervascularity and venous/late phase washout
Mass/nodule on US
< 1 cm 1-2 cm > 2 cm
4-phase CT or Dynamic
Contrast enhanced MRI
4-phase CT/Dynamic
Contrast enhanced MRI
Repeat US at 4 mo
Growing/Changing
Character Stable
1 or 2 positive techniques*:
HCC radiological Hallmarks**
1 positive technique:
HCC radiological Hallmarks**
Yes No
HCC Biopsy
Investigate
according to size
Inconclusive
Yes No
HCC Biopsy
Diagnostic recall policy
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
Aspetto tipico (wash-in e wash-out)
Nuovo nodulo in cirrosi
NO Sì
Altra metodica contrastografica
Aspetto atipico Aspetto tipico
Biopsia
Aumento (Ø > 1 cm)
NO Sì
Ecografia/3 mesi
Ø < 1 cm
TC, RM, CEUS
Ø > 1 cm
Aumento (Ø > 1 cm)
Ecografia/3 mesi (per 12 mesi)
NO
Ecografia/6 mesi
Sì
Altra diagnosi
HCC
Non diagnostica
Algoritmo diagnostico: politica del richiamo
Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACE Resection
Curative treatments (30%)
5-year survival (40–70%)
Target: 20%
OS: 20 mo (45-14)
Associated diseases
Yes No
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Target: 40%
OS: 11 mo (6-14)
Best supportive
care
Target: 10%
OS: <3 mo
BCLC staging system
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
The BCLC is the only staging system that proposes a therapeutic algorithm for
HCC. However, the AISF expert panel points out that BCLC treatment allocation
should be considered as a general frame indicating the most beneficial treatment
option available for the group of patients included in each stage of the disease.
The definitive therapeutic choice should be personalized at the individual level,
taking into account several clinical variables and regional organizational setting
that may lead to combined/sequential treatments (5-D). Inclusion of patients into
therapeutic trials is suggested in the case of contra-indications to conventional
treatment or treatment failures (5-D).
Position Paper
The Multidisciplinary Approach to HCC
Performance Status
(Eastern Cooperative Oncology Group)
Grade ECOG
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry
out work of a light or sedentary nature, e.g., light house work, office work
2 Ambulatory and capable of all selfcare but unable to carry out any work
activities. Up and about more than 50% of waking hours
3 Capable of only limited selfcare, confined to bed or chair more than 50% of
waking hours
4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or
chair
5 Dead
Oken, et al., Am J Clin Oncol 5:649-655, 1982
Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACE Resection
Curative treatments (30%)
5-year survival (40–70%)
Target: 20%
OS: 20 mo (45-14)
Associated diseases
Yes No
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Target: 40%
OS: 11 mo (6-14)
Best supportive
care
Target: 10%
OS: <3 mo
BCLC staging system
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
PST 0-1
Paz. 58 aa, Child-Pugh A, PS 0, 2 noduli HCC (3.6 cm e 2.7 cm), no invasione portale,
N 0, M 0, senza comorbilità.
Sorafenib
BCLC staging system
Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACE Resection
Curative treatments (30%)
5-year survival (40–70%)
Target: 20%
OS: 20 mo (45-14)
Associated diseases
Yes No
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Target: 40%
OS: 11 mo (6-14)
Best supportive
care
Target: 10%
OS: <3 mo
BCLC staging system
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
RF results in Child-Pugh A patients
with a single HCC 2 cm
Livraghi et al., Hepatology 2008
Mortality 0
Major complications 1.8%
(1 seeding case)
Complete radiological necrosis
- 1st course 86%
- 2nd course 12%
- Total 98%
Sustained complete response 97%
(median follow-up 31 mo)
Treatment failure 3%
232 pts
218 pts
6 pts (2.6%)
unfeasibility
Survival of patients with single HCC <2 cm
treated by ablation
Analysis by surgical candidacy (100 vs 118)
Livraghi et al., Hepatology 2008
Results of RFand resection in patients with
very early HCC (single <2 cm)
Propensity analysis (resection 52 vs RF 9152)
Wang JH et al., J Hepatol 2012
One-to-one near-neighbor matching for:
sex, age, HBsAg, anti-HCV, platelet, Child-Pugh, AFP, ALT, BMI, hypertension, diabetes.
• Negligible mortality
• Lower liver mutilation
• Lower costs
• Shorter hospital stay
• Easy repeatibility
Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACE Resection
Curative treatments (30%)
5-year survival (40–70%)
Target: 20%
OS: 20 mo (45-14)
Associated diseases
Yes No
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Target: 40%
OS: 11 mo (6-14)
Best supportive
care
Target: 10%
OS: <3 mo
BCLC staging system
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
Ishizawa et al., Gastro 2008
CPA = Child Pugh Class A; CPB = Child Pugh Class B; PHT = Portal Hypertension
Resection for HCC Single nodule vs Multiple nodules
MELD score
9 - 10
Serum sodium level
Cirrhotic patients eligible
for liver resection
≥ 140 mEq/L < 140 mEq/L
Segmentectomy
or
bisegmentectomy
Segmentectomy
or limited
resection
Major
hepatectomy
(up to 4 segments)
Risk of
IPLF>15% in
all types of
hepatectomy
> 10 < 9
0 - 3.3% 0 - 2.5% 0 Mortality
Simple algorithm based on pre-operative variables to determine the
extent of safe hepatectomy in cirrhotic patients with HCC
Cescon et al., Arch Surg 2009
For patients with solitary HCC and preserved liver function without evidence of portal
hypertension, liver resection is a first choice treatment. This is particularly true for HCC 2-5 cm,
whereas for smaller HCC (< 2 cm) the clinical outcome of surgery is comparable to
radiofrequency thermal ablation (RFTA) if this can be safely and effectively performed. As the
only available radical treatment for single HCC > 5 cm is surgical resection, the feasibility of this
option should be always assessed also in these patients, preferably in a multidisciplinary setting
(3b-B).
In the presence of portal hypertension, hyperbilirubinemia, multinodularity, patients must be
evaluated by a multidisciplinary team with great expertise, and the surgical option must be
accurately weighed against the risk of decompensation after surgery (4-C).
Position Paper
The Multidisciplinary Approach to HCC
For HCC 2 cm, in the setting of a multi-disciplinary evaluation, RFTA can be considered the
first-line treatment when performed in expert centers (3b-B).
For HCC of 2.1-3 cm, the choice between surgery and RFTA should be made on a case-by-case
after a multi-disciplinary evaluation (5-D)
Patients with nodules > 3 cm should be treated with surgery, when feasible (5-D).
In case of failure of percutaneous ablation, patients should be reassessed by a multidisciplinary
team for the most appropriate treatment modality, at first considering surgery if feasible.
When technically feasible, RFTA should be preferred to PEI due to better efficacy and
predictability of treatment result (2a-B).
In non-resectable cases where RFTA is not feasible (due to insufficient ultrasound visibility or
proximity to hollow organs or coagulopathy), video-laparoscopic RFTA, performed in expert
centers, should be considered (5-D).
Position Paper
The Multidisciplinary Approach to HCC
Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACE Resection
Curative treatments (30%)
5-year survival (40–70%)
Target: 20%
OS: 20 mo (45-14)
Associated diseases
Yes No
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Target: 40%
OS: 11 mo (6-14)
Best supportive
care
Target: 10%
OS: <3 mo
BCLC staging system
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
Mazzaferro et al., Lancet Oncol 2009
1556 pts. from 36 centres (1122 Milano-out at pathology examination)
5-year overall-survival
Liver transplantation for HCC outside Milan criteria
1 5 15 10 85 20 25 30 35 50 45 40 55 60 65 75 70 80
Size of the largest tumor (mm)
Down-staging:
5.1-6 cm
3.1-5 cm “Milano-in” after down-staging
≤ 4 cm each, sum Ø 12 cm
0
20
40
60
80
100
0 12 24 36
Actu
aria
l su
rviv
al
(%)
Milano-in Down-staging
Post-Tx (88 vs 32 pts)
0
20
40
60
80
100
0 12 24 36
Actu
aria
l su
rv
iva
l (%
)
Milano-in Down-staging
Intention-to-treat (129 vs 48 pts)
Ravaioli et al., Am J Transplant 2008
Liver transplantation for HCC outside Milan criteria
Down-staging: Bologna criteria
Down-staging:
8 cm
5 cm each, sum Ø 8 cm
≤ 3 cm each, sum Ø 12 cm
Yao et al., Hepatology 2008
Inizio down-staging
Liver transplantation for HCC outside Milan criteria
Down-staging: UCSF criteria
LT is a well established treatment for HCC patients, and the Milan criteria represent the
benchmark for patient selection (1a-A).
LT listing should be considered even in patients with intermediate stage HCC (BCLC B) slightly
beyond Milan criteria. These patients should be (re)-evaluated at transplant centers adopting
"expanded criteria" or "down-staging" protocols (4-C). Tumor vascular invasion and metastases
always are absolute contraindications to LT (4-C). Due to the limited accuracy of the available
indicators of recurrence, patients with non conventional criteria should be considered eligible for
LT only in centers with well-established interventional algorithms or in the context of clinical
trials (5-D).
Position Paper
The Multidisciplinary Approach to HCC
Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACE Resection
Curative treatments (30%)
5-year survival (40–70%)
Target: 20%
OS: 20 mo (45-14)
Associated diseases
Yes No
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Target: 40%
OS: 11 mo (6-14)
Best supportive
care
Target: 10%
OS: <3 mo
BCLC staging system
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
Recommendation Contraindications and
specifications
BCLC stage B pts not eligible for surgery or ablation (1a-A).
Best candidates are asymptomatic (PS 0) Child-Pugh class A pts (1b-A);
Child-Pugh score of B7 or PS 1 can be considered (5-D)
Jaundice, untreatable
ascites, portal or main
branch thrombosis and
HCC >10 cm
TACE can be utilized in pts with early stage HCC if surgical or ablative
techniques are not applicable (technical reasons and/or comorbidities)
TACE should be performed with a selective or super-selective
(segmental or sub-segmental) technique to optimize risk/benefit ratio and
increase likelihood of complete response (2b-B)
For bi-lobar HCCs not
treatable with a super-
selective approach,
treating a single lobe per
session should be
considered (5-D)
Peripheral, segmental or intra-tumoral thrombosis is not an absolute
contraindication to TACE, and should be used in association with a
systemic treatment (5-D)
Should be considered in
the frame of controlled
clinical studies
Position Paper
The Multidisciplinary Approach to HCC
Prognostic power of the response to TACE
according to the criteria utilized
EASL1 RECIST1 mRECIST1
Survival similar with EASL and mRECIST, and better in pts. with an overall
response, assessed at an early time point (median 64 days)1:
Responder Non-responders P
• EASL: 22.0 months 12.7 months 0.019
• mRECIST: 20.7 months 13.3 months 0.009
• RECIST 1.1: 12.4 months 16.8 months n.s
1. Shim et al. Radiology 2012;262(2):708-18; 2. Llovet JM, Ducreux M, et al. J Hepatol. 2012;56:908-943
Response to TACE should be evaluated using the modified RECIST criteria (5-D).
Results of conventional TACE should be preferentially evaluated using MRI if available (4-C),
while CT and MRI are equivalent in evaluating results of DEB-TACE (5-D). CEUS can be used
to ascertain disease persistence in patients in which the targets are one or two lesions.
The first radiologic assessment of TACE results should be performed at 1 month, and thereafter
repeated at 3-4 month intervals (5-D).
Position Paper
The Multidisciplinary Approach to HCC
Proposed algorithm for TACE
Second TACE
New lesion Growth of
existing lesion
Raoul J-L et al. Cancer Treat Rev 2011;37:212–20
No PVT
No EHS
Child-Pugh A or
B7
First TACE
CT or MRI
CT or MRI
Liver deterioration or
major complications
Disease control
(CR or PR or SD)
Disease
progression
Follow-up /
3 months
Consider retreatment
with TACE
Consider
Sorafenib
Patient / disease characteristics
Acceptable?
Acceptable?
Why?
HCC CANDIDATO A TACE - No trombosi portale (ammessa trombosi di ramo segmentario)
- No malattia extraepatica
- Classe di Child Pugh A o B7
Deterioramento epatico,
complicazioni maggiori * CR ***
RM o TC
trimestrale
Recidiva di malattia *** PR ***
Risoluzione No
Palliazione Sì
Progressione di malattia
(DP) o non risposta al
trattamento (SD) ***
Nuova
lesione
Crescita lesioni
trattate o SD***
Considera
SORAFENIB
Considera nuovo trattamento
(cTACE o DEB-TACE)
Trattamento cTACE o DEB-TACE
RM o TC
(dopo 1 mese)
Trattamento cTACE o DEB-TACE
RM o TC
(dopo 1 mese)
Position Paper
The Multidisciplinary Approach to HCC
Per-nodule response rate to 1st TACE
Role of tumour size
• Retrospective cohort study: 271 patients eligible to TACE with 635 treated nodules
• cTACE* performed ‘on demand’ upon demonstration of viable tumour (non-CR)
• Tumour assessment according to mRECIST (after 1 month and then every 3–4 months)
• Mean follow-up: 12 months (range 1-51)
Golfieri R et al. submitted for publication
≤2 cm (N=386) 2.1-5 cm (N=211) >5 cm (N=36)
N. nodes % N. nodes % N. nodes %
Tumour response
CR 263 68 134 64 9 25
PR 123 32 77 36 27 75
Local Recurrence Rate 52 20 36 27 6 57
Only 25% of large (>5 cm) nodules achieve CR and, in these nodules,
local relapse is very frequent.
Wang W et al., Liver International 2010; 30: 741-749
Survival
1 year: 512 pts → OR = 3.26 (95% CI = 1.23-8.69)
2 years: 437 pts → OR = 4.53 (95% CI = 2.62-7.82)
3 years: 425 pts → OR = 3.50 (95% CI = 1.75-7.02)
Comparison Trials
• TACE + PEI vs. TACE 4
• TACE + RF vs. RF 2
• TACE + PEI vs. PEI 1
• TACE + RF vs. TACE 1
• TACE + PEI vs. TACE o PEI 1
• TACE + RF vs. TACE o RF 1
Recurrence rate
Combined locoregional treatments
In non-surgical cases, a combined/sequential approach (TACE plus PEI, RFTA, or
microwave ablation) should be considered, on an individual basis, for multinodular
HCCs and for each nodule >3 cm, after a multidisciplinary assessment (2b-B).
Position Paper
The Multidisciplinary Approach to HCC
Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACE Resection
Curative treatments (30%)
5-year survival (40–70%)
Target: 20%
OS: 20 mo (45-14)
Associated diseases
Yes No
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Target: 40%
OS: 11 mo (6-14)
Best supportive
care
Target: 10%
OS: <3 mo
BCLC staging system
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012 ;56 :908-43
n = 107
n = 245
n = 150
n = 45
n = 183
Sorafenib ASIA-PACIFIC (Cheng, Lancet Oncol. 2009)
Sorafenib SHARP (Llovet, NEJM. 2009)
TARE (Sangro, Hepatology. 2011)
TARE EHD+ (Salem, Gastro. 2011)
TARE EHD– (Salem, Gastro. 2011)
Sangro B, et al. J Hepatol 2012; 56:464-73
Advanced stage
Radioembolization for HCC
Position Paper
The Multidisciplinary Approach to HCC
Systemic chemotherapy with conventional agents, octreotide, interferon, tamoxifen, and anti-
androgenic drugs has no role in HCC treatment (1b-A).
Full dose sorafenib is the recommended treatment for HCC patients with preserved liver function
who are not amenable to surgery and loco-regional treatments or in whom TACE failed,
according to the Italian National Health Service rules (1b-A). In patients intolerant to full dose
sorafenib, the tolerance to a reduced dose (400 mg/day) is to be pursued before definitively
suspending the treatment (2b-B).
TARE may be indicated in patients with large masses and/or portal thrombosis/invasion, but it
should be utilized in the context of prospective studies aimed at ascertaining its cost-effectiveness
profile (5, D).
www.webaisf.org, March 2013
Raccomandazioni AISF per la gestione integrata
del paziente con epatocarcinoma
11th AISF PRE-MEETING
THE MULTIDISCIPLINARY APPROACH TO THE
TREATMENT OF HEPATOCELLULAR CARCINOMA
Roma, February 20, 2013