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Clinical Management of Hepatocellular Carcinoma: Current Options

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Clinical Management of Hepatocellular Carcinoma: Current Options Abdel-Naser Elzouki, MBChB, DTM&H, MSc, MD, PhD, FRCP (UK) Professor & Sr. Consultant, Department of ... – PowerPoint PPT presentation

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Title: Clinical Management of Hepatocellular Carcinoma: Current Options


1
Clinical Management of Hepatocellular Carcinoma
Current Options
  • Abdel-Naser Elzouki, MBChB, DTMH, MSc, MD, PhD,
    FRCP (UK)
  • Professor Sr. Consultant, Department of
    Medicine,
  • Hamad Medical corporation, Doha, Qatar
  • Email nelzouki_1999_at_yahoo.com

2
Hepatocellular Carcinoma (HCC) Content
  • Burden of HCC
  • Diagnosis of HCC
  • Staging of HCC
  • Treatment of HCC
  • - Very early / early HCC
  • - Intermediate HCC
  • - Advanced HCC
  • A Look to the future

3
HCC Common and Increasing
  • 694,000 deaths from liver cancer yearly
    worldwide1
  • Age-adjusted US incidence has increased 2-fold
    from 1985-19982
  • - Expected to continue to increase until
    2015-20203
  • American Cancer Society statistics for liver
    cancer in 20104
  • - Estimated new cases 24,120
  • - Estimated deaths 18,910
  • - 5th leading cause of cancer deaths in males

1. GLOBOCAN 2008. 2. SEER stat fact sheets liver
and intrahepatic bile duct. 3. Llovet JM. J
Gastroenterol. 200540225-235. 4. American
Cancer Society. Cancer facts figures 2010.
4
Evolving Guidelines for Clinical Management of
Hepatocellular Carcinoma
www.aasld.org
5
Radiological Diagnosis of Hepatocellular
Carcinoma in Patients With Cirrhosis EASL/AASLD
Guidelines
Imaging techniques contrast-enhanced
US, contrast-enhanced spiral CT and
gadolinium-enhanced MRI Pathognomonic features
wash-in followed by wash-out lt 2 cm
node two concordant contrast imaging
techniques gt 2 cm node one contrast
imaging technique only
Prospective validation 89 patients with a
7-20 mm nodule
CE-USMRI Sensitivity 33.3
Specificity 100
EASL, AASLD JSH Conference, Barcelona 2005
AASLD Practice Guidelines 2007 Forner et al 2008
6
Abdominal tri-phasic spiral CT
Right lobe hepatic focal lesion 5 x 4.5 cm, with
arterial enhancement and wash out in the
porto-venous phase.
7
Ultrasound Diagnosis of Early-stage HCC in
Patients with Cirrhosis. Meta-analysis
Ultrasound alone
Ultrasound AFP
Singal et al Aliment Pharmacol Ther
20093037-47
8
2010 AASLD Algorithm for Investigation of Small
Nodules Found On Screening in Patients with
Cirrhosis
Liver nodule
lt 1 cm
gt 1 cm
4 phase MDCT/dynamic Contrast enhanced MRI
Reapeat US at 3 months
Arterial hypervascularity AND venous or delayed
phase washout
Growing/changing character
Stable
Other contrast enhanced Study (CT or MRI)
No
Yes
Arterial hypervascularity AND venous or delayed
phase washout
Biopsy
HCC
Investigate according to size
Yes
No
Bruix J and Sherman M. AASLD Practice Guidelines
2010 Management of Hepatocellular Carcinoma
www.aasld.org
9
Staging Systems and Treatment Strategies in
Hepatocellular Carcinoma
10
Variables Used in HCC Staging Systems
Marrero JA, et al. Hepatology. 200541707-716.
11
Comparison of HCC Staging Systems
  • BCLC system uses key independent predictors of
    survival
  • Performance score, portal vein thrombosis, tumor
    diameter
  • Compared with other staging systems in cohort
    study
  • BCLC had best stratification of survival across
    all stages
  • BCLC was only system to have independent
    predictive value on survival
  • BCLC is the only staging system that stratifies
    patients into treatment groups

Marrero JA, et al. Hepatology. 200541707-716.
12
The Barcelona Clinic Liver Cancer (BCLC) Staging
Classification for Hepatocellular Carcinoma Is
Endorsed by EASL/AASLD
Performance status
Tumor volume,number and invasiveness
Expected survival
BCLC stage
Child-Pugh
A Very Early/Early B Intermediate C
Advanced D End-stage
0 0 1-2 3-4
Single lt 5 cm or 3 nodes lt 3 cm each
Large/multinodular Vascular invasion
and/or extrahepatic spread Any of the above
A B A B A B C
50-75 at 5 yr 16 months 6 months lt 3
months
13
Therapies used in the management of HCC
  • Surgery
  • - Resection
  • - Liver transplantation
  • Locoregional therapy
  • - Percutaneous ethanol injection
  • - Radiofrequancy thermal ablation
  • - Trans-Arterial Chemo-Emobilisation (TACE)
  • - Trans-Arterial Radio-Emobilisation (TACE)
  • Systemic therapy
  • - Targeted molecular therapy
  • - Symptomatic treatment

14
Treatment of Very Early / Early Stage HCC
15
The Barcelona Clinic Liver Cancer (BCLC) Staging
Classification for Hepatocellular Carcinoma Is
Endorsed by EASL/AASLD
Performance status
Tumor volume,number and invasiveness
Expected survival
BCLC stage
Child-Pugh
A Very Early/Early
0
Single lt 5 cm or 3 nodes lt 3 cm each
A B
50-75 at 5 yr
16
Early Stage Hepatocellular Carcinoma Survival
after Resection Is Influenced by Portal
Hypertension and Bilirubin
  • Best candidates for resection Solitary HCC 5
    cm
  • Child-Pugh A Low portal hypertension
  • Normal bilirubin

Llovet JM et al, Hepatology 1999301434-40
17
Liver Transplantation for HCC Milan Criteria
(Stage 1 and 2)
Up to 3 tumors, none gt 3 cm
Single tumor, not gt 5 cm
Absence of macroscopic vascular
invasion, absence of extrahepatic spread
Strategy to expand criteria include use of
locoregional therapy to downstage patients to
Milan criteria
Ref Mazzaferro V, et al. N Engl J Med.
1996334693-699.
18
Treatment of Early Stage HCC Liver
Transplantation in Cirrhotic Patients Selected by
Milan Criteria

Explanted livers 35 (73) Milan () with 95
survival 13 (27) Milan (?) with 59 survival
4-yr survival
19
Patients with Cirrhosis and a HCC within Milan
Criteria Liver Resection or Transplantation
Hong-Kong, Queen Mary Hosp. Data-base 1995-2004.
Cirrhotics with HCC within Milan criteria 204
resected and 43 transplanted (30 LDLT). 218 (88)
HBsAg pos. 33 (13) 2 or 3 nodules.
Per-Protocol Analysis
ITT Analysis
100
100
Transplantation (n43)
80
80
Resection (n228)
Resection (n204)
60
60
Cumulative survival ()
Cumulative survival ()
Transplantation (n85)
40
40
20
20
p0.017
p0.088
0
0
0
12
24
36
48
60
0
12
24
36
48
60
Months after surgery
Months
Poon RTP et al Ann Surg 200724551-58
20
Treatment of Early HCC the Initial Tumor Volume
Predicts Survival After Percutaneous Ablation
A retrospective study of 282 consecutive patients
with a HCC within Milan criteria treated at BCLC,
Barcelona during a 15-yr period.
Sala M et al Hepatology 2004401352-1360
21
Ablation of HCC
  • Percutaneous ethanol injection (PEI)
  • Cryotherapy
  • Radiofrequency ablation (RFA)

22
Superiority of Resection vs Alcohol Injection in
the Treatment of 2-5 cm HCC A Nationwide Survey
in Japan
Clinical stage 1 solitary node 2-5 cm size
The Liver Cancer Study Group 1988-1996
Arii S et al, Hepatology 2000321224-1229
23
Radiofrequency vs Percutaneous Ethanol Injection
Therapy for Hepatocellular Carcinoma a
Meta-analysis
Mortality rates
Germani G et al J Hepatol 201052380-388
24
(No Transcript)
25
Treatment of Intermediate Stage HCC
26
The Barcelona Clinic Liver Cancer (BCLC) Staging
Classification for Hepatocellular Carcinoma Is
Endorsed by EASL/AASLD
Performance status
Tumor volume,number and invasiveness
Expected survival
BCLC stage
Child-Pugh
A Very Early/Early B Intermediate
0 0
Single lt 5 cm or 3 nodes lt 3 cm each
Large/multinodular
A B A B
50-75 at 5 yr 16 months
27
Treatment of HCC Chemoembolization
  • Normal liver gets 75 of blood supply from portal
    vein and 25 of blood supply from hepatic artery
  • Tumor receives most of its blood supply from the
    hepatic artery
  • Injection into the hepatic artery spares most of
    the normal liver
  • Embolization of the hepatic artery induces
    ischemic necrosis of tumor

Catheter placement for chemoembolization
Tumor
Hepatic artery
Liver
Portal vein
Selective arterial radiotherapy with Y90
microspheres
28
Intermediate HCC The Outcome of
Chemoembolization A Meta-analysis
Bruix J et al, Gastroenterology 2004127S179-88
29
Treatment of Advanced Stage HCC
30
The Barcelona Clinic Liver Cancer (BCLC) Staging
Classification for Hepatocellular Carcinoma Is
Endorsed by EASL/AASLD
Performance status
Tumor volume,number and invasiveness
Expected survival
BCLC stage
Child-Pugh
A Very Early/Early B Intermediate C Advanced
0 0 1-2
Single lt 5 cm or 3 nodes lt 3 cm each
Large/multinodular Vascular invasion
and/or extrahepatic spread
A B A B A B
50-75 at 5 yr 16 months 6 months
31
Levels of Evidence in the Assessment of Benefits
in the Treatment of Advanced HCC
LLovet JM et al JNCI 2008100698-711
32
Randomized Controlled Trials of Sorafenib in
Advanced Hepatocellular Carcinoma
1 Llovet JM et al NEJM 2008359378-390 2 Cheng
A et al Lancet Oncol 20091025-34
33
Treatment of Terminal Stage HCC
34
The Barcelona Clinic Liver Cancer (BCLC) Staging
Classification for Hepatocellular Carcinoma Is
Endorsed by EASL/AASLD
Performance status
Tumor volume,number and invasiveness
Expected survival
BCLC stage
Child-Pugh
A Very Early/Early B Intermediate C
Advanced D End-stage
0 0 1-2 3-4
Single lt 5 cm or 3 nodes lt 3 cm each
Large/multinodular Vascular invasion
and/or extrahepatic spread Any of the above
A B A B A B C
50-75 at 5 yr 16 months 6 months lt 3
months
35
Tailoring Treatment According to the Clinical
Stage of HCC
HCC
Very early stage (0)
Early stage (A)
Intermediate stage (B)
Advanced stage (C)
Terminal stage (D)
Single HCC
3 nodules 3cm
Portal pressure bilirubin
Associated diseases
Increased
Normal
Yes
No
PEI/RF
Liver transplantation
Resection
Chemoembolization
Sorafenib
RCTs (50-60) Median survival untreated 6-16
months
Symptomatic treatment (10) Survival lt3 months
Curative treatments (30) 5-year survival 5070
Adapted from Bruix J and Llovet JM, Lancet
2009373614616
36
A Look To The Future
37
Molecular Therapies Under Evaluation for HCC in
Phase III (2011)
NEGATIVE ASCO 2010
HALTED 2010
38
Conclusion
  • Burden of HCC is increasing
  • Requirements for diagnosis depends on patient
    characteristics and tumor characteristics
  • BCLC staging system recommended by US and
  • European guidelines
  • BCLC system provides framework for selection of
    treatment
  • Many studies ongoing for treatment of HCC

39
(No Transcript)
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