Transcript Hepatocellular Carcinoma

HEPATOCELLULAR CARCINOMA
Manal Abdel Hamid
Associate Prof. Of medical oncology
Epidemiology
Hepatocellular carcinoma is the 5th most common malignancy
worldwide & the 3rd cause of cancer related death with male-tofemale ratio
– 5:1 in Asia
– 2:1 in the United States
Tumor incidence varies significantly, depending on geographical
location.
HCC
with age.
– 53 years in Asia
– 67 years in the United States.
Incidence of HCC
Etiology
• Hepatitis B
-increase risk 100 -200 fold
- 90% of HCC are positive for (HBs Ag)
• Hepatitis C
• Cirrhosis
- 70% of HCC arise on top of cirrhosis
• Toxins
-Alcohol
-Tobacco
- Aflatoxins
• Autoimmune hepatitis
• States of insulin resistance- Overweight in males
Diabetes mellitus
Incidence according to etiology
Abbreviations: WD, Wilson′s disease; PBC, primary biliary cirrhosis, HH,
hemochromatosis; HBV, hepatitis B virus infection; HCV, hepatitis C virus infection.
hereditary
Signs & symptoms
 Nonspecific symptoms
–
–
–
–
abdominal pain
Fever, chills
anorexia, weight loss
jaundice
 Physical findings
–
–
–
–
abdominal mass in one third
splenomegaly
ascites
abdominal tenderness
Guidlines
(a) which patients are at high risk for the development
of HCC and should be offered surveillance
(b) what investigations are required to make a definite
diagnosis
(c) which treatment modality is most appropriate in a
given clinical context.
Guidlines
(a) which patients are at high risk for the development of HCC &
should be offered surveillance
- M &F with established cirrhosis due to HBV and/ or HCV, particularly
those with ongoing viral replication
- M &F with established cirrhosis due to genetic haemochromatosis
- M with alcohol related cirrhosis who are abstinent from alcohol or likely to
comply with treatment
- M with primary biliary cirrhosis
Abdominal US and AFP/ 6 months
Diagnosis
(b) what investigations are required to make a
definite diagnosis
1)
2)
AFP produced by 70% of HCC
> 400ng/ml
AFP over time
Imaging
- focal lesion in the liver of a patient with cirrhosis is highly likely to
be HCC
- Spiral CT of the liver
- MRI with contrast enhancement
Diagnosis
3) Biopsy is rarely required for diagnosis
seeding
in 1–3%.
Biopsy of potentially operable lesions should
be avoided where possible
Diagnosis
Cirrhosis +
Mass > 2 cm
Raised
AFP
Normal
AFP
Confirmrd
diagnosis
CT, MRI
Diagnosis
Cirrhosis + Mass < 2 cm
Normal AFP
Raised
AFP
CT, MRI
Assess for
surgery
lesion by exam
Confirmed
diagnosis
FNAC or biopsy
Treatment (Surgery)
 The only proven potentially curative therapy for HCC
 Hepatic resection or liver transplantation
 Patients with single small HCC (≤5 cm) or up to three lesions ≤3
cm
 Involvement of large vessels (portal vein, Inferior vena cava)
doesnt automatically mitigate against a resection; especially in
fibrolamellar histology
 No randomised controlled trials comparing the outcome of
surgical resection and liver transplantation for HCC.
Treatment (Surgery)
 Hepatic resection should be considered in HCC and a non-
cirrhotic liver (including fibrolamellar variant)
 Resection can be carried out in highly selected patients with
cirrhosis and well preserved hepatic function (Child-Pugh A) who
are unsuitable for liver transplantation. It carries a high risk of
postoperative decompensation.
 Perioperative mortality in experienced centres remains between
6% and 20% depending on the extent of the resection and the
severity of preoperative liver impairment.
 The majority of early mortality is due to liver failure.
Treatment (Surgery)
 Recurrence rates of 50–60% after 5 years after resection are
usual (intrahepatic)
 Liver transplantation should be considered in any patient with
cirrhosis
 Patients with replicating HBV/ HCV had a worse outlook due to
recurrence and were previously not considered candidates for
transplantation.
 Effective antiviral therapy is now available and patients with small
HCC, should be assessed for transplantation
Treatment (non-Surgical)
should only be used where surgical therapy is not
possible.
1) Percutaneous ethanol injection (PEI)
• has been shown to produce necrosis of small HCC.
• It is best suited to peripheral lesions, less than 3 cm in
diameter
2) Radiofrequency ablation (RFA)
• High frequency ultrasound to generate heat
• good alternative ablative therapy
• No survival advantage
• Useful for tumor control in patients awaiting liver transplant
Treatment (non-Surgical)
3) Cryotherapy
•
intraoperatively to ablate small solitary tumors outside a
planned resection in patients with bilobar disease
4) Chemoembolisation
•
Concurrent administration of hepatic arterial chemotherapy
(doxirubicin) with embolization of hepatic artery
•
Produce tumour necrosis in 50% of patients
•
Effective therapy for pain or bleeding from HCC
•
Affect survival in highly selected patients with good liver
reserve
Complications: (pain, fever and hepatic decompensation)
•
Treatment (non-Surgical)
5) Systemic chemotherapy
– very limited role in the treatment of HCC with poor esponse
rate
– Best single agent is doxorubicin (RR: 10- 20%)
– Combination chemotherapy didn’t
response but
survival
– should only be offered in the context of clinical trials
6) Hormonal therapy
-
Nolvadex, stilbestrol and flutamide
7) Interferon-alfa
8) retinoids and adaptive immunotherapy (adjuvant)
Targeted therapy for HCC
Selection of agents for targeted therapy
in HCC
Name
Target
Gefitinib
Erlotinib
Lapatanib
Cetuximab
Bevacizumab
Sorafenib (Nexavar)
Sunitinib
Vatalanib
Cediranib
Rapamycin
Everolimus
Bortezomib (Velcade)
EGFR
EGFR
EGFR
EGFR
VEGF
Raf1, B-Raf, VEGFR , PDGFR
PDGFR, VEGFR, c-KIT, FLT-3
VEGFR, PDGFR, c-KIT
VEGFR
mTOR (mammalian target of rapamycin)
mTOR
Proteasome
Targeting angiogenesis for HCC
 HCC is one of the most vascular tumor
 Major driver of angiogenesis is vascular endothelial growth
factor (VEGF)
 Sorafenib and bevacezumab target VEGF in HCC
•
Bevacizumzb: Median OS of approximately 12 months
•
Bevacizumab + erlotinib: Medain OS 15-17 months
Investigational combination therapies in
HCC
 Combinations under investigations
–
–
Bevacizumzb + erlotinib
Sorafenib +erlotinib
 Combination therapy will likely be used to treat
HCC in the future
HCC (Whats ahead?)
 Combinations therapy
•
•
Bevacizumzb or Sorafenib + Erlotinib
Sorafenib + mTOR inhibitor
 Early sequential therapies