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-to-
female 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, hereditary
hemochromatosis; HBV, hepatitis B virus infection; HCV, hepatitis C virus infection.
 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) AFP produced by 70% of HCC

> 400ng/ml
AFP over time

2) 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 Normal
AFP AFP

Confirmrd CT, MRI

diagnosis
 Diagnosis
Cirrhosis + Mass < 2 cm

Raised Normal AFP

AFP

CT, MRI

Assess for
surgery lesion by exam

Confirmed FNAC or biopsy

diagnosis
 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 EGFR
Erlotinib EGFR
Lapatanib EGFR
Cetuximab EGFR
Bevacizumab VEGF
Sorafenib (Nexavar) Raf1, B-Raf, VEGFR , PDGFR
Sunitinib PDGFR, VEGFR, c-KIT, FLT-3
Vatalanib VEGFR, PDGFR, c-KIT
Cediranib VEGFR
Rapamycin mTOR (mammalian target of rapamycin)
Everolimus mTOR
Bortezomib (Velcade) 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