HEPATOCELLULAR CARCINOMA Manal Abdel Hamid Associate Prof. Of medical oncology

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HEPATOCELLULAR CARCINOMAManal Abdel
HamidAssociate Prof. Of medical oncology
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Epidemiology

• Hepatocellular carcinoma is the 5th most common
  malignancy worldwide the 3rd cause of cancer
  related death with male-to-female ratio
• 51 in Asia
• 21 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.

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Incidence of HCC
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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

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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.
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Signs symptoms

• Nonspecific symptoms
• abdominal pain
• Fever, chills
• anorexia, weight loss
• jaundice
• Physical findings
• abdominal mass in one third
• splenomegaly
• ascites
• abdominal tenderness

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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.

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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
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Diagnosis

• (b) what investigations are required to make a
  definite diagnosis
• AFP produced by 70 of HCC
• gt 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

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Diagnosis

• 3) Biopsy is rarely required for diagnosis
  in
  13.
• Biopsy of potentially operable lesions should be
  avoided where possible

seeding
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Diagnosis
Cirrhosis Mass gt 2 cm
Normal AFP
Raised AFP
Confirmrd diagnosis
CT, MRI
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Diagnosis
Cirrhosis Mass lt 2 cm
Normal AFP
Raised AFP
CT, MRI
Assess for surgery
lesion by exam
FNAC or biopsy
Confirmed diagnosis
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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.

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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.

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Treatment (Surgery)

• Recurrence rates of 5060 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

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Treatment (non-Surgical)

• should only be used where surgical therapy is not
  possible.
• 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
• 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

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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)

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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 didnt 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)

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Targeted therapy for HCC
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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
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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

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Investigational combination therapies in HCC

• Combinations under investigations
• Bevacizumzb erlotinib
• Sorafenib erlotinib
• Combination therapy will likely be used to treat
  HCC in the future

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HCC (Whats ahead?)

• Combinations therapy
• Bevacizumzb or Sorafenib Erlotinib
• Sorafenib mTOR inhibitor
• Early sequential therapies

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