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 .

Aflatoxins • Autoimmune hepatitis • States of insulin resistance.70% of HCC arise on top of cirrhosis • Toxins -Alcohol -Tobacco .Overweight in males Diabetes mellitus .90% of HCC are positive for (HBs Ag) • Hepatitis C • Cirrhosis .Etiology • Hepatitis B -increase risk 100 -200 fold .

hemochromatosis. hepatitis B virus infection. HH. PBC. hepatitis C virus infection. HBV. HCV. primary biliary cirrhosis.Incidence according to etiology Abbreviations: WD. hereditary . Wilson′s disease.

chills anorexia. weight loss jaundice  Physical findings – – – – abdominal mass in one third splenomegaly ascites abdominal tenderness .Signs & symptoms  Nonspecific symptoms – – – – abdominal pain Fever.

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. .

M with primary biliary cirrhosis Abdominal US and AFP/ 6 months .M &F with established cirrhosis due to genetic haemochromatosis .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.M with alcohol related cirrhosis who are abstinent from alcohol or likely to comply with treatment . particularly those with ongoing viral replication .

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 .MRI with contrast enhancement .Spiral CT of the liver .focal lesion in the liver of a patient with cirrhosis is highly likely to be HCC .

Diagnosis 3) Biopsy is rarely required for diagnosis seeding in 1–3%. Biopsy of potentially operable lesions should be avoided where possible .

MRI .Diagnosis Cirrhosis + Mass > 2 cm Raised AFP Normal AFP Confirmrd diagnosis CT.

MRI Assess for surgery lesion by exam Confirmed diagnosis FNAC or biopsy .Diagnosis Cirrhosis + Mass < 2 cm Raised AFP Normal AFP CT.

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)  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.

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)  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.

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. should be assessed for transplantation .  Effective antiviral therapy is now available and patients with small HCC.

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 . 1) Percutaneous ethanol injection (PEI) • has been shown to produce necrosis of small HCC.Treatment (non-Surgical) should only be used where surgical therapy is not possible. • It is best suited to peripheral lesions.

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) • .

20%) – Combination chemotherapy didn’t response but survival – should only be offered in the context of clinical trials 6) Hormonal therapy Nolvadex.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. stilbestrol and flutamide 7) Interferon-alfa 8) retinoids and adaptive immunotherapy (adjuvant) .

Targeted therapy for HCC .

c-KIT VEGFR mTOR (mammalian target of rapamycin) mTOR Proteasome . VEGFR .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. c-KIT. PDGFR PDGFR. B-Raf. VEGFR. PDGFR. FLT-3 VEGFR.

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 .