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    Hepatocellular Carcinoma

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    Ethan Matthew Hunt
    This document discusses hepatocellular carcinoma (HCC). It notes that HCC is the 5th most common cancer worldwide and the 3rd leading cause of cancer death. Major risk factors include hepatitis B and C infections and cirrhosis. Diagnosis involves imaging and blood tests. Treatment depends on the stage but may include surgery such as resection or transplantation, ablation procedures, chemoembolization, targeted therapies like sorafenib, or clinical trials of combination therapies. Ongoing research focuses on combination targeted therapies and sequential treatment approaches to improve outcomes for HCC patients.

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    Hepatocellular Carcinoma

    Uploaded by

    Ethan Matthew Hunt
    597 views24 pages
    This document discusses hepatocellular carcinoma (HCC). It notes that HCC is the 5th most common cancer worldwide and the 3rd leading cause of cancer death. Major risk factors include hepatitis B and C infections and cirrhosis. Diagnosis involves imaging and blood tests. Treatment depends on the stage but may include surgery such as resection or transplantation, ablation procedures, chemoembolization, targeted therapies like sorafenib, or clinical trials of combination therapies. Ongoing research focuses on combination targeted therapies and sequential treatment approaches to improve outcomes for HCC patients.

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    Cancer of the Liver

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    hepatocellular carcinoma.ppt

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    This document discusses hepatocellular carcinoma (HCC). It notes that HCC is the 5th most common cancer worldwide and the 3rd leading cause of cancer death. Major risk factors include hepatitis B and C infections and cirrhosis. Diagnosis involves imaging and blood tests. Treatment depends on the stage but may include surgery such as resection or transplantation, ablation procedures, chemoembolization, targeted therapies like sorafenib, or clinical trials of combination therapies. Ongoing research focuses on combination targeted therapies and sequential treatment approaches to improve outcomes for HCC patients.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    597 views24 pages

    Hepatocellular Carcinoma

    Uploaded by

    Ethan Matthew Hunt
    This document discusses hepatocellular carcinoma (HCC). It notes that HCC is the 5th most common cancer worldwide and the 3rd leading cause of cancer death. Major risk factors include hepatitis B and C infections and cirrhosis. Diagnosis involves imaging and blood tests. Treatment depends on the stage but may include surgery such as resection or transplantation, ablation procedures, chemoembolization, targeted therapies like sorafenib, or clinical trials of combination therapies. Ongoing research focuses on combination targeted therapies and sequential treatment approaches to improve outcomes for HCC patients.

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    of 24

    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, Wilsons 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) 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 13%.

    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

    Raised AFP

    Normal 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 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

    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 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)

    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

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