Slide 1
Treatment Options for Liver Cancer: What You Need to Know
Presented by: Robert G. Gish, MD
A dedicated program of the Hepatitis B Foundation
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Treatment Options for Liver Cancer
What You Need to Know
[April 27, 2015]
Presented by: Robert G. Gish, MD
Professor Consultant, Stanford University, California
Medical Director, Hepatitis B Foundation
A dedicated program of the Hepatitis B Foundation
How Liver Cancer Develops
Healthy Liver
Cirrhotic Liver
Liver Cancer
In a healthy liver, chemical signals tell liver cells when to
grow/multiply, and when to stop
In a liver damaged by hepatitis infection, cirrhosis (scarring),
or other diseases, abnormal cells may grow out of control and
become cancerous
you do not have to have cirrhosis to have liver cancer
A dedicated program of the Hepatitis B Foundation
In a healthy liver, chemical signals tell liver cells when to
grow and multiply to form more cells, and when to stop growing and
multiplying
In a liver damaged by the hepatitis virus (HBV or HCV),
cirrhosis, or other diseases, abnormal cells may grow and multiply
out of control, and become cancerous
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How Liver Cancer Develops
1540 years
Chronichepatitis
Cirrhosis
3%5% per year
Liver cancer
(HCC)
HBV or HCV
Diabetes
Alcohol
Aflatoxins
Inflammation
Cell damage
Uncontrolled cell growth
Fatty Liver
Iron
Risk factors
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Pathogenesis of human hepatocellular carcinoma (HCC). Chronic
hepatitis B and C and associated liver cirrhosis represent
major risk factors for HCC development, being implicated in more
than 70% of HCC cases worldwide. Additional etiological
factors,
which often represent co-factors of an underlying HBV- or
HCV-related chronic liver disease, include toxins and drugs (e.g.,
alcohol,
aflatoxins, microcystin, anabolic steroids), metabolic liver
diseases (e.g., hereditary hemochromatosis, a1-antitrypsin
deficiency),
steatosis, non-alcoholic fatty liver diseases and diabetes.
Hepatocarcinogenesis is a multistep process that may last for
decades and
involves the progressive accumulation of different genetic
alterations ultimately leading to malignant transformation.
Regardless of the
etiological agent, malignant transformation of hepatocytes is
believed to occur through a pathway of increased liver cell
turnover,
induced by chronic liver injury and regeneration, in a context
of inflammation and oxidative DNA damage. Dysplastic nodules
and
macroregenerative nodules are considered as pre-neoplastic
lesions. The detailed analysis of HCC development in
experimental
animals and the comparison of the results with HCC in humans has
identified a variety of genomic and molecular alterations in
fully
developed HCC and to a lesser extent in morphologically defined
pre-neoplastic precursor lesions. At least four pathways that
regulate
either cell proliferation or cell death (i.e., the
phospho-retinoblastoma (pRb), p53, transforming growth factor-b
(TGF-b) a nd
b-catenin pathways) are affected in HCCs.
Viral hepatitis and liver cancer: the case of hepatitis C
M Levrero
Oncogene (2006) 25, 38343847
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Spotlight on Prevention
Liver cancer can be prevented by eliminating the major risk
factors
Prevention of hepatitis B and C infections
The hepatitis B vaccine is the worlds first anti-cancer vaccine
because it prevents hepatitis B, a leading cause of liver
cancer
There is no vaccine for hepatitis C, but treatments can
eliminate the virus
Prevention of cirrhosis
About 80% of people with liver cancer also have cirrhosis
Prevent cirrhosis by preventing hepatitis B and C infections,
eliminating alcohol intake, and maintaining a healthy weight and
diet
Liver Cancer Prevention
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Prevention is the most effective treatment.
Liver cancer is largely preventable through elimination of the
major risk factors.:
Chronic hepatitis B or C
Cirrhosis (eg, associated with excessive alcohol intake, fatty
liver disease, aflatoxins)
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Why Are Screening and Surveillance So Important?
In people with chronic HBV infection, liver cancer can develop
with or without cirrhosis, so regular screening/surveillance is
essential
In people with chronic HCV infection, cirrhosis occurs before
liver cancer develops
Screening/surveillance increases likelihood of finding liver
cancer early
More treatment options for early-stage liver cancer
Early detection may increase treatment success
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Who Needs Liver Cancer Screening?
Family history of liver cancer (or family history unknown)
Asian and Pacific Islander immigrants and their children
African immigrants and their children
Co-infection with HIV, HBV and/or HCV
Elevated HCC biomarkers, such as AFP, AFPL3% and or DCP
Screening: first test; Surveillance: all subsequent testing
American Association for Study of Liver Diseases recommends:
Men with hepatitis B: start screening/surveillance at age 40
years
Women with hepatitis B: start screening/surveillance at age 50
years
People with cirrhosis
But the following high-risk groups may need
screening/surveillance earlier and more frequently:
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Liver Cancer Screening and Surveillance
The goal is to diagnose liver cancer as early as possible
Screening: the first test
Surveillance: all subsequent testing (regular monitoring)
Common blood tests
- Complete blood count (CBC)
- Alpha-fetoprotein blood test (AFP)
- Additional FDA-cleared blood tests include
AFPL3% and DCP
Imaging studies
- Ultrasound (US)
- Computed tomography (CT or CAT scan)
- Magnetic resonance imaging scans (MRI)
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American Association for the Study of Liver Diseases (AASLD) and
Asian Pacific Association for the Study of the Liver (APASL)
guidelines recommend AFP and US screening every 6-12 months.
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Diagnosing Liver Cancer
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Diagnosis of liver cancer is made by imaging
Liver tumor biopsy is sometimes used to confirm diagnosis of
liver cancer or stage disease
Most common biopsy type is percutaneous needle biopsy
Surgical removal of a small piece of liver to examine under the
microscope
Usually performed as an outpatient hospital procedure
Procedure is relatively short with a 6- to 8-hour recovery
period in the hospital to prevent bleeding at biopsy site
Staging of Liver Cancer
Staging is a medical term to describe how far the cancer has
progressed in a patient
Helps health care providers determine the best course of
treatment
Liver cancer often is diagnosed at more advanced stages because
many people dont have symptoms in early stages
There are several staging systems for liver cancer; not all
health care providers use the same system
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4 Stages of Liver Cancer
Staging helps determine treatment options
Stage I
The tumor is small and found in one part of the liver
Stage II
There are several small tumors or a single tumor that has spread
to nearby blood vessels
Stage III
There are one or more tumors that might have spread to nearby
parts of the body, such as the stomach, blood vessels or lymph
nodes
Stage IV
There are one or more tumors in the liver, and cancer cells have
spread to other parts of the body
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Managing Liver Cancer
A dedicated program of the Hepatitis B Foundation
Managing Liver Cancer
How well the liver is working when the person is diagnosed
Stage of cancer, including number/size of tumors and whether the
cancer has spread outside the liver
Overall health of the person being treated
An individual treatment plan depends on several factors
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Deciding the Treatment Plan
Liver Cancer
Resectable
Liver function OK
Labs OK
Surgery
Transplant Candidate
1 tumor < 5cm
2-3 tumors < 3 cm
Not Resectable
< 2 cm
Image
every 3 months
>2 cm
Embo/Ablation
Image
every 3 months
Liver function not OK
Labs not OK
8 cm radio embolization
Systemic therapy Sorafenib
Palliative care
Hospice care
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Team Approach for Treatment
Treating liver cancer requires a team approach:
Hepatologist (liver specialist)
NP/PA/RN team
Pharmacist
Surgeon
Pathologist
Radiologist (diagnostic and interventional)
Medical oncologist (cancer specialist)
Radiation oncologist (radiation cancer specialist)
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Treatment OptionsLiver Transplantation
Surgical replacement of diseased liver with healthy liver
Transplantation only possible if tumors are small and have not
spread to nearby blood vessels or outside the liver
Orthotopic transplantation: use a healthy liver from a person
who has recently died
Living donor transplantation: use part of a healthy liver from a
living person
Most people needing a new liver are placed on a waiting list
and continue to receive treatment while waiting
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Treatment OptionsSurgery
Resection: Surgical removal of tumor
Treatment of choice if tumor is small, in one section of the
liver and patient does not have portal hypertension
Possible in persons with good liver function, despite liver
disease (eg, cirrhosis, chronic hepatitis B or C, fatty liver)
Many patients not eligible (e.g., tumor too large or too many;
reduced liver function caused by cirrhosis)
Only 30% of tumors are resectable
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Treatment OptionsLocalized
Procedures that damage or eliminate the tumor locally
for tumors that cannot be surgically removed
to prepare a patient for surgical treatment or transplant
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Radiofrequency ablation (RFA)
Transarterial bead chemoembolization (TABE)
Transarterial chemoembolization (TACE)
Radiotherapy
Radioembolization (TARE)
Treatment OptionsLocalized
Radiofrequency (or microwave[MwA]) ablation (RFA):
High-frequency electrical currents destroy tumor
RFA probe
Tumor
Radiofrequency heat
Images: Society of Interventional Radiology (SirWeb.org), Johns
Hopkins (hopkins-gi.org)
This can cure small tumors
Some patients have combination therapy
Best option for patients who cannot have surgery or transplant
if disease is localized
Side effects include pain or bleeding: rare
Very rare events of tumor spreading (seeding or tracking)
Target higher concentration of drugs to the tumor with less
exposure to other parts of the body
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Normal liver gets 75% of blood supply from portal vein; 25% from
hepatic artery
Tumor gets most of its blood supply from the hepatic artery
Injection into the hepatic artery spares most of the normal
liver
Prevents chemotherapy drugs being absorbed into circulation and
kills the tumor by cutting off its blood supply
Tumor
Hepaticartery
Catheter placement forchemoembolization
Liver
Portal vein
Treatment Options
Chemoembolization (TACE)
Hepaticartery
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Multiple studies with anti tumor effect, no survival benefit
Chemoembolization of Unresectable Hepatocellular Carcinoma: A
Review
Douglas E. Ramsey, AB, Jean-Francois H. Geschwind, MD
Appl Radiol.2004;33(3).
http://www.medscape.com/viewarticle/474054_3.
Image adapted from/can be found at:
http://www.uphs.upenn.edu/radiology/patient/services/ir/info/chemo.html
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Treatment OptionsLocalized
Images: Society of Interventional Radiology (SirWeb.org), Johns
Hopkins (hopkins-gi.org)
Delivers embolic material to tumor to cut blood flow
Slowly delivers chemotherapy
Can kill localized tumors that are up to 7-9 cm
Transarterial bead chemoembolization (TABE):
Anticancer drugs delivered directly into tumor to block blood
supply to the tumor
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Improving Survival in Liver Cancer
Precision TACE using beads can improve survival
% probability of survival at 12 months
~98% with TABE; ~82% with TACE
% probability of survival at 24 months
~91% with TABE; ~63% with TACE
TABE, Transarterial bead chemoembolization
A dedicated program of the Hepatitis B Foundation
Treatment OptionsLocalized
Images: Society of Interventional Radiology (SirWeb.org),
CancerHelp UK (cancerhelp.org.uk)
Radiotherapy:
High-energy radiation kills cancer cells and shrinks tumor
Radioactive beads or external beam radiation
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Transarterial radioembolization (TARE):
Reduces tumor size, but is not a cure
May make patients eligible for other therapies (e.g.,
radiofrequency ablation, surgery, transplantation)
One FDA-approved method uses implanted glass beads or resin to
deliver high-dose radiation directly to tumor; spares healthy liver
cells
Usually an outpatient procedure
Treatment OptionsTargeted Therapies
Therapies that enter the bloodstream and reach the whole body
(systemic)
Newer biologic therapies that specifically target the tumor
Unlike chemotherapy, which kills both tumor cells and healthy
cells, targeted therapies block specific pathways in the tumor
may have different or less severe side effects than
chemotherapy
Targeted therapies may be oral (pills, tablets)
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Treatment OptionsTargeted Oral Drug
Nexavar (sorafenib) is the first FDA-approved oral drug to treat
liver tumors that cannot be surgically removed
A targeted oral therapy approved for primary liver cancer in
more than 70 countries
Blocks tumor cell signals so tumor cells cant grow or
multiply
Reduces formation of new blood vessels that provide oxygen and
nutrients to the tumor cells
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What to Ask Your Health Care Team
What are my treatment options and how will they help?
If I have hepatitis B or C, do I need antiviral treatment?
There are all oral therapies that can cure HCV or suppress
HBV
Can you explain my blood test or imaging results to me?
Do I need more tests before we decide on my treatment?
Do I need to see any other doctors before I start treatment?
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What to Ask Your Health Care Team
What will the treatment involve?
What are the possible side effects of treatment?
What are the chances that the cancer will come back?
Can I get a copy of all of the results?
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Life After Treatment
Take time to recover, heal and discover your new normal
May still feel the effects of treatment
May experience changes in food, activities, support
Make sure you keep all medical follow-up visits
Talk to your health care team about a wellness plan
Talk to your health care provider about your familys cancer
risk
For more information
Read Facing Forward from the National Cancer Institute
Visit www.LiverCancerConnect.org
A dedicated program of the Hepatitis B Foundation
Follow-Up Care: What Is Involved?
Medical follow-up visits are very important
To check that the cancer has not spread or returned
To manage any side effects that might occur
Regular imaging and blood tests will be required for several
years after surgery and/or a liver transplant
Maintain your health insurance since you will have follow-up
visits for many years
Keep records of all blood test results, imaging studies, surgery
and discharge reports, and list of medications
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Treatment OptionsWhats in the Pipeline?
Treatments being developed
Combination therapies
New ways to deliver chemotherapy/radiation directly into
tumor
Immunotherapy (use patients immune system to kill tumor)
Many therapies being studied in clinical trials
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Many of these therapies in development are being studied in
clinical trials. Ask your health care team if there are any trials
that might be suitable for you.
Why Immunotherapy?
Spontaneous immune responses frequently observed
Strategy does not depend on liver function
Can be combined with ablation
Currently this is for research programs only
A dedicated program of the Hepatitis B Foundation
Types of Immunotherapy
Checkpoint inhibitors
Target molecules that regulate immune response to cancer
cells
Cancer vaccines
Encourage immune system to attack cancer cells
Adoptive T-cell therapy
Genetically/chemically modify patients immune cells (T cells) to
specifically attack cancer cells
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All of the strategies mentioned here are in clinical trials. For
more information, visit the website of the National Cancer
Institute or clinicaltrials.gov
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Types of Immunotherapy
Monoclonal antibodies
Attack specific targets on cancer cells
Cytokines
Messenger cells help control immune system
Cancer-killing virus therapy
Modified virus causes tumor to self-destruct; stimulates immune
response to cancer
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All of the strategies mentioned here are in clinical trials. For
more information, visit the website of the National Cancer
Institute or clinicaltrials.gov
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Tremelimumab with Chemoembolization or Ablation
Cancer drug that helps immune system recognize and kill cancer
cells
Can it be used to treat advanced liver cancer?
Used in combination with:
TACE: inject chemotherapy into tumor through arterial blood
vessel
RFA: heated probe destroys tumor tissue
Being studied in clinical trial
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The National Cancer Institute is studying several therapies for
liver cancer. For example, they are studying tremelimumab, a cancer
treatment drug that helps the immune system recognize and destroy
cancer cells. Researchers want to see if it can be used to treat
advanced liver cancer. The drug will be given with one of two types
of treatment for liver cancer. The first type, transarterial
catheter chemoembolization (TACE), injects chemotherapy drugs into
the tumor through the main blood vessel that is feeding it. That
blood vessel is then closed off to help keep the drugs in the tumor
longer. The second type, radiofrequency ablation (RFA), uses a
heated probe to destroy the tumor tissue. Researchers want to study
how safe and effective these treatments are with the study
drug.
Objectives:
- To test the safety and effectiveness of Tremelimumab with TACE
or RFA for advanced liver cancer.
Eligibility:
- Individuals at least 18 years of age who have advanced liver
cancer that has not responded to other treatments.
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Clinical Trials
Study whether a drug is safe and effective in people
May not get study treatment, but will get standard treatment
Learn more about clinical trials
Join our webinar on Wed May 27, 1:30 pm EST
Register at www.livercancerconnect.org
A dedicated program of the Hepatitis B Foundation
The Hepatitis B Foundations Liver Cancer Connect program is
organizing a webinar on clinical trials. Please join us on May 27
at 1:30 pm Eastern standard time to learn about clinical trials are
and how you can participate. You can register for the webinar on
the liver cancer connect website, www.livercancerconnect.org.
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Patient Resource on Liver Cancerwww.LiverCancerConnect.org
Treatment options
Clinical trials
A Dedicated Program of the Hepatitis B Foundation
A dedicated program of the Hepatitis B Foundation
Liver cancer centers
Information for newly diagnosed
Talking to your health care team
Drug watch
The Hepatitis B Foundations website, Liver Cancer Connect, is a
patient-focused resource on liver cancer. It provides a directory
of liver cancer centers, a drug watch, a list of clinical trials,
and information in easy-to-understand language about diagnosis,
screening, and treatment options.
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Liver Cancer Connect Drug Watch
A dedicated program of the Hepatitis B Foundation
The Liver Cancer Connect website has a drug watch- a list of
therapies in development for liver cancer. The list is updated
regularly.
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Key Messages
Know your risk - Family history, hepatitis, cirrhosis...
Get screened and regular monitoring (surveillance) Early
diagnosis saves lives
Know the symptoms - Get checked immediately if you have any
signs or symptoms of liver cancer
Get informed - Talk to your health care provider about treatment
options and clinical trials for liver cancer
A dedicated program of the Hepatitis B Foundation
Question and Answer Time
Use the chat box on your screen to type and send your questions
to the presenter
Your questions will be seen only by the presenter
Please note, the presenter cannot give treatment recommendations
or advice on a persons personal medical condition
A dedicated program of the Hepatitis B Foundation