treatment options for liver cancer
DESCRIPTION
This webinar will help you gain an understanding of how liver cancer develops, the importance of early detection through screening and surveillance, as well as treatment options for managing liver cancer.TRANSCRIPT
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
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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 be at risk for, or 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)
Hepatitis B or C
Diabetes
Alcohol
Aflatoxins
Inflammation
Cell damage
Uncontrolled cell growth
Fatty Liver
Iron
Risk factors
A dedicated program of the Hepatitis B Foundation
0.5% per year
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
No hepatitis C vaccine, but treatments can eliminate (cure) the virus and prevent cancer
Prevention of cirrhosis
~ 80% of people with liver cancer also have cirrhosis
Prevent cirrhosis by preventing hepatitis B and C infections, treating HBV, curing HCV, eliminating alcohol intake, maintaining a healthy weight / diet
Liver Cancer Prevention
A dedicated program of the Hepatitis B Foundation
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 for Early Detection of HCC?
In people with chronic HBV infection, liver cancer can develop with or without cirrhosis, so 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 and offering the chance of better survival
More treatment options for early-stage liver cancer
Early detection may increase treatment success
Offer cure to some patients with HCC
Proceed to liver transplant before the cancer is too large
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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 liver cancer biomarkers (AFP, AFPL3%, or DCP)
Screening: first test; Surveillance: all subsequent testing
American Association for Study of Liver Diseases recommends:
All men with hepatitis B: start screening/surveillance at age 40 years
All women with hepatitis B: start screening/surveillance at age 50 years
HBV patients with cirrhosis
And 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%, DCP)
Imaging studies
- Ultrasound (US)
with elastography- 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
A minimally invasive surgical removal of a small piece of liver cancer tissue to examine under the microscope
Usually performed as an outpatient hospital procedure
Procedure is relatively short with a 3- to 8-hour recovery period in the hospital to prevent bleeding at biopsy site
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Staging of Liver Cancer
Staging is a medical term to describe how far the cancer has progressed in a patient and the status of the patients liver as well as the patient functional status
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: TMN
Staging helps determine treatment options
Stage I
Tumor is small and found in one part of the liver
Stage II
Several small tumors or a single tumor that has spread to nearby blood vessels
Stage III
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
One or more tumors in the liver, and cancer cells have spread to other parts of the body
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5 Stages of Liver Cancer: BCLC
Staging helps determine treatment options
Stage 0
Tumor is small and found in one part of the liver, no cirrhosis; surgery is recommended
Stage A
Several small tumors or a single tumor in the setting of cirrhosis;
transplant is recommended
Stage B
One or more tumors that might have spread to nearby parts of the body;
ablation therapy is recommended
Stage C
One or more tumors in the liver, and cancer cells have spread to other parts of the body;
systemic therapy is recommended
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Stage D: extensive disease: palliative care is recommended
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Managing Liver Cancer
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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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Team Approach for Treatment
It takes a team to treat liver cancer:
Hepatologist (liver specialist)
NP/PA/RN team
Pharmacist
Surgeon/transplant 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 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 (very early cirrhosis, chronic hepatitis B or C, fatty liver)
Many patients not eligible (tumor too large or too many; reduced liver function or portal hypertension [large spleen, varices, low platelet] caused by cirrhosis)
Fewer than 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)Microwave ablation (MwA)
Transarterial chemoembolization (TACE)
Transarterial bead chemoembolization (TABE)
Radiotherapy
Radioembolization (TARE)
Cryotherapy (freeze the tumor)
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 with TABE or TARE
Best option if patient cannot have surgery / transplant but disease is localized with bilirubin less than 3 and no ascites
Side effects include pain or bleeding: rare
Very rare events of tumor spreading (seeding or tracking)
Target heat to the tumor with less exposure to other parts of the liver
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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 and into the tumor spares most of the normal liver
Prevents most of chemotherapy drugs being absorbed into circulation; kills the tumor by cutting off its blood supply
Treatment Options
Chemoembolization (TACE) or Bead (TABE)
Tumor
Catheter placement forchemoembolization
Liver
Portal vein
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Hepaticartery
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 decrease/cut blood flow
Slowly delivers chemotherapy so systemic effect of drugs is small
Can kill most of localized tumors that are up to 7-9 cm
Transarterial bead chemoembolization (TABE):
Anticancer drugs delivered on plastic beads directly into tumor to block blood supply to the tumor and have slow release of the cancer drugs
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Improving Survival in Liver Cancer
Precision TACE using beads (TABE)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
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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 (radiofrequency ablation, surgery, transplantation)
One FDA-cleared 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?
Oral therapies can cure HCV or suppress HBV
Can you explain my blood test or imaging results to me?
Do I need more tests or need to see any other doctors before we decide on my 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
Stay active, eat a healthy diet, coffee and tea are safe and good for liver health
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
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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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Therapies in DevelopmentWhats in the Pipeline?
Treatments being developed; in clinical trials
New targeted therapies
Combinations of targeted therapies
Immunotherapy (use patients immune system to kill tumor)
New ways to deliver chemotherapy/radiation directly into tumor
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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.
Strategies in Development
Attack proteins that help tumor grow
Tivantinib, cabozantinib, foretinib, lenvatinib, axitinib
Target cancer stem cells
Combinations of targeted therapies
Sorafenib with chemotherapy
Sorafenib with RFA, TACE, TABE, TARE, radiotherapy
Combinations of TACE, RFA, proton therapy
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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.
Immunotherapy
Drugs that help immune system recognize and kill cancer cells
Spontaneous immune responses frequently observed
Strategy does not depend on liver function
Can be combined with ablation
Currently this is only for research (clinical trials)
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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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Promising Immunotherapies
Ramucirumab
Phase III REACH study- improved overall survival
Nivolumab
Tremelimumab
Phase II trial in patients with hepatitis C (HCV)
Reduced time to progression of cancer
Reduced HCV viral load by stimulating immune system to attack HCV
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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.
All of the therapies listed here are in clinical trials.
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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 liver cancer clinical trials
Join our webinar on Wed May 27, 1:30 pm EDT
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 time to learn about what clinical trials are and how you can participate in a trial.
You can register for the webinar on the liver cancer connect website, www.livercancerconnect.org.
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www.LiverCancerConnect.org
A Dedicated Program of the Hepatitis B Foundation
A dedicated program of the Hepatitis B Foundation
Treatment options
Clinical trials
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
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39
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
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