Treatment Options for Liver Cancer (Audio Recording)

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


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

o you do not have to have cirrhosis to be at risk for, or to have, liver cancer


How Liver Cancer Develops

1540 years Chronic

hepatitis 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


0.5% per year

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


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


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:


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)


Diagnosing Liver Cancer


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

o 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

o Procedure is relatively short with a 3- 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 and the status of the patients liver as well as the patient functional status o Helps health care providers determine the best course

of treatment o 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


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


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


Stage D: extensive disease: palliative care is recommended

Managing Liver Cancer


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


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) A dedicated program of the Hepatitis B Foundation

Treatment Options Liver 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 A dedicated program of the Hepatitis B Foundation

Treatment Options Surgery

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) o Fewer than 30% of tumors are resectable


Treatment Options Localized

Procedures that damage or eliminate the tumor locally for tumors that cannot be surgically removed to prepare a patient for surgical treatment or transplant


o Radiofrequency ablation (RFA) Microwave ablation (MwA)

o Transarterial chemoembolization (TACE) o Transarterial bead chemoembolization (TABE) o Radiotherapy o Radioembolization (TARE) o Cryotherapy (freeze the tumor)


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)

o This can cure small tumors o Some patients have combination therapy with TABE or TARE o Best option if patient cannot have surgery / transplant but disease is localized

with bilirubin less than 3 and no ascites o Side effects include pain or bleeding: rare o Very rare events of tumor spreading (seeding or tracking)

Target heat to the tumor with less exposure to other parts of the liver


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 for chemoembolization

Liver Portal vein


Hepatic artery


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 drugs


Improving Survival in Liver Cancer

Precision TACE using beads (TABE)can improve survival % probability of survival at 12 months

o ~98% with TABE; ~82% with TACE

% probability of survival at 24 months o ~91% with TABE; ~63% with TACE

TABE, Transarterial bead chemoembolization



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


Transarterial radioembolization (TARE): Reduces tumor size, but is not a cure

o May make patients eligible for other therapies (radiofrequency ablation, surgery, transplantation)

o One FDA-cleared method uses implanted glass beads or resin to deliver high-dose radiation directly to tumor; spares healthy liver cells

o Usually an outpatient procedure

Treatment Options Targeted 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 o may have different or less severe side effects than

chemotherapy

Targeted therapies may be oral (pills, tablets)


Treatment Options Targeted 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


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?

o 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? A dedicated program of the Hepatitis B Foundation

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?


Life After Treatment Take time to recover, heal and discover your new normal

o May still feel the effects of treatment o May experience changes in food, activities, support o 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


Follow-Up Care: What Is Involved? Medical follow-up visits are very important

o To check that the cancer has not spread or returned o 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


Therapies in Development Whats in the Pipeline?

Treatments being developed; in clinical trials o New targeted therapies o Combinations of targeted therapies o Immunotherapy (use patients immune system

to kill tumor) o New ways to deliver chemotherapy/radiation

directly into tumor


Strategies in Development Attack proteins that help tumor grow

o Tivantinib, cabozantinib, foretinib, lenvatinib, axitinib

Target cancer stem cells Combinations of targeted therapies

o Sorafenib with chemotherapy o Sorafenib with RFA, TACE, TABE, TARE,

radiotherapy Combinations of TACE, RFA, proton therapy


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)


Types of Immunotherapy

Checkpoint inhibitors o Target molecules that regulate immune response

to cancer cells

Cancer vaccines o Encourage immune system to attack cancer cells

Adoptive T-cell therapy o Genetically/chemically modify patients immune

cells (T cells) to specifically attack cancer cells


Types of Immunotherapy

Monoclonal antibodies o Attack specific targets on cancer cells

Cytokines o Messenger cells help control immune system

Cancer-killing virus therapy o Modified virus causes tumor to self-destruct;

stimulates immune response to cancer


Promising Immunotherapies

Ramucirumab o Phase III REACH study- improved overall survival

Nivolumab Tremelimumab

o Phase II trial in patients with hepatitis C (HCV) o Reduced time to progression of cancer o Reduced HCV viral load by stimulating immune

system to attack HCV


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 o Join our webinar on Wed May 27, 1:30 pm EDT o Register at www.livercancerconnect.org


www.LiverCancerConnect.org 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

Liver Cancer Connect Drug Watch


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


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

Slide Number 1Slide Number 2How Liver Cancer DevelopsHow Liver Cancer DevelopsSpotlight on PreventionWhy Are Screening and Surveillance So Important for Early Detection of HCC?Who Needs Liver Cancer Screening?Liver Cancer Screening and SurveillanceSlide Number 9Staging of Liver Cancer4 Stages of Liver Cancer: TMN5 Stages of Liver Cancer: BCLCSlide Number 13Managing Liver CancerTeam Approach for TreatmentTreatment OptionsLiver TransplantationTreatment OptionsSurgeryTreatment OptionsLocalized Treatment OptionsLocalized Slide Number 20Treatment OptionsLocalized Improving Survival in Liver Cancer Treatment OptionsLocalizedTreatment OptionsTargeted TherapiesTreatment OptionsTargeted Oral DrugWhat to Ask Your Health Care TeamWhat to Ask Your Health Care TeamLife After TreatmentFollow-Up Care: What Is Involved?Therapies in DevelopmentWhats in the Pipeline?Strategies in DevelopmentImmunotherapyTypes of ImmunotherapyTypes of ImmunotherapyPromising ImmunotherapiesClinical Trialswww.LiverCancerConnect.orgLiver Cancer Connect Drug WatchKey MessagesQuestion and Answer Time

Treatment Options for Liver Cancer (Audio Recording)

Documents

prevention liver cancer

liver cancer screening

liver cells

liver transplant

family history of liver

leading cause of liver

hepatitis b foundation

cancer prevention of