a patient’s Guide to Mesothelioma

MeSotheLIoMa IS a rare CanCer, with 2,000 to 3,000 new cases

diagnosed each year,  and understanding the disease is important in

making decisions about care and treatment.

MeSotheLIoMa ForMS in the mesothelium,a protective membrane covering internal organs, such as the lungs and heart. The mesothelium is made up of two layers—one surrounding the organ itself and the other  forming an outer sac. Between the layers is a lubricating fluid that lessens friction between the membranes and permits the organs to glide smoothly against each other. This is particularly important to the heart and lungs, because they produce significant movement as they function.Mesothelioma is defined by the site of the primary tumor. Pleural mesothelioma, in which cancer cells surround the lungs and/or the chest wall, accounts for about 85 percent of malignant mesotheliomas. Mesothelioma can also grow across the thin mesothelial

tissue that lines the abdomen (peritoneum) or, rarely, the heart or testicles. Mesothelioma is different from other cancers because it’s tightly linked with an environmental cause—asbestos exposure, which accounts for the majority of cases. Most mesothelioma patients worked or lived in a place where they were exposed

to asbestos. Typical mesothelioma patients worked in shipyards or as miners and are men age 60 and older, but family members of these workers have also developed the disease—many with relatively little direct exposure. Also, because mesothelioma can take decades to develop, most patients are older at diagnosis.

The geographic distribution of this disease is not uniform across the United States, with the highest death rates appearing in the Northeastern states, along the Pacific Coast, and in Illinois, Florida, Wyoming, and Colorado. As with the demographic imbalance, the geographic distribution can also be explained by asbestos exposure—the regions with the highest death rates are (or were) home to either factories that manufactured asbestos-containing products or shipbuilding facilities (asbestos materials were commonly

used as insulation in ships).Although the average patient survives only four to 18 months after diagnosis, and only 10 percent of patients survive at least five years, there have been reports of long-term survivors who have no evidence of disease many years following treatment.

Causes & risk Factors

aSBeStoS expoSUre IS the MoSt CoMMon

cause of mesothelioma. the term “asbestos” actually refers to several minerals with shared properties: long, flexible fibers that are resistant to stretching, heat, and corrosion. It’s because of these properties that asbestos was used in products such as insulation, roofing, floor and ceiling tiles, and brake pads.Though the asbestos industry launched in the late 1800s, scientists didn’t link the mineral to mesothelioma until the 1950s. In the United States, asbestos continued to be mined and used—particularly for insulation—until the 1980s. Of the various types of asbestos, the fibers most commonly used in the United States are chrysotile (white asbestos), crocidolite (blue asbestos), and amosite (brown asbestos). Chrysotile is most widely used because its fibers are curled, a property that makes it less likely to fragment than the other types of asbestos. Crocidolite and amosite are typically used in limited, specialized applications because their needle-like tructure makes them highly susceptible to fragmenting. This is important because if asbestos is easily

crushed, it remains airborne longer, which increases the likelihood of inhaling the fibers that cause mesothelioma. Generally, it takes 20 to 40 years or more for mesothelioma to develop following

asbestos exposure. The exact means by which asbestos causes cancer has not yet been fully

determined, but it is known when asbestos is inhaled, about two-thirds of the fibers are

eliminated from the body by coughing or swallowing. The remaining fibers travel through the airways, and some may reach the alveoli, the tiny air sacs in the lungs. Although the method by which asbestos fibers arrive at the mesothelium is not certain, it is likely that this journey takes years, a belief that fits with the

extended period of time necessary to develop mesothelioma. It has never been established if there are any “safe” levels of asbestos exposure. However, there is at least circumstantial evidence that even low nvironmental levels of asbestos exposure can increase the risk of mesothelioma.

Interestingly, smoking is not a risk factor for mesothelioma. However, smoking does increase the risk of lung cancer, which is frequent in people with asbestos exposure. Thus, people with both a history of smoking

and asbestos exposure have an elevated risk of developing lung cancer—approximately

60-fold higher than nonsmokers with no asbestos exposure.While asbestos is the most common

cause of mesothelioma, certain characteristics of the disease suggest that asbestos exposure is not the only cause. Other suspects include:SIMIan VIrUS 40Due to conflicting research, perhaps the

most controversial link to mesothelioma is exposure to simian virus 40 (SV40), a virus

that contaminated polio vaccines during the 1950s and 1960s. In the ’50s, monkeys were

used to develop a vaccine against polio, but in 1961, it was discovered that these monkeys

were infected with SV40, which meant the polio vaccines were likely contaminated. Shortly

thereafter, animal studies showed that SV40 was capable of causing cancer, producing

significant alarm regarding the cancer-causing potential of the contaminated polio vaccines.

Some research supports the possibility that SV40 and asbestos may work together

to cause mesothelioma. For instance, cells with chromosomal abnormalities (such as

those caused by asbestos exposure) can gain cancer-like characteristics more easily

when infected with SV40 compared to cells with normal chromosomes. erIonIteErionite is a non-asbestos mineral fiber that is similar in physical characteristics to crocidolite. Erionite has been identified as

a cause of mesothelioma based on studies of mesothelioma rates among residents of

Cappadocia, Turkey, where erionite has been used in building materials. Of 141 deaths

in four villages during a four-year period, 24 percent were due to mesothelioma. Erionite

deposits can be found throughout the western United States, primarily in areas with a low

population density. To date, however, there have been no cases of mesothelioma attributed to

erionite exposure in the United States.GenetIC preDISpoSItIonFurther examination of the link between

erionite exposure in Turkey and the high mesothelioma death rate produced evidence

that genetic predisposition might also be a factor in development of the disease.

Although all homes in that region contained similar amounts of erionite, mesothelioma occurred in some homes and not in others. In addition, mesothelioma development followed a dominant genetic inheritance

pattern, in which half of the children of parents with mesothelioma also developed mesothelioma. This pattern is consistent with a single genetic mutation from one

Who’s at Risk?

CanCer patients often wonder why they got the disease. Most cases of mesothelioma

involve asbestos exposure, but you may be unsure when, or even how, your exposure

occurred. Although minute levels of asbestos exist in the air, water, and soil, most people

do not develop mesothelioma from this type of exposure. People who develop the disease

generally have regular asbestos exposure, such as from a job.

In the 1970s, legislation was enacted to protect workers from asbestos exposure, but

prior to that, workers in certain industries may have had regular exposure to asbestos. Some

of these occupations are:n Insulation work in buildings and other

structures

n Demolition work, especially in older buildings

n Drywall workers

n Firefighters

n Automobile mechanics

n Steel mill workers

n Shipyard and shipbuilding trades

n Navy veterans

Family members of asbestos-exposed

workers may develop mesothelioma because

of regular exposure to the fibers brought home

on clothing, shoes, and hair. Regular exposure

may have occurred from tasks such as washing

of the parents causing the disease. While

these observations cannot be considered

conclusive evidence for a genetic

predisposition to mesothelioma, they do

provide reason to further study the role of

genetics as a risk factor.

Diagnosis & Staging

DIaGnoSInG MeSotheLIoMa can be a

complicated process. Symptoms do not typically arise until the disease has reached

the late stages, and when they do arise, most are nonspecific, including weight loss, fatigue,

and night sweats. Depending on the type of mesothelioma, organ-specific symptoms may be present.

For instance, most patients with pleural mesothelioma experience lung-related symptoms, such as consistent chest pain and progressively worsening shortness of breath. The pain is typically caused by

invasion of cancer into the chest wall, and shortness of breath is often caused by pleural effusion (excess fluid in the pleural linings of the lungs). The presence of cough, or coughing up blood, can occasionally occur

with pleural mesothelioma.Proper diagnosis requires a combination of physical, radiological, and pathological

examinations, as well as an accurate patient history, including potential asbestos exposure.For patients with pleural effusions, a sample of the fluid is examined for the presence of malignant cells. In most cases, even when a pleural fluid sample is available, a biopsy of the pleural tissue is required to make a diagnosis. Examination of the biopsy samples includes immunohistochemistry (IHC) tests, in which the samples are processed in a way that allows the pathologist to look for specific signs, called markers, of mesothelioma. There are no known markes that correspond to mesothelioma alone, so in order to diagnose mesothelioma, the pathologist generally evaluates the presence or absence of several markers.

Radiological analysis using contrastenhanced computed tomography (CT)

scan provides a three-dimensional view

of the entire pleural surface. It can help

determine the extent of disease and can aid

the physician in finding the desired tissue

for biopsy. Magnetic resonance imaging

(MRI) and positron emission tomography

(PET) scans may also be used to diagnose

mesothelioma.

Once the diagnosis is made, the disease

stage is evaluated. As with any type of

cancer, determining the extent of the disease

is used to predict a patient’s outcome and to

determine the best course of treatment.

In stage 1, the disease is confined to

the mesothelium and has not spread to the

lymph nodes or any other organs. Stage 1A

refers to a tumor in the outer layer of the

mesothelium, whereas stage 1B refers to a

tumor that has reached both the outer and

inner layer. Stage 1 is the most treatable,

and patients with this stage disease have the

best prognosis (expected outcome).

Stage 2 disease is characterized by the

spread of cancer beyond the mesothelium

and into the lung tissue and/or diaphragm,

but not yet into the lymph nodes. Patients

with stage 2 mesothelioma may be

candidates for surgical removal of the tumor.

For stage 3 mesothelioma, the cancer has

spread into the fatty part of the mediastinum

(the space behind the breastbone and

between the lungs) and/or to the lymph

nodes within the thorax.

Stage 4 is metastatic disease, where the

cancer has spread to other organs, such as

the heart or opposite lung. The cancer may

also have spread into the peritoneum, to the

lymph nodes, or into the spine.

Finding a

Specialist

BeCaUSe MeSotheLIoMa IS a rare CanCer,

it requires disease-specific expertise.

Here are some places you can go to find a

mesothelioma specialist:

n Local hospital referral services

n Your nearest National Cancer Institutedesignated cancer center (search by state at

www.cancer.gov/cancertopics/factsheet/NCI/

cancer-centers)

n American Board of Medical Specialties at

www.abms.org

n American Medical Association’s

DoctorFinder at webapps.ama-assn.org/

doctorfinder/home.jsp

n American Society of Clinical Oncology’s

patient site at www.cancer.net

n American College of Surgeons at

www.facs.org/patienteducation

n Mesothelioma Applied Research

Foundation at www.marf.org Once you have found several doctors who seem like a good fit, call and ask a few questions—does the doctor take your insurance, is he or she board certified—before scheduling an appointment to meet and interview the doctor/surgeon.You may also want to get a second opinion. Most oncologists expect their patients to seek second opinions, and many suggest it themselves. If your doctor doesn’t recommend a specialist, you can use the resources listed to find a doctor who can offer a second opinion.Nurse coordinators at large medical centers can be particularly helpful in finding physicians who give second opinions. Support groups and other cancer survivors may also be good sources for recommending

Questions to Ask

prepare for your appointment by formulating

a list of questions to ask. You may want to

divide questions into two categories:

What to aSk the DoCtor

n Do you have experience treating

mesothelioma?

n How long have you been in practice, and

how many cases of mesothelioma have you

treated?

n What types of treatment do you usually

recommend?

n How many times have you performed the

surgery I need, and what’s your success

rate?

n Are you involved in clinical trials and

research?

n Who else will be on my health care team,

and what are their qualifications?

What to aSk YoUrSeLF

n Did the doctor give you a chance to ask

questions?

n Did you feel like the doctor was listening to

you?

n Did the doctor seem comfortable

answering your questions?

n Did the doctor talk to you in a way you

could understand?

n Do you feel the doctor respected you?

n Did the doctor ask your preferences for

treatment?

oncologists and specialists. Keep in mind

that these consultations can be expensive

and may not be covered by insurance.

For some insurance plans, second

opinions are covered or even required before

the plan approves payment for treatment, but

you may be limited to certain physicians or

hospitals.

After you weigh your options, you must

choose your medical team. The comfort level,

treatment options proposed, and medical

expertise should all be evaluated when

making a decision.

treatment options

IMproVeMentS In treatMent have been made in recent years, giving mesothelioma

patients hope. an overview of current and investigational therapies are detailed here.

SUrGerYAlthough complete surgical removal of the

tumor is desired, this is rarely achievable for most patients because microscopic tumor

tissue is generally left behind. However, surgery is still used to treat patients with the

goal of removing the vast bulk of the tumor and thus alleviating symptoms. The surgical

procedures include:

n Video-assisted thoracoscopic (VatS) talc pleurodesis is primarily used to treat pleural

effusions, but a biopsy can be obtained at the same time for diagnostic purposes. With VATS

talc pleurodesis, a camera is inserted into the pleura through a small incision in the chest,

and surgical instruments are inserted through two other incisions. The camera allows the

surgeon to maneuver instruments into the pleural space, where the surgeon first drains

the excess fluid and then blows talc (similar to common talcum powder, but sterilized),

causing an inflammatory reaction that literally glues the lung to the inner surface of the rib

cage. Eventually, scar tissue forms, creating permanent bonds that eliminate the space

in which fluid can develop. This procedure should relieve the shortness of breath that

accompanies pleural effusions.n pleurectomy/decortication (p/D) is

performed with the goal of removing as much of the tumor as possible by removing part of

the pleura as well as the fibrous covering of the lungs, which may restrict lung expansion.

This procedure, which can be performed by VATS or through a larger incision on the side

of the chest, is associated with a number of postoperative complications, including air

leak, bleeding, and pus formation. Conflicting evidence exists regarding the impact of P/D,

with some studies suggesting it prolongs life and others indicating it does not.

n extrapleural pneumonectomy (epp),the most aggressive surgical treatment

for malignant mesothelioma, involves the removal of both layers of the pleura along

with the involved lung, some of the lymph nodes, the diaphragm, and the pericardium

(the latter two are reconstructed with synthetic materials). Although EPP has

inherent dangers, it permits the use of radiation therapy following surgery since the

involved lung has been removed. Evidence suggests radiation after surgery may reduce

recurrence at the original tumor site and

prolong survival in patients with earlystage disease. Chemotherapy is now often

incorporated into the treatment plan as well, either before or after surgery. However,

because of the morbidity and mortality associated with this procedure, EPP is only

performed on patients with early-stage disease, good cardiac health, no history

of certain cardiac or lung surgeries, no significant kidney or liver disease, and little,

if any, chest pain.

raDIatIon therapY

Radiation therapy is generally used to treat localized patches of tumor recurrence

or small areas of tumor left behind after surgery. There is no evidence to suggest

radiation alone improves survival, but it does alleviate pain for approximately half of the

patients receiving it.

CheMotherapY

The goals of current chemotherapy regimens are to prolong the survival of mesothelioma

patients and improve their quality of life by relieving disease-related symptoms.

The approval of Alimta (pemetrexed) in 2004 has led to the largest improvement in

patient outcomes. When added to cisplatin, Alimta, which works by inhibiting cellular

proteins that stimulate cancerous cells to grow, was shown in a clinical study to prolong

average survival by almost three months. Alimta also relieved pain and shortness

of breath, and improved lung function in some patients. Alimta plus cisplatin given

intravenously once every three weeks has become standard therapy for newly diagnosed

mesothelioma. (Clinical studies of Tomudex [raltitrexed], a drug in the same class as

Alimta, have also shown improved response rates and survival times when given with

cisplatin compared with cisplatin alone.)Premedication with folic acid and vitamin

B12 is necessary when taking Alimta in order to reduce the frequency of side effects,

which can include fatigue, nausea, vomiting, anorexia (loss of appetite), constipation,

mouth sores, and low blood cell counts. More severe side effects, including renal failure and

hearing loss, occur in rare instances.

InVeStIGatIonaL therapIeSA number of important mesothelioma

studies were presented at the 2009 annual meeting of the American Society of Clinical

Oncology. A phase III trial comparing Adriamycin (doxorubicin) with or without the

experimental drug Onconase (ranpirnase), showed the average survival of both groups

was nearly identical: 10.7 months for the Onconase group versus 11.1 months for

patients receiving Adriamycin alone. However,

when investigators looked only at patients who had already received one course of

chemotherapy, they found that those patients survived longer, on average, when Onconase

was added to treatment: 10.5 months for the Onconase group versus nine months for

patients receiving Adriamycin alone. Also presented at ASCO’s annual meeting

were results from studies with the targeted agents cediranib and NGR-hTNF, both of

which target the tumor’s blood supply. Cediranib and NGR-hTNF were examined

as single agents, and both demonstrated the ability to slow disease progression in

patients with relapsed mesothelioma. As a result of these findings, new clinical trials are

being planned.

An ongoing phase III trial is investigating Zolinza (vorinostat), which is already

approved for a rare type of lymphoma, to see if it improves survival of patients with

mesothelioma. In this trial, patients whose disease progressed after treatment with

Alimta will be given either Zolinza or placebo. New treatments in phase II development

include drugs approved by the Food and Drug Administration for other cancers—Sprycel

(dasatinib), Velcade (bortezomib), Sutent (sunitinib), Afinitor (everolimus), and Eloxatin

(oxaliplatin)—as well as investigational drugs that are not approved (pazopanib,

vandetanib, and vatalanib).Find ongoing mesothelioma clinical trials at

www.curetoday.com/trialcheck.

Legal Issues

CoMpanIeS InVoLVeD In the ManUFaCtUre and distribution of products containing asbestos

can be held liable for the development of mesothelioma in workers exposed to asbestos.

Statutes of limitations vary from state to state and may limit the time in which

you can file a lawsuit after diagnosis. The limitation period can be as short as one

year or as long as three years or more, but the sooner you start the legal process, the

sooner you will receive compensation to help with medical bills and other expenses. Your

case may be expedited depending on your symptoms and the stage of the disease.

The most common types of lawsuits include:n personal injury: These lawsuits are filed

for personal suffering and pain associated with the illness, which can occur from direct

or secondhand exposure to asbestos. Compensation is based on the degree of

incapacity, loss of income, and quality of life related to mesothelioma symptoms and

treatment. Damages are awarded for medical expenses, lost wages, lost prospects, travel

expenses for treatment, pain, and suffering.n Wrongful death: This type of lawsuit

is filed on behalf of the family after the patient’s death. The damages awarded are

for payment of mesothelioma-related medical bills, lost income, counseling related to the

patient’s death, legal advice, personal loss, and other illness-related services.

Choosing an attorney is a personal decision, just as when choosing a medical

team. You should feel comfortable with the answers you receive to your questions, the

way you are treated by the attorney and staff, the level of experience and positive

outcomes the law firm has had with other mesothelioma and asbestos-related cases,

and the firm’s reputation. A word of caution: An attorney should never promise you a

specific amount of compensation. There are no guarantees; each case is unique.

Legal advice and the process of filing a lawsuit is an expensive undertaking.

Most attorneys accept a case based on a contingency fee, meaning you will have no

out-of-pocket expenses and the attorney will receive a percentage of your settlement money

as payment. The contingency fee pays for legal work done on your behalf, court filing fees,

expert witness fees, and legal representation in court. If an award is not granted, you may

be responsible for some expenses depending

on the contingency fee agreement. Once you decide to hire an attorney, you

will meet with the legal staff to provide information about your work history and

personal history to determine the type and degree of asbestos exposure you sustained.

Authorizations will be obtained to get copies of your medical records, and you should not

have to undergo any further medical testing for the purposes of the lawsuit.

Next, you will be asked to give a deposition (getting your testimony on tape) in case

you are not able to appear in court. Some attorneys also have a videographer follow

you for a day to document what a typical day with mesothelioma is like for you. This can be

shown in court to support your case.Many patients worry that with a lengthy

litigation process, they may die before the case is settled. If you pass away, your loved

ones can continue to litigate in your place if you have designated an executor of your

estate and beneficiaries in your will.

preparing for

end of Life

enD oF LIFe Care FoCUSeS on

comfort and symptom relief, while incorporating spiritual and psychological counseling to help

prepare for a good death. Preparing for death also involves drawing up

legal documents, such as a health care power of attorney and living will. With a health care

power of attorney, you will want to choose a person to make medical decisions and initiate

your care plan when you are no longer able to speak for yourself. Sometimes close family

members are not able to separate emotions from logic and may have difficulty carrying

out your wishes, so discuss your wishes with your appointee to verify his/her cooperation

and comfort with serving as your health care power of attorney.

A living will, sometimes referred to as an advance directive, defines what, if any,

extraordinary measures a person would want to be taken to prolong his or her life.

Many of the documents you’ll need can be found at www.caringinfo.org, a website run

by the National Hospice and Palliative Care Organization.Hospice services are designed to provide

symptom relief, pain management, and support to patients and their families. A

person is referred to hospice services when life expectancy is less than six months. Most

hospice services take place in patients’ homes, assisted living facilities, or nursing

homes.Depending on where you live, you may have

multiple options when choosing a hospice provider. Just as carefully as you chose the

health care team to treat your mesothelioma, you will want to do the same in selecting a

hospice provider. Set up an interview and start by asking the following questions:

n Does the provider serve the area in which you live?

n How long has the provider been in operation?

n Does Medicare certify the provider?

n Does the provider accept Medicaid?

n Does your insurance cover the provider?

n Is the provider licensed by the state?

n What additional services does the provider cover, such as follow-up phone calls,

mailings, support groups, and retreats or

activities for families?

n What services, if any, are not provided?

n Is participation in care by a family member required for enrollment in services?

n What is expected from the family

caregiver?

n What, if any, out-of-pocket charges can be

expected?

n How flexible is the schedule of visits?

n Who provides the on-call coverage?

n Does the provider have a residential

facility?

n What types of services are provided for

funeral arrangement support?

n How are bereavement services managed,

and how long do they last?

After answering your questions, if you are

still uncertain whether the provider is right for

you, you can request an evaluation visit. This

will give you the chance to interact with the

staff in a comfortable environment and get a

better idea of how the services will work. You

may also want to research the reputation of

the agency by asking your doctor, a chaplain,

other health care professionals, and families of

previous patients for advice and information

resources

asbestos Disease awareness organization

www.asbestosdiseaseawareness.org

Provides education and advocacy on behalf of

asbestos victims.

Cancer Legal resource Center

213-THE-CLRC (743-2572)

www.disabilityrightslegalcenter.org/about/

cancerlegalresource.cfm

Provides information on cancer-related legal

issues for cancer patients and their families.

hospice Foundation of america

800-854-3402

www.hospicefoundation.org

Offers practical information about coping with

death and grief, a blog, and teleconferences.

Mesothelioma applied research Foundation

877-363-6376

www.marf.org

Provides education, support, and advocacy

for mesothelioma patients. MARF also funds

research and has established a grant program to help newly diagnosed patients travel

to consult with an expert.

national association of hospital hospitality

houses

800-542-9730

www.nahhh.org

Provides accommodations for patients receiving medical treatment away from home.

national hospice and palliative Care

organization

800-658-8898

www.caringinfo.org

The NHPCO is an association of programs

that provide hospice and palliative care.

For additional resources, visit www.cure

today.com/toolbox.

Glossary

asbestos > A group of minerals that take the form of tiny fibers. Loose asbestos fibers breathed into the lungs can cause lung

cancer and malignant mesothelioma.Malignant mesothelioma > A rare type of

cancer in which malignant cells are found in the lining of the chest or abdomen.

Mesothelium > A membrane that covers and protects most of the internal organs. The

mesothelium produces a lubricating fluid that allows moving organs to glide easily against

adjacent structures. The mesothelium has different names, depending on its location

in the body.pericardium > The thin layer of tissue that

forms a sac surrounding the heart.

peritoneum > The tissue that lines the abdominal wall and covers most of the organs

in the abdomen.

pleura > A thin layer of tissue that covers the

lungs and lines the interior wall of the chest

cavity.

SOURCE: National Cancer Institute

. . . . .

Content by Jennifer Klem, PhD, Nanette LavoieVaughan, MSN, APN, and Lena Huang

Cover Illustration by Jan Pults

Published in CURE Fall 2009

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