Carcinoma Introduction

The Basics of Breast Cancer

2006-05-01T08:03:00.000-07:00

What is the breast?

The breast is a collection of glands and fatty tissue that lies between the skin and the chest wall. The glands inside the breast produce milk after a woman has a baby. Each gland is also called a lobule, and many lobules make up a lobe. There are 15 to 20 lobes in each breast. The milk gets to the nipple from the glands by way of tubes called ducts. The glands and ducts get bigger when a breast is filled with milk, but the tissue that is most responsible for the size and shape the breast is the fatty tissue. There are also blood vessels and lymph vessels in the breast. Lymph is a clear liquid waste product that gets drained out of the breast into lymph nodes. Lymph nodes are small, pea-sized pieces of tissue that filter and clean the lymph. Most lymph nodes that drain the breast are under the arm in what is called the axilla.

What is breast cancer?

Breast cancer happens when cells in the breast begin to grow out of control and can then invade nearby tissues or spread throughout the body. Large collections of this out of control tissue are called tumors. However, some tumors are not really cancer because they cannot spread or threaten someone's life. These are called benign tumors. The tumors that can spread throughout the body or invade nearby tissues are considered cancer and are called malignant tumors. Theoretically, any of the types of tissue in the breast can form a cancer, but usually it comes from either the ducts or the glands. Because it may take months to years for a tumor to get large enough to feel in the breast, we screen for tumors with mammograms, which can sometimes see disease before we can feel it.

Am I at risk for breast cancer?

Breast cancer is the most common malignancy affecting women in North America and Europe. Every woman is at risk for breast cancer. Close to 200,000 cases of breast cancer were diagnosed in the United States in 2001. Breast cancer is the second leading cause of cancer death in American women behind lung cancer. The lifetime risk of any particular woman getting breast cancer is about 1 in 8 although the lifetime risk of dying from breast cancer is much lower at 1 in 28.

Risk factors for breast cancer can be divided into those that you cannot change and those that you can change. Some factors that increase your risk of breast cancer that you cannot alter include being a woman, getting older, having a family history (having a mother, sister, or daughter with breast cancer doubles your risk), having a previous history of breast cancer, having had radiation therapy to the chest region, being Caucasian, getting your periods young (before 12 years old), having your menopause late (after 50 years old), never having children or having them when you are older than 30, and having a genetic mutation that increases your risk. Genetic mutations for breast cancer have become a hot topic of research lately. Between 3% to 10% of breast cancers may be related to changes in either the gene BRCA1 or the gene BRCA2. Women can inherit these mutations from their parents and it may be worth testing for either mutation if a woman has a particularly strong family history of breast cancer (meaning multiple relatives affected, especially if they are under 50 years old when they get the disease). If a woman is found to carry either mutation, she has a 50% chance of getting breast cancer before she is 70. Family members may elect to get tested to see if they carry the mutation as well. If a woman does have the mutation, she can get more rigorous screening or even undergo preventive (prophylactic) mastectomies to decrease her chances of contracting cancer. The decision to get tested is a highly personal one that should be discussed with a doctor who is trained in counseling patients about genetic testing.

Certain factors which increase a woman's risk of breast cancer can be altered including taking hormone replacement therapy (long term use of estrogens with progesterone for menopause symptoms slightly increases your risk), taking birth control pills (a very slight increased risk that disappears in women who have stopped them for over 10 years), not breastfeeding, drinking 2 to 5 alcoholic drinks a day, being overweight (especially after menopause), and not exercising. All of these modifiable risk factors are not nearly as important as gender, age, and family history, but they are things that a woman can control that may reduce her chances of developing a breast malignancy. Remember that all risk factors are based on probabilities, and even someone without any risk factors can still get breast cancer. Proper screening and early detection are our best weapons in reducing the mortality associated with this disease.

How can I prevent breast cancer?

The most important risk factors for the development of breast cancer cannot be controlled by the individual. There are some risk factors that are associated with an increased risk, but there is not a clear cause and effect relationship. In no way can strong recommendations be made like the cause and effect relationship seen with tobacco and lung cancer. There are a few risk factors that may be modified by a woman that potentially could influence the development of breast cancer. If possible, a woman should avoid long-term hormone replacement therapy, have children before age 30, breastfeed, avoid weight gain through exercise and proper diet, and limit alcohol consumption to 1 drink a day or less. For women already at a high risk, their risk of developing breast cancer can be reduced by about 50% by taking a drug called Tamoxifen for five years. Tamoxifen has some common side effects (like hot flashes and vaginal discharge), which are not serious and some uncommon side effects (like blood clots, pulmonary embolus, stroke, and uterine cancer) which are life threatening. Tamoxifen isn't widely used for prevention, but may be useful in some cases. There are limited data suggesting that vitamin A may protect against breast cancer but further research is needed before it can be recommended for prevention. Other things being investigated include phytoestrogens (naturally occurring estrogens that are in high numbers in soy), vitamin E, vitamin C, and other drugs. Further testing of these substances is also needed before they can be recommended for breast cancer prevention. Right now, the most important thing any woman can do to decrease her risk of dying from breast cancer is to have regular mammogram screening, learn how to perform breast self exams, and have a regular physical examination by their physician.

What screening tests are available?

The earlier that a breast cancer is found, the more likely it is that treatment can be curable. For this reason, we screen for breast cancer using mammograms, clinical breast exams, and breast self-exams. Screening mammograms are simply x-rays of each breast. The breast is placed between two plates for a few seconds while the x-rays are taken. If something appears abnormal, or better views are needed, magnified views or specially angled films are taken during the mammogram. Mammograms often detect tumors before they can be felt and they can also identify tiny specks of calcium that could be an early sign of cancer. Regular screening mammograms can decrease the mortality of breast cancer by 30%. The majority of breast cancers are associated with abnormal mammographic findings. Woman should get a yearly mammogram starting at age 40 (although some groups recommend starting at 50), and women with a genetic mutation that increases their risk or a strong family history may want to begin even earlier.

Between the ages of 20 and 39, every woman should have a clinical breast exam every 3 years; and after age 40 every woman should have a clinical breast exam done each year. A clinical breast exam is an exam done by a health professional to feel for lumps and look for changes in the size or shape of your breasts. During the clinical breast exam, you can learn how to do a breast self-exam. Every woman should do a self breast exam once a month, about a week after her period ends. If you find any changes in your breasts, you need to contact your doctor. About 15% of tumors are felt but cannot be seen by regular mammographic screening.

There are some experimental screening modalities that are currently being studied. These include MRI, ductal lavage, ultrasound, optical tomography, PET scan, and digital mammograms.

What are the signs of breast cancer?

Unfortunately, the early stages of breast cancer may not have any symptoms. This is why it is important to follow screening recommendations. As a tumor grows in size, it can produce a variety of symptoms including:

lump or thickening in the breast or underarm
change in size or shape of the breast
nipple discharge or nipple turning inward
redness or scaling of the skin or nipple
ridges or pitting of the breast skin

If you experience these symptoms, it doesn't necessarily mean you have breast cancer, but you need to be examined by a doctor.

How is breast cancer diagnosed and staged?

Once a patient has symptoms suggestive of a breast cancer or an abnormal screening mammogram, they will usually be referred for a diagnostic mammogram. A diagnostic mammogram is another set of x-rays; however, it is more complete with close ups on the suspicious areas. Sometimes, particularly if your doctors think that you may have a cyst or you are young and have dense breasts, you may be referred for an ultrasound. An ultrasound uses high-frequency sound waves to outline the suspicious areas of the breast. It is painless and can often distinguish between benign and malignant lesions.

Depending on the results of the mammograms and/or ultrasounds, your doctors may recommend that you get a biopsy. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to get cells that can be examined under a microscope. There are different types of biopsies; they differ on how much tissue is removed. Some biopsies use a very fine needle, while others use thicker needles or even require a small surgical procedure to remove more tissue. Your team of doctors will decide which type of biopsy you need depending on your particular breast mass.

Once the tissue is removed, a doctor known as a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, then the pathologist will characterize it by what type of tissue it arose from, how abnormal it looks (known as the grade), whether or not it is invading surrounding tissues, and if the entire lump was excised, the pathologist can tell if there are any cancer cells left at the borders (also known as the margins). The pathologist will also test the cancer cells for the presence of estrogen and progesterone receptors as well as a receptor known as

HER-2/neu. The presence of estrogen and progesterone receptors is important because cancers that have those receptors can be treated with hormonal therapies. HER-2/neu expression may also help predict outcome. There are also some therapies directed specifically at tumors dependent on the presence of HER-2/nue.

In order to guide treatment and offer some insight into prognosis, breast cancer is staged into five different groups. This staging is done in a limited fashion before surgery taking into account the size of the tumor on mammogram and any evidence of spread to other organs that is picked up with other imaging modalities; and it is done definitively after a surgical procedure that removes lymph nodes and allows a pathologist to examine them for signs of cancer. The staging system is somewhat complex, but here is a simplified version of it:

Stage 0 (called carcinoma in situ)

Lobular carcinoma in situ (LCIS) refers to abnormal cells lining a gland in the breast. This is a risk factor for the future development of cancer, but this is not felt to represent a cancer itself.

Ductal carcinoma in situ (DCIS) refers to abnormal cells lining a duct. Women with DCIS have an increased risk of getting invasive breast cancer in that breast. Treatment options are similar to patients with Stage I breast cancers.

Stage I
early stage breast cancer where the tumor is less that 2 cm across and hasn't spread beyond the breast

Stage II
early stage breast cancer where the tumor is either less than 2 cm across and has spread to the lymph nodes under the arm; or the tumor is between 2 and 5 cm (with or without spread to the lymph nodes under the arm); or the tumor is greater than 5 cm and hasn't spread outside the breast

Stage III
locally advanced breast cancer where the tumor is greater than 5 cm across and has spread to the lymph nodes under the arm; or the cancer is extensive in the underarm lymph nodes; or the cancer has spread to lymph nodes near the breastbone or to other tissues near the breast

Stage IV
metastatic breast cancer where the cancer has spread outside the breast to other organs in the body

Depending on the stage of your cancer, your doctor may want additional tests to see if you have metastatic disease. If you have a stage III cancer, you will probably get a chest x-ray, CT scan and bone scan to look for metastases. Each patient is an individual and your doctors will decide what is necessary to adequately stage your cancer.

What are the treatments for breast cancer?

Surgery

Almost all women with breast cancer will have some type of surgery in the course of their treatment. The purpose of surgery is to remove as much of the cancer as possible, and there are many different ways that the surgery can be carried out. Some women will be candidates for what is called breast conservation therapy (BCT). In BCT, surgeons perform a lumpectomy which means they remove the tumor with a little bit of breast tissue around it but do not remove the entire breast. BCT always needs to be combined with radiation therapy to make it an option for treating breast cancer. At the time of the surgery, the surgeon may also dissect the lymph nodes under the arm so the pathologist can review them for signs of cancer. Some patients will have a sentinel lymph node biopsy procedure first to determine if a formal lymph node dissection is required. Sometimes, the surgeon will remove a larger part (but not the whole breast), and this is called a segmental or partial mastectomy. This needs to be combined with radiation therapy as well. In early stage cancers (like stage I and II), BCT is as effective as removal of the entire breast via mastectomy. Most patients with DCIS that have a lumpectomy are treated with radiation therapy to prevent the local recurrence of DCIS (although some of these DCIS patients may be candidates for close observation after surgery). The advantage of BCT is that the patient will not need a reconstruction or prosthesis to appear like she did before the procedure.

More advanced breast cancers are usually treated with a modified radical mastectomy. Modified radical mastectomy means removing the entire breast and dissecting the lymph nodes under the arm. Patients with DCIS that have a mastectomy do not need to have the lymph nodes removed from under the arm. Some patients are candidates for BCT but choose modified radical mastectomy for personal reasons. Your surgeon can discuss your options and the pros and cons of either procedure. Most women who have modified radical mastectomies choose to undergo a reconstruction. There are many different procedures for creating a new breast mound, and you should talk to your plastic surgeon before your surgery to discuss your options and decide on how you would like to proceed.

Chemotherapy

Despite the fact that the tumors are removed by surgery, there is always a risk of recurrence because there may be microscopic cancer cells that have spread to distant sites in the body. In order to decrease a patient's risk of recurrence, many breast cancer patients are offered chemotherapy. Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. The higher the stage of cancer you have, the more important it is that you receive chemotherapy; however, even stage I patients may benefit from chemotherapy in certain cases. In early stage patients, the risk of recurrence may be small, and thus the benefits of the chemotherapy are even smaller. However, the option to receive chemotherapy should be offered to most patients with breast cancer and they can decide if the potential benefits of chemotherapy outweigh its side effects in their own particular case.

There are many different chemotherapy drugs, and they are usually given in combinations for 3 to 6 months after you receive your surgery. Depending on the type of chemotherapy regimen you receive, you may get medication every 3 or 4 weeks; and you may have to go to a clinic to get the chemotherapy because many of the drugs have to be given through a vein. Two of the most common regimens are AC (doxorubicin and cycolphosphamide) for 3 months or CMF (cyclophosphamide, methotrexate, and fluorouracil) for 6 months. There are advantages and disadvantages to each of the different regimens that your medical oncologist will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your lifestyle.

Sometimes patients have a recurrence of their cancer, or present in stage IV with disease outside of their breast. These patients will all need chemotherapy, and a variety of different agents may be tried until a response is achieved. Sometimes we give chemotherapy before surgery, and this is called neoadjuvant chemotherapy. This is usually reserved for very advanced cancers that need to be shrunken before they can be operated on.

Radiotherapy

Breast cancer commonly receives radiation therapy. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. It comes from an external source, and it requires patients to come in 5 days a week for up to 6 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Radiation therapy is used in all patients who receive breast conservation therapy (BCT). It is also recommended for patients after a mastectomy who had large tumors, lymph node involvement, or close/positive margins after the surgery. Radiation is important in reducing the risk of local recurrence and is often offered in more advanced cases to kill tumor cells that may be living in lymph nodes. Your radiation oncologist can answer questions about the utility, process, and side effects of radiation therapy in your particular case.

Hormonal Therapy

When the pathologist examines your tumor specimen, he or she finds out if the tumor is expressing estrogen and progesterone receptors. Patients whose tumors express estrogen receptors are candidates for therapy with an estrogen blocking drug called Tamoxifen. Tamoxifen is taken by pill form for 5 years after your surgery. This drug has been shown to drastically reduce your risk of recurrence if your tumor expresses estrogen receptors. However, there are side effects commonly associated with Tamoxifen including weight gain, hot flashes and vaginal discharge that patients may be bothered by. There are also very uncommon side effects like blood clots, strokes, or uterine cancer that may scare patients from choosing to take it. You need to remember that your chances of having a recurrence of your cancer are usually higher than your chances of having a serious problem with Tamoxifen, but the decision to undergo hormonal therapy is a personal one that you should make with your doctor. There are also newer drugs, called aromatase inhibitors that act by decreasing your body's supply of estrogen; these drugs are reserved for patients who have already gone through menopause. Talk to your doctors about these new therapies.

Biologic Therapy

The pathologist also examines your tumor for the presence of HER-2/neu overexpression. HER-2/neu is a receptor that some breast cancers express. If your cancer expresses it, you usually have a higher chance of having your tumor recur after surgery. A compound called Herceptin (or Trastuzumab) is a substance that blocks this receptor and helps stop the breast cancer from growing. Some patients are candidates for this medicine. Talk to your medical oncologist to see if Herceptin is right for you.

Follow-up testing

Once a patient has been treated for breast cancer, they need to be closely followed for a recurrence. At first, you will have follow-up visits every 3-4 months. The longer you are free of disease, the less often you will have to go for checkups. After 5 years, you could see your doctor once a year. You should have a mammogram of the treated and untreated breasts every year. Because having had breast cancer is a risk factor for getting it again, having your mammograms done every year is extremely important. If you are taking Tamoxifen, it is important that you get a pelvic exam each year and report any abnormal vaginal bleeding to your doctor.

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.

Medulloblastoma

2006-04-29T17:43:00.000-07:00

T1 Tumor <3>
T2 Tumor >3 cm in diameter
T3a Tumor >3 cm in diameter with spread
T3b Tumor >3 cm in diameter with definite spread into the brain stem (part of brain that controls breathing, hearing, seeing, and other important functions)
T4 Tumor >3 cm in diameter with extension up past the aqueduct of Sylvius and/or down past the foramen magnum

In addition to “T” staging, medulloblastoma staging has been modified by including “M” staging, where the “M” stands for metastasis. Remember, this is a word that describes how far the tumor cells have spread from the original location, if at all. The M stage is determined not only by the surgeon’s observations, but also in combination with MRI scans and lumbar cytology, and consists of 5 possible groups:

M0 No evidence of metastasis
M1 Tumor cells found in cerebrospinal fluid (by lumbar puncture and cytology study)
M2 Tumor beyond primary site but still in brain
M3 Tumor deposits (“seeds”) in spine area that are easily seen on MRI
M4 Tumor spread to areas outside the CNS (outside both brain and spine)

Each patient is assigned a combination of one T stage and one M stage. As mentioned in the introduction, one of the reasons staging is important is that it helps predict how a patient might do in the long run, or how “curable” their cancer is, in a way. For medulloblastomas, the M stage is considered far more important in determining ultimate patient outcome and survival than the T stage. In other words, regardless of what the T stage may be, children who are in the M0 group do far better than those in M1, who tend to fare better than M2 kids, who in turn do better than M3 or M4 children.

Of course, each case of medulloblastoma is different, and while staging tries to group patients together, any one individual patient may not follow the rules, so to speak.

How is medulloblastoma treated?

Surgery

Surgery is typically the first component of therapy, although it is no longer acceptable as the only component. Long-term results of medulloblastoma patients treated as far back as the 1930’s have taught us that surgery alone does not cure this tumor.

It is, however, very important to perform as maximal and complete a surgery as possible, with the goal being removal of all visible tumor while sparing as much surrounding brain tissue as possible. This is then confirmed after surgery with a post-operative MRI scan of the brain to look for any leftover, or residual tumor. Based on what the MRI shows, the surgery is classified as one of the following:

Gross total resection = No evidence of any tumor left behind either at time of surgery or on post-surgery MRI
Near-total resection = More than 90% of original tumor removed by surgery
Subtotal resection = Anywhere from 51-90% of original tumor removed by surgery
Partial resection = Anywhere from 10-50% of original tumor removed by surgery
Any surgery that removed less than 10% of the original tumor is basically considered just a biopsy, or sampling, of the tumor.

So the ideal situation is a gross total resection, but this is not always possible. For example, sometimes the tumor is invading into or stuck onto other parts of the brain, making safe surgery very difficult. Nonetheless, the overall goal is to take as much of the tumor out as possible without risking severe brain deficits, as the long-term survival of medulloblastoma patients is directly influenced by the degree of surgery. In other words, the more complete the surgery, the better the long-term outcome.

Radiation Therapy

After surgery, external radiation to the entire CNS (craniospinal irradiation, or CSI) is recommended to prevent the tumor from coming back in this area (recurrence, or relapse). Even if complete surgery is performed, low-dose radiation to the brain and spine is very important for local control, local meaning within the CNS. This is the region that is most at-risk for the tumor returning.

Data from old clinical studies of medulloblastoma patients clearly shows that as many as 60-70% of children who got good surgery and no other treatment had recurrence of the tumor. In contrast, patients who got good surgery followed by CSI had lower rates of tumor recurrence. The long-term disease-free survival (patient living without tumor) with the modern radiotherapy techniques of today is as high as 60-65%.

After radiation of the entire cranium and spine to a lower dose of radiation, the area of the original tumor, including where the surgeon operated, continues to receive radiation to a higher final dose (so-called radiation “boost”). This is because the region in the brain where the tumor first started is the most likely place to still have some lingering, unseen, microscopic tumor cells.

Much attention has understandably been paid to the possible long-term complications of radiation therapy to the brain and spine of a growing child. These can include deficits in memory, learning, and social/emotional adjustment, and growth problems. The development of such side effects depends on many factors, including extent of pre-radiation surgery, amount and location of brain that is treated, and how much radiation dose is given, among others.

However, modern radiotherapy techniques and proper attention to minimizing radiation dose to important brain structures whenever feasible can allow for safe and effective treatment, even in younger children. While no therapy is without its side effects, radiation therapy can be planned and delivered in such a way as to minimize potential long-term side-effects. This is best accomplished at a major radiation oncology center where physicians and staff are familiar with pediatric patients and technologically capable of treating childhood cancers.

Chemotherapy

At the present time, the role of chemotherapy in medulloblastoma is primarily as an additional treatment following surgery and radiation to help increase long-term disease-free survival. Clinical trials document disease-free survival at 5 years from diagnosis of about 85%, which is very good. However, these high rates were achieved with chemotherapy drugs such as cisplatin, vincristine, and CCNU, all of which have associated side effects. Furthermore, the addition of chemotherapy to the previous standard of surgery and postoperative radiation has not resulted in overall survival benefits, which are obviously a very important endpoint in pediatric cancer trials. Nonetheless, the use of chemotherapy after surgery, CSI and boost radiation is considered the current standard of care.

Importantly, studies are ongoing looking at the use of chemotherapy not only for disease control, but as a possible means to lower craniospinal radiation doses in particularly young children without compromising local tumor control.

In light of the potentially severe long-term side effects of radiation to the CNS of a very young child, this is certainly a worthwhile research endeavor, and results of such studies may be incorporated in future treatment of medulloblastomas

Craniopharyngioma

2006-04-29T17:37:00.000-07:00

Some Background

Almost 20% of all childhood cancers start in the central nervous system (CNS), which consists of the brain, the spinal cord, and the surrounding fluid (cerebrospinal fluid, or CSF), lining tissues (meninges) and bone (cranium and vertebrae).

In the past several years, the incidence of pediatric CNS tumors has been increasing. This increase is partially explained by medical advances that have led to earlier detection and diagnosis of brain tumors.

There are many different types of pediatric CNS cancers, all of which have long, rather complicated names. The diagnosis typically depends on two things: 1) where in the CNS the tumor starts, or the location, and 2) how the tumor looks under a microscope, also known as the histology. Primary brain tumors are tumors that arise in the brain, while primary spinal tumors grow in the spinal cord. However, some brain tumors can spread to involve parts of the spine, and vice versa. On rare occasion, certain types of tumors can even spread to areas outside of the CNS, such as distant bones or bone marrow.

Of course, ultimately, every cancer treatment plan is individualized for every patient, and takes into account not only the stage and the clinical data, but also the goals and desires of the patient and his or her family.

What is a craniopharyngioma?

Craniopharyngioma is a benign* brain tumor that accounts for about 3-9% of all pediatric CNS cancers. This tumor results from abnormal overgrowth of a part of the brain called Rathke's pouch, located near the pituitary gland. It typically consists of a combination of calcium deposits mixed with cysts, or pockets, of fluid. The fluid characteristically contains protein, lipid (fat) and cholesterol pieces, giving it a so-called "crankcase oil" texture.

The word tumor itself refers to an abnormal growth or mass of cells, also referred to in general terms as a "cancer".

Tumors (cancers) can be either "benign" or "malignant", depending on how "bad" the tumor cells look under a microscope. In simple terms, "benign" tumor cells have a sort of "innocent" appearance under the microscope; they usually do not have features associated with invasion or spread (metastasis) to other locations. In contrast, "malignant" tumors have cells that can, and are likely to, invade and spread, especially if left untreated.

However, it is very important to realize that a benign microscopic tumor is NOT necessarily clinically benign or innocent. Remember, a benign tumor is still a tumor, and it represents uncontrolled, inappropriate growth. Although benign tumors may not spread far beyond where they started, they can continue to grow and thus can still cause trouble from local expansion, particularly in an otherwise small, enclosed space like the brain. Pressure and obstruction from a growing mass can lead to severe neurological deficits and, worst case scenario, even death.

Who gets this tumor, and how?

Craniopharyngiomas can occur in both children and adults, with a peak in incidence at 9 to 14 years of age. In fact, more than 50% of patients are under the age of 18 years. There is no clear association of the tumor with a particular gender or race. It is not really known what causes craniopharyngiomas, but they do not appear to "run in families" or to be directly inherited from the parents.

What are the signs of a craniopharyngioma?

The most common symptoms of this tumor are visual changes, most often loss
of peripheral vision in one eye (visual field cuts) or blurriness. This is because of the proximity of craniopharyngiomas to the visual nerve pathways in the brain. Similarly, craniopharyngiomas are also close to the pituitary gland, and thus children can present with hormonal, or endocrine, problems. This is because the pituitary gland controls various important hormone systems, including those vital for body growth, sexual organ maturation, and thyroid gland function. Up to half of children can even develop notable personality changes or cognitive deficits. Finally, general signs like nausea, vomiting and headache may occur due to increased and excessive pressure in the brain from the tumor.

Please note that the symptoms mentioned here do not necessarily or automatically mean a child has a brain tumor, but further medical evaluation is required to rule out the possibility of a brain tumor such as craniopharyngioma.

How is a craniopharyngioma diagnosed?

Typically, the diagnosis is made based on a radiology study such as magnetic resonance imaging (MRI) scan of the brain with gadolinium contrast-enhancement. A craniopharyngioma has a very characteristic appearance on MRI scan: a well-defined mass with a combination of solid and cystic parts. Importantly, this is a tumor that occurs in the suprasellar region, a part of the brain also containing the optic chiasm (contains nerves for vision) and hypothalamus (regulates release of growth, thyroid, and stress hormones, among others).

As mentioned earlier, craniopharyngioma is a benign tumor and thus is not expected to spread from the brain to the spine, cerebrospinal fluid (CSF), or other sites outside the CNS. Thus, no additional scans are required unless indicated by symptoms or physical exam findings.

How is craniopharyngioma treated?

Ironically, although craniopharyngiomas are benign tumors that should have relatively good long-term outcome, the optimal management of them is a very controversial issue in pediatric neurooncology. One major explanation for this is the inherent conflict between wanting to "cure" the patient and wanting to minimize the long-term morbidity, or negative side effects. Physicians are understandably hesitant to recommend and pursue the most aggressive treatment, if it risks leaving the child with worse neurologic problems than the underlying tumor itself.

So although no clear consensus has been reached in the medical community on the best therapeutic regimen for craniopharyngioma, presented below are some general management principles. It is important to remember, however, that each patient's case should be approached individually, and the therapy plan designed accordingly.

Surgery and Radiation Therapy

Surgery is typically the initial and major component of therapy, although the "right" or "best" extent of surgery is a matter of much debate. Some believe that the main goal should be gross total resection of the tumor, or in other words, complete surgical removal of all visible tumor. It is technically possible to perform a total resection in about 70-90% of cases. The success rate of total resection alone also ranges from 70-90%, (meaning the tumor comes back in about 10-30% of patients), which is quite good. So if total tumor resection is achieved based on both what the surgeon describes and what the post-surgical MRI scan shows, then careful observation after surgery is reasonable. Any additional treatment could be used only if and when indicated (ie: if the tumor comes back in future).

A complete surgery with no other required treatment sounds great, but bear in mind that the rates of serious surgical complications following complete tumor resection are high: 50-90% risk of damage to the hypothalamus, 1-12% risk of brain hemorrhage during the surgery, small risk of even death. Not surprisingly, the skill and experience of the surgeon plays an important role in the outcome, both in terms of better tumor control and fewer surgical complications.

However, even in the best of hands, there are many cases in which the craniopharyngioma may press against or grow rather close to various critical brain structures (optic chiasm, hypothalamus, blood vessels), thereby making total resection essentially impossible. Instead, the surgeon removes as much as tumor as is safely possible. Simply observing after such a surgery would seem like a bad idea, since there is known tumor still left behind and untreated.
This has led to several important questions: Can you perform a partial* resection in these difficult cases, but then follow it with radiation therapy to eradicate, or "mop up", the remaining tumor cells? Could this approach achieve equally good results as a total resection (if it had been possible), while decreasing the possible long-term side effects of a big surgery? In fact, knowing that the naked eye at the time of surgery can not possibly see individual, microscopic tumor cells that might be left behind, should gross total resection alone EVER be done? Instead, should partial surgery and postoperative radiation for residual tumor be the goal for all patients, thus minimizing surgical risk and maximizing microscopic tumor control.

Studies have tried to answer these questions, and found that craniopharyngioma patients treated with partial resection and radiation have 10-year and 20-year progression-free-survival rates as high as 70-90%. In other words, these patients are living without signs of growing or returning tumor as long as 10 and 20 years after treatment. Notice that this is comparable to the rates mentioned earlier for complete surgery alone, but with much lower rates of problems like hypothalamus damage or brain hemorrhage.

A few words specifically regarding post-surgical radiation therapy: Firstly, a post-operative MRI scan of the brain is usually obtained to look for any leftover tumor. Residual craniopharyngioma can appear as anything from calcified little "flecks", to a more standard-looking cystic-solid mass. Based on what the MRI shows, together with what the surgeon reports he or she was able to do in the operating room, the surgery is classified as a "total" versus "less-than-total" (aka "partial", "subtotal", or "incomplete") resection.

If it is a partial resection, the patient should receive radiation therapy to the tumor site to reduce the risk of local tumor recurrence. If the radiation is delayed in such cases and the patient is observed, the tumor will undoubtedly return within 3 years (70-100% of these patients experience relapse). On top of that, treatment at the time of relapse is often more complicated and dangerous. Thus it is generally recommended that patients who get partial resections should receive the radiation therapy upfront, rather than delaying it till the tumor comes back. In the postoperative setting, radiation is usually delivered only to the region of the original tumor, including the surgical area and all remaining tumor. Surrounding brain tissue and other critical structures are excluded from the treatment field as much as possible.

Much attention has understandably been paid to the possible long-term complications of radiation therapy to the brain and spine of a growing child. These can include deficits in memory, learning, and social/emotional adjustment, among other things. The development of such side effects depends on many factors, including extent of pre-radiation surgery, amount and location of brain that is treated, and how much radiation dose is given, among others.

However, modern radiotherapy techniques and proper attention to minimizing radiation dose to important brain structures whenever feasible can allow for safe and effective treatment, even in younger children. While no therapy is without its side effects, radiation therapy can de planned and delivered in such a way as to minimize any potential long-term side-effects. This is best accomplished at a major radiation oncology center where physicians and staff are familiar with pediatric patients and technologically capable of treating childhood cancers.

Chemotherapy

There is currently no real role for chemotherapy in the treatment of craniopharyngioma. As it is a benign tumor, disease spread to distant locations is not typically expected, and thus systemic (ie: "body-wide") medication like chemotherapy has not been extensively studied.

Overview of Brain Metastases and Available Treatments

2006-04-29T17:17:00.000-07:00

Brain Tumors versus Brain Metastases

Differing between these two types of brain lesions is a common source of confusion for many people. Primary brain tumors are tumors that start in the brain, and are actually quite rare, with an estimated 18,500 new cases in 2005. Brain metastases are far more common, and are tumors that have traveled to the brain from another area of the body. There are an estimated 170,000 patients who develop brain metastases each year.

Let's use an example to better understand this latter concept: a lung cancer is first formed in the lung tissue, but tumor cells can break off from the original mass and travel through the bloodstream or lymph system to other areas of the body, including the brain. This spreading of the tumor is known as “metastasis”. When a lung cancer metastasizes to the brain, this “brain tumor” is actually lung cancer cells.

Sounds odd, but if the pathologist took a biopsy of the brain lesion and looked at it under a microscope, it would look like lung cancer cells. It is important to understand the difference between primary brain tumors and brain metastases because they are treated differently. I occasionally hear the media refer to a person who died of lung cancer and brain cancer, when, in actuality, it was lung cancer that had metastasized to the brain.

Among tumor types, lung cancers account for the highest number of brain metastases, with 25% of patients being affected at some time in their disease. Other cancers that commonly metastasize to the brain include melanoma, breast cancer, colon cancer, and renal cell (kidney) cancer. Although these are the most likely types to do so, technically any type of cancer could spread to the brain.

All Tumors Are Not Created Equal

One thing to keep in mind is that all cancers are not equal. Some are more aggressive and/or less susceptible to our treatments than others, and for this reason, prognoses vary greatly from tumor to tumor. These variations are also important to consider when choosing treatments. For instance, primary lung cancers are quite sensitive to radiation, but melanomas are not. This susceptibility to radiation, or radiosensitivity, does not change once the tumor spreads to the brain. In turn, treatment decisions vary based on the primary (original site) tumor type. This holds true for chemotherapy as well. If a primary tumor is sensitive to a particular drug, the brain metastases from that tumor type are more likely to be affected by the same drug. For example, lung cancer is often treated with cisplatin, but breast cancer is not as sensitive to cisplatin, so another drug would be used for brain metastasis from primary breast cancer.

Brain Metastases on the Rise

The oncology community has seen a rise in the number of brain metastases in recent years. Researchers have known for years that many of the chemotherapy agents commonly used are not able to cross the blood-brain barrier, meaning that the drugs are not able to penetrate the brain, and therefore cannot effectively kill cancer cells that make their way to this sanctuary. It is thought that as newer chemo-, bio-, and immunotherapies all become increasingly more effective at treating cancer in the rest of the body, some cancer cells run for cover, so to speak, and hide out in the brain. In turn, there are a limited number of medications for treating brain metastases, and most therapies center around surgical and radiation techniques. We will review the various techniques available and the relevant supporting data.

Unfortunately, in most cancers, once a person develops brain metastases, the tumor is not curable. With current treatments, patients can live from months to years, depending on the number of brain metastases, the type of tumor, and the amount of cancer present in the rest of the body. There are exceptions to this rule in the case of tumors that are highly sensitive to chemotherapy, such as germ cell tumors (testicular), lymphomas, leukemias, and the odd case here and there in other cancer types.

Classifying Brain Metastases

The Radiation Therapy Oncology Group (RTOG) found that certain factors clearly affected the survival of patients and developed a classification system to better evaluate outcomes and help in making treatment decisions. This classification is called recursive partitioning analysis (RPA). The groups are broken down as follows:

Class I : Karnofsky performance status** > 70 (meaning can do normal activity with effort; some signs or symptoms of disease, or better), age <> 70 (meaning normal activity with effort; some signs or symptoms of disease, or better), age > 65, uncontrolled primary tumor, or metastases other than brain

Class III : Karnofsky performance status** <>**(Karnofsky performance status is a measure of how well a patient functions. It is commonly used by physicians to classify impairment of function. It rates patients from 0 to 100, with 100 being no complaints with normal functioning and 0 being deceased).

The RTOG found that patients in class I had a median survival of 7.1 months (median is the point at which half of the patients have died and half are still alive); class II had a median survival of 4.2 months; and class III had a median survival of 2.3 months. More analysis has revealed that class II patients that have controlled primary disease have a survival similar to class I patients. These class groupings allow researchers to better determine which patients will benefit from certain treatments.

Treatment Options

Initial Treatment

The danger of brain metastases is the space they take up in the brain and the pressure they put on surrounding tissue. This pressure can cause the symptoms associated with brain lesions, such as headaches, speech difficulties, seizures, nausea/vomiting, weakness of a limb, or visual disturbances. The goal of initial therapy is to relieve some of this pressure on the brain tissue by decreasing swelling using drugs called corticosteroids (dexamethasone, hydrocortisone), either orally or through an intravenous (IV) line. Some patients may see relief of symptoms after starting steroids, but this does not mean the tumor is gone, and so they will still require additional treatment. Some patients will also be given an anti-seizure medication, typically to help prevent further seizures in those who have already experienced one or more seizure events. These medications will help to stabilize the patient until further treatment can be planned.

Whole Brain Radiation Therapy

Whole brain radiotherapy (WBRT) is just what it sounds like – giving radiation to the entire brain. This is generally given in 10 to 15 doses (also called fractions), and is often used in patients with poor prognostic factors (RPA classes II & III), patients who are not candidates for surgery, or patients with more than 3 brain lesions. Many patients may receive WBRT in combination with another therapy (surgery, radiosurgery). You may wonder why one would want to treat the whole brain, when only a small portion contains tumor. The thinking is that there may well be cancer cells in the normal-appearing brain, but just not enough of them yet to form a mass and get “picked up” by radiology studies, so we want to go ahead and attempt to kill them all.

WBRT has been reported to improve symptoms of brain metastases in 70-90% of patients, although some of this benefit is also a result of the corticosteroids. Despite this symptom improvement, recurrence is common, and control of brain metastases is probably only achieved in half of the patients. Patients with tumors that are more sensitive to the effects of radiation fare better (lung and breast, for example) than those with relatively radioresistant tumors (melanoma, colon, and renal cancers). It has been difficult to evaluate the long-term effects of WBRT, given the small numbers of patients that survive long-term. These effects could possibly include dementia and gait difficulties (difficulty walking). Studies are looking at combining WBRT with the other therapies, which will be discussed further.

Radiosurgery or Stereotactic Radiosurgery

Radiosurgery is a confusing term. It is actually not surgery at all, but highly precise administration of a large dose of radiation to the tumor site. This radiation can be administered by a traditional radiation machine (called a linear accelerator) or a specialized machine (called Gamma Knife®, XKnife™, or CyberKnife®). This method delivers several hundred beams of radiation from many directions, forming a concentration of radiation at the point where all the beams meet (see photo). This allows for a high dose of radiation to be delivered to the tumor, while sparing the surrounding tissue from damage from the high dose. Radiosurgery is highly dependent on accuracy, and requires that the patient's head be securely stabilized using a helmet, so there is no movement during the treatment. The radiation beams go through hundreds of holes in the helmet to converge on the tumor. Unlike traditional external beam radiation, which is usually given daily over many weeks, this therapy is administered in a single dose or several non-daily doses. More than one brain tumor can be treated during one session (for example, if a patient had 2 separate brain metastases, both could be treated on the same day).

There have been several studies looking at combining radiosurgery and WBRT (radiosurgery in combination with WBRT vs. WBRT alone). None of these studies has found a significant improvement in survival with the addition of radiosurgery in patients with multiple brain metastases. One study, however, found a benefit for patients with a single metastasis. Patients with a single metastasis who received radiosurgery with WBRT had an average survival of 6.5 months, versus 4.9 months in the group that received WBRT only. This may seem like a small increase, but it tells researchers that the combined therapy may be better than WBRT alone in single brain metastasis. Reviews have found that surgery (actually cutting out the metastasis) has similar results to radiosurgery, but radiosurgery may result in lower rates of recurrence.

Surgery

For patients with a single brain lesion, surgery may be a good option, given the tumor is under control in the rest of the body. Although no conclusive evidence exists to support surgery, previous studies have found an increase in survival for patients who were able to have all metastatic lesions removed. In studies, most patients received WBRT following surgery. One large review found that in patients who had surgery to remove brain metastases, survival was improved from 6 months to 14 months in those who were able to have all lesions removed, versus those who could not. Surgery is often the treatment of choice in life-threatening lesions, but in other lesions the evidence is not as clear. Comparative studies are needed to determine the impact of traditional surgery versus radiosurgery.

Chemotherapy

It is widely thought that most chemotherapy agents are unable to cross the blood brain barrier; in other words, they move through the blood stream, but cannot enter the brain. This makes the brain a safe haven for cancer cells that “escape” the chemo and make their way there. That being said, researchers have found that brain metastases from tumor types that are particularly sensitive to chemotherapy (testicular, lymphomas, and small cell lung cancer) are also sensitive to chemotherapy. In addition, patients that have not already received a lot of chemotherapy may have a greater reduction in brain metastases with chemotherapy treatment. This leads researchers to believe that there is some penetration of the blood brain barrier by chemotherapy, just not always in effective amounts

One of the most promising chemotherapy agents is temozolomide (Temodar® ), an oral medication that is capable of crossing the blood-brain barrier. This medication is approved for use by the Food & Drug Administration in primary brain tumors and metastatic melanoma lesions. The encouraging results in these diseases led to clinical trials in brain metastases. Early studies have been done in conjunction with WBRT and have shown some benefit, particularly in younger patients with better performance statuses (how well they can carry out daily activities). Larger, more conclusive studies still need to be conducted in brain metastases patients.

Other agents being studied in brain metastases in lung cancer include: gefitinib (Iressa), topetecan, paclitaxel, and cisplatin. Studies in other tumor types generally use chemotherapies with known efficacy for that particular tumor type.

Brachytherapy

Brachytherapy is a variation of radiation therapy and is sometimes called “internal radiation”. The patient can have radioactive seed implanted in the area of the tumor during surgery. This material delivers a dose of radiation to a small, surrounding area. Brachytherapy can spare damage to healthy tissue in the area, but has the potential for one major complication called radiation necrosis. Radionecrosis is basically death and rotting of the irradiated tumor cells. If this dead cellular debris is not “cleared out” and absorbed over time by the body, surgical removal might be needed.

A newer brachytherapy technique, called Gliasite Radiation Therapy System, utilizes a port implanted into the tumor site. A radioactive liquid is put into the port for a period of time (usually 3-7 days) based on desired treatment dose. The fluid is then removed, and then the port is removed. This technique is still being studies in clinical trials, but early results suggest it is safer than the seed implants, with few complications.

Hyperfractionated Stereotactic

Radiotherapy Hyperfractionated stereotactic radiotherapy (HSRT) is a technique similar to radiosurgery, except that the helmet used for locating the lesion is less invasive, the doses of radiation are spread out over several sessions, and lesions > 3cm in size can be treated (which stereotactic radiosurgery cannot). Some have suggested this as an alternative to radiosurgery, but this has not been well studied in clinical trials.

Investigational Agents

One of the reasons that brain lesions are difficult to treat with radiation is based on the fact that radiation requires oxygen to work. Brain lesions (both primary and metastases) are generally lacking oxygen. Some agents being investigated are attempting to increase the levels of oxygen in the tumor, making it more sensitive to radiation therapy (sometimes called “radiosensitizers”). The two agents most recently studied using this theory of increased oxygen are: motexafin gadolinium (Xcytrin) and Efaproxyn (efaproxiral or RSR13).

Motexafin gadolinium is thought to have an effect on cell functioning that leads to cell death, as well as an increase in sensitivity to radiation. Although trials were conducted in several tumor types, it was only found to have significant activity in non small-cell lung cancer (NSCLC). It did not prolong survival, but it did improve time to progression, and improved memory and functioning in NSCLC patients. A Phase III trial was recently completed in NSCLC, and the company is currently analyzing the data from this study. Efaproxiral did not shown a benefit for brain metastases overall, but the patients in the study who had breast cancer did have improvement in survival. For this reason, a phase III study is ongoing with this drug for metastatic breast cancer to the brain.

Preventing Brain Metastases with WBRT

Small cell lung cancer is associated with a very high risk for brain metastases; approximately 50% of patients develop lesions within 2 years of diagnosis. For this reason, researchers looked at utilizing whole brain radiation as a way to prevent future brain metastases from developing. Studies utilizing this technique have seen significant decreases in brain metastases (from 55% to 19% at 2 years and from 56% to 35% at 3 years) and increases in overall survival. Some have suggested there may be long-term neurologic impairment from this treatment, but this has not been found in trials. These results have made prophylactic WBRT the standard of care for patients with limited-stage small cell lung cancer who have complete remission after local therapy. Studies are ongoing to assess any benefits of this practice in other tumor types, but no data exists thus far.

Conclusions

Brain metastases have proven to be very difficult to treat, regardless of the primary tumor type. Clinical trials of new agents and techniques continue to seek better therapies for patients affected by these tumors.

Brain Cancer: The Basics

2006-04-29T07:03:00.000-07:00

Clarification of the jargon

Although many in the general public use the term "brain cancer", this is not a term used often by the medical community. The medical community uses the term primary brain tumor for tumors arising from the brain. There are a number of different origins of the tumor cells in the brain that are described below. The medical community uses the term metastatic cancer to the brain for tumors that have spread to the brain from other sites.

What is the brain?

The brain is the organ in a person's skull that controls the functions of all of the other organs. Together, the brain and spine make up the central nervous system. The brain is responsible for the experience of the five senses (taste, touch, sight, hearing and smell). The brain is also the seat of thought, language, personality, creativity and memory. The brain controls movement, sensation, balance, and coordination. In order to do its job, the brain requires an enormous amount of the oxygen and nutrient energy that a person takes in regularly.

The brain is comprised of nerve cells (called neurons ) which carry signals, and the cells which support the nerve cells (called glial cells ). There are a number of different types of glial cells, all with different names and functions. The glial cells outnumber the neurons in the brain by a ratio of 10:1.

What are brain tumors?

Brain tumors occur when cells in the brain begin to divide out of control and start to displace or invade nearby tissues. Large collections of this "out of control" tissue are called tumors. Occasionally, brain tumors can spread throughout the body. Tumors that have the potential to spread to other sites of the brain or body are called malignant. When tumors start in the brain, they are called primary brain tumors. Any of the various normal cell types of the brain can mutate and become a primary tumor, and the particular cell type which makes up the tumor controls how the tumor is likely to behave. Brain tumors are not really thought of as a single disease, but rather as a collection of several diseases that are characterized by the cell type that makes them up, by how they behave, and by how they are treated. One of the special characteristics of brain tumors is that benign (non-cancerous) tumors in the brain can be just as bad as malignant (cancerous) brain tumors. This is because the brain is such an important organ. It is locked into place by the skull and can't move out of the way if a tumor is growing near it. Even a benign tumor can cause pressure on the brain, and this pressure can be both symptomatic and life-threatening.

The brain is also a frequent site of metastases. Metastases are tumors which have spread from a cancer that started in a different body part; they do not start in the brain, but instead take up residence there after traveling from a separate cancer (like a lung cancer or breast cancer). These are not classified as primary brain tumors, but instead as brain metastases.

How are brain tumors classified?

Brain tumors are classified by the both the cell of the brain that makes them up, and how the tumor looks under a microscope. Primary brain tumors can arise from any of the cells in the brain. They can come from the neurons, the glial cells, the lining of the brain, or from specific structures in the brain. Metastases can travel from a variety of different cancer types. When a special type of doctor (called a pathologist ) looks at brain tumors under a microscope, he/she can get a sense of how aggressive the tumor is by the way the cells look.

Am I at risk for a brain tumor?

In the United States in 2005, it is estimated that there will be 18,500 new cases of primary brain tumors, and 12,760 deaths from primary brain tumors. For women, brain tumors represent the 10 th most common cause of cancer death, although they do not quite make the list of top 10 causes of cancer death for men. Brain tumors generally comprise about 1% of all newly diagnosed adult cancers.

Exposure to radiation has been linked to the development of certain types of primary brain tumors, especially if the exposure took place in childhood. Higher radiation doses are generally felt to increase the risk of eventually developing a brain tumor, and radiation-induced brain tumors can take anywhere from 10-30 years to form.

Although many chemicals have been shown to cause brain tumors in laboratory animals, there have never been any definite associations with chemical exposures proven in human beings. Chemicals that have been shown to cause brain tumors in animals include n-nitroso compounds, vinyl chloride, and certain organic solvents. However, when examining populations exposed to these various chemicals (like pesticide workers or workers in the petrochemical industry), there has never been any conclusive evidence to suggest that they get brain tumors at a higher rate than people without the chemical exposures.

Certain hereditary disorders can predispose someone to the development of certain brain tumors. Genetic diseases like neurofibromatosis type 1, neurofibromatosis type 2, von Hippel-Lindau disease, and tuberous sclerosis are all associated with an increased risk of developing a primary brain tumor.

With the recent popularity of cellular phones, many people have worried that their use may be a risk factor for developing brain tumors. However, there has never been any data to support this idea. In fact, a few studies have looked at this question and have always failed to show any correlation between cell phone use and brain tumors.

Because there are so many different types of brain tumors, there are different risk factors for developing each of them. To learn about the risk factors for developing a specific a specific type of brain tumor, please refer to the OncoLink overview on that particular cancer.

How can I prevent brain tumors?

Currently, there are no proven strategies to prevent the development of primary brain tumors. Studies of diets rich in anti-oxidants have not shown any benefits in terms of lowering the risk of developing primary brain tumors.

It is possible to decrease the risk of developing brain metastases from certain tumors by decreasing the risk of developing the initial primary tumor in the first place. (See the OncoLink overviews about specific primary cancers for more information on preventing various malignancies.) Sometimes, when patients have certain cancers (ie: lung) that are well controlled, they will be offered preventive radiation therapy to the brain in order to decrease the likelihood of developing brain metastases in the future. This is called prophylactic cranial radiation.

What screening tests are available?

Primary brain tumors are rare enough that they are not screened for with any specific tests. The best way to pick up a diagnosis of a brain tumor early is to see your doctor regularly for a thorough physical examination and to report any new, worrisome symptoms promptly. People with genetic disorders that predispose them for the development of primary brain tumors will often get periodic imaging studies of their brains to look for any evidence of abnormalities.

What are the signs of brain tumors?

Unfortunately, the very early stages of brain tumors may not cause any symptoms. As the tumor grows in size, it can produce a variety of symptoms, including:

headache
nausea
vomiting
loss of appetite
seizures
memory loss
weakness
visual changes
problems with speech and language
personality changes
thought processing problems

Many of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you have any of these problems. Because the brain controls so many different functions, the symptoms caused by brain tumors can be extremely variable. Headache is the most common symptom for patients with brain tumors, occurring in about 50% of cases.

How are brain tumors diagnosed and staged?

When a patient presents with symptoms suggestive of a brain tumor, the physician will perform a thorough history and physical examination. After that, the key to making the diagnosis is appropriate imaging.

Imaging can be performed with either a CT scan or MRI scan. A CT scan is a three dimensional x-ray, and patients will often be injected with a contrast agent to help visualize any abnormalities. CT scans are good tests because they are quick and easy to obtain, and will often be used as the first step towards making a diagnosis. However, an MRI scan is a better test for evaluating abnormalities in the brain. MRI scans utilize powerful magnets to make a three-dimensional picture. An MRI picks up finer detail than a CT scan, and is the study of choice to make the diagnosis of a brain tumor. MRI scans are usually obtained with the use of an injectable contrast agent as well.

For many types of brain tumors, the imaging characteristics are distinctive enough to give physicians a pretty good idea of the diagnosis. The primary management of most brain tumors is surgery. If imaging reveals that a mass suspicious for a brain tumor is in a surgically accessible spot, the patient is generally scheduled for surgery without any further diagnostic testing. After surgery, the specimen can be examined under the microscope by a pathologist, and a final diagnosis can be made. However, sometimes, tumors are not in a safe location for surgery. In those cases, in order to make a diagnosis, patients will often need a biopsy. A biopsy is a procedure where a small piece of the tumor is obtained using a needle under image guidance.

Primary brain tumors do not have a classic staging system the way most other cancers do. This is because the size of a brain tumor is less important than its location and the type of brain cell that makes it up. The likelihood of curing a brain tumor has to do with its location, the cell that makes it up, and how the tumor cells look under a microscope. Your doctor will give you a sense of how dangerous your tumor is and how it should be treated after weighing these factors.

Brain metastases are considered within the staging system of the cancer from which they originated. Thus, the presence of brain metastases automatically makes the primary tumor a stage IV cancer, because stage IV means the presence of any metastasis.

What are the treatments for brain tumors?

There are a number of different treatments for brain tumors. Most brain tumors are treated with a combination of multiple different types of therapy. The exact location and type of brain tumor will dictate which treatments are recommended.

Surgery

Surgical resection is recommended for the majority of brain tumors. It is rare that a primary brain tumor can be cured without a surgical resection. However, the location of the brain tumor will dictate whether or not surgery is an option. Some tumors are seated in places in the brain that are just too dangerous to operate on, and surgery cannot be employed. The risks to the patient from surgery depend on the location and size of the tumor. Talk to your neurosurgeon about the specific risks of your planned surgery.

Chemotherapy

Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. These drugs may be given through a vein or with pills by mouth. One of the special challenges in treating brain tumors with chemotherapy is that there is a natural barrier between the brain and the blood, which blocks many medications from entering the brain. Only certain chemotherapy drugs can cross this blood-brain barrier to treat disease in the nervous system. One of the new ways that chemotherapy can be delivered for brain tumors is by implantation on a biodegradable wafer that is inserted by the neurosurgeon into the space left behind after surgery (called the tumor bed ). The chemotherapy wafer can then deliver high doses of chemotherapy to a localized area. Chemotherapy wafers are only approved for certain brain tumors, although future research may prove this approach useful for more diseases.

There are many different chemotherapy drugs used for brain tumors, and your medical oncologist can explain why he or she recommends one particular regimen over another in your case.

Radiation

Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. Radiation can come from an external source (called external beam radiation therapy ), and it requires patients to come in 5 days a week for up to 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. External beam radiation therapy is often employed for brain tumors, both as primary treatment for unresectable tumors and in addition to surgery.

Radiation therapy can also be given to a very focused area of the brain using a technique called stereotactic radiosurgery . Stereotactic radiosurgery requires a patient to have a head frame attached, so that a precise map can be made of the patient's head. Radiation is then focused from a variety of different angles to deliver a large radiation dose to the tumor or tumor bed. This can be performed using the same machine that delivers external beam radiation or by a special machine called a gamma knife.

Radiation can also be given internally by implanting high strength radioactive sources in the vicinity of the tumor or the tumor bed. This is called brachytherapy. Your radiation oncologist can answer questions about the utility, process, and side effects of the recommended radiation therapy in your particular case.

Follow-up testing

Once a patient has been treated for a brain tumor, he or she needs to be closely followed for a recurrence. At first, the patient will have follow-up visits fairly often. The longer he or she is free of disease, the less often he or she will have to go for checkups with examinations. The doctor will decide when to obtain follow-up MRI scans or PET scans.

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.

Bladder Cancer: The Basics

2006-04-29T06:22:00.000-07:00

What is the Bladder?

The bladder serves as a reservoir for urine in our bodies. It permits the storage of urine for a period of time before releasing it as we urinate. It can be thought of as a muscular balloon; a flattened structure when there is no urine (immediately after a person urinates) but able to be filled to up to a liter (though this would be very uncomfortable) with urine. Normally, as the bladder nears 500 cc (1/2 of a liter), we feel the urge to urinate. The muscular structure of the bladder also helps other pelvic muscles push the urine out when it is released. The bladder is located deep in the pelvis, just above the pubic symphysis, which is a bone that can be felt in the midline on the front of our pelvis. In fact, when the bladder is over distended, it can be felt by a physician. Ureters empty urine into the bladder from the kidneys, and the urethra leads out from the bladder, emptying urine out of our bodies.

What is bladder cancer?

The definition of a tumor is a mass of quickly and abnormally growing cells. Tumors can be either benign or malignant. Benign tumors have uncontrolled cell growth, but without any invasion into normal tissues and without any spread. A malignant tumor is called cancer when these tumor cells gain the propensity to invade tissues and spread locally as well as to distant parts of the body. In this sense, bladder cancer occurs when cells in the lining of the bladder grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.

Cancers are described by the types of cells from which they arise. Bladder cancers arise almost exclusively from the lining of the bladder. In the United States, 98% of bladder cancers are called transitional cell carcinomas. This simply means that the cancer started in the lining of the bladder, which is made up of transitional cells that appear elliptical under the microscope. Less commonly are other types of cancers that arise from the lining of the bladder, called adenocarcinomas, squamous cell carcinomas and small cell carcinomas. A common way for bladder cancers to grow is called a papillary growth pattern. When a bladder cancer grows this way, it can be noninvasive, i.e., not invading into tissues at all, and hence not having a risk for distant spread (as long as it is treated). In addition to other invasive cancers, patients are sometimes diagnosed with precancerous lesions, called carcinoma-in-situ. Carcinoma-in-situ occurs when the lining of the bladder undergoes changes similar to cancerous changes without any invasion into the deeper tissues. Hence, while the cells themselves have cancer-like qualities, there is no risk of spread, as no invasion has occurred. However, both papillary bladder cancers and cancer-in-situ may become invasive and cause problems if not treated.

Am I at risk for bladder cancer?

Bladder cancer is the fourth most common cancer in men and the eighth most common cancer in women. Over 50,000 cases are diagnosed every year in the United States, with over 12,000 deaths. Internationally, the incidence of bladder cancer varies substantially, with highest rates in Europe and North America and in areas (Northern Africa) endemic with a type of fluke called Schistosoma haematobium, which induces a predominance of squamous cell carcinomas. Classically, bladder cancer is thought of as a disease that affects older men, with men affected more than women by a 3:1 ratio and 2/3 of the cases diagnosed in people over the age of 65.

Cigarette smoking is the largest risk factor for bladder cancer (yet another reason to stop smoking). Smokers have 2-4 times the risk of having bladder cancer, and it contributes to up to 50% of all bladder cancers that are diagnosed. Other than the previously mentioned Schistosoma haematobium infections, the only other risk factors known are from occupational exposures, such as polychromatic hydrocarbons (benzene, benzidine). More recently, an association has been made between chlorinated drinking water and bladder cancer. Though there have been suggestions of saccharin and high intake of dietary fat and cholesterol being causative for bladder cancer, these have yet to be substantiated.

How can I prevent bladder cancer?

Smoking is the strongest risk factor associated with the development of bladder cancer. Therefore, smoking cessation is the best way to prevent bladder cancer. Also, obviously reducing the exposure to carcinogenic compounds should decrease the risk of developing bladder cancer. Other than these preventative measures, decreasing the risk of bladder cancer relies on early detection of symptoms and possibly screening high-risk individuals.

What screening tests are available?

The goal of screening tests are to detect cancers early and initiate treatment when the cancer is in an early stage, or even before it becomes invasive. Cytologic examination of urine (looking for abnormal cells in urine) has been the most commonly tested screening tool. It involves testing urine for the presence of abnormal cells, which would indicate the possibility of a cancer. This method is fairly inexpensive and without risk to the patient. If abnormal cells are seen, over 95% of the time it accurately predicts the presence of bladder cancer. However, a fair amount of cancers can be missed using this method. Also, the incidence of preclinical (too small to cause any symptoms) bladder cancer in the general population is likely too low for cytologic examination of urine to be useful as a mass screening tool. Routine examination of the urine for the detection of blood (by far the most common presentation of bladder cancer) has also been tested and also appears to be inadequate for mass screening. Therefore, there is no tried screening method for bladder cancer, so the best method for detecting bladder cancer and preventing an aggressive bladder cancer is to not smoke or stop smoking and to not ignore the symptoms of bladder cancer, which usually involves blood noted in the urine (see below).

What are the signs of bladder cancer?

By far the most common sign of bladder cancer is the presence of blood in the urine, called hematuria. The blood in the urine can either be noticeable by the naked eye, called gross hematuria, or noted only when the urine is analyzed in a laboratory, called microscopic hematuria. Either gross hematuria or microscopic hematuria is present in over 80% of cases of bladder cancer. Therefore, when someone is noted to have blood in the urine, it must be proven to be something other than bladder cancer.

Other signs of bladder cancer could include symptoms of a urinary tract infection. These include increased frequency of urination, a feeling of urgency to urinate, pain (burning) with urination, and the feeling of incomplete bladder emptying. These are all caused by irritation of the bladder wall by the tumor.

In advanced cases of bladder cancer, the tumor can actually obstruct either the entrance of urine into the bladder or the exit of urine from the bladder. This causes severe flank pain, infection, and damage to the kidneys. Obviously, bladder cancers that cause these symptoms need to be dealt with immediately.

How is bladder cancer diagnosed and staged?

Diagnosis

Anyone with either gross or microscopic hematuria should undergo a work-up to insure the symptoms are not from bladder cancer. Often, the first thing that is done is a urine cytology, which as mentioned above, is looking at the urine under a microscope to detect cancerous appearing cells. Again, if these cells are seen, it is diagnostic. However, the test does not detect all cases of bladder cancer. If bladder cancer is highly suspected, or after diagnosis, X-ray imaging of the upper urinary tract (including the ureters and kidneys) is done, to rule out any involvement of these structures with cancer. Ultrasound can be used to study the kidneys and a CT scan is often very good at studying the entire length of the urinary tract. A simpler method of studying the (upper) urinary tract is with an intravenous pyelogram (IVP). This involves administering a dye through a patient's vein and taking a regular x-ray a short time later. The dye can be seen in the x-ray, showing the full extent of the kidney collecting system, ureters, and often the bladder.

Though the above tests are useful or even required, the mainstay of diagnosis and staging is endoscopic evaluation. In this case, this type of evaluation is called a cystoscopy. It involves placing a fiberoptic camera into the bladder via the urethra. Cystoscopy allows for direct visualization of the entire bladder and also allows for biopsy for any suspicious lesions. If the biopsy reveals cancer, a repeat cystoscopy and resection (called a transurethral resection (TUR)) is done to completely evaluate the tumor and the extent and depth of disease.

With a diagnosis of bladder cancer obtained, a complete physical examination is done as well as the previously mentioned radiologic studies to fully evaluate the urinary tract, the local extent of disease, and any metastatic disease.

Staging

The staging of a cancer basically describes how much it is grown before the diagnosis has been made, documenting the extent of disease. Bladder cancer often presents at an early stage, as it produces hematuria early on in the course of the disease. Unfortunately, sometimes bladder cancer can advance to invasive disease prior to causing symptoms. As will be discussed in the treatment section, a big distinction is whether the bladder cancer is superficial or invading into the muscle, because the treatments are much different. Before the staging systems are introduced, first some background on how cancers grow and spread, and therefore advance in stage.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. Bladder cancers often start very superficial, involving only the lining of the bladder. Eventually, however, bladder cancers can invade into the bladder, involving the muscular layers of the wall. If the bladder cancer is allowed to grow long enough or is aggressive enough, it may eventually invade the entire way through the wall and into the fat surrounding the bladder or even into other organs (prostate, uterus, vagina). This local extension is the most common way bladder cancer spreads.

Cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Bladder cancer can spread this way. If it does, it usually first spreads to the lymph nodes surrounding the bladder (perivesicular lymph nodes). From there, it can spread to lymph nodes that are in close proximity to the external iliac and internal iliac arteries and veins, which are the very large blood vessels that run into the leg and into pelvis, respectively. The presence of lymph node spread is best evaluated by CT scan or at surgical exploration.

Bladder cancer can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and the tumors that arise from cells' travel to other organs are called metastases. Cancers of the bladder generally spread locally or to lymph nodes before spreading distantly through the bloodstream, though this is not always the case. If spread through the bloodstream does occur, the lungs and bones are the most common sites to be involved.

The staging system used to describe bladder tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the throat itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases).

There are two "T" stages that are often reported: the clinical stage, which is based on the physical exam of the physician, and the pathologic stage, which is noted after the tumor is resected, or taken out surgically.

Clinical Staging

T1-Physician feels nothing on exam prior to transurethral resection (TUR)
T2-Physician feels nothing on exam after TUR
T3a-Any visually incomplete TUR or persistent tumor felt after TUR
T3b-Any tumor that extends beyond bladder on exam
T4-Tumor that involves other organs

Pathologic Staging

Ta-noninvasive papillary tumor
Tis-carcinoma-in-situ (explained above)
T1-tumor invading the mucosa (lining of bladder)

Above are considered "superficial"

T2-tumor invades superficially into muscle of wall
T3a-tumor invades deeply into muscle of the bladder wall
T3b-tumor invades the entire way through the wall
T4-tumor invades other organs

The "N" stage is as follows:

N0-no spread to lymph nodes
N1-tumor spread to a single lymph node, but this tumor spread must be less than 2 cm
N2-tumor spread to lymph nodes sized 2-5 cm
N3-tumor spread to lymph nodes greater than 5 cm

The "M" stage is as follows:

M0-no tumor spread to other organs
M1-tumor spread to other organs

The overall stage is based on a combination of these T, N, and M parameters. Though complicated, these staging systems help physicians determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed. An important distinction in bladder cancer is between superficial disease (Ta, Tis, T1) or muscular invasive disease. It has large implications for treatment, as will be discussed below.

What are the treatments for bladder cancer?

Superficial Bladder Cancer

Superficial bladder cancer is that which has not invaded at all into the muscle. As noted above, the extent of disease is based mainly on the transurethral resection (TUR). Likewise, the primary treatment for superficial disease is the TUR. Given the fact that the cancer is superficial, all of the tumor should be able to be removed by the TUR. However, superficial bladder cancer has a high incidence of recurrence, and hence the goal of treatment switches to the prevention of these recurrences and to prevent progression to an invasive stage. The treatment of a superficial bladder cancer always involves TUR. In high grade tumors, large tumors, multiply recurrent superficial tumors, or any tumor that invades into the lining of the bladder (T1 tumors), additional agents are infused directly into the bladder to help to decrease recurrences. The most commonly used is a compound that causes an inflammatory reaction, called BCG. BCG is instilled directly into the bladder for several treatments over several months. Though other agents have also been used, BCG has the best results, decreasing recurrence rates and progression rates in patients with superficial cancers. Though BCG is successful, it is not without side effects-causing bladder spasm and irritation, often with every instillation.

Muscle Invading Bladder Cancer

The standard of care in treating more advanced cancers has always involved surgically removing the entire bladder in a procedure called a cystectomy. A large concern in performing this surgery is how to divert the urine so that the patient can still excrete it. In the past, this was done using an "ileal conduit", where the urine drained through a portion of the small intestine and out through the skin into a bag. More recently, techniques creating new bladders have been used. This allows the ureters to be implanted into the newly created bladder and the urethra to lead out of the new bladder. In the right surgical hands, the patient can continue to have very high rates of continence. In addition to cystectomy, superior results have been demonstrated by using chemotherapy, either before the surgery or after the surgery. Though trials using chemotherapy in addition to surgery have not demonstrated an overall survival benefit, they have shown decreased bladder cancer rates. With this, and evidence that many patients have metastases at presentation that cannot be detected, most physicians recommend some type of chemotherapy to go along with surgery.

An alternative to cystectomy that has been advocated recently is using a combination of chemotherapy and radiation to spare the patient of a significant surgical procedure. Regimens that have the best results all start with maximum resection of the bladder tumor via TUR, just like with superficial bladder cancers. The patient then starts a treatment course of radiation with chemotherapy (usually with the chemotherapy drug cisplatin) for 4-5 weeks. Patients are then reevaluated by a repeat cystoscopy procedure to determine if the chemotherapy and radiation had made the tumor completely disappear. If the tumor is gone by examination, further chemotherapy and radiation is given for an additional 2-3 weeks. This method has comparable survival rates to cystectomy and has the advantage of allowing the patient to keep his or her bladder, and subsequently, continence. Again, though, there are side effects of this treatment. The most concerning of these are decreased bladder capacity (leading to more frequent urination), bladder spasm, and perhaps chronic burning or pain with urination, or hematuria from the damage done by the chemotherapy and radiation.

Overall, there are different treatment methods available for bladder cancer. All have curative potential. Like many other sites of cancer, there has been a development of regimens that allow for a higher quality of life after the treatment is completed. The exact method of treatment should be chosen individually by the patient, after discussing it with a team of physicians adept at treating bladder cancer, to maximize chance of cure and function. Obviously the best treatment for cancer is prevention of ever developing cancer. By far, the best prevention is not smoking or immediate smoking cessation.

Mesothelioma: Questions and Answers

2006-04-29T03:13:00.000-07:00

Mesothelioma is a rare form of cancer in which malignant (cancerous) cells are found in the mesothelium, a protective sac that covers most of the body’s internal organs. Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles.

What is the mesothelium?

The mesothelium is a membrane that covers and protects most of the internal organs of the body. It is composed of two layers of cells: One layer immediately surrounds the organ; the other forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the beating heart and the expanding and contracting lungs) to glide easily against adjacent structures.

The mesothelium has different names, depending on its location in the body. The peritoneum is the mesothelial tissue that covers most of the organs in the abdominal cavity. The pleura is the membrane that surrounds the lungs and lines the wall of the chest cavity. The pericardium covers and protects the heart. The mesothelial tissue surrounding the male internal reproductive organs is called the tunica vaginalis testis. The tunica serosa uteri covers the internal reproductive organs in women.

What is mesothelioma?

Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Cancer cells can also metastasize (spread) from their original site to other parts of the body. Most cases of mesothelioma begin in the pleura or peritoneum.

How common is mesothelioma?

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. About 2,000 new cases of mesothelioma are diagnosed in the United States each year. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age.

What are the risk factors for mesothelioma?

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure at work is reported in about 70 percent to 80 percent of all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos.

Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.

Smoking does not appear to increase the risk of mesothelioma. However, the combination of smoking and asbestos exposure significantly increases a person’s risk of developing cancer of the air passageways in the lung.

Who is at increased risk for developing mesothelioma?

Asbestos has been mined and used commercially since the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace. People who work with asbestos wear personal protective equipment to lower their risk of exposure.

The risk of asbestos-related disease increases with heavier exposure to asbestos and longer exposure time. However, some individuals with only brief exposures have developed mesothelioma. On the other hand, not all workers who are heavily exposed develop asbestos-related diseases.

There is some evidence that family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibers, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

What are the symptoms of mesothelioma?

Symptoms of mesothelioma may not appear until 30 to 50 years after exposure to asbestos. Shortness of breath and pain in the chest due to an accumulation of fluid in the pleura are often symptoms of pleural mesothelioma. Symptoms of peritoneal mesothelioma include weight loss and abdominal pain and swelling due to a buildup of fluid in the abdomen. Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions. It is important to see a doctor about any of these symptoms. Only a doctor can make a diagnosis.

How is mesothelioma diagnosed?

Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient’s medical history, including any history of asbestos exposure. A complete physical examination may be performed, including x-rays of the chest or abdomen and lung function tests. A CT (or CAT) scan or an MRI may also be useful. A CT scan is a series of detailed pictures of areas inside the body created by a computer linked to an x-ray machine. In an MRI, a powerful magnet linked to a computer is used to make detailed pictures of areas inside the body. These pictures are viewed on a monitor and can also be printed.

A biopsy is needed to confirm a diagnosis of mesothelioma. In a biopsy, a surgeon or a medical oncologist (a doctor who specializes in diagnosing and treating cancer) removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs.
Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. If the cancer is in the abdomen, the doctor may perform a peritoneoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument called a peritoneoscope into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.

If the diagnosis is mesothelioma, the doctor will want to learn the stage (or extent) of the disease. Staging involves more tests in a careful attempt to find out whether the cancer has spread and, if so, to which parts of the body. Knowing the stage of the disease helps the doctor plan treatment.

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs.

How is mesothelioma treated?

Treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient’s age and general health. Standard treatment options include surgery, radiation therapy, and chemotherapy. Sometimes, these treatments are combined.

Surgery is a common treatment for mesothelioma. The doctor may remove part of the lining of the chest or abdomen and some of the tissue around it. For cancer of the pleura (pleural mesothelioma), a lung may be removed in an operation called a pneumonectomy. Sometimes part of the diaphragm, the muscle below the lungs that helps with breathing, is also removed.

Radiation therapy, also called radiotherapy, involves the use of high-energy rays to kill cancer cells and shrink tumors. Radiation therapy affects the cancer cells only in the treated area. The radiation may come from a machine (external radiation) or from putting materials that produce radiation through thin plastic tubes into the area where the cancer cells are found (internal radiation therapy).

Chemotherapy is the use of anticancer drugs to kill cancer cells throughout the body. Most drugs used to treat mesothelioma are given by injection into a vein (intravenous, or IV). Doctors are also studying the effectiveness of putting chemotherapy directly into the chest or abdomen (intracavitary chemotherapy).

To relieve symptoms and control pain, the doctor may use a needle or a thin tube to drain fluid that has built up in the chest or abdomen. The procedure for removing fluid from the chest is called thoracentesis. Removal of fluid from the abdomen is called paracentesis. Drugs may be given through a tube in the chest to prevent more fluid from accumulating. Radiation therapy and surgery may also be helpful in relieving symptoms.

Mesothelioma: The Basics

2006-04-29T03:05:00.000-07:00

What is mesothelial tissue?

The mesothelium is a protective sac that covers and protects most internal organs in the body. It is composed of two layers, one layer covers the organ and the second layer forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the lungs) to move easily. The area between the two layers is often called the pleural space. Mesothelial tissue is found lining the abdominal cavity organs, the lungs and the heart. What is mesothelioma?

Mesothelioma occurs when the mesothelial cells grow out of control. These cells also lose the ability to stop producing the lubricating fluid when there is enough. This results in organs being encased with a thick rind of tumor tissue and excess fluid build up, causing symptoms. These cells can grow and invade other organs, or spread to other areas of the body. When the cells spread to other areas of the body, it is called metastasis.

The majority of mesotheliomas are found in the lining of the lung. About ten percent of cases are found in the abdominal cavity lining, and even more rarely, mesothelioma is found in the lining of the heart.

Am I at risk for mesothelioma?

Mesothelioma is a rare cancer, with only 2,300 cases diagnosed in 2000, in the United States. It is eight times more common in men, which is due in most part to work-related exposure to asbestos. Risk also increases with age. The biggest risk factor for developing the disease is exposure to asbestos, accounting for 70 to 80 percent of all cases. Asbestos has been used in many products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. Particles can be released from these products, particularly during the manufacturing process, and inhaled. Prior to knowing the dangers, asbestos miners and other workers exposed to asbestos worked without wearing any protection. Since the 1970's, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure and requires protective equipment in the workplace. Family members of people who worked with asbestos were also exposed to the toxin when it was carried home on clothing and hair, putting them at increased risk for mesothelioma. It takes 20 to 40 years from the time of asbestos exposure until mesothelioma is detected. This exposure was usually over a period of time, but has been reported to be as little as one or two months of exposure. Smoking does not seem to increase the risk of developing the disease.

The incidence of mesothelioma in Western Europe is much higher, with 5,000 new cases in 2000. This is because maximal exposure to asbestos in Europe occurred around 1970, whereas the maximum exposure in the U.S. was from the 1930s to 60s. It is expected that rates in the U.S. should begin to decline, whereas rates in Europe are expected to plateau in 2018 before declining.

How can I prevent mesothelioma?

By decreasing exposure to asbestos, the risk of mesothelioma is decreased. Workers who are exposed to asbestos on the job should wear protective clothing and masks. These workers should change their clothing before leaving the work site to avoid carrying any particles home. OSHA has set standards regulating these procedures. What screening tests are available?

There is no good screening test for mesothelioma. Radiologic studies (x-ray, CT scan) are not sensitive enough to detect tumors before symptoms occur.

What are the signs of mesothelioma?

The symptoms of mesothelioma are caused by a build-up of tumor tissue surrounding the lung and fluid in the pleural space that prevents the lung from expanding fully. This causes pressure on the lung, leading to pain and shortness of breath. As the disease progresses, patients may lose weight and have a dry, hacking cough. In the abdomen, this fluid and tumor tissue causes abdominal swelling, pain and weight loss.

How is mesothelioma diagnosed and staged?

Patients who present with symptoms worrisome for mesothelioma may have a chest x-ray done, indicating a build-up of fluid in the lining of the lung. These patients would then undergo CT scan to further evaluate the cancer. In the case of abdominal mesothelioma, a CT scan obtained to visualize the anatomy in the abdomen.

Patients would then undergo a biopsy to have the diagnosis confirmed. In the lung, a thoracoscope is used to go through the chest wall, between the ribs to obtain a sample of the tissue. A peritoneoscope is used to enter the abdomen to obtain a tissue sample in abdominal mesothelioma.

Staging refers to determining the extent of the disease and this dictates the treatment. Physicians use the TNM system (also called tumor - node - metastasis system). This describes the size of the tumor (T), if the lymph nodes are involved (N), and if it has spread to other areas of the body (M). This is then interpreted to a stage between one and four. Patients with earlier stage tumors tend to live longer and respond better to available treatments.

What are the treatments for mesothelioma?

Treatment is dependent on the stage of the disease, the location of the tumor, the patient's age and state of health at the time. Younger, healthy patients, with early stage disease may be candidates for surgery that removes the mesothelial tissue around the tumor. This surgery is extensive and it is not well understood how much benefit it provides the patient.

Traditional radiation therapy has not shown a benefit, and can cause damage to the healthy lung tissue in the process of treating the cancer. Research is investigating ways of giving radiation directly to the tumor, using implants or UV light therapy. Chemotherapy has often been used to treat patients with mesothelioma, but until recently trials did not find any one medication to be superior to others. These medications have had responses in 10 to 20 percent of patients, but combining more than one medication has not increased these rates. Recently, a new medication called pemetrexed (Alimta) was given in combination with cisplatin with positive results. Patients received either cisplatin alone or cisplatin in combination with pemetrexed. Patients who received the combination of drugs had increased response rates, survived longer, and had fewer side effects. This regimen is now considered standard of care for mesothelioma not treatable with surgery. Researchers are conducting studies that administer the chemotherapy directly into the pleural space. So far, the results of these studies have been disappointing.

Because the current therapies have limited effectiveness, researchers are studying new ways to treat mesothelioma. Some of the treatments being investigated include interleukin 2 (a biologic therapy), lovastatin (a cholesterol-lowering drug), immunotherapy, gene therapy (a method that attempts to correct the abnormal gene that causes the cancer to grow out of control), and Photodynamic Therapy (PDT-a treatment that uses a laser to activate a photosensitizing drug during the surgical removal of the cancer). Patients should talk with their physicians about current clinical trials for mesothelioma.

One problem that patients may encounter is the recurring build-up of fluid in the pleural space. This fluid can be removed with a chest tube (a tube that is put into the chest wall and left in for a period of time to allow drainage) or a procedure called thoracentesis (a small needle is put through the chest wall, into the pleural space, the fluid is drained, and the needle removed). In the abdomen, the procedure to remove fluid is called paracentesis. In this procedure, a needle is inserted through the abdomen into the fluid filled space, and the fluid is drained.

If this is a chronic problem, patients may have a catheter placed in the chest semi-permanently, allowing them to drain the fluid themselves at home as they need to. Removal of the fluid alleviates the difficulty breathing and chest pain caused by the build-up.

Follow-up testing?

The physician will follow the patient with physical examinations, chest x-rays, and CT scans.

The Basics of Anal Cancer

2006-04-29T02:51:00.000-07:00

What is the anus?

The anus is an organ that lies at the end of the digestive tract below the rectum. It consists of two sections: the anal canal and the anus (or anal verge). The anal canal is a 3-4 cm long structure that lies between the anal sphincter (one of the muscles controlling bowel movements) just below the rectum and the anal verge which represents the transition point between the digestive tract and the skin on the outside of the body. Muscles within the anal canal and anus control the passage of stool from the rectum to outside the body.

What is anal cancer?

Normally, cells in the body will grow and divide to replace old or damaged cells in the body. This growth is highly regulated, and once enough cells are produced to replace the old ones, normal cells will stop dividing. Tumors occur when there is an error in this regulation and cells continue to grow uncontrolled. Tumors can either be benign or malignant. Although benign tumors grow uncontrolled, then do not break off and spread beyond where they started and do not invade into surrounding tissues. Malignant tumors, however, will grow uncontrolled in such a way that they invade and damage other tissues around them. They also gain the ability to break off from where they started and spread to other parts of the body, usually through the blood stream or through the lymphatic system where the lymph nodes are located. Over time, the cells within a malignant tumor become more abnormal and appear less like normal cells. This change in the appearance of cancer cells is called the tumor grade, and cancer cells are described as being well-differentiated, moderately-differentiated, poorly-differentiated, or undifferentiated. Well-differentiated cells are quite normal appearing and resemble the normal cells from which they originated. Undifferentiated cells are cells that have become so abnormal that often, we cannot tell what types of cells they started from.

Anal cancer is a malignant tumor of either the anal canal or anal verge. In the United States , 80% of anal cancers are squamous cell cancers, resembling the types of cells seen from the skin. However, this is not true in other parts of the world. In Japan , 80% of anal cancers are adenocarcinomas, resembling the glandular cells seen in the rectum. It appears that anal cancers frequently start as anal dysplasia. Anal dysplasia is made up of cells of the anus that have abnormal changes, but do not show evidence of invasion into the surrounding tissue. The most severe form of anal dysplasia is called carcinoma in situ where the cells appear like cancer cells, but have not invaded beyond where the normal cells lie. Over time, anal dysplasia eventually changes to the point where they become invasive and gain the ability to metastasize, or break way to other parts of the body. Anal dysplasia is sometimes referred to as anal intraepithelial neoplasia (AIN). When anal cancer does spread, it most commonly spreads through direct invasion into the surrounding tissue or through the lymphatic system. Spread of anal cancer through the blood is less common, although it can occur. Cancers arising from the anal verge represent 25% of all anal cancers and are often treated like skin cancers; however, they often respond more poorly to treatment than do other skin cancers or cancers of the anal canal.

What causes anal cancer and am I at risk?

Each year, there are approximated 4000 cases of anal cancer in the United States . In general, the incidence of anal cancers has been increasing over the past 30-40 years. The vast majority (~85%) of cases are in Caucasians. The incidence of anal cancer increases with age: patients with anal cancer have an average (median) age of 62 years. Cancers of the anal canal are more common in women, while the incidence of cancers of the anal verge is roughly equal in both men and women.

Several factors have been associated with anal cancer. Most importantly, infection with the human papilloma virus (HPV) has been shown to be related to anal cancers and has been associated with several other cancers including cervical cancer and cancers of the head and neck. HPV can be transmitted from person to person through sexual contact, so individuals with a history of multiple sexual partners, anal receptive intercourse, and genital warts are at an increased risk for infection. Another sexually transmitted virus, the human immunodeficiency virus (HIV), has been linked to anal cancers, and individuals infected with HIV are at increased risk for infection with HPV.

Several other factors have been linked to anal cancer. Anal cancer has been associated with smoking. Patients who smoke are three times more likely to develop anal cancer as those that don't smoke. The risk of anal cancer increases with the number of cigarettes smoked per day and the number of years that a person has been smoking. Because anal cancer appears to first start as anal dysplasia before progressing to anal cancer, patients with a history of AIN are at increased risk to develop anal cancer. There may be an association between anal cancer and suppression of the immune system. The rate of anal cancer is higher in patients who are immunosuppressed after organ transplants, although this relationship is not clear.

Although there appears to be an increased rate of anal cancer in patients who have benign anal conditions such as anal fistulae, anal fissures, perianal abscesses, or hemorrhoids, it does not appear that these benign conditions are a cause of anal cancer. Alternatively, an undiagnosed anal cancer may actually be causing these conditions, and then is subsequently diagnosed when the benign condition is being treated.

How are anal cancer and HIV/AIDS related?

HIV is the virus responsible for Acquired Immune Deficiency Syndrome (AIDS), a severe disease that results in loss of the ability of the body to fight off certain types of infections. The incidence of anal cancer is increased in patients with HIV. This is likely related to the fact that patients with HIV are at an increased risk for infection with HPV as well. This relationship between HIV and HPV is not related to the immune status or the sexual practices of the patient infected with HIV. The rate of infection of HPV is increased in patients with HIV even if they do not engage in anal receptive intercourse and do not have evidence of suppression of their immune system. A patient is considered to have progressed from being HIV positive to having AIDS if they develop certain infections or diseases that are uncommon except in AIDS patients. Currently, anal cancer is not considered an AIDS-defining illness. However, frequently, patients who have been newly diagnosed with anal cancer are tested for HIV if they have other risk factors for infection with HIV.

How can I prevent anal cancer?

Anal cancer is an uncommon cancer, and the risk of developing anal cancer is quite low. However, by avoiding the factors that are known to be related to anal cancer, the risk of developing anal cancer will become even lower. By far, the most important factor in developing anal cancer is infection with HPV. Recent studies have shown that giving vaccines against HPV prophylactically to patients at high risk for cervical cancer (which is also caused by HPV) reduces the risk that patients will develop cervical cancer. It is likely that HPV vaccines would result in a similar reduction in the risk of anal cancers; however, to date, no studies have been published confirming this. However, a number of studies examining the role of HPV vaccines and anal cancer are currently under development. In addition, it is possible that treatment of patients who are already infected with HPV with antiviral medications may also reduce the risk of anal cancers. Again, this method is still unproven and studies using antiviral treatment to prevent anal cancer are under development.

Avoiding smoking and unsafe sexual practices can reduce the risk of anal cancer. In patients who are known have anal dysplasia, careful surveillance can result in early detection of anal cancer, and a higher rate of cure with treatment. However, removal of areas of anal dysplasia is usually unsuccessful. The rate of recurrence of anal dysplasia after surgical or laser removal is very high. This is likely due to the fact that even if areas of dysplasia are removed, the patient remains infected with HPV, which can cause the development of additional areas of anal dysplasia.

What are the signs of anal cancer?

In about 50% of cases, the initial symptom of anal cancer is bleeding. Pain is somewhat less common, seen in about 30% of patients presenting with anal cancer; however, it can be quite severe. Occasionally, patients have the sensation of having a mass in the anus and can experience itching or anal discharge. Rarely, in advanced cases, anal cancers can disrupt the function of the anal muscles, resulting in loss of control of bowel movements. In general, these symptoms are vague and non-specific. As a result, in one-half to two-thirds of patients with anal cancer, a delay of up to 6 months occurs between the time when symptoms start and when a diagnosis is made.

How is anal cancer diagnosed?

When anal cancer is suspected, the physician should perform a thorough history and physical examination. The physical exam should consist of a digital rectal examination (DRE) as well as visualization of the anal canal using an anoscope or protoscope (a long, thin instrument that is inserted into the anus to allow the physician to see the inside of the anus and rectum). Ultimately, anal cancer can only be diagnosed with a biopsy. To perform a biopsy, the physician uses a needle or a small pair of scissors or clamps to remove a piece of the tumor. It is common for there to be some mild bleeding after a biopsy is taken, and this bleeding can last for a few days after the procedure. The tissue is then sent to a pathologist who looks at the tissue underneath a microscope to determine whether the tumor is cancerous or not. Because a number of benign tumors and lesions can resemble anal cancer on physical examination, a biopsy should always be performed before initiating treatment for anal cancer.

How is anal cancer staged?

Once a diagnosis of anal cancer is made, additional test should be ordered to determine the extent of the disease. A CT scan or MRI of the abdomen and pelvis should be performed to look for abnormally enlarged lymph nodes, which can result from spread of the cancer, and to examine the liver for metastatic disease. A chest x-ray is often performed to look for spread of the cancer to the lungs. Occasionally, an ultrasound of the tumor using a probe that is inserted into the anus can be used to determine the amount of invasion of the tumor into the surrounding tissues.

Anal cancer is most commonly staged using the TNM staging system which is determined by the American Joint Committee on Cancer. The "T stage" represents the extent of the primary tumor itself. The "N stage" represents the degree of involvement of the lymph nodes. The "M stage" represents whether or not there is spread of the cancer to distant parts of the body. These are scored as follows:

T Stage

Tis Carcinoma in situ
T0 No evidence of primary tumor
T1 Tumor £ 2 cm in greatest dimension
T2 Tumor >2 cm but £ 5 cm in greatest dimension
T3 Tumor >5 cm in greatest dimension
T4 Tumor of any size that invades adjacent organs including the vagina, urethra, or bladder. Tumors that invade the anal sphincter only do not quality as T4 tumors

N Stage

N0 No evidence of spread to the lymph node
N1 Spread of cancer to the lymph nodes directly adjacent to the rectum (perirectal lymph nodes)
N2 Spread of the cancer to lymph nodes of the inguinal or internal iliac lymph node chains on one side
N3 Spread of the cancer to lymph nodes of the inguinal or internal iliac lymph node chains on both sides OR cancer involvement of both the perirectal lymph nodes and the inguinal lymph nodes

M Stage

M0 No evidence of distant spread of the cancer
M1 Evidence of distant spread of the cancer including spread to lymph node chains other than the ones lists under "N stage"

The stage of the cancer is reported by stating the stage of the T, the N, and the M. For example, a patient with a 4 cm tumor that had spread to perirectal lymph nodes, but did not invade into adjacent organs or spread to any other lymph nodes would be classified as T2N1M0. The staging can be further condensed into a stage group, which takes the various combinations of TNM and places them into groups designated stage 0-IV. While there is a system for stage grouping of anal cancers, these tumors are more commonly referred to by their direct TNM stage.

Although this system of cancer staging is quite complicated, it is designed to help physicians describe the extent of the cancer, and therefore, helps to direct what type of treatment is given.

How is anal cancer treated?

Radiation Therapy

Radiation therapy has become the mainstay of treatment of anal cancer. The radiation comes in the form of high energy x-rays that are delivered to the patient only in the areas at highest risk for cancer. These x-rays are similar to those used for diagnostic x-rays, only of a much high energy. The high energy of x-rays in radiation therapy results in damage to the DNA of cells. Because cancer cells are not as good as normal, healthy cell at repairing DNA damage, radiation results in relatively more damage to the cancer cells than to normal cells. Radiation therapy exploits this difference to treat cancers while relatively sparing normal tissue.

Typically, radiation for anal cancer is given daily, Monday through Friday, for 5 to 6 weeks. The radiation treatments themselves are short, lasting only a few minutes. Like diagnostic x-rays, radiation treatments cannot be felt and do not hurt. Radiation is delivered like a beam of light. It only goes where it is aimed. The side effects of treatment are limited to the areas being treated. Most commonly, radiation treatment for anal cancer can result in irritation to the skin. This reaction can be quite severe with redness, dryness, and breakdown of the skin. Often, patients will require a break during radiation treatment to allow the skin to heal prior to resuming treatment. Other side effects of radiation can include fatigue, diarrhea, and lowering of blood counts.

Chemotherapy

Chemotherapy is a medication that is usually given intravenously or as a pill. It goes to the bloodstream and throughout the body to kill cancer cells. This is one of the big advantages of chemotherapy. If cancer cells have broken off from the tumor and are somewhere else inside the body, chemotherapy has the chance of finding those cells and killing them. With anal cancer, chemotherapy is most commonly given at the same time as radiation.

A number of different chemotherapeutic agents exist, each with their own side effects. The most commonly used agents in anal cancer are 5-flourouracil (5-FU) with either mitomycin C or cisplatin. Exactly which chemotherapeutic agents are given for anal cancer varies according the physician given them. It is important to discuss the risk of each of these medications with your medical oncologist. Based on your own health status and the risks of side effects that you are willing to accept, the choice of chemotherapy can vary.

Chemotherapy can also be given if the cancer has spread to distant sites. In this setting, unless there are specific local symptoms from anal cancer, the mainstay of treatment becomes chemotherapy, because as discussed above, chemotherapy can travel throughout the entire body. Unfortunately, in this setting, chemotherapy has not been very successful at controlling the cancer.

Combined Modality (Chemoradiotherapy)

Chemotherapy has been shown to be radiosensitizing when given at the same time as radiation therapy. This means that the effect of the radiation is increased when given together with chemotherapy. Several large trials have shown that local control of the tumor is significantly improved when chemoradiotherapy is used compared to radiation alone. However despite this improvement in local control of the tumor, no difference in overall survival has been seen with combined modality therapy compared to radiation alone. Regardless, combined modality therapy is now the standard treatment for most patients with anal cancer, unless the patient is unable to tolerate combined treatment.

Surgery

Although surgery was the primary treatment for anal cancer 20 years ago, its role has greatly diminished since then. When performed, surgical resection usually is an abdominal perineal resection (APR), which consists of a wide excision of the anus, including the anal muscles, with placement of a permanent colostomy. A colostomy is performed by connecting the bowel to a hole in the abdominal wall (called a stoma). The stool that passes through the stoma is collected in a bag that is attached to the outside of the abdominal wall with adhesive. This bag can then be emptied by the patient as needed. Because the combination of chemotherapy and radiation therapy result in similar rates of local control and survival when compared to surgery, chemoradiation has been favored over surgery because it offers patients a good chance at preserving anal sphincter function, avoiding the need to place a permanent colostomy.

There are several situations in which surgery should be considered for anal cancer. Patients with carcinoma in situ or small, well-differentiated anal cancers that have not invaded into the anal sphincter can sometimes undergo a surgical excision without removing the anal muscles. In these early cases, the results of surgical excision can be quite good, and the patient can be spared to potential side effects of chemoradiotherapy. Alternatively, extensive anal cancers that have destroyed the anal sphincter, such that the patient cannot control bowel movements, are often treated with an APR. In these cases, patients have already lost their sphincter function, and require a colostomy to handle bowel movements. In these cases, surgical resection is often performed, and radiation with or without chemotherapy is given post-operatively. Surgery can also be performed in patients who cannot otherwise tolerate radiation therapy. Finally, surgery is often performed in the case of a local recurrence following previous treatment with radiation therapy if additional chemotherapy and radiation cannot be given.

After I am treated for anal cancer, how will I be followed?

After treatment for anal cancer, patients are usually followed every 3-6 months for several years with or without CT scans. The most important aspect of follow-up after completion of treatment is a thorough physical examination including a digital rectal exam. Anal cancers can take some time to respond to treatment and often continue to shrink months after chemotherapy and radiation have ended. Therefore, it is not unusual to have a residual mass immediately after treatment. The presence of a residual mass does not mean that the treatment did not work. Overall, the chance of long-term cure of anal cancer depends on the extent of the disease at the time it was first diagnosed. Patients who present with smaller disease without lymph node involvement or distant metastases have a better chance at long-term tumor control than those with larger disease or with lymph node involvement or distant metastases. If anal cancers do recur, they usually do so within the first 2 years after treatment, although recurrences after 2 years can occur. In general, the further out from treatment a patient is without evidence of a recurrence, the better the chances that the cancer will never come back.

The treatment of anal cancer should be a cooperative effort among the patient, the radiation oncology, the medical oncologist, and the surgeon. It is important that all patients with anal cancer know about their disease so that they can make an informed decision about their treatment. This article was intended to help answer some of the common questions patients face when they have anal cancer. If you have any additional questions, please contact your doctor.

AIDS-Related Lymphoma

2006-04-28T09:43:00.000-07:00

General Information About AIDS-Related Lymphoma

AIDS-related lymphoma is a disease in which malignant (cancer) cells form in the lymph system of patients who have acquired immunodeficiency syndrome (AIDS).

AIDS is caused by the human immunodeficiency virus (HIV), which attacks and weakens the body's immune system. The immune system is then unable to fight infection and diseases that invade the body. People with HIV disease have an increased risk of developing infections, lymphoma, and other types of cancer. A person with HIV disease who develops certain types of infections or cancer is then diagnosed with AIDS. Sometimes, people are diagnosed with AIDS and AIDS-related lymphoma at the same time.

Lymphomas are cancers that affect the white blood cells of the lymph system, part of the body's immune system. The lymph system is made up of the following:

Lymph: Colorless, watery fluid that travels through the lymph system and carries white blood cells called lymphocytes. Lymphocytes protect the body against infections and the growth of tumors.

Lymph vessels: A network of thin tubes that collect lymph from different parts of the body and return it to the bloodstream.

Lymph nodes: Small, bean-shaped structures that filter substances in lymph and help fight infection and disease. Lymph nodes are located along the network of lymph vessels found throughout the body. Clusters of lymph nodes are found in the underarm, pelvis, neck, abdomen, and groin.

Spleen: An organ that produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach.

Thymus: An organ in which lymphocytes grow and multiply. The thymus is in the chest behind the breastbone.

Tonsils: Two small masses of lymph tissue at the back of the throat. The tonsils produce lymphocytes.

Bone marrow: The soft, spongy tissue in the center of large bones. Bone marrow produces white blood cells, red blood cells, and platelets.

There are many different types of lymphoma.

Lymphomas are divided into two general types: Hodgkin's lymphoma and non-Hodgkin's lymphoma. Both Hodgkin's lymphoma and non-Hodgkin's lymphoma may occur in AIDS patients, but non-Hodgkin's lymphoma is more common. When a person with AIDS has non-Hodgkin's lymphoma, it is called an AIDS-related lymphoma.

AIDS-related lymphomas grow and spread quickly.

Non-Hodgkin's lymphomas are grouped by the way their cells look under a microscope. They may be indolent (slow-growing) or aggressive (fast-growing). AIDS-related lymphoma is usually aggressive.

There are three main types of AIDS-related lymphoma:

Diffuse large B-cell lymphoma.
B-cell immunoblastic lymphoma.
Small non-cleaved cell lymphoma.

Possible signs of AIDS-related lymphoma include weight loss, fever, and night sweats.

These and other symptoms may be caused by AIDS-related lymphoma. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

Weight loss or fever for no known reason.
Night sweats.
Painless, swollen lymph nodes in the neck, chest, underarm, or groin.
A feeling of fullness below the ribs.

Tests that examine the body and lymph system are used to help detect (find) and diagnose AIDS-related lymphoma.

The following tests and procedures may be used:

Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.

Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:

The number of red blood cells, white blood cells, and platelets.
The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
The portion of the sample made up of red blood cells.

Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to look for cancer cells. One of the following types of biopsies may be done:

Excisional biopsy: The removal of an entire lymph node.
Incisional biopsy or core biopsy: The removal of part of a lymph node.
Needle biopsy or fine-needle aspiration: The removal of a sample of tissue from a lymph node with a needle.

Bone marrow biopsy: The removal of a small piece of bone and bone marrow by inserting a needle into the hipbone or breastbone. A pathologist views both the bone and bone marrow samples under a microscope to look for signs of cancer.

HIV test: A test to measure the level of HIV antibodies in a sample of blood. Antibodies are made by the body when it is invaded by a foreign substance. A high level of HIV antibodies may mean the body has been infected with HIV.

Epstein-Barr virus (EBV) test: A test to measure the level of EBV antibodies in a sample of blood, tissue, or cerebrospinal fluid (CSF). Antibodies are made by the body when it is invaded by a foreign substance. A high level of EBV antibodies may mean the body has been infected with EBV.

Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

The stage of the cancer.
The number of CD4 lymphocytes (a type of white blood cell) in the blood.
Whether the patient has ever had AIDS-related infections.
The patient's ability to carry out regular daily activities.

Stages of AIDS-Related Lymphoma

After AIDS-related lymphoma has been diagnosed, tests are done to find out if cancer cells have spread within the lymph system or to other parts of the body.

The process used to find out if cancer cells have spread within the lymph system or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment, but AIDS-related lymphoma is usually advanced when it is diagnosed. The following tests and procedures may be used in the staging process:

CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radionuclide glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells.

MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium is injected into the patient through a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).

Bone marrow biopsy: The removal of a small piece of bone and bone marrow by inserting a needle into the hipbone or breastbone. A pathologist views both the bone and the bone marrow samples under a microscope to look for signs of cancer.

Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.

Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that produces it. The blood sample will be checked for the level of LDH (lactate dehydrogenase).

Stages of AIDS-related lymphoma may include E and S.

AIDS-related lymphoma may be described as follows:

E: "E" stands for extranodal and means the cancer is found in an area or organ other than the lymph nodes or has spread to tissues beyond, but near, the major lymphatic areas.

S: "S" stands for spleen and means the cancer is found in the spleen.
The following stages are used for AIDS-related lymphoma:

Stage I

Stage I AIDS-related lymphoma is divided into stage I and stage IE.

Stage I: Cancer is found in one lymph node group.

Stage E: Cancer is found in an area or organ other than the lymph nodes.

Stage II

Stage II AIDS-related lymphoma is divided into stage II and stage IIE.

Stage II: Cancer is found in two or more lymph node groups on the same side of the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).

Stage IIE: Cancer is found in an area or organ other than the lymph nodes and in lymph nodes near that area or organ, and may have spread to other lymph node groups on the same side of the diaphragm.

Stage III

Stage III AIDS-related lymphoma is divided into stage III, stage IIIE, stage IIIS, and stage IIIS+E.

Stage III: Cancer is found in lymph node groups on both sides of the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).

Stage IIIE: Cancer is found in lymph node groups on both sides of the diaphragm and in an area or organ other than the lymph nodes.

Stage IIIS: Cancer is found in lymph node groups on both sides of the diaphragm and in the spleen.

Stage IIIS+E: Cancer is found in lymph node groups on both sides of the diaphragm, in an area or organ other than the lymph nodes, and in the spleen.

Stage IV

In stage IV AIDS-related lymphoma, the cancer either:

is found throughout one or more organs other than the lymph nodes and may be in lymph nodes near those organs; or

is found in one organ other than the lymph nodes and has spread to lymph nodes far away from that organ.

Patients who are

infected with the Epstein-Barr virus or whose AIDS-related lymphoma affects the bone marrow have an increased risk of the cancer spreading to the central nervous system (CNS).

For treatment, AIDS-related lymphomas are grouped based on where they started in the body, as follows:

Peripheral/systemic lymphoma

Lymphoma that starts in lymph nodes or other organs of the lymph system is called peripheral/systemic lymphoma. The lymphoma may spread throughout the body, including to the brain or bone marrow.

Primary CNS lymphoma

Primary CNS lymphoma starts in the central nervous system (brain and spinal cord). Lymphoma that starts somewhere else in the body and spreads to the central nervous system is not primary CNS lymphoma.

Treatment Option Overview

There are different types of treatment for patients with AIDS-related lymphoma.

Different types of treatment are available for patients with AIDS-related lymphoma. Some treatments are standard (the currently used treatment), and some are being tested in clinica trials. Before starting treatment, patients may want to think about taking part in a clinical trial. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Treatment of AIDS-related lymphoma combines treatment of the lymphoma with treatment for AIDS.

Patients with AIDS have weakened immune systems and treatment can cause further damage. For this reason, patients who have AIDS-related lymphoma are usually treated with lower doses of drugs than lymphoma patients who do not have AIDS.

Highly-active antiretroviral therapy (HAART) is used to slow progression of HIV (which is a retrovirus). Treatment with HAART may allow some patients to safely receive anticancer drugs in standard or higher doses. Medicine to prevent and treat infections, which can be serious, is also used.

AIDS-related lymphoma usually grows faster than lymphoma that is not AIDS-related and it is more likely to spread to other parts of the body. In general, AIDS-related lymphoma is harder to treat.

Three types of standard treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Intrathecal chemotherapy may be used in patients who are more likely to have lymphoma in the central nervous system (CNS).

Colony-stimulating factors are sometimes given together with chemotherapy. This helps lessen the side effects chemotherapy may have on the bone marrow.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

High-dose chemotherapy with stem cell transplant

High-dose chemotherapy with stem cell transplant is a method of giving high doses of chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.

New types of treatment are being tested in clinical trials. These include the following:

Monoclonal antibody therapy

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading.
Monoclonal antibodies are given by infusion. These may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

Treatment Options for AIDS-Related Lymphoma

AIDS-Related Peripheral/Systemic Lymphoma

There is no standard treatment plan for AIDS-related peripheral/systemic lymphoma.

Treatment is adjusted for each patient and is usually one or more of the following:

Combination chemotherapy.
High-dose chemotherapy and stem cell transplant.
A clinical trial of monoclonal antibodies.
A clinical trial of different treatment combinations.

AIDS-Related Primary Central Nervous System Lymphoma

Treatment of AIDS-related primary central nervous system lymphoma is usually radiation therapy.

Adrenal Cancer

2006-04-28T00:17:00.000-07:00

What are the adrenal glands?

The adrenal glands are small glands that are located just above each of your kidneys (they are sometimes called the suprarenal glands for that reason). They are triangular in shape and consist of several distinct parts.

The central part of the gland is called the adrenal medulla and produces the chemicals epinephrine (also called adrenaline) and norepinephrine. Both of these chemicals play an important role in the regulation of the nervous system. Epinephrine controls the short-term stress response (aka fight-or-flight response). While norepinephrine also plays a role in short-term stress response, it functions in regulating mood and attention, as well.

The outside part of the gland surrounding the medulla is the adrenal cortex . This part of the adrenal gland is largely responsible for producing steroid hormones in the body. There are several types of steroids hormones that are produced by the adrenal glands. Mineralocorticoids (such as aldosterone ) are hormones that help regulate the salt levels in the body by controlling the absorption and excretion of salt and water in the kidneys, which in turn helps to regulate blood pressure. Glucocorticoids (such as cortisol ) are hormones that play a critical role in the regulation of sugar within the body. These hormones also help to regulate the fat stores within the body, act as a strong anti-inflammatory force, and play an important role in fetal development, particularly in lung maturation. The adrenal cortex also produces several sex hormones, including androgens (critical for male sexual development) and precursors to estrogen (critical for female sexual development).

What are adrenal tumors, and what types of adrenal tumors are there?

Normally, cells in the body will grow and divide to replace old or damaged cells. This growth is highly regulated, and once enough cells are produced to replace the old ones, normal cells will stop dividing. Tumors occur when there is an error in this process, and cells continue to grow in an uncontrolled manner. Tumors can either be benign or malignant. Although benign tumors can grow uncontrolled, they do not break off and spread beyond where they start, nor do they invade into surrounding tissues. Malignant tumors (also known as cancers) will grow uncontrolled in such a way that they invade and damage other tissues around them. They also gain the ability to break off from where they start and spread to other parts of the body, usually through the blood stream or through the lymphatic system where the lymph nodes are located (a process known as metastasis ).

The most common tumor of the adrenal gland is actually a benign tumor called an adrenal adenoma . In most patients, these benign tumors never cause a patient to have any symptoms and do not need to be treated. The most common malignant tumors found in the adrenal gland are tumors that come from cancer cells that have metastasized (or spread) from other parts of the body to the adrenal gland through the blood stream. This can occur in a number of different types of cancers, but most commonly occur with melanomas, lung cancers, and breast cancers. The adrenal glands are the fourth most common site in the body for cancer cells to metastasize to, after the lungs, liver, and bone.

Cancers can arise directly within the adrenal glands themselves; however, these are relatively rare. Cancers can arise directly from the adrenal cortex. These cancers can either be functioning (meaning they secrete excess steroid hormones) or non-functioning (meaning they do not secrete steroids). Functioning adrenal cortical cancers are more common than non-functioning cancers. Cancers can also arise within the adrenal medulla, the most common of which are pheochromocytomas . These cancers are discussed in more detail in the section entitled "Pheochromocytomas" and are not discussed further in this review.

Other types of adrenal cancers can occur, such as lymphoma; however, these cases are rare.

What are the signs of adrenal cortical tumors?

Both adrenal adenomas and adrenal cortical cancers can be produce excess steroid hormones. Symptoms vary depending on the steroid that is produced. If too much aldosterone is produced, Conn 's syndrome (also known as primary hyperaldosteronism ) can develop. Conn 's syndrome most commonly occurs with pituitary adenomas, but it can also occur in the setting of adrenal hyperplasia (an overgrowth of normal adrenal cortical tissue) and adrenal cortical cancers. Patients who have Conn's syndrome have elevated blood pressure, decreased levels of potassium in the blood, and decreased levels of a chemical produced by the kidneys called renin in the blood. In most cases of Conn 's syndrome, elevations in blood pressure are mild to moderate. Other symptoms include weakness, muscle cramps, increased thirst, and increased frequency of urination.

If too much cortisol is produced, Cushing's syndrome (also known as hypercortisolism ) can develop. This syndrome is seen not only with adrenal tumors, but can also be the result of excessive levels of adrenal cortical stimulating hormone (also known as ACTH, a hormone that is responsible for stimulating the adrenal glands to produce cortisol) produced by the pituitary gland or another tumor in the body or though the use of corticosteroids as treatment for another disease. The symptoms of Cushing's syndrome can vary greatly from patient to patient and involve a number of different parts of the body. Symptoms include weight gain and water retention resulting in a round face and collection of fat on the back of the shoulders and neck. Red streaks can appear on the skin. Excessive hair growth (called hirsutism) can be seen. Excessive cortisol levels can interfere with the body's immune system predisposing a patient to unusual infections. Patients with Cushing's syndrome can develop diabetes. They can also have mental changes, including mood swings, irritability, and in the worst case, psychotic episodes. Virilization can occur, particularly in women, resulting in deepened voice, loss of hair, and increase in the size of the clitoris. Women can have irregular menstrual periods or stop menstruating altogether, and men can experience sexual impotence. In children, excessive cortisol can lead to premature sexual development and maturation (also called precocious puberty ).

Adrenal tumors can also cause symptoms if they grow large enough. Patients with large adrenal tumors may experience feelings of abdominal fullness or localized pain. Patients may feel as though they are quickly full when eating and may experience weight loss. In some cases of large adrenal tumors, patients may actually feel a mass in their abdomen.

What causes adrenal cortical cancers and am I at risk?

Each year, there are approximately 500 cases of adrenal cortical cancers in the United States. These most commonly occur in patients between the ages of 30 and 50; however, children under the age of 5 develop adrenal cortical cancers at a higher rate than the rest of the population. Males are more likely to develop non-functioning adrenal carcinomas, while females are more likely to develop functioning adrenal carcinomas. In general, it is not known what causes adrenal cortical cancers. It is not associated with smoking and does not run in families. Despite this, certain genetic mutations have been associated with its formation, and research is ongoing in trying to identify the causes of these cancers.

How can I prevent adrenal cortical cancers?

Given that the causes of adrenal cortical cancers are unclear, there are no known interventions that can reduce the risk of developing them.

How are adrenal cortical cancers diagnosed, and how do you tell them apart from adrenal adenomas?

Functioning adrenal cortical cancers and adenomas are frequently diagnosed because of the symptoms caused by the steroids. Patients with Cushing's syndrome need to be evaluated to see if the syndrome is caused by a problem in the adrenal glands or by production of ACTH from the pituitary gland or another tumor somewhere else in the body. The first step is measuring the amount of cortisol in the urine (called a 24-hour urinary free cortisol test ). This test is sometimes performed while giving the patient an extra dose of steroids to see how the body responds. After this is done, most patients undergo a dexamethasone suppression test where patients are given a high dose of the steroid dexamethasone. In normal patients and in patients with Cushing's syndrome due to a problem in the pituitary gland, a high dose of dexamethasone will cause the levels of cortisol in the blood and urine to decrease. In patients with adrenal tumors or another tumor in the body that produces ACTH, cortisol levels remain high even after a patient receives a high dose of dexamethasone.

In patients with excess levels of aldosterone, patients should be tested for blood levels of the chemical renin. In cases of hyperaldosteronism due to a tumor in the adrenal gland, renin levels should be low. In patients who have elevated aldosterone levels due to a problem with the blood vessels of the kidney (a condition called renal artery stenosis), renin levels in the blood are high.

In addition to tests for increased steroid production, radiographic imaging is an important part of the diagnosis of adrenal tumors. Computed Tomography (CT or CAT) scans are commonly used. CT scans use x-rays to form a three-dimensional picture of the inside of the body. If the adrenal tumor is larger than 6 centimeters (cm) on CT scan, it is much more likely to be an adrenal cancer than an adrenal adenoma. In most cases, CT scans can also tell the difference between a normal adrenal gland and adrenal hyperplasia.
Ultrasound is sometimes used in the diagnosis of adrenal tumors. Ultrasounds use sound waves to form a picture of the inside of the body. At times, it can be difficult to tell if an adrenal tumor is an adenoma or a cancer. For tumors that are larger than 3 cm, ultrasound is a good method of telling the difference between the two.

Another type of imaging that is used when it is unclear if an adrenal tumor is an adenoma or cancer is Magnetic Resonance Imaging (MRI). MRI uses magnets to produce a very sharp picture of the inside of the body. Certain types of changes on MRI are more commonly seen in adrenal cancers than adenomas and can be used to tell the two apart.

Positron Emission Tomography (PET) scans use radioactively labeled sugar to find rapidly growing cells within the body. When cells are dividing quickly, they require a lot of energy, and the main source of energy in the body is sugar. Areas of actively dividing tissue will require more sugar than slowly dividing tissue. Because cancer cells are rapidly dividing and growing, they take up more the radioactively sugar than the surrounding tissue and this can be detected by the PET scanner. PET scans have been very useful in detect a number of different types of cancers. Its use in adrenal cancers is still being studied.

Ultimately, the only way to tell for sure if an adrenal tumor is an adrenal adenoma or cancer, part of the tumor must be examined underneath a microscope. In most cases of tumors or cancers in other parts of the body, this is done by obtaining a biopsy of the tumor. A small piece of the tumor is taken, usually through a needle, and examined underneath a microscope. In the case of adrenal tumors, this procedure is usually performed while the patient is undergoing a CT scan, so that the radiologist can see where the needle is going in the body. In some cases, this can also be done using an ultrasound to guide the biopsy.

How are adrenal cortical cancers staged?

In addition to diagnosing adrenal cortical cancers, the radiographic imaging performed also helps to determine the stage of the patient. In general, patients with adrenal cortical cancer are divided into one of four stages.

Stage I: The cancer is smaller than 5 cm and has not spread outside of the adrenal gland.

Stage II: The cancer is larger than 5 cm and has not spread outside of the adrenal gland.

Stage III: The cancer has spread into the fat surrounding the adrenal gland or has spread to lymph nodes near the adrenal gland.

Stage IV: The cancer has spread to other parts of the body, has spread into other organs near the adrenal gland, or has spread into both the fat around the adrenal gland and the lymph nodes near the adrenal gland.

Although this system of cancer staging is quite complicated, it is designed to help physicians describe the extent of the cancer, and therefore, helps to direct what type of treatment is given.

How are adrenal adenomas treated?

Most adrenal adenomas are detected on a CT scan or MRI scan that is performed for an unrelated reason. It is only necessary to treat them if they are causing symptoms. Otherwise, they can be followed with repeated scans periodically. In the event that an adenoma does need to be treated, surgical removal is the most frequent treatment used. In many cases, this can be performed using a laparoscopic procedure. A laparoscope is a small fiberoptic camera that can be inserted into the abdomen through small incisions. Other small instruments can also be inserted through these incisions. The adrenal adenoma can be resected while inside the body, without making a large incision in the abdomen, and removed through the small holes through which the camera and other instruments are inserted. Occasionally, because of the size or location of the adenoma, a laparoscopic procedure cannot be performed, and a large incision will need to be made in the abdomen in order to remove the tumor.

In the majority of cases of hyperaldosteronism, symptoms resolve with surgical removal of the adenoma; however, 30% of patients will have repeat episodes of high blood pressure even after the adenoma is removed. If the adrenal adenoma produces cortisol, the patient should take steroids by mouth before and for some time after the surgery until the body is able to produce these steroids on its own again.

How are adrenal cortical cancers treated?

Surgery

Currently, the only known curative treatment for adrenal cortical cancers is complete resection of the tumor. Unfortunately, this is only possible in a limited number of patients with this disease. At least half of patients with adrenal cortical cancers have metastases or cancer invading into other organs, such that a complete resection of the cancer is not possible. The best results with surgical resection have been with an en bloc resection, meaning that the entire tumor is removed in one piece. This also includes removing the entire kidney on the same side as the adrenal cancer. Because of this, it is unusual for adrenal cancers to be removed using a laparoscopic procedure, although as techniques of laparoscopic resection improve, more patients are being treated with this method. Occasionally, adrenal cancers will grow into the large blood vessel that carries blood back from the lower body to the heart (the vena cava ). Even in these cases, complete resections of the cancer can sometimes be performed. If this is the case, a very large surgery is required involving both a general surgeon or urologist and a vascular surgeon.

Even in cases where the tumor cannot be removed in its entirety, surgical removal of as much tumor as possible can improve symptoms, particularly if they are due to excessive steroid secretion.

Chemotherapy

Chemotherapy is a medication that is usually given intravenously or orally as a pill. It goes to the bloodstream and throughout the body to kill cancer cells. This is one of the big advantages of chemotherapy. If cancer cells have broken off from the tumor and are somewhere else inside the body, chemotherapy has the chance of finding those cells and killing them. A number of different chemotherapeutic agents exist, each with its own side effects. You should discuss the potential side effects of any chemotherapy you may receive with your medical oncologist.

Although chemotherapy is used in some cancers as neoadjuvant or adjuvant treatment (meaning it is given routinely before or after surgery to improve the chances that the cancer stays away), chemotherapy has not been shown to be beneficial in adrenal cancers that have been completely resected. However, chemotherapy is often used in cases where the adrenal cortical cancer has metastasized or where the adrenal gland can not be completely resected. The most commonly used agents for adrenal cortical cancers are mitotane and cisplatin. Mitotane acts to block the hormones produced by the cancer and can also kill adrenal cancer cells. It has been found to cause shrinkage of the tumor in over one-third of patients tested, and in some cases causes complete disappearance of the cancer on radiographic imaging. Despite these good responses, the adrenal cancer usually comes back at some point down the road.

There are a number of other types of chemotherapy used for adrenal cancers. Exactly which chemotherapeutic agents are given varies according to the physician giving them. Based on your own health status and the risks of side effects that you are willing to accept, the choice of chemotherapy can vary.

Radiation Therapy

Radiation therapy is used in a number of cancers as both the main method of killing cancer cells or in combination with surgery (either before or after). The radiation comes in the form of high-energy x-rays that are delivered to the patient only in the areas at highest risk for cancer. These x-rays are similar to those used for diagnostic x-rays, only of a much higher energy. The high-energy of x-rays in radiation therapy results in damage to the DNA of cells, causing tumor cells to die.

Radiation therapy is not part of the routine management of adrenal cancers, particularly in cases where the cancer is completely removed by surgery. Radiation has been tried in cases where surgical removal of the cancer is incomplete or in cases where the cancer comes back after surgery. In these cases, the radiation is usually delivered daily, Monday through Friday, 5 days a week, for a total of 5 to 7 weeks. In general, the side effects associated with this treatment include fatigue, skin redness and irritation, nausea, and diarrhea.

What are the results of treatment for adrenal cortical cancers?

In general, adrenal cortical cancers are curable only in cases where the entire tumor is removed at surgery. Unfortunately, these tend to be aggressive cancers. Even when complete surgical removal is performed, they have a tendency to come back. The likelihood of this happening after a complete surgical resection is dependent upon the stage of the tumor. The 5-year overall survival describes the percentage of patients who are alive at 5 years after cancer treatment. After en bloc resection for stage I and II adrenal cortical cancers, the 5-year overall survival rate is 40-60%. For stage III cancers, the 5-year overall survival is 20%. For stage IV patients, the 5-year overall survival is 10%. There is a small percentage of patients who have slow-growing adrenal cortical cancers that can take a number of years to progress. It is unclear why these adrenal cancers act differently than the majority of adrenal cancers; however, these cases explain why 10% of patients who have disease that has spread to other parts of the body at the time of diagnosis (stage IV) are still alive at 5 years after diagnosis, despite the generally aggressive nature of these cancers.

How are other cancers that have spread (metastasized) to the adrenal gland treated?

In most cases, when other cancers spread to the adrenal glands, they are treated with chemotherapy that is known to be effective against the original cancer type. In some cases, if the adrenal gland is the only site in the body where the cancer appears to have spread, surgical resection of metastatic cancer and the adrenal gland can be performed, followed by treatment to the primary site where the cancer started. This has been shown to be curative in a small number of patients, particularly in the case of lung cancer.

After I am treated for an adrenal cortical tumor, how will I be followed?

Shortly after treatment for functional (secreting) adrenal tumors, blood will be drawn to measure hormone levels in the body. If the hormone levels have returned to normal after therapy, regular follow-up will occur. You will be followed every 3-6 months for several years after treatment. In the case of non-functional (non-secreting) adenomas and adrenal cortical cancers, periodic follow-up MRI or CT of the abdomen will be obtained for the first few years

The treatment of pituitary tumors should be a cooperative effort among the patient, radiation oncologist, neurosurgeon, and neurologist. It is important that all patients with pituitary tumors know about their disease so that they can make an informed decision about their treatment. This article was intended to help answer some of the common questions patients face when they have a pituitary tumor. If you have any additional questions, please contact your doctor.