Retinoblastoma

What is cancer?
The body is made up of hundreds of millions of living cells. Normal body cells grow, divide, and die in an orderly fashion. During the early years of a person's life, normal cells divide faster to allow the person to grow. After the person becomes an adult, most cells divide only to replace worn-out or dying cells or to repair injuries. Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-of-control growth of abnormal cells. Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. Cancer cells can also invade (grow into) other tissues, something that normal cells cannot do. Growing out of control and invading other tissues are what makes a cell a cancer cell. Cells become cancer cells because of damage to DNA. DNA is in every cell and directs all its actions. In a normal cell, when DNA gets damaged the cell either repairs the damage or the cell dies. In cancer cells, the damaged DNA is not repaired, but the cell doesnt die like it should. Instead, this cell goes on making new cells that the body does not need. These new cells will all have the same damaged DNA as the first cell does. People can inherit damaged DNA, but most DNA damage is caused by mistakes that happen while the normal cell is reproducing or by something in our environment. Sometimes the cause of the DNA damage is something obvious, like cigarette smoking. But often no clear cause is found. In most cases the cancer cells form a tumor. Some cancers, like leukemia, rarely form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues where they grow. Cancer cells often travel to other parts of the body, where they begin to grow and form new tumors that replace normal tissue. This process is called metastasis. It happens when the cancer cells get into the bloodstream or lymph vessels of our body.

No matter where a cancer may spread, it is always named for the place where it started. For example, breast cancer that has spread to the liver is still called breast cancer, not liver cancer. Likewise, prostate cancer that has spread to the bone is metastatic prostate cancer, not bone cancer. Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer. Not all tumors are cancerous. Tumors that arent cancer are called benign. Benign tumors can cause problems they can grow very large and press on healthy organs and tissues. But they cannot grow into (invade) other tissues. Because they cant invade, they also cant spread to other parts of the body (metastasize). These tumors are almost never life threatening.

What are the differences between cancers in adults and children?

The types of cancers that develop in children are different from the types that develop in adults. There are exceptions, but childhood cancers tend to respond better to chemotherapy. Children's bodies also tend to tolerate chemotherapy better than adults' bodies do. But because chemotherapy can have some long-term side effects, children who survive their cancer need careful attention for the rest of their lives. Since the 1960s, most children and adolescents with cancer have been treated at specialized centers designed for them. Being treated in these centers offers them the advantage of a team of specialists who know the differences between adult and childhood cancers, as well as the unique needs of children with cancers. This team usually includes pediatric oncologists, pathologists, surgeons, radiation oncologists, pediatric oncology nurses, and nurse practitioners. These centers also have psychologists, social workers, child life specialists, nutritionists, rehabilitation and physical therapists, and educators who can support and educate the entire family. Most children with cancer in the United States are treated at a center that is a member of the Children's Oncology Group (COG). All of these centers are associated with a university or children's hospital. As we have learned more about treating childhood cancer, it has become even more important that treatment be given by experienced experts.

What is retinoblastoma?
Most cancers are named for the part of the body where the cancer starts. Retinoblastoma is a cancer that starts in the retina, the very back part of the eye. It is the most common

type of eye cancer in children. Rarely, children can have other kinds of eye cancer, such as medulloepithelioma, which is described briefly below. But the information in this document focuses on retinoblastoma and not other kinds of eye cancer. To understand retinoblastoma, it helps to know something about the normal structures of the eye and how they work.

About the eye

The main part of the eye is the eyeball (also known as the globe), which is filled with a jelly-like material called vitreous. The front of the eyeball has a lens with an iris (the colored part of the eye that acts like a camera shutter), which allows light to enter the eye and focuses it on the retina. The retina is the inner layer of cells in the back of the eye. It is made up of specialized nerve cells that are sensitive to light. These light-sensing cells are connected to the brain by the optic nerve, which runs out the back of the eyeball. The pattern of light (image) that reaches the retina is sent through the optic nerve to an area of the brain called the visual cortex, allowing us to see.

How does retinoblastoma develop?

The eyes develop very early as babies grow in the womb. During the early stages of development, the eyes have cells called retinoblasts that divide into new cells and fill the retina. At a certain point, the cells stop dividing and develop into mature retinal cells. Rarely, something goes wrong with this process. Instead of developing into special cells that detect light, some retinoblasts continue to grow rapidly and out-of-control, and form a cancer known as retinoblastoma.

The chain of events that lead to retinoblastoma is rather complex, but it is always started by an abnormality (mutation or change) in a gene called the retinoblastoma (Rb or RB1) gene. The normal RB1 gene helps keep cells from growing out of control. Depending on when and where the change in the RB1 gene occurs, 2 different types of retinoblastoma can result.

Congenital (hereditary) retinoblastoma

In about 1 out of 4 retinoblastomas, the abnormality in the RB1 gene is congenital (present at birth) and is in all the cells of the body (known as a germline mutation). This includes all of the cells of both retinas. In most of these children, there is no family history of this cancer. Only about 25% of the children born with this gene abnormality inherit it from a parent. In about 75% of cases the gene change first occurs during early development in the womb. (The reasons for this are not clear.) Children born with a mutation in the RB1 gene usually develop retinoblastoma in both eyes (bilateral retinoblastoma). Within the eyes there are often several tumors (multifocal retinoblastoma). Because all of the cells in the body have the changed RB1 gene, these children also have a higher risk of developing cancers elsewhere in the body. A small number of children with this form of retinoblastoma will develop another tumor in the brain, usually in the pineal gland at the base of the brain (a pineoblastoma). This is also known as trilateral retinoblastoma. For survivors of hereditary retinoblastoma, the risk of developing another cancer later in life may be as high as 40%. (For more information, see the section, "What happens after treatment for retinoblastoma?")

Sporadic (non-hereditary) retinoblastoma

In about 3 out of 4 cases of retinoblastoma, the abnormality in the Rb1 gene develops on its own in only one cell in one eye. It is not known what causes this change. A child who has sporadic (non-hereditary) retinoblastoma develops only one tumor in one eye. This type of retinoblastoma is often found at a later age than the congenital form.

How does retinoblastoma grow and spread?

If retinoblastoma tumors are not treated, they can continue to grow and may fill much of the globe (eyeball). The cells may break away from the retinal tumor and float through the vitreous to reach other parts of the eye, where they form more tumors. If these tumors block the channels that circulate fluid within the eye, the pressure inside the eye can rise. This can cause glaucoma, one of the serious complications of retinoblastoma, which can lead to pain and loss of vision in the affected eye.

Most retinoblastomas are found and treated before they have spread outside the globe. But retinoblastoma cells can occasionally spread to other parts of the body. The cells sometimes grow along the optic nerve and reach the brain. Retinoblastoma cells can also grow through the covering layers of the globe and into the eye socket, eyelids, and nearby tissues. Once tissues outside the globe are affected, the cancer may then spread to lymph nodes (small bean-shaped collections of immune system cells) and to other organs such as the liver, bones, and bone marrow.

Medulloepithelioma
Medulloepithelioma is another type of eye tumor. It is not a type of retinoblastoma, but it is mentioned here because it also usually occurs in young children. These tumors are very rare. Most medulloepitheliomas are malignant (cancerous), but they rarely spread outside the eye. They usually cause eye pain and decreased vision. The diagnosis is made when a doctor finds a tumor mass in the eye by using an ophthalmoscope (an instrument that helps doctors to look inside the eye). Like retinoblastoma, the diagnosis is usually made based on the appearance and location of the tumor inside the eye. A biopsy (removing cells from the tumor to be looked at under a microscope) to confirm the diagnosis is almost never done because it might harm the eye or risk spreading the cancer outside of the eye. Treatment for medulloepithelioma is almost always surgery to remove the eye.

What are the key statistics about retinoblastoma?

Retinoblastoma is a rare disease. Only about 300 children are diagnosed with retinoblastoma each year in the United States. It is more common in infants and very young children than in older children. The average age of children when they are diagnosed is 2. It rarely occurs in children older than 6. About 3 out of 4 children with retinoblastoma have a tumor in only one eye. In about 1 case in 4, both eyes are affected. Retinoblastoma occurs about equally in boys and girls and in different races and ethnicities. It also occurs equally in the right or left eye. Overall, more than 90% of children with retinoblastoma can be cured, but the outlook is not nearly as good if the cancer has spread to other parts of the body.

What are the risk factors for retinoblastoma?

A risk factor is anything that affects a person's chance of getting a disease such as cancer. But risk factors don't tell us everything. Different cancers have different risk factors.

Lifestyle-related risk factors such as diet, body weight, physical activity, and tobacco use play a major role in many adult cancers. But these factors usually take many years to influence cancer risk, and they are not thought to play much of a role in childhood cancers, including retinoblastomas.

Age
Most children diagnosed with retinoblastoma are younger than 3 years old. Most congenital or hereditary retinoblastomas are found during the first year of life, while noninherited retinoblastomas tend to be diagnosed in 1- and 2-year-olds. Retinoblastomas are extremely rare in older children and in adults.

Heredity
About 1 out of 4 cases of retinoblastoma are caused by a mutation (change) in the RB1 gene that is present in all the cells of the body, and therefore can be passed on to the next generation. However, of these cases, only about 1 in 4 is inherited from one of the child's parents. In the rest, the gene mutation has not been inherited, but has occurred during early development in the womb. Children born with a mutation in the RB1 gene usually develop retinoblastoma in both eyes. The remaining 3 out of 4 cases occur as a result of a random RB1 gene mutation that occurs only in one cell of one eye; they are not inherited from a parent. Non-hereditary retinoblastomas always affect one eye only. The way in which inherited gene changes make certain children likely to develop retinoblastoma is explained in the next section, "Do we know what causes retinoblastoma?"

Do we know what causes retinoblastoma?

Retinoblastoma is caused by mutations (changes) in certain genes. Over the past few decades, scientists have made great progress in understanding how certain changes in a person's DNA can cause cells of the retina to become cancerous. DNA is the chemical in each of our cells that makes up our genes the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects much more than the way we look. Some genes have instructions that control when our cells grow, divide, and die. Certain genes that speed up cell division are called oncogenes. Others that slow down cell division, or cause cells to die at the right time, are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. The most important gene involved in retinoblastoma is the RB1 tumor suppressor gene. This gene makes a protein (pRb) that helps stop cells from growing too quickly. Each cell normally has 2 RB1 genes. As long as a retinal cell has at least one RB1 gene that works

as it should, it will not form a retinoblastoma. But when both of the RB1 genes are mutated or missing, a cell can grow unchecked. This can lead to further gene changes, which in turn may cause cells to become cancerous.

Hereditary or bilateral retinoblastoma

About 1 out of 4 children with retinoblastoma have a germline mutation in one RB1 gene; that is, all the cells in the body have the defective RB1 gene. The majority of these children (75%) have developed this mutation after conception while in the womb The other 25% have inherited it from one of the parents. About 90% of children who are born with this germline mutation of the RB1 gene develop a retinoblastoma in one or both eyes. This happens when the second RB1 gene is lost or mutated. Every person has 2 RB1 genes but passes only 1 on to each of their children (the other RB1 gene comes from the other parent). The odds that a parent with bilateral retinoblastoma will pass the mutated gene on to his or her child are 1 out of 2. Most children with bilateral retinoblastoma don't have an affected parent (the RB1 mutation occurs while in the womb). But these children will eventually be at risk of passing the disease on to their children. This is why we call this bilateral or congenital form of retinoblastoma "hereditary" (even though neither of the child's parents may have been affected).

Non-hereditary (sporadic) retinoblastoma

The remaining 3 out of 4 children with retinoblastoma do not have the RB1gene mutation in all the cells of the body. Instead, the RB1 gene mutations happen during their early life and first occur only in one cell in one eye. Whether the changes in the RB1 gene are hereditary or sporadic, what causes these changes is not known. They may result from random gene errors that sometimes occur when cells reproduce and divide. There are no known lifestyle-related or environmental causes of retinoblastomas, so it is important to remember that there is nothing these children or their parents could have done to prevent these cancers.

Can retinoblastoma be prevented?

With many cancers in adults, the risk of cancer can be reduced by avoiding certain risk factors, such as smoking or exposure to hazardous chemicals in the workplace. But there are no known avoidable risk factors for retinoblastoma. So there is nothing that a parent or child can do to prevent this cancer. If your child does develop retinoblastoma, it is important to realize that you or your child did nothing to cause it. About 1 in 4 cases of retinoblastoma are hereditary, so survivors should consider genetic counseling before having children, to understand the risks of passing the gene change on

to their children and perhaps to explore ways to avoid this. For example, an option some people might consider would be to use in vitro fertilization and implant only embryos that don't have the gene change. If a preventive option is not used, children born into a family with a history of retinoblastoma should be screened for this cancer starting shortly after birth because early detection of this cancer greatly improves the chance for successful treatment. See the next section, "Can retinoblastoma be found early?" for more information.

Can retinoblastoma be found early?

Many retinoblastomas can be found early. During children's physical exams, doctors routinely check their eyes. Retinoblastomas may be found during these exams. In some cases, parents may notice that a child's eye has an unusual appearance, prompting a visit to the doctor. The signs and symptoms of retinoblastoma are described in the section, "How is retinoblastoma diagnosed?" For children in families known to have an abnormal RB1 gene, which means a high risk of hereditary retinoblastoma, doctors recommend repeated eye exams during the first years of life to detect tumors at an early stage. These children often have an eye exam a few days after birth, again at about 6 weeks of age, then every few months until at least age 3. Since this genetic defect can now be found by a special blood test, most doctors recommend that children with parents or siblings with a history of retinoblastoma have this blood test done during the first weeks after birth. The results of the test then help define how often eye exams should be done. Most cases of hereditary retinoblastoma develop and are diagnosed in infants only a few months old. Usually, if tumors develop in both eyes, it happens at the same time. But in some children tumors develop in one eye first, then a year or more later in the other eye. So even after retinoblastoma is diagnosed in one eye, these children continue to need regular exams of both eyes. If the retinoblastoma is thought to be inherited, doctors recommend these children also have magnetic resonance imaging (MRI) scans of the brain at regular intervals to check for a trilateral retinoblastoma (brain tumor such as a pineoblastoma). For more information, see the section, "How is retinoblastoma diagnosed?"

How is retinoblastoma diagnosed?

Most types of cancer can be found by physical exam and imaging tests, but treatment is usually not begun until a biopsy (removing a sample from the tumor and looking at it under a microscope) confirms the diagnosis. But biopsies are not usually done to diagnose retinoblastoma for 2 reasons. First, retinoblastoma can be recognized with great accuracy by doctors who have experience with this disease, and it is unlikely to be confused with other eye problems of children. Second, taking a biopsy specimen from the tumor cannot be done easily without harming the eye and risking spreading the cancer cells outside of the eye.

Signs and symptoms

Retinoblastomas are usually found because a parent or pediatrician notices a child's eye looks unusual. Normally when you shine a light in a child's eye, the pupil (the dark spot in the center of the eye) looks red because of the blood in vessels in the back of the eye. In an eye with retinoblastoma, the pupil often appears white or pink instead. This white glare of the eye may be noticed by a parent after a flash photograph is taken or by the child's doctor during a routine eye exam. This is the most common early sign of retinoblastoma. Sometimes both eyes do not appear to look in the same direction, a condition often called lazy eye. (Doctors call this strabismus.) There are many possible causes of this in children. Most of the time lazy eye is caused by a mild weakness of the muscles that control the eyes, but retinoblastoma is also one of the rare causes. Less common symptoms and signs of retinoblastoma include: Vision problems Eye pain Redness of the white part of the eye Bleeding in the front part of the eye A pupil that does not get smaller when exposed to bright light

Medical history and physical exam

If your child has signs or symptoms that might be due to retinoblastoma, the doctor will want to examine your child's eyes and take a complete medical history. The doctor will probably ask about the family history of retinoblastoma or other cancers, and about the child's symptoms. This information is important when deciding if more tests and exams by specialists are needed. Your family history is also useful for determining whether other relatives could possibly pass this gene on to their children or develop this cancer themselves (if they are young children) and might benefit from genetic counseling. If a retinoblastoma is suspected, the doctor will probably refer you to an ophthalmologist (a doctor who specializes in eye diseases), who will examine the eye closely to be more certain about the diagnosis. The ophthalmologist will use special lights and magnifying lenses to look at the retina. Usually, the child needs to be under general anesthesia (asleep) during the exam so that the doctor can take a careful and detailed look. If the diagnosis is retinoblastoma, imaging tests will be done to find out how far it may have spread within the eye and to see if it has spread to other parts of the body. Usually an ophthalmologist who specializes in treating cancers of the eye will make the final determination. This doctor should also be part of the team of doctors treating the cancer.

Imaging tests
Imaging tests use x-rays, sound waves, magnetic fields, or radioactive substances to create pictures of the inside of the body. The tests themselves are painless, but some may require injections. Imaging tests may be done for a number of reasons, including: To help distinguish between retinoblastoma and other eye diseases To determine how large the cancer is and how far it has spread To help determine if treatment has been effective Children with retinoblastoma may have one or more of these tests.

Ultrasound
Ultrasound, also known as ultrasonography, uses sound waves to create images of tissues inside the body, such as the inner parts of the eye. For this test, a small ultrasound probe is placed on the surface of the eye. The probe releases sound waves and detects the echoes that bounce off the tissues inside and around the eye. The echoes are converted by a computer into a black and white image of the eye and nearby tissues that is displayed on a computer screen. Ultrasound is one of the most commonly used imaging tests to confirm the diagnosis of retinoblastoma. It is painless and does not expose the child to radiation, but the child may need to be sedated (made sleepy) so that the doctor can get a good look at the eye. This test can be very useful when tumors in the eye are so large they prevent doctors from seeing inside the whole eye because ultrasound can "see through" tissues.

Computed tomography (CT) scan

The CT scan is an x-ray test that produces detailed cross-sectional images of parts of the body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around your child while he or she lies on a table. A computer then combines these pictures into images of slices of the part of the body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body. Before the scan, your child may receive an IV (intravenous) injection of a contrast dye that helps better outline structures in the body. The dye may cause some flushing (a feeling of warmth, especially in the face). Some people are allergic and get hives. Rarely, more serious reactions like trouble breathing or low blood pressure can occur. Be sure to tell the doctor if your child has any allergies or has ever had a reaction to any contrast material used for x-rays. CT scans take longer than regular x-rays, but not as long as MRI scans. Your child will need to lie still on a table while they are being done. During the test, the table slides in and out of the scanner, a ring-shaped machine that completely surrounds the table. Some people feel a bit confined by the ring they have to lie in while the pictures are being

taken. In some cases, your child may need to be sedated before the test to stay still and help make sure the pictures come out well. Spiral CT (also known as helical CT) is now used in many medical centers. This type of CT scan uses a faster machine. The scanner part of the machine rotates around the body continuously, allowing doctors to collect the images much more quickly than with a standard CT. This lowers the chance of blurred images occurring as a result of body movement. It also lowers the dose of radiation received during the test. The image slices are also thinner, which yields more detailed pictures. CT scans can help determine the size of a retinoblastoma tumor and how much it has spread within the eye and to tissues near the eye. Normally, either a CT or an MRI scan (see the next section) is needed to do this, but usually not both. Because CT scans give off radiation, some doctors prefer to use MRI.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays, so there is no radiation involved. The energy from the radio waves is absorbed by the body and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. A contrast material called gadolinium may be injected into a vein before the scan to better see details. MRI scans may take up to an hour. Your child may have to lie inside a narrow tube, which is confining and can be upsetting. Newer, more open MRI machines can help with this, but the test still requires staying still for long periods of time. The machines also make buzzing and clicking noises that may be disturbing. Some doctors may suggest medicine be given to young children to help keep them calm or even asleep during the test. MRI is often recommended to evaluate retinoblastomas because it provides very detailed images and does not use radiation. This test is especially good at looking at the brain and spinal cord. Most patients with retinoblastoma will have at least one MRI scan to assess their tumor. For children with bilateral retinoblastomas, many doctors continue to do MRI scans of the brain for several years after treatment to screen for tumors of the pineal gland.

Bone scan
A bone scan can help show if the retinoblastoma has spread to the skull and other bones. Most patients with retinoblastoma do not need to have a bone scan. It is normally used only when there is a strong reason to think retinoblastoma may have spread beyond the eye. For this test, a small amount of low-level radioactive material is injected into a vein (intravenously, or IV). The material settles in areas of damaged bone throughout the entire skeleton over the course of a couple of hours. Your child then lies on a table for

about 30 minutes while a special camera detects the radioactivity and creates a picture of the skeleton. This may require sedation. This test shows the entire skeleton at once. Areas of active bone changes appear as "hot spots" on the skeleton that is, they attract the radioactivity. These areas may suggest the presence of cancer, but other bone diseases can also cause the same pattern. To distinguish among these conditions, other imaging tests such as plain x-rays or MRI scans, or even a bone biopsy might be needed. For more detailed information on imaging tests, see our document called Imaging (Radiology) Tests.

Other tests
Some other types of tests are not commonly needed for retinoblastomas, but they may be helpful in some situations.

Biopsy
For most cancers, a biopsy (removing a tissue sample from the tumor and looking at it under a microscope) is needed to make a diagnosis. Trying to biopsy a tumor at the back of the eye can often damage the eye and may spread tumor cells, so this is almost never done to diagnose retinoblastoma. Instead, doctors make the diagnosis based on the eye exam and on imaging tests such as those listed above. This is why it is very important that the diagnosis of retinoblastoma is made by experts.

Lumbar puncture (spinal tap)

Retinoblastomas may grow along the optic nerve, which connects the eye to the brain. If the cancer has spread to the surface of the brain, cancer cells can often be found in samples of cerebrospinal fluid (the fluid that surrounds the brain and spinal cord). Most patients with retinoblastoma do not need to have a lumbar puncture. It is normally used only when there is a reason to think retinoblastoma may have spread into the brain. For this test, the doctor first numbs an area in the lower part of the back over the spine. The doctor may also recommend that the child be given something so they will sleep and not move during the procedure. This can help ensure the spinal tap is done cleanly. A small, hollow needle is then placed between the bones of the spine to withdraw a small amount of the fluid. The fluid is then looked at under a microscope to check for cancer cells.

Bone marrow aspiration and biopsy

These 2 tests may be done to see if the cancer has spread to the bone marrow, the soft, inner part of certain bones. These tests are usually not needed unless the retinoblastoma has spread to tissues next to the eye and doctors suspect that the cancer may have also spread through the bloodstream to the bone marrow.

The tests are typically done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, but in some cases they may be taken from the sternum (breastbone) or other bones. In bone marrow aspiration, the skin over the hip and the surface of the bone are numbed with a local anesthetic. This test can be painful, so the child will probably be given other medicines to reduce pain or even be asleep during the procedure. A thin, hollow needle is then inserted into the bone, and a syringe is used to suck out (aspirate) a small amount of liquid bone marrow. A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is twisted as it is pushed down into the bone. Once the biopsy is done, pressure will be applied to the site to help stop any bleeding. The samples are then looked at under a microscope to see if tumor cells are present.

How is retinoblastoma staged?

Staging is the process of finding out where and how much a cancer has spread. The outlook (prognosis) for people with cancer depends, to a large extent, on the cancer's stage. The stage of a cancer is one of the most important factors in choosing treatment. Retinoblastoma is staged based on the results of eye exams, imaging tests, and any biopsies that were done. These tests were described in the previous section, "How is retinoblastoma diagnosed?" A staging system is a standardized way for your child's cancer care team to describe how far a cancer has spread. Doctors use a staging system to predict the outlook for saving the child's vision, as well as for survival and the likelihood that certain treatments will be effective. Several detailed systems can be used to stage retinoblastoma. For practical purposes, when determining the best treatment options, doctors often divide retinoblastomas into 3 main groups: Intraocular: it is still within the eye Orbital: it has spread to the eye socket Metastatic: it has spread to distant parts of the body In the United States, most retinoblastomas are diagnosed before they have spread outside of the eye. This is why the staging systems that apply only to intraocular retinoblastoma are used most often in this country. There are 2 staging systems for intraocular retinoblastomas. It is important to know that regardless of the stage, almost all children with intraocular retinoblastoma can be cured if they are properly treated.

The Reese-Ellsworth staging system

Some doctors may still use the Reese-Ellsworth staging system to classify retinoblastomas that have not spread beyond the eye. This system can help determine the likelihood of preserving vision while still effectively treating the tumor. This system was developed in the 1960s, when most children were being treated with external beam radiation therapy (EBRT). The terms favorable, doubtful, unfavorable, etc. in this staging system refer to the likelihood that the cancer could be treated effectively while preserving the affected eye. These terms do not refer to the likelihood of the child's survival. Indeed, more than 90% of children with intraocular retinoblastomas are cured. The major challenge is saving their sight. To explain the groupings below, it will help to define a few terms. The optic disk is the end of the optic nerve where it is attached to the retina. Retinoblastomas are diagnosed by looking at the retina through an ophthalmoscope, so doctors cannot measure their size directly using a ruler. Instead they compare the size of the tumor with the size of the optic disk, which is usually about 1.5 millimeters (1/16 inch) across. For example, a tumor estimated to be 3 times the size of the disk (3 disk diameters or 3 DD) would be about 4.5 millimeters (3/16 inch) across. The equator is an imaginary line that divides the front and back halves of the eyeball. The Reese-Ellsworth staging system divides intraocular retinoblastoma into 5 groups. The higher the group number, from 1 to 5, the lower the chance of controlling the retinoblastoma or of saving the eye or any useful vision.

Group 1 (very favorable for saving [or preserving] the eye)

1A: one tumor, smaller than 4 disc diameters (DD), at or behind the equator 1B: multiple tumors smaller than 4 DD, all at or behind the equator

Group 2 (favorable for saving [or preserving] the eye)

2A: one tumor, 4 to 10 DD , at or behind the equator 2B: multiple tumors, 4 to 10 DD, all at or behind the equator

Group 3 (doubtful for saving [or preserving] the eye)

3A: any tumor in front of the equator 3B: one tumor, larger than 10 DD, behind the equator

Group 4 (unfavorable for saving [or preserving] the eye)

4A: multiple tumors, some larger than 10 DD 4B: any tumor extending anteriorly (toward the front of the eye) to the ora serrata (front edge of the retina)

Group 5 (very unfavorable for saving [or preserving] the eye)

5A: tumors involving more than half of the retina 5B: vitreous seeding (spread of tumors into the gelatinous material that fills the eye) This staging system was first designed to determine how useful radiation therapy might be in a given patient, but it can still provide some useful information about which current treatments might be most effective. For example: A group 1 retinoblastoma can very likely be controlled with chemotherapy, photocoagulation, cryotherapy, thermotherapy, brachytherapy, or external beam radiation therapy while still preserving vision in the eye. A group 4 or especially group 5 retinoblastoma is very unlikely to be controlled with chemotherapy or radiation therapy. Even if it were controlled, the vision in the eye would be very poor.

International Classification for Intraocular Retinoblastoma

The International Classification for Intraocular Retinoblastoma is a newer staging system, which takes into account what has been learned about the disease in recent decades. Many doctors now use this system. It divides retinoblastomas into 5 groups, labeled A through E, based on the chances that the eye can be saved using current treatment options.

Group A
Small tumors (3 mm across or less) that are confined to the retina and are not near important structures such as the optic disk (where the optic nerve enters the retina) or the foveola (the center of vision).

Group B
All other tumors (either larger than 3 mm or small but close to the optic disk or foveola) that are still confined to the retina.

Group C
Well-defined tumors with small amounts of spread under the retina (subretinal seeding) or into the gelatinous material that fills the eye (vitreous seeding).

Group D
Large or poorly defined tumors with widespread vitreous or subretinal seeding. The retina may have become detached from the back of the eye.

Group E
The tumor's large size, location, or other factors mean there is almost no chance the eye can be saved.

Other staging systems

Other staging systems that include both intraocular retinoblastomas and those that have spread beyond the eye may be used by some doctors. These may be especially useful in countries where these cancers are more likely to have spread by the time they are found. For example, the American Joint Commission on Cancer (AJCC) has developed a staging system that takes into account 3 key pieces of information: T: the size of the main (primary) tumor and how far it has grown within and outside of the eye N: whether or not the cancer has reached the lymph nodes (small, bean shaped collections of immune cells, to which cancers sometimes spread) M: whether or not the cancer has spread (metastasized) to distant sites, such as the bone marrow, brain, skull, and long bones This system can be used to describe the extent of retinoblastomas in detail, but it does not divide them into groups like the other systems do. Be sure to ask your child's doctor which system is being used, and what it means in your child's case.

How is retinoblastoma treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience. The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor. Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

General treatment information

Retinoblastoma is rare, so few doctors other than those in specialty eye hospitals and major children's cancer centers have much experience in treating it. Children with retinoblastoma and their families have special needs that can best be met by these children's cancer centers. These centers have teams of specialists who know about retinoblastoma and the unique needs of children with cancer. This gives the child the best chance for recovery and, if possible, keeping their sight.

Ask your child's doctor about finding a children's cancer center near you that has expertise in treating babies and children with this rare form of cancer. Ask about the services offered at your treatment center. Your child's doctor or nurse can tell you what is available to help with any problems you or your child might have. A team approach is recommended that includes the child's pediatrician as well as ophthalmologic oncologists (doctors who diagnose and treat eye cancers), pediatric oncologists (doctors who treat children with cancer), and radiation oncologists (doctors who use radiation to treat cancer). The team will also include other doctors, nurses, therapists, and technologists who have essential roles in diagnosis and treatment and can help retinoblastoma patients with recovery after treatment is finished. There is a lot for you to think about when choosing the best way to treat or manage your child's retinoblastoma. Often you may have more than one treatment to choose from. You may feel that you need to make a decision quickly. But give yourself time to absorb the information you have learned. Talk to the cancer care team. To get some ideas, look at the list of questions in the section, "What should you ask your child's doctor about retinoblastoma?" Then add your own. You may want to get a second opinion. Your child's doctor should not mind if you do this. Check with your insurance provider about their policy on second opinions.

General treatment principles

The goals of treatment for retinoblastoma are: To get rid of the cancer and save the child's life To preserve as much vision as possible To save the eye To avoid second cancers, which may also be caused by treatment, particularly in children with inherited retinoblastoma The most important factors that will determine treatment are: Whether the tumor is just in one eye or both How good the vision is Whether the tumor has extended beyond the eyeball Overall, more than 90% of children can be cured of retinoblastoma. The chances of longterm survival are much better if the tumor has not spread beyond the eyeball. Depending on the stage of the tumor and other factors, one or more of the following types of treatment may be used: Surgery Radiation therapy (brachytherapy or external beam radiation therapy) Photocoagulation (using lasers to kill small tumors) Cryotherapy (using small, very cold probes to freeze and kill small tumors)

 Thermotherapy (using heat to kill small tumors) Chemotherapy The next few sections describe these treatments in more detail and discuss which treatments may be used in different situations.

Surgery (enucleation)
Surgery is not needed for all retinoblastomas, especially for smaller tumors. But if a tumor gets quite large before it is diagnosed, vision has often already been destroyed, with no hope of getting it back. The usual treatment in this case is an operation to remove the whole eye, plus part of the optic nerve attached to it. This operation, known as enucleation, is done while the child is under general anesthesia (in a deep sleep). During the same procedure, an orbital implant is usually put in to take the place of the eyeball. The implant is made out of silicone or hydroxyapatite (a substance similar to bone). It is attached to the muscles that moved the eye, so it should move the same way as the eye would have. The operation itself often takes less than an hour, and your child may be able to leave the hospital the same day. Within a few weeks, your child can visit an ocularist (a specialist in eye prostheses) to be fitted with an artificial eye that has been made to match the size and color of the remaining eye. The artificial eye is a thin shell that fits over the orbital implant and under the eyelids. Once the eye is in place, it will be very hard to tell it apart from the real eye. When retinoblastoma occurs in both eyes, enucleation of both eyes would result in complete blindness. This is the safest treatment if neither eye has useful vision because of damage caused by the cancer. But doctors may advise more conservative types of treatment if there is any chance of saving useful vision in one or both eyes. Possible side effects: The most obvious side effect of enucleation is the loss of vision in that eye, although in most cases the vision has already been lost because of the cancer. Removing the eye also can affect the future growth of bone and other tissues around the eye socket, which can make the area look somewhat sunken. Using an orbital implant can sometimes lessen this effect. (Radiation therapy, the other major treatment option in such cases, may cause the same side effect.)

Radiation therapy
This treatment uses high energy x-rays or particles to kill cancer cells or slow their rate of growth. Radiation therapy is an effective treatment for some patients with retinoblastoma. Compared with surgery, it has the advantage of possibly preserving vision in the eye. But radiation therapy also has some disadvantages. (See Possible side effects below.) Two types of radiation therapy can be used to treat children with retinoblastoma.

External beam radiation therapy

External beam radiation therapy focuses radiation beams from a source outside the body on the cancer. It is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless. Before treatments start, the radiation team takes careful measurements with imaging tests such as MRI scans to determine the correct angles for aiming the radiation beams and the proper dose of radiation. Each actual treatment lasts only a few minutes, but the setup time getting your child into place for treatment usually takes longer. The child's head is positioned in a customfitted mold that is similar to a cast used to treat broken bones. Young children may be given medicine to make them fall asleep so they will not move during the treatment. Usually, radiation treatments are given 5 days a week for several weeks. Newer forms of radiation therapy: Many centers now use newer types of external radiation therapy, such as intensity modulated radiation therapy (IMRT) or proton beam radiation therapy. These approaches are able to target the tumor more precisely, which lowers the doses that surrounding normal tissues get. This may help reduce side effects. These newer techniques are described in the section, "What's new in retinoblastoma research and treatment?" Possible side effects: Some of the side effects of external radiation therapy will go away after a short while and are not serious. The skin in the area treated may look sunburned and then tan, but will usually return to normal within 6 to 12 months. Some children also lose small patches of hair for a while. More importantly, external radiation therapy can damage surrounding normal tissue. This may eventually lead to cataracts (clouding of the lens of the eye) and damage to the retina or optic nerve, which could reduce vision. It can also lead to problems with the growth of bone and other tissues near the eye. External radiation therapy can also increase the risk of developing a second cancer in the area. This is especially important in survivors of the hereditary form of retinoblastoma, who are already at increased risk for developing other types of cancer. Newer forms of radiation therapy, such as IMRT and proton beam therapy, target the tumor more precisely and spare more normal tissue. This may make some side effects less likely than in the past.

Brachytherapy
The use of brachytherapy, also known as internal radiation therapy or plaque radiotherapy, is limited to small tumors. During brachytherapy, a small amount of radioactive material is temporarily placed on the outside of the part of the eyeball where the tumor is. The radioactive material is put in a small carrier (known as a plaque), which is shaped like a very small bottle cap. The plaque is made of gold or lead to shield nearby

tissues from the radiation. The radiation travels a very short distance, so most of it will be focused only on the tumor. The plaque is sewn in place on the eyeball with tiny stitches during a short operation. It is then removed during a second operation several days later. Both procedures are done while the child is under general anesthesia (in a deep sleep). The child typically stays in the hospital during the time between the operations. Possible side effects: Brachytherapy is less likely to cause side effects than external radiation. The main concern is damage to the retina or optic nerve, which can affect vision. Recent advances in treatment may make this problem less likely. Brachytherapy has not been linked to an increased risk of developing a second cancer.

Laser therapy (photocoagulation)

Photocoagulation is a type of laser therapy that uses laser beams aimed through the pupil or the side of the eyeball. The laser is focused on the tumors and the blood vessels that supply them, destroying them with the heat caused by the beam. Photocoagulation is effective only for smaller tumors. Your child will be under general anesthesia (in a deep sleep) during the treatment. The treatment is usually given 2 or 3 times, with about a month between treatments. Possible side effects: In some cases, laser therapy can damage the retina, which can lead to blind spots or temporarily cause the retina to become detached from the back of the eyeball.

Cryotherapy
Cryotherapy uses a small probe that is cooled to very low temperatures, killing the retinoblastoma cells by freezing them. It is only effective for relatively small tumors and is not routinely used for children with several tumors. The child will be under general anesthesia (in a deep sleep) during the treatment. After the child is asleep, the probe is placed on the outer surface of the eyeball next to the tumor, which is then frozen and thawed several times. Cryotherapy is usually given 2 or 3 times, with about a month between treatments. Possible side effects: Cryotherapy may cause the eye and eyelid to swell for a few days. As with laser therapy, cryotherapy can damage the retina, which can lead to blind spots or temporarily cause the retina to become detached from the back of the eyeball.

Thermotherapy
Thermotherapy uses ultrasound, microwaves, or infrared rays to apply heat to the eye. Infrared rays are typically used to treat retinoblastoma. The temperatures are not quite as high as those used in laser therapy, so some of the blood vessels on the retina may be spared. Thermotherapy may be used alone for very small tumors, or along with

chemotherapy for larger tumors, where the combination may have a more potent effect. (This is called thermochemotherapy.) The treatment is similar to standard laser therapy. It is given while the child is asleep, usually for less than 10 minutes at a time. Typically, 3 treatments are given, about a month apart. When used as part of thermochemotherapy, thermotherapy is given 1 or 2 hours after chemotherapy. Possible side effects: Thermotherapy can sometimes cause part of the iris (the colored part of the eye) to shrink. Other possible effects include clouding of part of the eye lens or damage to the retina.

Chemotherapy
Chemotherapy uses anti-cancer drugs to treat the retinoblastoma. The drugs are usually injected into a vein (IV) or given by mouth. These drugs enter the bloodstream and reach all areas of the body, which makes this a type of systemic therapy. There are a few situations in which chemotherapy may be used. Chemotherapy may be used as the first treatment to shrink some tumors that have not spread outside the eye. This is called chemoreduction. These tumors can then be treated more effectively with focal therapies such as photocoagulation, cryotherapy, thermotherapy, or brachytherapy to completely kill the tumor. In some cases of advanced intraocular disease, higher doses of chemotherapy are needed inside the eye. Along with systemic chemotherapy, one of the drugs (carboplatin) may be injected in the tissues around the eye, where it slowly diffuses into the eyeball. This is called periocular or subtenon chemotherapy. These injections are done while the child is under anesthesia and may cause significant redness and swelling around the eye. Doctors are also testing a newer way of giving chemotherapy by injecting it directly into an artery leading into the eye. This is described in the section, "What's new in retinoblastoma research and treatment?" Systemic chemotherapy reaches all areas of the body, so it may also be given to children whose tumors do not seem to have spread beyond the eye, but seem likely to spread because of the size and/or location of the cancer. It is also used in some cases when the eye has already been removed, but the tumor was found to extend into some critical areas in the eye that make it more likely the cancer may have spread. This type of treatment is called adjuvant chemotherapy. Finally, chemotherapy is used to treat children whose retinoblastoma has spread beyond the eye; a much more critical situation. These tumors may shrink for a time with standard doses of chemotherapy, but unfortunately, they will usually start growing again. This is why doctors often prefer to use a more intense chemotherapy regimen, usually along with a stem cell transplant. (See the next section, "High-dose chemotherapy and stem cell transplant.")

Doctors give chemotherapy in cycles, with each period of treatment followed by a rest period to allow the body time to recover. Each chemotherapy cycle typically lasts for a few weeks. Some of the drugs that can be used to treat children with retinoblastoma include: Carboplatin Cisplatin Vincristine Etoposide Teniposide Cyclophosphamide Doxorubicin In most cases, 2 or 3 drugs are given at the same time. A standard combination used for chemoreduction of intraocular retinoblastoma is carboplatin and vincristine, with or without etoposide. Other drugs may be used if these are not effective. A drug called cyclosporine is sometimes given with chemotherapy. Cyclosporine is not a chemotherapy drug (it does not directly kill cancer cells), but it may make the tumor cells more sensitive to chemotherapy drugs. Possible side effects: Chemotherapy drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects. Children seem to do better than adults when it comes to chemotherapy. They tend to have less severe side effects and to recover from side effects more quickly. One benefit of this is that doctors can give them the high doses of chemotherapy that are necessary to kill the tumor. The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are taken. General side effects of chemotherapy drugs can include: Hair loss Mouth sores Loss of appetite Nausea and vomiting Increased chance of infections (because of low white blood cell counts) Easy bruising or bleeding (because of low blood platelet counts) Fatigue (because of low red blood cell counts) Most of these side effects are short-term and tend to go away after treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help

prevent or reduce nausea and vomiting. Be sure to discuss any questions about side effects with your child's cancer care team. Along with those listed above, certain medicines cause specific side effects. For example: Cyclophosphamide can damage the bladder. This can be avoided or minimized by giving it along with plenty of fluids and with a drug called mesna, which helps protect the bladder. Cisplatin and carboplatin can affect the kidneys. Giving the child plenty of fluids during treatment can help reduce this risk. These drugs can also affect hearing in some cases. Your child's doctor may check this with hearing tests (audiograms) during or after treatment. When carboplatin is injected directly into the tissues near the eye (periocular chemotherapy), it can cause redness and swelling in the area. Doxorubicin can cause heart damage. The risk of this happening goes up as the total amount of the drug that is given goes up. Doctors try to reduce this risk as much as possible by not giving more than the recommended doses of doxorubicin and by checking the heart with a test called an echocardiogram during treatment. Vincristine can damage nerves. Some people may feel tingling and numbness, particularly in their hands and feet. Some drugs used to treat retinoblastoma, such as etoposide, can increase the risk of later developing a cancer of white blood cells known as acute myeloid leukemia. Fortunately, this is not common. For more information about chemotherapy, see our document called Understanding Chemotherapy: A Guide for Patients and Families.

High-dose chemotherapy and stem cell transplant

Doctors are studying the use of this type of treatment in children with retinoblastoma that has spread outside the eye and who are unlikely to be cured with other treatments. A peripheral blood stem cell transplant (PBSCT) allows doctors to give very high doses of chemotherapy (higher than could safely be given otherwise). In the past, this type of treatment was commonly referred to as a bone marrow transplant. The bone marrow is the soft, inner part of some bones where new red blood cells, white blood cells, and platelets are formed. Red blood cells carry oxygen to all parts of the body. White blood cells are part of the immune system, which fights off infections. Platelets are needed to help the blood clot to stop bleeding. The usual doses of chemotherapy drugs can affect quickly dividing cells like those in the bone marrow. Even though higher doses of these drugs might be more effective in treating tumors, they can't be given because they would cause severe damage to bone marrow cells, leading to life-threatening shortages of blood cells. To try to get around this problem, the doctor may treat the child with high-dose chemotherapy and then give a PBSCT to "rescue" the bone marrow.

How is it done?
The first step in a PBSCT is to collect, or harvest, the child's own blood-producing stem cells to use later. (These are the cells that make the different types of blood cells.) This type of transplant, where the stem cells are taken from the patient (as opposed to coming from someone else), is known as an autologous transplant. In the past, the stem cells were often taken from the child's bone marrow, which required a minor operation. But doctors have found that these cells can be taken from the bloodstream during a procedure known as apheresis. This is similar to donating blood, but instead of going into a collecting bag, the blood goes into a special machine that filters out the stem cells and returns the other parts of the blood to the person's body. The stem cells are then frozen until the transplant. Once the stem cells have been stored, the child gets high-dose chemotherapy. When the chemotherapy is complete, the stem cells are thawed and returned to the body in a process similar to a normal blood transfusion. The stem cells travel through the bloodstream and settle in the bones. Over the next 3 or 4 weeks, the stem cells start to make new, healthy blood cells in the child's bone marrow. Until this happens, the child is at high risk of infection because of a low white blood cell count, as well as bleeding because of a low platelet count. To avoid infection, protective measures are taken, such as using special air filters in the hospital room and having visitors wear protective clothing. Blood and platelet transfusions and treatment with IV antibiotics may also be used to prevent or treat infections or bleeding problems.

Practical points
A PBSCT is a complex treatment. If the doctors think your child may benefit from a transplant, the best place to have this done is at a nationally recognized cancer center where the staff is experienced in doing the procedure and managing the recovery period. A stem cell transplant is also very expensive, often costing well over $100,000 and requiring a lengthy hospital stay. Because the procedure is so expensive, you should have an idea of how the costs might be covered beforehand. Be sure to get a written approval from your insurer if the procedure is recommended for your child.

Possible side effects

Possible early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy (see the "Chemotherapy" section), and are caused by damage to the bone marrow and other quickly dividing tissues of the body. Side effects can include low blood cell counts (with increased risk of infection and bleeding), nausea, vomiting, loss of appetite, mouth sores, and hair loss. One of the most common and serious short-term effects is an increased risk of infection. Antibiotics often are given to try to keep this from happening. Other side effects, like low

red blood cell and platelet counts, may require blood product transfusions or other treatments. Some complications and side effects can last for a long time or may not occur until years after the transplant. Be sure to talk to your child's doctor before the transplant to learn about long-term effects your child may have. For more information on stem cell transplants, see our document called Bone Marrow and Peripheral Blood Stem Cell Transplant.

Clinical trials
You may have had to make a lot of decisions since you've been told your child has cancer. One of the most important decisions you will make is deciding which treatment is best. You may have heard about clinical trials being done for this type of cancer. Or maybe someone on your health care team has mentioned a clinical trial to you. Clinical trials are carefully controlled research studies that are done with patients who volunteer for them. These studies are done to get a closer look at promising new treatments or procedures. If you would like your child to take part in a clinical trial, you should start by asking your doctor if your clinic or hospital conducts clinical trials. You can also call our clinical trials matching service for a list of clinical trials that meet your medical needs. You can reach this service at 1-800-303-5691 or on our Web site at www.cancer.org/clinicaltrials. You can also get a list of current clinical trials by calling the National Cancer Institute Cancer Information Service toll free at 1-800-4-CANCER (1-800-422-6237) or by visiting the NCI clinical trials Web site at www.cancer.gov/clinicaltrials. Your child will have to meet certain requirements to take part in any clinical trial. If your child does qualify for a clinical trial, you will have to decide whether or not to enter (enroll) the child into it. Older children, who can understand more, usually must also agree to take part in the clinical trial before the parents' consent is accepted. Clinical trials are one way to get state-of-the-art cancer care for your child. They are the only way for doctors to learn better methods to treat cancer. Still, they are not right for every child. You can get a lot more information on clinical trials in our document called Clinical Trials: What You Need to Know. You can read it on our Web site or call our toll-free number (1-800-227-2345) and have it sent to you.

Complementary and alternative therapies

When your child has cancer you are likely to hear about ways to treat his or her cancer or relieve symptoms that your doctor hasn't mentioned. Everyone from friends and family to Internet groups and Web sites offer ideas for what might help. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

What exactly are complementary and alternative therapies?

Not everyone uses these terms the same way, and they are used to refer to many different methods, so it can be confusing. We use complementary to refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor's medical treatment. Complementary methods: Most complementary treatment methods are not offered as cures for cancer. Mainly, they are used to help the person with cancer feel better. Some methods that are used along with regular treatment are: art therapy or play therapy to reduce stress; acupuncture to help relieve pain; or peppermint tea to relieve nausea. Some complementary methods are known to help, while others have not been tested. Some have been proven not be helpful, and a few have even been found harmful. Alternative treatments: Alternative treatments may be offered as cancer cures. These treatments have not been proven safe and effective in clinical trials. Some of these methods may pose danger, or have life-threatening side effects. But the biggest danger in most cases is that your child may lose the chance to be helped by standard medical treatment. Delays or interruptions in medical treatments may give the cancer more time to grow and make it less likely that treatment will help.

Finding out more

It is easy to see why parents who have children with cancer think about alternative methods. You want to do all you can to help fight the cancer, and the idea of a treatment with few or no side effects sounds great. Sometimes medical treatments like chemotherapy can be hard to take, or they may no longer be working. But the truth is that most of these alternative methods have not been tested and proven to work in treating cancer. As you consider your child's options, here are 3 important steps you can take: Look for "red flags" that suggest fraud. Does the method promise to cure all or most cancers? Are you told not to use regular medical treatments? Is the treatment a "secret" that requires you to take your child to certain providers or to another country? Talk to your child's doctor or nurse about any method you are thinking about. Contact us at 1-800-227-2345 to learn more about complementary and alternative methods in general and to find out about the specific methods you are looking at.

The choice is yours

You always have a say in how your child is treated. If you want to use a non-standard treatment, learn all you can about the method and talk to your child's doctor about it. With good information and the support of your child's health care team, you may be able

to safely use the methods that can help your child while avoiding those that could be harmful.

Treatment of retinoblastoma based on extent of the disease

A number of factors may affect the choice of treatments your doctor recommends. Some of these include: Whether tumors are in one or both eyes The size and location of the tumor in the eye(s) The chance for saving vision in the eye(s) Whether the tumor is still confined within the eye(s) or may have spread elsewhere Ask your doctor which treatments he or she recommends and why. A very important factor is whether the cancer has affected one or both eyes. Treatment is very different depending on whether retinoblastoma affects one eye or both. For children with only one eye affected, treatment depends on whether vision in the eye can be saved. If the chance to save vision is poor, the treatment is often surgery (to remove the eye). Surgery was used even more frequently in the past, as it offered the best option to ensure all of the cancer was removed. In recent years, doctors have become more comfortable with using other treatments if there is a good chance of saving vision in the eye. Most children with retinoblastoma in both eyes will be treated with chemotherapy to shrink the tumors (called chemoreduction), followed by some form of local treatment and possibly radiation therapy. Surgery (removal of the eye) is reserved for the most advanced tumors.

What if the eye can see and probably can be saved?

For some smaller tumors, local treatments such as laser therapy or cryotherapy may be the only treatment needed. More often, tumors are larger or in more difficult-to-treat areas. Treatment usually includes a combination of chemotherapy and focal treatments. Chemotherapy is given for about 6 months to shrink the tumor as much as possible. Depending on how much the tumor shrinks and where it is located, different focal treatments are applied, usually starting after the first or second cycle of chemotherapy. These treatments may include brachytherapy (plaque radiotherapy), cryotherapy, laser therapy, or thermotherapy. Regardless of which of these treatments is used, it is very important that it is given by experts at state-of-the art treatment centers. External radiation therapy may also be required, but it is usually delayed until the end of chemotherapy. If the combination of these treatments doesn't control the disease, surgery to remove the eye may be needed.

What if the eye cannot see or cannot be saved?

If there is no vision in the eye, or the tumor is so advanced that there is no hope of cure by other means, or if there is painful glaucoma, then surgery is done to remove the eye and place an orbital implant in the socket. If the disease affects only one eye, no other treatments may be required. But sometimes, after looking at the removed eye under the microscope, the doctors conclude that some retinoblastoma cells may have escaped the eye and thus may recur later in other parts of the body. These patients may be given chemotherapy, possibly along with radiation therapy. In some instances where there are large tumors in both eyes, chemotherapy may be used first to try to shrink the tumors and avoid the need for surgery in both eyes. If chemotherapy shrinks the tumors enough, local therapies such as brachytherapy (plaque radiotherapy), cryotherapy, laser therapy, or thermotherapy may allow at least one eye to be saved. Some children with retinoblastoma in only one eye may actually have the hereditary form of retinoblastoma, which means they will probably develop disease in the other eye as well. Therefore, it is very important that children with retinoblastoma in one eye continue to have the other eye regularly examined after treatment.

What if the cancer has spread outside the eye?

In this uncommon situation, treatment is usually a combination of chemotherapy, radiation, and in some cases surgery. If the cancer has spread only to the orbit (the area around the eye), treatment with chemotherapy, surgical removal (enucleation) of the eye, and radiation therapy to the orbit is often successful. If the cancer has spread outside the orbit to distant areas such as the liver or the bones and bone marrow, the chances of a cure using standard chemotherapy and other treatments are low. In these cases, using higher doses of chemotherapy followed by a stem cell transplant can often be successful. Cancers that have spread to the brain (including trilateral retinoblastomas, which are retinoblastomas that usually start in the pineal gland) are very hard to treat, and the chances of a cure using current treatments are very low. High-dose chemotherapy and stem cell transplant has shown some promise for these cancers in a recent small study. Clinical trials using other newer treatments may be an option in this situation as well.

What if the cancer comes back in the eye after initial treatment?
Treatment of cancer that recurs in the eye depends on the size and location of the tumor and on what treatments were used the first time. If the tumor is small, the child's sight can often be saved while the cancer is destroyed with local treatments such as cryotherapy,

laser therapy, radiation therapy (if not already used), or other treatments. Chemotherapy may be given first. If the child's sight cannot be saved, the eye may need to be removed. Either way, the possibility of a cure is quite good as long as the cancer is confined to the eye.

What if the cancer comes back outside the eye after initial treatment?
Cancers that recur outside the eye are harder to treat. Options may include chemotherapy and radiation, or high-dose chemotherapy with a stem cell transplant in some cases. In this situation, the treatment and the chances of cure are similar to what is described above (when the cancer has spread outside the eye before initial treatment). Many patients will receive several different types of therapy throughout their treatment. Treatments over months or years may be necessary, especially in eyes treated with cryotherapy and/or photocoagulation after chemotherapy. In summary, if the cancer is in only one eye and the potential for saving sight is good, local treatments (often along with chemotherapy) may be used. Otherwise the eye will likely need to be removed. If the cancer is in both eyes, then the doctors will try to save as much vision as possible. The treatment usually starts with chemotherapy, followed by focal treatments such as cryotherapy, laser therapy, thermotherapy, and radiation. In any case, children who have had retinoblastoma need to be followed closely for some time after treatment.

More treatment information

For more details on treatment options including some that may not be addressed in this document the National Cancer Institute (NCI) and CureSearch are good sources of information. The NCI provides treatment guidelines via its telephone information center (1-800-4CANCER) and its Web site (www.cancer.gov). Detailed guidelines intended for use by cancer care professionals are also available on www.cancer.gov. CureSearch is a combined effort of the National Childhood Cancer Foundation and the Children's Oncology Group (COG). CureSearch can be contacted via telephone at 1-800458-6223 or on the Web at www.curesearch.org.

What should you ask your child's doctor about retinoblastoma?

When talking about cancer and cancer treatment you need to have frank, open discussions with your child's doctor and feel free to ask any question on your mind, no matter how small it might seem. Here are some questions you might want to ask. What kind of eye cancer does my child have? Is it retinoblastoma?

 Has the tumor spread beyond the eye? What is the stage of the cancer, and what does that mean? Are there other tests that need to be done before we can decide on treatment? How much experience do you have treating this type of cancer? What other doctors will we need to see? What treatment options do we have? Can my child's sight be saved? If so, how much? What do you advise and why? Are there any clinical trials we should consider? How long will treatment last? What will it involve? Where will it be done? What should we do to be ready for treatment? What are the risks or side effects to the treatments you suggest? What type of follow-up will my child need after treatment? Based on what you've learned about the cancer, what is the chance my child will be cured? What would we do if the treatment doesn't work or if the cancer recurs? Is there any risk of this type of tumor occurring in our other children or relatives? Should they consider genetic testing? If the results are positive, what should be done? Along with these sample questions, be sure to write down some of your own. For instance, you might want more information about recovery times so you can plan your schedules. You may also want to ask about getting a second opinion.

What happens after treatment for retinoblastoma?

Following treatment for retinoblastoma, the main concerns for most families are the immediate and long-term effects of the tumor and its treatment, and concerns about possible recurrence of the tumor. It is certainly understandable to want to put the tumor and its treatment behind you and to get back to a life that doesn't revolve around cancer. But it's important to realize that follow-up care is a central part of this process that offers your child the best chance for recovery and long-term survival.

Follow-up exams
Once treatment is finished, the health care team will discuss a follow-up schedule with you, including which tests should be done and how often. It is very important to go to all follow-up appointments. Follow-up is needed to check for cancer recurrence, as well as possible side effects of certain treatments. Doctor visits and tests are done more frequently at first. If nothing abnormal is found, the time between tests can then be extended. If a child with retinoblastoma in only one eye has been treated by enucleation (removal of the eye), regular exams are needed to look for tumor recurrence, metastases, or any growth irregularities related to surgery. It is also important to have the remaining eye checked regularly so that if a second retinoblastoma develops later on it can be found and treated as early as possible. For children treated with radiation therapy, laser therapy, cryotherapy, or treatment other than removal of the eye, close follow-up exams by an ophthalmologist are very important. In children with hereditary retinoblastoma, it is very common for new tumors to form until they are 3 or 4 years old. This is not a failure of the treatment, but the natural process in bilateral retinoblastoma. Therefore, it is very important that even after completing all treatments, children are examined regularly by specialists. General anesthesia (where the child is asleep) may be needed to keep a young child still enough for the doctor to do a thorough exam. This is done to be certain the cancer has been completely destroyed, to find recurrences as early as possible, and to find problems with vision caused by treatments. It is important for you to report any new symptoms your child is having, such as pain or vision problems, to your doctor right away, since they could be an early warning of cancer coming back or long-term side effects of treatment.

Genetic counseling and testing

If you have a child diagnosed with retinoblastoma, your family may be referred for genetic counseling. This is because some cases of retinoblastoma are caused by a genetic mutation that can be inherited. If a child is diagnosed with retinoblastoma in both eyes, it can be assumed that they have the hereditary form of the disease, which means they carry the mutant RB1 gene in all their cells. It's also possible that children with retinoblastoma in only one eye carry the mutant RB1 gene in all their cells. This can be confirmed with a blood test. Children with this mutant gene are at increased risk for developing cancer later in life. (See the section, "Second cancers.") If the child carries the mutated RB1 gene, then other children in the family may have inherited the same abnormal gene as well, and are at risk of being affected. Meeting with a genetic counselor can give you a better idea of what this risk might be and if other children in the family should be tested for the mutation. The genetic counselor will:

 Review the child's medical records and ask questions about other relatives to estimate the likelihood of an inherited gene affecting some family members. Provide information and answer questions about genetic testing, and schedule tests for other children in your family (if needed) so that their risk of developing retinoblastoma can be determined. If tests show your children are at risk of developing retinoblastoma, their doctors will follow them very closely to find retinoblastoma at the earliest possible stage, if it occurs. It is very helpful to be able to tell which children have inherited the mutation that leads to retinoblastoma, since those children will need to be monitored closely. In some cases it is not possible to tell with certainty if a child inherited the RB1 gene mutation. In those cases the safest plan is to monitor children in the family closely for retinoblastoma with frequent eye exams.

Keeping good medical records

As much as you may want to put the experience behind you once treatment is completed, it is also very important to keep good records of your child's medical care during this time. This can be very helpful for your child later on as an adult and his or her doctors. Be sure your child's doctors have the following information: A copy of the pathology report(s) from any biopsies or surgeries If there was surgery, a copy of the operative report(s) If there were hospitalizations, copies of the discharge summaries that doctors prepare when patients are sent home If there was chemotherapy treatment for the cancer, a list of the drugs, drug doses, and when they were given If there was radiation therapy, a summary of the type and dose of radiation and when and where it was given

Long-term effects of cancer treatment

With major advances in treatment in recent decades, many children treated for retinoblastoma are now surviving into adulthood. Doctors have learned that the treatment may affect children's health later in life, so watching for health effects as they get older has become more of a concern in recent years. Just as the treatment of childhood cancer requires a very specialized approach, so does the care and follow-up after treatment. The earlier any problems can be recognized, the more likely it is they can be treated effectively. The risk of late effects depends on a number of factors, such as the specific treatments the child received, the doses of treatment, and the age of the child when being treated. These late effects may include:

 Reduced kidney function Heart or lung problems after receiving certain chemotherapy drugs or radiation therapy to these parts of the body Slowed or decreased growth and development Changes in sexual development and ability to have children Development of other cancers (See the next section, "Second cancers.") To help increase awareness of late effects and improve follow-up care of childhood cancer survivors throughout their lives, the Children's Oncology Group (COG) has developed long-term follow-up guidelines for survivors of childhood cancers. These guidelines, written for doctors and other health care professionals, describe in detail the suggested long-term follow-up care based on the treatments the child has received. It is very important to discuss possible long-term complications with your child's health care team, and to make sure there is a plan in place to watch for these problems and treat them, if needed. To learn more, ask your child's doctors about the COG survivor guidelines, and see our document called Childhood Cancer: Late Effects of Cancer Treatment.

Second cancers
Survivors of the hereditary form of retinoblastoma have a much higher risk for developing other types of cancer throughout their lives. This is because each cell in the body has an abnormal RB1 tumor suppressor gene, which would normally help stop some of these cancers from forming. Most of these cancers are very treatable if detected early, which is why it is very important that these children are followed closely throughout life. The entire body must be carefully examined to avoid missing these second cancers. The most common secondary cancers among retinoblastoma survivors include: Osteosarcoma (a type of bone cancer) Soft tissue sarcomas (cancers that develop in muscle, tendons and ligaments, and fatty tissue) Melanoma (a type of skin cancer) Brain tumors Lung cancer Lymphoma Breast cancer The risk for these cancers is increased if any of these areas received radiation during radiation therapy for retinoblastoma. Younger children treated with radiation therapy are more likely than older children to develop side effects such as second cancers or problems with bone growth in the irradiated area. Chemotherapy with certain drugs can also increase the risk of some cancers.

Because of the increased risk these children face, it's important that they're taught about other factors that might increase their risk of cancer as they get older. For example, sun exposure will increase the melanoma risk even further, and smoking will increase lung cancer risk. Children with hereditary retinoblastoma also have a small risk of developing a tumor in the pineal gland within a few years. (This is known as trilateral retinoblastoma.) The pineal gland is a bean-sized structure lying under the middle of the brain. It can have cells similar to retina cells, which is why tumors can start there. This is why doctors often recommend that MRI scans be done regularly for 3 or 4 years to try to detect such tumors as early as possible.

Psychosocial issues for retinoblastoma survivors and their families

Most cases of retinoblastoma develop during a very sensitive time in a child's life. The effect will often be greatest during the first year of treatment. The treatment center should evaluate the patient's family situation as soon as possible. Some common family concerns include financial stresses, transportation to and from the cancer center, and the need of family members to take time off from work. If the patient or family members have concerns, they can be addressed before they become a crisis. Centers that treat many patients with retinoblastoma may have programs to introduce new patients and their families to others who have finished their treatment. Seeing another patient with retinoblastoma doing well is often helpful for the patient and family. If needed, centers can also refer patients to special programs and facilities for the visually impaired. Most patients treated for retinoblastoma in only one eye will have normal vision in the unaffected eye, but they may have a cosmetic deformity in the treated eye. The cosmetic problems can often be lessened by treatment in a center with expertise in reconstructive surgery. Early intervention and counseling can also help address any psychological effects of changes in appearance.

What's new in retinoblastoma research and treatment?

Research on retinoblastoma is being done at many medical centers, university hospitals, and other institutions across the world.

Genetics, genetic counseling, and gene therapy

The defective gene responsible for retinoblastoma (the RB1 gene) was identified in 1986. This discovery, together with technical advances in analyzing DNA changes, has made genetic testing a possibility.

A great deal of research has gone into figuring out how certain DNA changes in retinal cells cause them to become cancerous. Scientists understand these changes better for retinoblastoma than for most other cancer types. Although probably still years away, researchers hope that this understanding will one day lead to gene therapies, very specific treatments that can repair or counteract these DNA changes.

Treatment
Research is continuing the progress made in treating retinoblastoma over the past few decades.

Radiation therapy
External radiation therapy can effectively treat retinoblastoma, but it can cause side effects because the radiation often reaches nearby tissues as well. Newer forms of radiation therapy are better able to target the tumor yet spare nearby tissues. For example, intensity modulated radiation therapy (IMRT) lets doctors shape the radiation beams and aim them at the tumor from several angles, as well as to adjust the intensity (strength) of the beams to limit the dose reaching the nearby normal tissues. Many major hospitals and cancer centers now use IMRT. Another technique now being studied is proton beam therapy. Protons are positive parts of atoms. Unlike the x-rays used in standard radiation, which release energy both before and after they hit their target, protons cause little damage to tissues they pass through and then release their energy after traveling a certain distance. This means that proton beam radiation may be able to deliver more radiation to the tumor and cause less damage to nearby normal tissues. Early results with proton beam therapy are promising, but there is very little long-term data on its use for retinoblastoma. The machines needed to make protons are expensive, and there are only a handful of them in use in the United States at this time.

Other local treatments

Doctors continue to improve the instruments used for cryotherapy, laser therapy, and other local treatments. The goal is to more precisely kill tumor cells while sparing other parts of the eye.

Chemotherapy
Chemotherapy has played a more prominent role in treating many retinoblastomas in recent years. Systemic chemotherapy: Chemotherapy is now commonly used to shrink tumors before local treatments such as cryotherapy or laser therapy. Doctors are now studying whether giving chemotherapy after local treatments (known as adjuvant chemotherapy) might help prevent the recurrence of retinoblastoma, especially outside the eye. Doctors are also

studying the use of different chemotherapy drugs such as topotecan, as well as new ways of combining current drugs, to try to improve the effectiveness of chemotherapy. Localized chemotherapy: Chemotherapy can help shrink most retinoblastomas, but when it is given into the bloodstream it can cause side effects in different parts of the body. This limits the doses that can be given. Newer techniques may help keep the chemotherapy concentrated in the areas around the tumors. This may help doctors get higher doses of chemotherapy to the tumors while reducing some of these side effects. For example, doctors are studying injecting the chemotherapy around the diseased eye (known as subconjunctival, subtenon, or periocular chemotherapy). This might allow higher doses of chemotherapy to reach the tumor while limiting side effects elsewhere. There has been some success, but many doctors still consider this to be an experimental approach. New methods for periocular delivery are being studied, including placing small reservoirs loaded with chemotherapy outside the eye, which would release the drug into the eye for prolonged periods. If it proves to be useful, it will most likely be combined with other treatments. Another new approach is to inject chemotherapy directly into the ophthalmic artery, the main artery feeding the eye. In this technique, a very thin catheter (a long, hollow, flexible tube) is inserted into a large artery on the inner thigh and slowly threaded all the way up into the ophthalmic artery. (This is done with the child under general anesthesia.) The chemotherapy is then infused into the artery. Early results with this technique have been promising, with good tumor control and few side effects in most cases, although further study is needed. High-dose chemotherapy and stem cell transplant: Retinoblastomas that have spread widely are much harder to treat than those still confined to the eye. The doses of chemotherapy that can be given are limited by the side effects they cause, especially in the bone marrow (where new blood cells are made). Researchers are now testing the value of giving very high-dose chemotherapy, followed by a stem cell transplant to replace the body's bone marrow cells, which were killed by the chemotherapy. Several clinical trials are studying this approach.

Additional resources
More information from your American Cancer Society
The following related information may also be helpful to you. These materials may be ordered from our toll-free number, 1-800-227-2345. After Diagnosis: A Guide for Patients and Families (also available in Spanish) Bone Marrow and Peripheral Blood Stem Cell Transplant Childhood Cancer: Late Effects of Cancer Treatment Children Diagnosed With Cancer: Dealing With Diagnosis (also available in Spanish)

Children Diagnosed With Cancer: Financial and Insurance Issues Children Diagnosed With Cancer: Returning to School Children Diagnosed With Cancer: Understanding the Health Care System (also available in Spanish) Clinical Trials: What You Need to Know (also available in Spanish) Family and Medical Leave Act (FMLA) Nutrition for Children With Cancer (also available in Spanish) Health Professionals Associated With Cancer Care Pediatric Cancer Centers Understanding Chemotherapy: A Guide for Patients and Families (also available in Spanish) Understanding Radiation Therapy: A Guide for Patients and Families (also available in Spanish) What Happened to You, Happened to Me (children's booklet) When Your Brother or Sister Has Cancer (children's booklet) When Your Child's Treatment Ends: A Guide for Families (booklet)

Books
The following books are available from the American Cancer Society. Call us at 1-800227-2345 to ask about costs or to place your order. Because... Someone I Love Has Cancer (kids' activity book) Caregiving: A Step-By-Step Resource for Caring for the Person with Cancer at Home Jacob Has Cancer: His Friends Want to Help (coloring book for a child with a friend who has cancer) Let My Colors Out (picture book for young children)

National organizations and Web sites*

In addition to the American Cancer Society, other sources of patient information and support include: American Childhood Cancer Organization (formerly Candlelighters) Toll-free number: 1-800-366-2223 Web site: www.candlelighters.org

Cancer Kids Web site: www.cancerkids.com CureSearch (National Childhood Cancer Foundation and Children's Oncology Group) Toll-free number: 1-800-458-6223 Web site www.curesearch.org National Cancer Institute Toll-free number: 1-800-422-6237 (1-800-4-CANCER) Web site: www.cancer.gov National Children's Cancer Society, Inc. Toll-free number: 1-800-532-6459 (1-800-5-FAMILY) Web site: www.children-cancer.org National Dissemination Center for Children with Disabilities (NICHCY) Toll-free number: 1-800-695-0285 (also for TTY) Web site: www.nichcy.org Starlight Children's Foundation Toll-free number: 1-800-315-2580 Web site: www.starlight.org
*Inclusion on this list does not imply endorsement by the American Cancer Society.

Other publications*
For adults
100 Questions & Answers About Your Child's Cancer, by William L. Carroll and Jessica Reisman. Jones and Bartlett Publishers, 2004. Cancer & Self-Help: Bridging the Troubled Waters of Childhood Illness, by Mark A. Chester and Barbara K. Chesney. University of Wisconsin Press, 1995. Care for Children and Adolescents with Cancer: Questions and Answers. National Cancer Institute. Available at: www.cancer.gov/cancertopics/factsheet/NCI/childrenadolescents or call 1-800-332-8615. Childhood Cancer: A Parent's Guide to Solid Tumor Cancers, by Honna Janes-Hodder and Nancy Keene. O'Reilly and Associates, 1999. Childhood Cancer: A Handbook from St Jude Children's Research Hospital, by Grant Steen and Joseph Mirro (editors). Perseus Publishing, 2000. Childhood Cancer Survivors: A Practical Guide to Your Future, by Nancy Keene, Wendy Hobbie, and Kathy Ruccione. O'Reilly and Associates, 2000.

Children with Cancer: A Comprehensive Reference Guide for Parents (2nd Edition), by Jeanne Munn Bracken and Pruden Pruden. Oxford University Press, 2005. Educating the Child With Cancer: A Guide for Parents and Teachers, edited by Nancy Keene. Candlelighters Childhood Cancer Foundation, 2003. Living with Childhood Cancer: A Practical Guide to Help Families Cope, by Leigh A. Woznick and Carol D. Goodheart. American Psychological Association, 2002. Surviving Childhood Cancer: A Guide for Families, by Margo Joan Fromer. New Harbinger Publications, 1998. When Bad Things Happen to Good People, by Harold Kushner. G.K. Hall, 1982. When Someone You Love Is Being Treated for Cancer. National Cancer Institute. Available at: www.cancer.gov/cancertopics/when-someone-you-love-is-treated, or call 1800-332-8615. Young People with Cancer: A Handbook for Parents. National Cancer Institute, 2003. Available at: www.cancer.gov/cancertopics/youngpeople, or call 1-800-332-8615. Your Child in the Hospital: A Practical Guide for Parents (2nd Edition), by Nancy Keene. N. O'Reilly & Associates. 1999. (Also available in Spanish.)

Books for teens and children

Although these books are intended for children, younger kids are helped more when an adult reads with and helps the child reflect about what different parts of the book mean to the child. The Amazing Hannah, Look at Everything I Can Do! by Amy Klett. Childhood Cancer Foundation, 2002. For ages 1 to 6. (Also available in Spanish.) Chemo, Craziness and Comfort: My Book about Childhood Cancer, by Nancy Keene. Candlelighters Childhood Cancer Foundation, 2002. Can be ordered from www.candlelighters.org. For ages 6 to 12. Childhood Cancer Survivors: A Practical Guide to Your Future (2nd Edition), by Kathy Ruccione, Nancy Keene, and Wendy Hobbie. Patient Centered Guides, 2006. For older teens. Going to the Hospital, by Fred Rogers. Paperstar Book, 1997. For ages 4 to 8. Life Isn't Always a Day at the Beach: A Book for All Children Whose Lives Are Affected by Cancer by Pam Ganz. High-Five Publishing, 1996. Workbook for ages 6 to 10. Little Tree: A Story for Children with Serious Medical Problems, by Joyce C. Mills. Magination Press, 2003. For ages 4 to 8. Living Well With My Serious Illness, by Marge Heegaard. Fairview Press, 2003. For ages 8 to 12.

Me and My Marrow, by Karen Crowe. Published by Fujsawa Healthcare, 1999. For teens. My Book for Kids with Cansur [sic], by Jason Gaes. Viking Penguin, 1998. For ages 4 to 8. Oncology, StupologyI Want to Go Home! by Marilyn K. Hershey. Butterfly Press, 1999. For ages 8 to 12. (Also available in Spanish.) What About Me? When Brothers and Sisters Get Sick, by Allan Peterkin and Frances Middendorf. Magination Press, 1992. For brothers and sisters (ages 4 to 8) of a child with cancer. When Someone Has a Very Serious Illness: Children Can Learn to Cope with Loss and Change, by Marge Heegaard. Woodland Press, 1991. For ages 6 to 12. Why, Charlie Brown, Why? A Story About What Happens When a Friend Is Very Ill, by Charles M. Schultz. Ballantine Publishing Group, 1990. For ages 6 to 12.
*Inclusion on this list does not imply endorsement by the American Cancer Society.

No matter who you are, we can help. Contact us any time day or night for information and support. Call us at 1-800-227-2345 or visit www.cancer.org.

References
Abramson DH, Dunkel IJ, Brodie SE, Marr B, Gobin YP. Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma (chemosurgery). Ophthalmology. 2010;117:16231629. Abramson DH, Schefler AC. Update on retinoblastoma. Retina. 2004;24:828847. Dome JS, Rodriguez-Galindo C, Spunt SL, Santana VM. Pediatric solid tumors: Retinoblastoma. In: Abeloff MD, Armitage JO, Niederhuber JE. Kastan MB, McKenna WG, eds. Abeloff's Clinical Oncology. 4th ed. Philadelphia, Pa: Elsevier; 2008:2107 2112. Dunkel IJ, Jubran RF, Gururangan S, et al. Trilateral retinoblastoma: Potentially curable with intensive chemotherapy. Pediatr Blood Cancer. 2010:54:384-387. Hurwitz RL, Shields CL, Shields JA, et al. Retinoblastoma. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2006: 865888. Lin P, O'Brien JM. Frontiers in the management of retinoblastoma. Am J Ophthalmol. 2009;148:192198. National Cancer Institute. Physician Data Query (PDQ). Retinoblastoma Treatment. 2010. Accessed at www.cancer.gov/cancertopics/pdq/treatment/retinoblastoma/healthprofessional on November 9, 2010.

Russell HV, Pappo AS, Nuchtern JG, et al. Solid tumors of childhood: Retinoblastoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008:20532056. Shields CL, Meadows AT, Leahey AM, et al. Continuing challenges in the management of retinoblastoma with chemotherapy. Retina. 2004;24:849862. Wilson MW, Haik BG, Liu T, et al. Effect on ocular survival of adding early intensive focal treatments to a two-drug chemotherapy regimen in patients with retinoblastoma. Am J Ophthalmol. 2005;140:397406.

Last Medical Review: 1/26/2011 Last Revised: 1/26/2011 2011 Copyright American Cancer Society