Treatment for retinoblastoma (eye cancer in children)

Most children with eye cancer who begin treatment before the retinoblastoma has spread beyond the eye are cured. A major goal of treatment in children with retinoblastoma is preserving vision. Most children retain their vision and more than 95 percent of children with retinoblastoma can be cured.

Treating unilateral retinoblastoma

The amount of retinoblastoma in a child’s eye is graded by the International Retinoblastoma Classification Grouping.  Group A designates the least involvement whereas Group E is the most advanced intraocular group.

When only one eye is involved, and the eye is Group E, enucleation (removal of the involved eye) is usually the treatment of choice. Children adjust very well to the loss of one eye, and their vision does not suffer a great deal.

However, if a child is very young, there is a risk that a tumor will develop in the other eye, so the goal in these children is to remove as much of the tumor as possible while preserving vision.  In these cases, chemotherapy can be recommended.

Small tumors can often be treated successfully using local measures, including:

• Cryotherapy. Extreme cold may be used to destroy cancer cells. The procedure is done in the operating room. The child is discharged the same day after recovering from anesthesia.
• Thermotherapy. Heat may be used to destroy cancer cells.
• Plaque radiotherapy. Radioactive plaque therapy is a way to deliver continuous, concentrated radiation while sparing other parts of the eye. It is used to treat small tumors that recur after other therapies and are not near the macula. Radioactive "seeds" are placed on a metal shield and sewn into the eyelid to make sure the radiation is delivered to the exact location. This shield stays on for 5-7 days and is removed after the required dose of radiation is delivered. There will be a bandage placed over the shield. The procedure is performed in the operating room (OR). The child can be an outpatient during this time until the plaque is then removed in the OR.

Treating bilateral retinoblastoma

Chemotherapy

Chemotherapy is medication used to destroy cancer cells. When tumors are too large to apply local measures, we may recommend chemotherapy to shrink the tumors so local therapy can be used successfully.

Because chemotherapy can also affect normal cells along with cancer cells, certain side effects can occur. Any plan of chemotherapy will include a discussion of the potential side effects, the ways in which they can be prevented, and what tests we may need to do to look for them.

All of the chemotherapy medications given for retinoblastoma can be given via an intravenous (IV) catheter placed in your child's arm or foot. Some children may require a semi-permanent type of IV catheter, called a central venous catheter, which is placed under the skin in the chest.

Each child is affected differently by chemotherapy. Before each cycle of chemotherapy, a pediatric oncologist will examine your child.

Intra-arterial chemotherapy (IAC)

Intra-arterial chemotherapy (IAC) is a method of delivering concentrated doses of cancer-killing medicine directly to the affected area of the eye. In IAC, the chemotherapy dose is released into the ophthalmic artery, the primary blood supply at the back of the eye. Learn more about IAC for retinoblastoma.

Radiation therapy

Historically, radiation therapy was the treatment of choice for children with bilateral disease. However, radiation may produce damage to the retina many years after it has been given. That damage can result in loss of vision.

Radiation, when given to very young children, also results in decreased growth of the bone surrounding the orbit. It can also increase the risk of second non-retinoblastoma cancers from 10 to 50 years after treatment. For these reasons, radiation therapy is no longer considered a front-line therapy for children with retinoblastoma.

Although radiation therapy is not front-line therapy for retinoblastoma, except for Stage 2 patients, it can be used for patients with relapsed or refractory disease. In these patients, proton therapy can be employed.

Types of retinoblastoma (eye cancer in children)

Hereditary retinoblastoma 

Retinoblastoma can occur in one of two forms: hereditary retinoblastoma and nonhereditary (sporadic) retinoblastoma. 

About 40 percent of retinoblastoma patients have the hereditary form of disease. Hereditary retinoblastoma is caused by alterations, also known as mutations, to specific areas within an individual’s genetic information. Each of us has a large amount of genetic information that is organized into smaller segments known as “genes.” Genes provide the necessary instructions that our cells require to perform their different functions within our bodies.

In patients with hereditary retinoblastoma, the disorder develops as the result of alterations in a specific gene known as RB1, which is located on chromosome 13 at position q14.1-q14.2. RB1 is the only gene known to be associated with hereditary retinoblastoma. The protein produced by the RB1 gene acts as a “tumor suppressor,” which means that it helps to keep cells from growing and dividing too quickly and it promotes cell death.

With the exception of egg and sperm cells, each cell of the body normally has two working copies of the RB1 gene. Patients with hereditary retinoblastoma generally carry an alteration in one copy of the RB1 gene in all the cells of their body. If the second copy of the gene undergoes a change within a developing retinal cell, a retinoblastoma tumor can develop. Since every cell of the body already has an alteration in the first copy of RB1, it is relatively common for more than one retinal cell to undergo a change in the second RB1 gene copy. Therefore, about 85-90 percent of children with hereditary retinoblastoma develop multiple tumors that affect both eyes (bilateral disease). The remaining 10-15 percent of patients with hereditary retinoblastoma develop only a single eye tumor (unilateral disease).

During the first five years of life, almost all individuals carrying an alteration in RB1 will develop retinoblastoma. However, in some families, the risk to develop retinoblastoma is much less. In these families, the alterations in the RB1 gene appear to be less damaging.

Children with the hereditary form of retinoblastoma are also at a slightly increased risk to develop tumors in the pineal gland (a small gland located in the brain) and possibly another cancer, such as a bone or muscle cancer, later in life. Individuals with hereditary retinoblastoma who receive external beam radiation therapy have an increased risk (30-50 percent or higher) to develop second primary tumors, most commonly within the radiation field, over the course of their lives.

How is hereditary retinoblastoma inherited?

In 10-20 percent of cases of hereditary retinoblastoma, children inherit an alteration in one RB1 gene copy from an affected parent who carries the same genetic mutation. Interestingly, most children with hereditary retinoblastoma do not have a parent with retinoblastoma.

In many of these cases, a child develops hereditary retinoblastoma as the result of a “new” mutation in the RB1 gene in one of the father’s sperm, the mother’s eggs, or in a cell of the developing fetus. If this is the case, the child will carry the RB1 gene alteration in all the cells of the body, although they will be the first person in the family to have hereditary retinoblastoma.

Less commonly, one parent may have a condition known as “gonadal mosaicism," meaning that the parent carries a genetic alteration in one copy of the RB1 gene in only certain cells of the body, such as the egg or sperm cells, while other cells of the body (including the cells in the retina) have two working copies of RB1. Therefore, this parent will not develop retinoblastoma, but a proportion of their children can inherit the genetic alteration present in the egg or sperm cells.

All children with hereditary retinoblastoma have a 50 percent (or one in two) chance of passing the RB1 genetic alteration on to each of their offspring.

Cancer risks

During the first five years of life, almost all individuals carrying an alteration in RB1 will develop retinoblastoma. However, in some families, the risk to develop retinoblastoma is much less. In these families, the RB1 gene alterations appear to be less damaging.

Individuals with hereditary retinoblastoma are also at a slightly increased risk to develop tumors of the pineal gland.
Later in life, patients may develop other tumors, most commonly bone or muscle tumors. Individuals with retinoblastoma who receive external beam radiation therapy have an increased risk (30-50 percent or higher) to develop second primary tumors over the course of their lives.

Recommended cancer screening protocol for individuals at risk to develop retinoblastoma

Individuals at risk to develop retinoblastoma who should undergo cancer surveillance include:

• Individuals with retinomas (benign tumors of the retina)
• Children who have inherited an RB1 disease-causing mutation OR children at risk for hereditary retinoblastoma who have not yet had genetic testing

For these children, it is recommended that they undergo eye exams by an ophthalmologist knowledgeable about retinoblastoma starting directly after birth, performed every three to four weeks until age 1 and then less frequently until 5 years old. Young or uncooperative children may need to be examined under anesthesia.

To monitor for the development of pineal gland involvement, patients should undergo MRI examinations of the brain every six months until age 5. There is currently no consensus regarding recommendations for surveillance for older children with hereditary retinoblastoma who are at-risk to develop second malignancies. These individuals should lead a healthy lifestyle, avoid the use of tobacco products and excess sun exposure, and wear sunscreen and a hat when outdoors. They should also be vigilant for unexplained aches and pains, and seek medical attention should these occur, as they could indicate an underlying malignancy.

Non-hereditary (sporadic) retinoblastoma

About 60 percent of children with retinoblastoma have the non-hereditary form of the disease, which always manifests as a unilateral disease. They do not carry an alteration in one RB1 gene copy in every cell of the body. It is believed that most children with non-hereditary disease develop a retinoblastoma tumor because both RB1 gene copies become damaged within a single developing retinal cell. Children with sporadic retinoblastoma are not at increased risk of developing pineal gland or other tumors. They are also not at increased risk of transmitting the trait to develop retinoblastoma to their children.

If neither parent has had retinoblastoma and the child is at least 2 years old at diagnosis, the probability of having the hereditary form is very small. There is a genetic test that can be done to determine whether a child has hereditary or non-hereditary retinoblastoma.

Your child’s oncologist will discuss with you which form of retinoblastoma your child might have, whether genetic testing is warranted, and what this information means for follow-up for the child and for other members of your family.

Retinoblastoma genetic testing

All children with bilateral eye involvement and somewhere between 10 and 15 percent of children with unilateral disease have the hereditary form of retinoblastoma. To determine on a molecular level whether a person has the hereditary or nonhereditary form of retinoblastoma, a genetic test may be performed.

Testing when eye tumor tissue is available

If eye tumor tissue from the affected individual is available, DNA is isolated from the tumor sample and the two copies of the RB1 gene are evaluated by direct DNA sequencing. Sequencing is a process by which a person’s genetic code is compared to a “normal” reference code. DNA sequencing is performed on the tumor tissue first in order to identify the two RB1 alterations present in the tumor. DNA from a sample of peripheral blood is then screened for the presence of one of the two RB1 gene alterations that was found in the tumor.

If one of the RB1 alterations identified in the tumor sample is also identified in the affected individual’s blood sample, this would strongly support a diagnosis of hereditary retinoblastoma. The absence of any retinoblastoma gene abnormalities in DNA from the blood sample typically confirms a diagnosis of sporadic (non-hereditary) retinoblastoma.

Testing when eye tumor tissue is not available

Eye tumor tissue may not be available for testing in all cases. DNA sequencing can still be performed on a blood sample from the affected individual to investigate for the presence of an alteration in RB1. However, when no tumor is available for comparative genetic study, the failure to identify an alteration in RB1 alteration in the individual’s blood sample does not rule out the possibility that the individual has hereditary retinoblastoma as it remains possible that this individual carries an RB1 mutation that escaped detection due to technical issues related to the genetic testing process.

RB1 genetic test results can provide important information for other family members. Knowing the specific alteration that is present in a person with cancer allows other family members to have testing to determine whether they also carry this alteration in the RB1 gene. 

Options for people considering pregnancy

There are several options for an individual who is found to have an alteration in RB1 and who does not want to pass this alteration on to his or her future children. To do prenatal testing, the familial RB1 mutation must be identified in the affected parent.

• Prenatal diagnosis. DNA is isolated from the cells of the developing baby though one of two procedures — chorionic villus sampling (CVS) or amniocentesis. Each type of prenatal test is offered at a different time during the pregnancy.
• Preimplantation Genetic Diagnosis (PGD). Available to individuals who are known to have a genetic alteration that causes a condition such as hereditary retinoblastoma. PGD is performed in combination with in vitro fertilization (IVF) and offers a way to test the potential parent's embryos for genetic disorders before transferring them into the uterus.

If a parent carrying an RB1 alteration does not wish to undergo prenatal testing for retinoblastoma, genetic testing can be performed at birth to determine whether the child inherited the familial mutation. Children who have inherited the familial mutation are at risk to develop retinoblastoma and should follow the surveillance guidelines listed below. Children who did not inherit the familial mutation do not have hereditary retinoblastoma. These children should have eye exams performed as needed for routine pediatric care.

Late effects/cancer survivorship

Some children treated for retinoblastoma develop complications years later. Our Cancer Survivorship Program provides information about the potential long-term effects of the specific treatment your child received, including ways of monitoring and treating these effects.