Radiation Therapy for Pediatric Brain & Spinal Cord Tumors

The central nervous system is composed of the brain and spinal cord. Radiation therapy is commonly used to treat central nervous system tumors and can be given alone or in combination with surgery or chemotherapy. A doctor who specializes in delivering radiation therapy to treat tumors is called a radiation oncologist. The radiation oncologist will develop a unique treatment plan for each child based on tumor location, cell type, and stage. This plan includes the exact dose of radiation, the size and shape of the radiation beams, and the number of treatment sessions. Radiation therapy is either delivered externally or internally. In external radiation therapy, a machine aims high-energy radiation at the tumor site from outside the brain or spinal cord. The majority of CNS tumors are treated with external radiation.

Before starting treatment, the radiation oncologist uses a process called simulation to carefully define the treatment area. Typically, radiation is delivered in “fractions,” where the dose is given over multiple treatment sessions, most commonly using one fraction per day. With each additional treatment, or fraction, radiation accumulates at the site of the tumor. Extending treatment over several sessions helps decrease the risk of side effects to healthy tissues near the tumor. As radiation therapy has evolved, treatment modalities have emerged that allow more precise planning and delivery.

Above: Intensity modulated radiation therapy (IMRT) allows treatment of the tumor while sparing important normal structures such as the ears and the optic chiasm. This technology limits both short-term and long-term toxicities for children.

Conventional External-Beam Radiation Therapy

In most cases, radiation is focused precisely on the tumor from a source outside the body. This is called external beam radiation therapy (EBRT). Each treatment is much like getting an x-ray, but the dose of radiation is much higher. Treatment is not painful. For each session, your child will lie on a special table while a machine precisely delivers the radiation. Your child may be fitted with a plastic mold resembling a body cast to keep him or her in the same position during each treatment session. Some younger children may need to be sedated to make sure they don't move during the treatment. Each treatment session lasts about 15 to 30 minutes, but most of this time is spent preparing for the treatment. Exposure to the radiation beam is typically a few minutes. After treatment ends, tumor cells keep dying for days or even months. Radiation oncologists aim high doses of radiation at the tumor while exposing surrounding healthy tissue to the lowest possible radiation doses. Several newer techniques help doctors focus radiation precisely.

Three-Dimensional Conformal Radiation Therapy

In recent years, a sophisticated type of external beam radiation therapy called Three-dimensional Conformal Radiation Therapy (3D-CRT) has become widely used. In this treatment, the radiation oncologist combines multiple 3-dimensional brain images to more precisely define tumor boundaries and volume. Radiation beams and their angles of direction are shaped accordingly. The “conformed” or shaped beams are delivered from several angles and intersect at the tumor. This provides a much larger absorbed dose at the tumor site while largely sparing healthy tissue, minimizing adverse side effects.

Intensity-Modulated Radiation Therapy

Intensity-modulated radiation therapy (IMRT) is a more complex version of 3D-CRT in which the radiation oncologist can change the dose intensity or strength of each beam. This increases the radiation dose aimed at the tumor while minimizing the dose to normal tissue.

Stereotactic Radiosurgery

This type of radiation treatment delivers a large, precise radiation dose to the tumor area typically in a single session. Radiation oncologists perform stereotactic radiosurgery with the Gamma Knife or CyberKnife. These are machines that focus radiation at the tumor from hundreds of different angles for a short period of time. There is no actual surgery involved in this treatment. The effectiveness of radiosurgery when compared to external beam radiation for children is not yet clear. Because a high dose of radiation is given at once instead of divided in fractions, this is only a treatment option for very small tumors. It may also be useful for some tumors in parts of the brain or spinal cord that cannot be treated with surgery or when a child's health does not permit surgery.

Particle Beam Irradiation

In particle beam irradiation, radiation consists of beams of particles (usually protons) instead of photons (X-rays and gamma rays are both types of photons). Protons have physical characteristics that allow the dose to fall more sharply beyond the tumor, a feature known as the “Bragg peak.” This allows for potential sparing of critical structures. For some tumors, such as skull-base chordomas, protons are generally accepted as superior to photons but for other tumors the superiority of protons over other radiation technologies remains controversial. Furthermore, the physical advantages of proton beam radiotherapy must be weighed against proton-beam contamination by neutrons that may contribute significantly to risks of second malignancies, particularly in children. Therefore, the choice of proton-beam radiotherapy is one that must be made individually for each patient based on multiple factors.

Brachytherapy

This is a type of internal radiation treatment. The clinician implants a small radiation source directly inside or adjacent to the tumor. The radiation given off travels a very short distance from the source, so it primarily affects the tumor. The further tissue is from the source, the lower the dose of radiation it will receive. The radiation source can be either temporary or permanent. Brachytherapy is not as frequently used as 3D-CRT or IMRT for pediatric CNS tumors.

Side Effects

Because children’s brains are actively developing, radiation side effects can be particularly harmful. While not every child will have all, or any, side effects, most will experience some of them to one degree or another. It can sometimes be difficult to determine what side effects are from the tumor itself, surgery, chemotherapy, or radiation therapy. Radiation oncologists are constantly testing lower doses or different ways of giving radiation to see if they can be as effective as standard therapy while also decreasing side effects. Side effects to radiation treatment are typically divided into (a) acute reactions that occur during treatment; (b) sub-acute or early delayed reactions that occur a few weeks to 2 months after treatment; and (c) late reactions which occur several months to years after treatment.

A. Acute Reaction Side Effects:
Acute reactions are due to radiation directly affecting normal tissues during treatment.

Nausea and vomiting
Radiation treatment often causes nausea. Medications called antiemetics can help reduce these symptoms. Also, children may experience diminished appetite.

Fatigue
Brain irradiation may cause increased tiredness immediately following treatment and also for the next few weeks. Many patients require rest before resuming normal activity levels. Children can also become more irritable than normal. Irregular sleep, poor diet, and some medications can worsen post radiation fatigue. A routine of regular naps and a consistent bed time as well as mild physical activity as tolerated can improve quality of sleep and lessen tiredness.

B. Sub-Acute Reaction Side Effects:
Sub-acute reactions occur weeks to a few months after radiation treatment. They are often due to the fact that radiation causes inflammation, or swelling, within and near the tumor. Sub-acute treatment reactions typically resolve on their own in a few weeks or months.

Hair Loss
Radiation therapy damages cells that are actively reproducing including hair follicles. Very rarely, this hair loss can be permanent.

Skin Irritation
Skin can become red, dry, or itchy after radiation therapy. The skin should not be treated with typical childhood rash medications. Also, it is important to limit sun exposure and cover skin while outside during and in the weeks after treatment.

Vision Changes
Radiation therapy can cause swelling or excess fluid in the brain due to inflammation. This extra fluid can lead to changes in eyesight, including double vision.

C. Late Reaction Side Effects:
These occur beyond 6 to 12 months after radiation treatment and the effects are typically permanent. Late reactions are the most severe treatment reactions: they can be progressive and irreversible. The total radiation dose, the volume of brain tissue treated, and the time between treatments influence development of late reactions. Moreover, the risk of late reactions increases with preexisting brain injury and whether surgery and chemotherapy are combined with radiation therapy. Therefore, the radiation oncologist must balance an effective dose of radiation and control of the tumor with the risk of late side effects. If treating a large area of brain tissue, for example, the radiation oncologist can lower the dose or split treatments into more sessions. Normal brain cells grow quickly in the first several years of life, making them very sensitive to radiation. Because of this, radiation therapy is often not used or postponed in children younger than 3 years old to avoid damage that might affect brain development. It is important that you talk with your child's doctor about the risks and benefits of treatment.

Radiation Necrosis
Long-term inflammation from radiation treatment can also damage the cells that support neurons and blood vessels in the brain. Damaging blood vessels reduces the flow of oxygen to tissues and can begin a process of cell destruction called necrosis (cell death). Necrosis occurs months to many years after radiation and surgery maybe needed to remove the necrotic tissue. Necrosis occurs in less than 5% of patients.

Leukoencephalopathy
This is damage to the cells that surround and support neurons called glial cells. Glial cells make up the white matter of the brain. When damage to white matter occurs on a progressive scale, the support to neurons decreases and they can die.

Second malignancy

Radiation can damage genes in normal cells (just as it does in tumor cells). As a result, there is a small risk of developing a second cancer after radiation therapy. This generally occurs years after radiation treatment. Secondary tumors can be either benign or malignant. This small risk of second malignancy should not keep children from receiving possibly life saving treatment. It is important to continue close follow-up with the pediatric or radiation oncologist so any problems can be managed early.

Hormonal Changes
Damage to the part of the brain producing growth hormone (the pituitary gland) can affect a child’s height. Other hormones produced by the pituitary and hypothalamus can also be affected by radiation, depending on radiation doses to these structures. Radiation for spinal cord tumors can also cause growth deficits due to direct affects on bone growth. If hormone levels are affected by the tumor or any component of the treatment such as surgery or radiation, these hormones can be replaced to assure their normal levels.

Memory loss
Radiation therapy can affect memory abilities and thought processing. Effect on learning and memory depends on radiation dose, volume, and age of the child. Younger patients (less than 7 years of age) have a higher rate of neurocognitive deficits. Eventually, brain cell damage can lead to learning problems. The radiation oncologists will monitor patients for early cognitive effects and refer for neurocognitive therapy if needed.

Emotional and Behavioral Side Effects

Brain tumors can affect your child’s behavior and emotions. Radiation therapy can contribute to this change as well. It is often difficult to determine the causes of behavioral changes. If the changes are severe, the radiation oncologist will refer the child to a psychologist to better understand causes and treatment.

Anxiety
Fear and worry are normal responses to treatment. If they are severe, however, the radiation oncologist will refer the child to a neuropsychologist or social worker.

Depression
Feelings of sadness are entirely normal while dealing with a brain tumor and loss of normal activities. However, severe depression can negatively affect treatment and needs to be assessed. Tell your radiation oncologist if you notice signs of depression.

Increased Family Stress
The entire family is affected by diagnosis of a brain tumor in a child. This can affect stability of relationships between parents and with siblings. If family stress becomes a severe challenge, support is available from child life specialists, psychologists, social workers, and spiritual care providers.

Conclusion

While radiation therapy plays a key role in the treatment of childhood brain tumors, delivery of adequate therapy must be balanced with potential treatment-related toxicity. As the field has evolved treatments have emerged that allow more precise planning and radiation delivery. As more children are cured of their tumors and live to experience the long-term sequelae of radiation treatment, identifying and minimizing side effects becomes more important.