Radiation doses below 2500 cGy

Children who have stem cell transplants may receive radiation to the brain. Depending on the year children received transplants, they most commonly received 1000 to 1200 cGy of total body irradiation (TBI).

Cognitive late effects/learning difficulties. Children who received 1200 to 1800 cGy often develop learning difficulties that may be subtle. The changes are more pronounced in those who received 2400 cGy. Greater doses of chemotherapy into the brain from intrathecal medications or high-dose systemic methotrexate may increase the effects from the radiation. Very young children (younger than 5 and particularly those younger than 2) whose brains are growing and developing are more at risk than are older children and adolescents (Smibert E,1996; Brown RT, 1996). Changes in the way children or adolescents think, remember, and learn are called cognitive late effects.

Physical changes to the head/face/teeth. The growth of the skull (cranium) of young children who receive cranial radiation may slow, leaving the child with a smaller head than normal. The areas on either side of the eyes may develop a slightly pinched look. This late effect develops in approximately 3 out of 10 children. Children under the age of 5 when treated are most at risk. Children exposed to total brain radiation may also develop oral and dental problems. Children under the age of 2 are most at risk for dental late effects. This is discussed in more detail in Chapter 12, Head and Neck.

Effects on emotions and social interactions. Parents of children who had cranial radiation sometimes report that the child’s affect (i.e., emotions shown on the face) has changed. Rather than a face that reflects what one is thinking and feeling, the face expresses no emotion and appears expressionless. This can have a negative effect on socializing and making and keeping friends because facial expressions and other body language play a big role in effective communication. Other parents may notice a lack of or reduced curiosity and interest in friends, social life or leisure events. Although not much research has been done on these late-effects, they are included here because they occur in some survivors and can affect the way those survivors deal with the world. See Chapter 2, Emotions for more explanation of research related to emotional, behavioral and overall mental health of childhood cancer survivors.

Slower mental processing. Slow processing speeds can impact overall decision making and ability to make good judgment calls. The amount of information a survivor has available to make decisions may be lessened, because the process of considering options might be slower. Again, this is not a universal late-effect for all survivors, but it does affect a significant percentage of survivors who received cranial radiation (Krull, 2018).

Hormone production, puberty, and general health. Children who received cranial radiation doses of 1800 or 2400 cGy are at risk for problems with hormone production, puberty, and growth. Children who were younger than age 8 when they received radiation are at highest risk. There is also a small risk that the thyroid might not produce enough thyroxin. This risk increases if spinal radiation was also received. It is important to remember that the risk continues throughout life, and in some children, the effects do not appear until a decade or two after treatment has ended. These issues are covered in depth in Chapter 10, Hormone-Producing Glands.

Children, especially girls, who received radiation to the brain at a young age are at risk for becoming overweight. The exact reason why some children become overweight after radiation is unclear. This is discussed in Chapter 18, Muscles and Bones.

A rare effect from radiation to the brain that occurs during treatment and may be progressive is leukoencephalopathy. Children who develop this disorder may have lasting problems with balance (ataxia), difficulty swallowing (dysphagia), or speech problems (dysarthria). Leukoencephalopathy usually occurs in children or teens who relapsed and received cranial radiation plus high total doses of intravenous and/or intrathecal methotrexate.

Radiation doses above 2500 cGy

In the past, many children or teens with brain tumors received 3500 cGy to the whole brain with a boost of up to 5540 cGy to the tumor bed (i.e., the place where the tumor originated). Others received high-dose radiation only to the tumor itself. Currently, lower doses of radiation to the whole brain are used with many times the boost remains at 5500 cGy. Specific disabilities may partly depend on which area of the brain received the highest dose of radiation. However, in general, the higher the dose and the younger the age, the more dramatic the effect on brain functioning.

Higher doses of radiation cause slower brain processing speeds and greater drops in IQ scores. The location of the tumor also influences the type and severity of learning disabilities that may develop. For example, children with temporal lobe tumors may have problems with memory. Learning may also be affected by medications used to treat seizures or by surgical complications, hydrocephalus, vision problems, and hearing loss.

Children or adolescents with brain tumors who get very high-dose radiation to the brain can have multiple and life-altering late effects. Brain tumor survivors can develop seizure disorders, gait and balance problems, hand/eye coordination problems, personality changes, and learning disabilities. Radiation to the pituitary and hypothalamus can cause problems with growth, puberty, and fertility (see Chapter 10, Hormone-Producing Glands). Vision problems, cataracts, and diminished hearing can also develop after radiation (see Chapter 11, Eyes and Ears). All of the above late effects from high doses of radiation to the brain can range from mild to severe. With the use of proton beam radiation, there is hope that the risks to healthy brain tissue will be minimized.

Chemotherapy

Chemotherapy used to treat leukemia and some sarcomas can also cause learning disabilities that are sometimes subtle. Intrathecal methotrexate and high-dose methotrexate with leucovorin rescue can cause learning disabilities, although usually much milder than those caused by radiation (Schatz, 2000). Therapy for acute lymphoblastic leukemia sometimes includes triple intrathecals (methotrexate, hydrocortisone, and ARA-C) and has been associated with learning disabilities similar to those seen with lower doses of radiation (Montour-Proulx, 2005). Very young children (younger than age 5 and particularly younger than 2) whose brains are growing and developing are more at risk from chemotherapy to the brain than are older children and adolescents.

Surgery to the brain

Surgery to the brain can cause a host of late effects. The body system and amount of damage depend on the part of the brain where the surgery was performed, the amount of healthy tissue removed, and complications after surgery.

As with all the late effects described in this book, cognitive late effects are not an all-or-nothing phenomenon. You may have none, a few, or many. The lists of possible problems are not meant to fit you into a category, but rather to cover all possibilities so that if they develop, they are identified, and treated early to give the best possible outcomes.

Seizure disorders

Seizure disorders are another lasting effect that can develop in the brain after surgery, radiation, or chemotherapy. They occur most commonly during treatment, although sometimes begin many years after therapy. Seizures are caused by electrical disruptions in the brain. There are many types ranging from mild partial seizures during which the child does not lose consciousness to generalized seizures that involve convulsions and loss of consciousness. Signs and symptoms of seizures include the following:

• Staring into space

• Not hearing people talking

• Glassy eyes

• Auras (i.e., an abnormal smell, taste, abdominal sensation, or emotion that precedes a seizure)

• Stiff body

• Smacking lips and mumbled words

• Convulsions

• Jerking or twitching in parts of the body

Methods to screen for and treat all these late-effects are covered in the next part of this chapter.

Neuropsychological testing for cognitive problems

Any child at risk for cognitive problems should have neuropsychological testing performed as soon as possible after diagnosis. This should happen after treatment starts when the child starts feeling better or after treatment ends. The first test is called a baseline screening.

Neuropsychological testing is performed by PhD- prepared neuropsychologists who specialize in evaluating how children learn and think. Testing usually takes 4 to 6 hours, and can be scheduled over 2 days for younger children or those who are easily fatigued. All of that time is spent with the child, and the parents are interviewed separately. The psychologist gives a series of general tests appropriate for the child’s age level and then another series of more specific subtests based on the results of the general ones. Pediatric psychologists usually adjust the testing format and make it enjoyable for children. Children should be informed before testing appointments that the testing will be fun, and not to fear or worry.

The baseline testing is used as a yardstick to measure future changes in brain functioning. Many institutions perform baseline tests and repeat them every two to three years until adulthood. Parents and older survivors use the information from these tests to advocate for the most appropriate education and any special education or disability accommodations that might be necessary in school or college. The process for scheduling neuropsychological tests, applying for insurance or funds to pay for them, and advocating for the survivor’s best education environment are covered in more detail in Chapter 5, Navigating the System.

Yearly follow-ups

Survivors at risk for long-term effects from treatment to the brain need extensive, periodic evaluations throughout their lives. These should include:

• an educational analysis every year while in school

• yearly dental exams

• yearly evaluations of puberty and growth,

• yearly eye and hearing examinations

• education about second cancers

• a discussion about any new problems that have developed