Radiotherapy irradiates healthy tissues, due to the technical challenge of focusing beams only to the cancer.
Side effects can occur as a result of damage to these healthy tissues.
Some side effects are short term, disappearing when treatment ends. Some may last for several weeks or months (medium term). Long term effects may not become apparent until years after treatment. They may affect the eye area and the brain.
Radiotherapy increases life-long risk of second primary cancers in children with a constitutional RB1 mutation.
Short Term Side Effects
The severity of short term side effects will depend on the sensitivity and size of the area being treated. The radiation oncologist is familiar with side effects and will be responsible for their treatment. Possible short-term side effects are:
- taste changes that may cause a loss of appetite
- nausea and vomiting
- fatigue that may increase as treatment progresses
- sore skin and an itchy, sticky eye
- hair loss in the radiation field – a small patch of hair may be lost from the back of the head at the exit site of the beam when whole eye radiation is used
Medium Term Side Effects
Somnolence syndrome: characterized by prolonged drowsiness and deep sleep (up to 24hrs at a time is common), difficulty speaking, and flu-like symptoms (low grade fever, nausea, vomiting, headache and irritability).
This can be alarming if you are not prepared, but it is a normal reaction to cranial radiotherapy that occurs up to three months after treatment has ended.
Radiation retinopathy: may occur after high doses of radiotherapy (above 5000cGy), causing some degree of vision loss.
Long Term Side Effects – Orbital
Cataracts
Cataract is a clouding of the lens (part of the eye that focuses light), causing vision to appear blurred. They also cause a white eye glow, similar to that caused by tumours.
Whole-eye radiotherapy causes cataracts, usually 2-3 years after treatment. Higher doses cause earlier, more severe cataract. They also tend to develop faster in younger children.
A fairly minor surgery (lensectomy) removes the lens so vision is not impaired.
An artificial lens may be inserted, or the child may be prescribed glasses.
This surgery is not advised until tumours have been inactive for at least three years. This is because any surgery that involves putting a needle directly into the eye may cause active cancer cells to escape beyond the eye.
When the lens has been removed, the eye is usually more sensitive to bright lights, and children sometimes need to wear tinted glasses on sunny days.
Lensectomy poses a risk of spreading cancer outside the eye if tumours are still active. For this reason, surgery will not be done until retinoblastoma has been inactive for at least 3 years.
When cataracts form while tumours are still active, or very soon after the last tumour activity, they can prevent thorough examination of the eye. If this happens, it may be necessary to remove the eye to protect the child’s life.
Photoleukocoria (white pupil in photos)
As cancer dies after radiation, it calcifies, taking on a chalky appearance that may remain throughout life. This can generate a white reflection in flash photographs, similar to the common early sign of retinoblastoma.
Hypoplasia (reduced orbital bone growth)
Reduced orbital bone growth may occur in the treatment field. This usually affects children who receive radiotherapy as infants, when orbital bone structures are still rapidly developing.
Typically, the temporal bone (on the side of the eye nearest the ear), and the bridge of the nose are suppressed, and the eye socket may develop a sunken appearance. Soft tissue growth may also be reduced.
In some cases, reconstructive surgery may be possible. However, this is often a very painful process, and may have implications for remaining vision.
Stunted growth of tooth roots has also been observed. This may affect both milk (baby) teeth and adult teeth.
Telangiectasia (bleeding in the eye)
Small dilated blood vessels in the eye may haemorrhage 1-2 years after a total radiation dose greater than 3000cGy. The body often reabsorbs the blood over a period of months.
Haemorrhage may happen while tumours are still active, or very soon after the last tumour activity. This bleeding can prevent thorough examination of the eye, and if this happens, it may become necessary to remove the eye to protect the child’s life.
Secondary Dry Eye
Radiotherapy may damage the lachrymal gland, reducing the eye’s ability to produce tears. Scarring from treatment may also prevent the eye lids from closing fully during sleep. This can cause the eye to become dry and sore.
Regular application of artificial tears and other ocular lubricants before dry eye arises can reduce the risk of associated complications later.
Photophobia (sensitivity to light)
Sensitivity to light may be moderate or severe. Tinted lens glasses, window blinds and strategic lighting can lessen the impact
Corneal Scarring and Ulcers
This may occur when the total radiation dose is greater than 4000 cGy. Vision may be damaged or lost completely in severe cases. Keeping the eye well hydrated with regular lubricating drops may reduce the risk of corneal damage, or slow its progress.
Glaucoma (raised pressure in the eye)
Increased pressure within the eye may occur many years after radiotherapy. Glaucoma can often be managed with medication. In severe cases, the eye may be surgically removed.
Long Term Side Effects – Neurological
Children often require cranial radiotherapy when cancer has spread outside the eye, which can have a range of neurological side effects. Scatter from radiation to the eye may cause mild neurological side effects. The type of neurological impact will depend on the radiotherapy site and surrounding regions of the brain.
The following may be an effect of doses as low as 1800 cGy. In general, the higher the dose, and the younger the child at time of treatment, the greater the effects are likely to be.
These effects may alter the child’s personal learning techniques and/or social behaviour. Parents, carers, medical professionals and teachers should be vigilant and advocate appropriate positive early intervention.
Cognitive Skills
Doctors cannot accurately predict the type and extent of cognitive deficiencies caused by radiotherapy. In general, preschool age children, particularly those under two years, are at greatest risk.
Learning difficulties are usually apparent to the child’s parents and teachers within 3-5 years of treatment. Maths, problem solving, spatial relationships, attention span, concentration and memory skills may be particular issues.
Slower processing speeds will restrict the amount of information available in a given time frame. This may impair a child’s ability to make sound judgements quickly.
The child may become frustrated by their inability to keep up with peers in class. This may foster a belief that they are less intelligent and less likely to succeed. Many children who exhibit these effects are very bright. Specific interventions may boost their confidence and help them achieve their full potential.
Hormone Dysfunction
Radiotherapy may cause permanent damage to the hypothalamus and pituitary gland. The hypothalamus produces substances that control release of hormones from the pituitary gland.
Implications of damage to these structures may be dramatic as they are responsible for the overall function of the endocrine system. Damage to this system often results in stunted growth and precocious puberty.
Slow or stunted growth can be treated with regular growth hormone injections.
Precocious puberty is an earlier than normal onset of puberty. This is regarded as less than 8 in girls and less than 10 in boys. This may result in short stature as bones stop growing when the body reaches sexual maturation.
Children should be monitored by an endocrinologist if it is suspected that radiotherapy may interfere with the hypothalamic/pituitary region of the brain.
Seizures
Seizures may affect the entire brain, or a specific area. They range from a slight loss of awareness (often mistaken as daydreaming), to severe events involving loss of consciousness and convulsions (shaking).
Scarring of the brain tissue may cause seizures to develop years after radiotherapy. Many treatments available today can effectively control them.
Long term Side Effects – Second Primary Cancers
Second primary cancers are the most significant long term side effect of radiotherapy for retinoblastoma. The risk is higher in children with a constitutional RB1 mutation, especially is radiation is given before one year of age.
This is why eye-salvage radiotherapy is reserved as a last resort to save a second eye in children with bilateral retinoblastoma. Primary radiotherapy is usually only used when no other eye salvage therapy is available and there is a good chance of saving vision.
Second primary cancers may occur within and outside the radiation field. These are primarily bone and soft tissue sarcomas, melanoma (skin cancer) and brain tumours.
Trilateral Retinoblastoma
Chemotherapy was introduced in the 1980s as the primary treatment for retinoblastoma. Since then, doctors have noticed that fewer children develop trilateral retinoblastoma. This is likely a result of less radiation exposure. Chemotherapy may also “get to work” on trilateral retinoblastoma before anyone knows the cancer is developing.
Research Results
A number of studies show an increased risk of second cancers to children who had radiotherapy for retinoblastoma. However, many of these include patients treated several decades ago.
Older forms of radiation used a bone dose 2 ½ times higher than modern techniques, and radiation fields were less accurate. Modern radiotherapy machines deliver much lower doses to normal tissue, but studies are not yet available to show whether they offer a reduced risk of second primary cancers.
Oncology Follow Up
Children and adults treated with radiotherapy for retinoblastoma should be closely followed in a long term survivors oncology clinic. Any unexplained lumps, bumps, headaches and other symptoms that persist for more than two weeks should be promptly checked out if they persist for more than two weeks.
Primary doctors should be made aware of these risks so they can quickly investigate symptoms. Children must also be made aware of their risks as they grow up, so they can become responsible advocates for themselves.
