How radiation slows down cancer
Long-term effects after radiation therapy
Author: Gesche Tallen, last changed: 02.10.2019
Long-term effects after radiation therapy in childhood or adolescence arise from permanent tissue damage caused by radiation. Long-term effects can impair body growth and puberty development, hormone production, salivation and the functions of the nervous system, eyes, ears, liver, heart and lungs. Three out of four former patients develop long-term effects after cancer therapy in childhood or adolescence.
The risk and extent of long-term effects after radiation therapy vary from patient to patient. Numerous different factors, such as the underlying cancer, the type of chemotherapy, the consequences of the operation or existing comorbidities (e.g. neurofibromatosis), as well as the age of the patient at the time of therapy, all influence in different ways whether a patient has certain long-term effects will develop and if so, which ones [TIM2018a].
Important to know: The risk and extent of long-term effects after radiation therapy in children or adolescents are not determined by radiation therapy alone.
This means that it is not possible to precisely predict long-term effects individually. However, the treatment team takes the known risk factors into account when planning the treatment. For example, a patient with concomitant neurofibromatosis usually receives lower radiation doses than a patient without this concomitant but with the same cancer. This is because the tissues of neurofibromatosis patients are more sensitive to radiation and therefore more prone to radiation damage. The recommended follow-up examinations after radiation or cancer therapy are essential for all children and adolescents.
Important to know: In order to prevent long-term effects after radiation therapy and so that they can be recognized and treated in good time, all patients after cancer therapy should make use of the options of early and long-term follow-up care.
Long-term effects on the irradiated body region
In relation to the irradiated region of the body, the following information provides an overview (that is: not necessarily always or occurring in every patient) of late effects after radiation therapy in children or adolescents, which accordingly require special attention during follow-up care [COG2018] [TAL2015 ] [TIM2018a]
Soft tissues and bones (skeleton)
Both bone and soft tissue are particularly susceptible to radiation damage during the growth spurts in childhood and adolescence, i.e. in infancy (up to 6 years of age) and before and during puberty (11 to 13 years of age). Depending on the radiation dose administered, these can later cause health problems, in particular delays in body length growth to growth stagnation (short stature) and inadequate development of organs (hypoplasia).
Even low doses of radiation (> 1-2 Gy / Gray) in the area of the testes can later impair sperm development (spermatogenesis), higher doses (> 20 Gy) can also impair the production of male sex hormone (testosterone) and thus lead to infertility.
Girls who have received radiation in the area of the ovaries can later also experience disturbances in egg development (oogenesis) and reduced production of female sex hormones (estrogens, progestins).
Area of the diencephalon (hypothalamus) and pituitary gland (pituitary gland)
Radiation doses of 35 - 60 Gy in the area of the pituitary gland and hypothalamus cause functional disorders of these structures in the central nervous system. As a result, there is a reduced or absent production of important hormones: the most sensitive to radiation there is the production of growth hormones, followed by hormones that control the formation and release of certain hormones in various body organs. These include TSH (thyroid-stimulating hormone) to control thyroid hormone production in the thyroid (see below), certain pregnancy hormones (luteinizing hormone - LH, follicle-stimulating hormone - FSH), the so-called adrenocorticotropic hormone (ACTH) for the formation of steroid hormones in the adrenal gland, as well as the milk-producing hormone (prolactin) and vasopressin (antidiuretic hormone - ADH), a hormone that contributes significantly to the regulation of the water balance in the kidneys.
If these hormones are only produced to a limited extent or not at all, various disorders occur (hypothalamic syndrome), such as short stature, hypothyroidism, impaired fertility and disorders of the water balance (diabetes insipidus).
In order to prevent these hormonal problems or to be able to treat them promptly and successfully, for example by giving growth and / or thyroid hormone tablets, regular checks of the hormone levels are necessary as part of follow-up care.
The thyroid function can be impaired not only indirectly, as in the hypothalamic syndrome, after radiation in the area of the diencephalon (see above), but also directly - for example after radiation in the neck area, especially after radiation doses above 20 Gy. As a rule, there is a decreased production of thyroid hormone (hypothyroidism) 2 to 5 years or later after the end of radiation therapy. The higher the radiation dose in the thyroid area, the greater the risk of developing hypothyroidism within 20 years after the end of therapy. For this reason, the blood levels of the thyroid hormone (thyroxine) are regularly checked in former patients after radiation in the neck area.
A deficiency in thyroid hormone goes hand in hand with a slowdown in all metabolic processes in the organism. Patients with hypothyroidism typically often complain of decreased physical and mental performance, weight gain, and constipation. Development delays can also occur in children and adolescents.
Therefore, hypothyroidism usually requires hormone replacement therapy (regular intake of thyroid hormone in tablet form) and regular check-ups by a hormone specialist (endocrinologist).
Depending on the radiation dose, the skin after radiation therapy can suffer acute and temporary damage, such as hair loss and reddening of the skin 2-3 weeks after radiation therapy, or later permanent damage, e.g. dilatation of small blood vessels (telangiectasia) or scarring.
Radiation-related problems in the digestive tract are dose-dependent and result from damage to the highly radiation-sensitive mucous membranes that line the inside of the mouth, throat, esophagus, stomach, small, large and rectum.
- acute, temporary radiation damage, which usually begins in the 3rd week after the end of the exposure and is associated with inflammatory changes in the mucous membranes and subsequently with abdominal pain and diarrhea
- Chronic, permanent changes in the mucous membranes and their blood vessels such as reduced blood flow, scarring (fibrosis) with intestinal constrictions (stenoses), as a result of inadequate absorption of nutrients from food (malabsorption) and digestive disorders.
The liver is generally considered to be less sensitive to radiation. Therefore, long-term damage to this organ is rare. However, the risk increases if the liver was irradiated with more than 30 Gy, or if chemotherapy with liver-damaging cytostatics was administered and the organ was irradiated with more than 15 Gy.
The rays can damage the liver tissue by scarring the organ (liver cirrhosis) and thereby causing liver dysfunction up to and including liver failure. Irradiation of the liver can also damage the hepatic veins: there is calcification in the vessel walls, and this leads to vasoconstriction (stenoses), slowed blood flow or congestion of venous blood, which then often seeps into the surrounding liver tissue and becomes inflammatory there Triggers changes and functional disorders (veno-occlusive disease). Patients who have had whole-body irradiation are particularly at increased risk of developing this so-called veno-occlusive disease (VOD).
- Tiredness (fatigue), decreased performance, difficulty concentrating
- Yellowing of the skin and whites of the eyes (jaundice)
- Enlargement of the spleen (due to congestion of blood between the liver and the digestive tract)
- Reduced production of certain body proteins (so-called liver synthesis disorders) - as a result, for example, skin bleeding and an increased tendency to bruise (due to reduced production of coagulation factors), hormone deficiency symptoms (due to reduced production of hormone components), fluid accumulation in the abdominal cavity (ascites, due to reduced production of protein Albumin)
Regular check-ups of the liver function (for example by physical examination, ultrasound, determination of the liver values in the blood) are standard as part of the follow-up examinations after cancer therapy.
The bone marrow is highly sensitive to radiation: even after low doses (1 - 2 Gy), a few weeks to months after the end of the radiation there is a marked reduction in blood formation in the affected bone marrow region. First the formation of white, then that of red blood cells is affected. However, up to a quarter of the entire bone marrow can be irradiated with higher doses without a dangerous decrease in blood formation. This is because the non-irradiated bone marrow regions become more active and take over the work of the damaged area. But even this compensation mechanism has its limits: If more than 50% of the bone marrow has more than 50 Gy, adequate blood formation can no longer take place.
In addition to the radiation dose received by the bone marrow in a particular region, the extent of this so-called bone marrow depression (myelosuppression) also depends on whether and which chemotherapy was administered to suppress bone marrow.
Central nervous system (CNS: brain and spinal cord)
The long-term damage that can occur years after cranial or spinal cord irradiation is the result of permanent damage to both the blood vessels in the brain and in the nervous tissue itself Radiation field, the underlying disease and other important therapy elements such as surgery and chemotherapy. The brains of infants and young children are highly sensitive to radiation. For this reason, radiation therapy is generally avoided in these age groups. Most older children and adolescents generally tolerate radiation therapy (with doses of up to 60 Gy) better - their overall risk of developing severe long-term sequelae 5 years after the end of treatment is 5%. These long-term effects include, for example:
- mental and emotional / psychosocial developmental disorders
- increased risk of stroke
- Cranial nerve paralysis, especially of the facial nerve with functional impairment of the facial muscles, of the optic nerve with loss of vision (see: Possible late effects after irradiation of the eye socket and the visual pathway) and the auditory nerve with balance and hearing disorders (see: Possible long-term effects after irradiation of the hearing)
- Hormonal failures (see: Possible long-term effects after radiation in the area of the diencephalon and pituitary gland)
- Disorders of the growth of the spine (e.g. short stature / reduced seat size, kyphosis, scoliosis)
- Disorders of mouth / jaw and tooth development (see: Possible late effects after irradiation in the mouth and jaw area)
Patients whose heart was irradiated with more than 30 Gy have an increased risk of developing cardiac dysfunction after radiation therapy. The risk increases if chemotherapy with anthracyclines was also administered. The rays can lead to pathological changes in the coronary arteries and heart valves. These changes can reduce the heart's pumping capacity. In order to recognize a reduced cardiac output in good time, regular checks of the cardiac function (e.g. by means of EKG and echocardiography) take place as part of the follow-up examinations.
The lungs are very radiation-sensitive organs. Radiation can permanently damage the cells of the lung tissue (pneumocytes) and connective tissue cells (fibroblasts) as well as the walls of the lung vessels and the structures that are responsible for oxygen uptake (so-called alveolocapillary membranes). Acute inflammatory reactions (pneumonitis) often occur first. However, these can later turn into irreparable, i.e. no longer curable, scarring of the lung tissue (pulmonary fibrosis) and thus impair lung function.
Overall, the risk of radiation-related long-term damage to the lungs depends on how high the radiation dose to the lung tissue and how large the irradiated lung portion was (in relation to the non-irradiated portion) and on how well the patient's lungs worked before the start of radiation therapy. For example, if only small regions of the lungs were irradiated with high doses (> 40 Gy), later health problems rarely occur. However, if both lungs have received a dose of more than 12-18 Gy and / or a residual tumor in the lungs has been irradiated with an additional dose, the risk of permanent deterioration in lung function, such as difficulty breathing or growth disorders, increases in the area of the bony chest (especially after irradiation of the lungs in infancy).
Urogenital tract (kidneys, urinary bladder, lower urinary tract)
From a dose of 15-25 Gy, radiation can lead to inflammatory reactions and later scarring and consequently to functional disorders of the kidneys 6-12 months after the end of radiation therapy.
If the urinary bladder receives a total of more than 45 Gy during radiation therapy, the patient has a high risk of later developing problems urinating or of developing more frequent bladder infections.
After irradiation of the breast, depending on the age or stage of development of the patient, doses below 5 - 10 Gy can lead to disturbances in breast development and to an increased risk of later breast cancer.
Eye socket and visual pathway
The eye socket contains many different structures such as the eyeball with its lens, the cornea, and the retina as well as the lacrimal glands.
Accordingly, the long-term effects after irradiation of the eye socket are varied and the former patients should be examined regularly by an ophthalmologist. Typical late effects after irradiation in the area of the eye socket are clouding of the eye lens (cataract) after doses between 2 and 12 Gy, as well as increased eye pressure (glaucoma) and the so-called "dry eye syndrome" (keratoconjunctivitis sicca) as Result of a shrinkage (so-called atrophy) of the lacrimal gland after radiation doses over 40 Gy.
From doses over 50 Gy, permanent eyelash loss can occur. In addition, after irradiation with 50 Gy and more, the risk of permanent damage to the optic nerve and the optic nerve junction (optic chiasm), if these are in the radiation field, as well as retinal damage (retinopathy) with loss of vision increases significantly. In patients with accompanying diabetes mellitus, the risk of later developing retinopathy is higher than in patients without diabetes.
Hearing loss can occur after high doses of radiation (30 - 50 Gy), especially if chemotherapy with platinum substances (cisplatin, carboplatin) has also been administered. Patients with neurofibromatosis have an additional increased risk of hearing loss after irradiation.
Mouth, jaw and face area
Radiation-related damage in the mouth, jaw and face area can occur in children and adolescents after direct exposure to doses over 10 Gy. They include in particular:
- Disorders of tooth development
- increased risk of tooth decay
- Disturbances in the development of the temporomandibular joint and bones with cosmetic problems and problems with speaking or chewing
- constant dry mouth.
Second cancers (secondary malignancies)
Patients who have received radiation therapy with therapeutic doses of 10-50 Gy as part of cancer therapy bear a certain risk of developing a new cancer or tumor years to decades after the end of treatment. This risk is increased in combination treatment with certain cytostatics (especially alkylating agents), genetic factors (e.g. retinoblastoma, neurofibromatosis or hereditary cancer syndromes) and the young age of the patient at the time of treatment.
Typical, radiation-induced secondary tumors are dependent on the radiation field, for example, tumors of the central nervous system, soft tissue and bone tumors (sarcomas), breast cancer (breast cancer) and thyroid cancer.
Further information on secondary cancers not only after radiation therapy, but also after cancer treatment in childhood or adolescence in general can be found here
Treatment of the long-term effects of radiation therapy
The underlying cancer as well as the age of the patient at the time of treatment, the type and intensity of the accompanying chemotherapy and concomitant diseases are important factors that are responsible for an increased risk and the severity of radiation-related long-term effects.
Precisely because long-term effects after cancer therapy in childhood and adolescence are multifactorial, they are also associated with very individual characteristics and influence the state of health and quality of life of the former patients in very different ways.
That is why the management or treatment of these long-term effects is also individual. As already mentioned, the follow-up examinations after cancer therapy are indispensable, not only in order to prevent relapses of the disease as well as possible long-term effects and to detect them as early as possible. An individual plan can then be drawn up together with the patient and the parents, which defines how best to deal with long-term effects.
on fertility and fertility maintenance
Girls / adolescent patients or boys / adolescent patients can find out about the options for maintaining fertility here before cancer treatment.
The brochures "Luzie would like to be a mother" and "Mischa would like to be a father" are aimed at young patients with cancer. They provide information on the topic of fertility after cancer therapy and on ways to maintain fertility through preventive and therapeutic measures. With the kind permission of the Berliner Krebsgesellschaft e.V. (publisher) and the author (Prof. Dr. med.Anja-Borgmann-Staudt) you can download the brochure here as a PDF. It can also be ordered from the Berlin Cancer Society.
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