Radiotherapy is a local treatment modality and therefore the side effects are almost invariably local. The adverse effects depend on the target area for as well as on the single and total doses of the radiotherapy. Typical adverse effects are caused by a damage to the cells capable of dividing.
Skin reactions comprise redness and dry or moist epithelitis.
Other symptoms include, depending on the location of the target area for radiotherapy, mucosal injuries, fibrosis, cataract, radiation pneumonitis, and after extensive radiotherapy also leuco- and thrombocytopenia.
Growth disturbances in the bone and cartilage tissues are seen in growing children in the areas that have received radiation doses large enough to destroy tumours. Mental development may be retarded especially in small children if the radiation is directed into the area of the head and brains.
Skin injury appears as reddening during 2 to 3 weeks after the start of the treatment. A mild reaction will heal by itself within two to four weeks.
Severe skin reactions are treated like burn wounds.
Late symptoms include thinning of skin and even telangiectasia; no specific treatment is needed. The function of sweat glands is impaired, and the skin feels thin and dry.
Loss of hair from the irradiated area occurs three to six weeks after the start of therapy. Generally the hair will regrow, albeit sometimes in different colour or more curled. Regrowth depends on the radiation dose.
Depending on the site of irradiation, mucosal irritation manifests as stomatitis, oesophagitis, intestinal irritation or diarrhoea. Adverse effects are usually particularly severe when radiotherapy is combined with cytostatic drugs.
Irritation of the mouth and oesophagus is treated with careful oral hygiene, topical antifungal agents and, if required, anaesthetic gel before a meal. Very warm, coarse and spicy foods must be avoided. Ensuring adequate nutrition is a special challenge when the symptoms are at their worst. The mucosae usually heal within a month after the treatment has ended.
Diseases of the teeth and mouth should be treated before radiotherapy to the jaw area. After radiotherapy special attention should be paid on oral and dental hygiene and regular check ups and treatment are necessary . Gingival and dental operations should be avoided; if needed urgently, these should be performed at specialist dental units.
The mouth becomes dry if the majority of the salivary glands are within the target area. The recovery of the salivary glands may continue for up to two years, but usually the drying of the mouth is at some level permanent. The drying of the mouth may be alleviated by using artificial saliva and by providing dietary councelling.
Disturbances of senses of taste and smell are usually transient adverse effects. Thinning and contractures of masticatory muscles and other nearby tissues are also possible long-term adverse effects.
The treatment of diarrhoea is symptomatic, ensuring sufficient hydration. Persistent diarrhoea calls for faecal culture; treatment is based on the result of the culture. Late effects may include intestinal stenoses up to several years afterwards.
Irritation of the urinary bladder manifests as frequent micturition, sometimes as pain. Infections have to be excluded and treated. Treatment consists of analgesics according to the severity of symptoms.
Irradiation of the eye region causes conjunctivitis. Treatment consists of locally administered eye drops. Late problems include dryness and ulceration.
Other organ damage
Cataract is a late effect from irradiation of the eye lens and occurs already at low radiation doses. Treatment consists of cataract surgery.
Radiation pneumonitis can appear two to six months after irradiation hitting the lungs. The symptoms comprise dry, nonproductive cough and mild fever. Chest x-rays may show shadowing in the irradiated area, but the diagnosis is based primarily on patient history and symptoms. Radiation pneumonitis is treated with anti-inflammatory agents and antitussives, sometimes with codeine tablets. An antibiotic and prednisolone at 10-25 mg three times daily may be administered for two to four weeks. Extensive fibrosis may be visible for years but smaller areas are not detected in plain chest x-rays.
Parts of renal tissue are usually spared in a way that the damage does not cause clinical symptoms. Local reactions include atrophy and fibrosis.
Radiotherapy to the heart area may cause fibrosis, increased cardiac morbidity and, in the worst case, constrictive pericarditis as late sequelae.
The hormone and gamete production of the reproductive system is damaged by a fairly low dose of irradiation. However, contraception must be taken care of when needed.
The spinal cord tolerates about 45-55 Gy in 5 weeks. Higher total and single doses involve the risk of progressing paraparesis that begins within months of the treatment and that may often be difficult to distinguish from symptoms caused by a tumour.
Osteoradionecrosis is an adverse effect of radiotherapy; predisposing factors include oral surgery procedures and poor oral hygiene.
Bone fractures may sometimes occur as a rare, late adverse effect after high-dose radiotherapy, after a course of radiotherapy for lung cancer or breast cancer, for example.
Haematological adverse effects
Leuco- and thrombocytopenia, sometimes anaemia, are encountered after extensive radiotherapy, such as half- or total-body radiotherapy. These are in most cases self-limiting and subside within a few weeks. In rare cases, blood cell transfusions, growth factors or even stem cell transplantation may be required. A moderate decrease in blood count after normal radiotherapy does not require treatment; however, severe neutro- or thrombopenia is managed in an oncology unit.
Radiotherapy of the head can cause oedema and elevation of intracranial pressure. The treatment is dexamethasone 3-12 mg three times daily tapered off gradually after the end of radiotherapy.
Nausea may result from total-body, half-body, intestinal or head irradiation. Treatment consists of metoclopramide and, in central nervous system irritation, glucocorticoids. Administration of serotonin (5HT3 receptor) antagonists is worth trying if other drugs are not effective.
The occurrence of fatigue and mental symptoms is variable. The treatment is symptomatic. Take into account differential diagnostics of the problems associated with the primary disease and arrange appropriate mental support.
In total-body radiotherapy and radiation accidents the first symptoms appear within minutes or hours. After high doses of radiation these include nausea, fatigue, loss of muscle strength, and confusion. A person who is initially asymptomatic may develop the gastrointestinal syndrome within a few days (nausea, diarrhoea, mucosal damage of the intestine, bleeding). If left untreated the syndrome can progress to fatal paralytic ileus. Even a lower dose of irradiation causes leuco- and thrombopenia within a few weeks, which can also be fatal.
References
Kielbassa AM, Hinkelbein W, Hellwig E, etl al. Radiation-related damage to dentition. Lancet Oncol 2006;7(4):326-35. [PubMed]
Mercadante V, Al Hamad A, Lodi G, et al. Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis. Oral Oncol 2017;66():64-74. [PubMed]
Greco E, Simic T, Ringash J, et al. Dysphagia Treatment for Patients With Head and Neck Cancer Undergoing Radiation Therapy: A Meta-analysis Review. Int J Radiat Oncol Biol Phys 2018;101(2):421-444. [PubMed]