Patients treated with radiotherapy or chemotherapy are prone to experiencing various oral complications, such as mucositis, xerostomia or osteoradionecrosis, among others. 

Cancer is a disease caused by a group of cells that multiplies uncontrollably and autonomously. It can invade tissues locally and remotely, which is known as metastasis. Metastases are the leading cause of death from cancer. Over 200 different types of cancer are known, and the most common are skin, lung, breast and colorectal. 

Cancer is now the second leading cause of death worldwide after cardiovascular disease, according to the World Health Organization (WHO). Largely due to growth and aging of the population, cancer mortality is expected to increase by 45% between 2007 and 2030, from 7.9 to 11.5 million deaths worldwide ⁽¹⁾. 

Mucositis is the most severe non-hematologic complication among patients receiving nonsurgical antineoplastic therapy 

The occurrence of cancer has been associated with several common risk factors such as smoking and alcohol consumption, poor diet, lack of physical activity, exposure to carcinogens in the workplace or in the environment, radiation and some viral infections. 

Cancer treatment can include surgery, radiation therapy, chemotherapy or a combination of all three. In this article we will explain non-surgical treatment options and the complications these may cause in the oral cavity. 

Head and neck radiation therapy and chemotherapy  

Radiation therapy is a form of treatment based on the use of ionising radiation such as x-rays or radioactivity, including gamma rays and alpha particles. This is an important tool in head and neck cancer treatment, either by itself or combined with surgery and chemotherapy. Radiation therapy can be applied using an external beam, which is most common, and involves aiming the particles or rays carefully at the tumour from outside of the body. Internal beam radiation also exists, where the beam is placed directly inside the body. 

Chemotherapy is the most frequently used drug treatment. These drugs intend to block or slow down cell division and, depending on the type of cancer, they can also be used in combination with other treatments. Chemotherapy can cure, delay or prevent the spread of cancer, or make symptoms improve. Usually multiple cycles and frequency over time will depend on the needs in each particular case. 

In general, antineoplastic therapy has a major limitation, which is its low specificity. The mechanism of action involves cell alteration in the synthesis of nucleic acids, in cell division or in protein synthesis. The action of the different cytostatics used varies depending on the dose administered. Because of its low specificity it may affect other normal body cells and tissues, especially if they are actively dividing, such as blood cells and epithelial cells. 

The degree of damage depends on factors related to the treatment regimen, such as the type of radiation used, the total dose administered, the size of the field irradiated for radiotherapy and type of drug used for chemotherapy. 

Oral Complications from head and neck radiation therapy and from chemotherapy 

Oral complications associated with non-surgical antineoplastic therapy are classified according to the chronology of occurrence. The more immediate and frequently occurring complications include mucositis, dysgeusia, glossodynia and xerostomia. In the medium term, bacterial infections may also occur, such as, caries and periodontal disease, fungal infections and viral infections. 

Dysfunctional occlusion, dysphagia, and soft tissue necrosis may also occur. Finally, long-term osteoradionecrosis of the jaws, dental and skeletal growth abnormalities and developmental disorders in paediatric patients may occur. These complications can be partially or totally reversible or irreversible. 

Mucositis is the most severe non-hematologic complication in patients who undergo non-surgical antineoplastic therapy. It is characterised by oral tissue inflammation, which generally appears as a sore or as red patches at first, and later as ulcers, particularly on non-keratinised oral mucosa. Mucositis is an inflammation of tissues in the mouth. Following high-dose radiation therapy, there is a lifetime risk associated with invasive surgical procedures such as extractions and periodontal surgery It also presents with pain and there may be a superinfection by opportunistic microorganisms. 

Radiation-induced mucositis usually begins in the second or third week after initiation of therapy, then intensifies and finally disappears within two or three weeks after the end of treatment. Chemotherapy-induced oral mucositis may begin between the fifth and the seventh day after starting chemotherapy, it usually involves bleeding, and if no superinfection occurs, it normally subsides from two to four weeks after its onset. 

The pathogenesis of mucositis is based on the cytotoxicity that both radiation therapy and chemotherapy induce on a cellular DNA level. Thus, cell death and destruction of mucosal tissues occur, facilitating the entry of infection. Also, the mucosa is more susceptible to injury, and bleeding may be increased in the presence of thrombocytopenia. 

It is a major cause of morbidity during antineoplastic therapy. It affects patient quality of life, as it causes severe pain and ulcers that lead to difficulties in eating, swallowing and phonation. It is also associated with more days of fever, parenteral nutrition and the administration of opiate derivatives and increased risk of infections⁽²⁾. 

Xerostomia is caused by a marked reduction in the secretion of saliva from the salivary glands, especially the minor glands. The signs and symptoms of xerostomia include dry mouth, burning tongue sensation, cracks in the corners of the mouth, atrophic dorsal tongue surface, difficulty using dentures and increased thirst. It may also affect speech, sleep and taste. 

Both chemotherapy and radiation therapy can damage salivary glands and cause xerostomia. 

Chemotherapeutic drugs that are used alone or in combination and that might cause xerostomia have not been well documented, although approximately 40% of patients report this side effect during treatment. Normally this effect is short term and recovery has been observed from two to eight weeks following therapy. 

In contrast, radiation therapy, even at low doses, can cause permanent damage to both major and minor glands that are within the radiation field. Salivary gland cells are particularly sensitive to radiation, eventually resulting in fibrosis, degeneration and atrophy of the glandular cells⁽³⁾. 

Another very severe complication is osteoradionecrosis. After high-dose radiation therapies, there is a lifetime risk associated with invasive surgical procedures, such as extractions or periodontal surgery. In the event that such procedures are necessary, they must always be a year after radiation therapy and with antibiotic coverage. 

Furthermore, if doses of radiation are administered in excess of 6500 rads (65 Gy), hyperbaric oxygen therapy may be necessary to stimulate angiogenesis before and after surgical treatment. Nevertheless, interconsultation with the radiologist will always be mandatory for proper management of these patients⁽⁴⁾.