Oral Management of Patients Undergoing Radiation Therapy

Function

Radiation Therapy Biology

Radiation therapy uses ionizing radiation to damage malignant cells by acting on the DNA, leading to cellular death or inhibiting their multiplication capacity.[4] Although several types of ionizing radiation exist, most treatments use photons.[5] Radiation can be delivered by external beam radiation (from outside the body) or brachytherapy (from inside the body). External beam radiation is more common, and brachytherapy is implemented mainly in gynecological and prostate cancers.

Radiotherapy can be used to cure or alleviate symptoms caused by malignancy; it can be given in combination with surgery, immunotherapy, or chemotherapy.[4] When radiation is given pre-surgery, it usually has the objective of decreasing the size of the tumor. When it is given after surgery, it aims at eliminating residual microscopic malignant cells.[4]

Radiotherapy works on the principle of damaging the genetic material of cells (DNA), acting on both cancerous and normal cells. During mitosis, the DNA content of cells duplicates; therefore, cells with high mitotic activity are more susceptible to radiation than those with low mitotic activity. In other words, tissues with higher division activity are more radiosensitive, which is usually the case with malignant tumors. Different tumors have different multiplication capacities, making some more radiosensitive than others.[5]

Normal tissues located in the radiation path also suffer the effects of ionizing radiation, which in the oral cavity leads to complications such as oral mucositis, xerostomia, and radiation-related caries. However, normal cells have a faster repair rate and a better ability to return to normal function than cancerous cells. The lower repair rate of cancerous cells is what causes differential malignant cell killing.[5] 

The newer radiotherapy modalities like 3-D confrontation therapy, intensity modulated therapy (IMRT), and proton beam therapy can deliver radiation to localized areas, thus, sparing the normal tissue more efficiently.[6]

Issues of Concern

Oral Complications of Radiation Therapy in The Head and Neck

Oral Mucositis

Oral mucositis is a frequent complication of head and neck radiation therapy (RT), occurring in up to 91% of patients.[7] It also develops as an adverse effect of chemotherapy in 20 to 40% of cases.[8] The basal layer of the oral epithelium has a high mitotic activity, making it more susceptible to radiation injury, and leading to oral mucositis.[9] Symptoms usually appear after the first week of RT and may last for several months.[2]

Oral lesions include erythema, atrophy, swelling, and ulcerations that may be covered by pseudomembranes. Patients report debilitating pain, loss of taste, eating, drinking, and speaking difficulties, which may require parental nutrition.[2] Radiation treatment has sometimes to be paused, affecting the overall prognosis of the malignancy.[10] Oral mucositis usually resolves within two to three weeks after finishing radiotherapy.[10][11][3]

Xerostomia

Xerostomia is an expected side effect of radiotherapy on the head and neck, which starts soon after initiating treatment and may be irreversible in some cases.[1] The salivary glands are susceptible to radiation, and even low doses to the head and neck can cause cell death and fibrosis, leading to gland dysfunction.[2]

Salivary gland damage results in hyposalivation (decreased salivary flow) and thickening of the saliva, perceived as xerostomia. This causes speaking, eating, and swallowing difficulties and affects taste perception. Also, a decreased salivary flow makes the oral cavity more vulnerable to candidiasis, gingivitis, and dental caries.[2]

Oropharyngeal Candidiasis

Patients undergoing radiation therapy for head and neck cancer are at an increased risk of developing fungal infections. This may be a consequence of the salivary flow reduction experienced during radiation therapy [1] and possibly, also due to a decreased phagocytic activity of salivary granulocytes.[5]

Clinically, radiation-related oropharyngeal candidiasis may present as pseudomembranous, erythematous, or angular cheilitis.[12] The erythematous forms are harder to diagnose as they may be confused with radiotherapy-induced oral mucositis. Oral candidiasis most commonly presents as a scrapable white pseudomembrane or erythematous patch on the tongue, commissures, and palate.[5] Patients usually report a burning sensation in the mouth, dysgeusia, and halitosis. The occurrence of oral candidiasis depends on the salivary flow rate, oral hygiene status, and, if present, the severity of oral mucositis.[13]

Dysgeusia

Dysgeusia is an unpleasant or abnormal alteration of taste, frequently described as metallic.[3] Infections, head and neck trauma or surgery, drugs, and radiotherapy have been identified to cause dysgeusia.[14]

Altered taste perception is reported by about 70% of patients receiving radiotherapy, which is also linked to loss of appetite and weight. Symptoms appear after the second or third week of treatment, and taste perception usually goes back to normal 60 to 120 days after finishing radiotherapy.[5]

Radiation-related Caries

Radiation-related caries is a very aggressive type of tooth decay that develops in dental surfaces normally refractive to caries.[15] The labial surfaces of the cervical areas are mostly involved.[2] The lingual aspect of lower anterior teeth, which are not normally prone to caries, are also affected by radiation-related caries.[16] The etiology is not well understood, but it is believed to be caused by the decreased salivary flow levels experienced during radiotherapy and direct radiation damage to the dental structures.[16]

Radiation caries are generalized and precipitate about six to twelve months after head and neck radiation treatment. Lesions usually begin as enamel cracks and fractures and evolve into brown-black enamel discoloration.[16] If the lesions are not diagnosed and treated promptly, they will soon progress to incisal-cuspal wear and widespread cervical caries, eventually leading to the amputation of the crown.[16]

Osteoradionecrosis (ORN)

Osteoradionecrosis (ORN) of the jaws is a late complication of radiation therapy of the head and neck, where exposed irradiated bone becomes necrotic and fails to heal for at least three months with no signs of tumor recurrence.[17] The condition mainly affects the mandible and rarely develops in the maxilla.[2] 

Risk factors include poor oral health and hygiene, pre-head and neck radiation surgery, dental surgery, and tobacco and alcohol consumption.[3] The risk of ORN is also incremented when the radiation dose exceeds 60 Gy.[18] Osteoradionecrosis clinically presents as exposed bone with or without mucosal dehiscence, and as the condition advances, intraoral and extraoral fistula and later pathological fracture may develop.

Clinical Significance

Pre-radiotherapy Dental Management

Pre-radiation dental treatment is done to prevent further infection and avoid the need for invasive procedures during and after radiotherapy. All efforts are directed at minimizing the risk and severity of head and neck radiotherapy complications: oral mucositis, oropharyngeal candidiasis, xerostomia, radiation-related caries, and osteoradionecrosis.

During this stage, patients must be informed of the importance of maintaining excellent oral hygiene and given careful oral care instructions and dietary advice. All carious lesions must be restored. Scaling, oral prophylaxis, and periodontal therapy should be performed. All sharp cusps and restorations should be smoothened.[2] If the patient wears dentures, these should be checked to ensure they are well-fitted and not at risk of causing ulceration.

If a definitive restoration cannot be placed due to time limitations, carious tissue must be removed and teeth restored with glass ionomer cement. Amalgam restorations should be avoided as they often backscatter and cause local mucosal irritation.[19]

Performing pre-radiation dental extractions is a controversial topic since the evidence available is contradictory. Some studies have shown that pre-radiation extractions may increase the risk of osteoradionecrosis, and others show that the lack of pre-radiation extractions increases this risk too. If extractions are performed before the first cycle of radiation therapy, the ideal interval between extraction and the beginning of RT should be between ten days and three weeks so that complete soft tissue healing occurs.[2]

The urgency to start RT is a critical dictating factor in whether to extract teeth or not.[20] Radiation treatment should not be unnecessarily delayed as it diminishes a patient's survival. Wound dehiscence could be a limiting factor in delaying therapy at times. Daily wound dressing, irrigation, and antibiotic cover may hasten the process.

Finally, obtaining dental impressions pre-radiation therapy for study models that will be useful for fabricating soft mouth guards or medicament-carrying trays is recommended.[2]

Management of Oral Complications During Radiotherapy

Oral Mucositis

Uncomplicated oral mucositis is usually self-limiting, and palliative care tends to be sufficient.[8] The main management recommendations include basic oral care, dietary advice, and pain control. Low-level laser therapy is also recommended to prevent or reduce the severity of oral mucositis in adult patients receiving radiotherapy alone or in combination with chemotherapy.[21]

Basic oral care includes enhancing the patient's oral hygiene (increasing frequency of tooth brushing, clean interproximally, using soft brushes, and replacing the toothbrush more often); rinsing the oral cavity with bland rinses like saline water or sodium bicarbonate every four hours; lubricating the oral mucosa using mousses or topical barrier gels, and avoiding irritants like tobacco or alcohol.[8]

Foods that may unintendedly injure or irritate the oral mucosa must be avoided, such as hard, sharp, and spicy food.[8] Consultation with a dietician to facilitate oral intake may be required. A bland, high-calorie, soft diet is recommended.[11]

MASCC/ISOO guidelines recommend topical morphine 0.2% for pain management.[21] Other formulations are available such as the "magic mouthwash," which contains an anesthetic, diphenhydramine, and antacid and may have steroids and anti-micotics.[8] However, topical morphine 0.2% has proven to be more efficient.[8]

Xerostomia

The aim of treatment is symptomatic relief, and management mainly includes patient education measures. Patients must be advised to frequently sip water, chew sugar-free gum, suck sugar-free candy, avoid caffeine, tobacco, alcohol, and hard or dry food, and increase fluid intake to prevent dehydration.[22] Bland rinses used for oral mucositis are also recommended for xerostomia to clean the oral tissues. Saliva substitutes are available, but they have limitations: short duration of action, unpleasant taste, unreliability, and high cost.

Pharmacological treatment is reserved for when local measures are ineffective. The systemic drugs pilocarpine and cevimeline are approved by the FDA for managing xerostomia.[22] They both work on muscarinic receptors. However, the adverse effects of these drugs limit their use; pilocarpine side effects include nausea, diarrhea, sweating, and rhinitis. Bronchospasm has also been reported.[22] Pilocarpine is contraindicated in patients with glaucoma, asthma, and hypertension.[23] Cevimeline also induces increased sweating and should be avoided in patients with glaucoma and cardiac issues.

Oropharyngeal Candidiasis

Oropharyngeal candidiasis is managed with topical treatment in milder cases, and systemic antifungals are indicated when disseminated candidiasis is suspected, the patient is at higher risk (myelosuppression, immunodeficiency) and upon failure of topical measures.

The first-line treatment includes topical fluconazole, miconazole, or nystatin. When systemic antifungals are indicated, fluconazole is the drug of choice. Generally, systemic therapy with fluconazole is more efficient than topical antifungals in patients with cancer.[3] Patients should be advised to maintain excellent oral hygiene, lubricate the oral mucosa, and avoid tobacco and alcohol consumption.[2]

Management of Oral Complications After Radiotherapy

Radiation-related Caries

Prevention, early detection, and treatment are vital. The risk of radiation caries should be explained to patients before, during, and after radiation therapy. Prevention regimens must be implemented immediately after the cancer diagnosis.[16] Patients must be referred to a dental professional for a complete check-up.[16] During this stage, the oral needs are identified and treated: new restorations, adjustment of old restorations, endodontic and periodontal treatment, and extraction of unrestorable teeth.[16]

The importance of maintaining excellent oral hygiene must be emphasized, including gentle tooth brushing with a soft-bristled toothbrush twice or four times per day, interproximal cleaning, and fluoride supplementation.[16] Sodium bicarbonate rinses are also recommended.[2] Fluoride trays and topical fluoride applications significantly reduce the risk of radiation caries.[2] Prescription fluoride should be utilized minimally twice per day. Furthermore, as radiation caries are believed to be partly caused by hyposalivation, managing xerostomia is essential.[2]

The restoration of radiation caries poses a tremendous challenge to the dentist, mainly due to limited mouth opening, poor access and visibility, and changes in the tooth structure that alter the adhesive properties of dental materials.[15] Resin-modified glass ionomer cement (GIC) is a good option to restore these teeth due to its fluoride-releasing property. It also has a quick and simple bonding procedure and better strength than conventional GIC.[24][25]

When the pulp is involved, endodontic treatment is preferred over extraction.[15] Root canal treatment can be a more appropriate option, even in unrestorable teeth, to control the infection and symptoms and decrease the risk of osteoradionecrosis. However, limited mouth opening and difficulty in rubber dam isolation may pose a few challenges, like doing a suitable access cavity.[2]

Some authors suggest opening the tooth through the vestibular or incisal surfaces or decoronating teeth with gross caries to improve access.[2] If extraction is unavoidable minimal trauma technique by an experienced dental surgeon should be done. A limited number of teeth should be removed in a single visit.[2]

Osteoradionecrosis

The mainstay of osteoradionecrosis treatment is prevention. Oral health should be stabilized before radiotherapy. All necessary dental and periodontal interventions must be performed, oral hygiene instructions carefully instructed, and oral health closely monitored before, during, and after radiation treatment. This is to avoid infection and the need for invasive procedures during and after radiation treatment.[3]

If a tooth is deemed unrestorable, it is recommended that endodontic treatment is tried first. If extraction becomes unavoidable, general practitioners can extract teeth located outside the radiation field, or if in the radiation field, the dose must be less than 50 Gy.[2] However, referral to the oral and maxillofacial surgery department must be made when teeth are in radiation fields of more than 50 Gy.[2]

The patient must be referred to a tertiary maxillofacial department for treatment if osteoradionecrosis is diagnosed.[2] The condition can be managed with conservative measures, ranging from oral hygiene improvement, antibiotics, and analgesics, to sequestrectomy, ultrasound, and hyperbaric oxygen therapy.[26] 

The need for more radical surgical management depends on the severity of the condition.[26] Pharmacological treatment with pentoxifylline, clodronate, or tocopherol, can also be indicated as adjuvants.[27]

Other Issues

Recurrence of Cancer

Chronic nonhealing ulcers with indurated margins usually indicate recurrence.[28] Suspicious cases should be biopsied and sent for histopathological examination.[28]

Enhancing Healthcare Team Outcomes

The management of head and neck cancer involves oncologists, radiotherapists, dental practitioners, dental hygienists, nurses, dieticians, and a counselor.[20][29][30] Communication between the dentist and the oncology radiotherapist regarding the treatment plan is important, e.g., the area covered in the radiation field, unilateral or bilateral salivary gland involvement, and radiation dose.[30] 

Often, it is a race against time to start therapy and treat the dental ailment. During the therapy usually, complications are handled by radiotherapists and nurses, and dental inputs can help to manage the condition better. The need for meticulous planning by the dentist and discussion with other professionals involved in managing the patient is highly recommended to lower morbidity and improve outcomes.[30]

While delivering radiation treatment in the head and neck region, pre-RT dental management, along with management of adverse effects during and after RT, can have a major effect on the patient's quality of life.[30][31] For good treatment outcomes, interprofessional communication between a dentist who specializes in dealing with patients with head and neck cancer, an oncologist, and a radiotherapist is vital.[30]

Nursing, Allied Health, and Interprofessional Team Interventions

Since oral intake is compromised because of complications like radiation mucositis and limited mouth opening, the role of dietitians is important.[32] Communication with the treating dentist and dental hygienists is important as a high-carbohydrate diet may predispose to radiation caries.[32] The role of nurses in radiation therapy patients can range from educating about self-care and providing psychosocial support to collaborating with the treating physician in managing adverse effects.[33]

Proper training and expertise of nurses can provide better care.[33] The dentist should also train the spouse or other caretaker family members in maintaining excellent oral hygiene.[34][35] Counseling by psychologists can help patients in overcoming stress because of compromised quality of life.[34][35]