Side effects of radiation treatment for head and neck cancer

Radiation therapy (RT) is often used to treat head and neck cancer. The goal of radiation therapy is to kill cancer cells. Because these cells divide and grow at a faster rate than normal cells they are more likely to be destroyed by radiation. In contrast although they may be damaged, healthy cells generally recover. 

If RT is recommended the radiation oncologist sets up a treatment plan

that includes the total dose of radiation to be administered, the number of treatments to be given, and their schedule. These are based on the type and location of the tumor, the patient's general health, and other present or past  treatments.

The side effects of RT for head and neck cancer are divided into early (acute) and long term (chronic) effects. Early side effects occur during the course of therapy and during the immediate post therapy period (approximately 2-3 weeks after the completion of a course of RT). Late effects can manifest any time thereafter, from weeks to years later.

I described my own experiences getting RT in my book “My Voice” in chapter 4 ”Getting irradiated”, and chapter 5 "Life after irradiation".

A lecture about life challenges after laryngectomy that includes discussion of late side effects of radiation can be viewed on YouTube.

Patients are usually most bothered by the early effects of RT, although these will generally resolve over time. However, because long term effects may require lifelong care it is important to recognize these in order to prevent them and/or deal with their consequences. Knowledge of the radiation side effects can allow their early detection and proper management. 

Individuals with head and neck cancer should receive counseling about the importance of smoking cessation. In addition to the fact that smoking is a major risk factor for head and neck cancer, the risk of cancer in smokers is further enhanced by alcohol consumption. Smoking can also influence cancer prognosis. When smoking is continued both during and after RT, it can increase the severity and duration of mucosal reactions, worsen the dry mouth (xerostomia), and compromise patient outcome. Patients who continue to smoke while receiving RT have a lower long-term survival rate than those who do not smoke.

Early side effects

Early side effects include inflammation of the oropharyngeal mucosa (mucositis), painful swallowing (odynophagia), difficulty swallowing (dysphagia), hoarseness, lack of saliva (xerostomia), orofacial pain, dermatitis, nausea, vomiting, and weight loss. These complications can interfere with, and delay treatment. To some degree these side effects occur in most patients and generally dissipate over time.

The severity of these side effects is influenced by the amount and method by which the RT is given, the tumor’s location and spread, and the patient’s general health and habits (i.e. continued smoking, alcohol consumption).

Skin damage

Radiation can cause a sunburn-like damage to the skin which can be further aggravated by chemotherapy. It is advisable to avoid exposure to potential chemical irritants, direct sun and wind, and local application of lotions or ointments prior to RT that might change the depth of radiation penetration. There are a number of skin care products that can be used during radiation treatment to lubricate and protect the skin.

Dry mouth 

The loss of saliva production (or xerostomia) is related to the administered irradiation dose and the volume of salivary tissue irradiated. Drinking adequate fluids and rinsing and gargling with a weak solution of salt and baking soda are helpful ito refreshing the mouth, loosen thick oral secretions, and alleviate mild pain.

Artificial saliva and constant wetting of the mouth with water may also be helpful.

Alterations in taste

Radiation can induce changes in taste as well as tongue pain. Such side effects can further decrease food intake. The altered taste and tongue pain gradually dissipate in most patients over a six month period, although in some cases taste recovery is incomplete. Many individuals experience a permanent alteration in their taste. 

Inflammation of the oropharyngeal mucosa (mucositis)

Radiation, as well as chemotherapy, damage the oropharyngeal mucosa resulting in mucositis, which develops gradually, usually 2-3 weeks after starting RT. Its incidence and severity depend upon the field, total dose and duration of RT. Chemotherapy can aggravate the condition. Mucositis can be painful and interfere with food intake and nutrition. .

Management includes meticulous oral hygiene, dietary modification, and topical anesthetics combined with an antacid and antifungal suspension ("cocktail"). Spicy, acidic, sharp, or hot food should be avoided,as well as alcohol. Secondary bacterial, viral (i.e. Herpes), and fungal (i.e. Candida) infections are possible. Control of the pain (using opiates or gabapentin) may be needed.

Mucositis can lead to nutritional deficiency. Those who experience significant weight loss or recurrent episodes of dehydration may require feeding through a gastrostomy feeding tube.

Orofacial pain

Orofacial pain is common in patients with head and neck cancer. It occurs in up to half of the patients before RT,  80% of patients during treatment and about one third of patients six months after treatment. The pain can be caused by mucositis which can be aggravated by concurrent chemotherapy, and by damage from the cancer, infection, inflammation, and scarring due to surgery or other treatments.

Pain management includes the use of analgesics and narcotics.

Nausea and vomiting

RT may cause nausea. When it occurs, it generally happens from two to six hours after a RT session and lasts about two hours. Nausea may or may not be accompanied by vomiting.

Management includes:

·       Eating small, frequent meals throughout the day instead of three large meals. Nausea is often worse if your stomach is empty.
·       Eating slowly, chewing the food completely, and staying relaxed.
·       Eating cold or room temperature foods. The smell of hot or warm foods may induce nausea.
·        Avoiding difficult to digest foods, such as spicy foods or foods high in fat or accompanied by rich sauces.
·        Resting after eating. When lying down, the head should be elevated about 12 inches.
·        Drinking beverages and other fluids between meals instead of drinking beverages with meals.
·        Drinking 6-8 ounce glasses of fluid per day to prevent dehydration. Cold beverages, ice cubes, popsicle, or gelatin are adequate.
·        Eating more food at a time of the day when one is less nauseous.
·        Informing one's health care provider before each treatment session when one develops persistent nausea.
·        Treating persistent vomiting immediately as this can cause dehydration.
·        Administering anti-nausea medication by a health care provider.

Persistent vomiting can result in the body losing large amounts of water and nutrients. If vomiting persists for more than three times a day and one does not drink enough fluids, it could lead to dehydration. This condition can cause serious complications if left untreated.

Signs of dehydration include:

·        Small amount of urine
·        Dark urine
·        Rapid heart rate
·        Headaches
·        Flushed, dry skin
·        Coated tongue
·        Irritability and confusion

Persistent vomiting may reduce the effectiveness of medications. If persistent vomiting continues, radiation treatments may be stopped temporarily. Fluids administered intravenously assist the body in regaining nutrients and electrolytes.

Tiredness (fatigue)

Fatigue is one of the most common side effects of RT. RT can cause cumulative fatigue (fatigue that increases over time). It usually lasts from three to four  weeks after treatment stops, but can continue for up to two to three months.

Factors that contribute to fatigue are anemia, decrease food and liquid intake, medications, hypothyroidism, pain, stress, depression, and lack of sleep (insomnia) and rest.

Rest, energy conservation, and correcting the above contributing factors may ameliorate the fatigue. 

Other side effects

These include trismus and hearing (see below) problems.

LATE side EFFECTS 

Late side effects include permanent loss of saliva, osteoradionecrosis, ototoxicity, fibrosis, lymphedema, hypothyroidism, and damage to neck structures.

Permanent dry mouth

Although the dry mouth (xerostomia) improves in most people with time, it can be long lasting.

Management includes salivary substitutes or artificial saliva and frequent sips of water. This may lead to frequent urinaton especially during the night, in men with prostatic hypertrophy and in those with small bladders. Available treatment includes medications such as salivary stimulants (sialagogues), pilocarpine, amifostine, cevimeline, and acupuncture.

Osteoradionecrosis of the jaw

This is one potentially severe complication that can necessitate surgical intervention and reconstruction. Depending on the location and extent of the lesion, symptoms may include pain, bad breath, taste distortion (dysgeusia), “bad sensation”, numbness (anesthesia) , trismus, difficulty with mastication and speech, fistula formation, pathologic fracture, and local, spreading, or systemic infection.

The jaw bone (mandible) is the most frequently affected bone, especially in those treated for nasopharyngeal cancer. Maxillary involvement is rare because of the collateral blood circulation it receives.

Tooth extraction and dental disease in irradiated areas are major factors in the development of osteoradionecrosis.  In some cases it is necessary to remove teeth before RT if they will be in the area receiving radiation and are too decayed to preserve by filling or root canal. An unhealthy tooth can serve as a source of infection to the jawbone, that can be particularly difficult to treat after radiation. 


Repair of nonrestorable and diseased teeth prior to RT may reduce the risk of this complication. Mild osteoradionecrosis can be conservatively treated with debridement, antibiotics, and occasionally ultrasound. When necrosis is extensive, radical resection, followed by microvascular reconstruction is often used.

Dental prophylaxis can reduce this problem. Special fluoride treatments may help with dental problems along with brushing, flossing, and regular cleaning by a dental hygienist.

A home care dental lifelong routine is recommended:

1. Flossing each tooth and brushing with toothpaste after each meal.

2. Brushing the tongue with a tongue brush or a soft bristled toothbrush once a day.

3. Rinsing with a baking soda rinse daily. Baking soda helps neutralize the mouth.
One teaspoon added to 12 oz. of water. The baking soda rinse can be used throughout the day.

4. Using fluoride in fluoride carriers once a day. Fluoride carriers are custom made by a professional dentist. A 1.1% sodium fluoride or 0.4 % stannous fluoride is placed in the fluoride carriers and applied over the teeth for 10 minutes. One should not rinse, drink, or eat for 30 minutes after fluoride application. 

Hyperbaric oxygen therapy (HBO) has been often used in patients at risk or those who develop osteoradionecrosis of the jaw. However, the available data are conflicting about the clinical benefit of HBO for prevention and therapy of osteoradionecrosis.

Patients should remind their dentists about their RT prior to extraction or dental surgery. Osteonecrosis may be prevented by administration of a series of  HBO therapy before and after these procedures. This is recommended if the involved tooth is in an area that has been exposed to a high dose of radiation. Consulting the radiation oncologist who delivered the radiation treatment can be helpful in determining the extent of prior exposure.   

Fibrosis and trismus

High doses of radiation to the head and neck can result in fibrosis. This condition may be aggravated after head and neck surgery where the neck may develop a woody texture and have limited movement. Late onset of fibrosis can also occur in the pharynx and esophagus, leading to stricture, and temporomandibular joint problems.

Fibrosis of the muscles of mastication can lead to the inability to open the mouth (trismus or lockjaw) which can progress over time. Generally eating becomes more difficult but articulation is not affected. Trismus impedes proper oral care and treatment and may cause speech/swallowing deficits. This condition may be intensified by surgery prior to radiation. Patients likely to develop trismus are those with tumors of the nasopharynx, palate, and maxillary sinus. Radiation of the highly vascularized temporomandibular joint (TMJ) and muscles of mastication can often lead to trismus. Chronic trismus gradually leads to fibrosis. Trismus impedes proper oral care and treatment and may cause speech/swallowing deficits. Forced opening of the mouth, jaw exercises and the use of a dynamic opening device (TherabiteTM) can be helpful. This device is increasingly used during radiation therapy as a prophylactic measure to prevent trismus.

Exercise can reduce neck tightness and increases the range of neck motion. One needs to perform these exercises throughout life to maintain good neck mobility. This is especially the case if the stiffness is due to radiation. Receiving treatment by experienced physical therapies who can also break down the fibrosis is very helpful. The earlier the intervention, the better it is for the patient. A new treatment modality using external laser is also available. There are physical therapy experts in most communities who specialize in reducing swelling.

Fibrosis in the head and neck can become even more extensive in those who have had surgery or further radiation. Post radiation fibrosis can also involve the skin and subcutanous tissues, causing discomfort and lymphedema. 

Swallowing dysfunction, due to fibrosis often requires a change in diet, pharyngeal strengthening, or swallow retraining especially in those who have had surgery and/or chemotherapy. Swallowing exercises are increasingly used as a preventing measure.
Partial or total oropharyngeal stricture can occur in severe cases.

Wound healing problems

Some laryngectomees may manifest wound healing problems following surgery, especially in areas that have received RT. Some may develop a fistula ( an abnormal connection between the inside of the throat and the skin). Wounds that heal at a slower pace can be treated with antibiotics and dressing changes by specialists.

Lymphedema

Obstruction of the cutaneous lymphatics results in lymphedema. Significant pharyngeal or laryngeal edema may interfere with breathing and may require temporary or long term tracheostomy. Lymphedema, strictures, and other dysfunctions predispose patients to aspiration and the need for a feeding tube.

Hypothyroidism

RT is almost always associated with hypothyroidism. The incidence varies; it is dose-dependent and increases as time elapsed since the RT.

Neurological damage

RT to the neck can also affect the spinal cord, resulting in a self-limited transverse myelitis, known as "L’hermitte syndrome". The patient notes an electric shock-like sensation mostly felt with neck bending (flexion). This condition rarely progresses to a true transverse myelitis which is associated with Brown-Séquard syndrome. (A loss of sensation and motor function caused by the lateral cutting of the spinal cord).

RT can also cause peripheral nervous system dysfunction resulting from external compressive fibrosis of soft tissues and reduced blood supply caused by fibrosis. Pain, sensory loss, and weakness are the most commonly observed clinical features of peripheral nervous system dysfunction. Autonomic dysfunction with resultant orthostatic hypotension (an abnormal decrease in blood pressure when a person stands up) and other abnormalities can also be seen.

RT of head and neck cancer seemed to have adverse but insignificant effects on the cognitive functions of the patients.

Damage to the the ear (ototoxicity) 

Radiation to the ear may result in serous otitis (otitis with effusion). High doses of irradiation can cause and sensorineural hearing loss (damage to the inner ear, the auditory nerve, or the brain). 

Damage to neck structures

Neck edema and fibrosis are common after RT. Over time the edema may harden, leading to neck stiffness. Damage can also include carotid artery narrowing (stenosis) and stroke, carotid rupture, oropharyngo-cutaneous fistula (the last two are associated also with surgery), and carotid artery baroreceptors damage leading to permanent and proxysmal (sudden and recurrent) hypertension.  

Carotid artery stenosis: The carotid arteries in the neck supply blood to the brain. Radiation to the neck has been linked to carotid artery stenosis or narrowing, representing a significant risk for head and neck cancer patients, including many laryngectomees. Stenosis can be diagnosed by ultrasound as well as angiography. It is important to diagnose carotid stenosis early, before a stroke has occurred.

Treatment includes removal of the blockage (endarterectomy), placing a stent (a small device placed inside the artery to widens it) or a prosthetic carotid bypass
grafting.

Hypertension due to baroreceptors damage: Radiation to the head and neck can damage the baroreceptors located in the carotid artery. These baroreceptors help in regulating blood pressure by detecting the pressure of blood flowing through them, and sending messages to the central nervous system to increase or decrease the peripheral vascular resistance and cardiac output. Some individual treated with radiation develop labile or paroxysmal hypertension.

Labile hypertension. In this condition the blood pressure fluctuates far more than usual within the day. It can rapidly soar from low (e.g.120/80 mm Hg) to high (e.g. 170/105 mm Hg). In many instances these fluctuations are asymptomatic but may be associated with headaches. A relationship between blood pressure elevation and stress or emotional distress is usually present.

Paroxysmal hypertension. Patients exhibit sudden elevation of blood pressure (which can be greater than 200/110 mm Hg) associated with an abrupt onset of distressful physical symptoms, such as headache, chest pain, dizziness, nausea, palpitations, flushing, and sweating. Episodes can last from 10 minutes to several hours and may occur once every few months to once or twice daily. Between episodes, the blood pressure is normal or may be mildly elevated. Patients generally cannot identify obvious psychological factors that cause the paroxysms. Medical conditions that can also cause such blood pressure swings need to be excluded (e.g. pheochromocytoma).

Both of these conditions are serious and should be treated. Management can be difficult and should be done by experienced specialists.  Dr Samuel Mann from Weill-Cornell Medical Center in New York City is one of the leading experts in treating paroxysmal hypertension. 

More information about complications of RT can be found at the National Cancer Institute Web site.