October 2003, Vol. 69, No.

9 585 Journal of the Canadian Dental Association

C L I N I C A L P R A C T I C E
S
urgery, chemotherapy and radiotherapy are the
options for treatment of head and neck cancers. Each
modality is associated with a number of considera-
tions related to treatment of the cancer and quality of life
of the patient. When the oral cavity and salivary glands are
exposed to high doses of radiation, there can be dramatic
effects on the patients oral health. This paper offers the
dental team an overview of the consequences associated
with radiotherapy to facilitate collaboration with the
patients medical team
1,2
(summarized in Table 1).
Oral Assessment before Treatment
To a signicant degree, the oral problems associated with
radiation therapy can be prevented or minimized through
optimal management. The acute effects of radiation ther-
apy include mucositis, altered salivary gland function and
risk of mucosal infection. The long-term effects are due to
changes in the vascularity and cellularity of soft tissue and
bone, damage to the salivary glands and increased collagen
synthesis resulting in fibrosis. These changes lead to
hypovascularity, hypocellularity and hypoxia of the tissues.
The affected bone and soft tissue have a reduced capacity
to remodel and may be at increased risk of infection and
necrosis.
A consultation with a dental team experienced in caring
for patients undergoing treatment for head and neck cancer
should be completed before the start of therapy.
3,4
Many
oral conditions, such as poor oral hygiene, broken teeth,
defective restorations and periodontal disease, are likely to
precipitate complications during and after a course of
radiation therapy (Table 1).
In addition to the clinical examination, a thorough ra-
diographic examination is crucial to determine the presence
of inflammatory periapical abnormalities, periodontal
status, other dental disease and tumour invasion of bone.
A panoramic radiograph plus selective periapical or
bitewing lms (or both) should be available for preradio-
therapy dental assessments. Consultation with the patients
physician on the timing, nature (external beam radiother-
apy or radioactive implant) and features (location and size
of treatment elds, radiotherapy fractionation and total
dose) of the radiotherapy is essential for overall risk assess-
ment and scheduling of any required dental intervention.
Oral and Dental Management Related to
Radiation Therapy for Head and Neck Cancer
Pamela J. Hancock, BSc, DMD
Joel B. Epstein, DMD, MSD, FRCD(C)
Georgia Robins Sadler, BSN, MBA, PhD
A b s t r a c t
The clinical management of squamous cell carcinoma of the head and neck causes oral sequelae that can compro-
mise patients quality of life and necessitate abandonment or reduction of optimal therapeutic regimens, which in
turn reduces the odds of long-term survival. Such sequelae can be prevented or at least better managed if dental
and medical health care providers work together. It is therefore essential that dentists have an understanding of
cancer therapy and a sound working knowledge of the prevention and management options for the oral sequelae
of cancer treatment. This paper offers the dental team an overview of the consequences associated with radiother-
apy, as well as a systematic overview of preventing or managing acute and chronic conditions before and during
radiotherapy. In addition, it reviews considerations for continued treatment needs during the patients lifetime.
MeSH Key Words: cranial irradiation/adverse effects; osteoradionecrosis/prevention & control; stomatitis/prevention & control;
xerostomia/prevention & control
J Can Dent Assoc 2003; 69(9):58590
This article has been peer reviewed.
Journal of the Canadian Dental Association 586 October 2003, Vol. 69, No. 9
Hancock, Epstein, Sadler
All teeth, but especially those located within the radia-
tion elds, should be closely evaluated. A UK study found
that only 11.2% of patients who reported regular visits with
a general dentist before a diagnosis of oral cancer were
considered to have no dental conditions that required treat-
ment before radiation therapy.
5
The criteria used for dental
extractions before radiation therapy are not universally
accepted and are subject to clinical judgement. However,
teeth in the high-dose radiation eld should be considered
for extraction before radiotherapy if they are nonrestorable;
if they require significant restorative, periodontal or
endodontic intervention or if they have moderate to severe
periodontal disease (pockets of 5 mm or more).
6
Factors to consider when assessing preradiotherapy
dental status include the overall condition of the patients
dentition (caries, periapical status, inammatory periapical
abnormalities), previous dental care, current oral hygiene,
the urgency of the cancer treatment, the planned therapy
(radiation elds and dose) and the prognosis of the cancer
therapy (cure or palliation). A more aggressive dental
management strategy should be considered for patients
with limited previous dental care, poor oral hygiene and
evidence of past dental or periodontal disease (Table 2).
During Therapy
Monitoring of the oral cavity should be increased during
radiation therapy in an effort to decrease the severity of side
effects. Systematically applied oral hygiene protocols may
reduce the incidence, severity and duration of oral compli-
cations.
7
This, in turn, reduces the odds that patients
optimal therapeutic course will need to be modied, which
thereby increases patients odds of survival. Therefore, it is
imperative that patients continue their oral hygiene
regimen throughout their course of cancer therapy.
8
The
patients self-care procedures should include frequent
brushing with a soft-bristled toothbrush and uoride tooth-
paste or gel to help prevent plaque accumulation and
demineralization or caries of the teeth.
3
Side Effects of Radiation
The oral tissues directly affected by head and neck
radiation therapy include the salivary glands, the mucosal
membranes, the jaw muscles and bone. Dry mouth
(xerostomia) is a common and signicant consequence of
head and neck radiotherapy. Because of the loss of saliva,
patients with xerostomia are more susceptible to
Table 1 Strategies for oral and dental management in relation to radiotherapy for head and
neck cancer
Component of care Notes
Before radiotherapy
Denitive diagnosis Tumour size and type
Medical history Prior cancer history, risk factors
Dental knowledge Past and current dental care
Oral hygiene Current practices
Complete dental examination Mucosa, dentition, periodontium, TMJ
Radiographic examination Panoramic, selected periapical, bitewing
Whole salivary ow rates Resting (> 0.1 mL/minute), stimulated (> 1.0 mL/minute)
Adjunctive tests as indicated Pulp tests, specic cultures (fungal, viral, bacterial)
Prognosis (cure or palliation)
Proposed radiation therapy Timing, dose, elds
During radiotherapy
Maintenance of good oral hygiene Brushing 2 to 4 times daily with soft-bristled brush; ossing daily
Daily topical uoride Custom trays, brush-on prescription-strength uoride
Frequent saline rinses
Lip moisturizer (non-petroleum based)
Passive jaw-opening exercises to reduce trismus
After radiotherapy
Complete dental work that was deferred during radiotherapy
Maintain integrity of teeth Especially those in radiation elds
Frequent follow-up appointments Check for oral hygiene, xerostomia, decalcication, decay, ORN,
metastatic disease, recurrent disease, new malignant disease
TMJ = temporomandibular joint, ORN = osteoradionecrosis
Table 2 Criteria for preradiotherapy extractions
Caries (nonrestorable)
Active periapical disease (symptomatic teeth)
Moderate to severe periodontal disease
Lack of opposing teeth, compromised hygiene
Partial impaction or incomplete eruption
Extensive periapical lesions (if not chronic or well localized)
October 2003, Vol. 69, No. 9 587 Journal of the Canadian Dental Association
Oral and Dental Management Related to Radiation Therapy for Head and Neck Cancer
periodontal disease, rampant caries, and oral fungal and
bacterial infections. Mucositis, characterized by inamma-
tion and ulceration of the oral mucosa, is the most signi-
cant acute side effect reported by patients and is a potential
source of life-threatening infection. Almost all patients
undergoing head and neck radiation therapy experience
conuent mucositis by approximately the third week of
treatment.
9,10
Another potential consequence of radiotherapy to the
oral cavity is brosis around the muscles of mastication,
leading to trismus. It is believed that jaw exercises may limit
the severity of trismus, but they will not mobilize brosis
once it has occurred.
11,12
Bone exposed to high levels of
radiation undergoes irreversible physiologic changes
including narrowing of the vascular channels (endarteritis),
which diminishes blood ow to the area, and loss of
osteocytes. The bone essentially becomes nonvital, which
leads to limited remodelling of bone and limited healing
potential.
Xerostomia
Systemic sialagogues may increase the production of
natural saliva from functional glands. There is no optimal
substitute for saliva that can be used when glands are
nonfunctional. Pilocarpine (Salagen) has shown promising
effects in increasing saliva but is only effective for salivary
glands with residual function.
13
Cevimeline (Evoxac), a
new sialagogue approved for use in the United States for
Sjogrens disease, may increase salivary ow in patients
undergoing head and neck radiotherapy. Two alternative
medications that may be benecial in stimulating salivary
glands include anethole trithione (Sialor) and bethanechol
(Urecholine)
14
(Table 3).
Although saliva replacements such as UniMist (Westons
Health), Mouth Kote (Parnell Pharmaceuticals) and Oral
Balance Gel (Laclede Pharmaceuticals) are poor salivary
substitutes, as they primarily attempt to mimic the texture
of saliva but do not simulate the rheologic properties, the
antimicrobial factors (e.g., antibodies, antimicrobial
proteins) and other components of saliva, patients may nd
that they offer some relief. Oral Balance Gel may be the
best accepted by patients because of its extended duration
of effect.
15,16
Sugarless gum or lozenges may stimulate
salivary secretion in patients with residual salivary gland
function. Sugar-free popsicles, plain ice cubes or ice water
may be used to keep the mouth cool and moist. Eating
foods high in ascorbic acid, malic acid or citric acid will
stimulate the glands to increase salivary ow, but this
measure is not recommended in dentate patients because
the acidity can further irritate oral tissues and contribute to
the demineralization of teeth.
For the prevention of rampant dental demineralization
and caries, patients should apply a 1.1% neutral sodium
uoride gel daily (for at least 5 minutes), using a custom-
tted vinyl tray if possible.
3,11,17
This practice may be started
on the rst day of radiation therapy and continued daily as
long as salivary ow rates are low and the mouth remains dry.
High-potency uoride brush-on gels and dentifrices may be
considered in those who are unable or unwilling to comply
with the use of uoride trays.
Oral Infection
Health care providers should be concerned about
preventing local and systemic infections in addition to
managing oral symptoms. Treating infections as soon as
they are detected will help to reduce pain, as well as the
spread of infection. A fungal, bacterial or viral culture is
recommended if infection is suspected.
In patients undergoing head and neck radiotherapy,
Candida colonization tends to increase throughout the
course of treatment and remains increased if xerostomia
occurs.
18,19
Nystatin rinses are the most widely prescribed
treatment for oral fungal infections, despite a lack of proven
efficacy. Nystatin has an unpleasant avour and may cause
nausea and vomiting,
17
and its high sucrose content is a
major concern in dentate patients. For more severe
infections, the use of a systemic antifungal medication
such as uconazole (Diucan) or amphotericin B is recom-
mended.
3
Systemic amphotericin B must be used with
caution because of its potential to cause liver toxicity
4
(Table 3). Topical antifungals to consider include clotrima-
zole, ketoconazole and chlorhexidine.
Chlorhexidine gluconate (0.12%; Peridex), an antimicro-
bial rinse, has both antifungal and antibacterial properties in
addition to antiplaque effects; however, its value is still
unconrmed. Its tendency to stain teeth and its alcohol
content, which can irritate inamed tissues, are draw-
backs.
18
If chlorhexidine is used, it is important to note that
nystatin and chlorhexidine should not be used concurrently,
because chlorhexidine binds to nystatin, rendering both
ineffective;
17
furthermore, chlorhexidine should be used at
least 30 minutes before or after the use of any other topical
agents with which it may bind.
For cancer patients with viral infections, such as
Herpes simplex 1, acyclovir (Zovirax, GlaxoSmithKline) or
derivatives are recommended for both prophylaxis and
treatment.
3,20
Penciclovir (Denavir, GlaxoSmithKline), a
newer topical antiviral with increased tissue penetration, is
now available.
Oral Mucositis
Maintaining a self-care regimen may decrease the
incidence of mucositis.
17
While many products and
combined product rinses have been suggested for clinical
use, they have not been studied in randomized controlled
trials and should be used with caution. Among the
concerns with the use of combinations of rinses are the risks
that some products may interfere with the action of others,
Journal of the Canadian Dental Association 588 October 2003, Vol. 69, No. 9
Hancock, Epstein, Sadler
and compounding may result in dilution of the individual
products to levels that may be ineffective.
The use of a common oral rinse, such as isotonic saline
or sodium bicarbonate, is often suggested, but no studies
have conrmed any benecial effect upon mucositis.
3
It has
been suggested that patients begin prophylactic rinses with
chlorhexidine to prevent the onset of microbial infection,
gum inammation and bleeding, and to reduce the risk of
caries. While some authors report that a chlorhexidine oral
rinse has potential effects on mucositis, others report no
effects,
9
and no effects have been reported for radiation-
induced mucositis to date. Use of other oral rinses, includ-
ing commercial alcohol-based mouthwashes and hydrogen
peroxide rinses, should be discontinued because of their
drying and irritating effects on the oral mucosa.
The discomfort of mucositis can be reduced with coat-
ing agents, topical anesthetics and analgesics, although
systemic analgesics are frequently needed.
3
Aluminum
Table 3 Therapies to deal with specic problems associated with head and neck radiotherapy
Therapy Dose Contraindications
Systemic sialogogue
Pilocarpine (Salagen
a
), 5 mg 36 tabs daily Asthma, glaucoma, liver dysfunction
Bethanechol (Urecholine), 25 mg 1 tab 3 times daily Asthma, peptic ulcer, bladder inammation
Anethole dithiolethione (Sialor),
b
25 mg 1 tab 3 times daily Hypersensitivity
Cevimeline (Evoxac),
c
30 mg 1 tab 3 times daily Asthma, glaucoma, liver dysfunction,
cardiovascular disease
Antifungal agents
Systemic
Fluconazole (Diucan), 100 mg 1 tab once daily Liver or renal dysfunction, coumadin, warfarin
Amphotericin B, 0.1 mg/mL (compounded) 5 mL, rinse > 1 minute, Hypersensitivity to drug class
then spit (3 times daily)
Topical
Nystatin suspension, 100,000 U/mL 510 mL, rinse, then spit Other topical medications;
(3 times daily) do not use in dentate patients
Nystatin cream or ointment, 100,000 U/g Apply to dry denture surface Hypersensitivity to drug class
3 times daily
Clotrimazole cream, 1% Apply to dry denture surface Hypersensitivity to drug class
3 times daily
Clotrimazole troches, 10 mg Dissolve in mouth, Hypersensitivity to drug class, liver dysfunction
5 times daily for 14 days
Ketoconazole, 200 mg 1 or 2 tabs by mouth Liver dysfunction
4 times daily
Chlorhexidine rinse (Peridex), 0.12% 510 mL, rinse > 1 minute, Hypersensitivity to drug class
then spit (3 times daily)
Mucosal coating agents
Milk of magnesia/Maalox 1530 mL by mouth Hypersensitivity to drug class, renal dysfunction
4 times daily as needed
Diphenhydramine liquid (Benadryl), 12.5 mg/5 mL 510 mL, rinse > 1 minute, Asthma, glaucoma, cardiovascular disease,
then spit (4 times daily) pulmonary disease
Sucralfate, 1 g /10 mL 510 mL, rinse > 1 minute, Hypersensitivity to drug class, renal dysfunction
then spit (4 times daily)
Topical anesthetics or analgesics
Benzydamine hydrochloride (Tantum) 5 mL, rinse > 1 minute, Hypersensitivity to drug class
then spit (as needed)
Viscous lidocaine, 4% 5 mL, rinse >1 minute, Hypersensitivity to drug class,
then spit (as needed) liver dysfunction
Doxepin suspension, 0.5% (compounded) 5 mL, rinse > 1 minute, Hypersensitivity to drug class, glaucoma,
then spit (4 times daily) urinary retention
Benzocaine, 20% in Orajel Apply topically to areas of pain Hypersensitivity to drug class
Sucralfate, 1 g/10 mL 510 mL, rinse > 1 minute, then Hypersensitivity to drug class, renal dysfunction
spit or swallow (4 times daily)
a
Brand names are included only as examples and not to promote any one product. The manufacturers are as follows: Salagen, Pharmacia; Urecholine, Merck;
Sialor, Paladin; Evoxac, SnowBrand Pharmaceuticals; Diucan, Pzer; Fungizone, Bristol-Myers Squibb Canada Inc.; Peridex, Zila Pharmaceuticals; Maalox, Novartis
Consumer Health; Benadryl, Pzer Consumer Healthcare; Tantum, 3M Pharmaceuticals; Orajel, Del Laboratories.
b
Over the counter; not available in the United States.
c
Not available in Canada.
October 2003, Vol. 69, No. 9 589 Journal of the Canadian Dental Association
Oral and Dental Management Related to Radiation Therapy for Head and Neck Cancer
hydroxide/magnesium hydroxide (milk of magnesia-
Maalox) and sucralfate have been suggested as coating
agents for the oral mucosa. Sucralfate suspension may also
be helpful in the treatment of oral pain, although the
effect on mucositis has not been clearly documented
2125
(Table 3).
Topical anesthetics used in rinse form may result in
intense but short-term anesthesia. However, the localized
anesthesia can increase the risk of aspiration, and their
systemic absorption can cause cardiac effects. When oral
mucosal pain is present, benzydamine hydrochloride
(Tantum), doxepin suspension 0.5% or an antihistamine
such as diphenhydramine can be prescribed.
10,26
Benzydamine is the only medication available that has been
shown in multicentre, double-blind controlled studies to
reduce mucositis and pain in patients with head and neck
cancer.
10,26
Topical anesthetics, such as benzocaine, viscous
lidocaine and topical benzocaine can be applied locally to
sites of pain with a swab or a soft vinyl mouth guard
3
(Table 3).
Of all available mouth rinses that can be used as treat-
ments for mucositis, the least costly and easiest for patients
to prepare is a simple mouthwash comprising a teaspoon
(10 mL) of salt and a teaspoon (10 mL) of baking soda
(sodium bicarbonate) in 8 ounces (250 mL) of water.
A comparison among salt and soda mouthwashes, mouth-
washes prepared from lidocaine and diphenhydramine with
Maalox, and mouthwashes of 0.12% chlorhexidine
gluconate found that the 3 options were equally effective
in the treatment of chemotherapy-induced mucositis.
27
Although chlorhexidine may also decrease oral Candida
counts and bacterial levels, studies on radiotherapy patients
have shown no effect on mucositis. According to the current
literature, good oral hygiene, topical uorides for caries
prevention and benzydamine offer the greatest benets.
After Therapy
After the completion of radiation therapy, acute oral
complications usually begin to resolve. Patients should
continue to follow an oral health self-care regimen to keep
the teeth and gums healthy and to facilitate repair of any
residual oral damage. Oral exercises should be continued or
introduced to reduce the risk and severity of trismus.
Additional dietary counselling sessions may be appropriate
for patients who must make long-term dietary adaptations
to accommodate permanent changes to their oral cavity
produced by surgery and radiation. The referral of patients
to support groups may also be a useful adjunct to patients
return to optimal functioning.
Long-term management and close follow-up of patients
after radiation therapy is mandatory. It is critical to
remember that patients at highest risk for a new or recur-
rent cancer are those previously treated for cancer of the
upper aerodigestive tract. Therefore, careful examination to
detect signs of recurrence or new primary malignant lesions
is essential. Close follow-up will facilitate the management
of any chronic complications that may occur, such as
xerostomia, mucosal sensitivity, increased risk of cavities,
candidiasis and persisting risk of osteoradionecrosis
(ORN).
The period after completion of cancer therapy is an
excellent time for patients to resolve any oral concerns that
were previously deemed not medically necessary and for
which care had been deferred. Since patients with cancer
are more likely to experience a recurrence or a new cancer
and require further therapy, resolution of any deferred
dental care should be a top priority.
Osteoradionecrosis
ORN is irreversible, progressive devitalization of irradi-
ated bone. The condition is characterized by necrotic soft
tissue and bone that fails to heal spontaneously. Most cases
of ORN occur in the mandible, where vascularization is
poor and bone density is high. Clinical manifestations of
ORN may include pain, orofacial stulas, exposed necrotic
bone, pathologic fracture and suppuration.
2830
One-third
of ORN cases occur spontaneously. Among cases where
ORN has been initiated by trauma the majority result from
extraction of teeth. The incidence of ORN is twice as
high in dentate patients as it is among edentulous patients.
Poor oral hygiene and continued use of alcohol and tobacco
may also lead to rapid onset of ORN.
31
Over the years, ORN has been treated by numerous
methods with variable success.
28
Hyperbaric oxygen ther-
apy is considered an adjunctive treatment for ORN, often
used in conjunction with surgery, and has been associated
with better success rates than surgery alone.
29,30,32,33
Conclusions
The complications of radiotherapy must be considered
thoroughly so that every effort is undertaken to minimize
the oral morbidity of these patients before, during and after
cancer treatment and throughout the patients lifetime. C
Dr. Hancock is a resident in the department of oral medicine,
University of Washington, Seattle, WA; and dentist in the department
of dentistry, Fraser Valley Cancer Centre, Surrey, B.C., and the
department of dentistry, Vancouver Hospital and Health Sciences
Centre, Vancouver, B.C.
Dr. Epstein is professor, department of oral medicine and diagnostic
sciences, director, interdisciplinary program in oral cancer, College of
Dentistry and College of Medicine, University of Illinois, Chicago,
Illinois; head of the department of dentistry, Vancouver Hospital and
Health Sciences Centre, Vancouver, BC; and staff, British Columbia
Cancer Agency, Vancouver, B.C.
Dr. Sadler is associate clinical professor of surgery, University of
California San Diego School of Medicine, and associate director for
community outreach, Moores UCSD Cancer Center, La Jolla,
California.
Correspondence to: Dr. J. Epstein, Department of Oral Medicine
and Diagnostic Sciences, MC 838 801 South Paulina St.,
Chicago, IL 60612. E-mail: [email protected].
Journal of the Canadian Dental Association 590 October 2003, Vol. 69, No. 9
Hancock, Epstein, Sadler
The authors have no declared nancial interests in any company
manufacturing the types of products mentioned in this article.
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