Vol. 88 No.

2 August 1999

ORAL SURGERY
ORAL MEDICINE
ORAL PATHOLOGY

MEDICAL MANAGEMENT UPDATE

Editor: James R. Hupp

Oral cancer
Complications of therapy
Sol Silverman, Jr., MA, DDS,a San Francisco, Calif
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:122-6)

Each year, approximately 31,000 new cases of oral

cancer are diagnosed in the United States. Unfortunately,
5-year survival rates are a dismal 50% despite improvements in surgical and radiation techniques as well as
advances in chemotherapy.
Smaller and localized tumors have a far lower mortality rate and less morbidity than advanced lesions.
Thus, staging of oral cancers is critically important,
inasmuch as more advanced tumors require more
aggressive therapy. As is to be expected, the more
intensive therapeutic approaches used to improve
survival also increase the complications. Therefore,
preventing or at least minimizing these complications
is vital to quality of life and successful rehabilitation.

RADIATION EFFECTS
Ionizing radiation delivered in doses that will kill
cancer cells induces unavoidable changes in the
surrounding normal tissues, causing compromises in
function and host defenses and severe complications.1-5
Mucocutaneous changes
Unless intraoral or interstitial treatment is used, most
patients will develop some erythema and moderate
tanning of the skin in the treatment portal. Hair follicles are quite radiosensitive; therefore, if hair is in the
treatment beam, it will cease to grow and will fall out.
This is often transient.
The acute oral mucosal reaction (mucositis) is
secondary to radiation-induced mitotic death of the
basal cells in the oral mucosa. If the radiation is delivaProfessor of Oral Medicine.
Accepted for publication Mar 25, 1999.
Copyright 1999 by Mosby, Inc.
1079-2104/99/$8.00 + 0 7/13/99401

122

ered at a rate compatible with the ability of the oral

mucosa to regenerate, then only mild mucositis will be
seen. Oral microorganisms probably play a role in
aggravating the impaired epithelium. Smoking is also a
factor.6 Clinically observed late or postradiationinduced atrophy and telangiectasis of the mucosa often
increase the risk for pain and/or necrosis.
Management of acute mucositis may sometimes
require a 1-week interruption of therapy. Topical anesthetics (eg, viscous xylocaine) may be of some value,
but the pain usually requires systemic analgesic
drugs.7,8 Because infections may be associated, appropriate diagnosis and antimicrobial agents must be
considered for either fungal or bacterial organisms.
Viral infections are rarely a complication of radiationinduced mucositis. A short course of systemic prednisone (40 to 80 mg daily for not more than 1 week) has
been helpful in reducing inflammation and discomfort.

Loss of taste
Taste buds, which occur primarily in the circumvallate and fungiform papillae, are very sensitive to radiation. Because of their location in the tongue, they are
included in the beam of radiation for most oral cancers.
Therefore, patients will develop a partial (hypogeusia)
or, more typically, a complete (ageusia) loss of taste
during treatment. The cells comprising the taste buds
usually will regenerate within 4 months after treatment. However, the degree of long-term impairment of
taste is quite variable from patient to patient.
Dietary consultations regarding recipes with pleasing
texture and perceptible and pleasing tastes are essential to
improve intake of food. However, there are tremendous
patient-to-patient differences, and this precludes standard
recommendations. Failure in taste perception, in addition

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Silverman 123

to pain, dysphagia, hyposalivation, and depression, is

associated with a loss of pleasure in eating and thus in a
loss of appetite. Weight loss, weakness, malaise, and
dehydration often follow. This is further complicated
when prior surgery has caused problems in mastication
and swallowing. Trials with zinc supplements (such as
ZnSO4) exceeding the usual recommended daily doses
(ie, the recommended daily allowance) appear to be
helpful.9 We have prescribed 100 mg of elemental zinc
daily with success in some patients. Although zinc serves
as a critical enzyme in many biochemical reactions, its
role in taste and saliva remains unknown. Saliva probably
has a modulating effect on the acuity of some tastes (sour,
bitter, salt, sweet) through biochemical interactions and
probably provides an ionic environment in signal transduction for taste cells.

dry mouth, although some favorable reports have been

published. In some patients in whom the salivary
complaint is related to the thickness of the saliva (ie,
there is an excess of mucous-type secretions), guaifenesin (Organidin NR) may help as a mucolytic agent
(200-400 mg, 3-4 times daily).10,11

Salivary function
Exposure of the major salivary glands to the field of
ionizing radiation induces fibrosis, fatty degeneration,
acinar atrophy, and cellular necrosis within glands. A
critical dose level has not been identified. The serous
acini appear to be more sensitive than the mucinous
acini. During irradiation, the glandular secretions are
usually diminished, thick, sticky, and bothersome to
the patient. Some patients are unable to produce more
than 1 mL of pooled saliva in 10 minutes. The duration
of this depressed salivary function varies from patient
to patient. Some regeneration can occur several months
after treatment, and the undesirable signs and symptoms of xerostomia (discomfort and difficulty in
speech and swallowing) may be modified. However,
recovery of adequate saliva for oral comfort and function may take up to 12 months. In some patients, the
saliva remains inadequate indefinitely and is the source
of major posttreatment complaints. It is when both
parotid glands are exposed to the treatment beam that
saliva diminution is most marked and the prognosis for
recovery is worst. Obviously, the higher the dosage of
irradiation, the worse the prognosis for xerostomia.
Frequent sips of water and water rinses are essential
for partial control of radiation-induced xerostomia.
Sugarless chewing gum and tart candy may be helpful.
In some patients, pilocarpine hydrochloride (solution or
tablets) has been effective in stimulating saliva production (5 mg 3 or 4 times daily). Side effects can include
sweating and stomach discomfort. Another salivary
gland stimulant, bethanechol (Urecholine), administered as tablets in divided doses varying from 75 to 200
mg daily, has been helpful in many xerostomic patients.
However, the drug has not been approved by the US
Food and Drug Administration for this effect.
Synthetic saliva solutions and saliva substitute lubricants have been of limited help in most patients with

Nutrition
Because of the painful mucositis, loss of taste, and
partial xerostomia, the lack of desire or frank inability
to eat is a common and almost universal complaint in
patients receiving external irradiation to the oral cavity.
A resultant weight loss tends to produce weakness,
inactivity, discouragement, further anorexia, and
susceptibility to infection. Therefore, close attention is
given to food intake and weight maintenance during
treatment and follow-up. Anemia, bleeding, or immune
deficiencies have not been complications of head and
neck radiation.
Dental caries
Patients who have not shown any degree of caries
activity for years may develop dental decay and
varying degrees of disintegration after irradiation. The
cervical areas are most typically affected. This condition appears to be due to the lack of saliva as well as to
changes in the salivas chemical composition.12
Radiation-induced dental effects primarily depend on
salivary changes, but direct irradiation of teeth may
also alter the organic or inorganic components in some
manner, making them more susceptible to decalcification. Remineralization of enamel by a salivary substitute has been reported. There do not appear to be any
clinical or histologic pulpal differences between
noncarious human adult teeth that have been in the
primary field of radiation and noncarious human adult
teeth that have not.
To prevent or at least minimize radiation caries, oral
hygiene must be maximal, including intensive home
care and frequent office visits for examination and
prophylaxis. Mouth rinsing is essential. Antiseptic
mouth rinseseg, chlorhexidine, if it can be toleratedare helpful in eliminating debris and controlling microbial flora. Daily applications of topical
fluoride, in the form of a solution for mouth rinsing,
a gel delivered by means of a tray, or a paste or gel
that is brushed on, are effective.13,14 Attempts should
be made to increase salivary flow by either local or
systemic means. Foods and beverages containing
sucrose should be avoided as much as possible. If
carious lesions develop, removal and restoration
should take place immediately. When indicated,
appropriate use of dental x-ray imaging is in order for
the monitoring of caries activity.

124 Silverman

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

August 1999

Candidiasis
Infections of the mouth by Candida albicans are
commonly seen in irradiated patients and are related to
the alterations in saliva.15 Clinically, the signs may be
confused with radiation mucositis or other sources of
infection. Candidiasis is usually painful. Management
is primarily accomplished through the use of antifungal
drugs. Systemic administration (200 mg of ketoconazole daily with food or 100 mg of fluconazole daily) is
usually more effective with respect to both response
and compliance. Duration of treatment depends on
control of signs and recurrences, inasmuch as complete
elimination of Candida from the oral flora usually does
not occur. Topical administration entails the use of
nystatin or clotrimazole tablets dissolved orally.
Because of pain from mucositis and dryness, patients
may experience difficulty in dissolving tablets topically.
A suspension is an alternative form of treatment, but
often this is not as effective as tablets because of limited
contact time between drug and fungus. Antiseptic
mouth rinses similar to those used for caries control
may be helpful, if they can be tolerated. In addition,
topical (viscous xylocaine) or systemic analgesics may
be required. Keeping the mouth moist is essential.
There is always a possibility of the development of
fungal resistance or a need for higher dosages when
these agents are used for prolonged periods of time.

surgery and antibiotics may be helpful in healing as a

result of angiogenesis induced by increased oxygen.
However, reproducible benefits remain uncertain.17-20

Osteoradionecrosis
Osteonecrosis is one of the more serious complications of head and neck irradiation for cancer. Bone
cells and vascularity may be irreversibly injured.
Fortunately, in many cases devitalized bone fragments
will sequestrate and lesions will spontaneously heal.
However, when radiation osteonecrosis is progressive,
it can lead to intolerable pain or fracture and may
necessitate jaw resection.
The risk for developing spontaneous osteoradionecrosis is somewhat unpredictable, but it is related
to the dose of radiation delivered and bone volume
(usually more than 6000 cGy).16 The mandible is at
higher risk than the maxilla. The risk is increased in
dentulous patients, even more so if teeth within the
treatment field are removed after therapy. Spontaneous
bone exposure usually occurs more than 1 year after
radiation is completed. The risk for osteonecrosis
continues indefinitely after radiation therapy.
If osteonecrosis does not progress clinically or radiographically, the usual management involves periodic
observation. If flares (swelling, suppuration, pain)
occur only occasionally, antibiotics are usually effective. If pain and/or flares occur too frequently or present
other difficulties for the patient, surgery must be considered. Hyperbaric oxygen treatments together with

Soft tissue necrosis

Soft tissue necrosis may be defined as the occurrence
of a mucosal ulcer in irradiated tissue that has no
residual cancer. The incidence of soft tissue necrosis is
related to dose, time, and volume irradiated. The risk is
far greater with interstitial implantation and intraoral
techniques because of the higher irradiation doses used.
Soft tissue necrosis is usually quite painful. Optimal
hygiene is required and analgesics are usually helpful,
but antibiotics are generally of little help in relieving pain
and promoting healing. Because these ulcerations are
often at the site of the primary tumor, periodic assessment for recurrence is essential until the necrosis heals.
DENTAL TREATMENT PLANNING
In view of the risk that accompanies high-dose irradiation, special attention to preradiation dental planning appears critical.21 Factors important in the dental
management of these patients include the following:
(1) anticipated bone dose; (2) pretreatment dental
status, dental hygiene, and retention of teeth that will
be exposed to high-dose irradiation; (3) extraction
techniques; (4) allowance of adequate healing time for
teeth extracted before radiotherapy; and (5) patient
motivation and capability of complying with preventive measures.
Because many infections occur months or years after
treatment, it is evident that the tissue changes induced
by radiation persist for long periods of time and may be
irreversible. Therefore, extreme care must be taken in
evaluating the status of the teeth and periodontium
before, during, and after treatment, and optimal oral
and periodontal hygiene must be maintained because
of the lowered biologic potential for healing in
response to physical irritation, chemical agents, and
microbial organisms. Such attention is critical because
of the potentially progressive nature of radiation
osteonecrosis, which may involve large segments of
bone and present a major therapeutic problem, possibly
requiring extensive resection.
It is impossible to establish precise formulas for
managing preradiation and postradiation dental problems. Extractions are considered primarily for teeth
with a prognosis that is poor because of such conditions as advanced periodontal disease, extensive caries
activity, and periapical lesions. Other considerations
are sources of chronic soft tissue irritation (trauma)
and the degree of patient cooperation in preventive
home care and dental office programs. The decision is
modified further for each patient on the basis of prog-

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Silverman 125

nosis, age, desires, economic considerations, and radiation delivery.

Reported studies and personal experience do not
substantiate the advisability of extracting all teeth
before treatment as a preventive measure. When teeth
are extracted before or after radiation, the alveolar
bone must be evenly trimmed and carefully smoothed
so that a primary tissue closure is possible. This is
necessary because suppression of bone cell viability
diminishes remodeling; if a suitable alveolectomy is
not performed, the resulting alveolar ridge will be
irregular, and this may increase the risk of subsequent
bone exposure and discomfort. A minimum of 7 to 10
days is arbitrarily allowed for initial healing before
radiation is instituted; however, if the situation permits,
more time is preferable, up to 14 or even 21 days.
Because dosages are fractionated, healing can usually
continue before damaging levels of radiation are delivered to a surgical area. Obviously, teeth completely out
of the treatment field are not affected similarly.
The use of antibiotics during the healing period is
important to minimize infection. Whenever possible,
an attempt is made to retain teeth to support toothborne
appliances for the tentatively planned rehabilitation of
these patients.
The periodontium is maintained in optimal condition
by means of periodic routine periodontal procedures.
When areas exposed to radiation are treated, extreme
care is exercised and antibiotics may be selectively
administered. Fluoride applications (daily, in the form of
mouth rinses or gels) appear to aid in minimizing tooth
decalcification and caries in these patients. There are no
unusual contraindications for endodontic procedures.22
In conclusion, review of the literature and our own
experience indicate that carefully controlled studies are
necessary before more definitive guidelines can be
formulated for managing dental structures that have
been or are to be radiated. This is particularly true
because of newer fractionation and dose regimens of
radiation and combinations with chemotherapy, all of
which are designed to attain better responses and
survival rates. Each case must be managed individually
on the basis of the patients needs, the status of the
tumor, and the risks known to exist for dental health in
irradiated tissues; a single-formula approach for all
patients is contraindicated.

equate, recurrences follow. Rehabilitation is usually

planned at the time of initial treatment and frequently
involves maxillofacial prosthodontics.

SURGERY
Surgical approaches to cancer control include
removal of malignant and adjacent normal tissue
(margins) in an attempt to remove all cancerous cells.
Such surgery results in defects that cause problems
with appearance and function, which in turn can cause
severe emotional disturbances. If the margins are inad-

CHEMOTHERAPY
Chemotherapy alone is not an effective treatment for
oral cancers, although some regimens can enhance
radiation and surgery. The toxic effects of chemotherapy are usually acute and may add to the morbidity
of treatment. Therefore, treatment must often strike a
balance between the adverse side effects of
chemotherapy and the benefits of trying to increase
response and survival.
When cytotoxic chemotherapeutic drugs are used, it
is extremely important to keep the patient free of oral
foci of infection and pain, minimize local infection and
bacteremia, and enable the patient to maintain a nutritious diet.23 The chemotherapeutic agents used to eradicate tumor production also adversely affect normal
cells, particularly those that have relatively high
turnover rates, such as oral epithelial tissues. The
depressant effect of therapy on oral epithelial mitoses
can result in thinning and ulceration of the tissues as
well as salivary gland and taste dysfunctions. The oral
ulcerations may be due to trauma, direct cellular cytotoxicity from the chemotherapeutic agents, increased
susceptibility to microorganisms as a result of
neutropenia (bone marrow suppression), or a combination of these factors.

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Reprint requests:
Sol Silverman, Jr., MA, DDS
Department of Oral Medicine
University of California, San Francisco
Box 0422, S-619B
San Francisco, CA 94143

CALL FOR LETTERS TO THE EDITOR

A separate and distinct space for Letters to the Editor was established by Larry J. Peterson, editor in
chief of Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics in his Editorial
in the January 1993 issue.
Dr Peterson also encouraged brief reports on interesting observations and new developments to be
submitted to appear in this letters section as well as Letters commenting on earlier published articles.
Please submit your letters and brief reports for inclusion in this section. Information for authors for
the Journal appears in this issue of Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and
Endodontics.
We look forward to hearing from you.