Professional Documents
Culture Documents
2 August 1999
ORAL SURGERY
ORAL MEDICINE
ORAL PATHOLOGY
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)
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
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
Silverman 123
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
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.
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
Silverman 125
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.
REFERENCES
1. Cooper JS, Fu K, Marks J, Silverman S Jr. Late effects of radiation therapy in the head and neck region. Int J Radiat Oncol Biol
Phys 1995; 31:1141-64.
2. List MA, DAntonio LL, Cella DF, et al. The performance status
scale for head and neck cancer patients and the functional
assessment of cancer therapyhead and neck scale: a study of
utility and validity. Cancer 1996;77:2295-301.
3. Silverman S. Radiation and chemotherapy injury: Pathophysiology, diagnosis, and treatment. Crit Rev Oncol Hematol
1993;15:63-7.
4. Silverman S. Oral cavity toxicity secondary to chemotherapy
and radiation therapy. In: Madu J, editor. Chemoradiation.
Philadelphia: Lea & Febiger: 1993.
5. Silverman S Jr. Oral cancer. 4th ed. Ontario, Canada: B.C.
Decker; 1998. p. 91-102.
6. Rugg T, Saunders MI, Dische S. Smoking and mucosal reactions
to radiotherapy. Br J Radiol 1990;63:554-6.
7. Bruera E, Pereira J, Watanabe S, et al. Opioid rotation in patients
with cancer pain: a retrospective comparison of dose ratios
between methadone, hydromorphone, and morphine. Cancer
1996;78:852-7.
8. Levy MH. Pharmacologic treatment of cancer pain. N Engl J
Med 1996;335:1124-32.
9. Ripamonti C, Zecca E, Brunelli C, et al. A randomized,
controlled clinical trial to evaluate the effects of zinc sulfate on
cancer patients with taste alterations caused by head and neck
irradiation. Cancer 1998;82:1938-45.
10. Reikle JW, Hafermann MD, Johnson JT, et al. Oral pilocarpine
for radiation-induced xerostomia: integrated efficacy and safety
126 Silverman
11.
12.
13.
14.
15.
16.
17.
Reprint requests:
Sol Silverman, Jr., MA, DDS
Department of Oral Medicine
University of California, San Francisco
Box 0422, S-619B
San Francisco, CA 94143