Management of the Patient

Undergoing Radiotherapy
or Chemotherapy

Edward Ellis Ill C 1 1 \ P 'I' E T

i

- -

DENTAL MANAGEMENT OF PATIENTS UNDERGOING Beginning of Radiotherapy

RADIOTHERAPY TO HEAD AND NECK Impacted Third Molar Removal Before Radiotherapy
Radiation Effects on Oral Mucosa Method of Dealing w i t h Carious Teeth After
Radiation Effects o n Salivary Glands Radiotherapy
Treatment of Xerostomia Tooth Extraction After Radiotherapy
Radiation Effects o n Bone Denture Wear i n Postirradiation Edentulous Patients
Other Effects o f Radiation Use o f Dental Implants i n Irradiated Patients
Evaluation of Dentition Before Radiotherapy Management of Patients Who Develop
Condition of Residual Dentition Osteoradionecrosis
Patient's Dental Awareness DENTAL MANAGEMENT OF PATIENTS ON SYSTEMIC
Immediacy o f Radiotherapy CHEMOTHERAPY FOR MALIGNANT DISEASE
Radiation Location Effects o n Oral Mucosa
Radiation Dose Effects o n Hematopoietic System
Preparation of Dentition for Radiotherapy and Effects o n Oral Microbiology
Maintenance After Irradiation General Dental Management
Method of Performing Preirradiation Extractions Treatment of Oral Candidosis
Interval Between Preirradiation Extractions and

DENTAL MANAGEMENT OF PATIENTS experience some undesirable effect. Any neoplasm can
UNDERGOING RADIOTHERAPY be destroyed by radiation if the dose delivered to the
TO HEAD-- AND NECK
-" - - -- neoplastic cells is sufficient. The limiting factor is the
Radiotherapy (i.e., radiation therapy, x-ray treatment) is amount of radiation that the surrounding tissues can
a common therapeutic modality for malignancies of the tolerate.
head and neck. Approximately 30,000 cases of head and Radiotherapy destroys neoplastic (and normal) cells by
neck cancer occur each year. Many of these are man- interfering with nuclear material necessary for reproduc-
aged by therapeutic irradiation. Its use is ideally tion, cell maintenance, or both. The faster the cellular
predicated on the ability of the radiation to destroy neo- turnover, the more susceptible the tissue is to the damag-
plastic cells while sparing normal cells. In practice, how- ing effects of radiation. Thus neoplastic cells, which are
ever, this is never actually achieved, and normal tissues usually reproducing at higher rates than normal tissue,
406 PART IV m Infections

are selectively destroyed (relatively). In practice, normal Treatment of Xerostomia

tissues with rapid turnover rates are also affected to some After radiotherapy, patients often complain of chronic
degree. Therefore hematopoietic cells, epithelial cells, dry mouth. At present no general agreement exists con-
and endothelial cells are affected soon after treatment cerning how to prevent these changes. Unfortunately, in
when radiotherapy begins. many cases, xerostomia never improves substantially,
Early in the course of radiotherapy, the oral mucosa and exogenous replacement of saliva is necessary. For the
shows the effects of treatment. The changes in and simplest form of replacement, water can be sipped
around the oral cavity as the result of destruction of the throughout the day. In addition, several saliva substitutes
fine vasculature are most notable to dentistry. Salivary can be obtained without a prescription at the pharmacy.
glands and bone are relatively radioresistant, but because These substitutes contain several of the ions in saliva and
of the intense vascular compromise resulting from radio- other ingredients (e.g., glycerin) to mimic the lubricating
therapy, these tissues bear a considerable hardship in the action of saliva. Unfortunately, artificial salivas on the
long run. market do not possess the protective proteins that are
present in the salivary secretions. The patients are there-
fore still prone to the problems induced by xerostomia.
Radiation Effects on Oral Mucosa
For comfort, however, many patients seem to be just as
The initial effect of radiotherapy on the oral mucosa, satisfied with plain water as artificial salivas and keep
which is seen in the first 1 or 2 weeks, is an erythema that small quantities available at all times to sip.
may progress to a severe mucositis with or without ulcer- Efforts to stimulate the patient's residual saliva have met
ation. Pain and dysphagia may be severe and make ade- with some success. The Food and Drug Administration
quate nutritional intake difficult. These mucosal reac- (FDA) has now approved the use of two medications to
tions begin to subside after completion of the course of stimulate the flow of saliva: (1) pilocarpine hydrochloride
radiotherapy. The taste buds, also comprised of epithelial and (2) cevimeline hydrochloride have been shown to
cells, show similar reactions. Loss of taste is a prominent relieve symptoms of xerostomia for patients with xerosto-
complaint early in treatment and gradually returns, de- mia.' Both are parasympathomimetic agents that function
pending on the quantity and quality of saliva that remains primarily as muscarinic agonists, causing stimulation of
after treatment. exocrine gland secretion. This can increase the production
The long-term effects of radiotherapy to the oral of saliva, even in patients whose salivary glands have been
mucosa are characterized by a predisposition to breakdown exposed to radiation. An oral dose of 5 mg of pilocarpine
and delayed healing, even after minor insult. The epitheli- four times each day or 30 mg of cevimeline three times a
um is thin and less keratinized, and the submucosa is less day has been shown to improve many symptoms of xeros-
vascular, which gives a pale appearance to the tissue. tomia without significant drug-related side effect^.^ The
Radiotherapy induces 5ubmucosal fibrosis, which makes administration of these medications may prove to be ben-
the mucosal lining of the oral cavity less pliable and less eficial for some patients with postradiation xerostomia.
resilient. Minor trauma may create ulcerations that take
weeks or months to heal. These ulcerations are often diffi-
cult to differentiate from recurrent malignant disease. Radiation Effects on Bone
One of the most severe and complicating sequelae of
radiotherapy for patients with head and neck cancer is
Radiation Effects on Salivary Glands osteoradionecrosis (Fig. 18-2). Basically, osteoradionecro-
Salivary gland epithelium has a very slow turnover rate; sis is devitalization of the bone by cancericidal doses of
therefore the salivary glands might be expected to be radiation. The bone within the radiation beam becomes
radioresistant. However, because of the destruction of the virtually nonvital from an endarteritis that results in
fine vasculature by the radiation, the salivary glands elimination of the fine vasculature within the bone. The
show considerable damage, with resultant atrophy, fibro- turnover rate of any remaining viable bone is slowed to
sis, and degeneration. This manifests clinically as xeros- the point of being ineffective in self-repair. The continu-
tomia (the decreased production of saliva) and gives the al process of remodeling normally found in bone does
patient a "dry mouth." The severity of xerostomia not occur, and sharp areas on the alveolar ridge will not
depends on which salivary glands were within the field of smooth themselves, even with considerable time. The
radiation. A dry mouth may be the patient's most signif- bone of the mandible is denser and has a poorer blood
icant complaint. supply than that of the maxilla. Thus the mandible is the
The effects of xerostomia on the oral cavity are devas- jaw most commonly affected with nonhealing ulcera-
tating. Because saliva is the principal protector of the oral tions and osteoradionecrosis.
tissues, absence results in serious complications. Rampant
"radiation caries" can swiftly destroy the remaining den-
Other Effects of Radiation
tition and predispose the patient to severe infections of
the jaws. Teeth thus affected exhibit decay around the Patients undergoing radiotherapy may have an alteration
entire circumference of the cervical portion (Fig. 18-1). in the normal oral flora, with overgrowth of anaerobic
Periodontitis is also accelerated in the absence of saliva. species and fungi. Most researchers feel that oral flora col-
Dysgeusia, dysphonia, and dysphagia are also caused by onizing the mucous membranes play an important role
xerostomia. in the severity of mucositis and subsequent healing
 ,Mnt~n'yer?~erlt
of tllc Prztierlt Undergoir~~y
Rtzdiotlfer(zpy or Cl~rtnotlferizpy m CHAPTER 18 407

FIG. ": A, Typical clinical appearance of radiation caries. B, Typical radiographic appear-
'

ance of radiation caries. Note the erosion around the cervical portion of the teeth.

pro~ess.~*"andida albicans commonly thrives in the oral tion have residual teeth throughout the course of radio-
cavities of patients who have been irradiated. It is not therapy. Thus the clinician may wonder what to do with
known whether the alteration in the flora is caused by the teeth before irradiation. Should teeth be extracted?
the radiation itself or the resultant xerostornia. Patients This question has no categorical answer; however, sever-
frequently require the application of topical antifungal al factors must be con~idered.~-I~'
agents, such as nystatin, to help control the amount of Comiition of ri'~i~!1lc?1 r i o n t j f i o i i . A11 teeth with a
Candida organisms present. Another oral rinse frequently questionable or poor prognosis should be extracted
prescribed is 0.1% chlorhexidine (Peridex). This agent has before radiotherapy. The more advanced the periodontal
been shown to have potent in vitro antibacterial and condition, the more likely the patient is to develop caries
antifungal effects. When used throughout the course of and continued periodontitis. Although this may not be in
radiation treatment, it has been shown in at least one keeping with usual dental principles, if in doubt, extract.
study to greatly reduce the prevalence and symptoms Extraction in these cases may Fpare the patient months or
associated with radiation-induced m u c o s i t i s . ~ t suse in years of suffering from osteoradionecrosis.
other studies has been equivocal."," The present state of the
I'ttticjrrt'c tfentrzl rrbr~[Link]~s\.
dentition and periodontium is a good clue to the past
care they have received. In patients with excellent oral
Evaluation of Dentition Before Radiotherapy hygiene and oral health, the clinician should retain as
The most feared side effect of radiotherapy is osteora- many of the teeth as possible. Conversely, in patients
dionecrosis. Most patients who develop this complica- who have neglected oral health for years, the chances are
 408 PART IV 117f?ctior~s

. ,' Progressive course of osteoradionecrosis. A, Radiograph showing radiolucencies in right

mandible and around apex of molar tooth. B, Six months later, during which time antibiotics and local
irrigations were used, radiolucent process is spreading into ramus. Molar was removed at this time.
C, Five months after tooth removal, extraction site did not heal and destructive process spread, result-
ing in pathologic fracture of mandible. D, Radiograph after removal of devitalized bone, showing
extent of process. (Courtesy Dr. Richard Scoot, Ann Arbor, MI.)

that they will continue to do so, especially in the face of but must work closely with the patient throughout the
severe xerostornia and oral pain, which will make oral course of radiotherapy and thereafter in an attempt to
hygiene even more difficult. Preradiotherapy patient maintain oral health as optimally as possible.
preparation is similar to preorthodontic patient prepara- Knclintiorl locution. The more salivary glands and
tion. I f an individual cannot or will not care for his or her bone involved in the field of radiation, the more severe
mouth before the application of the braces, it will be will be the resultant xerostomia and vascular compromise
impossible for him or her to do so when faced with future of the jaws. Thus the dentist should discuss with the
obstacles. radiotherapist the locations of the radiation beams and
If the radiotherapist
It::ir!!cJi!iirc ,t; o / r~lrfi!*tlrc~rtr/),v. estimate the severity of the probable xerostomia and
feels that thtrap); must be instituted urgently, there may bone changes. Xerostomia by itself may not result in
r?ot be time to perform the necessary extractions and severe problems if the dentition can be maintained,
allow for initial healing of the extraction sites. In this because the bone is still healthy. It is the combination of
instance the dentist may elect to maintain the dentition xerostomia and irradiated bone that usually causes the
 Management o f the Patient UndergoingRadiotllerapy or Cllemotheropy CHAM'IJR 18 409

problem. In individuals who will have radiation to the alized illness. In severe cases it may be necessary to feed
major salivary glands and a portion of the mandible, the patient via nasogastric tube to maintain a reasonable
preirradiation extractions should be considered. Fre- nutritional status.
quently the radiotherapist agrees to delay the institution After radiation treatment the dentist should set the
of irradiation for 1 to 2 weeks if the dentist feels that time patient every 3 t o 4 months. A prophylaxis is performed
is necessary to allow the extraction sites to begin to heal. during these postirradiation visits, and topical fluoride
Radiation dose. The higher the radiation dose, the applications are made. The patient should be fitted with
more severe is normal tissue damage. The radiotherapist custom trays to deliver topical fluoride applications. The
should discuss with the dentist the amount of radiation patient should be instructed in the use of the trays and
planned for the individual. Frequently the dose is not in daily self-administration of topical fluoride applica-
maximal, and tissue damage may be minimized. This tions. The use of a 1% fluoride rinse for 5 minutes each
tends to make the dentist more conservative in preirradi- day has been found to decrease the incidence of radia-
ation extraction considerations. tion caries." Over-the-counter fluoride rinses currently
Squamous cell carcinomas of the oral cavity make up available can be used without a customized delivery
approximately 90% of malignant tumors for which radi- splint with good success and seem to have better patient
ation therapy is used. Unfortunately, this cancer requires acceptance.
a very large dose of radiation (greater than 6000 rads [60
Gy]) to effect a result. Other malignancies, such as lym-
Method of Performing Preirradiation Extractions
phoma, require much less radiation for a response, and
the oral cavity will therefore be less affected. When the If the decision has been made to extract some or all teeth
total dose falls below 5000 rads (50 Gy), long-term side before radiotherapy, the question become$, "How should
effects, such as xerostomia and osteoradionecrosis, are the teeth be extracted?" In general, the principles of
dramatically decreased. atraumatic exodontia apply. However, the concepts of
bone preservation are disregarded, and an attempt is
made to remove a good portion of the alveolar process
Preparation of Dentition for Radiotherapy along with the teeth and achieve a primary soft tissue clo-
and Maintenance After Irradiation sure. With the onset of radiotherapy, the normal remod-
Every tooth to be maintained must be carefully inspected eling process is inhibited; if any sharp areas of bone exist,
for pathologic conditions and restored to the best state of ulceration occurs with bone exposure. Thus the teeth are
health obtainable. A thorough prophylaxis and topical usually removed in a surgical manner, with flap reflection
fluoride application should be performed before rsdio- and generous bone removal.
therapy. Oral hygiene measures and instructions should Atraumatic handling of the mucoperiosteal flaps is
be demonstrated and reinforced. Any sharp cusps should necessary to ensure a rapid soft tissue healing. Burs or
be rounded to prevent mechanical irritation. Impressions files should be used to smooth the bony edges under
for dental casts should be obtained for fabrication of cus- copious irrigation, because the remodeling capability of
tom fluoride trays to be used during and after treatment. the tissues is greatly decreased after radiotherapy.
Because tobacco use and alcohol consumption irritate the Prophylactic antibiotics are indicated under these
mucosa, the patient should be encouraged to stop these circumstances.
before commencement of radiation therapy.
During radiation treatment the patient should rinse Note: The dentist is i n a race agairr~ttitire. I f tire ii~nrrirrlfoils
the mouth at least 10 times a day with saline rinses. The to heal, the radiotherapy will be delayed. I f thr ralliation is
patient should be placed on chlorhexidine mouth rinses delivered before the wound heals, healing i ill toke rnotrtlis or
twice a day to help minimize the bacterial and fungal lev- even years.
els within the mouth. The dentist should see the patient
each week during the radiotherapy for observation and
oral hygiene evaluations. If an overgrowth of Candida
Interval Between Preirradiation Extractions
albicans occurs, nystatin or clotrimazole topical applica-
and Beginning of Radiotherapy
tions will bring this under control relatively rapidly. The No categorical answer exists to the question of how much
ability of the patient to open the mouth should be care- time should be allowed after extractions before beginning
fully monitored throughout the cause of radiation treat- radiotherapy. Obviously, the sooner radiotherapy is
ment. Radiation causes a progressive fibrosis within the begun, the more beneficial it may be. Thus when the soft
muscles of mastication that makes it difficult for the tissues have healed sufficiently, radio the rap^^ may begin.
patient to adequately open the mouth. Patients should be Traditionally, 7 to 14 days between tooth extraction and
instructed in physiotherapy exercises to maintain the radiotherapy have been ~ u g g e s t e d . ~ , ~ ~ , ' % oauthors
st
preradiation-treatment interincisal dimension. All base their recommendations on the clinical impression
patients must be weighed weekly to determine whether that reepithelialization has occurred in this period. How-
they are maintaining an adequate nutritional status. The ever, radiotherapy should be delayed for .! weeks after
combination of mucositis and xerostomia makes oral extraction, if possible. This helps to ensure that sufficient
intake extremely uncomfortable. However, malnutrition soft tissue healing has occurred. The radiotherapy should
causes further difficulties by delaying healing of the oral be delayed further, if possible, if a local wound dchis-
tissues and giving the patient an overall feeling of gener- cence has occurxed. In this instance daily local wound
410 PART IV m Infectiorls

care with irrigations and postoperative antibiotics are communities and, when present, are usually in select hos-
mandatory until the soft tissues have healed. pitals. A physician that is experienced in hyperbaric med-
icine manages patients referred to these facilities. The
Impacted Third Molar Removal patient usually undergoes one HBO session each day.
Before Radiotherapy Therefore it takes 4 to 6 weeks to get the 20 to 30 treat-
ments before surgery, and 2 weeks of treatment after sur-
If the patient has a partially erupted mandibular third gery. In a prospective clinical trial comparing this regi-
molar, removal may be prudent to prevent pericoronal men with the use of prophylactic antibiotics before den-
infection. In general, however, allowing a tooth that is tal extraction without hyperbaric oxygenation, Marx,
totally impacted within the bone of the mandible to Johnson, and Kline1"ound a significant decrease in the
remain in place is more expeditious than removing it and incidence of osteoradionecrosis (5.4% compared with
waiting for it to heal. 30'X)).
Because considerable controversy exists over how to
manage an extraction surgically in a patient who has
Method of Dealing with Carious
undergone irradiation, because few hyperbaric oxyge-
Teeth After Radiotherapy
nation chambers are available for use, and because the
Teeth that develop postradiotherapy caries must be incidence of severe complications is relatively high, it is
immediately cared for in an attempt to prevent further recommended that an oral and maxillofacial surgeon
spread of infection. Composites and amalgam are the manage the patient who has received irradiation and
materials of choice to repair the defects caused by decay. requires extractions.
Full crowns are probably not warranted, because recur-
rent decay is more difficult to detect under such restora-
tions. Oral hygiene measures, including fluoride applica- Denture Wear in Postirradiation
tion, must be reinforced in any patient who develops
Edentulous Patients
postirradiation caries. Patients who were edentulous before radiotherapy man-
If a tooth has necrotic pulp, endodontic intervention age very nicely with well-constructed dentures. However,
with systemic antibiotics can be carefully performed and patients rendered edentulous just before or after radio-
the tooth ground out of occlusion and maintained. Fre- therapy exhibit more problems with mucosal ulcerations
quently root canal treatment is difficult because of a pro- and subsequent osteoradionecrosis. The normal remodel-
gressive sclerosis of the pulp chamber that occurs in irra- ing process of the alveolar bone cannot smooth even the
diated teeth. In such instances the tooth can simply be most minor irregularities left by extraction. With denture
amputated above the gingiva and left in place. wear, these minor irregularities cause ulceration of the
mucosa.
Soft denture liners might seem an ideal solution for
Tooth Extraction After Radiotherapy patients who have received irradiation. However, the sili-
Can teeth be extracted after radiotherapy and, if so, how? cone soft liners proved to be not particularly useful for
These are probably the most difficult questions to answer. several reasons. At present, patients are probably best
Each dentist has a view on this subject, and the literaiure served with ordinary dentures.
is contradictory. Postirradiation extractions are also the Denture fabrication for patients who were previously
most undesirable extractions the dentist will ever per- edentulous can proceed once the acute effects of irradia-
form, because the outcome is always uncertain. tion have subsided. For patients who underwent extrac-
The answer to the question of whether extractions can tions just before or after radiotherapy, it is prudent to see
be done after radiotherapy is certainly, yes. The more them very frequently after delivery of their dentures to
important question is, How? If the tooth is to be extract- make adjiistments for sore spots that develop before they
ed, the dentist can either perform a simple extraction cause mucosal breakdown and bone exposure.
without primary soft tissue closure or a surgical extrac- When dentures are constructed, the dentist must be
tion with alveoloplasty and primary closure. Either of certain that the denture base and occlusal table are
these techniques yields similar results, with a certain con- designed so that forces are distributed evenly throughout
comitant incidence of osteoradionecrosis. The use of sys- the alveolar ridge and that lateral forces on the denture
temic antibiotics is recommended. are eliminated.
Another technique that has been shown to be effective
and that is gaining in popularity is the use of hyperbaric Use of Dental Implants in Irradiated Patients
oxygen (HRO) before and after tooth extraction. Hyper-
baric oxygen therapy is the administration of oxygen The dental rehabilitation of the edentulous patient who
under pressure to the patient. It has been shown to has received radiation therapy is one of the greatest chal-
increase the local tissue oxygenation and vascular lenges facing the reconstructive dentist. Many patients
ingrowth into the hypoxic tis~ues.'~,~"heusual protocol who have had ablative surgery for malignancy do not
for such treatments is to have between 20 and 30 HRO have the normal anatomy that makes denture wear pos-
dives before extraction and 10 more dives immediately sible. There may be n o vestibules to accommodate a den-
after extractions. HRO chambers are not available in all ture flange.
 Management of the Patient Undergoing Radiotherapy or Chemotherapy . CHAPTER 18 411

Often, portions of the tongue have been removed. Hyperbaric oxygen treatments have been shown to be
There may be hard and soft tissue defects and deficits. beneficial in such patients.20
When reconstructed, the bone may have poor form The time required for osseointegration will be pro-
for support of a tissue-borne prosthesis. Frequently such longed in irradiated patients because of the lower meta-
patients have thick, nonpliable soft tissue flaps that bolic activity in the bone, so the implants should not be
have been grafted from distant areas and are not adher- loaded for at least 6 months after placement. The dentist
ent to the underlying bone. All of these combine to must pay particular attention to oral hygiene in such
make conventional denture fabrication extremely chal- patients, because their tissues will not be as able to resist
lenging. In such instances the use of implant-borne bacterial invasion as tissues in patients who have not
prostheses are preferred from a functional standpoint. been irradiated. The prosthetic design should therefore be
For years, however, a history of irradiation has been a made as cleansable as possible, with frequent use of over-
relative contraindication to the placement of dental dentures. These patients will require more careful follow-
implants.17 The effects of radiation on bone and soft tis- up and hygiene measures.
sue present a formidable challenge to the use of implant- In spite of the fear that implants placed into irradiated
ed metallic devices. Not surprising, success rates for bone will lead to osteoradionecrosis, it is uncommonly
implants placed into radiated tissues are reported to be reported in the l i t e r a t ~ r e .However,
~ ~ , ~ ~ there has been an
lower than implants placed into nonirradiated tis- insufficient duration of experience to predict the long-
sues.I8,l9However, the benefits that can accrue from pro- term outcome of implant prosthetics in the patient who
viding this group of patients a functional and esthetic has undergone radiation.
dental reconstruction are great.
Such patients have been through a great deal of hard-
Management of Patients Who Develop
ship. They have lost portions of their anatomy, are fre-
quently deformed, and feel the uncomfortable effects of
Osteoradionecrosis
the radiation therapy, such as xerostomia, dysphagia, and Most mucosal breakdown and subsequent osteora-
dysgeusia. They relish the thought of being able to chew dionecrosis occur in the mandible. They occur most often
solid food with a functional'dentition. Implant-borne in mandibles that have received radiation in excess of
prostheses can help achieve this goal in these difficult sit- 6500 rads (65 Gy) and do not usually occur in mandibles
uations. However, the unpredictable reaction of soft and that have received radiation doses below 4800 rads (48
hard tissue in an irradiated patient and the surgical trau- Gy).2"25 Severe pain may follow. The patient should dis-
ma of treatment have all combined t o promote caution in continue wearing any prosthesis and try to maintain a
such cases. good state of oral health. Irrigations should be instituted
Many variables must be evaluated when considering to remove necrotic debris (Fig. 18-3). Only occasionally
placement of dental implants into irradiated bone, are systemic antibiotics necessary, because osteora-
including the radiation type, dose, sites, elapsed time dionecrosis is not an infection of the bone but rather a
since the treatment, protection provided to the bone dur- nonhealing hypoxic [Link] Because of the decreased
ing treatment, and the patient's own physiologic respons- vascularity of the tissues, systemic antibiotics do not gain
es (which themselves are affected by age, sex, genetics, ready access to the area to perform the function for which
smoking, and other systemic considerations). Other criti- they are intended. However, in acute secondary infec-
cal factors are whether the implants will be placed into tions, antibiotics may be useful to help prevent spread of
irradiated host mandibular bone, irradiated bone grafts, the infection. Any loose sequestra are removed, but no
or bone that has been transplanted after the radiation attempt is made initially to close the soft tissues over the
therapy. In the latter instance, if the mandible was recon- exposed bone. Most wounds smaller than 1 cm eventual-
structed using a microvascular graft in which the blood ly heal, although it may take weeks to months.
supply to the bone is brought in from a distant source For nonhealing wounds or extensive areas of osteora-
and has not been altered by the previous radiation thera- dionecrosis, surgical intervention may be indicated. In
py, no adverse tissue reaction should be expected after this instance resection of the exposed bone and a margin
placement of dental implants. of unexposed bone and primary soft tissue closure can be
When dental implants are to be placed into irradiated attempted (see Fig. 18-3). This is successful in many cases.
host or grafted bone, the dentist must proceed with cau- Greatly improved results have recently been obtained by
tion. Consultation with the radiotherapist is recom- the use of hyperbaric oxygen therapy in conjunction
mended to determine the amount of radiation that has with surgical intervention.14
occurred to the area of the jaws where the proposed Reconstructive efforts with bone grafts used for conti-
implants will be placed. It has been demonstrated that nuity defects can also be undertaken successfully in many
the success of implant retention is directly and positively patients who have undergone irradiation. Free microvas-
correlated with the amount of radiation to which the cular grafting techniques are becoming more popular for
bone was exposed.19 If the amount of radiation is less restoring continuity defects in patients who have
than approximately 4500 rads (45 Gy), implants may be received radiotherapy. These bone grafts have their own
placed with care. When the amount of radiation exceeds blood supply from a reconnection of blood vessels and
this amount, preoperative (20 to 30) and postoperative are therefore less dependent on the local tissues for incor-
(10) hyperbaric oxygen treatments should be considered. poration and healing.
412 PART IV Infections

FIG. 18-3 Osteoradionecrosis of the left mandible. This patient had a full course of tumoricidal
radiotherapy for squamous cell carcinoma. The dentition was removed at the time of the cancer resec-
tion. This patient was prepared for treatment of the osteoradionecrosis with pre- and postoperative
hyperbaric oxygen treatments. A, Exposed devital bone along alveolar ridge of left mandible.
B, Panoramic radiograph showing diffuse irregularity without good cortication of alveolar crest.
C, Surgical exposure of the area shows devital bone margins and a central crater devoid of bone.

Continued
 .\4oiic7p~i~1~r1t
o f the Potierlt Uilrlrr~yoir1,yKntliothrrapj, or Chernotlleropy 8 CHAPTER 18 413

FIG. 18-3-cont'd D, The bone of the alveolar crest is removed, and the remainder
smoothed with a bur until bleeding bone is encountered. The central crater is similarly burred
out. E, Resected specimen of alveolar crest.
Continued

DENTAL MANAGEMENT OF PATIENTS

ON SYSTEMIC CHEMOTHERAPY Effects on Oral Mucosa
FOR
. - MALIGNANT DISEASE Many chemotherapeutic agents reduce the normal
Destruction of malignant cells by tumoricidal chemother- turnover rate of oral epithelium, which results in
apeutic drugs has proved an effective treatment for a vari- atrophic thinning of the oral mucosa manifested clini-
ety of malignancies. Like radiotherapy, the antitumor cally as painful, erythematous, and ulcerative mucosal
effect of cancer chemotherapeutic agents is based on their surfaces in the mouth. The effects are most noted o n
ability to destroy or retard the division of rapidly prolif- the unattached mucosa and rarely seen on gingival sur-
erating cells, such as tumor cells, nonspecifically. Unfor- faces. These changes are seen within 1 week of the
tunately, normal host cells that have a high mitotic index onset of the administration of the antitumor agents.
are also adversely affected. Normal cells moct affected are The effects are usually self-limiting, and spontaneous
the epithelium of the gastrointestinal tract (including healing occurs in 2 to 3 weeks after cessation of the
oral cavity) and the cells of the bone marrow. agent.
 414 PART IV . Iiifcctioi7s

1 , Closure of soft t~ssuesG , Panoram~crad~ograph8 montlhs af!er culgery stio~v

Ing sl~ghtremodel~ngand heal~ngof the bone

Effects on Hematopoietic System

It is important to find out the type of neoplasm for
Myelosuppression, as manifested t ~ ) , Icuholwnia, ncu- ~vhiclithe patient is being treated. The t)q~eof neoplasm
tropenia, thrombocytopenia, and anemia, is ;I common dictatc3s the type of chcmothernpeutic agents to be used.
sequela of several forms of cancer chc~notticral)?..\Ziitllin 7 \Ian). hematologic ncoplacrns (e.g., leukemia) are treated
weeks of the beginning of chemothcrap?. adminictration, \\.it11 chemotherapeutic agents that result in profound
the white blood cell count falls to a n estrerncly low Icvcl. ;1lter;ltion5 in the function and number of bone marrow
The effect of myelosuppression in the oral ca\.it!. is mar- elemcnt5. (:ornparati\.cly, chemotherapeutic manage-
ginal gingivitis. Mild infections may de\,elop, and 1,lccci- ment of some n o n r n a r r o ~ solid
, tumors may not be asso-
ing from the gingiva is common. If the n c u t r o l ~ e ~ lii\ ; ~ ciated ~ v i t has sc\.ere a marrow aplasia as is found in
severe and prolonged, severe infection\ may tlc,~.clol~. 'l'hc ~ w t i c ~ n\vith
t j henlatologic neoplasms.
microornanisms involved in t l ~ e s cinfections ma\. be o\.cr-
growths of the usual oral flora, e5peclall!. tungl, h o ~ <,I, ~ c ~
other microor~anismsmav be c a ~ ~ s ac.t ~1 hrotnlxx-\
\ tope- Effects on Oral Microbiology
nia can be marked, and spontaneous bleeding ma!. [Link]. Cl~cmotliempcuticagent5, because of their immunosup-
This is especially common in the oral ca\.ity after oral 17ressir~cside effect, cause profound changes in the oral
hygiene measures. Recovery from m!.elosul~pressic,n is flora. For csaniplt, o\.crgrowth of indigenous microbes,
usually complete 3 weeks after ce5sation of chcmothcra~,).. super infection ~ v i t hgrani-negative bacilli, and oppor-
 Management of the Patient Undergoing Radiotherapy or Chemotherapy CHAPTER 18 415

tunistic infections are all common sequelae and lead to ified, minimal oral care should be practiced, because
patient discomfort and morbidity. Systemic infections are infection, severe bleeding, or both can occur. The patient
responsible for about 70% of the deaths in patients receiv- may even need to avoid flossing and to use an extremely
ing myelosuppressive cancer ~ h e m o t h e r a p y . ~ ~Oral
,~' soft toothbrush during these periods. Any removable
microorganisms have been shown to be a common source dental appliance should be left out at these times to pre-
of bacteremia in these patient~.~"hus most patients who vent ulceration of the fragile mucosa.
are on chemotherapy are treated concomitantly with sys-
temic antimicrobial agents. However, in spite of these reg-
Treatment of Oral Candidosis
imens, patients frequently develop overgrowth of some
organisms, most commonly the Candida spp.28-30 Initial treatment of candidosis is with topical application
of an antifungal medicati~n.~"he advantage of using
topical medication is that systemic side effects are mini-
General Dental Management
mized. Similarly in patients with persistent infection,
In general, the principles of dental management for the advantage can be gained by continuing topical agents in
patient who has had or will have radiotherapy apply addition to systemic medications. The use of this combi-
equally well to the patient who has had or will have nation may allow a reduced dose and duration of sys-
chemotherapy.",j2 However, because of the intermittent temic administration of the antifungal medication and
nature of the chemotherapy delivered in many instances, also may reduce the potential side effects.
the minimal effects on the vasculature, and the almost Topical agents are available as oral rinses, oral tablets,
normal state of the individual between chemotherapeutic and creams. In general, oral rinses provide a short contact
administrations, dental management can be much easier. time for the drug and are therefore of less efficacy. The
The effects of the chemotherapy are almost always tem- tablets are one of the most accepted forms of topically
porary, and, with the passage of time, systemic health treating candidiasis, because they can be dissolved slowly
improves to optimal levels, which allows almost routine in the mouth and provide increased exposure time of the
dental management. drug with the oral flora. The cream forms of topical anti-
Primary concerns for the dentist should be the severity fungals are helpful for Candida of the oral commissures or
and duration of bone marrow suppression. The dentist for application to the oral surfaces of prosthetic devices to
must be aware of the dates of chemotherapy and the prolong medication exposure.
hematologic status of the patient before beginning dental The most commonly administered topical medication
care. If the patient is being treated for a hematologic neo- for oropharyngeal Candida infections is nystatin. It is
plasm (e.g., leukemia), both the disease and the chemo- available in several forms and should be applied 4 times
therapy lead to decreases in the functional blood elements. daily.
Therefore these patients may be at great risk for infection Therapy should continue 2 weeks after cessation of
and hemorrhage at any time in the course of their disease. clinical signs and symptoms. An alternate drug is clotri-
Consultation with the patient's physician in these mazole. Troches of these medications are available and
instances is mandatory. In most cases of nonhematopoiet- can be dissolved in the mouth 4 or 5 times a day. For
ic neoplasm, the patient is at risk for infection and hemor- more stubborn cases, ketoconazole or fluconazole (i.e.,
rhage only during the course of the chemotherapy, after systemic antifungal medications) can be prescribed. How-
which recovery of the blood elements occurs. ever, the dentist must be careful with systemic adminis-
The decision of when to extract teeth before treatment tration of antifungal medications because of their toxic
is based on the condition of the residual dentition, the side effects. These vary widely with the type of medica-
patient's past dental hygiene practices, the immediacy of tion and can be serious.
the need for chemotherapy, and the overall prognosis of Another widely prescribed medication for oral candi-
the malignant disease. dosis is chlorhexidine mouth rinse. Chlorhexidine
Prechemotherapy dental measures that should rou- (Peridex) has been shown to have potent antibacterial
tinely be performed are a thorough prophylaxis, fluoride and antifungal properties in vitro. Its in vivo effects are
treatment, and any necessary scaling. Unrestorable teeth less well documented, especially for use against Candida
should be removed before chemotherapy begins. spp. in immunosuppressed individual^."^" However, it is
Patients who have begun chemotherapy must main- used in most of such patients on the basis that it proba-
tain scrupulous oral hygiene. This is difficult in the face bly does no harm and may prove beneficial in many
of mucositis and ulceration, which frequently occur. No instances.
dental procedures should be performed on any patient
receiving chemotherapy whose white blood cell and
platelet status is unknown. In general, patients who have REFERENCES -
a white blood cell count greater than or equal to 2000
1. Grisius M: Salivary gland dysfunction: a review of systemic
mm" with at least 20% polymorphonuclear leukocytes therapies, Oral Surg Oral Med Oral Path01 92:156, 2001.
and a platelet count greater than or equal to 50,000 mm3, 2. Khan Z, Jacobsen CS: Oral pilocarpine HC1 for post-irradiation
can be treated in routine fashion. Prophylactic antibiotics xerostomia in head and neck cancer patients. In Proceed-
should be administered if the patient has had chemother- ings of the First International Congress on Maxillofacial Pros-
apy within 3 weeks of dental treatment. If the white thetics, New York, 1995, Memorial Sloan-Kettering Cancer
blood cell count and platelet levels fall below those spec- Center.
416 PART IV . Infections

3. Spijkervet FK: Irradiation mucositis, Copenhagen, 1991, 19. Visch LL, Levendag PC, Denissen HW: Five-year results of
Mun ksgaard. 227 HA-coated implants in irradiated tissues. In Proceedings
4. Spijkervet FK et a]: Effect of selective elimination of the oral of the First International Congress on Maxillofacial Prosthetics,
flora on mucositis in irradiated head and neck cancer New York, 1995, Memorial Sloan-Kettering Cancer Center.
patients, 1 Surg Oncol46:167, 1991. 20. Granstrom G, Jacobsson M, Tjellstrom A: Titanium implants
5. Matheis MJ et al: Evaluation of oral mucositis in patients in the irradiated tissue. Benefits from hyperbaric oxygen, Int
receiving radiation therapy for head and neck cancer: a pilot I Oral Maxillofac Implants 7:15, 1992.
study of 0.12% chlorhexidine gluconate oral rinse. In Pro- 21. Albrektsson T: A multicenter report on osseointegrated oral
ceedings of the First International Congress on Maxillofacial Pros- implants, 1 Prosthet Dent 60:75, 1988.
thetics, New York, 1995, Memorial Sloan-Kettering Cancer 22. Taylor TD, Worthington P: Osseointegrated implant rehabil-
Center. itation of the previously irradiated mandible: results of a lim-
6. Ferretti GA et al: Chlorhexidine prophylaxis for chemotherapy- ited trial at 3 to 7 years, 1 Prosthet Dent 69:60, 1993.
and radiation-induced stomatitis: a randomized double- 23. Beumer J et al: Postradiation dental extractions: a review of
blind trial, Oral Surg Oral Med Oral Pathol 70:331, 1990. the literature and a report of 72 episodes, Head Neck Surg
7. Beumer J, Brady F: Dental management of the irradiated 6:581, 1983.
patient, Int I Oral Surg 7:208, 1978. 24. Murray CG et al: Radiation necrosis of the mandible: a
8. Beumer J, Curtis T, Harrison RE: Radiation therapy of the oral 10-year study. I. Factors influencing the onset of necrosis, Int
cavity. I. Sequelae and management, Head Neck Surg 1:301, 1 Radiat Oncol Biol Phys 6543, 1980.
1979. 25. Murray C G et al: Radiation necrosis of the mandible: a
9. Beumer J, Curtis T, Harrison RE: Radiation therapy of the oral 10-year study. 11. Dental factors: onset, duration, and man-
cavity. 11. Sequelae and management, Head Neck Surg 1:392, agement of necrosis, Int JRadiat Oncol Biol Phys 6549, 1980.
1979. 26. Greenberg MS et al: The oral flora as a source of septicemia
10. Beumer J, Curtis TA, Morrish RB: Radiation complications in in patients with acute leukemia, Oral Surg 53:32, 1982.
edentulous patients, 1 Prosthet Dent 36:193, 1976. 27. McElroy TH: Infection in the patient receiving chemothera-
11. Driezen S et al: Prevention of xerostomia-related dental py: oral considerations, \Am Dent Assoc 109:454, 1984.
caries in irradiated cancer patients, I Dent Res 56:99, 1977. 28. Epstein JB: Antifungal therapy in oropharyngeal mycotic
12. Bedwinek JM et al: Osteonecrosis in patients treated with infections, Oral Surg 69:32, 1990.
definitive radiotherapy for squamous cell carcinomas of the 29. Heimdahl A, Nord CE: Oral yeast infections in immuno-
oral cavity and naso and oropharynx, Radiology 119:665, compromised and seriously diseased patients, Acta Odontol
1976. Scand 48:77, 1990.
13. Starcke EN, Shannon IL: How critical is the interval between 30. Odds FC et al: Carriage of Candida species and C. albicans
extractions and irradiation in patients with head and neck biotypes in patients undergoing chemotherapy or bone mar-
malignancy? Oral Surg 43:333, 1977. row transplantation for haematological disease, ] Clin Pathol
14. Marx RE: A new concept in the treatment of osteora- 42:1259, 1989.
dionecrosis, I Oral Maxillofac Surg 41:351, 1983. 31. DePaola L G et al: Dental care for patients receiving
15. Marx RE: Osteoradionecrosis: a new concept in its patho- chemotherapy, I Am Dent Assoc 112:193, 1986.
physiology, I Oral Maxillofac Surg 41:283, 1983. 32. Wright WE et al: An oral disease prevention program for
16. Marx RE, Johnson RP, Kline SN: Prevention of osteo- patients receiving radiation and chemotherapy, 1 Am Dent
radioneaosis: a randomized prospective clinical trial of hyper- Assoc 110:43, 1985.
baric oxygen versus penicillin, / Am Dent Assoc 111:49, 1985. 33. Thurmond JM et al: Oral Candida albicans in bone marrow
17. Hobo S, Ichida E, Garcia LT: Osseointegration and occlusal reha- transplant patients given chlorhexidine rinses: occurrence
bilitation, Tokyo, 1989, Quintessence. and susceptibilitiesto the agent, Oral Surg 72:291, 1991.
18. Granstrom G et al: Bone-anchored reconstruction of the irra-
diated head and neck cancer patient, Otolaryngol Head Neck
Surg 108:334, 1993.