radiation effects word
TRANSCRIPT
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Date: 16.10.2012
THE RADIATION THERAPY PATIENT- TREATMENT
PLANNING AND POST TREATMENT CARE
Sreeprabha G Mohan
2nd
year PG student
Dept of prosthodontics
AECS Maaruti dental college
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Introduction:
Radiation is broadly used for diagnosis termed as diagnostic radiation and for
therapy termed as therapeutic radiation. The therapeutic radiation is higher in
intensity and delivers more grays of radiation to the tissues and to the health care
personnel. Hence meticulous planning and high-level expertise is mandatory prior toselecting this modality. Surgery and radiotherapy are the two forms of treatment,
which have a curative potential in orofacial cancer. These two modalities should be
regarded as complementary rather than rivals in majority of cases. In some patients
one or the other treatment modality may be preferable while in other patients both
are needed to give the greatest chance of care.
The prosthodontic treatment of head and neck cancer patients and its role in
improving quality of life is well recognized. Prior to the early 1960s, the dentist or
more frequently the prosthodontist, was engaged almost exclusively in dealing with
the dental rehabilitation of the head and neck cancer patient who had undergone
ablative surgery. With the increased use of radiation in the 1960s and cytoreductive
drugs in the 1970s, dentistry was challenged with the task of developing treatment
regimens for the oral complications associated with these forms of therapy. Although
relatively large numbers of patients were treated, the role of the dentist in managing
the oral complications associated with various cancer therapies was not completely
understood. This was the case despite the fact that the National Institute of Health in
a Consensus Development Statement estimated that as many as 400,000 patients
developed oral complications as a result of cancer treatment. The same document
noted that at a minimum, oral complications are painful, diminish the quality of life,
and lead to significant compliance problems, often discouraging the patient fromcontinuing treatment. As time has progressed, the oncology patients need for early
and continual dental care has been proven to be beneficial by a number of clinicians
and now recognized, for the most part, by the physician oncologist. Today the dental
oncologist at most major cancer centers and the oncology oriented general dental
practitioner in the private sector are valued participating members of oncology
treatment teams.
Definition:
Radiotherapy, also called radiation therapy, is the treatment of diseases with ionizing
radiation.
Principles of radiotherapy:
The radiotherapy is based on the basic premise that the fast growing and
metabolically hyperactive cancer cell is more sensitive to the high-energy radiation
as compared with the normal cell. This margin of safety is very marginal in some
tissues hence the different modalities, different dose and time variations and different
types of radiation deliveries.
Goal of radiotherapy is to sterilize tumor and to preserve adjacent normal
tissue. Ionizing radiation deposits energy that injures or destroys cells by damaging
their genetic material, making it impossible for these cells to continue to grow. Lethal
dose for normal and abnormal tissues is about the same Normal tissues have
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greater ability to repair sublethal damage between doses, of radiation than
neoplastic cells.
The effects produced depend on factors like Oxygen Enhancement Ratio (OER),
Linear Energy Transfer (LET), and Relative Biologic Effectiveness (RBE).
OER = ratio of dose required to produce a given amount of damage in hypoxiccondition to dose required to produce same amount of damage to oxygenated tissue.
RBE = Ratio of dose of 250 kV X-rays to dose of test radiation required to produce
equal amount of biologic effect
LET = Energy transferred by the radiation along the path of travel.
Sources of radiation:
X-rays were the first form of radiation to be used to treat cancer. Depending
on the amount of energy they possess, the rays can be used to destroy cancer cells
on the surface of or deeper in the body. The higher the energy of the x-ray beam, the
deeper the x-rays can go into the target tissue. Linear accelerators and Betatrons
are machines that produce x-rays of increasingly greater energy. In the mid-1970s
there has been much interest in the possible use of high-energy particles in
radiotherapy. These particles include neutrons, protons, deuterons, stripped nuclei,
and negative mesons. The radiotherapy is possible using the following types of
radiation and charged particles.
Gamma rays
X-rays
Charged particles
Protons
ElectronsNegative - mesons
Uncharged particles
Neutrons
RT with particulate radiation differs from photon radiotherapy in that it involves
the use of fast-moving subatomic particles to treat localized cancers. Most particles
(neutrons, pions, and heavy ions) deposit more energy along the path due to their
mass. This is referred to as high linear energy transfer (high LET) radiation thus
causing more damage to the cells they hit. Recent advance in radiotherapy research
is the use of radio labelled antibodies to deliver doses of radiation directly to the
cancer site (radio immunotherapy). Tumor-specific antibodies from certain tumor
cells are attached to radioactive substances (radio labeling) and injected into the
body, which actively seek out the cancer cells and destroy them by the cytotoxic
action of the radiation. This approach can minimize the risk of radiation damage to
healthy cells
Types Of Treatment
1. Radical radiotherapy.
Irradiation, which aims at cure, is termed as radical radiotherapy. Here the
aim is the local and regional control of the primary and metastatic lymph nodes. Itcan only be achieved when all tumor cells are killed.
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2. Palliative radiotherapy.
The aim here is to relieve the symptoms caused by the cancer, thus improving
the quality of life. This is usually indicated when there isnt a realistic likelihood of
cure.
3. Multi modal treatment concepts.Here the treatment is a combination of surgery and radiotherapy. Postop
irradiation is indicated when surgical wounds have healed and the interval should be
kept to a minimum.
In general radiotherapy the waiting period is between 2 to 4 weeks except in patients
with delayed wound healing.
Dosimetry
The purpose of dosimetry is to evaluate the amount of energy absorbed by
the tissues subject to radiation. Thus accurate treatment planning must consider:
type of radiation
: Energy
: Penetration depth (Dmax)
When a radiation beam penetrates tissue the dose decreases with depth of
penetration after the maximum dose has been reached i.e. the Dmax or the
penetration depth of the maximum dose.
The region from the surface to the depth of the maximum dose is called the build up
region. While the region beyond is called the fall off region.
The depth dose curves are visualized on a plane running along the axis of the
beam where points of equal dose are connected, as yielding curves known asIsodose curves.
Various kinds of external beam radiation used are
Single beam
Multiple beam
Single Beam: The penetration of a beam depends on its strength. Low energy x-
rays will result in the Dmax being superficial making it an excellent treatment
modality for superficial lesions.
With an increase in the energy the surface dose decreases, thus increasing the build
up region, resulting in the Dmax being further away from the surface. Thus a high-
energy beam has a skin sparring effect.
Thus a choice of the beam is made depending on the type of tumor and its location.
Multiple Beams-This is used when a tumor is large and is located deep. Thus it
becomes necessary, in order to maximize tumor dose and to minimize the dose to
normal tissues to use two or more beams. Beam configurations can vary from 2
simple opposed fields, angling fields, or 3 or more fields.
Radiation Therapy Techniques
Tele Therapy
Also known as external beam irradiation, and is performed with the radiation sourceoutside the patient. The beam penetrates the skin and is focussed to the treatment
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area. Most commonly used sources are the Tele-cobalt machines emitting gamma
rays and linear accelerators producing high energy X rays and electrons.
Brachy Therapy
Here irradiation is delivered from a radiation source placed surgically in deep-seated
tumors. Due to the proximity of the source the depth dose curves are very steep.
This causes an uneven distribution even within a few cms.
There is a fear of under dosage to the periphery, though there is greater sparring
of the normal tissues. This may be used in conjunction with Tele therapy to boost the
dosage to regional lymph nodes.
They may be either permanent or temporary depending in the type of isotopes used.
Radiation Effects on Tissues
They can manifest as acute changes or chronic changes and the clinical
sequelae are specific for each tissue .eg.-benign paralysis of motor nerves, atrophy
of muscles , fibrosis in connective tissues.
NTCP (normal tissue complication reaction) this is dependent on: -
Vol. of tissue irradiated.
Dose administered.
Fraction size.
Interval b/w the two fractions.
Individual and genetic factors.
Cofactors (wound infection)Radiation injury can either be direct or indirect.
Direct Injury
Destroys or damages susceptible cells causing a loss or disruption of tissue function
.eg. Salivary glands, mucosa, skin.
Indirect injury
This results from decreased vascularity and the subsequent changes in the
tissue. These changes are classified to be based on responses that are
Hypovascular
Hypocellular
Hypoxic
Radiation tissue injury is not a quantitative measurement but a clinical assessment
that explains the damage in terms of
Total dose
Dose rate
Anatomic designs of radiation portals
Clinical signs of injury.
These signs may be acute, immediate, or latent in their presentation
The short-term effects are:
MucositisXerostomia
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Concomitant change in oral microflora
Loss of taste
Increased sensitivity to spicy or strong tasting food.
Long-term problems include:
Reduced potential for bone healing and the risk of developing osteoradionecrosis(ORN)
Permanent loss of salivary function
Increased potential for dental caries
Increased susceptibility to oral infections of candidiasis
Trismus.
The dental management of these patients is broadly divided into
1. Dental examination before radiation therapy and treatment plan
2. Dental management during radiation therapy
3. Dental management following radiation therapy
Dental Examination before radiation therapy And Treatment Plan
1. Restorative procedures and dental extractions
2. Preradiation prosthodontic care
3. Postradiation prosthodontic care
Restorative procedures and dental exactions
Full mouth or panoramic radiographs are necessary as is a comprehensive clinical
examination of the periodontium and oral soft tissues. An assessment of the patients
oral hygiene is an important element in the initial examination. A dental prophylaxis
and review of oral hygiene procedures should be examined carefully for dental
caries. Definitive restorations should be placed and teeth considered no restorable orsalvageable with endodontic therapy should be extracted. The required extractions
must be accomplished expeditiously since a healing period of atleast 10 days to 3
weeks is essential before radiation treatment begins. Proposed extractions must be
discussed with the radiation oncologist and an understanding reached regarding the
time available for healing. When surgical removal of a tumor is planned prior to
radiation teeth can be conveniently removed in the operating room at the time of
tumor surgery thus ensuring an adequate healing period. It is generally advised that
teeth be removed with minimal trauma and the extraction sited be closed primarily.
Antibiotic coverage may improve the potential for healing in the case of diabetics and
other medically compromised individuals. Periodically involved teeth exhibiting
moderate to severe mobility should also be considered for removal. Some thought
must be given to the long term prognosis of the teeth in question. The patients abi lity
and willingness to perform all recommended oral hygiene procedures will also help
determine which teeth can be maintained. In questionable situations, it is perhaps
more prudent to err on the side of aggressive tooth removal, since extractions
following radiation treatment will present an increased risk of osteoradionecrosis. It
must also be remembered that wound healing will be compromised, and extensive
periodontal surgery following radiation will be contraindicated.
Frequently the dentist is faced with the decided to extract all remaining teeth. Thisshould be tempered to some degree by the knowledge that the patient rendered
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completely edentulous with no previous denture experience may find the process of
adjusting to complete dentures a difficult one. Soft tissues within the radiated field
will be easily irritated by the prosthesis retention. It is advisable to consider
maintaining strategically positioned, periodontally sound teeth to be used as
abutments for removable partial dentures or complete overdentures. Becauseirradiated bone loses the ability to remodel, radical alveolectomies must be
considered for those patients who are candidates for removable prosthesis. Removal
of tori and exostosis will help reduce soft tissue problems and improve the
opportunity for prosthodontic success. Patients who present with partially erupted or
impacted third molars are particular problems since a number of valid arguments can
be made for and against extraction. Two issues are of importance in regard to the
decision to extract these teeth. The principle concern is, once again the amount of
time the physician oncologist is willing to allow for healing. Impactions requiring
extensive bone removal may take longer to heal and are at greater risk for infections,
necessitating a possible delay in the start of the radiation treatment. These
extractions may be greater problems I the older, physically compromised individual
compared with a younger, healthier patient. Since the fully impact tooth does not
precipitate many major immediate problems following radiation the decision to
extract or not to extract these teeth can only be reached after careful review of all
factors. Partially erupted teeth must be considered for extraction particularly if they
have been the cause of previous episodes of pericoronal infections. Potential
restorative and surgical procedures will be difficult following radiation since resulting
trismus will limit access and surgery will result in a risk of compromised wound
healing. A limited ability to open makes surgery and restorative and endodonticprocedures in posterior quadrants very challenging and has a detrimental effects on
the quality of care provided. It is certainly an advantage to extract these partially
erupted teeth prior to radiation.
Criteria for pre irradiation extraction.
Dental disease factors.
Radiation delivery factors.
Pre irradiation surgery.
Post radiation dental disease. Dental maintenance.
Criteria for Pre Irradiation Extractions
Condition of the residual dentition
The goal is to place the dentition in optimal condition so that no high-risk
dental procedures need be performed in the post radiation phase.
The patients periodontal status is most important in this assessment.
An aggressive extraction protocol for dentition with periodontal involvement.
Moderate caries are less important as they can be restored and maintained easily.
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Dental awareness of patient
Patient Motivation
It is important that patients posses the motivation and ability to maintain the dentition
in sound health.
Without the patients health the risk of complications increase immeasurably The lessthe patients motivation the more aggressive should the extraction protocol be.
The patients oral hygiene at the initial examination is often a reliable indicator of
future performance.
Urgency Of treatment
The status and behaviour of the tumor may preclude any pre irradiation extractions
Delays secondary to healing can significantly compromise control of the disease.
Control of the tumor is the most important consideration.
Mode Of Therapy:
In external beam radiation there is more exposure to the tissues than implantation
technique.
While the risk of osteoradionecrosis is more when the implants are close to the
bone.
Thus all such factor should to be kept in mind before planning any pre extraction
surgeries.
Radiation field
The risk of caries and necrosis is dependent on the radiation field. Where theradiation fbeam includes the major salivary glands and a significant portion of the
body of the mandible, as in the base of the tongue, tonsillar pillar, and retromolar
trigone carcinomas, radiation-induced xerostomia is sever and the blood supply to
the mandile is compromised. This indicates increased incidence of caries and
osteoradionecrosis is high in this region. Thus aggressive approach to extraction of
teeth is justified.
Mandible Versus Maxilla
Almost all ORN occurs in the mandible and hardly any in the maxilla. Thus a
conservative approach regarding the maxillary teeth is justified.. So a more
aggressive approach is mandatory for mandibular teeth especially those that fall in
the radiation field.
Prognosis Of The Tumor
Prognosis is of more importance in-patients for whom palliative and relief measures
are indicated.
In such patients teeth, which would normally be otherwise extracted, are left in place,
as they would otherwise be troublesome and create unnecessary discomfort.
Pre Irradiation Surgical Procedures
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Radical alveolectomy to be performed, edges of the tissues should be everted and
primary closure is obtained.
Teeth should be extracted in segments, rather than singly, as it is easier to do
alveolectomy and obtain closure.
A period of 7-10 days is usually adequate for healing before therapy can commence.Extraction of impacted third molars is not usually indicated unless accompanied with-
Pain
Infection or Abscess
Cyst
Pericoronitis
Dental Maintenance
Patient is given oral hygiene instructions and a thorough oral prophylaxis is done.
Follow up is done weekly during the therapy and the instructions are reinforced.
Post therapy patient is placed on a recall schedule every 3 months for the first year.
Fluoride therapy is an integral part of the dental treatment and is initiated
immediately.
Can vary from fluoride gels to mouth rinses.
Has to be continued for a lifetime in some form or the other.
Bone
Since bone is 1.8 times as dense as soft tissue it absorbs a larger proportion of
radiation than does a comparable volume of soft tissue. The mandible absorbs more
radiation than the maxilla because of its increased density and this plus themandibles reduced vascularity compared to the maxilla accounts for the higher
incidence of mandibular osteoradionecrosis. The surgeon must smoothly contour the
alveolar ridge at the pre radiation dental extractions. If radical alveolectomies are not
performed on these patients the resulting alveolar ridge will not readily remodel and
will be quite irregular. Construction and wear of mandibular dentures on such an
irregular bony base is quite risky in an irradiated patient for it may lead to exposed
bone and subsequently to osteoradionecrosis.
PeriodontiumSpecific network of the fibers becomes disoriented and the periodontal ligament
thickens. Osteoradionecrosis are preceded by periodontal infection associated with
teeth in the primary beam of radiation when evaluating teeth for extraction prior to
treatment. The periodontal status of the dentition is the most important dental
consideration aside from preexisting acute infectious process. Cementum
demonstrates changes in its capacity for repair and regeneration is severely
compromised.
Teeth
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There appear to be significant changes in pulp tissue. Pulp shows a decrease in
vascular elements with accompanying fibrosis and atrophy. Clinically pulpal
response to infection, trauma and various dental procedures appears compromised.
Pulpal pain, however, is less severe even in the presence of advanced caries with
obvious pulpal exposure.Root sensitivity following full course radiotherapy may be severe in a very small
number of patients. Burnishing the exposed surface with a 1% fluoride solution has
been effective in reducing pain and sensitivity.
If exposure occurs before significant calcification is completed, the tooth bud
may be damaged or destroyed. Exposure at a later stage of development may arrest
growth and may result in irregularities in enamel and dentin.
Preradiation prosthodontic care
As noted previously many head and neck oncology patients are elderly and have
experienced limited dental treatment. A number wear removable complete or partial
dentures, and although in the opinion of the patient the prosthesis are serviceable
they may or may not conform to acceptable prosthodontic standards. Regardless of
the condition of the dentures, little definitive prosthodontic care is necessary prior to
radiation. The severity of resulting mucositis will limit the patients ability to tolerate
the prosthesis during therapy, whether or not retention or occlusion is adequate.
Since patients may experience a substantial weight loss over the treatment course
sufficient change will have occurred in the soft tissues to warrant the fabrication of
new dentures once radiation is complete. There is little advantage to relining ill fitting
dentures since the procedures can be moderately expensive and will not be a factorin patient comfort during various stages of mucositis. Soft temporary reline materials
because of their surface porosity and abrasiveness, make hygiene procedures
difficult, serve as a potential reservoir for fungal growth and may be a source of
additional mucosal discomfort.
Patients are advised that they will in most instances be better served by not wearing
dentures during therapy. The patient must be cautioned that continuing to wear the
dentures may be the source of significant additional mucosal irritation and lead to
delayed healing following the completion of radiation therapy. In most instances the
patient will object to being without dentures during therapy for the usual cosmetic
and functional reason. The clinician should approach this situation with a
sympathetic ear. It is important to the psychological well being of the cancer patient
that a degree of normalcy exists in daily life. Such patients have been bombarded
with discussions of serious potential problems resulting from radiation and then are
asked to suffer the additional indignity of going without dentures. It is important for
the patient to feel in control of the decision regarding the use of dentures. More often
than not a decision will be made to head the advice of the dentist. Dentate patients
with metallic crowns or fixed partial dentures in the treatment field may suffer
significant irritation to adjacent soft tissue as a result of backscatter. This problem
can be minimized with the use of a custom made, soft plastic stent. The stent shouldbe of sufficient thickness to displace the soft tissue in buccal and lingual directions.
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in some cases, the patients fluoride carrier may be used for this purpose. An
increasing number of patients with dental implants are being seen at treatment
centers.
Dental management during radiation therapyMucositis one of the earliest effects of radiation to the oral cavity is the
development of severe soft tissue irritation or mucositis. The soft tissue in the
treatment field after a week or two, demonstrates a moderate amount of erythema.
As radiation continues, the mucosa may exhibit varying degrees of desquamation
and frank ulceration. Resulting pain and dysphagia make it difficult for the patient to
eat a well balanced diet, resulting in what may be a significant weight loss. It may be
necessary to interrupt therapy if the weight loss becomes critical. The severity of the
mucositis is influenced by a number of factors and is not always predictable. Patients
with a history of alcohol abuse or smoking for example who continue these habits
during radiation suffer the greatest morbidity. Acute mucositis begins during the
second or third week of radiation therapy and subsides within 8 to 10 weeks once
treatment is completed. A variety of measures have been proposed to help alleviate
the patients discomfort, the most significant being good oral hygiene. Frequent daily
cleaning of the teeth with a soft brush and mild tasting toothpaste has proven to be
beneficial. Frequent oral rinses with a combination of salt and sodium bicarbonate in
water or dilute solutions of hydrogen peroxide and water appear to have a soothing
effect on the affected areas and aid in keeping the tissue clean and moist. Other
therapies have included rinsing with Benadryl elixirs, sucralfate solutions, and topical
anesthetics. The mucosa should be cleansed with either the hydrogen or saltsolution prior to using Benadryl or sucralfate. This helps remove debris and mucus
from the wounds and allows the medication to adhere more intimately to the tissues.
Topical anesthetics in dilute form effectively reduce discomfort and can be useful
during meals. Since large portions of the oral cavity are anesthetized for a significant
period of time, the patient must be cautioned not to inadvertently bite and additionally
injure the soft tissues.
Loss of taste
Loss of taste accompanies radiation to the tongue and palate. This loss occurs
rapidly during the first week or two of treatment and in most instances gradually
returns to normal once the treatment course is completed. Some questions have
been raised regarding the exact cause of the loss of taste. Damage to taste buds
and microvilli, disrupted innervations as a result of the radiation and lack of saliva
have all been mentioned as possible contributing factors. The condition is primarily
an annoyance but adds to the discomfort of the patient during the treatment course.
The loss of taste may lead to lack of desire for food and can be an additional cause
of weight loss during therapy. It is condition the patient must endure with the
understanding that it is rarely permanent.
Xerostomia and dental caries
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Changes in the quantity and quality of saliva as a result of radiation have been well
documented in the dental literature. Beginning with the first course of treatment,
salivary flow rates decrease, eventually reaching as low as 1% of normal.
Additionally there is a concomitant increase in the numbers of acidogenic and
cariogenic microorganisms resulting in a severe, aggressive from of dental caries.Lacking a specific preventive program, the dentist at once time was faced with the
unenviable task of continually restoring all tooth surfaces with little hope for success.
In an effort to reduce long term complications precipitated by this form of tooth decay
patients were frequently advised to have all remaining teeth regardless of their
condition extracted prior to radiation. Definitive studies regarding treatment and
cause of dental caries in the irradiated patient led to the knowledge that the most
effective method of treating this condition was through the daily use of topical
applications of fluoride. Both stannous or sodium fluoride have been used in variety
of forms with significant success. It has been noted that an additional advantage of
stannous fluoride is that it has an antimicrobial effect reducing S mutans counts.
Sodium fluoride because of its higher pH is less irritating to compromised soft tissue
and is substituted for the stannous form for patients who complain of a burning
sensation when using the stannous gel. Gels used with a tray are reported to better
cover all tooth surfaces than either fluoride rinses or gels applied with a brush.
Patients must be made to understand that they will need to use fluoride once a day,
every day for the remainder of their loves. Clinical experience has demonstrated that
discontinuing the fluoride applications even for short periods of time, may result in
renewed cariogenic activity. Preventive programs based on the topical applications
of fluoride coupled with meticulous oral hygiene can all but eliminate the cariesproblem. There is little reason for any irradiated head and neck cancer patient to
experience abnormal dental caries providing he or she is fully complaint monitored
regular and appropriately counseled by a dentist.
Immediately following the initial prophylaxis and before radiation treatments begin
irreversible hydrocolloid impressions are made. Custom trays or carriers which
extend to just below the marginal gingiva are fabricated and delivered taking care to
relieve any areas that may impinge on soft tissue. The edges of the tray should be
made as smooth as possible to avoid soft tissue irritation. This is an important step
since the patient will be expected to use the carrier during therapy while
experiencing severe mucositis. The patient is instructed to carefully brush his or her
teeth. Immediately following brushing the patient is directed to place a sufficient
amount of a sodium or stannous fluoride gel into the tray to cover all tooth surfaces.
Once positioned the tray and gel must remain in contact with the teeth for a minimum
of 5 min. Additionally the patient is asked not to rinse the mouth for approximately
30 min following removal of the tray. As the patient progresses through radiation
treatment courses, it is advisable for the dentist to frequently monitor oral hygiene
procedures and ensure proper use of the fluoride. Although the preventive treatment
described is generally considered the treatment of choice several groups of patients
experiencing only partial salivary gland dysfunction may achieve acceptable resultsby simply brushing with the fluoride gel.
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Saliva substitutes and sialogogues
The most persistent and certainly the most frustrating morbidity associated with
radiation to the head and neck is dry mouth. The condition begins in the first week of
therapy and gradually worsens overtime. The patient experiences a need tocontinually lubricate the mouth and is forced to ingest large quantities of fluid to aid
in swallowing at mealtimes. There is a disconcerting change in eating habits with an
increased intake of soft moist foods. Food debris accumulates on the oral mucosa
and teeth because of the absence of the self cleansing action of saliva making oral
hygiene much more difficult. Attempts have been made to stimulate salivary flow
rates with sialogogues such as pilocarpine and antholetrithoine. Therapeutic
regimens involving administration of these drugs have proven effective for patients
with Sjogrens syndrome and for individuals receiving low doses of radiation to limited
fields. There is no concrete evidence that the drugs are effective in those individuals
receiving high doses of radiation to all major salivary glands. Saliva substitutes have
been developed in an effort to alleviate the discomfort and harmful effects of
xerostomia. These products consist primarily of carboxymethylcellulose with various
salts and flavoring agents added. Results with the use of the substitutes are mixed,
related more to the subjective preference of the patient than to any appreciable
therapeutic effect. Patients should be offered an opportunity to try the substitute
early in the course of radiation treatment. While most individuals discontinue use
within a relatively short period, complaining of stickiness or unpleasant taste others
find it to be of some benefit. Clinical experience has demonstrated that patients are
quite resourceful in developing their own methods of coping with xerostomia. Manycarry containers with water or salt and soda solutions with them at all times, rinsing
or drinking frequently. Others have been reported to rinse with self developed
mixtures of glycerin and fruit juice or mouth rinses with some success.
Trismus and fibrosis
Trismus may begin shortly after radiation begins. Clinically the patient gradually
loses the ability to open the mouth. The condition may be exacerbated by surgery
prior to radiation and by radiation fields that include the muscles of mastication or the
TMJ. Patients suffering with tumors of the palate, nasopharynx and maxillary sinus
are most likely to develop trismus. If unmanaged trismus makes eating difficult and
the performance of dental procedures almost impossible.
Since primary treatment involves exercising the muscles involved a variety of bite
openers or exercise devices have been developed. Each has been proven through
clinical use to be substantial value and in most instances effectively increase the oral
openings. Positive results are more easily attained with the dentate patient. It must
be noted that improvement in the ability to open regardless of the exercise program
is not permanent and may regress over a period of even a few hours. The simplest
and least expensive method of exercising is with the use of tongue blades. A number
of tongue blades are placed along the occlusal surfaces of the posterior teeth. Thevertical opening is increased as an additional blade is added slowly and deliberately
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to the original stack. The patient is instructed to pause for a few minutes before
placing each additional blade. As trismus becomes chronic there is an appreciable
amount of discomfort involved in performing the exercises, regardless of the method
used, resulting in patient noncompliance. Chronic trismus gradually becomes fibrosis
of the elevator muscles and at this late stage is not amenable to stretching as asolution. Exercise must begin early in treatment and results are predicted on the
patients willingness to cope with the exercise regimen.
Use Of Prosthodontic Stents & Splints
Positioning stents
Shields
Recontouring devices
Positioning of direct source
Templates
Tissue bolus devices.
Shielding and positioning stents
In an effort to minimize morbidity associated with radiation to the oral cavity, soft
tissues not directly involved with tumor can be displaced or shielded. The radiation
oncologist frequently uses a tongue blade taped to a cork for example, when treating
lesions involving the tongue. This simply in effect lowers the mandible and tongue
preventing radiation to the nonaffected parotid gland and maxilla to some degree.
Over time dental oncologists in cooperation with radiation therapists have developed
more sophisticated shielding and positioning devices that have proven to be useful inlimiting radiation effects. The fabrication of one of these stents or splints is time
sensitive since it must used in the planning of treatment fields. The physician will
usually desire treatment to begin as quickly as possible and may have concerns
regarding the time involved in fabricating a customized stent or splint. Some
radiation oncologists find the fabrication of complex customized stent or splint. Some
radiation oncologists find the fabrication of the complex, customized stents
unnecessary. This opinion appears to be based more on the availability of an
oncology oriented dentist rather than unsuccessful clinical results. Generally
fabrication is a relatively uncomplicated procedure and can be completed
expeditiously using basic prosthodontic clinical and laboratory techniques.
Positioning stents
One of the frequently used positioning stents serves to lower the tongue and
places it in a repeatable position during therapy. Since the stent also serves to
separate the mandible and maxilla in an open position, maxillary structures such as
the palate upper gingiva and buccal mucosa are spared radiation effects. Maxillary
and mandibular impressions are made with irreversible hydrocolloid. In the case of
the completely edentulous patient, the impressions must be properly extended to
ensure stability of the finalized bases. An interocclusal record is obtained at thewidest opening necessary to ensure that maxillary structures are not included in the
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treatment field. Casts are recovered and mounted on a simple articulator. Baseplate
wax is softened and placed over the incisal and occlusal surfaces of all teeth. Two
sheets of baseplate wax are then attached to the right and left sides of the
mandibular segment. This flat sheet extends posteriorly as far as tolerable, covering
the entire tongue and maintaining it in the appropriate treatment position. An openingin the anterior portion of the stent between the pillars acts as a shelf upon which then
tip of the tongue rests and serves to help maintain a repeatable tongue position.
The waxed stent is evaluated in the mouth, and the radiation therapists verify tongue
position. Additionally an assessment is made regarding the patients ability to
tolerate the stent position it correctly and remove it easily. The waxed stent is flasked
and processed in clear heat cured or autopolymerizing resin. A length of stainless
steel wire is embedded in the horizontal lingual extension. The wire defines the
position of the dorsum of the tongue on stimulation films and is of value when
planning radiation fields. The stent is highly polished and checked carefully for any
scratches or sharp edges that may cause irritation during therapy. The radiation
therapists confirm the final treatment fields with the completed stent in place.
Shielding stents
It is possible when treating tumors of the buccal mucosa, skin or alveolar
ridge with electron beam therapy to protect uninvolved adjacent structures by means
of a shielding stent. It is known that a 1 cm thickness of a Lipowitz alloy consisting of
silver, copper, tin, antimony and lead will effectively reduce an 18MeV electron beam
by approximately 95%. The metal is only effective, however when electrons are
used. Generally an acrylic resin stent is made. A portion of the stent is removed andthe metal is heated, poured into the prepared recess, and allowed to cool. The metal
is then covered with a layer of acrylic resin to prevent backscatter to adjacent tissue.
Maxillary and mandibular impressions are made using a combination of modeling
plastic and irreversible hydrocolloid in an effort to displace the tongue laterally. An
interocclusal wax record is made in centric relation at a slightly opened vertical
dimension. The impressions are poured and the recovered casts are mounted on a
simple articulator in the open position. Baseplate wax is placed over the mandibular
teeth on the side to be treated and side to be treated and the articulator is closed to
form an index of both maxillary and mandibular teeth. A wax bolus is formed and
attached to the occlusal index. The bolus should extend approximately 1 to 2cm
lingually and contact both the palate and the floor of the mouth. The lingual surface
of these stent is made as flat as possible. The waxed stent should be tried in the
mouth to confirm appropriate extension posteriorly and sufficient displacement of the
tongue. Once the shape has been confirmed, the waxed stent is flasked and
processed in clear, heat cured or autopolymerizing acrylic resin. The stent is
recovered and polished as carefully as possible making certain that no sharp edges
or rough surfaces exist. A recess extending within 8 to 10mm of the entire
circumference of the stent is cut into the resin to an appropriate uniform depth
dependent on the megavoltage of the electrons to be used. The Cerrobend is heatedand the molten metal poured in the hollowed portion of the stent. The metal melts at
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1580F, at which temperature the acrylic resin will not be damaged. After cooling the
patients name can be cut into the metal surface with a round bur for identification
purposes. The exposed metal is covered with additional acrylic resin to prevent the
metal from contacting mucosal surfaces and to minimize backscatter. The completed
stent is tried in the mouth in consultation with the radiation therapists. Minor finalmodifications can be made at this time. It may also be necessary to adjust the stent
as treatment progresses to avoid irritation of radiated soft tissues and to
accommodate the limiting effects of trismus. In some situations both photons and
electrons are used in treatment. Since the tissues must be in the same position when
either modality is used, a duplicate stent without the metal is employed during the
photon phase of treatment. Modifications can be made in the basic design of the
positioning and shielding stents to accommodate the needs of the most treatment
situations. It may be advantageous to make the stent in several pieces. This
facilitates insertion and removal as treatment progresses and trismus becomes a
problem. A number of other stents have been described that function as carriers for
radioactive sources and positioning cones. The basic procedures for developing
these devises are essentially the same as those discussed above. There are only a
few fundamental rules governing fabrication of these stents and in many instances
design is based on the ingenuity of the dentist involved and a cooperative
relationship between dentist and radiation therapists.
Recontouring Devices To Simplify Dosimetry
Usually useful in treating skin lesions associated with upper and lower lip. Due
to the curvature of the lip the doses will be delivered less to the corners of the mouth.This stent aims to flatten the lip and the corners of the mouth thus placing the entire
lip in the same plane.
Positioning Of A Direct Source
Used in Brachy therapy. A previously fabricated stent or radiation carrier is
used to position the radioactive source. Radiopaque shields or tissue positioners can
be incorporated to avoid unnecessary radiation to the surrounding tissues.
Templates
This aids in direct positioning of the radiation sources and to gauge its depth
of insertion. Any pre existing prosthesis (CD) can also be used as templates for
positioning of these implants.
Tissue Bolus Devices
Irregular tissue contours create uneven dose distributions. As a result some
areas within the field get more doses and than others. A bolus is a tissue equivalent
material placed into irregular tissue contours to produce a more homogeneous dose
distribution. Commonly used materials are saline, wax and acrylic resin.
Dental Management Following Radiation
Soft Tissue Necrosis
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Is defined as a non neoplastic mucosal ulceration ring in the postradiation
field and which does not expose bone. These lesions occur most often following
treatment with interstitial implants and peroral cone modalities. These necroses
occur within 1 year after completion of radiation therapy.
A tumor recurrence usually presents with irregular, indurated margins, whereas softtissue necroses present with regular, non-indurated margins. Soft tissue necroses
are mostly precipitated by tongue and cheek biting which often warrants occlusal
adjustment in dentulous patient, or removal of mandibular denture in the edentulous
patient. Treatment consists of establishing the diagnosis and close follow-up. In
severe cases, healing can be accelerated by hyperbaric oxygen.
Mucositis and Loss of Taste
Once radiation treatment is complete, acute mucositis will subside gradually
over a period of 6 to 8 weeks. Since the affected soft tissue will remain constantly
irritated to some degree, the patient is advised to continue using rinses. The length
of the time necessary for recovery is dependent on the severity of damage to the soft
tissues and in some instances may take months. Generally taste acuity will return to
the levels that the patient perceives as normal.
Xerostomia and Dental Caries
The loss of salivary function is permanent, and salivary flow rates have been proven
to decrease with time. Oral tissues will remain dry and uncomfortable, forcing the
patient to rinse frequently with no hope for a positive therapeutic solution to the
problem.A program that includes meticulous oral hygiene, frequent daily rinsing and use
of saliva substitutes offers some hope for temporary relief.
Since dental caries is directly related to the effects of the decrease in saliva, it is
essential that the program of oral hygiene and the daily topical application of fluoride
be maintained.
Candidiasis
Causes
Xerostomic conditions and change in normal flora
Symptoms
Abnormally sore or burning mouth
Generalized inflammation involving the palate and cheeks, but lacking the whitish
patches generally associated with Candida
Treatment
Troches or rinses containing chlotrimazole or nystatin are prescribed. Bacterial
infection may be treated with appropriate antibiotics. Treatment is continuous for a
period of 2 weeks. It has been suggested that meticulous oral hygiene and frequent
rinsing with salt and soda or dilute solutions of hydrogen peroxide may have a
preventive effect.
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Clinical experience has demonstrated that Candida may be harbored in or on the
surface of dentures or obturators and play a role in chronic reinfection. Soaking
prostheses in an anti fungal solution or dilute hypochlorite for complete dentures has
proven to be an effective preventative measure.
Trismus and Fibrosis
Trismus and fibrosis will continue to be problems following radiation. In most
instances these conditions will increase in severity with time, leading to oral
openings of 10 to 15 mm. Patients will have difficulty in placing dentures or
obturators, with resultant compromise in nutrition. The condition is only improved
with constant exercise. The more frequent and diligent the exercise regimen, the
more beneficial is the result. It is recommended that the patient perform exercises
several times each day.
Dental Extractions
There is a great deal of controversy regarding dental surgery following
radiation. Some clinicians have reported few incidents of ORN after removal of teeth
following radiation therapy.
Localized periapical and periodontal infections can be managed conservatively with
antibiotics, avoiding the immediate need for tooth removal. In situations involving
single tooth, endodontics should be considered an option, even when the tooth is
considered non restorable. Following endodontic therapy, the badly decayed tooth
crown is amputated to prevent irritation to the tongue or cheek and the exposed
portion of the root canal is sealed with a permanent restoration. A tooth managed inthis manner may serve no function but, more important, extraction is avoided.
With the use of hyperbaric oxygen, extensive oral surgery can be performed
with a substantially diminished risk of necrosis.
Hyperbaric protocols involve a series of up to 20 dives before and after
surgery in a small, sealed hyperbaric chamber. Each daily dive is 90 minutes long.
The patient must be judged physiologically and psychologically capable of enduring
these conditions. A thorough medical evaluation is a prerequisite for treatment.
Teeth are extracted following the initial 20 dives, extractions are generally
performed in the operating room. Necessary surgery including extractions,
alveolectomies, and tori removal is completed using atraumatic technique. The
wounds are closed primarily. Following the surgical procedures, the patient returns
for the completion of the second phase of hyperbaric protocol. Additional dives may
be necessary if the wound healing is not complete. Clinical evidence indicates that
using this procedure greatly reduces the risk of ORN and serves as an important tool
in the management of the irradiated patient.
Osteoradionecrosis
Osteoradionecrosis is defined by Marx as the presence of exposed bone in
the region of radiation therapy for 6 months with or without pain.Predisposing factors
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Diseased teeth
Use of partial or complete dentures
Periodontal deficiencies associated with dentitions retained within the treatment field.
Treatment options
Osteoradionecro sis associated with external beam
Local irrigation and packing of iodoform gauze impregnated with tincture of benzoin,
when the dose to bone in the local area is less than 6500 cGy and the exposure is
localized. When the dose to the bone is above 6500 cGy, hyperbaric oxygen
combined with a surgical sequestrectomy should be considered. Sharp bony
projections should be smoothed with an airotor. Antibiotics are necessary only to
control local acute infectious episodes involving the adjacent soft tissues.
Osteoradionecrosis associated with external beam and Interstitial implants
If the external beam dose to the bone is below 5500 cGy the prospects for
conservative therapy are excellent and surgical sequestration in combination with
hyperbaric oxygen is rarely needed.
Hyperbaric Oxygen Therapy
A major advancement in the treatment of osteoradionecrosis has been the
use of hyperbaric oxygen. Hyperbaric oxygen therapy (HBOT) is a medical treatment
that uses the administration of 100 percent oxygen at a controlled pressure (greater
than sea level) for a prescribed amount of time-usually 60 to 90 minutes. It helps the
body heal itself by making oxygen available to body tissues, or organs, which are notreceiving an adequate supply because of illness or trauma.
The air we normally breathe contains about 21% oxygen, which is carried
throughout our bodies by red blood cells in blood. During HBOT, the 100% oxygen
we breathe, combined with higher pressure, delivers up to 15 times the oxygen
content to all body fluids, including plasma, cerebrospinal fluid surrounding the brain
and spinal cord, lymph, and intracellular fluids. This allows oxygen levels to increase
even in areas with blocked or compromised blood supply as a result of injury or
illness,as well as in areas of tissue damage.
Increasing tissue oxygen levels produces several important long term
therapeutic benefits including enhanced growth of new blood vessels; increased
ability of white blood cells to destroy bacteria and remove toxins; increased growth of
fibroblasts (cells involved in wound healing); and enhanced metabolic activity of
previously marginally functioning cells including brain neurons.
Hyperbaric oxygen stimulates neovascular proliferation in marginally necrotic
tissues, enhances fibroblastic proliferation, enhances the bactericidal activity of white
blood cells and increases the production of bone matrix.
The Marx protocol for the treatment of osteoradionecrosis
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Stage I: These patients have osteoradionecrosis but without pathologic fracture,
orocutaneous fistula, or radiographic evidence of bone resorption to the inferior
border of the mandible. Marx recommends that patients in this group be given 30
hyperbaric treatments (2.4 atmospheres, 100% oxygen for 90 min). If at the end of
the 30 treatments, there is clinical evidence of improvements, another 20 treatmentsare added. If no clinical improvement is noted the patient is considered as non-
responder and advanced to stage II.
Stage II: After 30 hyperbaric treatments, non-responders are taken to surgery. A
surgical sequestrectomy in the local area is performed, and the wound is closed
primarily in 3 layers over a base of bleeding bone. An additional 10 hyperbaric
treatments are given; if the wound dehisces the patient is identified as a non-
responder and advanced to stage III
Stage III: Non-responders from stage II therapy and patients presenting with
orocutaneous fistula, pathologic fracture or radiographic evidence of bone resorption
to the inferior border of the mandible, are considered stage III patients. Following the
initial 30 hyperbaric treatments, bony segments of non vital mandibular bone are
resected transorally with the aid of tetracycline fluorescence under ultra violet light.
External fixation of the mandibular segments is achieved, orocutaneous fistulae are
closed, and soft tissue deficits restored with local or distant flaps. Another 10
hyperbaric treatments are given and the patient is advanced to stage IIIR.
Stage III R:10 weeks after resection, the mandible is reconstructed with a bone graft
using a transcutaneous exposure. Oral contamination of the surgical wound is to be
avoided. Mandibular fixation is achieved and maintained for 8 weeks. Ten hyperbaric
treatments are given post operatively.Contraindications to hyperbaric treatment include persistent tumour, optic neuritis,
active viral disease states and untreated pneumothorax. Complications include
barotrauma of the ear, temporary myopia, and in rare instances, pulmonary fibrosis.
The pre-hyperbaric oxygen work up includes a history and physical examination,
chest film, ophthalmologic exam, hearing test, and a complete blood count.
Management of osteoradionecrosis with myocutaneous flaps or free flaps
The irradiated nonvital bone is removed surgically down to viable bone.
Administration of tetracycline prior to surgery, and use of an ultraviolet light source
during surgery, aids in identification of bone that retains its viability. The exposed
bone is then covered with a myocutaneous flap. These flaps bring their blood supply
along with them and thus facilitate healing.
Post Radiation Prosthodontic Care
Divided into dentulous and edentulous patients
Dentulous patients
Fluoride application
Follow-up and restorative care
Endodontic therapy as an alternative
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Edentulous patients
a. Soft liners: The silicones exhibit reduced wettability and this phenomenon
contributes to an increased drag that does not allow the denture to slide easily over
the dry mucosal surface during function. The high risk of tissue abrasion plus the
poor adjustability of silicone have influenced clinicians to abandon its use inirradiated patients. There is significant increase in fungal population in patients with
radiation-induced xerostomia resulting in rapid deterioration of silicone liners.
Since trauma caused by dentures may increase the potential risk of mucosal
irritation and subsequent bone exposure, some have suggested waiting at least 6
months to a year before dentures are contemplated.
Upon initial oral examination important clinical manifestations of the radiation
treatment include appearance of oral mucous membranes, scarring and fibrosis at
the tumour site, degree of trismus, presence and nature of lymphoedema and status
of salivary function.
Translucent boggy mucosa with prominent telengiectasia implies poor tolerance to
prosthodontic restorations. With an increased risk of compromising mucosal integrity
where severe mucosal changes are present, use of dentures may be delayed or
forbidden. Scar tissue is mostly unyielding and the slightest over extension may
result in a mucosal perforation.
The less saliva, the more difficulty the patient will have in tolerating the dentures. In
addition the retention of the maxillary complete denture may be compromised due to
the film thickness of scanty and more mucinous saliva. Mandibular ridges with
severe bilateral undercuts or excessive ridge resorption with little attached mucosa
are poor candidates for complete denture service following radiation therapy.b. Impression
If xerostomia is particularly profound, a thin coating of petrolatum may be applied
over the soft modeling plastic to prevent its sticking to the dry mucosa. Particular
attention should be paid to the lingual extension of the mandibular denture because
over extension could result in a mucosal perforation. Displacement of the tissues of
the floor of the mouth, in an attempt to obtain peripheral seal, is not advocated.
Peripheral seal is virtually impossible to obtain in these patients because of the
curtailment of the patients salivary flow. Efforts to develop the lingual flange should
be directed towards gaining stability and support rather than retention. Edema of the
tongue and floor of the mouth, which is particularly prominent if the patient has
undergone a radical neck dissection, will occasionally be sufficiently large to
compromise floor of mouth posture and limit the extent of the lingual flange. Cutting
away the denture base in regions in the field of irradiation has been advocated in
some patients.
c. Vertical dimension
The clinician should consider reducing the vertical dimension of occlusion. This
consideration is based on 2 lines of reasoning. First reducing the vertical dimension
may limit the extent of forces applied to the supporting mucosa and bone during a
forceful closure. Second in patients with clinically significant trismus, entrance of thebolus is more easily accomplished by increasing the interocclusal space.
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d. Occlusal forms
The authors have come to favor lingualised or monoplane occlusal schemes with
balance facilitated by posteriorly situated balancing ramps.
A well balanced non interfering occlusion is an absolute necessity regardless of the
tooth form usede. Delivery and post insertion care
An appointment to evaluate the waxed denture allows verification of interocclusal
records and provides the patient an opportunity to satisfy esthetic considerations.
The prosthesis is flasked and processed using heat cured polymethyl methacrylate.
Soft materials have been suggested for use as denture bases. In the past, these
materials have offered little advantage over hard base materials because of their
coarse surface and propensity for support of fungal growth. Delivery procedures
must be meticulously performed. Indicating paste is used to identify areas of
excessive pressure. Denture borders should be carefully evaluated for areas of
overextension, paying special attention to the retromylohyoid area. Remounting the
dentures provides an opportunity for verifying the accuracy of interocclusal records
and developing a noninterfering occlusion. Upon completion of these procedures, the
dentures are highly polished. Some clinicians advocate that the tissue bearing
surface of the denture also be polished to eliminate any surface roughness in an
effort to minimize tissue irritation. The patient should be advised regarding the effect
xerostomia and compromised mucosa have on the potential for prosthodontic
success and should be cautioned to remove the dentures if any soreness or irritation
develop and to see the dentist as quickly as possible. The benefits of removing the
dentures while asleep and maintaining appropriate oral hygiene procedures must beexplained. Additionally the patient must be seen at frequent intervals during the first
few weeks following delivery of the dentures. Two appointments a week provide
ample opportunity to intercept any problems that may develop.
Implants in irradiated tissues
Irradiation of head and neck tumour predispose to changes in bone, skin and
mucosa, which affect the predictability of osseointegrated implants. Long term
function of osseointegrated implants is dependent on the presence of viable bone
that is capable of remodeling and turn over as the implant is subjected to stresses
associated with supporting, retaining and stabilizing prosthetic restorations. The
viability of irradiated bone may not be sufficient for remodeling and turn over of bone.
Predictability of implants in irradiated bone
Long term function of osseointegrated implants is dependent on the presence of
viable bone that is capable of remodeling and turnover as the implant is subjected to
the stresses.
There is increased risk of ORN
. The success -failure rate is dependant on
1. Anatomical site.
2. Dose to the site.3. Use of hyperbaric oxygen.
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Implants already in place tend to add to the Backscatter thus the tissues around tend
to get as much as 15% more than other areas.
Osseointegration is impaired in bone that has received more than 5000 cGy of
treatment.
There is always a risk of failure and osteoradionecrosis when placing implants inirradiated bone.
Hyperbaric oxygen can help in its success.
Abutments and all super structures are to be removed prior to the therapy.
Mucosa should be closed over the implant fixtures.
They should only be used once therapy is over, then the prosthesis can be reseated
Side effects and complication of various doses of radiotherapy:
Under 3,000 cGy -mucositis, candidiasis, xerostomia & dysgeusia begin
Over 3,000 cGyxerostomia (permanent) and taste dysgeusia , altered saliva (thick,
more acid, changed flora)
Over 5,000 cGytrismusconcerns for osteoradionecrosis
Over 6,000-6,500 cGy significant concerns for osteoradionecrosis
Stimulated Whole Salivary Flow Rates - week after beginning RT 57% decrease &
after 5 weeks (end of treatment) 76% decrease; years after RT 95% decrease.
Endocrine abnormalities: Hypothyroidism, Parathyroid adenoma and
hyperthyroidism.
Atherosclerosis occurs in doses more than 50 Gy
Progressive muscle fibrosis may limit the neck and shoulder function. Some times
trismus may also seen.Visual impairment may occur due to radiation keratitis, cataract and optic neuritis.
Radiation neuritis.
Secondary infection.
Development of maxillofacial deformity and tooth development in children.
Conclusion
Radiotherapy is a boon to the cancer patients, by radiation therapy the affected part
is preserved from complete excition; but it do cause some adverse changes in
normal cell which are making them vulnerable to infections further results in tissue
necrosis. These adverse effects can be reduced by proper treatment planning and
patient education. Radiation Therapy will improve the patients quality of life if it is
used properly, we could say it as a properly planned radiotherapy will give the new
life to the cancer patients. As being a prosthodontist we need to know these adverse
effect as well as the construction of the protecting shields and maxillofacial
prosthesis.
References:
1.Taylor T T, Clinical Maxillofacial Prosthetics, Quintessence publications, 1stedition,
Illionis, 2000, pp 3752
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2.Beumer J I, Curtis T A, Marunick M T, Maxillofacial rehabilitation Prosthodontic
and surgical considerations, Tokyo, 1995, 43105
3. doktor.baromedical.hu/media/wysiwyg/PDF/Osteoradionecrosis.pdf