Absract: overall morbidity of cancer therapy and results

Multidimensional potential risk factors of dental implants failure must be
considered when planning implant placement therapy in patients undergoing
radiation therapy in head and neck region. Factors focusing on radiation
therapy were discussed, and the negative impacts of radiation therapy on dental
implant therapy are undeniable. The bene?t
of using implant-supported dentures over conventional dentures must outweigh
the risks. Meticulous treatment planning along with careful preoperative oral examination
and good coordination with oncologic specialists cannot be overemphasized. It
is also important for the dental profession to keep abreast of the latest
available radiation therapy technologies. Additional evidence-based clinical
guidelines for implant use in head and neck patients undergoing radiation
therapy are expected. Hence this paper reviews on literature behind the effect
of radiations on dental implants.

Head and neck cancer is common, it accounts for more than 550,000 cases
annually worldwide. It is the sixth prevalent cancer site with a survival rate
of 50% over 5 years. Although the survival rate in head and neck cancer
remained unchanged during the past few decades, there is evidence that
mortality rates have decreased over the last 20 years. Treatment modalities
include a combination of surgery and radiotherapy. Surgery may cause anatomical
alterations, and radiotherapy may result in oral mucositis, xerostomia,
irradiation caries, fibrosis of blood vessels and soft tissues, and reduction
of bone-healing capacity. Atrophied and erythematous mucosa and the condition
of jaw bones render the placement of removable prosthesis a challenging
procedure; thus, failure to restore satisfactory mastication usually adds to
the overall morbidity of cancer therapy and results in decreased quality of
life of head and neck cancer patients. The use of dental implants for
rehabilitation offered many benefits over the conventional tissue-born
prosthesis. These benefits include improved retention, mastication, and patient
acceptance however, dental implants rehabilitation is complex  and it was considered a contraindication in
the past for irradiated patients. Radiation causes injury to the remodeling
system by damaging osteoclasts and decreasing the proliferation of bone marrow,
collagen, and blood vessels. Vascular injury shows as hyperemia followed by
endarteritis and decreasing microcirculation. The bone marrow become hypocellular
and hypovascular and shows signs of marked fibrosis and fatty degeneration.
Correct placement is now facilitated by the recently introduced concepts of
computer-guided implants which improved the identification of the ideal implant
location during surgery. However, Primary placement may lead to interference
with or delay of the oncological therapy including radiotherapy and is not
always available to patients in the hospital settings. Secondary placement
allows evaluation of the postsurgical status of the patients and the cancer
prognosis. When secondary placement is considered, the patient by this time is
aware of the altered physical and physiological state due to oncologic
treatment, accepts the shortcomings and is psychologically prepared to extended
treatment and rehabilitation. There is no consensus in the literature about the
threshold dose of radiation that may affect dental implant survival.
Osteoradionecrosis and implant survival may depend on the dose of radiation. It
was reported in the literature that the risk of osteoradionecrosis increase
with doses that exceed 50Gy, 60Gy, 65Gy, and 70Gy. Soft tissue necrosis can
take place with doses lesser than 50Gy, and injury to salivary glands can occur
with doses of even lesser than 20Gy. The risk and severity of
osteoradionecrosis is related  to
radiation dose, volume of irradiated tissue, and to the dental health of the
patients. It was suggested that Prior to implant placement, consultation with
the radiation oncologist is valuable to obtain radiation dose distribution that
may assist planning the best locations for implants insertion. Several authors
reported better survival rates with lower doses of radiation doses.
Nevertheless, low incidence of small-dose radiation therapy studies preclude
confirming such findings. The role of timing of implant placement The timing of
implant placement whether before or after radiotherapy is a very important
issue which can affect the success or failure of osseointegration. The side
effects of such radiation therapy to the head and neck region are well documented
in the dental literature. This treatment modality creates long-term changes in
mucosa, vascularity, taste, salivary flow, and decreased healing potential.
These objective signs of radiation treatment are accentuated by the subjective
statements of patients who receive this treatment. It is not unusual to hear
the recipient of radiation therapy describe their tissues as “thin, weak,
sore or fragile.” The prognosis for removable partial dentures depends on
the quality and quantity of the anatomic structures, the ability of these
structures to tolerate increased physiologic demands from dental prostheses,
and the capacity of the patient to accept the artificial prostheses.
Therapeutic radiation will cause a number of physiologic changes that may
adversely affect prosthetic reconstruction. Xerostomia associated with
therapeutic radiation eliminates or greatly reduces the salivary film that is
beneficial for denture comfort and is required for denture retention. Decreased
salivary flow may be associated with an increase in the rate of dental caries.
Although caries in the xerostomic patient is not the direct result of radiation
to the teeth, it appears to be a multifactorial problem associated with loss of
the buffering capacity of the saliva, loss of the lubrication from the saliva,
decreased oral hygiene because of tissue discomfort, and other less obvious
factors. A more aggressive dental management strategy should be considered for
patients with limited previous dental care, poor oral hygiene and evidence of
past dental or periodontal diseases. During Therapy Monitoring of the oral
cavity should be increased during radiation therapy in an effort to decrease
the severity of side effects. Systematically applied oral hygiene protocols may
reduce the incidence, severity and duration of oral complications. This, in
turn, reduces the odds that patients’ optimal therapeutic course will need to
be modi?ed,
which thereby increases patients’
odds of survival. Therefore, it is imperative that patients continue their oral
hygiene regimen throughout their course of cancer therapyA more aggressive
dental management strategy should be considered for patients with limited
previous dental care, poor oral hygiene and evidence of past dental or
periodontal diseases. During Therapy Monitoring of the oral cavity should be
increased during radiation therapy in an effort to decrease the severity of
side effects. Systematically applied oral hygiene protocols may reduce the
incidence, severity and duration of oral complications. This, in turn, reduces
the odds that patients’ optimal therapeutic course will need to be modi?ed,
which thereby increases patients’
odds of survival. Therefore, it is imperative that patients continue their oral
hygiene regimen throughout their course of cancer therapy

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Radiotherapy is largely used for treatment of head and neck cancer. Although
the  radiotherapy can increase cure
rates, the irradiated patient is susceptible to secondary effects  and a series of potential orofacial
complications. Radiotherapy may result in progressive  fibrosis of blood vessels and soft
tissues,  xerostomia,  osteoradionecrosis, and  reduction of bone-healing capacity, among
others. Because of the cumulative effects of 
radiation on bone vascularity, the regenerative capacity of these
tissues is limited, and this  may have a
deleterious impact on subsequent implant osseointegration. It is believed that
the irradiated hypocellular, hypovascular and hypoxic tissue is the main cause
of failures in dental implants osseointegrationAll teeth, but especially those
located within the radiation ?elds,
should be closely evaluated. However, teeth in the high-dose radiation ?eld
should be considered for extraction before radiotherapy if they are
nonrestorable; if they require significant restorative, periodontal or
endodontic intervention or if they have moderate to severe periodontal disease
(pockets of 5 mm or more).6 Factors to consider when assessing preradiotherapy
dental status include the overall condition of the patient’s dentition (caries,
periapical status, in?ammatory
periapical abnormalities), previous dental care, current oral hygiene, the
urgency of the cancer treatment, the planned therapy (radiation ?elds
and dose) and the prognosis of the cancer.

(cure or palliation). Almost all patients undergoing head and neck radiation
therapy experience con?uent
mucositis by approximately the third week of treatment. nother potential
consequence of radiotherapy to the oral cavity is ?brosis
around the muscles of mastication, leading to trismus. It is believed that jaw
exercises may limit the severity of trismus, but they will not mobilize ?brosis
once it has occurred. Bone exposed to high levels of radiation undergoes
irreversible physiologic changes including narrowing of the vascular channels
(endarteritis), which diminishes blood ?ow
to the area, and loss of osteocytes. The bone essentially becomes nonvital,
which leads to limited remodelling of bone and limited healing potential.
Xerostomia Systemic sialagogues may increase the production of natural saliva
from functional glands. There is no optimal substitute for saliva that can be
used when glands are nonfunctional. Oral Balance Gel may be the best accepted
by patients because of its extended duration of effect. Sugarless gum or
lozenges may stimulate salivary secretion in patients with residual salivary
gland function. Sugar-free popsicles, plain ice cubes or ice water may be used
to keep the mouth cool and moist. Eating foods high in ascorbic acid, malic
acid or citric acid will stimulate the glands to increase salivary ?ow,
but this measure is not recommended in dentate patients because the acidity can
further irritate oral tissues and contribute to the demineralization of teeth.
For the prevention of rampant dental demineralization and caries, patients
should apply a 1.1% neutral sodium ?uoride gel
daily (for at least 5 minutes), using a custom ?tted
vinyl tray if possible. This practice may be started on the ?rst
day of radiation therapy and continued daily as long as salivary ?ow
rates are low and the mouth remains dry. High-potency ?uoride
brush-on gels and dentifrices may be considered in those who are unable or
unwilling to comply with the use of ?uoride
trays. Oral Infection Health care providers should be concerned about
preventing local and systemic infections in addition to managing oral symptoms.
Treating infections as soon as they are detected will help to reduce pain, as
well as the spread of infection. A fungal, bacterial or viral culture is
recommended if infection is suspected. In patients undergoing head and neck
radiotherapy, Candida colonization tends to increase throughout the course of
treatment and remains increased if xerostomia occurs. Nystatin rinses are the
most widely prescribed treatment for oral fungal infections, despite a lack of
proven efficacy. For more severe infections, the use of a systemic antifungal
medication such as ?uconazole (Di?ucan)
or amphotericin B is recommended. Systemic amphotericin B must be used with
caution because of its potential to cause liver toxicity. furthermore,
chlorhexidine should be used at least 30 minutes before or after the use of any
other topical agents with which it may bind. For cancer patients with viral
infections, such as Herpes simplex 1, acyclovir (Zovirax, GlaxoSmithKline) or
derivatives are recommended for both prophylaxis and treatment. Penciclovir
(Denavir, GlaxoSmithKline), a newer topical antiviral with increased tissue
penetration, is now available. Oral Mucositis Maintaining a self-care regimen
may decrease the incidence of mucositis. The use of a common oral rinse, such
as isotonic saline or sodium bicarbonate, is often suggested, but no studies
have con?rmed
any bene?cial
effect upon mucositis. It has been suggested that patients begin prophylactic
rinses with chlorhexidine to prevent the onset of microbial infection, gum in?ammation
and bleeding, and to reduce the risk of caries. While some authors report that
a chlorhexidine oral rinse has potential effects on mucositis, others report no
effects,9 and no effects have been reported for radiationinducedmucositis to
date. Use of other oral rinses, including commercial alcohol-based mouthwashes
and hydrogen peroxide rinses, should be discontinued because of their drying and
irritating effects on the oral mucosa. The discomfort of mucositis can be
reduced with coating agents, topical anesthetics and analgesics, although
systemic analgesics are frequently needed.3 Aluminum  hydroxide/magnesium hydroxide (milk of
magnesiaMaalox)  and sucralfate have been
suggested as coating agents for the oral mucosa. Sucralfate suspension may also
be helpful in the treatment of oral pain, although the effect on mucositis has
not been clearly documented. Topical anesthetics used in rinse form may result
in intense but short-term anesthesia. However, the localized anesthesia can
increase the risk of aspiration, and their systemic absorption can cause
cardiac effects. When oral mucosal pain is present, benzydamine hydrochloride
(Tantum), doxepin suspension 0.5% or an antihistamine such as diphenhydramine
can be prescribed. Benzydamine is the only medication available that has been
shown in multicentre, double-blind controlled studies to reduce mucositis and
pain in patients with head and neck cancer. According to the current
literature, good oral hygiene, topical ?uorides
for caries prevention and benzydamine offer the greatest bene?ts.
After Therapy After the completion of radiation therapy, acute oral
complications usually begin to resolve. Patients should continue to follow an
oral health self-care regimen to keep the teeth and gums healthy and to
facilitate repair of any residual oral damage. Oral exercises should be
continued or introduced to reduce the risk and severity of trismus. Additional
dietary counseling sessions may be appropriate for patients who must make
long-term dietary adaptations to accommodate permanent changes to their oral
cavity produced by surgery and radiation. Radiation therapy and its adverse
effects Cancer cells are in a continuous state of mitosis. Ionizingradiation produces
energy that injures or destroys cells by damaging nuclear DNA or altering the
molecular characteristics of individual cells. Most patients with head and neck
cancer receive between 50 and 70 Grays as a curative dose. For concomitant use,
45Gy are used preoperatively and 55 to 60 Gy postoperatively. These doses are
typically fractionated over a period of 5 to 7 weeks, once a day, 5 days a
week, with a daily dose of approximately 2 Gy. Normally, Initial changes in
bone caused by irradiation result from direct injury to the remodeling system
(osteocytes, osteoblasts, and osteoclasts). In addition, vascular injury
precedes hyperemia, followed by endarteritis, thrombosis, and a progressive
occlusion and obliteration of small vessels. With time, the bone marrow
exhibits marked a cellularity and avascularity, with marked ?brosis
and fatty degeneration. osteoradionecrosis occurs in the mandible more often
than the maxilla. Although 30% of cases may be asymptomatic, more patients with
osteoradionecrosis present pain, ?stula
formation, and in more severe cases, spontaneous bone fracture. Recent
systematic reviews found the risk of developing osteoradionecrosis in
irradiated head and neck cancer patients as low as2%; however, the risk can be
higher after tooth extraction. Radiation therapy on implant survival Many
studies have shown that dental implant therapy in irradiated patients is not
less favorable than in the non-irradiated population.


Survival rates of dental implants may be affected negatively by radiotherapy,
however, they can Osseointegrated and remain functionally stable and hence they
can be considered a viable treatment option for rehabilitation and improvement
of the quality of life of head and neck cancer patients. Maxillary sites, use
of bone grafts and higher radiation doses are negative prognostic factors.
Prospective cohort studies and randomized controlled trails are still needed to
draw more evidence based conclusions about survival of dental implants in head
and neck cancer patients.