Clinical dental management of the head and neck irradiated patient: topics of interest for clinicians

Aim: To discuss important topics regarding the dental procedures performed in patients before, during and after the radiotherapy treatment. The biological effects of ionizing radiation on bone tissue focusing on clinical care will be described. The invasive and not invasive procedures after radiotherapy treatment in the head and neck region will be addressed using scientific evidences to determine the appropriate moment for tooth extractions, periodontal management, and preventive procedures for osteoradionecrosis. Methods: Thirty-three studies including original studies and reviews were selected in MEDLINE database (PubMed). No year of publication restriction was applied. Language was restricted to the English, and the following Medical Subject Heading terms were used:

Aim: To discuss important topics regarding the dental procedures performed in patients before, during and after the radiotherapy treatment.The biological effects of ionizing radiation on bone tissue focusing on clinical care will be described.The invasive and not invasive procedures after radiotherapy treatment in the head and neck region will be addressed using scientific evidences to determine the appropriate moment for tooth extractions, periodontal management, and preventive procedures for osteoradionecrosis.Methods: Thirty-three studies including original studies and reviews were selected in MEDLINE database (PubMed).No year of publication restriction was applied.Language was restricted to the English, and the following Medical Subject Heading terms were used: radiotherapy, osteoradionecrosis, dental management.Studies of osteoradionecrosis involving clinical management of irradiated patients, with an emphasis on updated guidelines and protocols were selected.Results: Care in dental procedures were related about restorative treatment, endodontic treatment, rehabilitation for edentulous regions using prostheses and implants and periodontal procedures before, during and after RTX treatment.Conclusions: The dental procedures should and can be performed before, during but also after radiotherapy.However, the clinical procedures should be less invasive as possible.A maintenance plan that reduces the necessity for major and more invasive treatments after radiotherapy is recommended.

Introduction
Radiotherapy (RTX) treatment is widely used to treat various types of head and neck cancers 1 .The purpose of RTX is to control the growth or elimination of the tumor 1 , reducing the possibility of recurrence and improving the patient's quality of life 1 .RTX treatment is indicated as a palliative protocol of incurable cancers 1 .Despite of the benefits of this therapy, some patients frequently are involved with adverse effects caused by ionizing radiation 2,3 .The main complications associated with RTX are: mucositis, xerostomia, changes in salivary quality and quantity, opportunistic infections, tissue fibrosis, sensory dysfunctions such as dysgeusia, increased periodontal disease progression, caries and osteoradionecrosis (ORN) 4 .These intercurrences can have acute manifestation, during the treatment, or chronic manifestation after the completion of the treatment 4 .
The clinical characteristic of ORN is bone necrosis due to hypoxia, hypovascularization and hypocellularity 5 , with loss of mucosal integrity, associated or not with oral environment bone exposure 2 .The ORN is the most serious adverse effect of RTX, compromising the tissue integrity and health of the oral structures.The ORN incidence ranges from 5 to 30% of patients who have undergone head and neck RTX 3 .The incidence of RTX has decreased with the use of the most modern radiation techniques 3 .
Several risk factors are associated with the development of the ORN, such as smoking, periodontal disease, alcohol abuse, intensity and duration of radiation 2 .Controlling the risk factors is important to minimize the development of ORN.The approaches proposed for the treatment of ORN involve non-invasive techniques such as maintaining the quality of oral hygiene, the use of antibiotic therapy, and also extensive surgical procedures to remove the necrotic bone 2 .The high uncertainty rate of the infection control is a factor that must be considered for choosing the ideal treatment 2 .
The knowledge about the manifestations caused by ionizing radiation in the oral cavity has great importance for clinicians.Many professionals still have doubts regarding the treatment planning and the management of patients involved with RTX.Despite some other reviews have been focused on the management of the head and neck cancer patients 6,7 , the continuous update of the information about the specific care about the preventive and therapeutic procedures in patients' wit history of head and neck cancer is of a paramount importance.Therefore, this study aimed to describe and clarify the dental procedures performed by clinicians in cancer patients before, during and after RTX treatment.

Materials and methods
Thirty-three studies were included in this narrative review.twenty-one these studies were original researches while twelve were reviews.The reviews of literature were no excluded due to the informative nature of this review, approaching different protocols of care in the head and neck irradiated patient.These studies were searched in the MEDLINE databases (PubMed).All selected through the focus on the management of irradiated patients in the head and neck region.No pub-lication year restriction was applied.The language was restricted to English, and the following Medical Subject Heading terms were used: radiotherapy, osteoradionecrosis, dental management.Studies on osteoradionecrosis involving clinical management of irradiated patients, with an emphasis on updated guidelines and protocols, were selected.

Dental procedures before and during RTX treatment
Before starting RXT, the professional must perform all necessary adequacy of the oral environment 1 .Caries lesions treatment, subgingival scaling, endodontic treatments or tooth extraction that could be the focus of infection should be performed 2 .These procedures should be performed at least two weeks before to start the RTX treatment 2 .The prevention of ORN is based on elimination of the oral cavity infectious conditions at the pre-RXT phase, as well as to prevent the invasive procedures during and after RXT treatment 8 .Monitoring the quality of oral hygiene should be also always performed, since the development of ORN is also associated with poor oral hygiene 8 .
During the irradiation period, mucositis, opportunistic infections such as candidiasis, salivary gland dysfunctions such as xerostomia and taste alterations are frequently reported by patients 9 .During the RTX, invasive dental procedures are not recommended 2 .Prior monitoring the patient oral conditions should be performed 2 , except in cases the occurrence of an emergency, then the invasive procedures are necessary for maintaining the patient's safety and health.

Dental procedures after RTX treatment
Post-RXT patients may have chronic complications such as ORN, xerostomia and trismus 9 .The irradiated patients may need dental care requiring the performance of various dental procedures, such as tooth restorations, endodontics, rehabilitation, among others 10,11 .It is important that clinicians understand the consequences of RTX on the mucosa, bone tissue and dental tissue to prevent the installation of ORN and failure of clinical procedures 12 .
Ionizing radiation produces hypoxia, hypocellularity and hypovascularization that can alter the regenerative potential of the soft and hard tissues 2,13,14 .Changes in tooth and bone structure can occur due to degradations in amine components that can mechanically alter enamel 15,16 , dentin 12 , and bones 14,15,17 .The effect of ionizating radiaton on the salivary flow and the xerostomia reduce the protection of this fluid against pathogens and enhance the friction on the mucosa during the oral chewing that could be the trigger for the occurrence of the mucositis lesions 18 .

Extractions
Post-RTX extraction is an important risk factors for the development of the ORN 19 , then this procedure should be avoided during this period 3 .A safety period for the development of the ORN is inconclusive 3,12 .The tooth extractions performed during post-RTX can result on ORN, due the invasive procedure in bone and mucosa tissues, which can compromise the microarchitecture and vascularization 3,5,12,19 .
A retrospective study evaluated 32 patients with tooth extraction after RTX and showed the ORN in 12.1% (9 patients) 19 .The patients with ORN received higher radiation dose (62.0 Gy vs. 37.4 Gy) and longer treatment time until extraction (41.2 months vs. 28.2months) than the groups of patients without ORN.The recent systematic demonstrates that the presence of risk factors such as smoking, radiation dose and duration of treatment are more predictable aspects in decision-making when performing dental extractions than the time after RTX 3 .
The possibility of occurrence of ORN after tooth extraction is a possible and uncertain complication.If necessary, the extraction should be performed less traumatically possible, avoiding large flaps and osteotomies in order to improve the healing process 2 .Adjunct therapies, such as photobiomodulation, ozonetherapy, PENTOCLO protocol, hyperbaric chambers, may also be indicated, as early intervention may reduce the risk of ORN 20 .

Restorative treatment
In irradiated patients increased the risk of developing dental carious lesions due to multiple factors 21,22 .The development of carious lesions after RTX treatment can occur mainly from three months after irradiation and can lead to a severe oral health impact 15,22,23 .These effects can occur due to the degradation of the organic components of dentin and enamel, which stimulate the increasing of its rigidity, making less efficient to support occlusal forces, which leads to the tooth wear 23,24 .The reduction or qualitative alteration of salivary flow turns the patients as a greater risk for developing dental caries due the limited pH buffering function promoted by saliva, as well as the dryness of the oral mucosa that makes oral hygiene procedures more uncomfortable 18,24 .
The rapid progression of the carious lesions on enamel and dentin and the structural substrate changes make the restorative protocols a major challenge due the poorly adhesive interaction with the dental substrate 12,24,25 .It has been indicated the use of the neutral fluor application periodically 23,26 .In patients with xerostomia and high risk of radiation carious lesions and poor adherence to preventive fluoride therapy, the use of conventional and resin modified glass ionomer cement are more effective in protecting recurrent carious lesions 10 .

Surgical and non-surgical periodontal treatment
Periodontal disease occurs due to an imbalance between the periodontal microbiota and the host response, and the process of oral dysbiosis may be responsible in part for the disease progression 8 .RTX can be an important agent for periodontal microbiota dysbiosis due to reduced salivary flow, which is associated with less efficient oral hygiene 27 .RTX induced fibrotic effects on connective tissues make periodontal tissues less competent in regenerative processes due to reduced oxygenation found especially in terminal-type circulation 28 .These effects together increase the host's susceptibility to present more aggressive periodontal disease, increasing the risk of tooth loss after RTX treatment 29 .
Due to the risks of ORN after tooth extraction, a personalized treatment and maintenance plan must be indicated considering the periodontal health status and systemic conditions pre-RXT 8 .The treatments must be completed as soon as possible before RTX, being the full-mouth scaling technique is indicated 27,28 .Periodontal therapy for head and neck cancer implemented before, during and after treatments results in a significant improvement on periodontal health, but this therapy should be maintained, otherwise periodontal disease continues its progression 8,28 .

Endodontic treatment
Due to the increased carious lesions activity in patients after RTX, endodontic treatment should be necessary to avoids more aggressive procedures such as extraction 11,21 .However, some factors such as the reduction of the dental pulp oxygenation the structural tooth fragilization can complicate the diagnosis and reduce the endodontic treatment success 11,21 .Pulp oxygenation levels are reduced after 4-6 months, which can impair pulp diagnosis by promoting a negative sensitivity response in vital pulps and directing unnecessary endodontic interventions 21 .If pulp exposure is present, 6-12 months should be performed, due the transitory loss of pulp sensitivity caused by RTX 21 .The endodontic treatment associated with RTX, can increase the tooth structural weakening 21 .Resin composite restorations are recommended to direct restorative material for restoring the endodontically treated teeth, strongly avoiding the use of the amalgam 30 .It is also important and recommended to replace amalgam restorations prior to RTX treatment 31 .

Rehabilitation for edentulous regions using prostheses and implants
Most irradiated patients mainly seek treatment for edentulous regions, usually as a result of multiple tooth extractions performed before RTX treatment 12 .Oral rehabilitation is important to improve the patient's quality of life 31 .It is essential that the clinicians understand the procedures that should be avoided in this post-radiation period 32 .Treatments with partial or complete dentures must be carefully performed.The patient follow-up is essential so mismatched dentures can cause damage to the mucosa can generate trauma that predisposes ORN 31,33 .
It is not well established the safer rehabilitation procedure for post-RTX patients 32 .When fixed prostheses are indicated, it should be taking in consideration that the tooth substrate after the RTX become more fragile, reducing the predictability of this treatment 12 .Another alternative for oral rehabilitation is the use of dental implants supported prostheses without interfering with compromised mucous membranes and teeth 32,33 .The installation of implants prior to RTX is safer procedure with high success and survival levels 33 .The installation of implants after the RTX period present a slightly higher level of complication compared with the implants installed in the general population 32 .The innovations on macrostructure and microstructure implants surface, and on the implant installation techniques guided by surgery without flap opening, can make the rehabilitation of post-radiotherapy patients increasingly safer and more predictable, but this clinical procedures still requires further investigations.

Discussion
The treatment of head and neck cancer is an extremely challenging condition for maintain the patient's quality of life.The patients tend to resist to the highly aggressive treatments such as extensive surgery to remove the tumor, the RTX protocol, and in many situations to perform multiple tooth extractions prior to the RTX 3 .During and after the period of active treatment, therapeutic planning aiming proper oral rehabilitation is necessary in order to limit the acute and chronic damage caused by cancer treatment 2 .It is important to recognize that the effects of RTX are cumulative, and the indication of the dental procedures must consider the limitations imposed by the alterations on the dental and bone caused by irradiation, avoiding as much as possible the occurrence of ORN.
To avoid this complication, has been suggested not performing dental extraction due the ORN 19 .Bone tissue intervention should ideally be performed before RTX 3 .This indication is based on the progressive process of connective tissue fibrosis that reduces the vascularization, cellularity and oxygenation of oral tissues, especially bone tissue, which can impair the repair processes 5,12,13,28 .The bone tissue has the slower regenerative potential than soft tissues 2,5,14,28 .During the healing phase, especially the post-extraction alveolar repair occurred by second intention, makes this tissue more susceptible to contamination and subsequent development of necrotic lesions, which are difficult to treat 2 .
There is an important relationship between the occurrence of cancer in the head and neck region and poor periodontal conditions, since the risk factors are shared 27,29 .It is expected that patients indicated for RTX treatment may have more severe and active periodontal disease than the general population 29 .Periodontal treatment after RTX should be performed as quickly and less aggressively as possible, avoiding surgical procedures to access root surfaces 8,29 .Supportive periodontal therapy should be performed at least every 3 months to prevent disease progression that the risk of tooth loss 4 .It is recommended that teeth with a questionable periodontal prognosis should be removed at least 14 days prior to initiation of RTX 28 .
If the treatment plan and preventive procedures before RTX are indicated for the teeth maintenance.Special attention is essential due the changes in the protein portion on the dentin, enamel and at the cementoenamel junction substrate.Associated with the salivary flow reduction the developing radiation carious lesions is increased 15,22 .The adhesive systems efficiency is reduced in forming prober hybrid layer to dentin substrate and the different restorative materials 12 .Thus, restorative materials that allow the continuous release the fluoride, such as conventional or resin modified glass ionomer cements should be chosen, reducing the recurrent carious lesions, and the dependence on the bonding interface promoted by adhesive systems 12 .More extensive carious lesions with pulp involvement may indicate endodontic therapy, that will further weaken the tooth structure affected by RTX 34 .
The dosage used and the time elapsed of the RTX should be taken in consideration during the planning of the rehabilitation of the edentulous areas 28 .It has been described that muco-supported prostheses must be well adapted to avoid trauma to the mucosa, as this tissue is also fragile and can more easily lose its integrity and expose the adjacent bone tissue 31 .The denture-supported dentures planning must consider the quality of the remaining abutment teeth, avoiding involving teeth with large restorations with endodontic treatment as abutments 11,21 .Teeth with a history of periodontal disease are more susceptible to disease progression after RTX and should also be avoided as support for protheses 4 .
The security of the implant placement in patients after the RTX are inconclusive.It has been described that the rehabilitation with dental implants has been indicated as a good alternative to rehabilitate patients after RTX and has shown relatively good levels of clinical survival 33 .It has been also showed that the bone tissue surgery may present higher risk factor for the ORN installation 34 .Indeed, the myriad of protocols of RTX impairs a properly documentation regarding the safety for implants placement in these patients 19 .
Technological advances may improve the outcomes of the oral treatment in the RTX patients.The advances in the mechanical of the restorative materials associated with adhesive procedures, and preventive protocols may improve the treatment complication related with the carious lesions 11,30 .The implants design and microstructure advantages, as well as the use of less traumatic surgeries may enhance the oral rehabilitation predictability 35 .In addition, the dental therapy may become more safety as much the RTX protocols become more focused on injuries 33 .The dental treatment after RTX is possible to be performed, but they should be less invasive as possible.

Conclusion
In conclusion, the dental procedures before, during and after RTX should be performed, however they should be always less invasive as possible.However, the type complexity of the treatment is patient and moment dependent.A maintenance plan performed before, during and after RTX is strongly recommended to reduce the necessity for major and more invasive treatments after radiotherapy.