Almost all patients (90-100%) who have undergone radiation treatment (RT) of head and neck region develop at least one oral complication. Oral complications of head and neck RT can be acute and chronic. Acute complications occur during RT and include oral mucositis, dry mouth and taste sensation disorder. Chronic complications occur several weeks, months or years after RT cessation, and include radiation caries, osteoradionecrosis and trismus.Gotovo svi pacijenti (90-100%) koji su podvrgnuti terapijskom zračenju u području glave i vrata razviju neku od komplikacija u usnoj šupljini. Oralne komplikacije terapijskog zračenja glave i vrata mogu biti akutne i kronične. Akutne komplikacije nastaju tijekom zračenja i u njih ubrajamo oralni mukozitis, suhoću usta i poremećaj okusne osjetljivosti. Kronične
komplikacije nastaju nekoliko tjedana, mjeseci ili godina po završetku zračenja, i podrazumijevaju radijacijski karijes, osteoradionekrozu i trizmus

Ana Andabak Rogulj

Božana Lončar Brzak

Maja Milenović

Vanja Vučičević Boras

Vlaho Brailo

English

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89REVIEW Libri Oncol. 2017;45(2-3):89–93ORAL COMPLICATIONS OF HEAD AND NECK IRRADIATIONANA ANDABAK ROGULJ, BOŽANA LONČAR BRZAK, VANJA VUČIĆEVIĆ BORAS, VLAHO BRAILO and MAJA MILENOVIĆDepartment of Oral medicine, School of Dental medicine, University of Zagreb, Zagreb, CroatiaSummaryAlmost all patients (90-100%) who have undergone radiation treatment (RT) of head and neck region develop at least one oral complication. Oral complications of head and neck RT can be acute and chronic. Acute complications occur during RT and include oral mucositis, dry mouth and taste sensation disorder. Chronic complications occur several weeks, months or years after RT cessation, and include radiation caries, osteoradionecrosis and trismus.KEY WORDS: oral cavity, head and neck irradiation, acute complications, chronic compllications.ORALNE KOMPLIKACIJE ZRAČENJA GLAVE I VRATASažetakGotovo svi pacijenti (90-100%) koji su podvrgnuti terapijskom zračenju u području glave i vrata razviju neku od  komplikacija u usnoj šupljini. Oralne komplikacije terapijskog zračenja glave i vrata mogu biti akutne i kronične. Akutne komplikacije nastaju tijekom zračenja i u njih ubrajamo oralni mukozitis, suhoću usta i poremećaj okusne osjetljivosti. Kro-nične komplikacije nastaju nekoliko tjedana, mjeseci ili godina po završetku zračenja, i podrazumijevaju radijacijski karijes, osteoradionekrozu i trizmus.KLJUČNE RIJEČI: usna šupljina, radioterapija glave i vrata, akutne komplikacije, kronične komplikacije.* All article fi gures are from archive of Department of Oral medicine, School of dental medicine, University of Zagreb.INTRODUCTIONOral complications of head and neck irrradi-ation can be acute and chronic. Acute complica-tions occur during the radiation treatment (RT) and last 3-4 weeks after completion of therapy. These complications are result of toxic products that arise in irradiated tissue. Acute complications are oral mucositis, taste loss and dry mouth. Chronic complications develop gradually; weeks, months or years after the end of RT, as a result of decreased blood supply to the tissue, the forma-tion of connective tissue and muscle fi brosis, and changes in cell number (1). Chronic complications are radiation caries, trismus and osteoradionecro-sis (2).ACUTE COMPLICATIONS OF HEAD AND NECK IRRADIATIONOral mucositisThe fi rst acute and the most common oral complication of head and neck RT is oral mucositis Lib Oncol. 2017;45(2-3):89–9390(OM). This mucosal damage develops in 80-90% of the patients during the early phase of RT and con-tinues for 2–3 weeks post treatment period (3). Oral mucositis is defi ned as an infl ammation of the oral mucosa due to damage of DNA and subse-quent death of basal keratinocytes. Cli nically, OM manifests as ulcerative infl ammation (Figure 1) of the mouth associated with pain, dysphagia, odyn-ophagia and diffi  culty speaking which can lead to discontinuation of RT. Pathogenesis of OM in-volves fi ve stages: initiation, activation, signal am-plifi cation, ulceration and healing. During the ul-ceration stage, patients develop ulcerations colo-nized by microorganisms that further promote epithelial damage. The healing stage starts when DNA is no longer exposed to irradiation (4).The fi rst clinical sign of OM, which develops during the fi rst week of RT, is whitish of oral mu-cosa. During the third week of RT, patients devel-op ulcerations covered with fi brinous pseudo-membranes that are prone to secondary infection. The intensity of OM depends on several factors related to RT, and they include total dose, frac-tion size, fi eld size, number and frequency of frac-tion, and type of ionizing irradiation (3,4). Numer-ous scoring scales are available for the classifi ca-tion of OM (5-7), but the most used one is the one established by the World Health Organization (WHO) (8).The WHO scoring scale for OM according to WHO based on clinical appearance and functional status:• grade 0 (none) = no pain,• grade 1 (mild) = oral soreness and erythema,• grade 2 (moderate) = erythema and ulcerations, solid diet tolerated,• grade 3 (severe) = oral ulcers, liquid diet only,• grade 4 (life-threatening) = oral alimentation impossible.Up till now, there is still no eff ective therapy for the prevention of OM in head and neck irradi-ated patients. The treatment of OM is symptom-atic, and involves pain management, infection prevention and maintaining normal functioning of oral cavity (9).XerostomiaXerostomia is one of the most common and diffi  cult oral complication of RT. It develops in the early phase of RT and becomes chronic oral com-plication due to irreversible irradiation damage of salivary glands (Figure 2). Lack of saliva predis-poses other oral complications such as dental car-ies, oral infections, dysgeusia, dysphagia, oral pain and discomfort (10). Consequently, amount of saliva decreases, together with salivary compo-sition changes. Concentration of diff erent saliva ions and proteins increases, while the concentra-tion of the bicarbonate ion decreases, causing low pH and low buff er capacity (11,12). Parotid glands mostly produce stimulated, watery saliva and it’s serous acinar cells are more radiosensitive than mucous cells of submandibular and sublingual glands (13). The main etiologic factor for the de-velopment of xerostomia is irradiation of parotid glands, as well as total dose of irradiation (14). Xe-rostomia becomes chronic oral complication if ra-diation dose exceeds 40 Gy, which is usually the case in the treatment of head and neck tumors, when total dose is greater than 60 Gy. In that case, salivary production decrease up to 80% (1). It has been shown that use of intensity-modulated radi-ation therapy (IMRT) can reduce the radiation dose to salivary glands and decrease symptoms of xerostomia (15,16). Changes in saliva seriously af-fect the quality of life, and salivary glands preser-vation during RT may reduce long-term salivary gland hypofunction. Treatment options implies the use of saliva substitutes which are mainly based on carboxymethylcellulose (10).Taste disorderDuring RT most of patients develop complete or partial taste loss. The preavlence of taste disor-der in patients receiving RT alone is 66.5%, but when it is combined with chemotherapy it goes up to 76% (17). Taste disorder occurs as a result of direct radiation eff ect on taste buds which are ra-diosensitive and damaged at doses of 10 Gy (3). Except of taste buds damage, taste disorder also occurs due to changes in salivary fl ow and compo-sition. However, most of patients state their taste disorder as moderate. Mostly, taste sensation re-turn to normal within 2-6 months after RT cessa-tion, and for that reason treatment is not neces-sary. However, in about 15% of patients, taste dis-order can last longer, in some cases even after 5-7 years. To date, there are no recommended preven-tive and curative actions in this respect (17). Ami-fostine, zinc gluconate and dietary counseling 91Lib Oncol. 2017;45(2-3):89–93have been tested for prevention or treatment of RT related taste disorder, but with varying success (18,19).CHRONIC COMPLICATIONS OF HEAD AND NECK IRRADIATIONRadiation cariesRadiation caries is primarily result of sali-vary hypofunction, saliva composition changes and increase in acidogenic bacteria number. There-fore, secreted saliva is thick, sticky and viscous fol-lowed by decrease in pH values and increase in the number of acidogenic bacteria - S. mutans,  Lactobacillus sp. and Candida sp. (10) These saliva changes increase the risk for dental caries and oral infections development. Irradiation also has a di-rect harmful eff ect on dental hard tissue, which depends on radiation dose, in case the teeth are located in the radiation fi eld. Doses lower than 30 Gy cause minimal harmful eff ect on hard dental tissue, while doses greater than 60 Gy increase risk of tooth breakdown 10 times. Usually, radia-tion caries lesions are located in the cervical re-gion, and most aff ected teeth are mandibular inci-sors (Figure 3). These caries lesions are very pro-gressive and may lead to tooth breakdown in only few months (3,12). Despite their progressed clini-cal presentation, this lesions are painless (20).The risk of development of radiation caries in head and neck irradiated patients is lifelong, therefore proper oral hygiene, fl uoride products usage and regular dental check-ups (every one to Figure 1. Oral mucositisFigure 2. XerostomiaFigure 3. Radiation cariesFigure 4. Mandibular osteoradionecrosisLib Oncol. 2017;45(2-3):89–9392three months) to avoid the most serious complica-tion, which is osteoradionecrosis, are extremely important.OsteoradionecrosisThe most serious chronic and irreversible ra-diation complication is osteoradionecrosis (ORN), a consequence of the harmful radiation eff ect on the bone. The defi nition of ORN is considered to be „exposed bone area without signs of healing for at least 3 months and without relapse of the underlying disease“ (1). However, there is no uni-versally accepted ORN defi nition in the literature, therefore, prevalence and incidence data of jaw ORN are not known. In the literature, relative fre-quency data ranges from 0-7.1%, but for the pa-tients with oral cancer it is signifi cantly higher and goes up to 13.6% (21). Two-thirds of ORN cases localized in the orofacial region are associated with some traumatic events such as tooth extrac-tion, traumas with unadapted prosthesis, biopsy and periodontal surgery. For that reason, dental extractions must be avoided after RT cessation. In case dental extractions are necessary, it is recom-mended to perform them during the fi rst 5-6 months after RT. Infl ammation and obliteration of the blood vessels that appear after RT, and cause hypovascularization with decreased healing abil-ity, is not process which occurs during one night. It takes 5-6 months to develop this degenerative processes. These changes are irreversible and pro-gressive, and risk for ORN development remains viable. In one-third of cases ORN can occur spon-taneously (22,23).Risk of ORN increases with total radiation dose (> 65 Gy), volume of irradiated bone, irradia-tion mode and additional chemotherapy. Other risk factors reported in the literature are poor oral hygiene, malnutrition, trauma, smoking, uncon-trolled diabetes and alcoholism (21,22). The most commonly aff ected bone in the orofacial region is the mandible (Figure 4). Subjective symptoms of ORN are pain, although in the initial stage it can be completely painless, taste changes, halitosis, dyses-thesia and food accumulation in necrotized areas of exposed bone. Untreated ORN can lead to the fi s-tula formation and pathological fractures of the af-fected bone (24). Management of ORN includes conservative treatment, surgical debri dement with the use of adjunctives therapies of antibiotics and/or hyperbaric oxygen (HBO) treatment (25).TrismusTrismus or reduced mouth opening is a re-sult of harmful radiation eff ects on the masticato-ry muscles and/or temporomandibular joint. It develops 3-6 months after RT cessation and very often is irreversible. RT causes spasm and fi brosis of masticatory muscles leading to reduced mouth opening with interincisal space less than 35 mm. Not every patient who receives RT of head and neck will develop trismus, and the prevalence of this condition, reported in the literature, is be-tween 5-40% (26,27). The severity of trismus varies depending on the mode of irradiation, total dose of radiation, treatment modality, tumor location and physical condition (28,29). In the literature, reported data show that a total dose of radiation greater than 60 Gy increases the incidence of  trismus up to 47% (28). Furthermore, use of IMRT decreases the incidence of trismus. Development of trismus negatively aff ects quality of life, result-ing in diffi  culties with food intake, speech and maintaining oral hygiene (30). It is very important to identify early signs of trismus considering the fact that early treatment can signifi cantly aff ect its prevention. For the prevention as well as for the treatment of reduced mouth opening passive and active physiotherapy can be performed (31).REFERENCES 1. Sciubba JJ, Goldenberg D. Oral complications of radio-therapy. Lancet Oncology. 2006;7:175-183. 2. Huang SH, O’Sullivan B. Oral cancer: Current role of radiotherapy and chemotherapy. Medicina Oral, Pato-logia Oral Y Cirugia Bucal. 2013;18(2):e233-e240. 3. Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP. Oral sequelae of head and neck radiotherapy. 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Support Care Cancer. 2010;18(8):1033-8.Corresponding author: Ana Andabak Rogulj, Department of Oral medicine, School of Dental medicine, University of Zagreb, Gundulićeva 5, Zagreb, Croatia. e-mail: anaanda-bak@gmail.com

Oralne komplikacije zračenja glave i vrata

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