Impact of radiotherapy to the head and neck region on the oral condition

Investigations of the oral function of patients undergoing radiotherapy (RT) to the head and neck region are relevant for the overall quality of life. Considering the possible impact of the side-effects on nutrition, the recovery of these patients might be impaired. This study aimed at Research, Society and Development, v. 9, n. 10, e3299108753, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i10.8753 2 investigating the oral condition of patients submitted to RT to the head and neck region. A single-center, cross-sectional mixed analysis assessing the oral conditions of patients before RT (group 1) and after 12-months of RT (group 2) was performed. Following inclusion and exclusion criteria consideration, fifty (n=25) patients were included in this study. A calibrated examiner conducted the oral examination, the following variables were assessed: a) DMF index: decayed, missing and filled teeth; b) xerostomia and dysgeusia, subjective assessment of salivary function and taste; c) simplified oral hygiene index – OHI-S, with plaque disclosing solution; d) unstimulated sialometry, assessment of salivary function. Statistical analysis compared the groups considering a significance level of 5%. The group evaluated after 12 months of RT showed high rate of dry mouth (92%) and dysgeusia complaint (72%) while no patient reported in group 1. Statistically significant difference was observed in the comparison of group 1 and 2 regarding DMF index (> 64%), OHI-S index (>38%), and unstimulated sialometry (<70%). Patients submitted to RT to the head and neck region for the treatment of cancer experience oral complications even at 12 months after the last session of RT.

investigating the oral condition of patients submitted to RT to the head and neck region. A single-center, cross-sectional mixed analysis assessing the oral conditions of patients before RT (group 1) and after 12-months of RT (group 2) was performed. Following inclusion and exclusion criteria consideration, fifty (n=25) patients were included in this study. A calibrated examiner conducted the oral examination, the following variables were assessed: a) DMF index: decayed, missing and filled teeth; b) xerostomia and dysgeusia, subjective assessment of salivary function and taste; c) simplified oral hygiene index -OHI-S, with plaque disclosing solution; d) unstimulated sialometry, assessment of salivary function. Statistical analysis compared the groups considering a significance level of 5%. The group evaluated after 12 months of RT showed high rate of dry mouth (92%) and dysgeusia complaint (72%) while no patient reported in group 1. Statistically significant difference was observed in the comparison of group 1 and 2 regarding DMF index (> 64%), OHI-S index (>38%), and unstimulated sialometry (<70%). Patients submitted to RT to the head and neck region for the treatment of cancer experience oral complications even at 12 months after the last session of RT.
Keywords: Radiotherapy; Oral Health; Head and Neck Neoplasm.

Introduction
Malignant neoplasms of the lip and oral cavity is considered the fourth most common site and the sixth cause of cancer deaths in middle-and low-income countries (Ferlay, 2018).
Currently, primary treatment of oral cancer is surgical resection, which is frequently complemented by radiotherapy (RT). Chemotherapy, most often using cytotoxic, platin-based agents is also used in more advanced cases or in the treatment of recurrences (Rajesh, 2017).
These complications are well-stablished as side-effects of RT in the oral cavity, some of them reverberate over 6 months from the start of RT (Rajesh, 2017). Investigations of the oral function of patients undergoing RT to the head and neck region are relevant for the overall quality of life and, considering the possible impact of these side-effects on nutrition, also for the recovery of these patients. This study aimed at investigating patients' oral condition before and after RT to the head and neck region.

Study design and population
This is a single-center, cross-sectional mixed analysis assessing the oral conditions of head and neck cancer patients before and after radiotherapy to the head and neck region. The institutional review board at Lauro Wanderley University Hospital at the Federal University of Paraíba (Brazil) approved the study protocol and an informed consent was obtained from all volunteers (CAAE n o 55164516.5.0000.5188).
Patients scheduled for the treatment of cancer through radiotherapy to the head and neck region and patients who underwent the mentioned treatment 12 months before screening, at Napoleão Laureano Hospital, João Pessoa, Brazil, were eligible to participate in the study. This is a public hospital dedicated only to the treatment of cancer. Patients were invited to Research, Society and Development, v. 9, n. 10, e3299108753, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i10.8753 5 participate in the study, as they appear for treatment at the hospital. If the patient volunteered to take part in the study, exclusion criteria were assessed. Exclusion criteria included the following: (1) patients with any type of syndrome; (2) patients with physical, sensory, behavioral, cognitive, or even emotional disability; (3) patients with less than 20 remaining teeth; (4) patients under 40 or over 70 years of age.

Data collection
Fifty participants were included in this study, this sample was divided in Group 1 (n = Anamnesis and clinical oral examination were performed at the dental clinic of the faculty of dentistry in the same institution mentioned previously, both in the same day. All patients were examined during the same period of the day, middle morning. Only one examiner conducted the whole assessment, the following criteria were used: a) DMF index: decayed, missing and filled teeth, proposed by the World Health Organization (WHO); b) for xerostomia and dysgeusia, subjective assessment of salivary function and taste c) for the simplified oral hygiene index -OHI-S, the eviplac plaque disclosing solution (Biodynamics, Ibiporã, Paraná, Brazil) was used. d) unstimulated sialometry, assessment of salivary function.
Baseline features, medical history, tumor characteristics and stage were assessed in the same opportunity. Examiner was calibrated and reliability was tested previous to patients assessment (κ = 0.87) (Landis, 1977). Distortion of the sense of taste and dry mouth perception were considered as present or absent, other variables were recorded as continuous data.

Statistical Analysis
Baseline descriptive data (categorical and continuous) were presented in terms of absolute values, percentages, mean, and standard deviations (sd). Baseline differences were examined using unpaired t test (independent means) for continuous data, chi-squared and Fisher's exact-test for qualitative data. Groups differences regarding oral complications were tested by unpaired t test (independent means) and Fisher's exact-test. P values less than 0.05 Research, Society and Development, v. 9, n. 10, e3299108753, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i10.8753 6 were considered as statistically significant. GraphPad Prism 6.0 software was used for analysis of data.

Results
Social-demographic data were collected for all subjects at baseline and were presented on Table 1. Seven variables were studied across the two investigated groupsage, age groups, sex, education, marital status, employment status, and harmful habits, no significant difference in distribution of any of the variables between the groups was found. There was neither significant difference in distribution of any of the social-demographic variables between the two groups nor even in tumor characteristics and stage (all p < 0.01) ( Table 2).  Data regarding dysgeusia and dry mouth sensation were obtained for both groups, revealing an increase of 72% and 92%, respectively, both differences were considered statically significant comparing to the group evaluated before RT. There was no report of dysgeusia and dry mouth sensation in patients screened before RT. Statistical difference was also noted in comparison of the groups in relation to teeth conditions and plaque disclosing.
The mean unstimulated whole salivary flow for all subjects together declined significantly from 1.1 ml/min (SD .24) before RT to 0.32 ml/min (SD .08) after RT (p < .0001). Data on oral condition before and after RT are presented on Table 3.

Discussion
The current analysis investigates oral complications expected to occur after RT to the head and neck region for the treatment of cancer, these include impact in salivary function, oral hygiene and tooth decayed/missed. Our results suggest that the impacts of RT reverberate over 1 year from the end of RT, providing additional insights about potential recovery of salivary flow rates at 12 months after RT to the preceding reports (Rajesh, 2017;Punita, 2018).
Xerostomia, or dry mouth sensation, develops at initial phase of RT due to irradiation damage of salivary glands (Ana, 2017). The reduced availability of saliva predisposes other oral complications such as distortion of the sense of taste, impaired swallowing, discomfort, increased microbial proliferation in view of the reduced buffer capacity in the oral environment, and consequently oral infections and dental caries (Bruno, 2006;Jensen, 2010).
In our study, 92% of patients assessed after RT complain of dry mouth symptoms.
Reports suggest that xerostomia becomes present if radiation dose exceeds 40 Gy, which is usually the case of RT to the head and neck region, when total dose usually reaches around 70Gy and salivary flow might be impacted up to 80% (Dirix , 2010;Sciubba, 2006;Kaae, 2019). In our study unstimulated salivary flow rate was measured as 1.1 mL/min in patients before RT and .32 mL/min for those evaluated after RT, similar results were obtained in other studies (Rajesh, 2017;Punita, 2018). Punita and collaborators (2018) reported that salivary flow rates continue to decrease until 6 months after RT (.295 mL/min), and a minimal recovery is observed at 12 months (.362 mL/min). Stimulated saliva also appears to be affected proportionally, mean stimulated whole salivary flow declined from 1.09 to 0.47 mL/min at 6 months in other report (Rajesh, 2017). Salivary gland hypofunction after RT seriously affected the quality of life. A recent study found that in most cases the patient with xerostomia after RT had to find their own solution to overcome this problem due to the lack of information from professionals (Nan, 2018). Saliva substitutes, mainly based on carboxymethylcellulose, might be indicated (Jensen, 2010).
Modifications in salivary flow may also provoke gustatory disturbance (dysgeusia), but this side effect is rather related to taste buds damage during RT (Joel, 2019). Prevalence of taste disorder in patients who underwent RT was found to be around 66% (Epstein, 2016).
There is no well-established curative therapy in this respect. Deficit is worse immediately after the end of RT and symptoms are attenuated during the follow up, difficulty in the identification of the sour taste is most detected in patients who had the oral cavity irradiated Research, Society and Development, v. 9, n. 10, e3299108753, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i10.8753 9 (José, 2019). In our investigation, no patients complained of dysgeusia in the group 1, but in group 2, 18 patients (72%) mentioned dysgeusia symptoms.
Saliva composition changes increase the risk of dental caries and oral mucositis.
Microbiome shift was reported to be associated to the increase of cariogenic cocci and yeast population (Elerson, 2018). Twenty bacteria genera were found to be positively related to radiation dose, and periodontal pathogenic bacteria was coincidently abundant when the onset of severe mucositis was noted, which were also associated with deterioration of hygiene (Jin, 2018). Oral hygiene and DMF index were significantly higher in group 2 comparing to group 1 for the present study.
This study does not investigate the prevalence of oral mucositis, mouth opening, and oral pain, what constitute a limitation of the study. Only a small sample was considered since exclusion criteria eliminates a lot of potential participants. However, the most relevant limitation of this study is the cross-sectional approaching of two independent groups, a longitudinal assessment could give more supportive data to the topic. It is important to consider the difficulty to carry out a 12-months follow up study with patients under RT to the head and neck region to treat cancer, a disease with a high fatality and mutilation rate. Then, our methods and results are enough to answer the raised question and give data on the impact of RT in the oral mouth in a first glance. Our research group has already designed a prospective cohort study (current under development) to further investigate the topic and eliminate the raised limitations.
There are many complications of the treatment of cancer in the head and neck region, as we see in the present study, most part of them are related to the oral cavity due to high radiotherapy dose. It is important to note that these oral complications directly affect patients' quality of life and systemic health. Health professionals, especially dental clinicians, must be informed of all risk factors and instructed about the oral management of these patients.

Conclusion
The present investigation demonstrates that patients submitted to RT in the head and neck region for the treatment of cancer experience oral complications even at 12 months after the last session of RT. These complications have a negative impact on oral function and quality of life, most part of them are developed at the expense of compromised salivary function.