Evaluation of pulp vitality using a pulse oximeter in patients undergoing radiotherapy for rhabdomyosarcoma or rhinopharynxcarcinoma

The oral cavity is highly susceptible to pathological changes due to the deleterious effects of radiation (RI) on tissues exposed during radiotherapy (RT). The aim of this study was to evaluate the feasibility of using pulse oximeter (PO) as a diagnostic instrument for assessing the pulp oxygenation level (%SpO2) of immature teeth previously exposure to Research, Society and Development, v. 10, n. 11, e107101119342, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i11.19342 2 IR. Pulp oxygenation saturation was evaluated in fifteen children or adolescent patients (Group RT) that received previous IR, 6.01 years ago (SD 4.08 years), and fifteen patients without a history of neoplasms or previous chemotherapy or radiotherapy (CO group). As result, the mean %SpO2 measured in Group RT and Group CO was 86.06% (SD 1.61%) and 91.11% (SD 0.87%), respectively. Conclusions: The use of the pulse oximeter adapted for dentistry for pulpal vitality evaluation in patients who received radiotherapy is feasible showing lower level of SpO2 than that of the control group (p<0.05).


Introduction
Advances in knowledge and technologies used in head and neck radiotherapy (RT) procedures have greatly improved survival rates. To enhance quality of life, it is also essential to maintain good oral conditions before and after ionizing radiation (IR), because patients who receive radiotherapy are highly susceptible to pathological changes in the oral cavity due to the deleterious effects of radiation on the exposed tissues (Sennhenn-Kirchner et al. 2009).
Previous studies have shown that when an erupted tooth is in the radiation pathway, the IR may decrease vascularization, resulting in increased fibrosis and atrophy of the dental pulp (Cooper et al. 1995;Grötz et al. 1998). The same effects were found in immature teeth during the odontogenesis period (Afanasyev & Liubarets 2020), resulting in the interruption of root formation or malformation (Guggenheimer et al. 1975), subsequent early tooth loss, and possibly, changes in facial development (Afanasyev & Liubarets 2020).
To plan an ideal treatment, the pulp status must be determined as part of the endodontic diagnosis. Commonly, the cold test (TPT) is used for this purpose because of its reliability, ease, and availability (Pigg et al. 2016). This diagnostic method assesses the tooth by its neuronal response (Abd-Elmeguid & Yu 2009). Despite its extensive use, thermal stimulation tests are unable to determine pulpal vitality because vitality is dependent on blood supply and oxygenation (Abd-Elmeguid & Yu 2009). In immature teeth, the subjectivity of the response is problematic, as the test results are dependent on the child's understanding and collaboration. Hence, these results are susceptible to misinterpretation (Gopikrishna et al. 2007).
Pulse oximetry (PO) is a noninvasive method commonly used in medicine to determine blood oxygen saturation (SpO2). Studies have shown that blood microcirculation within the pulp can be measured via the oxyhemoglobin saturation -HgO2 (Miller et al. 1992;McMorrow & Mythen 2006;Caldeira et al. 2016), and this has recently been achieved in teeth as well (Gopikrishna et al. 2007, Calil et al. 2008Jafarzadeh & Rosenberg 2009;Pozzobon et al. 2011). The assessment of pulp vitality using pulse oximetry has produced median oxygen saturation levels ranging from 75% (Gopikrishna et al. 2007) to 94% (Schnettler & Wallace 1991). Pulp tissues exposed to IR in the head and neck region showed microcirculatory changes with a consequent decrease in pulp oxygenation rates (Kataoka et al. 2011(Kataoka et al. , 2016, resulting in temporary loss of dental sensitivity (Garg et al 2015). The altered sensitivity and oxygen saturation tend to return to normal levels after a few weeks (Gupta et al. 2018).
PO adapted for dentistry is a prominent diagnostic method because of its degree of reliability and ease of use (Kataoka et al. 2016;Shahi et al. 2015) and high specificity (Gopikrishna et al. 2007).
There is little information regarding the late effects of IR on the pulp in children and adolescents with a history of head and neck RT. Therefore, this study aimed to evaluate the feasibility of using PO as a diagnostic instrument for assessing the pulp oxygenation level (%SpO2) of immature teeth previously exposure to IR.

Materials and Methods
This study was approved by the Ethics and Research Committee of the Federal University of São Paulo CAA 64688717.9.0000.5505 and authorized by the scientific committee of the Pediatric Oncology Institute GRAACC UNIFESP Ref.: 35/2016. Periapical radiographs of the anterior teeth were used to define the inclusion criteria: upper or lower central incisors, lateral incisors or canines with intact crowns or small restorations (<2mm), teeth without periapical disease, absence of resorptive or degenerative processes, and teeth without endodontic treatment. The criteria for general health were children and adolescents with good clinical health, showing stable SaO2 rates, when compared to the index finger saturation.
Metodology used was similar to used in previous studies (Kataoka et al. 2011(Kataoka et al. , 2016. Group RT consisted of fifteen patients (a mix of men and women) between the ages of 6 and 30 years who received IR for rhabdomyosarcoma, parameningeal sarcoma or rhinopharynx carcinoma in the head and neck region. In relation to tumor diagnosis, 40% (6 individuals) presented with rhabdomyosarcoma and 60% (9 individuals) presented with carcinoma.
The mean radiation dosage received by the patients was 6903.73cGy (SD 2815.38 cGy) Group CO included 15 patients (a mix of men and women) with the same age range (6-30years) as Group RT, and without a history of neoplasms, chronic diseases, or previous chemotherapy or radiotherapy.
The total number of teeth included for evaluation was 158 in the radiotherapy group (RT) and 336 in the control (CO) group (Table 1). Source: Authors.
The patients were evaluated for pulpal sensitivity and vitality. To exclude non-vital teeth, the pulpal sensitivity was assessed using the cold test (TPT), which involved cooling the dental surface. Difluorodichloromethane Endo-Frost, (Roeko GmbH, Langenau, Germany) was applied to the mid-vestibular tooth surface via a cotton pellet. Index finger saturation and pulp vitality evaluation of the selected tooth was verified using a pulse oximeter Rossmax SA210 ® (Rossmax Swiss GmbH, Heerbrugg, Switzerland) The pulse oximeter was adapted for dental use via the "Y" modified sensor (Figure 1), and these were manually positioned parallel to each other on the vestibular (emitting diode) and palatal/lingual (receiver diode) surfaces, under relative isolation (Figure 2).  Data were recorded. The Kolmogorov-Smirnov adherence analysis test and the student's t-test were used for statistical analyses.

Results
The mean age of Group RT (n=15, 60% male and 40 % female) was 11.47 years (SD 3,42 years). The mean age of patients in Group CO who had never had RT (n=30, 56.67% female and 43.33% male) was 18.83 years (SD 2.56 years). In Group RT, the time elapsed since the last RT exposure was 6.01 years (SD 4.08 years).
All evaluated teeth responded positively to the pulp sensitivity assessment via the cold test using difluorodichloromethane (EndoFrost) allowing their inclusion in the study. The mean %SpO2 in Group RT and Group CO was 86.06% (SD1.61%) and 91.11% (SD 0.87%), respectively (Table 2).

Discussion
Although recent knowledge in molecular biology, technology, and support treatment has significantly increased cancer survival rates in children, the sequelae of anti-neoplastic treatment are numerous and can manifest many years after termination of therapy (Wexler 2016;Prasad et al. 2017).
In cases of rare tumors, such as rhabdomyosarcoma, parameningeal sarcoma, and rhinopharynx carcinoma, radiotherapy is the main treatment method for local disease control (Ribassin-Majed et al. 2017). During treatment, these patients receive high doses of radiation (5000-6500cgs) in the head and neck region, which can decrease local vascularization, including the dental pulp (Epstein et al. 2012).
Faria et al. 2014 demonstrated pulp morphologic preservation immediately after irradiation, however in the course of time, RT could affect the pulpal tissues, causing inflammation, and reduced blood circulation and SpO2 levels with subsequent hypoxia (Kataoka et al. 2011, 2016, Anusha et al. 2017. A previous study demonstrated that the mean SpO2 levels decreased in the short-term (<6 months) after RT in adults (Kataoka et al. 2011) but the changes did not persist over time (Kataoka et al. 2016).
One limitation of this study was the small number of individuals (n=15) and teeth (n=158) included in the RT group, justified by the specificity of the tumor type and the age range of the children and adolescent patients.
Difficulties in obtaining reliable responses due to patient's fear and anticipatory anxiety in the face of cold sensitivity pulp tests are common (Calil et al. 2008). This occurs more frequently in pediatric oncological patients because these patients are often subjected to extensive treatment, pain-inducing interventions and emotional disorders (Pöder et al 2010). Thus, in these cases, the use of a pulse oximeter adapted for dental use for pulp vitality evaluation has been encouraged by publications that endorsed their efficiency and feasibility (Calil et al. 2008;Kataoka et al. 2011Kataoka et al. , 2016. In this study, evaluated teeth in group RT and group CO that presented positive results to the cold sensitivity test showed a mean SpO2 rate of 86.06% (SD 1.61%) and 91.11% (SD 0.87%) respectively. These results concurred with previous reports, in which the SpO2 values exceeded 75% (Gopikrishna et al. 2007) Irradiation induces hyposalivation and pH reduction which are definitively cariogenic, therefore, teeth often present large amount of substantial incipient caries (Silva et al. 2009 In this study, teeth in Group RT had lower oxygen saturation rates than those in Group CO group (p <0.0001). These results are different to those reported by Kataoka et al. 2016. In their study, the authors observed no statistical difference between teeth that underwent RT with a maximum average dose of 61.8GY after 4 to 6 years, compared to teeth that had never been exposed to IR. These differences detected in the RT groups in both studies may be due to the patient´s age. Individuals in our study showed a mean age of 11.47 years, whereas the average age for participant in the Kataoka et al. 2016 study was 49.4 years at the time of vitality evaluation.
Few studies have analyzed the changes in the immature tooth pulp following exposure to ionizing radiation for head and neck tumors (Kataoka et al. 2011(Kataoka et al. , 2016Faria et al. 2014;Garg et al 2015). Group RT was composed by children or adolescents with mean age of 11.47 years (SD 3.42 years), thus an incomplete root development was present in most cases of upper lateral incisors and canines. RT in immature tooth could lead to a chronic inflamed pulpal state similar to findings from Gheorghe et al. 2109 that showed histological and immunohistochemicals changes in vital abutment teeth characterized by an asympatomatic irreversible pulpitis who presented a continuous ageing process that reduces perfusion and SpO2 levels.
However, only a histologic examination of the pulp could correlate the pulpal status with its SpO2.
In conclusion, PO is a practicable method for diagnosing pulpal conditions prior to conservative or endodontic treatment in patients who received radiotherapy for rare tumors (rhabdomyosarcoma, parameningeal sarcoma, and rhinopharynx carcinoma).

Conclusions
The findings of this study suggested that: 1) The use of the pulse oximeter adapted for dentistry for pulpal vitality evaluation in patients who receivedradiotherapy is feasible, and 2) The mean pulpal SpO2 for irradiated patients was lower than that of the control group. Although the use of the pulse oximeter shows effectiveness in measuring pulp vitality in patients who received radiotherapy, further studies should be carried out.