|Year : 2021 | Volume
| Issue : 2 | Page : 123-128
The impact of radiotherapy on pulp vitality in patients with head and neck cancer: A systematic review
Hassan Abed1, Francesco Mannocci2, Abdulaziz Bakhsh3
1 Department of Basic and Clinical Oral Science, Faculty of Dentistry, Umm Al-Qura University, Makkah, Saudi Arabia; Department of Sedation and Special Care Dentistry, Guy's and St. Thomas' Foundation Trust, London, United Kingdom
2 Department of Conservative Dentistry, Guy's and St. Thomas' Foundation Trust, London, United Kingdom
3 Department of Conservative Dentistry, Guy's and St. Thomas' Foundation Trust, London, United Kingdom; Department of Conservative and Restorative Dentistry, Faculty of Dentistry, Umm Al-Qura University, Makkah, Saudi Arabia
|Date of Submission||31-May-2020|
|Date of Decision||11-Jun-2020|
|Date of Acceptance||31-Jul-2020|
|Date of Web Publication||8-May-2021|
Dr. Abdulaziz Bakhsh
Department of Conservative and Restorative Dentistry, Faculty of Dentistry, Umm Al-Qura University, P. O. Box: 14405, Makkah 21955, Saudi Arabia
Source of Support: None, Conflict of Interest: None
Introduction: Root canal treatment is considered an ideal treatment option instead of dental extraction to prevent the development of osteoradionecrosis in head and neck cancer (HNC) patients postradiotherapy (RT). This systematic review aimed to assess the impact of RT on pulp vitality in HNC patients.
Materials and Methods: The databases of MEDLINE and EMBASE were searched from 1946 up to February 2019 for pulp vitality of the teeth of HNC patients (>16 years old) post-RT. Two authors independently completed the review's stages. The results were summarized narratively. The Joanna Briggs Institute critical appraisal tools were used to assess quality of included papers.
Results: 1153 studies were identified and only 2 studies were included in data synthesis. In the two studies, the case and control groups were almost similar according to the source of a similar cohort. Both studies identified confounding variables clearly, but they did not explain strategies used to deal with confounding variables.
Conclusions: Pulp vitality might be affected with high doses of RT during treatment (>35 Gy) and at the end of treatment course (60–70 Gy).
Keywords: Head and neck cancer, osteoradionecrosis, pulp oxygen saturation, pulp vitality, radiotherapy
|How to cite this article:|
Abed H, Mannocci F, Bakhsh A. The impact of radiotherapy on pulp vitality in patients with head and neck cancer: A systematic review. Saudi Endod J 2021;11:123-8
|How to cite this URL:|
Abed H, Mannocci F, Bakhsh A. The impact of radiotherapy on pulp vitality in patients with head and neck cancer: A systematic review. Saudi Endod J [serial online] 2021 [cited 2021 Oct 22];11:123-8. Available from: https://www.saudiendodj.com/text.asp?2021/11/2/123/315638
| Introduction|| |
The National Cancer Institute describes head and neck cancers (HNCs) as the types of cancers that arise in the tissues and organs of the head and neck region. Radiotherapy (RT) and surgery are considered the main treatment for the majority of HNC. Treatment of HNC with RT is reported as a well-known successful result; however, it also leads to short- and long-term side effects on oral and dental health. For example, short-term side effects (acute form) could develop a few days after starting treatment with RT (i.e., mucositis, dry mouth, and loss of taste sensation). Long-term side effects (chronic form) could also develop, such as trismus, radiation caries, and osteoradionecrosis (ORN).
Dental extraction of teeth with poor prognosis is the most common reason found to be related to the development of ORN in HNC., Treatment of ORN is costly and unclear. Different treatment modalities are suggested, such as antibiotic agents, hyperbaric oxygen, and lastly by a combination of pharmacological approaches of antioxidant agents and Vitamin E.,, Therefore, dental assessment is highly recommended for any HNC patients prior to starting treatment with RT. This includes educating patients about possible side effects related to RT and its management, extraction of teeth with poor prognosis, and regular follow-up post-RT. However, some HNC patients have only a limited time prior to the start of RT, leaving them with poor oral health status, which requires dental treatment post-RT, including dental extractions. When treatment is needed for odontogenic pain and infections in post-RT patients, RCT is considered an ideal alternative to dental extractions to prevent the development of ORN. Shenoy et al. in their review reported that RT might lead to decreased vascularization, fibrosis, and atrophy of the dental pulp, which might compromise the pulpal response to infection, trauma, and dental procedures; hence, this result in a negative sensitivity testing. However, it is unclear how the pulp tissue is affected in HNC patient's post-RT at different levels of radiation doses. Therefore, the aim of the current systematic review was to assess the impact of RT on the pulp vitality in HNC patients.
| Materials and Methods|| |
Protocol and registration
The systematic review protocol was developed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 (PRISMA-P)., The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42018115238.
The eligibility criteria were based on the PICO model (Population, Intervention, Comparison, and Outcome) as follows:
- Population: HNC patients who had been treated with RT (>16 years, male or female, with any ethnicity, socioeconomic status, and/or other medical comorbidities)
- Intervention: Assessment of pulp vitality of teeth with normal or symptomatic pulp within the field of radiation
- Comparison: HNC patients who had been treated with surgery and/or chemotherapy, but not with RT, or healthy patients
- Outcomes: Pulp vitality.
Information sources and search strategy
The current systematic review was performed to locate relevant studies published from 1946 and the last search was completed in February 2019. Two database systems were searched: MEDLINE (OVID interface) and EMBASE (OVID interface). The British Library EThOS, https://ethos.bl.uk/Home.do?new=1 was also searched for any related grey literature. No restrictions by timing of search, type of setting, or language of study were considered by the reviewers. The reference list of retrieved articles was screened for further eligible studies. [Supplementary information files 1] and [Supplementary information files 2] present the search strategy keywords of the two databases that were used.
Study selection and data extraction
Reference management software (EndNote X7.7.1, Mac OS High Sierra, Clarivate Analytics, Philadelphia, USA) was used to upload the retrieved articles from the databases. The study details (i.e., journal title, study title, authors' names, years of publication, and abstract) were considered during the uploading process. In cases where the abstract was not available during the retrieval process, the full paper was obtained for further assessment. All uploaded studies were independently screened by two reviewers to help assess the eligibility of the studies. In case of any difference in opinion between the first two authors, the third author was planned to be involved. All duplicate studies were excluded through the EndNote filter service. The two reviewers were not blinded to the journal or authors of the studies during the screening stage. Two authors independently completed the data extraction form for each paper included in the review. [Supplementary information file 3] presents the extracted data items for the included studies.
Quality assessment and synthesis of results
Two reviewers independently assessed the quality of the included studies using the Joanna Briggs Institute (JBI) critical appraisal tools. The results were summarized narratively. A separate table was considered to record study quality.
| Results|| |
[Figure 1] presents a flow diagram of the selection process recommended by the PRISMA-P. The authors identified 1153 studies through MEDLINE and EMBASE databases. No additional records were identified through other sources or through hand searching. Following the exclusion of duplicate studies (n = 384), the authors screened 1149 studies and only 40 studies were assessed for eligibility. Finally, two studies were included in data synthesis. [Supplementary information file 4] presents the reasons for the exclusion of the other studies.
Quality assessment of the included studies
[Supplementary information file 5] shows a summary of the quality assessment of the two studies being reviewed., Two different tools were used for the case–control-matched study and for the prospective observational study. In the two studies, the case and control groups were almost similar according to the source of a similar cohort. However, the authors did not explain clearly how radiation was measured or assessed. In both studies, the authors identified confounding variables clearly; however, the authors did not explain strategies used to deal with confounding variables. In both studies, the follow-up time intervals were sufficient to assess association between confounding variables and outcomes. Moreover, in both studies, the authors only considered descriptive statistics for data analysis and there was no inferential statistics to assess the strength and direction of association between confounding variables and outcomes.
Demographic data of participants
Based on the inclusion criteria set for this study, two prospective observational studies investigated the impact of RT on pulp vitality in HNC patients [Table 1]. One study evaluated the long-term effects of ionizing radiation on pulp vitality in HNC patients with a history of RT 4–6 years after treatment. Patients who had malignant tumors and received RT were compared with the control group who had no HNC. Meanwhile, the second study compared the pulp vitality of teeth with intact crowns or small restorations away from the area to be tested in HNC patients at four different times (Time 1: before RT, Time 2: at beginning of RT with radiation doses between 30 and 35 Gy, Time 3: at the end of RT with radiation doses between 60 and 70 Gy, and Time 4: 4–5 months after the beginning of cancer treatment). The authors reported that the aim of the two studies was to analyze pulp vitality by measuring pulp oxygenation levels (%SpO2) in HNC patient's post-RT. The total sample size of the studies ranged between 20 and 180 participants., The mean age of the total sample was reported in one study (47.2 years), while it was reported for sub groups in one study. Ethnicity and gender of participants were not reported by either of the two studies.
Types and numbers of teeth tested and types of endodontic tests used
[Table 2] presents types and numbers of teeth tested (maxillary versus mandibular) post-RT and types of endodontic tests used in the studies being reviewed. In the maxilla, 344 teeth for one study and 22 teeth for the other study were tested post-RT. While in the mandible, 349 teeth for one study and 18 teeth for the other study were tested post-RT.
|Table 2: Types and numbers of teeth tested and types of endodontic tests used in the included studies being reviewed|
Click here to view
In two studies being reviewed,, the authors mainly considered similar types of endodontic tests post-RT (i.e., periapical radiographs, pulp % SpO2, cold thermal testing, and oxygraph pulse oximeter). All studies used only descriptive statistics.
The length of follow-up ranged between studies from the beginning of RT to 54 months post-RT. However, in the two studies, the length of follow-up closely ranged between 4 months post-RT to 4 years post-RT., One study reported sites of cancers in patients with malignant HNC, while the other study only reported that the sample had intraoral and oropharyngeal tumor. Different radiation doses were received in the whole sample in the two studies. For example, the first included study reported that patients received the mean of 61.8 Gy (SD: not reported), while the other included study reported different radiation doses at different stage (30–70 Gy). While in regard to the type of treatment, only one study reported that all patients received intensity-modulated radiation therapy (IMRT).
| Endodontic test results|| |
In one of the two studies, there was no statistically significant difference between case and control groups when the %SpO2 was measured post-RT. While other included study found that there was a statistically significant difference in %SpO2 when measured at different time points in the same group of HNC (before RT and at beginning of RT with radiation doses between 30 and 35 Gy: P < 0.01, before RT and at the end of RT with radiation doses between 60 and 70 Gy: P < 0.01, and before RT and 4–5 months after the beginning of cancer treatment: P < 0.01). Furthermore, one of the studies showed that there was a statistically significant difference for the comparison of %SpO2 when it was measured in the index fingers by Y-type sensors (System Partner, Sao Paulo, Brazil) that was adopted for dental use by Calil et al. and %SpO2 of teeth at three different times, but not before RT (Time 1) (i.e., before RT [Time 1]: tooth [93%] <finger [95%], at beginning of RT with radiation doses between 30 and 35 Gy [Time 2]: tooth [83%] <finger [94%], at the end of RT with radiation doses between 60 and 70 Gy [Time 3]: tooth [77%] <finger [94%], and 4–5 months after the beginning of cancer treatment [Time 4]: tooth [84%] <finger [95%]).
Only one study assessed impact of RT on the teeth when a cold thermal test was used by dichlorodifluoromethane at −50°C (Endo Frost; Roeko, Langenau, Germany), which was analyzed by the Cochran test and results were statistically significant (P < 0.0001). For example, the authors found that positive measures resulted on all teeth (100%) before RT (Time 1), while the tests were positive in only nine anterior teeth (23%) at the beginning of RT (Time 2) with radiation doses of 30–35 Gy and no teeth gave positive results to cold thermal testing at the end of RT with radiation doses of 60–70 Gy (Time 3) and at 4–5 months post-RT (Time 4).
| Discussion|| |
This systematic review aimed to investigate the impact of RT on pulp vitality in HNC patients post-RT. It is believed that biochemical effect of ionizing radiation might reduce vascularity within the pulp, which subsequently leads to fibrosis and atrophy. Two studies were identified that investigated the impact of RT on pulpal flow using pulse oximetry in HNC patients post-RT., Pulse oximetry is an objective tool used to assess the pulp vitality in trauma cases. It uses red and infrared wavelengths to transilluminate a tissue and utilize this data to identify pulse rate and oxygen saturation. However, there is still a lack of evidence on its practicality and its specificity.,
Two studies assessed %SpO2 of the pulp in HNC patient's post-RT. Both studies were conducted in the same country and by the same researchers but at a different time., In 2016, the authors found no significant difference in the %SpO2 between both groups post-RT (HNC group versus non-HNC group) 4–6 years after RT. They reported that all HNC patients in the study were treated with IMRT. In general, IMRT produces less structural changes on oral and dental tissues than other types of RT. Therefore, using IMRT may explain why there was no difference in %SpO2 between the case and control groups. Furthermore, researchers showed that vascular changes in the pulp tissues were revealed to occur because of the fraction of the RT; hence, this study supports that IMRT causes less harm to pulp tissues. While in 2011, the authors found significant differences in the %SpO2 in the same group of HNC post-RT at different times and with different radiation doses, but the authors did not report the type of RT used. For example, they found that the %SpO2 reduced significantly at the end of RT with high radiation doses (60-70 Gy) in comparison with the beginning of RT using low radiation dose (30-35 Gy). This reduction in the %SpO2 is explained in several studies. For example, due to the inflammatory process that developed post-RT in the pulp tissues,, partial pulp necrosis of the pulp tissues, reduced microcirculation developed by radiation-induced vascular injury, and congestion of damaged blood vessels, which leads to hypoxia and/or reduction in the atrial flow.
However, this reduction in %SpO2 returns to normal 4-5 months post-RT and this can be explained by the ability of pulp tissues to remodel and repair by different suggested mechanisms; for example, the von Willebrand factors, and Cluster of Differentiation protein (CD) (CD31, CD34 and CD105) in the pulp tissues which are indicative for repair and vasculogenesis. Moreover, radiation-related hypoxia acts as a trigger to activate hypoxia-inducible factor-1 alpha, which initiates the angiogenesis process, similar to trauma cases.
In 2011, the authors compared the pulp vitality within the same group of patients at different time points and they found that pulp vitality was regained after 4-5 months post-RT, while in 2016, the authors compared the pulp vitality using %SpO2 of HNC patients who underwent RT with controls and they found no significant difference after 4-6 years post-RT. Therefore, both studies were able to confirm that pulpal changes could be transient post-RT in short and long term., A retrospective hospital-based study of 439 HNC survivors found that the site of radiation had no effect on the site of tooth following treatment with RT.
Strengths and limitations
The current review followed the PRISMA-P guideline and the protocol is registered in PROSPERO. PROSPERO also showed that the current review is the first that aimed to assess the impact of RT on pulp vitality in HNC. The JBI Critical Appraisal tools were used to assess all studies included independently by two reviewers. On the other hand, only two studies were included in the current review with insufficient numbers of samples and all used only descriptive statistics. Furthermore, both studies were conducted by the same group of researchers in the same setting and place (Brazil); hence, this might affect external validity. It is worth mentioning that the same group of researchers conducted another study in 20 HNC patients to evaluate the effect of RT delivered by 3-dimensional conformal radiotherapy (3D-CRT) or IMRT on dental pulp sensitivity but not on the pulp vitality using pulse oximetry; hence, this study was excluded.
| Conclusions|| |
Within the limitations of this systematic review, pulp vitality might be affected during treatment (>35 Gy) and at the end of treatment course when patients received higher doses (60–70 Gy). However, this conclusion is based on only two studies; hence, an adequately powered study based on inferential statistics is required to better demonstrate such findings in irradiated teeth of HNC patients.
It is possible for HNC patients to have partial pulp necrosis during treatment with RT (>35 Gy) and at the end of RT period when patients may receive >60 Gy; this complicates the diagnosis of pulp diseases in such clinical contexts, potentially leading to unnecessary RCT. A thorough clinical examination in HNC patients during the course of RT and after RT treatment completion is recommended to establish if endodontic treatments are indicated.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Supplementary Information Files|| |
List of the Excluded studies
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[Table 1], [Table 2]