Review
Timing of dental extractions in patients undergoing radiotherapy and the incidence of osteoradionecrosis: a systematic review and meta-analysis

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Abstract

This systematic review aimed to examine whether the incidence of osteonecrosis differed between patients who have dental extractions before or after radiotherapy (RT). The reported incidence of osteoradionecrosis (ORN) of the jaws following RT to the head and neck varies widely in the literature. Currently, for patients with head and neck cancer there are no universally accepted guidelines on the optimal timing of dental surgery relative to RT to minimise incident ORN. A literature review was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria. A search of PubMed, EMBASE, Evidence-Based Medicine, and Web of Science databases targeted literature published up to and including 10 April 2020. Two independent reviewers assessed studies for eligibility against inclusion criteria. An assessment of bias was conducted for each of the included studies and relevant data extracted. A meta-analysis was undertaken using the statistical methods described. Twenty-four of 708 studies were included. They were heterogeneous and included a wide variation of RT methods, head and neck malignancies, and comorbidities. While some concluded that the incidence of ORN was dependent on the timing of dental extractions in relation to RT, with regard to the risk of its development, others reported additional factors such as age, comorbidities, extent of surgical resection, and dose and field of radiation, as more important predictors than timing. In many there was consistent lack of detail around the timing of dental procedures in relation to the delivery of RT. From 21 studies including 36,294 patients, of whom 14,389 had extractions before RT, the pooled incidence of ORN was 5.5% (95% CI: 2.1% to 10.1%). Significant heterogeneity was found in Cochran’s Q-test (p < 0.001) and Higgins I2 = 98.0%. From 21 studies including 37,805 patients, of whom 6030 had extractions after RT, the pooled incidence of ORN was 5.3% (95% CI: 2.9% to 8.2%). Significant heterogeneity was found in Cochran’s Q-test (p < 0.001) and Higgins I2 = 80.0%. There was no statistically significant difference between these two groups (random-effects model Q=0.12, p=0.73). Large, longitudinal studies with a priori-specified methods are needed to identify, recruit, and prospectively follow patients with head and neck cancer for the onset of ORN after dental surgery. This will allow clinical guidelines to be established to assist clinicians to plan treatment when extractions are indicated in patients undergoing RT to the head and neck.

Introduction

Radiotherapy (RT) is a common treatment for cancers of the head and neck.1, 2 As with all cancer therapies, there are acute and late side effects including those affecting the oral cavity, one of the more serious being osteoradionecrosis (ORN).3 ORN can be defined as the presence of exposed bone for more than three months in a previously irradiated site that is not associated with persisting or recurrent tumour.3 It is characterised by chronic necrosis and/or infection, and can lead to refractory orocutaneous fistulas, persistent exposure of bone, or pathological fracture of the jawbone.4 Health-related quality of life for patients with advanced ORN is reported to be poor, with impacts on speech, mastication, swallowing, and pain.4, 5, 6 Surgical resection and reconstruction of ORN is complicated and leads to only limited improvement in quality of life, which further emphasises the importance of its prevention.6

Several ORN staging systems have been proposed over time, but the crucial elements of them all are similar whereby earlier-stage disease is limited to dentoalveolar bone, and later-stage disease is more extensive, often involving pathological fracture, secondary infection, and pain.4, 7, 8, 9, 10

The reported risk of developing ORN after RT to the head and neck varies widely in the literature, but appears to have reduced in recent years due to advances in RT techniques and widespread adoption of protocols for dental care.11, 12

The pathogenesis of ORN remains a subject of debate. In 1970 Meyer proposed that it was the result of a radiation-induced osteomyelitis.13 In 1983, Marx proposed the hypovascular, hypocellular, and hypoxic aetiology, and postulated that ORN is a problem of wound healing rather than infection.9 More recently, a radiation-induced fibroatrophic process was proposed by Delanian and Lefaix.14 Although bone is more radioresistant than other tissues in the head and neck, its reparative capacity following exposure to radiation is compromised.15 It is generally accepted that radiation causes a degree of fibrosis, thrombosis, and obliteration of the vasculature within bone, impairing its capacity to respond to injury, and ultimately resulting in the necrotic process.16

Methods to identify with certainty those patients most at risk of developing ORN, as well as an optimal treatment pathway for established cases have not been clearly defined. Many different approaches have been reported based on the hypothesised underlying pathogenesis, including hyperbaric oxygen therapy, antimicrobial therapy, surgical debridement and, more recently, the pentoxifylline-tocopherol regimen.17, 18, 19, 20, 21 Given the complexity of managing advanced cases and the associated morbidity, strategies focused on prevention would appear to be the ideal approach.9, 17

It is generally accepted that non-functional teeth or those with a poor restorative or periodontal prognosis within the RT treatment field should be extracted before the commencement of RT to prevent the risk of ORN.22, 23, 24, 25 A minimum of 14 - 21 days is recommended for extraction sites to heal before commencement of RT.26 Ideally, extractions should have sufficient time for complete dentoalveolar healing, but they are often necessarily delayed until after the completion of RT due to the urgency to commence treatment.

This literature review targeted original research on people exposed to RT of the head and neck who required dental extractions. The primary objectives were to assess the incidence of ORN in patients who had dental extraction before, and those who had extraction after, the commencement of RT. The primary endpoint was a diagnosis of ORN defined as the presence of exposed bone for more than three months in a previously irradiated site that is not associated with persisting or recurrent tumour. The secondary objective was to determine whether there is a safe period to perform dental extractions when the incidence of ORN is reduced.

Section snippets

Material and methods

This systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.27, 28 Electronic literature searches were conducted by one author (TY) on 10 April 2020, in the PubMed (Ovid), Embase (Ovid), Evidence Based Medicine (EBM) Reviews (Ovid), and Web of Science (ISI) databases, with no restrictions placed on date of publication.

Search terms according to the syntaxes of each database are displayed in Supplementary

Study selection and characteristics

Twenty-four studies were included in this review, dating from 1972 to April 2020. They were conducted in the United States (n = 8), Canada (n = 1), Japan (n = 1), Brazil (n = 2), Australia (n = 1), Finland (n = 1), Singapore (n = 2), Hong Kong (n = 1), Sweden (n = 1), Korea (n = 1), Taiwan (n = 3), Belgium (n = 1), and Saudi Arabia (n = 1).

In total, 19 were retrospective, and five prospective observational. Data were included from 24 studies involving a total of 38,225 patients of whom 20,419 had extractions. There was

Discussion

The current systematic review aimed to investigate whether the literature supported a critical period of time before or after RT to the head and neck when the completion of dental extractions would significantly alter the risk of developing ORN. Despite extensive research, predictive factors for ORN cannot be stated with any certainty, and its recommended treatment appears to be based entirely on expert opinion, the operator’s experience, and institutional protocols. There is agreement that

Conflict of interest

We have no conflicts of interest.

Ethics statement/confirmation of patients’ permission

Not applicable.

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