Dental extractions prior to radiotherapy to the jaws for reducing post‐radiotherapy dental complications

Shiyana Eliyas; Ahmed Al‐Khayatt; Richard WJ Porter; Peter Briggs

doi:10.1002/14651858.CD008857.pub2

. 2013 Feb 28;2013(2):CD008857. doi: 10.1002/14651858.CD008857.pub2

Dental extractions prior to radiotherapy to the jaws for reducing post‐radiotherapy dental complications

Shiyana Eliyas ^1,^✉, Ahmed Al‐Khayatt ², Richard WJ Porter ², Peter Briggs ²

Editor: Cochrane Oral Health Group

PMCID: PMC8947952 PMID: 23450590

Abstract

Background

Radiotherapy as part of head and neck cancer treatment leaves patients requiring much dental rehabilitation in a compromised environment that is difficult for the patient and the dental team to manage.

Objectives

To assess the effects of maintaining the patient's natural dentition during radiotherapy in comparison to extracting teeth before radiotherapy in areas that are difficult to access by the patient and the dentist, should reduction in mouth opening occur after radiotherapy to the jaws.

Search methods

We searched the Cochrane Oral Health Group's Trials Register (to 22 November 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 11), MEDLINE via OVID (1946 to 22 November 2012), EMBASE via OVID (1980 to 22 November 2012), CANCERLIT via PubMed (1950 to 22 November 2012), CINAHL via EBSCO (1980 to 22 November 2012) and reference lists of articles. We advertised for currently ongoing studies via the Cochrane Oral Health Group website and the Cochrane Oral Health Group Twitter feed.

Selection criteria

Randomised controlled trials comparing extraction of teeth prior to radiotherapy with leaving teeth in situ during radiotherapy to the jaws.

Data collection and analysis

Three review authors independently assessed the results of the searches for inclusion in the review.

Main results

No randomised controlled trials were found.

Authors' conclusions

There are no randomised controlled trials to assess the effect of extracting teeth prior to radiotherapy compared to leaving teeth in the mouth during radiotherapy to the jaws.

Plain language summary

Dental extractions prior to radiotherapy to the jaws for reducing post‐radiotherapy dental complications

This review aimed to assess if removing the back teeth before radiotherapy would mean that patients had fewer tooth‐related problems after radiotherapy as part of head and neck cancer treatment, when compared to not removing the teeth. Electronic and handsearching found 357 titles of studies but none of them met the inclusion criteria for the review. There is currently no evidence available to answer this complex question.

Background

An estimated incidence of 640,000 cases of head and neck cancer were diagnosed globally in 2002 (Parkin 2005). Exact incidence rates are difficult to ascertain due to low rates of reporting in less affluent regions (Ferlay 2010). Rehabilitation and quality of life for those who have undergone successful oncology treatment is an important consideration. It is reasonable for these patients to want their post‐treatment appearance and function to be as close as possible to that prior to the oncology treatment.

Radiotherapy causes damage to the deoxyribonucleic acid (DNA) of rapidly dividing cells so that the usual mechanisms of DNA repair fail and death of cells occurs. Unfortunately, as well as cancer cells, normal cells that proliferate rapidly will also be affected by therapeutic radiation (Cancer Research UK 2010). Radiotherapy may have both immediate and delayed adverse effects including mucositis, erythema, trismus, fibrosis (scarring of the soft tissues) and reduced quality and quantity of saliva (Vissink 2003).

Description of the condition

Radiotherapy as a part of head and neck oncology treatment potentially causes hypocellularity (reduction in the number of cells in the tissue), hypovascularity (reduction in the blood supply to the tissue) and hypoxia in the tissues irradiated (Marx 1983). Salivary gland damage can lead to a reduction in saliva production and may also affect salivary buffering and remineralising capacity. There is less saliva available to wash away food debris from tooth surfaces and the saliva may be of poor quality, making it less able to neutralise acids. This coupled with the thin mucosa may result in mucositis, which can be very painful. Patients may use frequent washes of sweet drinks to manage the discomfort in their mouths putting them at particularly high risk of developing caries. In addition, the patient may be reluctant to brush or use fluoride mouthwashes or toothpaste as their oral mucosa is painful. Such an irradiated patient is potentially highly vulnerable to tooth decay (caries) and progression of periodontal disease. If these patients require extraction of teeth, there is the risk of developing necrosis of the jaw bone as a result of a reduced blood and oxygen supply (osteoradionecrosis), which can be very difficult to control. Restoration of teeth may be very difficult if the tooth decay is rapidly progressive and/or trismus is also present.

Description of the intervention

It is recommended that patients with head and neck cancers undergo a dental examination and complete any required treatment before they start radiotherapy (DoH 2004; NICE 2010). As part of this pre‐radiotherapy dental assessment it may be necessary or advisable to extract diseased teeth. This review looks at whether there are fewer complications for patients following radiotherapy if the teeth at the back of the mouth, which are decayed and need work done on them or healthy teeth that are in a potentially awkward position at the back of the mouth, are removed before radiotherapy starts.

How the intervention might work

The negative outcomes of radiotherapy to the head and neck include (Andrews 2001; Dijkstra 2004; Kielbassa 2006; Oh 2004; Scott 2008; Toljanic 1984; Vissink 2003):

possible loss of taste;
mucositis (inflammation of the mucous membranes);
reduced salivary gland function (less saliva and saliva that does not work as well);
radiation caries (tooth decay caused by the action of radiotherapy);
trismus (spasm of the muscles or scarring of the soft tissues which can keep the jaws from opening wide);
osteoradionecrosis (death of bone as a result of a reduced blood and oxygen supply because of radiotherapy) possibly as a result of infections related to teeth or trauma caused by dentures rubbing on the gums or trauma from tooth extractions following radiotherapy;
impact on the patients' quality of life (Duke 2005; Epstein 2001; Morton 2003; Scott 2008).

Other issues are: what kinds of complications occur if teeth are left in place, which particular teeth should be taken out and how much time ideally should be left between having the teeth extracted and starting radiotherapy to the jaws.

One potential negative effect of extractions prior to radiotherapy is a delay in starting radiotherapy due to the period of healing required following extractions. Commentaries have suggested that an interval of 14 days still poses a minor risk of development of osteoradionecrosis (death of bone following radiotherapy) and that the risk was reduced to zero if there was an interval of 21 days or more between extraction and radiation therapy (Vissink 2003).

Extraction of back teeth falling within the beam of radiation may make it easier for patients to maintain the remaining front teeth and still be able to smile. It may also be simpler, easier and more comfortable for a patient with limited mouth opening to tolerate dental treatment for the front teeth only. A patient with a small mouth opening might find it very difficult to keep a back tooth clean and this might lead to tooth decay and tooth infections that lead to tooth extractions, which might trigger the start of necrosis of the bone after radiotherapy.

Why it is important to do this review

At least 3% of global cancers are head and neck cancers (GLOBOCAN 2008). A number of these cases are likely to have successful cancer treatments, which may include radiotherapy. As outlined above, there are numerous potential negative effects of radiotherapy to the head and neck regions and in particular the mouth, teeth and jaws. As treatments for head and neck cancer improve, resulting in prolonged survival, more patients are going to be living with the effects of radiotherapy for longer.

There appears to be little agreement within the profession as to how to manage these patients prior to radiotherapy in regards to their teeth (Bruins 1999). This systematic review planned to look for randomised controlled trials on extracting healthy and diseased teeth before radiotherapy to the jaws, and the consequences of leaving the teeth in place during radiotherapy. It is important to know the consequences of each approach for the benefit of the patients' quality of life as well as the wider impact on dental health services and general health services. Dental treatment and maintenance of these patients can be difficult, time consuming and have an outcome which impacts on the patients' general well being which will have associated health economic considerations.

Objectives

Primary objectives

To assess whether pre‐radiotherapy extraction of diseased molar teeth results in reduced risk of tooth related complications compared to conservative treatment of these teeth (restoration of the teeth and leaving them in place with oral health education and dental disease prevention: improving oral hygiene, the use of fluoride and diet advice).
To assess whether pre‐radiotherapy extraction of healthy molar teeth results in reduced risk of tooth related complications compared to conservative treatment of these teeth (leaving them in place with oral health education and dental disease prevention: improving oral hygiene, the use of fluoride and diet advice).

Secondary objectives

To assess:

the nature and rate of complications associated with leaving molar teeth in place during radiotherapy to the jaws;
which teeth should be extracted;
the optimum length of time to allow for healing after extractions before starting radiotherapy to the jaws.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials, excluding split‐mouth and cross‐over trials.

All randomised controlled trials comparing pre‐radiotherapy dental extractions with leaving the teeth in place during radiotherapy would have been included if they existed; however, we acknowledge that it is unlikely that oncology patients would be randomly allocated to leaving teeth in place, extraction pre‐radiotherapy, during radiotherapy, post‐radiotherapy. It is more likely that patients could be allocated to have extraction compared with restoration of carious teeth/management of periodontal disease prior to radiotherapy and extraction of carious/periodontally involved teeth compared with preventative/conservative treatment followed by extraction of problematic teeth as and when there is a clinical indication to do so during or post‐radiotherapy. We anticipated that there would be no studies comparing pre‐radiotherapy extractions with post‐radiotherapy extractions.

Types of participants

All those patients who have been diagnosed with head and neck cancer and are planned to undergo any type of radiotherapy (including external beam radiotherapy, intensity modulated radiation therapy, image guided radiation therapy, brachytherapy, conformal radiation therapy and any other type of radiotherapy to the head and neck).

Any age, sex, socio‐economic status.
Any type of head and neck cancer, oral hygiene status, tobacco status (smoking and smokeless), alcohol status.
One or more courses of radiotherapy.
Any dose of radiation.
Radiation to any part of the jaws.
Unilateral or bilateral radiation.
With or without dental maintenance pre‐ and post‐radiotherapy.

Types of interventions

We would have included studies which compare complications related to pre‐radiotherapy extractions with those of either leaving the teeth in place during radiotherapy or post‐radiotherapy extractions. Trials would also have been included where the following were investigated.

Extraction of teeth prior to radiotherapy.
Extraction of teeth during radiotherapy.
Extraction of teeth post‐radiotherapy.
Preventative/conservative treatment ‐ leaving teeth in situ pre‐radiotherapy, during radiotherapy and post‐radiotherapy with oral hygiene instructions, fluoride use and dietary advice, restoration of caries and management of periodontal disease.

Types of outcome measures

Primary outcomes

Development of post‐radiotherapy dental complications (e.g. caries, fractured teeth, periapical infection, periodontal disease, osteoradionecrosis).

Secondary outcomes

Patients' quality of life.
Delay in start of radiation treatment.
Trismus preventing further restorative treatment.
Overall survival.

Search methods for identification of studies

For the identification of studies included or considered for this review, we developed detailed search strategies for each database searched. These were based on the search strategy developed for MEDLINE (OVID) but revised appropriately for each database (Appendix 3). The search strategy used a combination of controlled vocabulary and free text terms. The search of EMBASE was linked to the Cochrane Oral Health Group filter for identifying randomised controlled trials in EMBASE (Appendix 4), and the search of CANCERLIT was linked to the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomised trials in MEDLINE: sensitivity maximising version (2008 revision) as referenced in Chapter 6.4.11.1 and detailed in box 6.4.a of the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (updated March 2011) (Higgins 2011) (Appendix 5).

Electronic searches

The following electronic databases were searched.

The Cochrane Oral Health Group's Trials Register (to 22 November 2012) (Appendix 1).
The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 11) (Appendix 2).
MEDLINE via OVID (1946 to 22 November 2012) (Appendix 3).
EMBASE via OVID (1980 to 22 November 2012) (Appendix 4).
CANCERLIT via PubMed (1950 to 22 November 2012) (Appendix 5).
The Cumulative Index of Nursing and Allied Health Literature (CINAHL) via EBSCO (1980 to 22 November 2012) (Appendix 6).

If we had identified any studies for inclusion, all the first authors of trial reports would have been contacted in an attempt to identify any unpublished studies and clarify information about the published trials (including missing data, method of randomisation, blinding and withdrawals).

Searching other resources

We advertised on the Cochrane Oral Health Group website to attempt to identify any unpublished or ongoing studies. We also advertised via the Cochrane Oral Health Group's Twitter feed: @CochraneOHG.

Data collection and analysis

Selection of studies

Three review authors independently assessed the titles and abstracts of the search results for eligibility. The full report was obtained in cases where the studies appeared to meet the inclusion criteria and where there were insufficient data in the title and abstract to make a clear decision. The full reports were then studied independently by three review authors to establish whether the trials met the inclusion criteria. Disagreements were resolved by discussion and where resolution was not possible, a fourth review author was consulted.

If we had identified any studies meeting the inclusion criteria, they would have then undergone a risk of bias assessment and data extraction using a specially designed data extraction form. Studies rejected at this or subsequent stages would have been recorded in the 'Characteristics of excluded studies' table, with reasons for exclusion recorded.

Data extraction and management

If we had identified any studies for inclusion, at least two review authors would have independently extracted the data from the studies, and assessed the risk of bias. The following data would have been entered on a customised data collection form.

Trial design/location/number of centres.
Funding.
Recruitment period.
Year of publication.
Details of treatment and control intervention(s) and duration of treatment.
Numbers randomised to each group and numbers evaluated in each.
Trial inclusion criteria and patient characteristics (age/gender/socio‐economic group/tobacco status/alcohol status/general health/previous dental health).
Site of primary tumour, tumour staging and radiation dose.
Number and anatomical site of teeth extracted (molars/premolars/incisors).
Time period from each episode of extraction of teeth to first dose of radiotherapy.
Number of years of follow‐up.
Details of withdrawals by study group.
Primary and secondary outcomes and times these were measured.
Duration of follow‐up.
Sample size calculation.

Assessment of risk of bias in included studies

If we had identified any studies for inclusion, at least two review authors would have independently assessed the risk of bias of each study following the methods recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). This would have involved a two‐part tool addressing the following specific domains.

Random sequence generation (selection bias).
Allocation concealment (selection bias).
Blinding of participants and personnel, where feasible (performance bias).
Blinding of outcome assessment (detection bias).
Incomplete outcome data (attrition bias).
Selective reporting (reporting bias).
Other sources of bias.

Within each domain, a description of what happened, as reported in the study, would have been recorded in a 'Risk of bias' table within the 'Characteristics of included studies' table, along with a judgement of either low, high or unclear risk of bias.

Within a study, a summary assessment of low risk of bias would have been given if there was a low risk of bias for all key domains, unclear risk of bias if there was an unclear risk of bias for one or more key domains, and high risk of bias if there was a high risk of bias for one or more key domains. Across studies, a summary assessment would have been rated as low risk of bias when most information was from studies at low risk of bias, unclear risk of bias when most information was from studies at low or unclear risk of bias, and high risk of bias when the proportion of information from studies at high risk of bias was sufficient to affect the interpretation of the results.

The results of our risk of bias assessments would have also been presented graphically.

Measures of treatment effect

If we had identified any studies for inclusion, the outcomes would have been measured in terms of: risk ratios for dichotomous data, such as rate of post‐radiotherapy complications related to dental extractions or infection rate and survival; mean differences and standard deviations for continuous data, such as quality of life scores.

Dealing with missing data

If we had identified any studies for inclusion, where data from the trials were unclear or missing, we would have contacted the trial authors to clarify these details. If information supplied by the authors indicated that the trial did not meet the inclusion criteria for this review, the trial would have been excluded and recorded in the 'Characteristics of excluded studies' table. For drop‐outs of participants, an intention‐to‐treat analysis would have been carried out. Where there were missing statistics, original data would have been requested from the authors of the study and attempts would have been made to carry out the missing statistical analysis on the raw data.

Assessment of heterogeneity

If we had identified any studies for inclusion, clinical heterogeneity would have been assessed by examining the participants, interventions and outcome measures included in the trials. Statistical heterogeneity would have been assessed by inspection of a graphical display of the estimated treatment effects from the trials along with their 95% confidence intervals. The significance of any discrepancies in the estimates of the treatment effects from the different trials would have been assessed by means of Cochran's test for heterogeneity and quantified by the I² statistic.

Assessment of reporting biases

If we had identified any studies for inclusion, where the patient recalls his or her symptoms, reporting bias would have been assessed.

If we had identified any studies for inclusion, a funnel plot would have been drawn if a sufficient number of trials were identified. Asymmetry of the funnel plot may indicate publication bias and other biases related to sample size, though it may also represent a true relationship between trial size and effect size. If data had allowed, a formal investigation of the degree of asymmetry would have been undertaken using the method proposed by Egger 1997.

Data synthesis

If we had identified any studies for inclusion, for dichotomous outcomes, the estimates of effect of an intervention would have been expressed as risk ratios together with 95% confidence intervals. For continuous outcomes, mean differences and standard deviations would have been used to summarise the data. The statistical unit would have been the patient.

If we had identified any studies for inclusion, meta‐analyses would have been undertaken only on studies of similar comparisons reporting the same outcome measures. The Cochrane Collaboration guidance would have been followed, with effect estimates being combined using a random‐effects model where more than three trials were combined. The number needed to treat (NNT) would have been calculated as appropriate.

Subgroup analysis and investigation of heterogeneity

If we had identified any studies for inclusion, The Cochrane Collaboration's guidance on testing for heterogeneity would have been used providing there were sufficient trials included in the review.

Sensitivity analysis

If there had been sufficient trials included in the review, sensitivity analysis would have been undertaken for aspects of study quality and for potential sources of heterogeneity specified a priori as follows: excluding/including unpublished studies, excluding/including studies of low quality and excluding/including one or more large studies to assess how much they dominate the results. The association of radiotherapy with estimated effects would have been examined by performing random‐effects meta‐regression analysis in STATA version 7.0 (STATA Corporation, USA), using the program Metareg. Further potential sources of heterogeneity would have been investigated as determined from the study reports, although these would have been clearly identified as 'post‐hoc' analyses and the results treated with caution.

Results

Description of studies

Results of the search

The search results were merged and duplicates were removed. The search strategy and handsearching generated 360 titles (some with abstracts) of papers once duplicates were removed. Multiple reports of the same study were linked together. All review authors individually assessed these studies using a study eligibility form (Appendix 7). The review authors were not blinded to the names of the authors, institutions, journal of publication and results. All review authors were content area experts. We requested the full text for 142 papers, which appeared to be related to dental extractions and radiotherapy. 77 full text papers were found. For 65 abstracts, full papers were not found. None of the studies met the inclusion criteria for this review, as they were not randomised controlled trials (RCTs). There were no disagreements on the eligibility of the studies. Figure 1 is a study flow diagram.

There were no RCTs comparing the extraction of healthy or unhealthy teeth prior to radiotherapy with leaving teeth in place during radiotherapy.