Abstract
Head and neck cancer is the fastest accelerating cancer. Radiotherapy is commonly used to treat head and neck cancer. Whilst radiotherapy is an effective treatment modality for head and neck cancer, it is associated with significant early and late side effects which impact on the quality of life of patients. The late side effects of radiotherapy (depending on the volume and dose) may cause irreversible problems such as dysphagia, xerostomia, dental decay, and osteoradionecrosis.
We performed a retrospective analysis of head and neck cancer cases treated with radiotherapy at Leeds Teaching Hospitals Trust, UK. The aim of this process was to perform an exploratory analysis into the potential risk factors for osteoradionecrosis, focussing on risk factors that would be identifiable at a pre-radiotherapy dental screening appointments. This methodology was not utilised to determine statistically significant correlations, but to inform future studies which may involve regression analysis, and subsequent risk prediction.
Our study confirms findings from previous studies suggesting that variables such as the timing of pre-radiotherapy extractions, the number of pre-radiotherapy extractions, and the smoking status of the patient may increase the risk of osteoradionecrosis. We found new potential risk factors which require further investigation, including the presence of dental pathology on the pre-treatment PET-CT. This novel finding may provide further indication of the patient specific risk for osteoradionecrosis.
1
Introduction
Head and neck cancer (HNC) is the fastest accelerating cancer [ ] and is the 13th most common cancer worldwide [ ]. Radiotherapy is a commonly used to treat head and neck cancer. This may be used alone (radical radiotherapy), in conjunction with other curative treatments (adjuvant radiotherapy), or to provide palliative treatment of non-curative cancers. Radiotherapy is a significant part of the head and neck cancer management and is required in 75–80 % of cases (for curative or palliative management) [ , ].
Whilst radiotherapy is an effective treatment modality for head and neck cancer, it is associated with significant early and late side effects which impact on the quality of life of patients. The late side effects of radiotherapy (depending on the volume and dose) may cause irreversible problems such as dysphagia, xerostomia, dental decay, and osteoradionecrosis. This latter risk factor is the focus of this article [ , ].
The risk for ORN is long-standing owing to permanent changes to the vascular and bony architecture of irradiated tissues. Consequently, individuals may develop this complication many years following completion of treatment. It is estimated that 2–10 % of patients irradiated in the head and neck region will develop ORN [ , ], and approximately 6–7% of patients who require dental extractions after radiotherapy will develop ORN [ ]. This risk is increasingly concerning given the improvement in patient survival following the increase in HPV-mediated head and neck cancers.
Approximately 85% of cases of ORN present in the mandible, with the proposed risk factors for the development of ORN including pre-radiotherapy extractions, post-radiotherapy extractions, smoking, total radiotherapy dose, and oral mucositis [ ]. There is limited research reporting on the site specific radiotherapy dose received at sites which develop ORN [ ].
Pre-treatment oral screening by an appropriately trained dental specialist is considered to be an important step in minimising this risk [ ]. There is however limited published literature reporting on the risk attributable to different dental diagnoses at the pre-radiotherapy dental screening appointment. The prognosis of teeth can be challenging to predict pre-radiotherapy, and there is no recent research reporting on the risk for ORN attributable to specific dental pathologies such as apical periodontitis (infection at the root tip of teeth).
We performed a retrospective analysis of head and neck cancer cases treated with radiotherapy at Leeds Teaching Hospitals Trust, UK. The aim of this process was to perform an exploratory analysis into the potential risk factors for osteoradionecrosis, focussing on risk factors that would be identifiable at a pre-radiotherapy dental screening appointment. This methodology was not utilised to determine statistically significant correlations, but to inform future studies which may involve regression analysis, and subsequent risk prediction [ ].
2
Methods
A study method was developed through collaborative discussion with the multidisciplinary team (MDT). Ethical approval was obtained prior to the start of data collection. All head and neck cancer cases are discussed and logged at a weekly MDT meeting. Cases were identified through analysis of three years of MDT logs (2016–2018). This timescale was utilised to facilitate a five-year follow-up of cases. All cases which received curative radiotherapy (radical and adjuvant treatment modalities) and who received a pre-radiotherapy dental screen were analysed by a Consultant in Restorative Dentistry and Consultant Oncologist. Data were extracted from:
- 1.
MDT case logs
- 2.
Dental and medical electronic patient records
- 3.
Radiotherapy plans
- 4.
Medical and dental radiographs
The data extraction method involved analysis of the data sources outlined above in a Microsoft® Excel spreadsheet containing the data fields summarised below:
- 1.
Patient demographics: age, history of previous head and neck radiotherapy, history of antiresorptive therapy (e.g. bisphosphonates), osteoporosis, diabetes, smoking status, performance status (WHO)
- 2.
Cancer: site, stage, p-16 status, treatment provided
- 3.
Dental characteristics: tooth specific dental diagnoses (caries, periodontal bone loss, apical pathology), pre-radiotherapy dental extractions (site specific), pre-radiotherapy periodontal debridement, primary implant placement
- 4.
Radiotherapy characteristics: Total radiotherapy dose, number of fractions, use of concomitant chemotherapy
- 5.
Osteoradionecrosis: time between extractions and radiotherapy, ORN site specific radiotherapy dose (maximum dose at centroid of ORN), presence of dental diagnosis at the site of ORN
Data analysis was performed using an exploratory method by analysing each case individually and recording the potential risk factors that were identifiable at the pre-radiotherapy dental screening appointment. This process evolved through case based collaborative analysis. Where new risk factors were identified, all prior cases were reassessed thus developing a list of potential variables for future investigation. All noted risk factors were collated and analysed using simple descriptive statistics. This process was performed collaboratively by the authors.
3
Results
A total of 356 curative cases were analysed. The mean age of patients was 61 years. The male: female ratio was 60:40. 46% of patients were deceased at the end of follow-up time period. The median follow-up time was 4.3 years. 76% of patients underwent dental extractions with a mean of 4.1 teeth being extracted prior to radiotherapy. Of the teeth that were extracted: 58% were diagnosed with dental caries, 37% were associated with peri-apical pathology and 57% were associated with bone loss attributable to periodontal disease.
Sixty two percent of individuals were smoking at the time of radiotherapy or had quit within one month of start radiotherapy. In the cohort that developed ORN, 92% were smokers with a mean of 38 pack years. This compares to individuals that did not develop ORN of whom only 39% were smokers, 34% were previous smokers and 21% had never smoked. None of the patients who developed ORN had received antiresorptive therapy (for example, bisphosphonate therapy). Only one patient who develop ORN was diabetic.
The overall mean time between completion of dental extractions and the start of radiotherapy was 13.8 days. Of the cases which developed ORN: 53% had received a pre-radiotherapy dental extraction at the site of ORN. In these cases, the mean time between dental extraction and radiotherapy was 12.9 days.
Osteoradionecrosis developed in 9.0% of cases (n=32) with a median time between end of radiotherapy and diagnoses of ORN of 232 days (range 132–1185 days). Case specific analysis was performed in these cases using the methodology outlined above. The results of this process identified differences in the case characteristics of individuals who developed ORN with an ORN site specific dose >60Gy when compared to an ORN site specific dose <60Gy.
There was one outlier case. This was the only case involving ORN in the maxilla (0.3 % prevalence). In this instance ORN developed spontaneously. The case presented to the MDT with a T4aN1 retromolar squamous cell carcinoma, with an edentate maxilla. The site-specific radiotherapy dose was 61Gy. The patient was a non-smoker. No other risk factors were found.
All other cases of ORN involved the mandible. In cases with a site-specific dose >60Gy:
- •
78.9 % (n=15) of cases involved the posterior mandible (posterior to the second premolars), and 100 % of these cases involved erosion of the lingual cortex of the mandible.
- •
The anterior mandible was involved in 36.8 % (n=7) of cases (three of these cases had multiple sites of ORN).
- •
All three cases with multiple sites of ORN were diagnosed with T4 oral cavity tumours. In all of these the planned treatment volume (PTV) extended from the incisor region of the mandible to the angle of the mandible, and all affected sites received a radiotherapy dose >60Gy.
The site-specific radiotherapy dose in cases which develop ORN is summarised in Table 1 .
