Table 1 shows exact information of all the patients. The patients included were 92 males and 46 females, with an average age of 48 (12-72) years. All patients were administered intensity-modulated radiotherapy (IMRT) as planned, and 122 patients received 2-3 cycles of induction chemotherapy (docetaxel 75 mg/m2, D1 + cisplatin 25 mg/m2 D1-3, Q21d). In total, 114 patients were administered concurrent chemotherapy during radiotherapy (cisplatin 75 mg/m2, D1 and D22).
The median follow-up time was 30 (12-60) months. Twenty-eight patients (20.3%) suffered from radiotherapy-related caries, and the median onset time was 12(2-54) months after radiotherapy. Among them, 8 patients had dental caries in the incisor-canine region (28.58%), 6 patients had caries in the canine-molar region (21.43%), 6 patients had caries in the molar region (21.43%), and 4 patients showed full crown damage (14.29%).
Univariate and multivariate analyses of factors influencing radiotherapy-related caries
In order to investigate the factors influencing radiotherapy-related caries, this study recorded the radiation dose received by patients’ salivary glands during radiotherapy, oral saliva pH, lifestyle including dietary habits (whether they drink tea, coffee, or traditional Chinese medicine), and tooth brushing frequency based on which a time-dependent regression analysis was performed. Table 2 shows the results of univariate analyses of these factors. Oral saliva pH value (hazard ratio [HR]=0.352), different choices of radiotherapy techniques (IMRT vs. 3DRT HR=0.302; TOMO vs. 3DRT, HR=0.152), dietary habits (drinking tea vs. water, HR=2.263), and radiation dose received by the sublingual glands (HR=1.045) had a significant effect on the occurrence of radiotherapy-related caries. In contrast, patients’ gender, disease stage, dietary habits (preference for sweet food, vegetarians vs. non-vegetarians), and radiation dose received by the bilateral parotid glands, submandibular glands, and mandible had a minimal effect on the occurrence of radiotherapy-related caries. Limiting the radiation dose received by the sublingual glands to <32.52 Gy reduced the occurrence of radiotherapy-related caries (Figure 1).
Further multivariate analysis for these positive factors were done (Table 3), which revealed that, oral saliva pH value was an independent prognostic factor or radiotherapy-related caries (HR=0.390, 95% confidence interval [CI]=0.204-0.746, p value=0.04).
Oral saliva pH value node
During the follow-up period of more than 4 years, we found that the oral pH values of patients may show different trends according to the different follow-up durations. Some cases showed a trend of gradual decrease, whereas others showed an initial increase, followed by a decrease. Prior to receiving radiotherapy, the majority of patients showed oral saliva pH values that fell within a range of 5.5-7.0. After radiotherapy, there was a sharp decline in patients’ oral pH values, with nearly all patients showing values below 5.0 at the first follow-up, some of whom even reached a minimum of 4.3 with time. According to the logistic regression model (Table 4), the point at which oral saliva pH value fluctuates around 5.3 is a predictor with an ideal sensitivity (71.4%) and specificity (99.1%). In order to verify this pH node value, this study divided all patients at absolute time points into two groups. The first group followed Pattern 1, wherein the patients’ oral saliva pH values were consistently >5.3 or were initially <5.3, but increased to >5.3 over time. The second group followed Pattern 2, wherein the patients’ oral saliva pH values were consistently <5.3 or were initially >5.3 but later decreased to <5.3. Risk comparison was performed between these two groups according to the absolute time points. All patients with Pattern 2 showed a significantly higher risk of dental caries than patients with Pattern 1 (Table 5, Supplement Figure 1). From the 3rd to 48th month after radiotherapy, the risk value for Pattern 2 was about 15-24 times higher than that of Pattern 1. This further confirms the fact that increasing oral saliva pH value to >5.3 could be a new measure to prevent or reduce the occurrence of radiotherapy-related caries.
Prediction time node
The node for oral saliva pH value was obtained based on the conclusions from Table 4. By summarizing the distribution of all patients with caries, we observed that among the 28 patients with caries, more than 75% occurred within 12 months. Therefore, this study focused on analyzing the occurrence of caries within 24 months after radiotherapy, and found that the 9th month after radiotherapy during follow-up was the earliest and most optimal time period for prediction with an excellent sensitivity (77.4%) and specificity (99.1%, Supplement Table 1, Supplement Figure 2).