Radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) is the cornerstone of organ-sparing or adjuvant therapy for nearly all head and neck cancers. Unfortunately, aggressive RT or CCRT can result in severe late toxicities, such as osteoradionecrosis of the jaws (ORNJ). The incidence of ORNJ is currently less than 5–6% due to advances in dental preventive care programs, RT planning systems, and RT techniques. Although numerous patient-, tumor-, and treatment-related factors may influence the incidence rates of ORNJ, RT modality (equipment), technique, and dose-volume-related factors are three of the most influential factors. This is mainly because different RT equipment and techniques have different levels of success at delivering the prescribed dose to the focal volume of the treatment while keeping the “organ at risk” safe. ORNJ risk is ultimately determined by mandibular dose, despite the RT technique and method being known predictors. Regardless of the photon delivery method, the radiobiological effects will be identical if the total dose, dose per fraction, and dose distribution within the tissue remain constant. Therefore, contemporary RT procedures mitigate this risk by reducing mandibular dosages rather than altering the ionizing radiation behavior in irradiated tissues. In light of the paucity of studies that have examined the impact of RT modality, technique, and dose-volume-related parameters, as well as their radiobiological bases, the present review aims to provide a comprehensive overview of the published literature on these specific issues to establish a common language among related disciplines and provide a more reliable comparison of research results.

Background: To evaluate the utility of pretreatment systemic immune-inflammation index (SII) in predicting the teeth caries and need for tooth extraction after concurrent chemoradiotherapy (C-CRT) for locally advanced squamous-cell head and neck cancer (LA-SCHNC) patients. Methods: The records of LA-SCHNC patients who underwent formal dental evaluations at pre- and post-C-CRT periods were retrospectively analyzed. The pretreatment SII values were calculated using the platelet, neutrophil, and lymphocyte measures acquired on the first day of C-CRT: SII=Platelets×neutrophils/lymphocytes. Receiver operating characteristic (ROC) curve analysis was employed to identify the ideal pre-C-CRT SII cutoff that may predict the teeth caries and the need for tooth extraction after the C-CRT. The primary endpoint was the link between the pre-C-CRT SII and the need for tooth extraction during the follow-up period. Results: A sum of 126 patients were included. Median follow-up was 4.9 years (range: 2.7– 7.8). Nasopharyngeal and laryngeal cancers comprised the majority (75.4%) study cohort. Post-treatment teeth extractions were reported in 62.7% patients. The optimal cutoff was 558 [Area under the curve (AUC): %76.8 sensitivity: 72.3%; and specificity: 70.9%] that grouped the patients into two subgroups with significantly different post-C-CRT tooth extraction rates: Group 1: SII≤ 558 (n = 70) and SII> 558 (n = 56), respectively. Correlation analysis revealed a significant relationship between the pretreatment SII and the tooth extraction rates after the C-CRT (r_s:0.89: P = 0.001). The comparative analysis displayed that the teeth extractions rates were significantly higher in the SII> 558 group (77.1% versus 51.4% for SII≤ 558; Hazard ratio: 1.68; P = 0.001). Further analyses showed that the pre-C-CRT SII> 558 was the unique factor associated with meaningfully higher necessities for post-C-CRT teeth extractions. Conclusion: The present outcomes intimated that high pretreatment SII levels were linked to significantly increased post-treatment teeth extractions in LA-SCHNC patients undergoing definitive C-CRT.

Background: This retrospective study aimed to investigate whether the pretreatment hemoglobin-to-platelet ratio (HPR) could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (C-CRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: ORN cases were reported from the records of LA-NPC patients who had oral examinations before and after C-CRT. The pretreatment HPR values were calculated on the first day of C-CRT. The connection between HPR values and ORN occurrences was determined using receiver operating characteristic curve analysis. The primary endpoint was the relationship between the pretreatment HPR values and post-C-CRT ORN incidence rates, while secondary endpoints included the identification of other putative ORN risk factors. Results: We distinguished 10.9% incidences of ORN during the post-C-CRT follow-up period among 193 LA-NPC patients. The optimal cutoff for pre-C-CRT HPR was 0.48 that grouped the patients into two HPR groups with fundamentally different post-C-CRT ORN incidence rates: Group 1: HPR ≤ 0.48 (N = 60), and Group 2: HPR > 0.48 (N = 133). The comparative analysis indicated a significantly higher ORN incidence in HPR ≤ 0.48 group (30%; P < 0.001). The other factors associated with meaningfully increased ORN rates included the presence of pre-C-CRT ≥ 5 teeth extractions, mandibular volume receiving ≥ 64 Gy, post-C-CRT tooth extractions, mean mandibular dose ≥ 50.6 Gy, and C-CRT to tooth extraction interval > 5.5 months. Conclusion: Low pretreatment HPR levels were independently and unequivocally linked to significantly increased incidence of ORN post-C-CRT. Pre-C-CRT HPR levels may be used to estimate the incidence of ORN and be useful for taking preventive and therapeutic measures in these patients such as monitoring oral hygiene with strict follow-up, avoidance of unnecessary tooth extractions, particularly after C-CRT, and use of more rigorous mandibular RT dose limits.

To evaluate the value of the newly created GLUCAR index in predicting tooth extraction rates after concurrent chemoradiotherapy (C-CRT) in locally advanced nasopharyngeal carcinomas (LA-NPCs). Methods: A total of 187 LA-NPC patients who received C-CRT were retrospectively analyzed. The GLUCAR index was defined as ′GLUCAR = (Fasting Glucose × CRP/Albumin Ratio) by utilizing measures of glucose, C-reactive protein (CRP), and albumin obtained on the first day of C-CRT. Results: The optimal GLUCAR cutoff was 31.8 (area under the curve: 78.1%; sensitivity: 70.5%; specificity: 70.7%, Youden: 0.412), dividing the study cohort into two groups: GLUCAR ˂ 1.8 (N = 78) and GLUCAR ≥ 31.8 (N = 109) groups. A comparison between the two groups found that the tooth extraction rate was significantly higher in the group with a GLUCAR ≥ 31.8 (84.4% vs. 47.4% for GLUCAR ˂ 31.8; odds ratio (OR):1.82; p < 0.001). In the univariate analysis, the mean mandibular dose ≥ 38.5 Gy group (76.5% vs. 54.9% for <38.5 Gy; OR: 1.45; p = 0.008), mandibular V55.2 Gy group ≥ 40.5% (80.3 vs. 63.5 for <40.5%, p = 0.004, OR; 1.30), and being diabetic (71.8% vs. 57.9% for nondiabetics; OR: 1.23; p = 0.007) appeared as the additional factors significantly associated with higher tooth extraction rates. All four characteristics remained independent predictors of higher tooth extraction rates after C-CRT in the multivariate analysis (p < 0.05 for each). Conclusions: The GLUCAR index, first introduced here, may serve as a robust new biomarker for predicting post-C-CRT tooth extraction rates and stratifying patients according to their tooth loss risk after treatment.