Abstract
Objective
This study evaluated the prognostic value of the pretreatment number of natural teeth on progression-free survival and overall survival in patients with locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy.
Methods
We retrospectively analyzed 248 patients with locally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy–based concurrent chemoradiotherapy and adjuvant chemotherapy between June 2010 and December 2021. The number of natural teeth was assessed before concurrent chemoradiotherapy. A receiver operating characteristic curve analysis was performed to identify the optimal number of natural teeth threshold predictive of overall survival and progression-free survival.
Results
The optimal cutoff value for the number of natural teeth was 19.5 (area under the curve: 70.6%). Patients were grouped into those with a number of natural teeth <20 (n = 76) and those with a number of natural teeth ≥20 (n = 172). The number of natural teeth ≥20 group had significantly improved overall survival (not reached vs. 71.0 months; p < 0.001) and progression-free survival (117 vs. 38.0 months; p < 0.001). Multivariate analysis confirmed the number of natural teeth <20 as an independent predictor of worse outcomes.
Conclusions
A pretreatment number of natural teeth <20 independently predicts poorer survival in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy, suggesting that the number of natural teeth may serve as a simple, accessible prognostic biomarker in head and neck oncology.
Keywords
Introduction
Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor originating from the nasopharyngeal epithelium. Although significant progress has been made in screening techniques for the early detection of NPC, research indicates that >50% of the patients still present with advanced-stage disease, namely stages III and IV.1,2 This high percentage of late-stage diagnosis can be attributed to several factors, including the subtle and insidious nature of the initial symptoms associated with the disease, the complex anatomy of the nasopharyngeal region, and the intrinsic aggressive characteristics of NPCs, which promote rapid local, regional, and distant progression. Definitive concurrent chemoradiotherapy (CCRT) utilizing intensity-modulated radiotherapy (IMRT), with or without induction chemotherapy, is the current standard of care for patients with locally advanced nasopharyngeal carcinoma (LANPC) who are deemed medically fit.3–5 Although CCRT with IMRT achieves >90% locoregional tumor control, up to 10% and 20% of patients with LANPC still experience locoregional recurrences or distant metastasis (DM), respectively. Unfortunately, once recurrence or metastasis occurs, the chances of cure are minimal without effective salvage therapy.3–5
Currently, in patients with LANPC, the tumor-node-metastasis (TNM) staging system is universally recognized as the most reliable framework for predicting treatment outcomes. However, its prognostic power is limited because the comprehensive TNM system does not account for significant biological differences related to the tumor and the host, as it focuses solely on the local and regional extent of the primary tumor.6,7 However, patient- or disease-related biological differences among patients can result in varied clinical outcomes, even among patients with the same LANPC stage who receive identical cancer treatments. 7 This underscores the urgent need to identify innovative and robust biomarkers that could significantly improve prognostic stratification and guide individualized treatment in this patient population.
A potentially significant prognostic marker is the pretreatment number of natural teeth (NNT). Tooth loss, and consequently reduced NNT, is frequently associated with periodontitis in both the general population and individuals with cancer, affecting up to 90% of the patients. 8 Furthermore, reduced NNT has been well documented as being associated with quality of life, life expectancy, and disease prognosis across various health conditions, including several types of cancer.9–14 Although the exact causal relationship has not been established, poorer outcomes in patients with cancer with reduced NNT may be related to prolonged exposure to mild-to-moderate local and systemic inflammation caused by the underlying periodontitis and overall poor oral health.15,16 Furthermore, reduced NNT may indicate suboptimal nutritional status, compromising the immune response against cancer cells. 17
A recent extensive study of 2449 participants with head and neck squamous cell carcinoma (HNSCC), based on four studies from the International Head and Neck Cancer Epidemiology Consortium, found that a higher NNT was associated with significantly lower mortality rates. 18 Nevertheless, this study focused on patients with HNSCC of the oral cavity, oropharynx, hypopharynx, larynx, and HNSCCs not otherwise specified. As a result, no definitive conclusions can be drawn from this study regarding a potential relationship between the pretreatment NNT values and survival outcomes in patients with LANPC receiving definitive CCRT. To the best of our knowledge, although evidence indicates that up to 68% of the patients with natural dentition may require dental extractions primarily due to periodontal disease, 19 no research has evaluated the prognostic significance of pretreatment NNT in patients with LANPC undergoing definitive CCRT. Therefore, we conducted this retrospective study to assess whether pretreatment NNT values have a prognostic impact on overall survival (OS) and progression-free survival (PFS) outcomes in patients with LANPC who received IMRT-based definitive CCRT.
Patients and methods
Study design and ethics
This retrospective observational study was approved by the Institutional Review Board (IRB) of Başkent University Medical Faculty (project no: D-KA-2058, approval date: June 2022). The study was conducted in accordance with the Declaration of Helsinki (1975, revised 2024). The IRB waived the requirement for signed informed consent because anonymized retrospective data were used. This single-center investigation meticulously reviewed the records of patients diagnosed with LANPC who received CCRT at the Department of Radiation Oncology, Başkent University Medical Faculty, between June 2010 and December 2021. The reporting of this study follows Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. 20
Patients selection
Patients were identified through a systematic search of the institutional records pertaining to those with LANPC who consecutively underwent curative treatment at the Department of Radiation Oncology. Eligibility criteria included the following requirements: age 18–80 years, Eastern Cooperative Oncology Group performance score of 0–2, a body mass index of at least 18.5 kg/m2, accessible pretreatment clinical ear-nose-throat (ENT) examinations, oral examination and teeth count reports, head and neck magnetic resonance imaging (MRI) scans, and fluorodeoxyglucose–positron emission tomography–computed tomography (PET-CT) scans. Clinical or radiological staging of T3-4N0-3M0 or T1-4N1-3M0 NPC, according to the American Joint Committee on Cancer eighth edition criteria. Participants also required histological confirmation of nonkeratinizing or undifferentiated squamous cell carcinoma. Records of radiotherapy (RT) and chemotherapy charts, follow-up ENT examinations, and MRI and PET-CT scans were also required. Patients had to complete at least one cycle of platinum-based CCRT during RT, as this was a CCRT study. Patients with a history of other malignancies, immunosuppressive diseases, induction chemotherapy, or previous RT were excluded from the analyses. All patient details were deidentified to ensure privacy and anonymity.
Chemoradiotherapy protocol
All patients received definitive CCRT utilizing previously reported dosages of simultaneous integrated boost IMRT and chemotherapy: IMRT was administered in daily fractions over 7 weeks, 5 days per week. 21 In conjunction with the IMRT, each participant received at least one course of cisplatin (75–80 mg/m2) administered every 3 weeks. Following the completion of CCRT, all patients were advised to undergo two additional cycles of cisplatin-based doublet chemotherapy, depending on treatment tolerance. We enforced comprehensive supportive care measures to address the patient’s well-being during treatment. Supportive measures included antiemetic medications for nausea and vomiting, adequate hydration through intravenous fluids, and oral or enteral nutritional supplementation to maintain sufficient caloric intake and provide essential nutrients. All measures were continuously adjusted to accommodate the patient’s evolving conditions, dietary requirements, and preferences.
Pretreatment oral examination and NNT measures
All study participants underwent a thorough dental evaluation by a qualified oral and maxillofacial surgeon before CCRT, following guidelines established by the American Dental Association and the U.S. Food and Drug Administration. 22 Panoramic radiographs were obtained for all participants, following the manufacturer’s instructions (J Morita, Veraviewepocs 2 D, Kyoto, Japan), which is standard practice for all patients with head and neck cancer (HNC). Dental caries were assessed for all teeth using the World Health Organization criteria with illuminated mirrors and explorers. 23 Teeth with extensive decay beyond feasible rehabilitation, lacking adequate periodontal support, or having significant apical lesions unsuitable for root canal therapy were extracted. Superficial caries were managed with dental fillings. Patients received comprehensive oral hygiene instructions and dental scaling to improve their oral health practices. For each participant, the total number of remaining teeth, referred to as NNT, was meticulously recorded in a blinded manner before the commencement of CCRT to effectively minimize the possibility of observer bias, ensuring data integrity and reliability.
Response assessment
Although the study design was retrospective, we prospectively conducted the CCRT response evaluations according to our institution’s follow-up protocol for patients with LANPC. Patients were assessed every 3 months during the initial 2-year period of CCRT and then every 6 months from 3 to 5 years. After this timeframe, evaluations were scheduled annually or more frequently if clinically indicated. At each visit, an ENT specialist performed a thorough endoscopic examination to detect any potential local or regional tumor recurrences, as well as second primary tumors. Additionally, PET-CT scans were conducted to assess the metabolic response and the likelihood of DM until a complete metabolic response was achieved. We employed the PET Response Criteria for Solid Tumors (PERCIST) as the standard instrument to assess treatment responses. 24 Once a complete metabolic response was achieved, head and neck MRI and/or CT scans replaced the PET-CT scans. We used additional imaging methods to detect suspicious lesions or to reevaluate recurring malignancies only when necessary. The reported response rates indicated the highest level of response observed at any time point.
Endpoints and statistical analysis
The primary objective of this study was to determine whether there is a correlation between the pretreatment NNT and OS, defined as the time from the start of CCRT until death or the last follow-up record. The secondary objective was to assess the same association with PFS, defined as the duration from the initiation of CCRT until any of the locoregional recurrences, DMs, nonregional lymph node relapses, death, or the final visit. Continuous data were summarized using medians and ranges to effectively capture central tendencies and variability. Categorical variables were characterized by their frequency distributions, providing insight into their prevalence within the study population. To compare medians or frequency distributions across different patient groups, we employed appropriate statistical tests, including the Mann-Whitney U-test for non-normally distributed data, Student’s t-test for normally distributed continuous variables, chi-square test for associations between categorical variables, and Spearman correlations to assess relationships between ranked variables.
The current study utilized the receiver operating characteristic (ROC) curve analysis to evaluate the feasibility of establishing an optimal pretreatment NNT cutoff that divides the study population into two subgroups characterized by significantly divergent outcomes, with PFS and OS status defined as the events of interest. The optimal cutoff was methodically determined at the point on the curve where the Youden index reached its maximum value. Kaplan-Meier curves and log-rank tests were utilized to investigate the potential interactions between the various risk factors and the outcomes of PFS and OS. We employed the Cox proportional hazards model for multivariate analyses to evaluate the independence of those variables that exhibited statistical significance in univariate analyses. All group comparisons were two-tailed, with statistical significance specified at p-value < 0.05.
Results
This retrospective research aimed to investigate the impact of pretreatment NNT on OS and PFS outcomes in patients with LANPC who underwent definitive CCRT, followed by adjuvant chemotherapy. Patients meeting the inclusion criteria were selected from a cohort of patients with LANPC who received similar treatments and pretreatment and posttreatment evaluations at a single institution. The baseline patient and disease characteristics and treatment features of the 248 eligible patients are detailed in Table 1. The median age of the whole study group was 58 years (range: 21–79 years), with 56 participants (22.6%) aged >70 years. In the study population, 81.0% were male, 86.7% of patients had a history of smoking, and 66.9% reported consuming alcohol during the treatment period. Unfortunately, 18.5% and 13.7% of patients were reported to continue smoking and consuming alcohol during the treatment period, respectively. A substantial majority of participants were in the advanced stages of the disease, with 82.7% classified as T3-4 and 77.0% as N2-3. Overall, the CCRT demonstrated a favorable tolerance profile, with 174 patients (70.2%) completing the full three cycles of concurrent chemotherapy, while 74 patients (29.8%) completed one or two cycles. Additionally, 175 patients (70.6%) were able to receive 1–2 cycles of the prescribed two cycles of adjuvant chemotherapy following the CCRT phase (Table 1). Treatment-related fatalities were noted in only three cases, representing 1.2% of the total cohort studied. One case died due to an intractable carotid artery blow-out occurring 8 months after treatment. The remaining two cases died due to aspiration pneumonia attributed to tracheoesophageal fistulae that emerged in the 16th and 22nd months after CCRT, respectively.
Pretreatment and treatment characteristics.
ECOG: Eastern Cooperative Oncology Group; NNT: number of natural teeth; N-stage: nodal stage; T-stage: tumor stage; WHO: World Health Organization.
After a median follow-up period of 88.4 months (range: 4.0–164.0 months), 185 out of 248 participants (74.6%) were still alive, and 174 (70.2%) were free from disease progression. Treatment protocol achieved successful locoregional control (LRC) in 227 (91.5%) patients. Among the 63 deaths, 48 (76.2%) were due to cancer and its treatment (progressive LANPC: 41 (65.1%), and 3 (4.7%) late toxicities). Causes for non-NPC or treatment-unrelated deaths were identified in 15 (23.8%)—myocardial infection, 6 (9.5%); chronic obstructive pulmonary disease, 4 (6.3%); second cancers, 2 (3.2%); coronavirus disease (COVID-19), 1 (1.6%); traffic accident, 1 (1.6%); and earthquake, 1 (1.6%), respectively.
Using ROC curve analyses, we sought to determine optimal cutoff values for pretreatment NNT that would virtually stratify the study cohort into two distinct groups with significantly different outcomes in OS and PFS. The analyses identified a cutoff value of 19.5 as a common threshold for both OS (area under the curve (AUC): 70.6%; sensitivity: 73.5%; specificity: 69.8%; Youden index: 0.433) and PFS (AUC: 75.0%; sensitivity: 70.3%; specificity: 68.6%; Youden index: 0.389), as illustrated in Figure 1(a) and (b). Accordingly, we divided the study population into two groups for further analysis—Group 1: pretreatment NNT < 20 (N = 76) and Group 2: pretreatment NNT ≥ 20 (N = 172). As illustrated in Table 1, the characteristics related to pretreatment and treatment phases showed a balanced distribution across the two NNT groups, with statistical analysis revealing no significant differences (p > 0.05 for each parameter).
The results of the receiver operating characteristic curve analysis, illustrating the relationship between the pretreatment count of natural teeth and survival outcomes: (a) overall survival and (b) progression-free survival.
Comparisons between the two NNT groups at the time of the final analysis, focusing on tumor control rates, indicated that the LRC rates for the NNT ≥ 20 and NNT < 20 groups were 94.8% and 83.3%, respectively (p = 0.16). Overall, DMs was documented in 54 patients, representing 21.8% of the cohort. Notably, the DM rate was significantly lower in the NNT ≥ 20 group (17.4%) than in the NNT < 20 (33.3%) group counterpart (p = 0.006). Kaplan-Meier survival estimates revealed that the median PFS was 96 months, but the median OS time was not reached (NR) during the final analysis for the whole research cohort (Table 2). The corresponding 5-year and 10-year survival rates were 59.1% and 39.2% for PFS and 82.3% and 59.2% for OS, respectively (Table 2).
Survival results for the whole study cohort and per numbers of natural teeth group.
NNT: number of natural teeth; NR: not reached; OS: overall survival; PFS: progression-free survival.
Comparisons between the two NNT cohorts revealed that patients with NNT ≥ 20 exhibited significantly improved median PFS (117 months (95% CI: 14.3–39.7) vs. 38.0 months (95% CI: 14.3–39.7); p < 0.001) and OS (NR vs. 71.0 months (95% CI: 42.7–99.3); p < 0.001) compared to those with NNT < 20 (Table 2 and Figure 2(a) and (b)). Similarly, the 5-year and 10-year PFS and OS estimates for the NNT ≥ 20 group were quantitatively superior to those for the NNT < 20 group patients.
Survival outcomes per numbers of natural teeth (NNTs) groups (dark blue: NNT < 20; red: NNT ≥ 20): (a) overall survival and (b) progression-free survival.
The findings of the univariate analysis revealed that, in addition to a pretreatment NNT < 20 status, the factors of being an ever-smoker, having a T3/T4 tumor stage, and being classified as N2/N3 in the nodal stage were significantly associated with poorer outcomes in both PFS and OS (p > 0.05 for each factor), as presented in Table 3. The results of the multivariate analysis confirmed that each of these four significant factors from the univariate analysis independently adversely affected PFS (p < 0.05 for each factor) and OS outcomes (p < 0.05 for each factor), as shown in Table 3.
Results of univariate and multivariate analysis.
CI: confidence interval; ECOG: Eastern Cooperative Oncology Group; HR: hazard ratio; NNT: number of natural teeth; N-stage: nodal stage; OS: overall survival; PFS: progression-free survival; T-stage: tumor stage; WHO: World Health Organization.
Discussion
The primary objective of this retrospective study was to investigate the potential relationship between the pretreatment NNT status and survival outcomes, specifically PFS and OS, in patients with LANPC who were treated with definitive IMRT-based CCRT. To the best of our knowledge, this is the first study to address this issue within this patient population. Our findings indicated that a pretreatment NNT < 20 was associated with significantly shorter median, 5-year, and 10-year PFS and OS outcomes compared to presenting with a pretreatment NNT ≥ 20. Additionally, being an active smoker significantly predicted a NNT < 20 and was associated with poorer survival outcomes following CCRT.
Our study not only reaffirmed the well-established prognostic significance of higher T-stage (T3-4 vs. T1-2) and N-stage (N2-3 vs. N0-1) but also highlighted a significantly poor prognostic value associated with being an active smoker compared to a quit/never smoker.25–28 Specifically, the median PFS (38.0 vs. 117.0 months; p < 0.001) and OS (71.0 vs. NR; p < 0.001) durations were notably shorter for patients who were active smokers in comparison to their quit/never-smoked counterparts. The findings are consistent with the existing literature on HNSCCs and NPCs. For instance, a study by Hoff et al. 26 highlighted the significant negative impact of being an active smoker during RT for HNCs. It found that active smoking was linked to poorer 5-year LRC (44% vs. 65%; p = 0.001), disease-specific survival (56% vs. 77%; p = 0.003), and OS (39% vs. 66%; p = 0.0004) rates. The authors claimed that these results were attributable to impaired oxygen transport in the blood and higher levels of carboxyhemoglobin in smokers, a condition that led to decreased effectiveness of DNA damage fixation by oxygen and increased radioresistance in a state of reduced oxygen supply to tumors.26,27 Recently, Pala et al. 28 evaluated the prognostic factors in 73 patients with NPC treated with curative (chemo)radiotherapy. The authors documented that smoking for ≤5 years before curative (chemo)radiotherapy was associated with a four-fold higher risk of death compared to nonsmokers. Chronic exposure to tobacco smoke can also induce radioresistance due to tumorous and systemic hypoxia resulting from elevated levels of carbon monoxide in the blood circulation, which has an affinity for hemoglobin that is approximately 200 to 210 times greater than that of oxygen. 29 Furthermore, exposure to cigarette smoke has been demonstrated to hinder angiogenesis by inhibiting vascular endothelial growth factor through a reduction in the expression of hypoxia-inducible factor 1-alpha under hypoxic conditions, which may exacerbate the radioresistance in tumorous tissues. 30 Finally, tobacco smoke can create a hyperinflammatory and immunosuppressive environment that promotes tumor growth, increases invasiveness, and enhances metastatic capabilities, contributing to resistance to oncological therapies and resulting in a poor prognosis. 31 In summary, available data together with the results of our study presented here cumulatively underline the poor prognostic value of continued smoking during CCRT. Therefore, we strongly recommend dedicating substantial efforts to smoking cessation interventions for patients with LANPC, as well as for those patients presenting with other HNCs, to improve clinical outcomes.
Currently, the TNM staging system is recognized as the most comprehensive and dependable framework for predicting the prognosis of patients diagnosed with LANPC. This system categorizes cancer stages based on the tumor size and invasiveness (T), the extent and laterality of lymph node involvement (N), and DM (M), providing a standardized method for assessing disease progression. However, despite receiving comparable anticancer therapies, clinical outcomes can exhibit significant variability among patients at the same stage of the disease. 32 This inconsistency in patient responses may stem from various factors, including inherent biological differences related to tumor genetics, microenvironment, and the host’s nutritional status, immunity, and inflammatory response, complicating the prognostic assessments and treatment planning.33,34 These disparities and their unpredictable effects on clinical outcomes underscore the critical necessity for identifying novel and effective prognosticators, which can complement traditional TNM staging by offering additional insights into the patients’ biology, overall health status, and tumor behavior, ultimately leading to more precise prognostic classification and individually optimized therapeutic strategies. Although the existing data on LANPC remains limited, recent research indicates that the pretreatment oral health status of patients, specifically measured through the NNT, can serve as a valuable surrogate marker for predicting patient prognosis in a range of HNCs and other tumor primaries.18,35–39 Recently, Tasoulas et al. 18 conducted a pooled analysis involving 2449 participants with HNC from four studies associated with the International Head and Neck Cancer Epidemiology Consortium. This analysis incorporated data on various oral health factors, including periodontal disease, frequency of tooth brushing, mouthwash utilization, dental visits over the 10 years preceding a HNC diagnosis, and the NNT. The findings of this comprehensive study indicated that a remaining NNT of 10–19 (risk ratio (RR): 0.81) and an NNT ≥ 20 (RR: 0.88) were significantly correlated with improved OS. Similarly, Wu et al. 36 investigated the impact of tooth loss in 3271 cancer survivors and found that patients who experienced the loss of >5 teeth faced considerably higher mortality rates compared to those with five or fewer tooth losses. These findings were further supported by studies involving patients with non-HNSCC such as esophageal and colorectal cancers,36–39 highlighting the potential of pretreatment NNT and tooth loss as surrogate markers for oral health, overall well-being, and patient prognosis in these populations.
Considering the facts mentioned in the previous paragraph, our study’s key finding was establishing the first documented independent correlation between pretreatment NNT and outcomes of PFS and OS in patients with LANPC subjected to definitive CCRT and subsequent adjuvant chemotherapy. Specifically, patients in the NNT ≥ 20 group exhibited significantly improved median PFS (117 vs. 38.0 months; p < 0.001) and OS (NR vs. 71.0 months; p < 0.001) compared to those with NNT < 20. Similarly, the 10-year PFS (48.7% vs. 20.6% for NNT < 20) and OS (74.8% vs. 28.4% for NNT < 20) rates were also superior in the NNT ≥ 20 group patients, suggesting the long-term durability of the prognostic impact of pretreatment NNT in patients with LANPC. These results align with findings from previously reported large-scale studies by Tasoulas et al. 18 and those of Wu et al. 36 However, neither study included patients with LANPC in their analysis. Consequently, our study differs by exclusively focusing on patients with LANPC treated with standard CCRT, followed by adjuvant chemotherapy. Although further research is necessary to clarify the precise reasons behind these findings, a lower pretreatment NNT may indicate poor oral health, characterized by persistent mild-to-moderate local and systemic hyperinflammation, compromised immunity, and inadequate nutritional status. These factors may collectively create an environment conducive to cancer initiation, progression, and ultimately poor prognosis in cancers, including LANPC and other HNSCCs. Additionally, the notably higher DM rate observed in the NNT < 20 group (33.3% vs. 17.4% for the NNT ≥ 20 group; p = 0.006) may indicate a more aggressive LANPC phenotype driven by chronic inflammation, potentially resistant to existing chemotherapeutic agents. However, this issue requires further investigation through carefully designed studies to yield more reliable insights into the exact mechanisms underlying this observation.
The uniform application of similar treatment protocols for IMRT, CCRT, and adjuvant chemotherapy among all patients enhanced the strength of the study presented here. However, this investigation had its limitations. First, it was a retrospective analysis conducted at a single institution, which may introduce selection biases inherent to such studies. Second, the absence of an internal or external validation cohort, coupled with the lack of propensity score matching methodologies, may have compromised the robustness of our findings. Therefore, future studies incorporating these statistical techniques could be beneficial in yielding more trustworthy outcomes. Third, our ROC analysis used censored data rather than a time-dependent approach. As OS and PFS are time-to-event outcomes, the prevailing methodology may not fully capture the complexities inherent in survival analysis, and this may limit the interpretation of the AUC. Fourth, our investigation did not examine the factors that may have contributed to significant tooth loss before CCRT, such as periodontitis, particularly among patients with a NNT < 20.15,16 Given that periodontitis induces chronic local inflammation and destruction in the supporting tissues of the teeth, timely prevention or treatment of this condition within the general population could potentially reduce excessive tooth loss in patients with LANPC and positively affect their survival outcomes. Fifth, the lack of Epstein–Barr virus (EBV) titers as a prognostic factor may have unintentionally influenced the outcomes, favoring one of the NNT groups. 40 Nevertheless, it is essential to emphasize that no established relationship exists between EBV status and tooth loss in patients diagnosed with LANPC. Sixth, the lack of reliable data concerning the nutritional and socioeconomic status of our study cohort, along with the prevalence and routine use of well-fitted dentures, may have unintentionally influenced the outcomes presented here. Therefore, addressing these concerns in future well-designed prospective studies could yield valuable insights into the potential connections between these factors and patient outcomes. Lastly, differences among the salvage therapies in patients who experienced recurrences might also have unpredictably altered our results in favor of one group. Hence, we recommend that the findings presented herein be regarded merely as preliminary results concerning the prognostic significance of pretreatment NNT on the survival outcomes of patients with LANPC who have undergone radical CCRT, until well-designed future studies address the noted limitations and provide further insights.
Conclusion
The findings of our study suggest that a presenting NNT < 20 is associated with significantly poorer PFS and OS outcomes in patients with LANPC undergoing definitive CCRT. These results highlight the potential importance of proper oral care, encompassing oral hygiene training, regular dental check-ups, and necessary dental treatments, in improving outcomes in this patient population. However, further research is crucial to substantiate these findings before they can be effectively incorporated into routine oncological practice.
Footnotes
Acknowledgments
The authors confirm that no artificial intelligence tools were used for manuscript preparation.
Author contributions
All authors contributed to study conception, data collection, analysis, and manuscript drafting. All authors approved the final manuscript.
Consent for publication
We ensure that all patients signed an informed consent form before the beginning of the evaluation, either themselves or their legally authorized representatives, for the acquisition and analysis of their sociodemographic, dental, and medical records, blood samples, and publication of the outcomes.
Data availability
Data are available from Başkent University Institutional Data Access Committee for researchers meeting criteria for confidential data access.
Declaration of conflicting interests
The authors declare no conflicts of interest.
Ethics approval and consent to participate
Before acquiring any information from the patient, the Institutional Review Board of the Başkent University School of Medicine approved the study design and complied with the Declaration of Helsinki.
Funding
None.
