Role of Natural Killer Cells as Cell-Based Immunotherapy in Oral Tumor Eradication and Differentiation Both In Vivo and In Vitro.

Despite advancements in the field of cancer therapeutics, the five-year survival rate remains low in oral cancer patients. Therefore, the effective therapeutics are needed against oral cancer. Also, several studies including ours, have shown severely suppressed function and number of NK cells in oral cancer patients. In this review, we discuss the approach to inhibit the tumor growth and metastasis by direct killing or NK cell-mediated tumor differentiation. This review also provides an overview on supercharging NK cells using osteoclasts and probiotic bacteria, and their efficacy as cancer immunotherapeutic in humanized-BLT mice.

Neoadjuvant Radiochemotherapy Alters the Immune and Metabolic Microenvironment in Oral Cancer-Analyses of CD68, CD163, TGF-ß1, GLUT-1 and HIF-1α Expressions.

BACKGROUND: The first-line treatment of oral squamous cell carcinoma (OSCC) involves surgical tumor resection, followed by adjuvant radio(chemo)therapy (R(C)T) in advanced cases. Neoadjuvant radio- and/or chemotherapy has failed to show improved survival in OSCC. Recently, neoadjuvant immunotherapy has shown promising therapeutic efficacy in phase 2 trials. In this context, the addition of radio- and chemotherapy is being reconsidered. Therefore, a better understanding of the tumor-biologic effects of neoadjuvant RCT would be beneficial. The current study was conducted on a retrospective cohort of patients who received neoadjuvant RCT for the treatment of oral cancer. The aim of the study was to evaluate the influence of neoadjuvant RCT on the immunological tumor microenvironment (TME) and hypoxic and glucose metabolisms. METHODS: A cohort of 45 OSSC tissue samples from patients were analyzed before and after RCT (total 50.4 Gy; 1.8 Gy 5× weekly; Cisplatin + 5-Fluorouracil). Immunohistochemistry for CD68, CD163, TGF-ß, GLUT-1 and HIF-1α was performed using tissue microarrays and automated cell counting. Differences in expression before and after RCT and associations with histomorphological parameters (T-status, N-status) were assessed using the Mann-Whitney U test. RESULTS: Tumor resection specimens after neoadjuvant RCT showed a significant decrease in CD68 infiltration and a significant increase in CD163 cell density. The CD68/CD163 ratio was significantly lower after RCT, indicating a shift toward M2 polarization. The GLUT-1 and HIF-1α expressions were significantly lower after RCT. Larger tumors (T3/T4) showed a lower GLUT-1 expression. Other biomarkers were not associated with the T- and N-status. CONCLUSIONS: Neoadjuvant RCT with 50.4 Gy induced a shift toward the M2 polarization of macrophages in the TME. This change in immune composition is not favorable and may be prognostically negative and counteract immunotherapeutic approaches. In addition, the decreased expressions in GLUT-1 and HIF-1α indicate reductions in the glucose metabolism and hypoxic energy metabolism in response to "high dose" neoadjuvant RCT, which may be therapeutically desirable.

Factors associated with recurrence in patients with oral cancer in Mongolia.

INTRODUCTION: In Mongolia, there has been limited research on the posttreatment survival rate, recurrence, and occurrence of oral cancer. The goal of this study is to investigate the risk factors that contribute to the recurrence of oral cancer to increase survival rates, facilitate early detection, and improve treatment accuracy. METHOD: A retrospective cohort method was used, with medical records from 173 patients diagnosed with squamous cell carcinoma of the mouth at the National Cancer Center of Mongolia's Department of Head and Neck Surgery, Radio, and Chemotherapy between 2012 and 2017. The Mongolian National University of Medical Sciences' Research Ethics Committee approved the project. RESULTS: The findings revealed that 109 cases (63.0%) were men and 64 (37.0%) were females, with a large proportion of patients (28.3%) falling between the ages of 61 and 70. Men had a 3.8 times higher risk of cancer recurrence than women (OR = 3.79, CI = 1.24-11.57). Furthermore, lymph node metastases and treatment were linked to oral cancer recurrence. CONCLUSION: This study offers light on the factors that influence the recurrence of oral cancer, giving useful insights for improving patient outcomes through early detection and proper treatment.

Light gradient boosting-based prediction of quality of life among oral cancer-treated patients.

BACKGROUND AND INTRODUCTION: Statisticians rank oral and lip cancer sixth in global mortality at 10.2%. Mouth opening and swallowing are challenging. Hence, most oral cancer patients only report later stages. They worry about surviving cancer and receiving therapy. Oral cancer severely affects QOL. QOL is affected by risk factors, disease site, and treatment. Using oral cancer patient questionnaires, we use light gradient Boost Tree classifiers to predict life quality. METHODS: DIAS records were used for 111 oral cancer patients. The European Organisation for Research and Treatment of Cancer's QLQ-C30 and QLQ-HN43 were used to document the findings. Anyone could enroll, regardless of gender or age. The IHEC/SDC/PhD/OPATH-1954/19/TH-001 Institutional Ethical Clearance Committee approved this work. After informed consent, patients received the EORTC QLQ-C30 and QLQ-HN43 questionnaires. Surveys were in Tamil and English. Overall, QOL ratings covered several domains. We obtained patient demographics, case history, and therapy information from our DIAS (Dental Information Archival Software). Enrolled patients were monitored for at least a year. After one year, the EORTC questionnaire was retaken, and scores were recorded. This prospective analytical exploratory study at Saveetha Dental College, Chennai, India, examined QOL at diagnosis and at least 12 months after primary therapy in patients with histopathologically diagnosed oral malignancies. We measured oral cancer patients' quality of life using data preprocessing, feature selection, and model construction. A confusion matrix was created using light gradient boosting to measure accuracy. RESULTS: Light gradient boosting predicted cancer patients' quality of life with 96% accuracy and 0.20 log loss. CONCLUSION: Oral surgeons and oncologists can improve planning and therapy with this prediction model.

Diagnostic Complexities of Oral Squamous Cell Carcinoma.

Prompt diagnosis of oral cancers is critical to increase survival rates. Treatment for oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) is mainly driven by cancer stage and may include surgery alone or surgery with adjuvant or neoadjuvant radiation, chemotherapy, and/or targeted therapy. This article describes a case of a patient who was referred by his general dentist to an oral medicine clinic for assessment of an exophytic lesion on the left lateral tongue. The case report discusses the differential diagnosis and treatment, examining critical elements in lesion assessment in the patient, who had a significant oral lesion history and who was ultimately diagnosed with OSCC. Highlighting various complexities that may arise in the diagnosis of OSCC, the article underscores the importance of surveillance, informed biopsy technique, and accurate interpretation of pathology reports to appropriately manage patients with potential oral malignancy.

Trends and predictors of unplanned hospitalization among oral and oropharyngeal cancer patients; an 8-year population-based study.

PURPOSE: The incidence of oral cancers, particularly HPV-related oropharyngeal cancer, is steadily increasing worldwide, presenting a significant healthcare challenge. This study investigates trends and predictors of unplanned hospitalizations for oral cavity cancer (OCC) and oropharyngeal cancer (OPC) patients in the province of Alberta, Canada. METHODS: This retrospective, population-based, cohort study used administrative data collected from all hospitals in the province. Using the Alberta Cancer Registry (ACR), a cohort of adult patients diagnosed with a single primary OCC or OPC between January 2010 and December 2017 was identified. Linking this cohort with the Discharge Abstract Database (DAD), trends in hospitalizations, primary diagnoses, and predictors of unplanned hospitalization (UH) and 30-day unplanned readmission were analyzed. RESULTS: Of 1,721 patients included, 1,244 experienced 2,228 hospitalizations, with 48 % being categorized as UH. The UHs were significantly associated with a higher mortality rate, 18.5 % as compared to 4.6 % for planned, and influenced by sex, age groups, comorbidities, cancer types, stages, and treatment modalities. The rate of UH per patient decreased from 0.69 to 0.54 visits during the study period (P = 0.02). Common diagnoses for UH were palliative care and post-surgical convalescence, while surgery-related complications such as infection and hemorrhage were frequent in 30-day unplanned readmissions. Predictors of UH included cancer stage, material deprivation, and treatment, while cancer type and comorbidity predicted readmissions. CONCLUSION: The rate of UHs showed a noteworthy decline in this study, which could be a result of enhanced care coordination. Furthermore, identified primary diagnosis and predictors associated with UHs and readmissions, provide valuable insights for enhancing the quality of care for cancer patients.

Identification of cuproptosis-related lncRNAs with the significance in prognosis and immunotherapy of oral squamous cell carcinoma.

Cuproptosis, a recently characterized programmed cell death mechanism, has emerged as a potential contributor to tumorigenesis, metastasis, and immune modulation. Long non-coding RNAs (lncRNAs) have demonstrated diverse regulatory roles in cancer and hold promise as biomarkers. However, the involvement and prognostic significance of cuproptosis-related lncRNAs (CRLs) in oral squamous cell carcinoma (OSCC) remain poorly understood. Based on TCGA-OSCC data, we integrated single-sample gene set enrichment analysis (ssGSEA), the LASSO algorithm, and the tumor immune dysfunction and exclusion (TIDE) algorithm. We identified 11 CRLs through differential expression, Spearman correlation, and univariate Cox regression analyses. Two distinct CRL-related subtypes were unveiled, delineating divergent survival patterns, tumor microenvironments (TME), and mutation profiles. A robust CRL-based signature (including AC107027.3, AC008011.2, MYOSLID, AC005785.1, AC019080.5, AC020558.2, AC025265.1, FAM27E3, and LINC02367) prognosticated OSCC outcomes, immunotherapy responses, and anti-tumor strategies. Superior predictive power compared to other lncRNA models was demonstrated. Functional assessments confirmed the influence of FAM27E3, LINC02367, and MYOSLID knockdown on OSCC cell behaviors. Remarkably, the CRLs-based signature maintained stability across OSCC patient subgroups, underscoring its clinical potential for survival prediction. This study elucidates CRLs' roles in TME of OSCC and establishes a potential signature for precision therapy.

Burning mouth in oncology care: a systematic review.

Burning mouth, also referred to as oral dysesthesia, is an underreported condition among cancer patients that may represent an early symptom of cancer or an adverse effect of treatment. This review sought to characterize this symptom in oncology care where burning symptoms may occur. A systematic review of the literature was performed based on the PRISMA statement, and the protocol was registered at PROSPERO database. A structured search was done using eight databases. The process of study selection was conducted in two distinct phases. The JBI Critical Appraisal Tools were utilized to evaluate the risk of bias in the studies included. Of the total number of studies assessed, sixteen met the eligibility criteria. Of these studies included, 7 were case reports, 7 cross-sectional studies, and 2 non-randomized clinical trials. Most studies presented low risk of bias (n = 9), while the remaining studies were evaluated and scored as moderate (n = 5) or high (n = 2) risk of bias. Burning mouth was reported as a first symptom of cancer in three studies, and as an adverse event of radiotherapy (n = 2), chemoradiotherapy (n = 2), and chemotherapy (n = 9). Burning mouth was a first symptom in 0.62% of oral squamous cell carcinoma (OSCC), and 3.3% of patients with pain as chief complaint. Oral dysesthesia prevalence was 13.6% in patients experiencing chemotherapy-induced oral adverse events. The symptom of burning mouth should be examined in oncology care, as it may be underreported and therefore undertreated. New therapies may be related to a higher risk of oral burning and studies assessing approach to management are needed. Current management borrows from the current management of burning mouth in the non-cancer setting.

Exosomes: A Cutting-Edge Theranostics Tool for Oral Cancer.

Exosomes are a subpopulation of extracellular vesicles (EVs) secreted by cells. In cancer, they are key cellular messengers during cancer development and progression. Tumor-derived exosomes (TEXs) promote cancer progression. In oral cancer, the major complication is oral squamous cell carcinoma (OSCC). Exosomes show strong participation in several OSCC-related activities such as uncontrolled cell growth, immune suppression, angiogenesis, metastasis, and drug and therapeutic resistance. It is also a potential biomarker source for oral cancer. Some therapeutic exosome sources such as stem cells, plants (it is more effective compared to others), and engineered exosomes reduce oral cancer development. This therapeutic approach is effective because of its specificity, biocompatibility, and cell-free therapy (it reduced side effects in cancer treatment). This article highlights exosome-based theranostics signatures in oral cancer, clinical trials, challenges of exosome-based oral cancer research, and future improvements. In the future, exosomes may become an effective and affordable solution for oral cancer.

Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma.

BACKGROUND: The novel form of regulatory cell death, cuproptosis, is characterized by proteotoxicity, which ultimately leads to cell death. Its targeting has emerged as a promising therapeutic approach for oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) participate in epigenetic regulation and have been linked to the progression, prognosis, and treatment of OSCC. Thus, this study aimed to identify new cuproptosis-related lncRNAs (CRLs), establish predictive models for clinical prognosis, immune response, and drug sensitivity, and provide novel insights into immune escape and tumor drug resistance. METHODS: The present study screened eight CRLs (THAP9-AS1, STARD4-AS1, WDFY3-AS2, LINC00847, CDKN2A-DT, AL132800.1, GCC2-AS1, AC005746.1) using Lasso Cox regression analysis to develop an eight-CRL prognostic model. Patients were categorized into high- and low-risk groups using risk scores. To evaluate the predictive ability of the model, Kaplan-Meier analysis, ROC curves, and nomograms were employed. Furthermore, the study investigated the differences in immune function and anticancer drug sensitivity between the high- and low-risk groups. To validate the expression of CRLs in the model, OSCC cell lines were subjected to quantitative real-time fluorescence PCR (qRT-PCR). RESULTS: The results of the study showed that the high-risk group had a shorter overall survival (OS) time in OSCC patients. Cox regression analysis demonstrated that the high-risk score was an independent risk factor for a poor prognosis. The validity of the model was confirmed using ROC curve analysis, and a nomogram was developed to predict the prognosis of OSCC patients. Furthermore, patients in the high-risk group with high TMB had a poorer prognosis. Patients in the low-risk group responded better to immunotherapy than those in the high-risk group. Additionally, the risk scores were significantly associated with drug sensitivity in OSCC patients. Finally, the findings of qRT-PCR supported the reliability of the proposed risk model. CONCLUSION: The study identified and established the 8-CRL model, which represents a novel pathway of lncRNA regulation of cuproptosis in OSCC. This model provides guidance for the prognosis and treatment of OSCC and offers a new insight into immune escape and tumor drug resistance.

Lingual Denervation Improves the Efficacy of Anti-PD-1 Immunotherapy in Oral Squamous Cell Carcinomas by Downregulating TGFß Signaling.

PURPOSE: Intratumoral nerve infiltration relates to tumor progression and poor survival in oral squamous cell carcinoma (OSCC). How neural involvement regulates antitumor immunity has not been well characterized. This study aims to investigate molecular mechanisms of regulating tumor aggressiveness and impairing antitumor immunity by nerve-derived factors. EXPERIMENTAL DESIGN: We performed the surgical lingual denervation in an immunocompetent mouse OSCC model to investigate its effect on tumor growth and the efficacy of anti-PD-1 immunotherapy. A trigeminal ganglion neuron and OSCC cell coculture system was established to investigate the proliferation, migration, and invasion of tumor cells and the PD-L1 expression. Both the neuron-tumor cell coculture in vitro model and the OSCC animal model were explored. RESULTS: Lingual denervation slowed down tumor growth and improved the efficacy of anti-PD-1 treatment in the OSCC model. Coculturing with neurons not only enhanced the proliferation, migration, and invasion but also upregulated TGFß-SMAD2 signaling and PD-L1 expression of tumor cells. Treatment with the TGFß signaling inhibitor galunisertib reversed nerve-derived tumor aggressiveness and downregulated PD-L1 on tumor cells. Similarly, lingual denervation in vivo decreased TGFß and PD-L1 expression and increased CD8+ T-cell infiltration and the expression of IFNγ and TNFα within tumor. CONCLUSIONS: Neural involvement enhanced tumor aggressiveness through upregulating TGFß signaling and PD-L1 expression in OSCC, while denervation of OSCC inhibited tumor growth, downregulated TGFß signaling, enhanced activities of CD8+ T cells, and improved the efficacy of anti-PD-1 immunotherapy. This study will encourage further research focusing on denervation as a potential adjuvant therapeutic approach in OSCC. SIGNIFICANCE: This study revealed the specific mechanisms for nerve-derived cancer progression and impaired antitumor immunity in OSCC, providing a novel insight into the cancer-neuron-immune network as well as pointing the way for new strategies targeting nerve-cancer cross-talk as a potential adjuvant therapeutic approach for OSCC.

Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics.

Glucocorticoid and Mineralocorticoid receptors are principally ligand-dependent intracellular transcription factors that are known to influence the development and growth of many human cancers. Our study investigates the potential of these receptors to act as a target for oral cancer treatment since findings in this regard are sparse till date. Leveraging the aberrant behavior of steroid hormone receptors (SHRs) in cancer, we have targeted oral cancer cells in 2D-culture using liposomes containing both synthetic as well as crude, natural SHR ligands isolated from an aqueous Indian medicinal plant. Lipoplexes thus formulated demonstrated targeted transfectability as indicated by expression of green fluorescent protein. Transfection of oral squamous cell carcinoma cells with exogenous, anticancer gene p53 lipoplexed with crude saponin-based liposome induced apoptosis of cancer cells via regulation of BAX and B-cell leukemia/lymphoma-2 (BCL2) protein levels at levels comparable with pre-established delivery systems based on synthetic SHR ligands. Our findings strongly indicate a possibility of developing plant saponin-based inexpensive delivery systems which would target cancer cells selectively with reduced risks of off target delivery and its side effects.

Targeting ENPP1 depletion may be a promising therapeutic strategy for treating oral squamous cell carcinoma via cytotoxic autophagy-related apoptosis.

ENPP1 depletion closely related with modulation immunotherapy of several types of cancer. However, the role of ENPP1 correlation with autophagy in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown. In this study, effects of ENPP1 on OSCC cells in vitro were examined by cell proliferation assay, transwell chamber assay, flow cytometry analysis and shRNA technique. Cellular key proteins related to cell autophagy and apoptosis were evaluated by Western blot and immunofluorescent staining. Moreover, functions of ENPP1 on OSCC process were observed in nude mouse model. We reported that overexpression of ENPP1 promote the growth of OSCC cell xenografts in nude mouse model. In contrast, ENPP1 downregulation significantly inhibits OSCC cancer growth and induces apoptosis both in vitro and in vivo, which are preceded by cytotoxic autophagy. ENPP1downregulation induces a robust accumulation of autophagosomes, increases LC3B-II and decreases SQSTM1/p62 in ENPP1-shRNA-treated cells and xenografts. Mechanistic studies show that ENPP1 downregulation increases PRKAA1 phosphorylation leading to ULK1 activation. AMPK-inhibition abrogates ENPP1 downregulation-induced ULK1-activation, LC3B-turnover and SQSTM1/p62-degradation while AMPK-activation potentiates it's effects. Collectively, these data uncover that ENPP1 downregulation induces autophagic cell death in OSCC cancer, which may provide a potential therapeutic target for the treatment of OSCC.

Evaluation of Dentist's Knowledge and Practice About Dental Management of Oral Cancer Patients.

BACKGROUND: Dentists play a key role in and the management of oral cancer treatment complications. This study aimed to evaluate the general and specialist dentists' knowledge and practice regarding the dental management of such patients. METHODS: This cross-sectional analytic study was conducted among 370 general and specialist dentists in Isfahan, Iran 2020. A self-administrative questionnaire was designed and validated. The questionnaire had 18 questions in Knowledge section, 10 questions to measure performance, and 3 questions to evaluate dentist's opinion toward their management ability. The collected data were analyzed by descriptive and analytic tests such as T-Test, Kruskal-Wallis, Mann-Whitney, Chi-square, and Fisher's Exact statistics (P ≤ 0.05). RESULTS: The mean knowledge score was 9.96±2.87 in specialists and 7.59±2.36 in general dentists (out of 18, P < 0.001). There was no statistically significant difference between the mean knowledge based on gender, employment type, work experience of general and specialist, or the number of working days in a week. In addition, there was a significant relationship between the mean knowledge and having patients with oral cancer undergoing radiotherapy or chemotherapy (P = 0.012). CONCLUSION: This study indicated that specialists'knowledge level is higher than general dentists. It was also shown that knowledge directly relates to practice and attitude. Besides, regarding insufficient knowledge of dentists in this field, it is necessary to hold training programs and retraining sessions.

Systemic and Local Administration of a Dual-siRNA Complex Efficiently Inhibits Tumor Growth and Bone Invasion in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-ß to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-ß complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-ß showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-ß represents a potential RNA-based gene therapy delivery system for OSCC.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

OBJECTIVES: The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. MATERIALS AND METHODS: Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. RESULTS: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. CONCLUSION: Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Predicting survival in patients with buccal cancer: A study based on SEER database and external validation in China.

OBJECTIVE: Buccal mucosa cancer (BMC) is one of the most common oral cancers and has poor prognosis. The study aimed to develop and validate nomograms for predicting the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) of BMC patients. METHODS: We collected and reviewed information on BMC patients diagnosed between 2004 and 2019 from the Surveillance Epidemiology and End Results database. Two nomograms were developed and validated to predict the OS and CSS based on predictors identified by univariate and multivariate Cox regression. An extra external validation was further performed using data from Sun Yat-sen Memorial Hospital (SYSMH). RESULTS: A total of 3154 BMC patients included in this study were randomly assigned to training and validation groups in a 2:1 ratio. Independent prognostic predictors were identified, confirmed, and fitted into nomograms for OS and CSS, respectively. The C-indices are 0.767 (Training group OS), 0.801 (Training group CSS), 0.763 (Validation group OS), and 0.781 (Validation group OS), respectively. Moreover, the nomograms exhibited remarkable precision in forecasting and significant clinical significance, as evidenced by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA). The final validation using our data from SYSMH also showed high accuracy and substantial clinical benefits within the nomograms. The C-indices are 0.849 (SYSMH group OS) and 0.916 (SYSMH group CSS). These indexes are better than tumor, node, and metastasis stage based on prediction results. CONCLUSIONS: The nomograms developed with great performance predicted 1-, 3-, and 5-year OS and CSS of BMC patients. Use of the nomograms in clinical practices shall bring significant benefits to BMC patients.

The impact of comorbidity on the diagnosis delay, treatment options and prognosis for advanced oral cancer: A retrospective result of the POROMS database.

This study aimed to reveal the underlying mechanisms linking advanced oral squamous cell carcinoma (OSCC) with its comorbidities. Data extracted from the POROMS database included 448 advanced OSCC patients in stage III or IV (AJCC 8th) with primary tumors between August 2015 and August 2021. Time to diagnosis delay increased from 4.5, 5.3-6.5 months when the Adult Comorbidity Evaluation-27 (ACE-27) worsened from none, mild (RR: 1.155, 1.043-1.279; P = 0.006) to moderate-severe (RR: 1.431, 1.251-1.636; P < 0.001). With the number of comorbidities increased from 0, 1-2 (RR: 1.188, 1.078-1.310; P = 0.001) to 3 (RR: 1.563, 1.296-1.885; P < 0.001), the time to diagnosis delay increased from 4.5, 5.4-7.1 months. As the level and number of comorbidities increased, the likelihood of treatment completion gradually declined, especially in those older than 65 years (P = 0.003). The presence of comorbidity was an independent prognostic factor for disease-free survival (HR: 1.431, 1.022-2.005; P = 0.037). Comorbidities may lead to poorer prognosis by directly causing delays in diagnosis, limiting treatment options, and increasing the risk of death in advanced OSCC patients.