A novel nomogram for predicting overall survival in patients with tongue squamous cell carcinoma using clinical features and MRI radiomics data: a pilot study.

OBJECTIVE: Tongue squamous cell carcinoma (TSCC) accounts for 43.4% of oral cancers in China and has a poor prognosis. This study aimed to explore whether radiomics features extracted from preoperative magnetic resonance imaging (MRI) could predict overall survival (OS) in patients with TSCC. METHODS: The clinical imaging data of 232 patients with pathologically confirmed TSCC at Xiangyang No. 1 People's Hospital were retrospectively analyzed from February 2010 to October 2022. Based on 2-10 years of follow-up, patients were categorized into two groups: control (healthy survival, n = 148) and research (adverse events: recurrence or metastasis-related death, n = 84). A training and a test set were established using a 7:3 ratio and a time node. Radiomics features were extracted from axial T2-weighted imaging, contrast-enhanced T1-weighted imaging, and diffusion-weighted imaging (DWI) sequences. The corresponding radiomics scores were generated using the least absolute shrinkage and selection operator algorithm. Kaplan-Meier and multivariate Cox regression analyses were used to screen for independent factors affecting adverse events in patients with TSCC using clinical and pathological results. A novel nomogram was established to predict the probability of adverse events and OS in patients with TSCC. RESULTS: The incidence of adverse events within 2-10 years after surgery was 36.21%. Kaplan-Meier analysis revealed that hot pot consumption, betel nut chewing, platelet-lymphocyte ratio, drug use, neutrophil-lymphocyte ratio, Radscore, and other factors impacted TSCC survival. Multivariate Cox regression analysis revealed that the clinical stage (P < 0.001), hot pot consumption (P < 0.001), Radscore 1 (P = 0.01), and Radscore 2 (P < 0.001) were independent factors affecting TSCC-OS. The same result was validated by the XGBoost algorithm. The nomogram based on the aforementioned factors exhibited good discrimination (C-index 0.86/0.81) and calibration (P > 0.05) in the training and test sets, accurately predicting the risk of adverse events and survival. CONCLUSION: The nomogram constructed using clinical data and MRI radiomics parameters may accurately predict TSCC-OS noninvasively, thereby assisting clinicians in promptly modifying treatment strategies to improve patient prognosis.

Obesity enhances the response to neoadjuvant anti-PD1 therapy in oral tongue squamous cell carcinoma.

OBJECTIVES: Previous studies have demonstrated that obesity may impact the efficacy of anti-PD1 therapy, but the underlying mechanism remains unclear. In this study, our objective was to determine the prognostic value of obesity in patients with oral tongue squamous cell carcinoma (OTSCC) treated with pembrolizumab and establish a subtype based on fatty acid metabolism-related genes (FAMRGs) for immunotherapy. MATERIALS AND METHODS: We enrolled a total of 56 patients with OTSCC who underwent neoadjuvant anti-PD1 therapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, and immunohistochemistry staining were performed. Additionally, we acquired the gene expression profiles of pan-cancer samples and conducted GSEA and KEGG pathway analysis. Moreover, data from TCGA, MSigDB, UALCAN, GEPIA and TIMER were utilized to construct the FAMRGs subtype. RESULTS: Our findings indicate that high Body Mass Index (BMI) was significantly associated with improved PFS (HR = 0.015; 95% CI, 0.001 to 0.477; p = 0.015), potentially attributed to increased infiltration of PD1 + T cells. A total of 91 differentially expressed FAMRGs were identified between the response and non-response groups in pan-cancer patients treated with immunotherapy. Of these, 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) were found to affect PD-1 expression and T cell infiltration in HNSCC, which may impact the efficacy of anti-PD1 therapy. CONCLUSION: This study demonstrates that obesity serves as a robust prognostic predictor for patients with OTSCC undergoing neoadjuvant anti-PD1 therapy. Furthermore, the expression of 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) plays a pivotal role in the context of anti-PD1 therapy and deserves further investigation.

Assessing survival outcomes of patients with oral tongue squamous cell carcinoma: Focus on age, sex, and stage.

BACKGROUND: The purpose of this study was to provide further insights into whether age and/or sex are associated with prognosis in oral tongue squamous cell carcinoma. METHODS: This was a retrospective cohort study utilizing hospital registry data from 2006 to 2016 obtained from the National Cancer Database. Identified patients were divided into various cohorts based on age, sex, and staging. A descriptive analysis was performed using chi-square tests and overall survival rates were estimated using Kaplan-Meier method. RESULTS: A total of 17 642 patients were included in the study. The 5-year overall survival rates were 82.0% (95% CI: 79.8%-84.0%) in younger patients versus 67.5% (95% CI: 66.7%-68.3%, p-value <0.0001) older patients. The median overall survival for females was 143.4 months (95% CI: 133.2-NA) versus 129.8 (95% CI: 125.4-138.7, p-value <0.0001) in males. CONCLUSIONS: Our analysis suggests that younger age and female sex are both predictors of improved survival in oral tongue squamous cell carcinoma.

Impact of Postoperative Radiotherapy on the Prognosis of Early-Stage (pT1-2N0M0) Oral Tongue Squamous Cell Carcinoma.

PURPOSE: To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS: This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS: Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, P = .003; disease-free survival (DFS), 88% versus 50%, P = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, P = .040; DFS, 87% versus 64%, P = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% v 58%; P = .022; DFS, 76% v 47%; P = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% v 64%; P = .006; 92% v 66%; P = .049) but did not significantly affect OS. CONCLUSION: Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.

Influence of Social Vulnerability in Treatment and Prognosis of Squamous Cell Carcinoma of the Tongue.

OBJECTIVE: To investigate the association of social determinants of health (SDoH) in squamous cell carcinoma of the tongue in the United States and to evaluate the real-world contribution of specific disparities. STUDY DESIGN: Retrospective cohort study. SETTING: United States. METHODS: The Centers for Disease Control and Prevention-Social Vulnerability Index (SVI) and National Cancer Institute-Surveillance, Epidemiology, and End Results Program database were used to study 62,103 adult tongue squamous cell carcinoma patients from 1975 to 2017. Regression analysis assessed trends in months of follow-up and survival across social vulnerability and 4 subcategories of social vulnerability. RESULTS: As overall SVI score increases (increased social vulnerability), there is a significant decrease in the average length of follow-up (22.95% decrease from 63.99 to 49.31 months; P < .001) across patients from the lowest and highest social vulnerability groups. As overall SVI score increases, there is a significant decrease in the average months of survival (28.00% decrease from 49.20 to 35.43 months; P < .001). There is also a significantly greater odds ratio (OR = 1.05; P < .001) of advanced cancer staging upon presentation at higher SVI scores. Patients with higher SVI scores have a lower OR (0.93; P < .001) of receiving surgery as their primary treatment when compared to patients with lower SVI scores. Patients with higher SVI scores also have a significantly greater OR (OR = 1.05; P < .001) of receiving chemotherapy as their primary treatment when compared to patients with lower SVI scores. CONCLUSION: Increased social vulnerability is shown to have a detrimental impact on the treatment and prognosis of patients with squamous cell carcinoma of the tongue.

Perineural invasion in incisional biopsy is an indication for in-continuity resection in oral squamous cell carcinoma of the tongue and floor of the mouth.

PURPOSE: The histologic finding of perineural invasion is a poor prognostic factor in oral squamous cell carcinoma patients. The aim of this study is to detect factors that influence prognosis in patients operated for oral cancer with perineural invasion in their histopathology report and to propose safer options of treatment with respect to recurrence and survival rates. PATIENTS AND METHODS: We performed a prospective cohort study of all oral squamous cell carcinoma cases operated in our department from January 2018 to January 2022. Overall, 75 cases of patients operated for oral squamous cell carcinoma were included in the study. Of these cases, 14 with perineural invasion were found. We created two groups: one group of patients treated with in-continuity resection and a second group of patients treated with a discontinuous resection between the primary site and the neck. Type of operation was considered the predictor variable and recurrence, survival or death, the outcome variables. RESULTS: Oral cancer patients with known perineural invasion treated with in-continuity resection had a much better overall and disease-specific survival than patients treated with a discontinuous manner (p < .001). The difference in recurrence rate between these two groups of patients was found to be very significant in our study (p < .0005). CONCLUSION: It is therefore our suggestion that in oral squamous cell carcinoma of the tongue and floor of the mouth with perineural invasion detected in the incisional biopsy, an extended in-continuity resection to include the affected nerves should be performed.

The modified Polsby-Popper score, a novel quantitative histomorphological biomarker and its potential to predict lymph node positivity and cancer-specific survival in oral tongue squamous cell carcinoma.

BACKGROUND: The significance of different histological spreading patterns of tumor tissue in oral tongue squamous cell carcinoma (TSCC) is well known. Our aim was to construct a numeric parameter on a continuous scale, that is, the modified Polsby-Popper (MPP) score, to describe the aggressiveness of tumor growth and infiltration, with the potential to analyze hematoxylin and eosin-stained whole slide images (WSIs) in an automated manner. We investigated the application of the MPP score in predicting survival and cervical lymph node metastases as well as in determining patients at risk in the context of different surgical margin scenarios. METHODS: We developed a semiautomated image analysis pipeline to detect areas belonging to the tumor tissue compartment. Perimeter and area measurements of all detected tissue regions were derived, and a specific mathematical formula was applied to reflect the perimeter/area ratio in a comparable, observer-independent manner across digitized WSIs. We demonstrated the plausibility of the MPP score by correlating it with well-established clinicopathologic parameters. We then performed survival analysis to assess the relevance of the MPP score, with an emphasis on different surgical margin scenarios. Machine learning models were developed to assess the relevance of the MPP score in predicting survival and occult cervical nodal metastases. RESULTS: The MPP score was associated with unfavorable tumor growth and infiltration patterns, the presence of lymph node metastases, the extracapsular spread of tumor cells, and higher tumor thickness. Higher MPP scores were associated with worse overall survival (OS) and tongue carcinoma-specific survival (TCSS), both when assessing all pT-categories and pT1-pT2 categories only; moreover, higher MPP scores were associated with a significantly worse TCSS in cases where a cancer-free surgical margin of <5 mm could be achieved on the main surgical specimen. This discriminatory capacity remained constant when examining pT1-pT2 categories only. Importantly, the MPP score could successfully define cases at risk in terms of metastatic disease in pT1-pT2 cancer where tumor thickness failed to exhibit a significant predictive value. Machine learning (ML) models incorporating the MPP score could predict the 5-year TCSS efficiently. Furthermore, we demonstrated that machine learning models that predict occult cervical lymph node involvement can benefit from including the MPP score. CONCLUSIONS: We introduced an objective, quantifiable, and observer-independent parameter, the MPP score, representing the aggressiveness of tumor growth and infiltration in TSCC. We showed its prognostic relevance especially in pT1-pT2 category TSCC, and its possible use in ML models predicting TCSS and occult lymph node metastases.

Advanced-stage tongue squamous cell carcinoma: a machine learning model for risk stratification and treatment planning.

BACKGROUND: A significant number of tongue squamous cell carcinoma (TSCC) patients are diagnosed at late stage. OBJECTIVES: We primarily aimed to develop a machine learning (ML) model based on ensemble ML paradigm to stratify advanced-stage TSCC patients into the likelihood of overall survival (OS) for evidence-based treatment. We compared the survival outcome of patients who received either surgical treatment only (Sx) or surgery combined with postoperative radiotherapy (Sx + RT) or postoperative chemoradiotherapy (Sx + CRT). MATERIAL AND METHODS: A total of 428 patients from Surveillance, Epidemiology, and End Results (SEER) database were reviewed. Kaplan-Meier and Cox proportional hazards models examine OS. In addition, a ML model was developed for OS likelihood stratification. RESULTS: Age, marital status, N stage, Sx, and Sx + CRT were considered significant. Patients with Sx + RT showed better OS than Sx + CRT or Sx alone. A similar result was obtained for T3N0 subgroup. For T3N1 subgroup, Sx + CRT appeared more favorable for 5-year OS. In T3N2 and T3N3 subgroups, the numbers of patients were small to make insightful conclusions. The OS predictive ML model showed an accuracy of 86.3% for OS likelihood prediction. CONCLUSIONS AND SIGNIFICANCE: Patients stratified as having high likelihood of OS may be managed with Sx + RT. Further external validation studies are needed to confirm these results.

Population-based comparative survival analysis of surgery with or without adjuvant radiotherapy and non-operative primary radiotherapy in patients with early-stage oral tongue squamous cell carcinoma.

PURPOSE: Although recent clinical guidelines do allow primary radiotherapy for selected patients with early-stage oral tongue cancer, there has been little knowledge on the treatment outcomes of non-operative radiotherapy using modern treatment techniques. This study evaluated recent prognostic differences between primary radiotherapy and surgical resection in T1‒2N0 oral tongue squamous cell carcinoma. METHODS: Patients diagnosed with T1‒2N0 oral tongue squamous cell carcinoma were identified from the Surveillance, Epidemiology, and End Results database. After propensity score matching, the disease-specific survival of primary radiotherapy and surgery was compared. RESULTS: From a total of 8,458 patients initially identified, we defined matched cohorts: cohort A, comparing surgery alone vs. primary radiotherapy (n = 230 vs. 230), and cohort B, comparing surgery plus adjuvant radiotherapy vs. primary radiotherapy (n = 230 vs. 230). The 7-year disease-specific survival rates were 77% vs. 35% (cohort A) and 65% vs. 35% (cohort B) (P < 0.001 for all comparisons). Primary radiotherapy was independently associated with worse disease-specific survival in both cohorts A (hazard ratio 4.06; 95% confidence interval 2.53‒6.52) and B (hazard ratio 2.81; 95% confidence interval 1.96‒4.04). Time-course hazard rate function plots showed a distinct short-term risk increment in disease-specific mortality in the primary radiotherapy group. CONCLUSION: In the contemporary treatment era, the use of radiotherapy as a definitive treatment resulted in an inferior prognosis in patients with T1‒2N0 oral tongue squamous cell carcinoma. The present population-based data suggest that primary radiotherapy cannot be used as an alternative to surgical management and it needs to be avoided as much as possible in early-stage tumors.

Prognostic impact of lingual lymph node metastasis in patients with squamous cell carcinoma of the tongue: a retrospective study.

Squamous cell carcinoma (SCC) of the tongue rarely metastasizes to the lingual lymph nodes (LLNs), which are inconstant nodes and often situated outside the areas of basic tongue tumor surgery. The current study evaluated the clinicopathological features and prognostic impact of LLN metastasis (LLNM), compared to that of cervical lymph node metastasis, in patients with tongue SCC. A total of 608 patients underwent radical surgery for tongue SCC at our department between January 2001 and December 2016. During neck dissection, we scrutinized and resected lateral LLNs, when present. Of the 128 patients with lymph node metastasis, 107 had cervical lymph node metastasis and 21 had both cervical lymph node metastasis and LLNM. Univariate analysis demonstrated that LLNM was significantly associated with the adverse features of cervical lymph node metastasis. The 5-year disease-specific survival (5y-DSS) was significantly lower in patients with LLNMs than in those without LLNMs (49.0% vs. 88.4%, P < 0.01). Moreover, Cox proportional hazards model analyses revealed that cervical lymph node metastasis at level IV or V and LLNM were independent prognostic factors for 5y-DSS. LLNM has a strong negative impact on survival in patients with tongue SCC. An advanced status of cervical lymph node metastasis may predict LLNM.