Search

Objectives: This study investigates the relationship between the total volume of oral tongue cancer pre-operatively and the RFFF volume post-operatively. Materials and methods: A total of 52 DICOM imaging datasets (CT or MRI) of 26 patients were included in this study. The volume of the desired structure was quantified using semi-automatic segmentation using the software ITK-SNAP. All extracted measurements were validated by two further clinicians at separate instances. Results: The variation of MeanVolTu can be predicted by MeanVolFlap moderately reliable with 59.1% confidence (R-Qua: 0.591). ANOVA Testing to represent how well the regression line fits the data, resulted in the overall regression model being statistically significant in predicting the MeanVolTu (p < 0.001). The flap volume may be predicted using the following algorithm: MeanVolFlap0 = 3241,633 + 1, 322 * MeanVolTu. Conclusion: The results of this study show positive correlation between tumor volume and flap volume, highlighting the significance of efficient flap planning with increasing tumor volume. A larger extraction volume of the radial forearm free flap from the donor site compromises the forearm more, thus increasing the probability of post-operative complications. Clinical relevance: Radial forearm free flap design in accordance with its corresponding 3D tumor volume. [ABSTRACT FROM AUTHOR]

Simple Summary: This study presents the experience of a single center in sentinel lymph node biopsy (SLNB) as an alternative to elective neck dissection (END) in T1/T2 cN0 oral tongue squamous-cell carcinoma (OTSCC) patients. A 20-year retrospective analysis was conducted at the Ear Nose Throat (ENT) and Maxillofacial Surgery department of the Istituto Nazionale Tumori in Naples. Between January 2002 to January 2022, 122 patients were eligible and were enrolled. Out of 122 patients, 24.6% showed positivity in SLN biopsy, with a 21.9% positivity ratio for resected nodes. Preoperative radioactive tracer injection and lymphoscintigraphy facilitated sentinel lymph node identification. This study suggests SLNB as a reliable staging tool, enabling early micrometastasis detection in clinically negative necks in patients affected by OTSCC. Oral tongue squamous-cell carcinoma (OTSCC) is the most prevalent malignancy in the head and neck region. Lymphatic spread, particularly to cervical lymph nodes, significantly impacts 5-year survival rates, emphasizing the criticality of precise staging. Metastatic cervical lymph nodes can decrease survival rates by 50%. Yet, elective neck dissection (END) in T1–2 cN0 patients proves to be an overtreatment in around 80% of cases. To address this, sentinel lymph node biopsy (SLNB) was introduced, aiming to minimize postoperative morbidity. This study, conducted at the ENT and Maxillofacial Surgery department of the Istituto Nazionale Tumori in Naples, explores SLNB's efficacy in early-stage oral tongue squamous-cell carcinoma (OTSCC). From January 2020 to January 2022, 122 T1/T2 cN0 HNSCC patients were enrolled. Radioactive tracers and lymphoscintigraphy identified sentinel lymph nodes, aided by a gamma probe during surgery. Results revealed 24.6% SLN biopsy positivity, with 169 SLNs resected and a 21.9% positivity ratio. The study suggests SLNB's reliability for T1-2 cN0 OTSCC patient staging and early micrometastasis detection. [ABSTRACT FROM AUTHOR]

ObjectiveThe local spread of oral tongue squamous cell carcinoma (OTSCC) follows pathways of dissemination along areas of lesser resistance. In more advanced scenarios, the tumor can extend beyond the hemi-tongue of origin, by passing through the lingual septum and following the fibers of the transverse muscle. This can lead to the invasion of the contralateral extrinsic muscles, the first being the genioglossus and more laterally the hyoglossus. An anatomically guided surgical resection of the tumor can be planned to ensure both oncological safety and an acceptable functional outcome. This approach aims to preserve the hyo-styloglossus unit (HSU) whenever feasible.MethodsBetween January 2019 and November 2022, six patients received extended glossectomy Type B (EG Type B), with preservation of the HSU. Preliminary oncological results and functional results in terms of swallowing (FOIS score) and quality of life (MDADI) are presented.ResultsFive out of the six patients are alive and disease-free, while one patient died due to other causes. All patients who were candidates for an EG Type B underwent a swallowing assessment prior to surgery and followed daily postoperative swallowing training. At discharge, the patients continued swallowing training in an outpatient clinic. Five out of the six patients reached a full oral diet within 1 year of follow-up.ConclusionThe oncological results confirm the safety of this technique. The importance of preserving the HSU, the minimal functional unit, shows very encouraging results in terms of swallowing rehabilitation.

Simple Summary: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive tumor phenotype in head and neck cancer (HNC) and an important adverse prognostic factor for recurrence, metastasis, and patient survival. According to the previous studies, the LNM characteristics of HNC (i.e., the growth and spread of LNM) well correlate with the ECS occurrence, but there has been a disagreement about the primary tumor characteristics and ECS. Thus, we investigated the risk factors of ECS across different HNC subsites comparatively. In this study, we confirmed that LNM variables were significant risk factors for ECS in all subsites of HNC. Interestingly, in oral tongue cancer, tumor dimensional variables were significantly related to ECS; however, in oro- and hypopharyngeal cancer, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. Site-dependent primary tumor characteristics or nodal status might contribute differentially to the ECS development of LNM in HNC. Background: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive primary tumor phenotype in head and neck cancer (HNC); however, the factors influencing ECS are poorly understood. Patients and Methods: This was a retrospective study, including 190 cases of oral tongue cancer (OTC), 148 cases of oropharyngeal cancer (OPC) (118 HPV-positive and 30 HPV-negative), and 100 cases of hypopharyngeal cancer (HPC). Tumor dimension, tumor biological variables (lymphovascular/perineural invasion and histologic grade), and LNM variables (LNM number and size) were analyzed according to the presence of ECS using multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. Results: LNM variables were significant factors for ECS in all subsites of HNC (p < 0.05), except HPV-positive OPC. In OTC, tumor dimensional variables were significantly related to ECS (p < 0.01). Meanwhile, in OPC and HPC, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. The predictability of ECS by ROC curve using multiple variables was 0.819 [95% confidence interval: 0.759–0.878] in OTC, 0.687 [0.559–0.815] in HPV-positive OPC, 0.823 [0.642–1.000] in HPV-negative OPC, and 0.907 [0.841–0.973] in HPC. Conclusion: LNM variables were correlated with ECS occurrence for most HNC subsites, and site-dependent primary tumor characteristics might contribute differentially to the ECS development of LNM in HNC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the oncologic outcomes among negative, close, positive, and dysplasia resection margins (RMs) with oral tongue squamous cell carcinoma (OSCC) and to investigate the impact of dysplastic RMs. Methods: The 565 patients were retrospectively analyzed and divided into four groups according to RM. Dysplasia was classified into mild, moderate, and severe subgroups. Results: RMs consisted of negative (62.1%), close (27.1%), positive (2.1%), and dysplastic (8.7%). In multivariate analysis, advanced T/N stages and positive RM were significant risk factors for overall survival, while dysplasia at the RM was not a significant risk factor for locoregional recurrence or overall survival. In subgroup analysis of patients with dysplastic margin, RM with severe dysplasia showed higher recurrence than mild and moderate dysplasia. Conclusions: Dysplastic RM was not a risk factor for recurrence and survival. Severe dysplasia RM should be carefully observed due to higher recurrence compared to other dysplasia RMs. [ABSTRACT FROM AUTHOR]

Background: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). Methods: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. Results: In the CTS group, survival and prognosis were significantly associated with positive lymph‐nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T‐N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause‐Specific Survival (CSS) of 3.24 (95% CI: 1.71–6.11; p < 0.001); HR Loco‐Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47–4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01–0.77; p = 0.03). Conclusion: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC. [ABSTRACT FROM AUTHOR]

Objective: To understand the accuracy of pre‐ and intraoperative estimation of tumor depth of invasion (DOI). Study Design: A retrospective case‐control study. Setting: Patients who presented at 1 institution with oral tongue squamous cell carcinoma that underwent oncologic resection between 2017 and 2019 were identified. Methods: Patients that met the inclusion criteria were included. Patients with nodal, distant, or recurrent disease, prior history of head and neck cancer, or preoperative tumor assessment and/or final histopathology that did not include DOI were excluded. Preoperative DOI estimation and technique and pathology reports were obtained. Our primary outcome was the sensitivity and specificity of DOI estimation modalities including full‐thickness biopsy (FTB), manual palpation (MP), punch biopsy (PB), and intraoperative ultrasound (IOUS). Results: Tumor DOI was assessed quantitatively preoperatively in 40 patients by FTB (n = 19, 48%), MP (n = 17, 42%), or PB (n = 4, 10%). Additionally, 19 patients underwent IOUS to assess DOI. The sensitivities of FTB, MP, and IOUS for DOI ≥ 4 mm were 83% (confidence interval [CI]: 44%‐97%), 83% (CI: 55%‐95%), and 90% (CI: 60%‐98%), respectively, and the specificities were 85% (CI: 58%‐96%), 60% (CI: 23%‐88%), and 78% (CI: 45%‐94%). Conclusion: Our study demonstrated that DOI assessment tools measured had similar sensitivity and specificity in stratifying patients with DOI ≥4 mm, with no statistically superior diagnostic test. Our results support the need for additional research into nodal disease prediction and continued refinement of ND decisions with respect to DOI. [ABSTRACT FROM AUTHOR]

Intraoperative ultrasound (IOUS) is a potentially useful adjunct to the resection of oral tongue cancers (OTC). IOUS images of the tumor‐normal tissue interface show different patterns of invasion. In this retrospective series of 29 patients treated for OTC, we evaluated if there was a correlation between IOUS findings of patterns of invasion and final histology and assessed if there was any associated risk of increased incidence of positive or close margins with different patterns of invasion as seen on ultrasound. Although we found no significant correlation between ultrasound patterns of invasion and histological evaluation, we did find that an infiltrative pattern of invasion on IOUS did result in a significant risk of a close margin. Further exploration of these findings in a larger prospective study could provide definitive information on the efficacy of this modality in OTC resections. [ABSTRACT FROM AUTHOR]

Abstract Background The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC). Methods A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area. Results The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan–Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09–3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11–2.48; P = 0.014). Conclusion Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.

Objective(s): There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature. Methods: A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage. Results: Eighty‐two patients (38 young, 44 old) were included in this study. Median follow‐up was 29.4 months. When compared to the older cohort (age >45), the younger cohort (age ≤45) demonstrated lower rates of 5‐year locoregional control (LC) (79.6% vs. 52.5%, p = 0.043) and distant metastasis‐free survival (88.1% vs. 61.8%, p = 0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease‐specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n = 7), 100% demonstrated in‐field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p = 0.004) and the advanced stage was a predictor of DSS (p = 0.03). Conclusions: Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in‐field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort. Level of Evidence: 3 Laryngoscope, 133:1110–1121, 2023 [ABSTRACT FROM AUTHOR]

Abstract The purpose of this study is to evaluate the risk of developing a second primary malignancy (SPM) in oral tongue cancer (OTC) patients, and identify the characteristics and survival outcomes of OTC patients with an SPM. Patients with first primary OTC were identified from the Surveillance, Epidemiology, and End Result (SEER) database, and were further divided into the only one primary malignancy (OOPM) group and SPM group. Baseline characteristics and survival outcomes between patients in two groups were compared. Furthermore, a Fine and Gray subdistribution hazard model was utilized to investigate the cumulative risk of developing an SPM in OTC patients. Then, a multivariate competing‐risk model was performed to explore risk predictors. Patients in the SPM group had older age and lower tumor stage than those in the OOPM group. Moreover, the proportion of receiving surgery in the SPM group was significantly higher than that in the OOPM group. Lung was the most common site of SPMs in whole patients. In male patients, the second common site of SPMs was prostate, while in female patients, it was female breast. OTC patients with an SPM of lung and bronchus had the worst overall survival. Finally, older age, male sex, primary site of ventral surface and anterior 2/3 of tongue, localized diseases, and the administration of surgery were considered as risk predictors of developing an SPM in OTC patients. OTC survivors had high risk of developing an SPM, and subsequent malignancy was an important COD. Careful monitoring is warranted in OTC survivors due to the high SPM‐specific mortality.

Background: The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC).Methods: A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area.Results: The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan-Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09-3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11-2.48; P = 0.014).Conclusion: Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system. [ABSTRACT FROM AUTHOR]

Inverse planning simulated annealing (IPSA) produces highly conformal dose distributions and quick optimizations for high-dose-rate interstitial brachytherapy (HDRBT). We report our dosimetry and overall outcomes using this approach for the accelerated post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue (OTSCC) with high risk of local recurrence. Patients with newly diagnosed pN0 OTSCC treated with partial glossectomy, neck dissection, and post-operative HDRBT alone from 2007 to 2021 were retrospectively reviewed. Patients received 30 Gy in 5 fractions over 2.5 days. Target volume and mandible dosimetry are reported. Actuarial rates of local control, regional control, disease-specific survival, and overall survival were estimated using the Kaplan-Meier method. Toxicity was categorized using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 19 consecutive patients were reviewed. Median follow-up was 3.2 years (IQR 1.4–8.2 years) with a 3-year estimated local control rate of 81%. Target volumes were generally small, as the median volume was 12.66 cc. Median V150% and V200% were 52% and 24%, respectively. D1cc and D2cc to the mandible were 17.31 Gy and 14.42 Gy, respectively. IPSA-HDRBT is feasible and highly efficient for post-operative treatment of the primary tumor bed in patients with pathologically node-negative squamous cell carcinomas of the oral tongue. Further technical optimization and prospective clinical evaluation in a larger patient cohort are planned. [ABSTRACT FROM AUTHOR]

Background. Jumonji domain-containing-3 (JMJD3) is reported to be a histone H3 lysine 27 (H3K27) demethylase and a tumor suppressor gene. The present study designed to investigate the crucial role of JMJD3 in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection. Methods. We enrolled a total of 156 OTSCC patients receiving surgical resection, including 73 patients (47%) with high expression of JMJD3 and 83 patients (53%) harboring low expression of JMJD3. Two OTSCC cell lines, SAS and Cal 27, were used to explore the modulation of cancer. GSK-J4, a potent inhibitor of JMJD3, was used to treat the two OTSCC cell lines. The Chi-square test was performed to examine between-group differences in categorical variables; the Kaplan≥Meier method was used to investigate survival outcome in univariate analysis, and the Cox regression model was used for multivariate analysis. Results. The median follow-up period was 59.2 months and he five-year disease-free survival (DFS) and overall survival (OS) rates were 46.2% and 50.0%, respectively. Better five-year DFS (59% versus 35%) and five-year OS (63% versus 39%) were mentioned in patients with high expression of JMJD3 compared to those with low expression of JMJD3. High expression of JMJD3 was significantly associated with superior DFS and OS in the univariate and multivariate analyses. Following successful inhibition of JMJD3 by GSK-J4, western blotting analysis showed the decreased expression of Rb and p21. Conclusion. Our study showed that high expression of JMJD3 is a good prognostic factor in OTSCC patients who underwent surgical resection. [ABSTRACT FROM AUTHOR]

Although there are many histopathologic prognosticators, grading of early oral tongue squamous cell carcinoma (OTSCC) is still based on morphological cell differentiation which has low prognostic value. Here we summarize the emerging histopathological markers showing powerful prognostic value, but are not included in pathology reports. Using PubMed, Scopus, Ovid Medline, and Web of Science databases, a systematic literature search was preformed to identify early OTSCC studies that investigated the prognostic significance of hematoxylin–eosin‐based histopathologic markers. Our meta‐analysis showed that tumor budding was associated with overall survival (hazard ratio [HR] 2.32; 95% CI 1.40–3.84; p < 0.01) and disease‐specific survival (DSS) (1.89; 95% CI 1.13–3.15; p = 0.02). Worst pattern of invasion was associated with disease‐free survival (DFS) (1.95; 95% CI 1.04–3.64; p = 0.04). Tumor–stroma ratio was also associated with DFS (1.75, 95% CI 1.24–2.48; p < 0.01) and DSS (1.69; 95% CI 1.19–2.42; p < 0.01). Tumor budding, worst pattern of invasion, and tumor–stroma ratio have a promising prognostic value in early OTSCC. The evaluation and reporting of these markers is cost‐effective and can be incorporated in daily practice. [ABSTRACT FROM AUTHOR]

While head and neck cancer incidence decreased worldwide due to reduced tobacco and alcohol consumption, oral tongue cancer (OTC) incidence has been reported to be increasing in several countries. Our study examines the incidence trends of OTC in France from 1990 to 2018, globally and by age; and compares the incidence trends with the evolution of the incidence of other human papilloma virus‐unrelated head and neck squamous cell carcinoma, that is, cancers of the remaining subsites of the oral cavity (RSOCC) and laryngeal cancers for the period 1990 to 2018. World age‐standardized incidence rates of oral tongue cancers (C02), cancers of the remaining subsites of the oral cavity (RSOCC, C03‐06) and laryngeal cancers (C32) were estimated using the French National Network of Cancer Registries for the period 1990 to 2018. Trends in national incidence rates were estimated from a mixed‐effect Poisson model including age and year effects using penalized splines and a district‐random effect. In women aged 30 and 40, a significant increase in OTC incidence was observed, while ROSCC showed a nonsignificant incidence decrease. In young men aged 25, a marginally significant increase of OTC incidence years was observed, while incidence rates of RSOCC significantly declined. The results suggest a tendency towards diverging incidence trends for OTC compared to RSOCC and laryngeal cancer in young adults. The observed trends may reflect changes in underlying exposures or emerging exposures not yet identified, and stress the need to further investigate the etiology of oral tongue cancers. [ABSTRACT FROM AUTHOR]

Background: TATE has been proposed as a prognostic factor in oral cancer staging; however, the controversial literature data limit its application in the routine diagnosis. The aim of this study was to evaluate the prognostic value of TATE in patients with oral tongue cancer. The second aim was to identify any difference in the methods of eosinophil quantification or in the cutoff values reported in literature. Methods: Clinic‐pathological data of 204 patients treated at "Ospedali Riuniti" Hospital, Ancona, Italy, were collected. Evaluation of TATE was performed on hematoxylin‐and‐eosin‐stained slides and correlation with survival outcomes was evaluated. The number of eosinophils per square millimeter was evaluated by using two methods, namely density (TATE‐1) and classical (TATE‐2) methods. For each of the 2 methods tested, patients were stratified into two or three groups, according to the most used cutoff values reported in literature. Results: Regardless of the method of eosinophil quantification or the cutoff values used, patients with high TATE had a significantly better disease‐specific survival. The density method (TATE‐1) showed a better predictive performance, in particular when applying a single cutoff of 67 eosinophils/mm2, two cutoffs of 10 and 100 eosinophils/mm2, or two cutoffs of 50 and 120 eosinophils/mm2. Conclusion: The evaluation of TATE is simple, cost‐effective, and easy to implement in daily practice with the aim of improving risk stratification of patients affected by oral tongue cancer. Results of prognostic performance analysis suggest using density (TATE‐1) method as the standard approach to evaluate TATE in future studies, enhancing replicability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stemness factors associated with tumorigenesis in different types of cancers have not been specifically studied in oral tongue SCC (OTSSC). Here, we aimed to quantify expression levels and distribution of KLF4 and SOX2, two relevant stemness factors, in oral SCC including OTSCC samples from different subsites. METHODS AND RESULTS: We determined KLF4 and SOX2 expression levels by immunostaining 35 biopsies of OSCC. Stained wholeslide images were digitized and subjected to automatic cell detection and unbiased quantification using Qupath software. We found statistically significant reduction in KLF4 positive cells density (p = 0.024), and fraction (p = 0.022) in OTSCC from tongue borders compared with other tongue subsites. Instead, quantitative SOX2 analysis did not show differences in expression levels between OTSCC from the borders versus OTSCC developed in others subsites. Notably SOX2 expression was revealed increased in moderately and poorly differentiated OSCC compared with well differentiated ones (positive cells density p = 0.025, fraction p = 0.006). No significant correlation between KLF4 and SOX2 expression was observed, neither in OSCC nor in OTSCC. CONCLUSIONS: KLF4 and SOX2 exhibit opposite expression profiles regarding subsite localization and differentiation level in OSCC. Our study prompts future OTSCC prospective studies looking for clinical prognosis to incorporate detailed subsite information in the analysis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the prognostic value of preoperative radiological findings for nodal recurrence in clinically node-negative (cN0) patients with oral tongue squamous cell carcinoma (SCC). Methods: The study population consisted of 52 patients with cT1-2N0 oral tongue SCC classified according to the 7th edition of the Union for International Cancer Control (UICC) staging system. The subjects had undergone preoperative radiological examinations, including magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography. All patients were treated with local resection and watchful waiting for neck management. Using an unpaired t test, Pearson's chi-squared test, and the Kaplan–Meier method, the MRI-derived depth of invasion (DOI), the standardized uptake value (SUV) on FDG-PET, and the T stage according to the 7th and 8th UICC were assessed as prognostic factors. Results: The MRI-derived DOI was recorded as ≤ 5 mm in 24 patients and > 5 mm in 28 patients. During the follow-up period, nine patients exhibited nodal recurrence, with the MRI-derived DOI being significantly higher in patients with positive than in those with negative (p = 0.011). The SUV was not significant. Five-year cumulative nodal recurrence probabilities were 4.5% for patients with an MRI-derived DOI ≤ 5 mm, while it was 32.1% for > 5 mm (p = 0.013). Although the T classifications were not significant, none of our patients whose T stage according to the 8th UICC was T1 suffered nodal recurrence. Conclusions: MRI-derived DOI can predict nodal recurrence, while preoperative information may assist in treatment planning for oral tongue SCC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate correlation of single photon emission computed tomography-computed tomography (SPECT-CT) data on lymph flow (LF) from oral tongue cancer (OC) and the topography of lymph nodes (LN) metastases; to determine the clinical value of lymph flow guided radiotherapy (LFGRT). Materials and Methods: SPECT-CT visualization of LF from the OC lesions was performed after peritumoral injection of 99mTc-phytate in 26 primary patients with clinical stage cT1-2N0M0 disease. We determined the individual drainage (unilateral/bilateral) from the tumor, and localization of sentinel LNs according to the neck levels. Metastases in LNs were verified with histology and a 2-year follow-up. Results: SPECT-CT detected bilateral LF in 10 (38.5%) of 26 patients; in 16 (61.5%) cases the drainage was unilateral. Histology revealed LNs metastases in three cases; regional recurrences were diagnosed in other four patients. In all seven observations metastases were located at the same site and level as the sentinel LNs. In eight (30.8%) of 26 patients sentinel LNs were visualized unilaterally at levels Ib-IIa; in five cases, unilaterally at levels I-IIa-III. In these patients, LFGRT demonstrated 59%-70% reduction of irradiated volume, and 26%-42% and 51%-70% decrease of the mean dose to the spinal cord and the contralateral parotid gland. In patients with a bilateral drainage the reduction of doses absorbed by the spinal cord and contralateral parotid gland was 19% and 6%, respectively. Conclusion: Localization of sentinel LNs determined by SPECT-CT corresponds to the localization of metastatic LNs in terms of side and levels. [ABSTRACT FROM AUTHOR]

The objective is to present a clinical case of combined treatment of cancer of the tongue and its progression to the contralateral lymph nodes of the neck using data on individual lymphatic outflow from the primary tumor of the tongue.Clinical case. Clinical, laboratory, radiological and pathomorphological data of a 50-year-old patient with a diagnosis of squamous human papillomavirus-negative cancer of the free part of the tongue and clinically negative lymph nodes of the neck with cT2N0M0. The patient underwent radical surgical treatment in the amount of hemiglossectomy and ipsilateral selective cervical lymphadenectomy after two courses of polychemotherapy according to the cisplatin + 5-fluorocracil regimen with partial regression and adjuvant treatment in the amount of conformal remote radiation therapy combined with chemotherapy. 9 months after the end of treatment, progression to the lymph nodes of the neck of the contralateral side was revealed, which accumulated a radiopharmaceutical before treatment.Conclusion. The described clinical case shows the importance of studying the lymphatic outflow from the primary tumor of the tongue to the regional lymph nodes in order to plan surgical treatment on the regional lymphatic collector in patients with squamous cell carcinoma of the free part of the tongue.

To date, April 19, 2021, the coronavirus disease 2019 (COVID-19) caused about 140,886,773 confirmed cases and more than 3,000,000 deaths worldwide since the beginning of the pandemic. Oncology patients are usually frail due to the fear of prognosis, recurrence, and outcomes of treatments. Thus, coping with cancer is a complicated process that is necessary to overcome oncological challenge, even more in case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease. This is a brief case report on a middle-aged man affected by advanced oral tongue cancer and COVID-19, describing his experience of cancer diagnosis, surgical treatment, and rehabilitation during the hospital quarantine for COVID-19. Besides the traumatic experience due to the functional alteration in breathing, eating, and speaking caused by major surgery and the concurrent facial disfigurement, our patient had to face a COVID-19 diagnosis, which implied hospital and social isolation. The aim of this perspective work is to focus on the role of the psychological support in the management of hospital distress related to COVID-19 psychophysical loneliness or alienation. In our experience, such support should anticipate patients' oncological surgery or treatment and should be implemented through telemedicine in case of isolation or after hospital discharge.

Objectives: To analyze the factors predicting survival outcomes in treatment naïve oral tongue squamous cell carcinoma (OTSCC). Materials and methods: A comprehensive review of 531 oral tongue carcinoma patients treated with upfront surgery followed by adjuvant radiotherapy or chemoradiotherapy was conducted from 2004–2018. Results: The mean age of presentation was 53 years (11–86) with a male to female ratio of 1.3:1. The associated risk factors were smoking (21%), betel nut (16%), naswar (9%) and alcohol (1%). Most of the cases were either well (45.1%) or moderately (46.2%) differentiated. Surgery was performed in 164 patients alone while 368 were treated with surgery in combination with adjuvant modalities. Overall (OS) and disease free survival (DFS) were 66 and 71%, respectively, with a median follow up of 2.5 years. Cox regression analysis showed nodal positivity, increased depth of invasion (DOI) and higher lymph node ratio (LNR) as significant prognosticators impacting OS and DSS. Conclusion: Nodal volume, DOI and LNR are the most consistent predictors of poor outcome in OTSCC. Nodal positivity, depth of invasion > 5 mm and lymph node ratio > 0.04 adversely affect OS and DSS. [ABSTRACT FROM AUTHOR]

Purpose: Consistent prognosticators are needed to guide adjuvant treatment in tongue squamous cell carcinoma (SCC). We validate the prognostic significance of histopathologic parameters in surgically treated tongue SCC. Methods: Archival specimens of 88 consecutive patients who were treated surgically for tongue SCC from 2003 to 2016 were re-analyzed by one pathologist. Patient records were retrospectively reviewed. Prognosticators of recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were identified using multivariate analysis. Results: Tumor depth of invasion (DOI) > 6 mm (OR 4.76; 95%CI 1.22–18.5; p = 0.024) and lymphovascular invasion (OR 5.61; 95%CI 1.00–31.5; p = 0.05) were independent predictors of nodal metastases. The overall 5-year RFS, OS and DSS were 70%, 82% and 84% respectively. Positive margins predicted poor RFS (HR 3.91; 95%CI 1.58–9.65; p = 0.003) and local recurrence-free survival (HR 4.96; 95%CI 1.36–18; p = 0.015). Presence of nodal metastases (HR 5.03; 95%CI 1.73–14.6; p = 0.003), tumor DOI > 6 mm (HR 9.91; 95%CI 1.26–78.0; p = 0.029) and positive margins (HR 8.26; 95%CI 2.75–24.8; p < 0.001) were independent predictors of poor OS. Presence of nodal metastases (HR 3.87; 95%CI 1.17–12.8; p = 0.027) and positive margins (HR 12.3; 95%CI 3.54–42.9; p < 0.001) also independently predicted poor DSS. Conclusion: Margins' status was the only independent predictor of local recurrence. Tumor DOI, nodal and margin status were key prognosticators of survival and may determine the necessity for adjuvant therapy. [ABSTRACT FROM AUTHOR]

Methods: A 42-year-old woman presented to our clinic with tongue pain and dysarthria. She had a smoking history of 22 pack-years and no history of alcohol consumption. A deep ulcer at the left side of the tongue and induration across the whole tongue were observed. The bilateral cervical lymph nodes were palpable. A biopsy from the ulcer revealed squamous cell carcinoma. PET/CT showed sternal bone metastasis resulting in the final diagnosis of left-sided oral tongue cancer (cT4aN2cM1). Systemic chemotherapy treatment involving 6 courses of the EXTREME regimen followed by weekly cetuximab administration was indicated. Results: After the first two courses, diminished tongue pain and improved dysarthria were observed; complete response was obtained after 6 courses. Re-examination of the biopsy specimen showed that the tumor was p16 positive. The p16 protein is a surrogate marker for HPV, but in this case HPV in-situ hybridization was negative. Locoregional or distant failure were not observed during the 5-year follow-up period. Conclusions: The treatment regimen unexpectedly proved successful. It may be beneficial to examine p16 expression in oral tongue cancer to identify patients that are more likely to benefit from the EXTREME treatment regimen. [ABSTRACT FROM AUTHOR]

To date, April 19, 2021, the coronavirus disease 2019 (COVID-19) caused about 140,886,773 confirmed cases and more than 3,000,000 deaths worldwide since the beginning of the pandemic. Oncology patients are usually frail due to the fear of prognosis, recurrence, and outcomes of treatments. Thus, coping with cancer is a complicated process that is necessary to overcome oncological challenge, even more in case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease. This is a brief case report on a middle-aged man affected by advanced oral tongue cancer and COVID-19, describing his experience of cancer diagnosis, surgical treatment, and rehabilitation during the hospital quarantine for COVID-19. Besides the traumatic experience due to the functional alteration in breathing, eating, and speaking caused by major surgery and the concurrent facial disfigurement, our patient had to face a COVID-19 diagnosis, which implied hospital and social isolation. The aim of this perspective work is to focus on the role of the psychological support in the management of hospital distress related to COVID-19 psychophysical loneliness or alienation. In our experience, such support should anticipate patients' oncological surgery or treatment and should be implemented through telemedicine in case of isolation or after hospital discharge. [ABSTRACT FROM AUTHOR]

AIM OF THE STUDY For tumours of the oral tongue, the most recent 8th edition of the AJCC/UICC staging system has introduced depth of infiltration (DOI) as a novel parameter. With this study we wanted to investigate its impact regarding this risk stratification compared with the preceding 7th edition. METHODS Between 2008 and 2017, 161 patients of two tertiary referral centres in Switzerland (Kantonsspital St. Gallen and University Hospital Zurich) with T1 N0 or T2 N0 tongue cancers were enrolled in this study. The primary tumours were restaged according to the 8th edition of the TNM classification. Kaplan-Meier curves for overall and disease-specific survival were calculated. RESULTS According to the 7th edition, of the 161 patients, 102 were staged after surgery as pT1 (stage I) and 59 as pT2 (stage II). According to the 8th edition, 36 patients (22.4%) were re-staged to a higher stage. Of these 36 patients, 8 (22.2%) experienced a recurrence, and 9 (25%) died. In the remaining, not re-staged group, 20 patients (16.0%) experienced a recurrence (p = 0.55) and 14 (11.2%) died (p = 0.025*). The 7th edition showed a statistically significant difference between pT1 and pT2 tumours for overall survival (p = 0.025), but not for disease-specific survival (p = 0.091), whereas the 8th edition was able to well discriminate between pT1, pT2 and pT3 for both overall (pT1 vs pT2, p = 0.016*; pT2 vs pT3, p = 0.031*) and disease-specific survival (pT1 vs pT2, p = 0.037*; pT2 vs pT3, p = 0.023*). CONCLUSION The recent TNM 8th edition provides a more accurate prediction of overall and disease-specific survival for this subgroup of patients. Hence, a more aggressive treatment should be considered for patients re-staged to pT3 due to depth of infiltration.

A role for incisional biopsy in preoperative prognostication is increasingly being advocated in oral tongue squamous cell carcinomas (OTSCC). Biopsies at two locations were compared, and prognostic factors in biopsies and their corresponding resections were evaluated. A total of 138 OTSCC biopsy slides from Finland and Saudi Arabia were compared for size (horizontal and vertical) and invasive front. The Finnish cases were assessed for tumor stroma ratio (TSR) and tumor‐infiltrating lymphocytes (TILs) using light microscopy and digital image analysis assessment and compared. Furthermore, TSR, TILs, and previously analyzed budding and depth of invasion (BD) score in biopsies were compared with their evaluation in the corresponding resections. Fifty‐nine percent of Finnish and 42% of Saudi Arabian biopsies were ≥ 5 mm deep, while 98% of Saudi Arabian and 76% of Finnish biopsies were ≥ 5 mm wide. Assessment of invasion front was possible in 72% of Finnish in comparison with 40% of Saudi Arabian biopsies. There was 86.8% agreement between TSR and 75% agreement between TIL evaluation using light microscopy and digital assessment. Significant agreement was obtained on comparing the TSR (p = 0.04) and BD (p < 0.001) values in biopsies and resections. Biopsies of ≥ 5 mm depth from representative OTSCC areas are essential for prognostic information. Clinical pathologists are advised to assess BD score and TSR for prognostic features in such biopsies. [ABSTRACT FROM AUTHOR]

Objectives: (1) To assess the statistical correlation between the tumor thickness (TT) by ultrasonography (USG) and microscopic measurement in cases of early oral tongue squamous cell carcinoma (OTSCC). (2) To assess the predictive capacity of TT by ultrasound in detecting nodal metastasis. Materials and Methods: Prospective analysis was performed in 24 patients for a period of 2 years from 2012 to 2013. Nodal status and TT measurement was done preoperatively by neck and intraoral USG respectively in cases of early (pT1 & T2, clinically N0) OTSCC. As per the institution protocol after histopathological confirmation of malignancy, all patients underwent resection of primary lesion and ipsilateral elective neck dissection (Level - I to IV). Measurement of TT was obtained intraoperatively from fresh glossectomy specimen and postoperatively from histopathological paraffin section examination. The statistical correlation between TT measured by USG and histopathology was assessed by Pearson’s correlation coefficient. Chi-square test was used to find the association of pathological T stage, TT with pathological nodal status. Results: Significant statistical correlation was seen between TT by USG and microscopic measures. Between the two, TT measurements were within 1 mm in 37.5% (9/24) of cases, within 2 mm in 29.16% (7/24), and was greater than 2 mm in 8 cases. The Pearson’s correlation r is 0.678 (P < 0.001) and ICC (interclass correlation coefficient) is 0.808. The average difference between microscopic and US thickness (Bias) is -0.14637 and the limits of agreement is (4.717, -4.863) with 95% limits of agreement. The rate of occult nodal metastasis was 16.6% and TT of

Background: The incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing among younger birth cohorts. The etiology of early‐onset OTSCC (diagnosed before the age of 50 years) and cancer driver genes remain largely unknown. Methods: The Sequencing Consortium of Oral Tongue Cancer was established through the pooling of somatic mutation data of oral tongue cancer specimens (n = 227 [107 early‐onset cases]) from 7 studies and The Cancer Genome Atlas. Somatic mutations at microsatellite loci and Catalog of Somatic Mutations in Cancer mutation signatures were identified. Cancer driver genes were identified with the MutSigCV and WITER algorithms. Mutation comparisons between early‐ and typical‐onset OTSCC were evaluated via linear regression with adjustments for patient‐related factors. Results: Two novel driver genes (ATXN1 and CDC42EP1) and 5 previously reported driver genes (TP53, CDKN2A, CASP8, NOTCH1, and FAT1) were identified. Six recurrent mutations were identified, with 4 occurring in TP53. Early‐onset OTSCC had significantly fewer nonsilent mutations even after adjustments for tobacco use. No associations of microsatellite locus mutations and mutation signatures with the age of OTSCC onset were observed. Conclusions: This international, multicenter consortium is the largest study to characterize the somatic mutational landscape of OTSCC and the first to suggest differences by age of onset. This study validates multiple previously identified OTSCC driver genes and proposes 2 novel cancer driver genes. In analyses by age, early‐onset OTSCC had a significantly smaller somatic mutational burden that was not explained by differences in tobacco use. Lay Summary: This study identifies 7 specific areas in the human genetic code that could be responsible for promoting the development of tongue cancer.Tongue cancer in young patients (under the age of 50 years) has fewer overall changes to the genetic code in comparison with tongue cancer in older patients, but the authors do not think that this is due to differences in smoking rates between the 2 groups.The cause of increasing cases of tongue cancer in young patients remains unclear. This study identifies 7 putative oral tongue squamous cell carcinoma driver genes (TP53, CDKN2A, CASP8, NOTCH1, FAT1, ATXN1, and CDC42EP1) and shows that early‐onset oral tongue squamous cell carcinoma has a significantly smaller somatic mutational burden that is not explained by differences in tobacco use. [ABSTRACT FROM AUTHOR]

Background: Histopathologic grading has been routinely used as a complement for clinical staging in the prognostication of patients with oral tongue squamous cell carcinoma (OTSCC). However, this subject remains contentious because there is no universally accepted grading system. Objectives: This study compared the prognostic significance of four histopathologic grading systems in 80 cases of oral tongue squamous cell carcinoma (OTSCC). Methods: Clinical and follow‐up information of the patients were obtained from medical records. Histopathologic malignancy grading of the tumor invasive front, Histologic risk assessment (HRA), World Health Organization (WHO) grading system, and Budding and Depth of invasion (BD) model were evaluated in the surgical specimens. Results: The HRA, histopathologic malignancy grading and WHO systems did not predict survival. Patients with larger tumor size [Hazard ratio (HR): 2.38; 95% confidence interval (CI): 1.07‐5.27; P = 0.026] and patients with BD model high‐grade tumors (HR: 2.99; 95% CI: 1.03‐8.68; P = 0.034) were significantly associated with a poor 5‐year overall survival rate. In the multivariate analysis, tumor size was identified as the only significant independent prognostic factor (HR: 2.23; 95% CI: 1.00‐4.99; P = 0.050). None of the grading systems studied was associated with 5‐year disease‐free survival rates. Conclusions: BD model was the only histopathologic grading system associated with the outcome of patients with OTSCC, indicating its potential value as an effective tool for the prognostication of OTSCC. [ABSTRACT FROM AUTHOR]

The incidence of oral tongue cancer, the majority subsite of oral cavity cancer, is rising among young people with less exposure to tobacco and alcohol. Viral causes have been proposed, including Merkel cell polyomavirus (MCPyV). We evaluated patient and tumor characteristics among 126 incident oral cavity cancers (OCCs). Consistent with generational norms, younger patients had less exposure to tobacco and a greater number of oral sexual partners than older OCCs. In addition, younger patients were more likely to present at an earlier stage and with cancer arising from the oral tongue (each P <.05). A subset of 44 cases was centrally tested for MCPyV large T antigen expression by immunohistochemistry. In the presence of controls, none of the tumors expressed MCPyV. These findings exclude consideration of MCPyV as an etiologic factor in OCC and may generate hypotheses for future examinations of the factors underlying the rise in oral tongue cancers. [ABSTRACT FROM AUTHOR]

Objective: Integrated PET/MRI with [18F]FDG is advantageous in that it enables simultaneous PET and MR imaging with higher soft-tissue contrast, multiplanar image acquisition, and functional imaging capability without using fat suppression and gadolinium-based contrast agents (GBCAs). The aims of this study were to demonstrate the feasibility of [18F]FDG PET/MRI for assessing the extent of the primary tumor (T) in oral tongue cancer (OTC) based on the 8th edition of American Joint Committee on Cancer (AJCC) cancer staging system, and to compare the diagnostic accuracy between [18F]FDG PET/MRI and contrast-enhanced MRI (ceMRI). Methods: 18 patients with biopsy-proven operable OTC underwent preoperative regional [18F]FDG PET/MRI and ceMRI within 2 weeks. For [18F]FDG PET/MRI, rainbow-colored PET images were overlaid on the corresponding MR images. Tumor size and the depth of invasion (DOI) were visually measured on [18F]FDG PET/MRI and ceMRI. The size, DOI, and clinical T stage were evaluated using the final surgical pathology as the reference. Results: Of the 18 OTCs, one was not detected by ceMRI due to metal artifacts from an artificial denture, and another due to superficial type (pathological DOI = 0 mm). Tumor sizes measured by ceMRI and [18F]FDG PET/MRI had significant positive correlations with the pathological size (r = 0.80 and r = 0.90, respectively), and DOIs measured by ceMRI and [18F]FDG PET/MRI had significant positive correlations with the pathological DOI (r = 0.74 and r = 0.64, respectively). The means ± SD of size (mm) were 20.4 ± 9.1, 22.9 ± 10.9, and 26.2 ± 10.0, and those of DOI (mm) were 7.1 ± 2.5, 6.9 ± 2.2, and 5.8 ± 3.2 for ceMRI, [18F]FDG PET/MRI, and pathology, respectively. A significant difference was observed in tumor size between ceMRI and pathology (p < 0.05), whereas no significant differences were observed between any other sizes, DOIs, or T stages. The accuracy for T status was 72% (13/18 including 2 undetectable cases) for ceMRI and 89% (16/18) for [18F]FDG PET/MRI. Conclusions: Although shallow DOIs are often overestimated, regional [18F]FDG PET/MRI without fat suppression and gadolinium enhancement is comparable to and may be substituted for ceMRI in preoperative T staging for OTC patients, reducing metal artifacts and avoiding the adverse effects of GBCAs. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) occurs in different subsites within the oral cavity. Our goal was to investigate the epidemiological features of OSCC with relation to age and subsite. Methods: Retrospective review of all patients treated for OSCC in a tertiary care center between 2000 and 2018. Results: A total of 360 patients were included. Five age groups were defined: 0 to 30, 31 to 45, 46 to 60, 61 to 75, and 76+. In the 0 to 30 and 31 to 45 groups, 94.6% of tumors originated in the oral tongue compared to 87%, 66%, and 61% in the 46 to 60, 61 to 75, and 76+ groups, respectively (P <.001). A higher proportion of oral tongue SCC (OTSCC) was found in nonsmokers (76% vs 62%, P =.02). In nonsmokers aged 0 to 60, 97.9% had OTSCC compared to 67.5% in the 61+ groups (P <.001). Conclusions: OSCC in young nonsmokers originates primarily in the tongue. The etiology of OTSCC in young patients may be different than other OSCC subsites and not related to smoking. [ABSTRACT FROM AUTHOR]

The 8th edition of American Joint Committee on Cancer's (AJCC) Cancer Staging Manual was modified by incorporating depth of invasion (DOI) in the T categorization of oral cavity cancer. This is because DOI is strongly associated with cervical lymph node metastasis, which is the most important negative prognostic factor of oral cavity cancer. This major change in the AJCC Cancer Staging Manual caused re-staging of T category in several cases. Although, the DOI on MRI and CT (radiological DOI; r-DOI) strongly correlated with pathological DOI (p-DOI), it is often 2-3 mm larger than p-DOI. Due to this variance, estimation of p-DOI based on r-DOI may not be accurate. However, when a lesion is undetectable on MRI, p-DOI was often smaller than 4 mm. On the other hand, when MRI depicts lesions with styloglossus and hyoglossus muscle invasion, p-DOI was always larger than 4 mm. These correlations between MRI findings and p-DOI are important when assessing the need for elective neck dissection, as the National Comprehensive Cancer Network (NCCN) recommends elective neck dissection in cases with DOI greater than 4 mm. [ABSTRACT FROM AUTHOR]

Little is known about the histopathological characteristics that may differentiate early oral tongue cancer (OTSCC) between young and older patients. From a total of 311 cases diagnosed with clinically early‐stage OTSCC at 6 institutions, only 42 patients were young patients were aged ≤45 years. For comparison, 42 patients >60 years old were matched for center of management, clinical stage and gender. We compared epithelial and stromal histopathologic parameters between the two groups. Most of the parameters were similar between the two groups, although the young patients appeared to have marginally higher intensity of tumor budding, histologic risk score, infiltrative pattern of invasion and tumor‐stroma ratio. However, none of the factors showed significant difference when comparing the two groups. The histological parameters reflect mechanisms of invasive growth and tissue response to invasive growth, but not the etiological difference in OTSCC between young and older patients. Further investigations are necessary to compare the genetic background of early OTSCC in the two groups. [ABSTRACT FROM AUTHOR]

Background: The present study aims to explore the role of sentinel lymph node biopsy (SLNB) with intraoperative frozen section in the management of early-staged oral tongue cancers. Materials and Methods: Fifty-two patients with clinical stages cT1/2N0 oral tongue cancers were included in the present study. The curative surgery was preceded by the performance of an SLNB using a dual technique. Results: The identification rate of sentinel lymph node (SLN) in this study was 98.07%. The sensitivity, specificity, positive predictive value (PPV), and the negative predictive value (NPV) of SLNB were 88.2%, 100%, 100%, and 94.5%, respectively. Further, the sensitivity, specificity, PPV, and the NPV of intraoperative frozen section of the SLN were 70.5%, 100%, 100%, and 87.5%, respectively. Conclusions: The addition of intraoperative frozen section could identify 70.5% of patients with occult metastasis. An intraoperative frozen section assessment of sentinel node has the potential to change the overall management of patients with early-oral tongue cancers. [ABSTRACT FROM AUTHOR]

Estimation of risk of recurrence in early-stage oral tongue squamous cell carcinoma (OTSCC) remains a challenge in the field of head and neck oncology. We examined the use of artificial neural networks (ANNs) to predict recurrences in early-stage OTSCC. A Web-based tool available for public use was also developed. A feedforward neural network was trained for prediction of locoregional recurrences in early OTSCC. The trained network was used to evaluate several prognostic parameters (age, gender, T stage, WHO histologic grade, depth of invasion, tumor budding, worst pattern of invasion, perineural invasion, and lymphocytic host response). Our neural network model identified tumor budding and depth of invasion as the most important prognosticators to predict locoregional recurrence. The accuracy of the neural network was 92.7%, which was higher than that of the logistic regression model (86.5%). Our online tool provided 88.2% accuracy, 71.2% sensitivity, and 98.9% specificity. In conclusion, ANN seems to offer a unique decision-making support predicting recurrences and thus adding value for the management of early OTSCC. To the best of our knowledge, this is the first study that applied ANN for prediction of recurrence in early OTSCC and provided a Web-based tool. [ABSTRACT FROM AUTHOR]

Purpose: By comparing styloglossus and hyoglossus muscle invasion (SHMI) of oral tongue squamous cell cancer (OTSCC) on MR imaging to pathological depth of invasion (DOI) and prognosis, we aimed to evaluate the clinical significance of MR imaging findings of SHMI.Method: Forty-five, early stages and clinically N0 OTSCCs were retrospectively reviewed. Data included pathological DOI, DOI on MR imagings, two-year potential cervical lymph node positive, locoregional control, disease-free survival, and overall survival. Data were statistically compared between the groups with MR evidence of SHMI (SHMI+) and without MR evidence of SHMI (SHMI-).Results: There were 17 SHMI + and 28 SHMI-. Elective neck dissections performed on 13 cases revealed five node positive cases, all of which were SHMI + . Pathological DOI in SHMI + was significantly larger than SHMI- (average 9.0 vs 4.6 mm, p < 0.001). All SHMI + revealed pathological DOI larger than 4 mm. The two-year potential cervical lymph node positive rate of SHMI + was significantly higher than SHMI- (p =  0.01). Locoregional control rate and disease-free survival of SHMI+ were significantly lower than in SHMI- (p =  0.02). There was no significant difference in overall survival. Interobserver agreement in evaluation of SHMI on MR imaging was good (kappa value = 0.72, p <  0.001).Conclusions: Pathological DOIs of SHMI + were all larger than 4 mm, which is the cut-off point that National Comprehensive Cancer Network recommends for neck dissection, and SHMI + had a worse prognosis than SHMI-. SHMI + can be used as a criterion for elective neck dissection. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To utilize the Surveillance, Epidemiology, and End Results (SEER) database to elucidate differences in predictors of survival in oral tongue squamous cell carcinoma (OTSCC) as stratified by age and sex.Study Design: Retrospective, population-based database analysis.Methods: The SEER registry was utilized to calculate survival trends for patients with OTSCC between 1973 and 2012. Patient data were then stratified by age (≤40 years vs. >40 years) and sex, then analyzed with respect to race, stage, grade, and treatment modalities. Overall survival (OS) and disease-specific survival (DSS) were calculated and compared.Results: There were 16,423 cases of OTSCC identified, with 526 and 706 young female and male patients, respectively. Young female patients had improved OS and DSS as compared to young male patients (75% vs. 67% at 5 years), which is better than older patients (P < .001). Younger patients were more likely to receive surgery (P < .001) and combination surgery and radiation (P < .001) as compared to older patients. On multivariate analysis, tumor stage was uniformly associated with worse OS and DSS (P < .05), with surgery predicting improved OS and DSS in all groups except young females (P < .05). Higher tumor grade predicted worse OS and DSS in older patients, but not younger patients (P < .05).Conclusions: OTSCC appears to present with relatively heterogeneous characteristics across different age groups and sexes. Despite the rising incidence of OTSCC in young individuals, our study demonstrates that young patients have improved survival rates compared to older patients.Level Of Evidence: NA Laryngoscope, 129:2076-2081, 2019. [ABSTRACT FROM AUTHOR]

Rationale and Objective: To evaluate the inter-rater reliability of the magnetic resonance imaging (MRI)-derived depth of invasion (DOI) and the agreement between MRI and pathological measurements of oral tongue cancer.Materials and Methods: The institutional review board approved this retrospective study. The study population consisted of 29 patients with clinical T2N0 oral tongue cancer treated by surgery. Routine pretreatment MRI was performed on a 3T superconducting imager. Two raters with 23 and 18 years of head-and-neck MRI experience, respectively, independently chosen MRI sequences for each patient, then delineate the tumor, and then used three protocols to measure the MRI-derived DOI: the axial reconstructed thickness (method 1), the axial invasive portion (method 2), and the coronal invasive portion (method 3). Then they consensually selected the optimal among the three methods for each patient; it was designated method 4. The Bland-Altman plots, intraclass correlation coefficients (ICCs), and the paired samples test were used. According to the median follow-up of 41 months, the relationship between the MRI-derived DOI and nodal recurrence was also investigated.Results: The inter-rater reliability of methods 2 and 4 was excellent (ICC of 0.829 and 0.807, respectively). The correlation between MRI and pathological measurements was good for method 4 (ICC of 0.611), however, all measurements recorded on MRI were 2-3 mm larger than on pathology. No patients whose MRI-derived DOI was less than 5 mm suffered nodal recurrence.Conclusion: The MRI-derived DOI was valuable for the preoperative staging. The optimal measurement method should be selected on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To characterize the demographics, clinicopathologic characteristics, and treatment and reconstructive outcomes of patients who underwent total glossectomy STUDY DESIGN: Retrospective chart review at an academic tertiary-care medical center.Methods: All patients who had undergone total glossectomy (as an individual procedure or as part of a more extensive resection) between January 1, 1995 and December 31, 2014 were included in the analysis. Patient characteristics and clinical outcomes were reviewed.Results: Forty-eight patients underwent total glossectomy for oral tongue and base of tongue cancer. The mean age of the patients was 56 (range, 29-92 years). History of tobacco and heavy alcohol use was found in 76% and 11% of patients, respectively. The majority of patients had advanced cancer (91.7% at stage IV), and 60.4% had salvage therapy for recurrent disease. T4 disease comprised 81% of patients. Sixty percent had clinical or radiographic evidence of nodal metastasis. Reconstruction of the defect was performed with free flaps from the rectus abdominus (40%), fibula (25%), anterolateral thigh (23%), and other donor tissues. One- and 5-year survival rates were 42% and 26%, with locoregional and distant recurrence reported at 36% and 25%, respectively.Conclusions: Total glossectomy for oncologic control is most commonly performed in patients who have stage IV cancers. Despite high reconstructive success rates, the likelihood of locoregional and distance recurrence was high. Most patients can communicate intelligibly and achieve decannulation, but swallowing outcomes remain guarded, especially considering previous irradiation and resection of the base of tongue.Level Of Evidence: 4 Laryngoscope, 129:1087-1092, 2019. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Adequate surgical resection of early stage oral tongue cancer provides the best chance at preventing locoregional disease recurrence. Determination of tumor dimensions and margin location is challenging and can lead to inadequate resections with close/positive margins. Ultrasonography has proven its utility in determining the thickness and extent of tongue tumors. Preoperative tumor dimension measurements carry increased significance with the addition of depth of invasion (DOI) to the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system. We report the results of a systematic review of the literature pertaining to the use of ultrasound in the diagnosis and management of oral tongue carcinoma.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analysis statement checklist was used to inform the design of this systematic review. All studies that utilized ultrasound in the diagnosis/management of primary carcinoma of the oral tongue were included. PubMed, Embase, and Cochrane were reviewed to identify eligible studies.Results: Nineteen articles were included in our analysis. Six hundred seventy-eight patients were studied in the articles included. Ultrasound tumor thickness measurements correlate well with those on histopathology and show promise as a predictor of cervical lymph node metastasis. Ultrasound can be safely used intraoperatively for deep margin assessment.Conclusions: Ultrasound is useful in the evaluation of oral tongue malignancies. More experience is needed to determine if it is reliable in determining preoperative DOI in light of the role this tumor parameter plays in the eighth edition of the AJCC staging manual. Laryngoscope, 129:662-670, 2019. [ABSTRACT FROM AUTHOR]

Purpose: To determine outcomes of interstitial high-dose-rate brachytherapy (HDR-BT) in patients with early stage oral tongue cancer. Material and methods : Ninety-two patients with stage I and II oral tongue cancer were treated with HDR-BT between 1999 and 2014: brachytherapy alone = 62 (67.4%), and combination of external beam radiotherapy (EBRT) and brachytherapy = 30 (32.6%). Median follow-up was 53.5 months. Patterns of failure, overall survival (OS), disease-free survival (DFS), local control rates (LCR), and nodal control rates (NCR) were determined. Results : 5-year OS, DFS, LCR, and NCR were 73.2%, 58.2%, 64.2%, and 83.8%, respectively. In total, 43 patients (46.7%) failed treatment: isolated local failures = 28 (30.4%), isolated nodal failures = 8 (8.7%), both local and regional failures = 7 (7.6%). While in T1 stage, 5 year LCR were significantly higher in brachytherapy alone group compared to combined EBRT and brachytherapy group (81.7% vs. 62.5%, p = 0.04), the isolated nodal failure rates were not significantly different among the two groups. For T2 stage, NCR were higher in combined EBRT and brachytherapy group compared to brachytherapy alone (92.9% vs. 74.3%). Acute mucositis (grade ≥ 2) was seen more in brachytherapy alone group compared to the combined modality group (87% vs. 66%), and this correlated significantly with the higher biological equivalent dose (BED) in the brachytherapy alone group. Conclusions : Our study recommends treating patients with brachytherapy alone in T1 stage, and demonstrates the need for addressing nodal region either by neck dissection or nodal irradiation in T2 stage patients. Also, the study highlights the need for dose escalation (from the doses used in the study) in both T1 and T2 stage tumors when using interstitial brachytherapy either as sole modality or as a boost.

Keywords: Histamine; Histamine H4 receptor; Oral Cancer (OC); Oral tongue cancer; head and neck cancer EN Histamine Histamine H4 receptor Oral Cancer (OC) Oral tongue cancer head and neck cancer 1 3 3 06/10/20 20200605 NES 200605 The past two decades have witnessed a substantial increase in our understanding of histamine interaction and functions. In this regard, cells that are able to produce and store large (often micromolar) concentrations of histamine in secretory granules (e.g. mast cells, basophils, and enterochromaffin-like cells) were termed "professional histamine producing cells." Histamine, Histamine H4 receptor, Oral Cancer (OC), Oral tongue cancer, head and neck cancer. [Extracted from the article]

Abstract Chemoradiation is an established approach in the treatment of advanced oral tongue squamous cell carcinoma (OTSCC), but therapy may cause severe side-effects due to signal interchanges between carcinoma and the tumour microenvironment (TME). In this study, we examined the potential use of our human 3D myoma disc and Myogel models in in vitro chemoradiation studies by analysing the effects of ionizing radiation (IR) and the combined effect of heparanase I (HPSE1) inhibitors and IR on OTSCC cell proliferation, invasion and MMP-2 and − 9 production. Finally, we analysed the long-term effects of IR by studying clones of previously irradiated and invaded HSC-3 cells. We found that in both human uterine leiomyoma-based extracellular matrix models IR inhibited the invasion of HSC-3 cells, but blocking HPSE1 activity combined with IR induced their invasion. Low doses of IR increased MMP expression and initiated epithelial-mesenchymal transition in cells cultured on myoma discs. We conclude that myoma models offer consistent methods for testing human carcinoma cell invasion and phenotypic changes during chemoradiation treatment. In addition, we showed that IR had long-term effects on MMP-2 and − 9, which might elicit different HSC-3 invasion responses when cells were under the challenge of HPSE1 inhibitors and IR. Highlights • Myoma-based ECM models are suitable for in vitro chemoradiation assays. • Blocking of HPSE1 activity combined with IR may induce tongue cancer cell invasion. • Low doses of IR may increase MMP expression and invasion in tongue cancer cells. [ABSTRACT FROM AUTHOR]