Tongue Cancer Patients Research Articles

Dosimetric Comparison of Intensity Modulated Radiotherapy (IMRT) and Intensity Modulated Proton Therapy (IMPT) for Novel Oral Tongue Avoidance Concept in Low-Risk Squamous Cell Carcinoma of the Oral Tongue

<h3>Purpose/Objective(s)</h3> A subset of favorable oral tongue squamous cell carcinoma patients who undergo adequate surgical resection are at low risk of local recurrence to the primary site. Since irradiation of the primary site is the major cause of treatment morbidity during adjuvant radiotherapy, avoidance of this target while still treating the at-risk lymph nodes including the intervening lymphatics between the tongue and neck is an attractive potential treatment strategy. Prior to initiation of an investigator-initiated trial, we sought to quantify the dosimetric advantage of this strategy, hypothesizing intensity modulated proton therapy (IMPT) may further reduce dose to organs at risk (OAR) when avoiding the oral tongue compared to intensity modulated radiation therapy (IMRT). <h3>Materials/Methods</h3> Five consecutive patients with oral tongue cancer treated with postoperative radiation therapy from 8/2020 to 9/2021 were retrospectively reviewed. Novel Clinical Target Volume (CTV) contours were generated that excluded the oral tongue while maintaining coverage of at-risk lymph nodes. Comparison IMRT (X) and IMPT (PBT) plans were generated using both standard treatment volumes (Control) and oral tongue avoidance volumes (Study) (n=4 plans per patient). Dosimetric variables for critical OARs were compared using the paired t-test. <h3>Results</h3> Patients had T1-2 and N0-N2b disease with complete margin-negative partial or hemiglossectomy and bilateral neck dissections. The prescribed dose was 60 Gy in 30 fractions. D95% CTV coverage was similar between X and PBT plans for both Control and Study target volumes. Comparing Control to Study plans, both X (58.9 Gy vs. 38.3 Gy, p=0.007) and PBT (60.2 Gy vs. 26.1 Gy, p<0.001) decreased the mean dose to the oral cavity (OC). Similar results were demonstrated for mean pharyngeal constrictor dose with X (47.7 Gy vs. 44.6 Gy, p=0.003) and PBT (45.0 Gy vs. 34.9 Gy, p=0.001). There was no difference between Control and Study plans for larynx (p>0.19) or parotid (p>0.11) mean dose, or mandible max dose (p>0.59). Comparing the Study plans alone, PBT resulted in a significant reduction in mean OC dose (38.3 Gy vs. 26.1 Gy, p=0.007) and reduction in mean parotid dose (23.3 Gy vs.19.3 Gy, p=0.03) compared to X. For Control plans, there was no difference in OC dose using PBT compared to X but an improvement in mean parotid dose (26.6 Gy vs 19.7 Gy, p=0.02). <h3>Conclusion</h3> This study quantifies the dosimetric advantage of avoiding the oral tongue while still treating the at-risk intervening lymphatics and the bilateral necks during adjuvant radiotherapy for oral tongue cancer. The dosimetric difference between PBT and X was most prominent with an oral tongue avoidance strategy. Prospective studies are warranted to evaluate the clinical efficacy of oral tongue avoidance for favorable oral tongue cancer patients with indications for elective nodal irradiation.

Second primary malignancies in oral tongue cancer: A Surveillance, Epidemiology, and End Result–based analysis evaluating the basic characteristics, survival outcomes, and predictive factors

AbstractThe 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.

Results of sole postoperative interstitial, high-dose-rate brachytherapy of T1–2 tongue tumours

PurposeTo describe the results of treating tongue cancer patients with single postoperative interstitial, high-dose-rate (HDR) brachytherapy (BT) after resection.MethodsBetween January 1998 and April 2019, 45 patients with squamous cell histology, stage T1–2N0–1M0 tongue tumours were treated by surgery followed by a single HDR BT in case of negative prognostic factors (close or positive surgical margin, lymphovascular and/or perineural invasion). The average dose was 29 Gy (range: 10–45 Gy) and rigid metal needles were used in 11 (24%) and flexible plastic catheters in 34 cases (76%). Survival parameters, toxicities and the prognostic factors influencing survival were analysed.ResultsDuring a mean follow-up of 103 months (range: 16–260 months) for surviving patients, the 10-year local and regional control (LC, RC), overall survival (OS), and disease-specific survival (DSS) probabilities were 85, 73, 34 and 63%, respectively. The incidence of local grade 1, 2 and 3 mucositis was 23, 73 and 4%, respectively. As a serious (grade 4), late side effect, soft tissue necrosis developed in 3 cases (7%). In a univariate analysis, there was a significant correlation between lymphovascular invasion and RC (p = 0.0118) as well as cervical recurrence and DSS (p < 0.0001).ConclusionSole postoperative HDR brachytherapy can be an effective method in case of negative prognostic factors in the treatment of early, resectable tongue tumours. Comparing the results of patients treated with postoperative BT to those who were managed with surgery or BT alone known from the literature, a slightly more favourable LC can be achieved with the combination therapy, demonstrating the potential compensating effect of BT on adverse prognostic factors, while the developing severe, grade 4 toxicity rate remains low.

A Comprehensive Grading System for a Magnetic Sentinel Lymph Node Biopsy Procedure in Head and Neck Cancer Patients.

Simple SummaryWith 30% of clinically negative early-stage oral cancer patients harboring occult metastasis, an accurate staging of metastatic lymph nodes (LN) is of utmost importance for treatment planning. A magnetic sentinel lymph node biopsy (SLNB) procedure is offered as an alternative to conventional SLNB in oral oncology, however, a grading system is missing. A proper grading system is preferred to connect the different components of the magnetic SLNB: preoperative imaging, intraoperative detection, and histopathological examination of sentinel lymph nodes (SLNs). This study aims to provide a first grading system based on the distribution of a magnetic tracer, by means of preoperative magnetic resonance imaging (MRI), intraoperative estimation of iron content, and histopathological assessment of resected nodes. Pre- and post-operative MRI and harvested SLNs of eight tongue cancer patients with successful magnetic SLNB procedure were used for analyses.A magnetic sentinel lymph node biopsy ((SLN)B) procedure has recently been shown feasible in oral cancer patients. However, a grading system is absent for proper identification and classification, and thus for clinical reporting. Based on data from eight complete magnetic SLNB procedures, we propose a provisional grading system. This grading system includes: (1) a qualitative five-point grading scale for MRI evaluation to describe iron uptake by LNs; (2) an ex vivo count of resected SLN with a magnetic probe to quantify iron amount; and (3) a qualitative five-point grading scale for histopathologic examination of excised magnetic SLNs. Most SLNs with iron uptake were identified and detected in level II. In this level, most variance in grading was seen for MRI and histopathology; MRI and medullar sinus were especially highly graded, and cortical sinus was mainly low graded. On average 82 ± 58 µg iron accumulated in harvested SLNs, and there were no significant differences in injected tracer dose (22.4 mg or 11.2 mg iron). In conclusion, a first step was taken in defining a comprehensive grading system to gain more insight into the lymphatic draining system during a magnetic SLNB procedure.

Neutrophil-to-Lymphocyte Ratio (NLR) as An Inflammation Degree Marker in Tongue Cancer Patient

Tongue cancer is one of the most common malignancies of all oral malignancies. Cancer staging is induced by a systemic inflammatory response with one of the markers, one of them is neutrophil-lymphocyte ratio (NLR). This study aims to provide an overview of the NLR as a marker of the degree of inflammation in patients with tongue cancer. This systematic literature review was conducted online from January 2021 to March 2021 against articles reporting RNL as a marker of inflammatory action in patients with tongue cancer. The search for articles referred to Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) and conducted through PubMed, PMC, ScienceDirect, and EBSCOhost with the publication year 2015-2020. Selected articles met the criteria according to the PICO framework (Population, Intervention, Comparison, Outcome). Article screening is done by reading the title and abstract, checking for duplication, and reading the entire text. Sixteen in 841 research articles with observational study design were identified, the NLR cut-off value ranges from 2.04-2.95. Nine in ten research articles suggested a relationship between the NLR value and several clinicopathological characteristics of the patient. Twelve articles mentioned that there was the association of RNL with patient overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). The NLR value can be an indicator of the degree of inflammation in patients with tongue cancer as assessed from the parameters of the clinicopathological assessment and can be a predictive factor for patient's prognosis or survival status.

Pannexin 1-Mediated ATP Signaling in the Trigeminal Spinal Subnucleus Caudalis Is Involved in Tongue Cancer Pain.

Pain is one of the most severe concerns in tongue cancer patients. However, the underlying mechanisms of tongue cancer pain are not fully understood. We investigated the molecular mechanisms of tongue cancer-induced mechanical allodynia in the tongue by squamous cell carcinoma (SCC) inoculation in rats. The head-withdrawal threshold of mechanical stimulation (MHWT) to the tongue was reduced following SCC inoculation, which was inhibited by intracisternal administration of 10Panx, an inhibitory peptide for pannexin 1 (PANX1) channels. Immunohistochemical analyses revealed that the expression of PANX1 was upregulated in the trigeminal spinal subnucleus caudalis (Vc) following SCC inoculation. The majority of PANX1 immunofluorescence was merged with ionized calcium-binding adapter molecule 1 (Iba1) fluorescence and a part of it was merged with glial fibrillary acidic protein (GFAP) fluorescence. Spike frequencies of Vc nociceptive neurons to noxious mechanical stimulation were significantly enhanced in SCC-inoculated rats, which was suppressed by intracisternal 10Panx administration. Phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) neurons increased significantly in the Vc after SCC inoculation, which was inhibited by intracisternal 10Panx administration. SCC inoculation-induced MHWT reduction and increased pERK-IR Vc neuron numbers were inhibited by P2X7 purinoceptor (P2X7R) antagonism. Conversely, these effects were observed in the presence of P2X7R agonist in SCC-inoculated rats with PANX1 inhibition. SCC inoculation-induced MHWT reduction was significantly recovered by intracisternal interleukin-1 receptor antagonist administration. These observations suggest that SCC inoculation causes PANX1 upregulation in Vc microglia and adenosine triphosphate released through PANX1 sensitizes nociceptive neurons in the Vc, resulting in tongue cancer pain.

Non-Coplanar vs. Coplanar Intensity-Modulated Radiation Therapy (IMRT) for Protection of Lip and Buccal Mucosa

In this study, by comparing the coplanar and non-coplanar intensity-modulated radiation therapy (IMRT) treatment planning in treating tongue cancer, the significance of non-coplanar fields in the protection of lip and buccal mucosa was determined, and a reasonable solution was selected.48 tongue cancer patients treated from June 2019 to Feb 2021 were selected and divided into coplanar field group and non-coplanar field group randomly: the former one used divided nine fields on average while the latter one adopted seven fields meanly with two other fields which needed to turn the bed 270 degrees for making the angle of radiation ray tangent to the region of mucous membrane. The mucosal dose limit changed from 15 Gy to 45 Gy for comparison of the two treatment plans. The evaluating indicators including conformal index (CI), homogeneity index (HI), D5, D50, D98 of the target volume. The dose of normal tissues and organs including spine, throat, bilateral parotid gland, pharyngeal constrictor and oral mucosa (lip, upper and lower buccal mucosa) were calculated under different mucosal dose limit. The clinical manifestations of lip and buccal mucositis of 48 cases were recorded and graded by NCI-CTCAE 4.0. Corresponding statistical analysis were performed.The difference of CI, HI, D98, D50 and D5 between two groups in the target volume has the tendency to become smaller when the mucosal dose limit is less than 30 Gy, with significant statistical difference (P < 0.05). When the limit exceeds 30 Gy, there are still statistical differences in other indicators except CI (P < 0.05). In terms of normal tissue, a certain gap of doses on normal tissues between two groups exists when the mucosal limit is lower than 20 Gy, with significant statistical difference (P < 0.05). When the limit exceeds 20 Gy, there was no statistical difference. There are statistical differences (P < 0.05) in D98, D50, D5, CI and HI of the target area between the two groups when the mucosal function setting is less than 30 Gy. When the mucosal function setting exceeds 30 Gy, there is no statistical difference in CI, but there were still statistical differences in others (P < 0.05). In normal tissue, there is statistical difference (P < 0.05) between two treatment plans when mucosal function setting is smaller than 20 Gy; if it exceeds, there is no statistical difference. The patients of non-coplanar group showed better results in terms of the radiation-related toxicity of lip and cheek membrane: the incidence rate and classification of severity were much lower. Patients usually developed lip and buccal mucositis after the fourth week during the radiotherapy, and symptoms of most cases were classified mild. 21 cases ranked grade I while the remaining 3 ranked grade II.Compared with coplanar field, non-coplanar field radiotherapy can effectively reduce the exposure dose of lip and buccal mucosa. The application of non-coplanar treatment plan has good clinical significance and deserves to be promoted.

Clinical outcomes and impact of prognostic factors following adjuvant radiotherapy in oral tongue cancer patients

BackgroundThe purpose of the study was to evaluate survival outcomes in post-operative oral tongue cancer patients undergoing adjuvant radiotherapy (RT) at a tertiary cancer care center and to critically review the impact of various clinical-pathological factors on recurrence and survival. Demographic factors, stage of all the histology proven oral tongue cancer, and treatment details were documented. Overall survival (OS) and recurrence-free survival (RFS) were analyzed along with the potential prognostic factors affecting outcome.ResultsOne hundred forty-four post-operative oral tongue cancer patients referred to our department for adjuvant treatment were evaluated. Median age at presentation was 45 years. Forty-seven patients had pathological early stage disease (stages I and II) and 95 had locally advanced (stages III and IV) disease while post-op details were not present in 2 patients. At a median follow-up of 87 months (60–124) of alive patients, the median RFS for entire cohort was 62 months while median OS was 74 months respectively. Age, perineural invasion (PNI), and grade of the tumor emerged as independent prognostic factors for OS and RFS. Among patients with early stage disease, depth of invasion (DOI), age, and PNI were found as independent prognostic factors for RFS and OS. In locally advanced disease, higher grade, age, and PNI independently impacted the respective survival end points.ConclusionsAge (> 45 years), higher grade, and presence of PNI showed inferior survival outcomes across the sub-groups (early versus locally advanced disease). This may warrant adjuvant treatment intensification. DOI > 10 mm was particularly found to worsen survival in early node negative SCC oral tongue patients.

Differential cancer risk and survival in Indian oral cancer patients with genic region FAS and FASL polymorphisms

To investigate the association of genic region polymorphisms of FAS and FASL in Indian patients with oral cancer. The study included 960 consenting control participants and patients with oral cancer. Genotyping was performed using Polymerase Chain Reaction -Restriction Fragment Length Polymorphism (PCR-RFLP). Cancer risk, 5-year survival, and hazards ratio (HRs), with respect to risk and clinical factors, were estimated using Fisher's exact test, Kaplan-Meier analysis, and Cox proportional hazards models. FASL IVS2nt-124 'AG' increased risk in males with buccal mucosa cancer (BMC) but decreased risk in females. FAS 21196 'CT' decreased risk of tongue cancer (TC) and BMC in females. The survival of the patients also differed between sexes in TC and BMC. FAS 21196 'CT' increased HR by 23-fold in females with BMC when adjusted for age, stage, grade, LVS, PNI, tobacco use, and alcohol. 'TT' genotype increased the HR in females with BMC when adjusted for age, stage, grade, lymphovascular spread (LVS), perineural invasion (PNI), and perinodal spread (PNS). Our bioinformatic study revealed the presence of CTCF binding regions and CpG islands near FAS and FASL. These single nucleotide polymorphisms (SNPs) altered the risk and survival of BMC and TC patients differentially that varied with clinical and risk factors.

Changes in Oral Function and Quality of Life in Tongue Cancer Patients Based on Resected Area.

Objective:Treatment of tongue cancer caused oral morbidities such as oral dryness, and dysphagia. The purpose of this study is to examine the time course of oral function and QOL based on resected area for patients after tongue cancer resection. Methods:31 patients who underwent tongue cancer resection at the Showa University Head and Neck Oncology Center. The participants were divided into two groups; 24 participants in partial/hemi glossectomy group (PG), and seven in subtotal/total glossectomy group (TG). Participants were evaluated swallowing function (FOIS and MASA-C), tongue pressure (TP: kPa), BMI, whole body muscle mass (kg), and QOL evaluation (EORTC QLQ-C30, H & N35). Participants were measured at baseline (before surgical treatment), 1, 3, and 6 months after surgical treatment (1M, 3M, and 6M). Results:At baseline, tongue pressure and FOIS score of PG were significant higher than that of TG. At 1M, TP, MASA-C, and FOIS score of PG were significant higher than that of TG. At 3M, TP, MASA-C, and FOIS score of PG were significant higher than that of TG. At 6M, TP and MASA-C were significantly higher than that of TG. QOL measurements did not noted any significant difference between groups before 6M. At 6M, Some QOL measurements of TG related tongue function (Swallowing, Senses, Speech, Social contact) were significantly lower than PG. Conclusions:The resected area had significant effects on oral morbidities and feeding function. It is necessary to develop more effective rehabilitation methods to improve patients QOL who had functional impairment remained.

State of the Russian Oncology Service: malignant neoplasms of the tongue C01, 02 (mortality rate and median survival of patients, taking into account the stage of the disease and histological structure of the tumor) Part 2

Malignant neoplasms of the tongue occupy 0.55% in the general structure of the cancer incidence in the Russian population. No information on other parameters (the number of deaths, mortality of patients, their distribution by stages of the disease and other analytical indicators) is provided in the official reporting.&#x0D; The opportunity appeared only with the development of Population-based Cancer Registries (PCR) system, but this wealth of material is not used for the official reporting.&#x0D; Tongue cancer is a visual localization with a high mortality rate, which requires special attention.&#x0D; The research was conducted in order to investigate the state of the Russian Oncology Service for tongue cancer patients with the calculations of one-year mortality rate, annual mortality rate, median survival, 1,3,5-year observed and relative survival rates. The research was undertaken at the level of the newly created Population-based Cancer Registry of the Federal District for the first time in Russia.&#x0D; The studies on the analysis of cancer survival rate at the population level are practically not carried out in Russia. Such investigations for all malignant tumor localizations have been conducted since 2000 on the basis of Saint Petersburg PCR database. The level of 5-year observed and relative survival rates of tongue cancer patients in Russia (Saint Petersburg and the NWFD RF) has been determined significantly lower than the EU average (Eurocare-4). To carry out this study, 5188 observations from the NWFD RF PCR database were selected. It has been established that during four periods of observation, the one-year mortality rate of tongue cancer patients in the NWFD RF has decreased under the C01 heading (malignant neoplasm of base of tongue) from 58.5 to 45.8%; and under the C02 heading (malignant neoplasm of other and unspecified parts of tongue) from 54.5 to 42.7%. The five-year survival rate of tongue cancer patients has increased by 23.3%.

Role of Adjuvant Radiotherapy in Early Stage Tongue Cancer: Need for Establishing Stringent Guidelines.

The primary objective of this study was to determine, using population-based data, whether the addition of postoperative radiotherapy (RT) provides an overall survival benefit in patients with early primary squamous cell carcinoma (SCC) of tongue. The study included the data of tongue cancer patients treated between January 2016 and July 2019 retrieved from our hospital database. Tumours limited to pathologic T1 and T2 category managed with primary surgery with or without postoperative external beam RT were included. Overall survival (OS) and disease-free survival (DFS) were the main outcomes of interest. A total of 211 cases of oral cancer were evaluated and all the patients had clear surgical and pathological margins. Postoperative adjuvant therapy (PORT) was received by 16 patients. Comparison of DFS and OS at 2-year follow-up depicted a similar outcome (p = 0.582 and p = 0.312 respectively). Findings from our study suggest that in the absence of any absolute advantage on quantifiable survival and disease control, it is necessary to define stringent criteria when advocating PORT in early tongue cancer.

Oncolytic herpes virus G47Δ injected into tongue cancer swiftly traffics in lymphatics and suppresses metastasis

The prognosis of oral squamous cell carcinoma (OSCC) largely depends on the control of lymph node metastases. We evaluate the therapeutic efficacy of G47Δ, a third-generation oncolytic herpes simplex virus type 1 (HSV-1), in mouse tongue cancer models. Intratumoral injection with G47Δ prolonged the survival in all orthotopic models investigated. In both athymic and immunocompetent models, G47Δ injected into the tongue cancer swiftly traffics to the draining cervical lymph nodes and suppresses lymph node metastases. In the immunocompetent KLN205-MUC1 model, in which the metastatic cascade that tongue cancer patients commonly experience is reproduced, intratumoral G47Δ injection even immediately prior to a tumor resection prolonged survival. Cervical lymph nodes 18 h after G47Δ treatment showed the presence of G47Δ infection and an increase in CD69-positive cells, indicating an immediate activation of T cells. Furthermore, G47Δ injected directly into enlarged metastatic lymph nodes significantly prolonged the survival at an advanced stage. Whereas intratumorally injected oncolytic HSV-1 does not readily circulate in the blood stream, G47Δ is shown to traffic in the lymphatics swiftly. The use of G47Δ can lead to entirely new treatment strategies for tongue cancer and other OSCC at all clinical stages.

Diagnostic accuracy of magnetic resonance imaging in detecting depth of invasion of tongue cancers

The recent eighth edition of the American Joint Committee on Cancer (AJCC) staging system has introduced depth of invasion (DOI) as one of its important components. DOI is also important for deciding neck management in superficial tongue cancers. Magnetic resonance imaging (MRI) is mainly used to assess DOI, and in this study we have evaluated the efficacy of MRI to detect it. This is a retrospective study consisting of 60 treatment-naïve tongue cancer patients operated on between July 2017 and June 2019. Patients underwent MR imaging on an Optima MR450W 1.5T unit, and MRI was reported by two experienced head and neck radiologists. Postoperative histological DOI was considered the gold standard. The correlation coefficient was derived for postoperative DOI and MRI-detected DOI. A subgroup analysis of superficial tongue cancer was also done. The mean MRI DOI was 13.7 mm and the mean histological DOI 12.45 mm. The shrinkage factor was 0.6 mm. Pearson’s correlation coefficient was 0.80 (p=<0.001) for Radiologist 1 and 0.85 (p=<0.001) for Radiologist 2. The interobserver variation was low, with a correlation coefficient between the two radiologists of 0.965 (p=<0.001). For superficial tongue cancers there was moderate correlation for MRI and histologically-detected DOI with a kappa value of 0.681 (p=0.03). As per the ROC curve, the cut-off value for MRI DOI to predict nodal metastasis was 4.6 mm. MRI has high reliability to predict the DOI of tongue cancers. The interobserver variation was low. The diagnostic accuracy in cases of superficial tongue cancer was moderate.

Comparison of tongue cancer survival among White and Black cancer patients: An exploratory analysis of the SEER database.

e18053 Background: Despite the relatively rare incidence of tongue cancer in the United States, 2,830 people were estimated to have died from it in 2020. Research has indicated disparities in oral cancer screenings among minority and low-income patients. The aim of the present study is to characterize the incidence of tongue cancer across in the US population and to determine mediators of survival months. Methods: SEER 18 regions database (November 2019 submission) was queried to obtain data on tongue cancer incidence, patient demographics, and clinical variables for patients (n=51,622) from 2000-2017 using SEER*Stat 8.3.8. Data analysis were performed using R and RStudio version 4.02, and 1.3.1073, respectively. For comparison between groups, Chi-squared test for independence, Fisher’s exact test, and Wilcoxon signed-rank test were applied where applicable. Univariate and multivariate regression models characterized the relationship between survival months and sex, race, primary site, and additional patient characteristics. Results: Several significant group differences were determined in the incidence of tongue cancer. Patient sex was significantly associated (P&lt;0.001), with survival months in White patients, with median survival months 33 (IQR 11,85) and 35 (IQR 12,82) for females and males respectively. Regression analysis found multiple patient level characteristics significantly mediating survival months. The odds ratio (OR) for reported patient race of Black were OR 0.78 (95% CI 0.68, 0.89; P&lt;.001) and OR 0.75 (95% CI 0.66, 0.86; P&lt;.001) for univariate and multivariate regression, respectively. Conclusions: The study indicates that health disparities vis-à-vis social determinants of health play a role in mediating differences in tongue cancer survival months for patients in the US. Further research should characterize and address persisting health inequities and potential solutions in oral cancer incidence and mortality.[Table: see text]

PRKCA Overexpression Is Frequent in Young Oral Tongue Squamous Cell Carcinoma Patients and Is Associated with Poor Prognosis.

Simple SummaryOver the last decades, the incidence of tongue cancer has risen among young patients who often show an aggressive course of disease. At the same time, exposure to the major risk factors, alcohol and tobacco, has decreased, indicating that a novel risk factor may be involved. In this study, we found that high expression of protein kinase C alpha (PRKCA) is frequent among young patients without alcohol and smoking history and associated with a poor prognosis. Our results suggest that PRKCA levels may serve as a molecular marker of an emerging high-risk subgroup of young tongue cancer patients. Elucidation of the underlying mechanisms may clarify whether PRKCA expression itself promotes disease progression and which genetic or environmental factors trigger its upregulation. Oral tongue squamous cell carcinomas (OTSCCs) have an increasing incidence in young patients, and many have an aggressive course of disease. The objective of this study was to identify candidate prognostic protein markers associated with early-onset OTSCC. We performed an exploratory screening for differential protein expression in younger (≤45 years) versus older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n = 97). Expression of candidate markers was then validated in an independent Austrian OTSCC patient group (n = 34) by immunohistochemistry. Kaplan–Meier survival estimates were computed, and genomic and mRNA enrichment in silico analyses were performed. Overexpression of protein kinase C alpha (PRKCA) was significantly more frequent among young patients of both the TCGA (p = 0.0001) and the Austrian cohort (p = 0.02), associated with a negative anamnesis for alcohol consumption (p = 0.009) and tobacco smoking (p = 0.02) and poorer overall survival (univariate p = 0.02, multivariate p< 0.01). Within the young subgroup, both overall and disease-free survival were significantly decreased in patients with PRKCA overexpression (both p < 0.001). TCGA mRNA enrichment analysis revealed 332 mRNAs with significant differential expression in PRKCA-upregulated versus PRKCA-downregulated OTSCC (all FDR ≤ 0.01). Our findings suggest that PRKCA overexpression may be a hallmark of a novel molecular subtype of early-onset alcohol- and tobacco-negative high-risk OTSCC. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA-overexpressing OTSCC.

A systematic review and meta-analysis of the prognostic role of age in oral tongue cancer.

While evidence suggests an increasing incidence of tongue cancer in young adults, published findings regarding the prognostic role of age at diagnosis are inconsistent. We performed a meta‐analysis of the literature to highlight key points that might help in understanding the association between age of oral tongue cancer patients at diagnosis and their prognosis. According to age at diagnosis, a systematic literature review of all published cohort studies assessing the recurrence risks and mortality associated with tongue cancer was conducted. We compared the risk estimates between patients aged >45 years and those aged <45 years at diagnosis. Random‐effects models were used to calculate summary relative risk estimates (SRRs) according to different clinical outcomes and sources of between‐study heterogeneity (I2) and bias. We included 31 independent cohort studies published between 1989 and 2019; these studies included a total of 28,288 patients. When risk estimations were not adjusted for confounders, no significant association was found between age at diagnosis and overall survival (OS). Conversely, after adjustment for confounders, older age at diagnosis was associated with a significantly increased risk of mortality. The difference between SRRs for adjusted and unadjusted estimates was significant (p < 0.01). Younger patients had a significantly higher risk of local recurrence. Younger patients with oral tongue cancer have better OS but a greater risk of recurrence than older patients. These findings should be validated in a large prospective cohort study which considers all confounders and prognostic factors.

Is it essential to remove the submandibular gland in neck dissection in tongue cancer patients?

IntroductionSubmandibular sialadenectomy is a part of the classic technique of neck dissection for oral cavity cancers. However, its removal is associated with a reduction in the salivary outflow in many patients, as well as, some uncommon complications such as lingual and hypoglossal nerve injuries. Assessment of the necessity of such maneuvers should be addressed. Patients and methodsThe data of 105 patients with tongue cancer who underwent neck dissection in the Oncology Center, Mansoura University from January 2008 to March 2019 were reviewed and analyzed retrospectively. ResultsIn all the included patients, whether showing pathologic positive or negative lymph nodes, none showed capsular or parenchymal submandibular gland metastasis except for one patient who showed direct infiltration of the gland by the primary tumor. ConclusionSubmandibular sialadenectomy may not be indicated as a part of neck dissection in tongue cancer patients. Further research should be conducted to focus on the effect of its preservation on disease-free and overall survival.

Free Flap Reconstruction in a Tongue Cancer Patient with Nephrotic Syndrome: A Case Report.

Free flap has become crucial for reconstruction in head and neck oncology post resection since the time of its advent. It has shown a high success rate and provides a better quality of life over loco regional flaps. Literature has shown the success of free flaps does get influenced by preexisting medical conditions of the patient. Nephrotic syndrome being a hypercoagulable state doesn't find much mention in literature and its effect on free flaps has been less studied. Hence, using a free flap in such condition creates a decision making dilemma. Here we present a case report to show the feasibility of such flaps in nephrotic syndrome patients under structured environment successfully.

The occult nodal metastasis rate of early tongue cancer (T1-T2): A protocol for a systematic review and meta-analysis.

Objectives:In this study, a meta-analysis was conducted to evaluate the occult lymph node metastasis rate in patients with early-stage (T1–T2) oral tongue squamous cell carcinoma. Also, the correlation between occult lymph node metastasis rate and T2 ratio among T1–T2 or the reported year of each study was analyzed to adjust other confound variables.Study Design:Literature search.Methods:A systematic computerized search of the electronic databases was carried out for articles published between January 1, 1980, and December 31, 2018, which reported occult nodal metastasis rate in T1 and T2 (separately) tongue cancer patients. Statistical analysis was performed using Comprehensive Meta Analysis version 3.3.070. Publication bias was assessed by the Egger test and Begg funnel plot method. The correlation between occult nodal metastasis rate and T2 ratio or reported year, respectively, was assessed by meta-regression analysis.Results:From 19 studies, a total of 1567 cases were included in the meta-analysis. By random effects model, the mean occult cervical lymph node metastasis was 24.4% (95% confidence interval; 0.205–0.248). The meta-regression revealed that the T2 ratio and the reported year of the studies did not have a significant effect on the occult metastasis rate (correlation coefficient = 0.531 and 0.002, respectively, and P = .426 and 0.921, respectively).Conclusion:The meta-analysis revealed that the early-stage oral tongue squamous cell carcinoma had a rate of 24.4% for occult nodal metastasis. The occult nodal metastasis rate was not significantly affected by neither T2 ratio among T1–T2 nor reported year of the studies.