Tongue cancer developing after haematopoietic stem cell transplantation for treatment of acute promyelocytic leukaemia: A case report.

Acute promyelocytic leukaemia (APL) is a form of acute myelogenous leukaemia. APL is characterised by anaemia due to suppression of normal haematopoiesis and infection. Haematopoietic stem cell transplantation (HSCT) is current option for the treatment of haematopoietic malignancies and is proving to be successful. Although HSCT has been effective for the treatment of haematopoietic malignant tumours, chronic graft-versushost disease (GVHD) but secondary cancers can occur, which is a serious complication and frequently involves the oral cavity and skin. Here, we report the case of tongue cancer occurring 17 years after transplantation in a patient who developed GVHD after haematopoietic stem cell transplantation and APL remission. To the best of our knowledge, this is the first report of secondary oral cancer after HSCT with APL as the primary disease.

Global research trends in tongue cancer from 2000 to 2022: bibliometric and visualized analysis.

OBJECTIVES: This study conducts a systematic bibliometric analysis of tongue cancer publications to identify key topics, hotspots, and research distribution. METHODS: We analyzed tongue cancer publications in the Web of Science core collection database, assessing their quantity and quality. We investigated contributors, including countries, affiliations, journals, authors, and categories, within collaborative networks. Additionally, we synthesized key research findings using various analytical techniques, such as alluvial flow, burstness analysis, cluster analysis, co-occurrence network of associations, and network layer overlay. RESULTS: From 2000 to 2022, this bibliometric study covers 2205 articles and reviews across 617 journals, involving 72 countries, 2233 institutions, and 11,266 authors. It shows consistent growth, particularly in 2016. Key contributors include China (499 publications), Karolinska Institute (84 publications), Oral Oncology (144 publications), and Tuula Salo (47 publications). Other notable contributors are the USA (16,747 citations), the National Cancer Institute (NCI) (2597 citations), and the Memorial Sloan-Kettering Cancer Center (MSK) (2231 citations). Additionally, there are significant teams led by Tuula Salo and Dalianis. We have identified six primary clusters: #0 apoptosis, #1 depth of invasion, #2 radiotherapy, #3 hpv, #4 tongue cancer, #5 oral cancer. The top ten highly cited documents primarily pertain to epidemiology, prognostic indicators in early-stage oral tongue cancer, and HPV. Additionally, we observed 16 reference clusters, with depth of invasion (#3), young patients (#4), and tumor budding (#6) gaining prominence since 2012, indicating sustained research interests. CONCLUSIONS: This analysis emphasizes the increasing scholarly interest in tongue cancer research. The bibliometric evaluation highlights pivotal recent research themes such as HPV, depth of invasion, tumor budding, and surgical margins. CLINICAL RELEVANCE: The bibliometric analysis highlights the key topics and studies which have shaped the understanding and management of tongue cancer.

Ultrasonography use for tongue cancer management: A scoping review.

BACKGROUND: Tongue cancer is associated with debilitating diseases and poor prognostic outcomes. The use of imaging techniques like ultrasonography to assist in the clinical management of affected patients is desirable, but its reliability remains debatable. Therefore, the aim of this study is to investigate the importance of ultrasound use for the clinicopathological management of tongue cancer. METHODS: A scoping review was carried out using specific search strategies in the following electronic databases: PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Collected data included bibliographical information, study design, ultrasound equipment, the aim of the ultrasonography use, the timing of ultrasound use during oncological treatment (pre-, trans-, and/or post-operatively), and the advantages and disadvantages of the use of the ultrasound. RESULTS: A total of 47 studies were included in this review after following the selection process. The majority of the studies investigated the use of ultrasound pre-operatively for the investigation of lymph node metastases or to determine the tumor thickness and depth of invasion. The sensitivity, specificity, and accuracy of ultrasound to determine clinical lymph node metastases ranged from 47% to 87.2%, from 84.3% to 95.8%, and from 70% to 86.2%, respectively. The sensitivity and specificity to determine the microscopic depth of invasion were 92.3% and from 70.6% to 82.1%, respectively. CONCLUSION: Ultrasonography seems to be a reliable imaging technique for the investigation of important prognostic parameters for tongue cancer, including depth of invasion and lymph node metastases.

Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma.

Introduction: The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined. Methods: We assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively. Results: MUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells in vitro, in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. Conclusion: The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.

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

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

Prognostic nomogram for patients with tongue squamous cell carcinoma: A SEER-based study.

OBJECTIVES: In order to predict the patients' prognosis with tongue squamous cell carcinoma (SCC), this study set out to develop a clinically useful and trustworthy prognostic nomogram. SUBJECTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program was used to compile clinical information on patients with tongue SCC between 2010 and 2015. The likelihood of Cancer-Specific Survival (CSS) and Overall Survival (OS) for specific patients was predicted using a prognostic nomogram created with the help of the RStudio software. The nomogram's predictive ability was evaluated using the consistency index (C-index) and decision curve analysis, and the nomogram was calibrated for 1-, 2-, 3-, 5-, and 10-year CSS and OS. RESULTS: Patients numbering 6453were enrolled in this study. The primary cohort (3895) and validation cohort (2558) were each randomly assigned. Sex, age, tumor-node-metastasis (TNM) stage, surgery, chemotherapy, and radiation were significant risk factors for OS, whereas age, TNM stage, surgery, chemotherapy, and radiotherapy were significant risk factors for CSS. Additionally, C-index and calibration curves indicated that the prognostic nomogram prediction and the actual observation in both cohorts would be very coherent. CONCLUSIONS: The predictive nomogram created in this study can offer patients with tongue SCC customized treatment and survival risk assessment.

Establishment of a Prognostic Nomogram for Cancer-Specific Survival in Patients With Base-of-Tongue Squamous Cell Carcinoma: A Retrospective Study Based on the SEER Database.

BACKGROUND: The aim of this retrospective study was to construct and clinically apply a nomogram for cancer-specific survival (CSS) in patients diagnosed with base-of-tongue squamous cell carcinoma (BOTSCC) to predict their survival prognosis. METHODS: We collected 8448 patients diagnosed with BOTSCC during 2004-2015 from the Surveillance, Epidemiology, and End Results (SEER) database and divided 30% and 70% of them into validation and training cohorts, respectively. We utilized backward stepwise regression in the Cox model to select variables. Predictive variables were subsequently identified from the variables selected above by using multivariate Cox regression. The new survival model was compared with the American Joint Committee on Cancer (AJCC) prognosis model using the following variables: calibration curve, time-dependent area under the receiver operating characteristic curve (AUC), concordance index (C-index), integrated discrimination improvement (IDI), decision-curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: A nomogram was established for predicting the CSS probability in patients with BOTSCC. Factors including sex, race, age at diagnosis, marital status, radiotherapy status, chemotherapy status, TNM AJCC stage, surgery status, tumor size, and months from diagnosis to treatment were selected through multivariate Cox regression as independent predictors of CSS. Calibration plots indicated that the model we established had satisfactory calibration ability. The AUC, C-index, IDI, DCA, and NRI results illustrated that the nomogram performed explicit prognoses more accurately than did the AJCC system alone. CONCLUSION: We identified the relevant factors affecting the survival of BOTSCC patients and analyzed the data on patients suffering from BOTSCC in the SEER database. These factors were used to construct a new nomogram to give clinical staff a more-visual prediction model for the 3-, 5-, and 8-year probabilities of CSS for patients newly diagnosed with BOTSCC, thereby aiding clinical decision making.

Au/Mn nanodot platform for in vivo CT/MRI/FI multimodal bioimaging and photothermal therapy against tongue cancer.

Surgical resection is the main method for oral tongue squamous cell carcinoma (OTSCC) treatment. However, the oral physiological function and aesthetics may be seriously damaged during the operation with a high risk of recurrence. Therefore, it is important to develop an alternative strategy with precise guidance for OTSCC treatment. Herein, multifunctional Au/Mn nanodots (NDs) are designed and synthesized. They can perform multimodal bioimaging, including computed tomography (CT) and magnetic resonance imaging (MRI) simultaneously, and exhibit bright near-infrared fluorescence imaging (FI) for navigation, and even integrate photothermal therapy (PTT) property. The localization of OTSCC relies on visual and tactile cues of surgeons while lacking noninvasive pretreament labeling and guidance. Au/Mn NDs provide CT/MRI imaging, giving two means of accurate positioning pretherapy. Meanwhile, the fluorescence of the Au/Mn NDs in the near-infrared region (NIR) is beneficial for noninvasive labeling and intuitive observation with the naked eye to determine the tumor boundary during PTT. Further, Au/Mn NDs showed excellent results in ablating tumors in vivo. Above all, the Au/Mn NDs provide a key platform for multimodal bioimaging and PTT in a single nanoagent, which demonstrated attractive performance for OTSCC treatment.

Construction and application of dynamic online nomogram for prognosis prediction of patients with advanced (Stage III/IV) tongue squamous cell carcinoma.

OBJECTIVES: The prognosis of patients with advanced tongue squamous cell carcinoma (ATSCC) is poor, and their overall survival (OS) is relatively short. Currently, the TNM stage system is often used clinically to assess the prognosis of patients, but the evaluation index of the TNM stage system is relatively single and does not specifically demonstrate relevant prognostic data. Therefore, the purpose of this study was to construct a dynamic online nomogram for predicting the prognosis of patients with ATSCC and to provide some reference for personalized clinical treatment of patients. METHODS: Clinical and prognostic information on patients with pathologically confirmed ATSCC from 2000 to 2018 was extracted from the SEER database and randomly divided into a training cohort and a validation cohort in a 7:3 ratio. Multifactorial and univariate Cox regression analyses were used to identify prognostic risk factors. Dynamic online nomogram were constructed using R software. Area under the curve (AUC), C-index, calibration curve, and decision curve analysis (DCA) with time-dependent ROC curves were used to assess the clinical utility of the nomogram. Kaplan-Meier survival curves were used to compare the prognosis of different patient categories. RESULTS: A total of 3828 patients with ATSCC were screened in the SEER database.Age,race, primary site, AJCC T,N and M stage, lymph nodes surgery, radiotherapy, chemotherapy and marital status were independent influences on OS(P < 0.05). In the training cohort, the C-index of the OS-related line plot was 0.733 and the AUC for predicting 3-year OS was 0.867. In the validation cohort, the C-index was 0.738 and the AUC for 3-year OS was 0.899. Calibration plots and DCA curves showed good predictive performance of the model in both the training and validation cohorts. Kaplan-Meier survival curves showed that chemotherapy, lymph nodes surgery,married,primary site(tongue base) and radiotherapy had better OS than the non-chemotherapy, non-surgery, single, primary site(tongue anterior), and non-radiotherapy groups, respectively (all P < 0.05). CONCLUSION: The established dynamic online nomogram has good predictive performance, which helps to personalize and combine the actual clinical patients to comprehensively predict the prognosis of ATSCC patients and may have better clinical application than the TNM stage system.

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

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

Prognostic histological markers in oral tongue squamous cell carcinoma patients treated with (chemo)radiotherapy.

Treatment of oral tongue squamous cell carcinoma (OTSCC) frequently includes surgery with postoperative radiotherapy (RT) or chemoradiotherapy (CRT). Resistance to RT or CRT remains a major clinical challenge and highlights the need to identify predictive markers for it. We included 71 OTSCC patients treated with surgery combined with RT or CRT. We evaluated the association between tumor budding, tumor-stroma ratio (TSR), depth of invasion (DOI), tumor-infiltrating lymphocytes (TILs), hypoxia-inducible factor-1alpha (HIF-1alpha) expression, octamer-binding transcription factor 4 (OCT4) expression, high-endothelial venules (HEVs), and disease-free survival (DFS) using uni- and multivariate analyses. No significant association was observed between the different histological and molecular markers (TSR, DOI, TILs, HEV, HIF-1alph, OCT4) and DFS. However, an associative trend between DOI, budding, and DFS was noted. Further studies with larger cohorts are needed to explore the prognostic value of DOI and budding for OTSCC patients treated with postoperative RT or CRT.

Association of Primary Tumor Volume With Survival in Patients With T3 Glottic Cancer Treated With Radiotherapy: A Study of the Canadian Head & Neck Collaborative Research Initiative.

Importance: The association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors. Objective: To evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study. Design, Setting, and Participants: This multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria. Exposures: Tumor volume as measured on diagnostic imaging by expert neuroradiologists. Main Outcomes and Measures: Primary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study. Results: The mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76). Conclusions and Relevance: Increasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.

Histopathological prognosticators and their clinicopathological correlation in oral squamous cell carcinomas of the tongue.

Background: Tongue carcinomas account for 25%-40% of intraoral squamous cell carcinomas (OSCCs). Although TNM staging systems is an international standard for cancer reporting, prognosis evaluation, and treatment planning, multiple histopathological risk assessment predictors such as tumor thickness (TT), tumor shape, tumor growth pattern, and invasive malignancy grading scoring systems have been studied and should form a basis for prediction and prognostication of such aggressive carcinomas. Aim: To evaluate and characterize the histomorphological prognostic indicators in OSCCs of tongue and compare it with OSCCs of other anatomic sites within the oral cavity. Furthermore, to elucidate the significance of histopathological indicators in predicting prognosis of tongue squamous cell carcinomas (SCCs). Materials and Methods: Forty SCC cases with 20 each of tongue and 20 from other intraoral sites were retrieved from department archives. Clinical data and staging were obtained for each case. Histomorphological parameters including pattern of invasion (POI), tumor budding (TB), depth of invasion (DOI), TT, lymphocytic host response, tumor-associated tissue eosinophilia (TATE), vascular invasion, perineural invasion (PNI), and muscular invasion were assessed. The results were statistically evaluated. Results: TB, DOI, and sarcolemmal spread were significant histologic predictors in tongue SCC. Upon correlation of histomorphological parameters with clinical staging, TT, POI, and TATE were observed to be significantly correlated (P ≤ 0.05). Conclusion: The histomorphological risk assessment model may serve as important addition to the existing prognosticators and may be used as a prognostic index to help plan and individualize treatment protocol in cases with aggressive high-risk disease for whom the use of multimodality treatment seems beneficial.

[Influencing factors of nutritional status and change in 50 patients with oral squamous cell carcinoma during treatment].

PURPOSE: To investigate the changes of nutritional status in patients with oral squamous cell carcinoma(OSCC) and analyze the influencing factors during treatment. METHODS: Anthropometry (weight, BMI, waistline, middle circumference of left and right upper arms) and laboratory index(serum prealbumin, serum albumin, transferrins, 25-hydroxyvitamin D) were measured to represent the nutritional status of 50 patients with OSCC before operation, two days, one month and three months after operation. SPSS 24.0 software package was used for statistical analysis of the data, and influencing factors of nutrition risk in OSCC patient were analyzed with binary logistic regression model. RESULTS: Univariate and multivariate analysis showed that advanced age(OR=1.127,95%CI: 1.053-1.207), low educational level (OR=5.250, 95%CI: 1.147-21.796), smoking(OR=6.182, 95%CI: 1.631-23.433), alcohol use(OR=5.227, 95%CI: 1.336-20.450), chemoradiotherapy (OR=3.984, 95%CI: 1.199-13.242), free flap surgery (OR=8.000, 95%CI: 2.060-31.068), tracheostomy(OR=3.960, 95%CI: 1.069-14.671), cervical lymph node metastasis(OR=4.821, 95%CI: 1.418-16.399), buccal carcinoma(OR=9.000, 95%CI:1.140-71.038), tongue cancer(OR=7.200, 95%CI: 1.081-47.962), tumor stage T3-4(OR=3.542, 95%CI: 1.066-11.771) were independent influencing factors of the nutritional status of patients with OSCC. CONCLUSIONS: Aging, low educational level, smoking history and drinking history in the general demographic characteristics of patients, and chemoradiotherapy, free flap surgery, tracheostomy during treatment, as well as buccal carcinoma, tongue cancer, advanced stage and cervical lymph node metastasis are clinical characteristics, which affect the nutrition level during the treatment for OSCC patients.

Post-Treatment Neck Dissection of Tonsillar and Base of Tongue Squamous Cell Carcinoma in the Era of PET-CT, HPV, and p16.

Human-papillomavirus (HPV)-positive tonsillar and base of tongue carcinomas (TSCC/BOTSCC) are rising in incidence and treatments with radiotherapy, chemoradiotherapy (RT/CRT), and neck dissections (NDs) have several side effects. Therefore, an improved selection of patients needing salvage NDs would be beneficial. We examined the prevalence and localisations of viable tumour cells in neck lymph nodes in patients post-RT/CRT, identified by fluorodeoxyglucose positron-emission tomography with computer-tomography (FDG PET-CT), with a focus on HPV-associated tumours. Patients with 217 TSCC/BOTSCC with tumours assessed for HPV-DNA and p16INK4a undergoing FDG PET-CT 12 weeks after treatment and/or an ND were included. The FDG PET-CT data were compared with the findings in the pathology report after the ND. In total, 36/217 (17%) patients were selected for an ND due to positive findings in post-treatment FDG PET-CT. Of these, 35/36 were HPV-associated, 10/36 (28%) had viable tumour cells in the pathology reports of the neck specimen, and 8/10 (80%) were consistent with the FDG PET-CT findings, while 2/36 (5%) were missed by FDG PET-CT. We conclude that FDG PET-CT 12 weeks after RT/CRT is useful, but not completely reliable for finding all the metastases of HPV-associated TSCC/BOTSCC. Nonetheless, our data indicate that an ND could be more selectively guided by FDG PET-CT.

Tongue squamous cell carcinoma resists hyperthermia treatment by promoting Id-1 expression mediated EMT.

Epithelial-mesenchymal transition (EMT) is a key initial step in the recurrence and metastasis of tongue squamous cell carcinoma (TSCC). Hyperthermia (HT) may reduce the rate of postoperative recurrence and distant metastasis by reversing the process of EMT of tumor cells, but the molecular mechanism is unclear. This study aims to investigate the role of inhibitor of differentiation/DNA binding-1 (Id-1) in HT mediated reversal of EMT of TSCC cells, and to provide a new approach for the treatment of TSCC using therapeutic gene targeting. After the combination of RNA interference with Id-1 and HT, the morphology of TSCC cells changed from spindle-like to pebble-like, and the arrangement of cells changed from loose and disorderly to compact and orderly. The silencing of Id-1 gene enhances the efficacy of HT by affecting the expression of EMT markers in TSCC cells. This study suggests that the Id-1 gene in TSCC cells can regulate transforming growth factor-beta 1, thereby affecting the expression of EMT markers, to achieve the effect of reducing HT.

Tongue cancer following hematopoietic cell transplantation for Fanconi anemia.

OBJECTIVES: The aim of this retrospective study was to determine the incidence and the clinical outcome of tongue cancer (TC) in patients affected by Fanconi anemia (FA) who received an allogeneic hematopoietic cell transplantation (HCT). MATERIALS AND METHODS: The patient database from the Bone Marrow Transplant Center of Pescara was reviewed to enroll FA patients. Patients', donors', HCT's, and screening's data were collected as well to look for the incidence and the treatment of TC. RESULTS: Twelve patients affected by FA were identified. Three patients died for transplant-related causes. Five of nine surviving patients were diagnosed with TC at a median of 21.7 years since transplantation and at a median age of 32.10 years. Interestingly, no patient manifested graft-versus-host-disease (GvHD). The 28-year cumulative incidence function of TC was 46.9% (95% CI, 36.9-56.9%). Two patients were treated with chemotherapy alone, two patients were treated with surgery alone, and one with surgery followed by chemotherapy. Overall, 4 patients with TC showed a clinical course characterized by a marked aggressiveness of the tumor disease which led to death due to cancer progression between 2 and 13 months. One patient is surviving 8 months after diagnosis of TC. CONCLUSIONS: Our study confirms the high incidence of tumors and in particular tongue tumors in allotransplanted FA patients. A careful screening has to be life-long maintained. CLINICAL RELEVANCE: Considering the rarity of FA and the frailty of FA patients, this study may add important information for the cancer management of these patients.

Emerging histopathologic markers in early-stage oral tongue cancer: A systematic review and meta-analysis.

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.

Effect of histopathological grade on treatment and survival in base of tongue adenocarcinoma.

OBJECTIVES: The purpose of this study was to investigate survival differences between low-grade and high-grade base of tongue (BOT) adenocarcinoma by examining demographics, tumor characteristics, and treatment modalities. METHODS: The National Cancer Database was queried for patients with BOT adenocarcinoma between 2004 and 2017. Univariate and multivariate analyses were performed for all cases of BOT adenocarcinoma. Subsequent analysis focused on low-grade (grade 1 and grade 2) and high-grade (grade 3 and grade 4) BOT adenocarcinoma. RESULTS: A total of 286 patients with BOT adenocarcinoma were included in the main cohort and divided into low grade (n = 137) and high grade (n = 66). The 5-year overall survival for all patients, low-grade, and high-grade was 67%, 85%, and 58%, respectively. Prognostic factors associated with decreased survival for the main cohort include advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02-1.06), non-white race (HR: 1.79; 95% CI: 1.04-3.25), public insurance (HR: 1.79; 95% CI: 1.02-3.14) and high-grade 3,4 (HR: 2.63; 95% CI: 1.51-4.56). The prognostic factor associated with increased survival for the main cohort was surgery (HR: 0.59; 95% CI: 0.36-0.96). Radiotherapy was associated with improved overall survival for high-grade BOT adenocarcinoma (HR: 0.09; 95% CI: 0.02-0.49) but not for low-grade BOT adenocarcinoma (HR: 0.93; 95% CI: 0.38-2.32). CONCLUSIONS: This investigation is the largest to date analyzing the association of treatment modalities with overall survival in BOT adenocarcinoma. Surgery remains standard of treatment, particularly in low-grade cases, with radiotherapy offering additional survival benefit for high-grade BOT adenocarcinoma.

Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register.

BACKGROUND: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated. MATERIAL AND METHODS: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition. RESULTS: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16-. 5-year overall survival (OS) was 68% (95% CI: 64-72%), with76% and 37% for p16+ patients and p16- patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II-III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone. CONCLUSION: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16- tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.