Elective neck dissection versus elective neck irradiation in cT3/4N0 maxillary sinus squamous cell carcinoma: a propensity score matching analysis.

BACKGROUND: Maxillary sinus squamous cell carcinoma (MS-SCC) is an infrequent malignancy, and determining the optimal neck management for patients with cT3/4N0 MS-SCC remains a topic of ongoing debate. The purpose of this study was to compare the prognoses and quality of life outcomes of patients who underwent either elective neck dissection (END) or elective neck irradiation (ENI) for cT3/4N0 MS-SCC. METHODS: In this retrospective study, we enrolled patients with surgically treated cT3/4N0 MS-SCC, and the impact of different neck management strategies on regional control and disease-specific survival was compared using propensity score matching. The effect of surgical intervention on quality of life was evaluated using the Mann-Whitney U test. RESULTS: Of the 120 patients included, 36 underwent END. After propensity score matching, our analysis indicated that END did not lead to superior outcomes than ENI, as demonstrated by comparable rates of regional control (p = 0.990) and disease-specific survival (p = 0.999). However, in the 70 returned questionnaires, patients who underwent END reported higher scores in the domains of appearance, chewing, and speech than did patients who underwent ENI. CONCLUSIONS: Our findings suggest that while END and ENI contribute to similar prognoses, END yields superior functional outcomes.

Transcutaneous carbon dioxide suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.

Cancer cachexia causes skeletal muscle atrophy, impacting the treatment and prognosis of patients with advanced cancer, but no treatment has yet been established to control cancer cachexia. We demonstrated that transcutaneous application of carbon dioxide (CO2) could improve local blood flow and reduce skeletal muscle atrophy in a fracture model. However, the effects of transcutaneous application of CO2 in cancer-bearing conditions are not yet known. In this study, we calculated fat-free body mass (FFM), defined as the skeletal muscle mass, and evaluated the expression of muscle atrophy markers and uncoupling protein markers as well as the cross-sectional area (CSA) to investigate whether transcutaneous application of CO2 to skeletal muscle could suppress skeletal muscle atrophy in cancer-bearing mice. Human oral squamous cell carcinoma was transplanted subcutaneously into the upper dorsal region of nude mice, and 1 week later, CO2 gas was applied to the legs twice a week for 4 weeks and FFM was calculated by bioimpedance spectroscopy. After the experiment concluded, the quadriceps were extracted, and muscle atrophy markers (muscle atrophy F-box protein (MAFbx), muscle RING-finger protein 1 (MuRF-1)) and uncoupling protein markers (uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3)) were evaluated by real-time polymerase chain reaction and immunohistochemical staining, and CSA by hematoxylin and eosin staining. The CO2-treated group exhibited significant mRNA and protein expression inhibition of the four markers. Furthermore, immunohistochemical staining showed decreased MAFbx, MuRF-1, UCP2, and UCP3 in the CO2-treated group. In fact, the CSA in hematoxylin and eosin staining and the FFM revealed significant suppression of skeletal muscle atrophy in the CO2-treated group. We suggest that transcutaneous application of CO2 to skeletal muscle suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.

Notch signaling genes and CD8+ T-cell dynamics: Their contribution to immune-checkpoint inhibitor therapy in oral squamous cell carcinoma: A retrospective study.

BACKGROUND: Aberrant Notch signaling pathway has been related with the tumorigenesis in head and neck region, involving oral cavity. Here, we report the correlation between mutations in the Notch signaling pathway and CD8+ T-cell infiltration via PD-L1, which lead to enhanced antitumor immunity and may target for immune-checkpoint inhibitors (ICIs) therapy. METHODS: This retrospective study analyzed the results of immunohistochemical staining for PD-L1 and CD8+ T-cell infiltration in 10 patients and whole-exome sequencing (WES) was conducted on five of these patients to identify frequently mutated genes. RESULTS: Four of 10 patients were positive for PD-L1 and CD8+ T. By analyzing WES in three of these four patients, we notably identified the mutations of NOTCH1, FBXW7, and noncoding RNA intronic mutation in NOTCH2NLR in two of these three patients. This study may enable better selection of ICI therapy with CD8+ T-cell infiltration via PD-L1 expression for oral squamous cell carcinoma patients with mutations in Notch signaling pathway.

Proton beam therapy for clival chordoma: Optimising rare cancer treatments in Australia.

With the anticipated launch of the Australian Bragg Centre for Proton Therapy and Research (ABCPTR) in Adelaide, Australia, proton therapy will become a significant addition to existing cancer treatment options for Australians. The anticipated benefits will be particularly evident in rare cancers such as clival chordomas, a challenging tumour entity due to the anatomical relationship with critical structures, and proven radio-resistance to conventional radiation therapy. The article synthesises key findings from major studies and evaluates the current evidence supporting various management strategies for clival chordomas. It also considers the influence of institutional volume and multidisciplinary team management on patient outcomes and outlines how high-quality care can be effectively delivered within the Australian healthcare system, emphasising the potential impact of proton therapy on the treatment paradigm of clival chordomas in Australia.

Use of Indocyanine Green Near-Infrared Imaging for Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Pilot Study.

PURPOSE: The current established technique for sentinel lymph node (SLN) biopsy is preoperative injection of 99mtechnetium-labeled nanosized colloids (99mTc) followed by single photon emission computed tomography and standard computed tomography (SPECT/CT) with subsequent intraoperative gamma probe-guided excision of the SLN. It is however time and resource consuming, causes radiation exposure and morbidity for the patient as the injection is done in the awake patient. Recently near-infrared imaging with indocyanine green (ICG) gained importance in SLN biopsy as a faster and more convenient technique. The objective of our study was to investigate the feasibility of SLN biopsy using ICG-imaging in early oral squamous cell carcinoma (OSCC). METHODS: Single-centre pilot study of five patients with early-stage OSCC. For all patients, both techniques (99mTc and ICG) were performed. We injected 99mTc preoperatively in the awake patient, followed by SPECT/CT imaging. Intraoperatively ICG was injected around the primary tumor. Then the neck incision was performed according to the SPECT/CT images and SLN were detected by using a gamma probe and near-infrared fluorescence imaging of the ICG-marked lymph nodes intraoperatively. The excised lymph nodes were sent to histopathological examination according to the SLN dissection protocol. RESULTS: In all five patients sentinel lymph nodes were identified. A total of 7 SLN were identified after injection of 99mTc, imaging with SPECT/CT and intraoperative use of a gamma probe. All these SLN were fluorescent and visible with the ICG technique. In two patients, we could identify additional lymph nodes using the ICG technique. Pathological analysis demonstrated occult metastasis in two of the cases. CONCLUSIONS: Our study shows that ICG-guided SLN biopsy is a feasible technique, especially in combination with conventional radioisotope method and may help for intraoperative localization of SLN. Validation studies with bigger patient cohorts are needed to prove our results.

Quantifying the severity of sarcopenia in patients with cancer of the head and neck.

BACKGROUND & AIMS: Existing skeletal muscle index (SMI) thresholds for sarcopenia are inconsistent, and do not reflect severity of depletion. In this study we aimed to define criterion values for moderate and severe skeletal muscle depletion based on the risk of mortality in a population of patients with head and neck cancer (HNC). Additionally, we aimed to identify clinical and demographic predictors of skeletal muscle depletion, evaluate the survival impact of skeletal muscle depletion in patients with minimal nutritional risk or good performance status, and finally, benchmarking SMI values of patients with HNC against healthy young adults. METHODS: Population cohort of 1231 consecutive patients and external validation cohorts with HNC had lumbar SMI measured by cross-sectional imaging. Optimal stratification determined sex-specific thresholds for 2-levels of SMI depletion (Class I and II) based on overall survival (OS). Adjusted multivariable regression analyses (tumor site, stage, performance status, age, sex, dietary intake, weight loss) determined relationships between 2-levels of SMI depletion and OS. RESULTS: Mean SMI (cm2/m2) was 51.7 ± 9.9 (males) and 39.8 ± 7.1 (females). The overall and sex-specific population demonstrated an increased risk of mortality associated with decreasing SMI. Sex-specific SMI (cm2/m2) depletion thresholds for 2-levels of muscle depletion determined by optimal stratification for males and females, respectively (male: 45.2-37.5, and <37.5; female: 40.9-34.2, and <34.2). In the overall population, Normal SMI, Class I and II SMI depletion occurred in 65.0%, 24.0%, and 11.0%, respectively. Median OS was: Normal SMI (114 months, 95% CI, 97.1-130.8); Class I SMI Depletion (42 months, 95% CI, 28.5-55.4), and Class II SMI Depletion (15 months, 95% CI, 9.8-20.1). Adjusted multivariable analysis compared with Normal SMI (reference), Class I SMI Depletion (HR, 1.49; 95% CI, 1.18-1.88; P < .001), Class II SMI Depletion (HR, 1.91; 95% CI, 1.42-2.58; P < .001). CONCLUSIONS: Moderate and severe SMI depletion demonstrate discrimination in OS in patients with HNC. Moderate and severe SMI depletion is prevalent in patients with minimal nutrition risk and good performance status. Benchmarking SMI values against healthy young adults exemplifies the magnitude of SMI depletion in patients with HNC and may be a useful method in standardizing SMI assessment.

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

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

Involvement of TGFBI-TAGLN axis in cancer stem cell property of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a significant healthcare burden globally. Previous research using single-cell transcriptome analysis identified TGFBI as a crucial marker for the partial-epithelial-mesenchymal transition (partial-EMT) program. However, the precise role of TGFBI in HNSCC progression remains unclear. Therefore, our study aimed to clarify the impact of TGFBI on the malignant behavior of HNSCC cells. Through RNA-sequencing data from the TCGA database, we validated that increased TGFBI expression correlates with a higher occurrence of lymph node metastasis and unfavorable prognosis in HNSCC cases. Functional experiments demonstrated that TGFBI overexpression enhances the ability of sphere formation, indicating stem-cell-like properties. Conversely, TGFBI depletion reduces sphere formation and suppresses the expression of cancer stem cell (CSC) markers. RNA-sequencing analysis of TGFBI-overexpressing and control HNSCC cells revealed TAGLN as a downstream effector mediating TGFBI-induced sphere formation. Remarkably, TAGLN depletion abolished TGFBI-induced sphere formation, while its overexpression rescued the suppressed sphere formation caused by TGFBI depletion. Moreover, elevated TAGLN expression showed correlations with the expression of TGFBI and partial-EMT-related genes in HNSCC cases. In conclusion, our findings suggest that TGFBI may promote CSC properties through the upregulation of TAGLN. These novel insights shed light on the involvement of the TGFBI-TAGLN axis in HNSCC progression and hold implications for the development of targeted therapies.

Utilizing the AJCC 8th Staging to Discriminate Survival Outcomes in HPV-associated Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: The American Joint Committee on Cancer (AJCC) staging 8th edition introduced major changes in the TNM staging of oropharyngeal squamous cell carcinoma (OPSCC) based on the human papillomavirus (HPV) status. This study aimed to observe how well the AJCC staging 8th edition precisely discriminates survival outcomes in patients with HPV-associated OPSCC using a large population database. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database between 2010 and 2016, 7,448 patients with HPV-associated OPSCC were enrolled. Patients diagnosed with OPSCC and tested positive for HPV with information on the TNM staging according to the AJCC staging 7th edition were selected. Next, T-, N-, and clinical staging were reconstructed based on the AJCC staging 8th edition. Survival probabilities in both AJCC staging 7th and 8th editions were estimated and compared. RESULTS: Most patients (93.44%) were down-staged from the 7th to the 8th edition. The AJCC staging 8th edition showed more discriminatory power in predicting survival of patients with HPV-associated OPSCC than the AJCC staging 7th edition, regardless of the primary subsites. Additionally, clinical stage I patients with HPV-associated OPSCC according to the AJCC 8th edition showed better prognosis in case of high T staging than high N staging. Clinical staging according to the AJCC 8th edition compared to that of the 7th edition was an independent prognostic factor in patients with HPV-associated OPSCC. CONCLUSION: This study emphasizes the advantages of the new classification system for discriminating survival in HPV-associated OPSCC according to various factors.

Cell fusion between tumor cells and macrophages promotes the metastasis of OSCC patient through the activation of the chemokine signaling pathway.

BACKGROUND: Tumor metastasis is responsible for the high mortality rate of patients with oral squamous cell carcinoma (OSCC). Although many hypotheses have been proposed to elucidate the mechanism of tumor metastasis, the origin of the metastatic tumor cells remains unclear. In this study, we explored the role of cell fusion in the formation of OSCC metastatic tumor cells. METHODS: Murine OSCC tumor cells and macrophages were fused in vitro, and the cell proliferation, migration, and phagocytosis abilities of hybrid cells and parental cells were compared. Subsequently, we compared the transcriptome differences between hybrid and parental cells. RESULTS: Murine OSCC tumor cells and macrophages were successfully fused in vitro. The cytological and molecular experimental results revealed that OSCC tumor cells obtained a migration-related phenotype after fusion with macrophages, and the migration ability of hybrid cells was related to the activation of the "chemokine signal pathway". CONCLUSION: After fusion with macrophages, the chemokine signaling pathway in OSCC tumor cells was activated, leading to metastasis.

Comparison of the prognostic value of lymph node yield, lymph node ratio, and number of lymph node metastases in patients with oral squamous cell carcinoma.

BACKGROUND: The aim of this study was to assess the prognostic significance of lymph node yield (LNY), lymph node ratio (LNR), and the number of lymph node metastases (LNMs) in patients affected by oral squamous cell carcinoma (OSCC). METHODS: The study included patients who underwent surgical treatment for primary OSCC. Receiver operating characteristic curves were generated to determine the optimal threshold values. Kaplan-Meier curves were employed, along with the log-rank test, for the analysis of survival. To compare the performance in terms of model fit, we computed Akaike's information criterion (AIC). RESULTS: This study enrolled 429 patients. Prognostic thresholds were determined at 22 for LNY, 6.6% for LNR, and 3 for the number of LNMs. The log-rank test revealed a significant improvement in both overall survival and progression-free survival for patients with a LNR of ≤6.6% or a number of LNMs of ≤3 (p < 0.05). Interestingly, LNY did not demonstrate prognostic significance. The AIC analyses indicated that the number of LNMs is a superior prognostic indicator compared to LNY and LNR. CONCLUSIONS: Incorporating LNR or the number of LNMs into the TNM classification has the potential to improve the prognostic value, as in other types of cancers. Particularly, the inclusion of the number of LNMs should be contemplated for future N staging.

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

BACKGROUND: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. METHODS: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. RESULTS: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). CONCLUSIONS: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.

Macroscopy of specimens from the head and neck.

Macroscopic examination of surgical resections from the head and neck may be difficult due to the complex anatomy of this area. Recognition of normal anatomical structures is essential for accurate assessment of the extent of a disease process. Communication with the surgical team, correct specimen orientation and sampling are critical for assessment and the importance of radiological and clinical correlation is emphasised. Tumour involvement at each subsite is highlighted with reference to where there are implications on pathological staging and the potential need for adjuvant therapy.

Computed tomography/magnetic resonance imaging for mandibular boundary invasion of oral squamous cell carcinoma assessment.

BACKGROUND: The range of mandibular invasion by a tumour needs to be determined accurately to minimize unnecessary damage to the mandible. This study aimed to compare tumour boundary lines on computed tomography/magnetic resonance (CT/MR) images with those from pathological findings during the preoperative assessment of mandibular invasion by oral squamous cell carcinoma (OSCC). By comparing the methods, the potential of CT/MR for this application could be further elucidated. METHODS: Eight patients with OSCC were imaged with CT/MR, mandibular specimens were collected, and the material site was measured. Haematoxylin-eosin staining was used for histopathological assessment. The presence and boundaries of bone invasion were evaluated. The CT/MR and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CT/MR and histopathological boundaries using the Fréchet distance. RESULTS: The mean Fréchet distance between the CT and pathological tumour boundaries was 2.69 mm (standard error 0.46 mm), with a minimum of 1.18 mm, maximum of 3.64 mm, median of 3.10 mm, and 95% confidence interval of 1.40-3.97 mm. The mean Fréchet distance between the tumour boundaries on the MR and pathological images was 3.07 mm (standard error 0.56 mm), with a minimum of 1.53 mm, maximum of 4.74 mm, median of 2.90 mm, and 95% confidence interval of 1.53-4.61 mm. CONCLUSIONS: CT/MR imaging can provide an effective preoperative assessment of mandibular invasion of OSCC. Pathology images can be positioned on CT/MR scans with the help of computer software to improve the accuracy of the findings. The introduction of the Fréchet distance to compare tumour boundary lines is conducive to computer image diagnosis of tumour invasion of jaw boundaries.

Role of primary tumor volume and metastatic lymph node volume in response to curative effect of definitive radiotherapy for locally advanced head and neck cancer.

BACKGROUND: Studies have shown mixed results concerning the role of primary tumor volume (TV) and metastatic lymph node (NV) volume in response to the curative effect of definitive radiotherapy for locally advanced head and neck squamous cell carcinoma (LAHNSCC). OBJECTIVE: We aimed to evaluate the impact of TV and NV on the efficacy of radical radiotherapy in LAHNSCC patients, with the goal of guiding individualized therapy. PATIENTS AND METHODS: Patients with LAHNSCC who received radical radiation therapy and were reexamined within 6 months post-therapy from January 2012 to December 2021 were selected. The volumes of the primary tumors and metastatic lymph nodes were calculated by software and then were divided into a large TV group vs small TV group and a large NV group vs small NV group according to the relationship with the median. Additionally, patients who received concurrent chemoradiotherapy (CCRT) or not were divided into the CCRT group and the radiotherapy (RT) group. Patients with lymph node metastasis were divided into node concurrent chemotherapy (N-CCRT) group and a node metastatic chemotherapy (N-RT) group according to whether they received concurrent chemotherapy or not. The volume shrinkage rate (VSR), objective response rate (ORR), local control rate (LCR) and overall survival (OS) were recorded and analyzed. RESULTS: 96 patients were included in the primary tumor volume group, and 73 patients were included in the metastatic lymph node group. Receiver operating characteristic (ROC) curves were constructed for objective remission (OR) endpoints, and a volume threshold was defined for TV and NV patients. The threshold primary tumor volume was 32.45 cm3, and the threshold metastatic lymph node volume was 6.05 cm3.The primary TV shrinkage rates of the small TV and the large TV groups were basically the same, P = 0.801. Similarly, the ORR and LCR were not significantly different between the small TV group and the large TV group (PORR = 0.118, PLCR = 0.315). Additionally, the TV shrinkage rate did not significantly differ between the CCRT group and the RT group, P = 0.133. Additionally, there was no significant difference in ORR or LCR in CCRT group (PORR = 0.057, PLCR = 0.088). However, the metastatic lymph node volume shrinkage rate in the small NV group was significantly greater than that in the large NV group (P = 0.001). The ORR and LCR of the small NV subgroup were significantly greater than those of the large NV subgroup (PORR = 0.002, PLCR = 0.037). Moreover, compared with that of the N-RT group, the NV shrinkage rate of the N-CCRT group was 84.10 ± s3.11%, and the shrinkage rate was 70.76 ± s5.77% (P = 0.047). For the ORR and LCR, the N-CCRT group and N-RT group were significantly different (PORR = 0.030, PLCR = 0.037). The median OS of the whole group was 26 months. However, neither TV/NV nor concurrent chemotherapy seemed to influence OS. CONCLUSION: Primary tumor volume is not a prognostic factor for the response to curative effect radiotherapy in LAHNSCC patients. Nevertheless, metastatic lymph nodes are a prognostic factor for the response to curative effect radiotherapy in LAHNSCC patients. Patients with smaller lymph nodes have better local control.

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

BACKGROUND: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth. METHODS: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system. FINDINGS: Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo. CONCLUSIONS: Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes. FUNDING: 1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).

Postoperative Radiotherapy and Survival in Oral Cavity Squamous Cell Carcinoma With Mandibulectomy.

Importance: Oral cavity squamous cell carcinoma (SCC) tumors with mandibular invasion are upstaged to pT4a regardless of their size. Even small tumors with boney invasion, which would otherwise be classified as pT1-2, are recommended for the locally advanced treatment pathway to receive administration of postoperative radiotherapy (PORT). Objective: To evaluate the association of PORT with overall survival according to tumor size among patients who received mandibulectomy for pT4aN0 oral cavity SCC. Design, Setting, and Participants: This was a retrospective analysis using data from the US National Cancer Database from January 1, 2004, through December 31, 2019. All patients who received mandibulectomy for treatment-naive pT4aN0 oral cavity SCC with negative surgical margins were included. Data analyses were performed in January 2023 and finalized in July 2023. Exposure: PORT vs no PORT. Main Outcomes and Measures: Entropy balancing was used to balance covariate moments between treatment groups. Weighted multivariable Cox proportional hazards regression was used to measure the association of PORT with overall survival associated with tumor size. Results: Among 3268 patients with pT4aN0 oral cavity SCC (mean [SD] age, 65.9 [12.1] years; 2024 [61.9%] male and 1244 [38.1%] female), 1851 (56.6%) received PORT and 1417 (43.4%) did not receive PORT. On multivariable analysis was adjusted for age, insurance status, Charlson Comorbidity Index score, tumor site, tumor grade, tumor size, and PORT. Findings indicated that PORT was associated with improved overall survival and that this relative survival advantage trended upwards with increasing tumor size. That is, the larger the tumor, the greater the survival advantage associated with the use of PORT. For the 1068 patients with tumors greater than 4 cm, the adjusted hazard ratio (aHR) in favor of PORT was 0.63 (95% CI, 0.48-0.82); for the 1774 patients with tumors greater than 2 cm but less than or equal to 4 cm, the aHR was 0.76 (95% CI, 0.62-0.93); and for 426 patients with tumors less than 2 cm, the aHR was 0.81 (95% CI, 0.57-1.15). Conclusions and Relevance: In this retrospective analysis of patients who received mandibulectomy for pT4aN0 oral cavity SCC, PORT was associated with improved overall survival, the benefit of which improved relatively with increasing tumor size. These findings suggest that tumor size should be considered in guidelines for PORT administration in this patient population.

Tumor-stroma ratio in preoperative biopsies and matched surgical specimens in oral squamous cell carcinoma: Concordance and impact on recurrence-free and overall survival.

Stroma-richness is commonly associated with decreased survival times as well as advanced tumor stages in various malignant tumors. A previous study on laryngeal squamous cell carcinomas showed very good agreement for tumor-stroma ratio assessment between pre-treatment biopsies and resection specimens. We therefore aimed to determine whether similar results could be shown for oral squamous cell carcinomas. 107 preoperative biopsies and matched surgical specimens were obtained from the histological archive, dating from 2011-2022. Tumor-stroma ratio was determined on all samples and cases were divided into stroma-rich (≥50% stroma) and stroma-poor (<50% stroma). Results were then correlated with recurrence-free and overall survival. Tumor-stroma ratio showed substantial agreement between preoperative biopsies and surgical specimens with a kappa correlation coefficient of 0.643. Concerning preoperative biopsies, 28 cases were stroma-rich (26.2%), in the group of tumor resections, 32 cases were stroma-rich (29.9%). No association with either recurrence-free or overall survival could be shown for both groups (p-values 0.158-0.495). Concordance between pre-treatment biopsies and resections was substantial in our study, however, as no association with survival times could be demonstrated, the prognostic significance in our cohort remains unclear. This might be attributable to the fact that almost 75% of our patients presented with early-stage tumors, which sometimes seem to show a less pronounced prognostic effect of the tumor-stroma ratio.

The prognostic role of single cell invasion and nuclear diameter in early oral tongue squamous cell carcinoma.

BACKGROUND: The clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC). METHODS: We used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC. RESULTS: Single cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224-3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080-2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216-3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067-2.538, P = 0.024). CONCLUSION: Single cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.

Traumatic Ulcerative Granuloma with Stromal Eosinophilia on the Tongue.

BACKGROUND: Traumatic Ulcerative Granuloma with Stromal Eosinophilia, commonly known as Eosinophilic Ulcer, is a reactive solitary and self-limiting benign lesion. It manifests as a punched-out ulcer with a distinct surrounding indurated border, often raising concerns about malignancy. METHODS: A 44-year-old male presented with a painless, indurated tongue ulcer evolving over three months. Despite being asymptomatic, the patient underwent an incisional biopsy due to suspicions of oral squamous cell carcinoma. RESULTS: Histological analysis revealed a disrupted epithelial lining, dense necrotic connective tissue, and a fibrino-purulent pseudomembrane. Proximal to the ulcer, a collar-like projection of reactive epithelial tissue hyperplasia was noted, accompanied by mononuclear cells and a predominantly histiocytic infiltrate in the submucosal layer surrounding skeletal muscle fibers. The final diagnosis was Traumatic Ulcerative Granuloma with Stromal Eosinophilia. Remarkably, the lesion spontaneously healed within 2 weeks post-biopsy, with no recurrence over 6 months. CONCLUSION: This case emphasizes considering this benign condition in the differential diagnosis of oral ulcers, highlighting the importance of accurate histopathological evaluation to rule out cancer.