Early Stage Tongue Cancer Research Articles

Assessment of oncologic and cosmetic outcomes of robotic elective neck dissection in early-stage tongue cancer

BackgroundRobotic neck dissection is emerging as an alternative to conventional open neck dissection. However, the oncologic safety of robotic elective neck dissection (END) and its indications in early-stage tongue cancer are unclear. MethodsWe retrospectively reviewed the data of 78 patients who underwent transoral excision for T1, T2 squamous cell carcinoma of tongue with simultaneous ipsilateral END. Patients were assigned to two groups: the robotic group (n = 32)—postauricular face-lift —and the conventional group (n = 46)— transcervical incision. We compared the survival, clinical, pathologic and cosmetic outcomes of the two groups, and evaluated the number of retrieved lymph nodes and robot console time in the robotic group. ResultsThe mean age was lower in the robotic group (43.6 ± 12.8 vs. 55.8 ± 14.0, p < 0.001) and the conventional group had more T2 patients (p = 0.01). The mean operation time was significantly longer in the robotic group than the conventional group (178.81 ± 33.9 vs. 92.28 ± 16.7, p < 0.001). The mean number of retrieved lymph nodes was not significantly different between the two groups (19.22 ± 8.51 vs. 20.7 ± 11.4, p = 0.41). The 5-year disease-free survival rate was not significantly different between the two groups (93.6 % vs. 82.9 %, p = 0.59). Overall scar satisfaction assessed by VAS score, the robotic group showed significantly better results compared to the conventional group (8.38 vs. 5.86, p = 0.033). ConclusionRobotic END by a postauricular facelift approach is a feasible and safe approach for early-stage tongue cancer.

A CT-based integrated model for preoperative prediction of occult lymph node metastasis in early tongue cancer.

Occult lymph node metastasis (OLNM) is an essential prognostic factor for early-stage tongue cancer (cT1-2N0M0) and a determinant of treatment decisions. Therefore, accurate prediction of OLNM can significantly impact the clinical management and outcomes of patients with tongue cancer. The aim of this study was to develop and validate a multiomics-based model to predict OLNM in patients with early-stage tongue cancer. The data of 125 patients diagnosed with early-stage tongue cancer (cT1-2N0M0) who underwent primary surgical treatment and elective neck dissection were retrospectively analyzed. A total of 100 patients were randomly assigned to the training set and 25 to the test set. The preoperative contrast-enhanced computed tomography (CT) and clinical data on these patients were collected. Radiomics features were extracted from the primary tumor as the region of interest (ROI) on CT images, and correlation analysis and the least absolute shrinkage and selection operator (LASSO) method were used to identify the most relevant features. A support vector machine (SVM) classifier was constructed and compared with other machine learning algorithms. With the same method, a clinical model was built and the peri-tumoral and intra-tumoral images were selected as the input for the deep learning model. The stacking ensemble technique was used to combine the multiple models. The predictive performance of the integrated model was evaluated for accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC-ROC), and compared with expert assessment. Internal validation was performed using a stratified five-fold cross-validation approach. Of the 125 patients, 41 (32.8%) showed OLNM on postoperative pathological examination. The integrated model achieved higher predictive performance compared with the individual models, with an accuracy of 84%, a sensitivity of 100%, a specificity of 76.5%, and an AUC-ROC of 0.949 (95% CI [0.870-1.000]). In addition, the performance of the integrated model surpassed that of younger doctors and was comparable to the evaluation of experienced doctors. The multiomics-based model can accurately predict OLNM in patients with early-stage tongue cancer, and may serve as a valuable decision-making tool to determine the appropriate treatment and avoid unnecessary neck surgery in patients without OLNM.

A Study of the Prognostic Factors for Late Cervical Lymph Node Metastasis and Distant Metastasis in Patients with cT1-2N0 Tongue Cancer.

Background: Early-stage tongue cancer has a good prognosis in general; however, high-risk patients with late cervical lymph node and distant metastases have a poor prognosis. Elective neck dissection and postoperative chemoradiotherapy are considered for these patients, although no clear criteria have been identified for their evaluation. Methods: This retrospective observational study aimed to determine the predictive factors for late cervical lymph node and distant metastases in 102 patients with cT1-2N0 tongue cancer. The data regarding the demographic characteristics, as well as the depth of invasion, tumor budding, histological grade, and tumor-stromal ratio, among other things, were extracted from medical records. Results: We found that the potential lymph node metastasis rate was 27.5%. The significant clinical predictors of late cervical lymph node metastasis were the tumor thickness and endophytic growth pattern and the significant histopathological factors were poorly and moderately differentiated tumors and ≥3 tumor buds. In addition, the prognostic factors for distant metastasis included ≥4 lymph node metastases, ≥7 tumor budding, and moderate and poor tumor differentiation. Conclusions: The usefulness of tumor budding as a predictor of metastasis for tongue cancer was suggested. The findings of this study can help establish the criteria for evaluating the metastasis risk and prognosis of patients with tongue cancers.

Risk factors for late postoperative bleeding after partial glossectomy for tongue cancer

Background Partial glossectomy is the most common procedure for early-stage tongue cancer. Although late postoperative bleeding occasionally occurs, the associated risk factors have not been adequately identified. Aims/objectives We aimed to investigate the rate and risk factors for late postoperative bleeding after transoral partial glossectomy with or without neck dissection for tongue cancer at our institution. Material and methods We analysed 211 patients who had undergone transoral partial glossectomy between January 2016 and January 2023. The potential risk factors associated with late postoperative bleeding were investigated using univariate and multivariate logistic regression analyses. Results Of the 211 patients, 40 (19%) showed late postoperative bleeding, with 19 (9%) classified as grade IIIa (Clavien-Dindo classification). Regarding all grades, late postoperative bleeding was significantly higher in patients aged <70 years and in those with polyglycolic acid (PGA) sheets (p = .046 and .030, respectively). For grade ≥ IIIa, late postoperative bleeding was significantly higher in patients with a history of anticoagulant/platelet administration, a mucosal defect covered with fibrin glue and a PGA sheet (p = .045 and .026, respectively). Conclusions and significance The findings of this study suggest that primary closure decreases the frequency of late postoperative bleeding.

Sentinel Node Biopsy detecting occult Metastasis on early stage Tongue Cancer: Case Report and Surgical technique

Sentinel Node Biopsy detecting occult Metastasis on early stage Tongue Cancer: Case Report and Surgical technique

Prognostic significance of the FSTL1-DIP2A axis in early-stage tongue cancer.

In tongue cancer, many patients already have metastasis at the time of diagnosis, and such cases are usually unresponsive to treatment, resulting in a poor prognosis. Therefore, there is an urgent need to develop more effective diagnostic and therapeutic methods to cure tongue cancer at the earliest possible stage in clinical practice. Follistatin-like 1 (FSTL1) is known as a negative effector molecule that induces and enhances the refractoriness of cancer cells directly and indirectly via suppressing anti-tumor immunity in various types of cancer. However, the molecular expression, functions, and clinical significance of FSTL1 and its receptor DIP2A in tongue cancer remains to be elucidated. In this study, we revealed that FSTL1, which is highly expressed in tongue cancer cells, plays a key role in its malignancy and is a significant risk factor for recurrence of early-stage tongue cancer. Basic study shows that FSTL1 is abundantly produced from human tongue cancer cell lines, and blocking FSTL1 with specific siRNAs or mAb significantly suppresses cellular functions. Clinical study shows that both FSTL1 and its receptor DIP2A are highly and correlatively expressed in tumor tissues of tongue cancer patients, and high expression levels of both in stage I tumors are significantly associated with shorter relapse-free survival. These suggest that targeting the FSTL1-DIP2A axis may be useful as a biomarker for early prediction of prognosis in tongue cancer patients, and as a therapeutic target for developing new drugs to treat tongue cancer more effectively. This strategy will contribute to improving clinical outcomes in tongue cancer.

A prediction of late cervical lymph node metastasis by ultrasound images of tongue cancer using deep learning method

ObjectiveOccult cervical lymph node metastasis is an important prognostic factor in squamous cell carcinoma of the tongue and is related to factors such as depth of invasion and angiogenesis. The objective of this study was to evaluate the performance of deep learning for predicting occult cervical metastasis from brightness mode (B-mode) ultrasound images of early-stage tongue cancer. Methods50 patients with early-stage tongue cancer who underwent ultrasound guided partial glossectomy at the Department of Oral Surgery at Saitama Cancer Center between 2015 and 2019 were divided into two groups: those with metastasis (n = 22) and those without metastasis (n = 28). B-mode ultrasound images of each patient's tongue cancer were cropped to a 128 × 128-pixel square, and images were assigned to training or testing data in an 8:2 ratio. The training iteration generation (number of epochs) was set to 120 using Neural Network Console software (Sony Corporation), and the resulting learning model was produced. Testing data were input into the learning model to evaluate its performance in predicting metastasis. ResultsPrediction of occult cervical lymph node metastasis by deep learning using B-mode ultrasound images had 79.8 % accuracy, 78.4 % sensitivity, 80.8 % specificity, 74.4 % positive predictive value, and 84.0 % negative predictive value. ConclusionThese findings suggest that deep learning using ultrasound images is useful for predicting postoperative cervical lymph node metastasis from tongue cancer.

WPOI-4/5 Correlates With Lymph Node Recurrence and Poor Prognosis in Early-stage Tongue Squamous Cell Carcinoma.

Neck management in patients with early-stage tongue cancer remains controversial. The worst pattern of invasion (WPOI) of the primary tumor has been associated with the incidence of regional metastasis. We investigated the prognostic role of WPOI, especially in relation to regional lymph node recurrence and disease-specific survival (DSS). We retrospectively reviewed medical records and evaluated tumor specimens of 38 patients with early-stage tongue cancer who underwent primary tumor resection without elective neck dissection. Regional lymph node recurrence rates were significantly higher in patients with WPOI-4/5 compared with WPOI-1 to -3. The 5-year DSS rates were significantly higher for WPOI-1 to -3 than for WPOI-4/5. Notably, patients with WPOI-1 to -3 achieved a 100% 5-year DSS rate with salvage neck dissection and postoperative treatment, even those with cervical lymph node recurrence, whereas patients with WPOI-4/5 had a poorer prognosis. Patients with WPOI-1 to -3 tumors can be followed up without neck dissection until regional lymph node recurrence is detected, with a good course after salvage treatment. In contrast, patients with WPOI-4/5 tumors who are followed up until the appearance of regional lymph node recurrence have a poor prognosis, even with adequate treatment for recurrent disease.

Lymphocytic Host Response and other Prognostic Factors in Early Stage Squamous Cell Carcinoma of Tongue: Retrospective Analysis from a Tertiary Cancer Center.

Aswin Anapathoor NagarajanIntroduction The tongue is the most common site of malignancy in the oral cavity, and squamous cell carcinoma is the commonest histology. The prognosis remains unfavorable despite treatment, resulting in higher mortality rates. Early stage carcinoma of the tongue is a distinct entity and is primarily treated with either surgery or radiotherapy. Various factors have been implicated in the prognosis of early stage tongue carcinomas. The main objective of this study is to access whether the lymphocytic host response (LHR) and other prognostic factors influence the survival. Patients and Methods The data of 129 patients with Stage I and Stage II (T1-2, N0) tongue cancer treated in our institute from January 2012 to December 2016 were retrospectively abstracted from the hospital case records. The various clinical and pathological factors were recorded. The Kaplan-Meier model was used for survival analysis. The disease-free survival (DFS) and the overall survival (OS) with respect to stage and LHR were calculated. Results On multivariate analysis, site of lesion, comorbidities, habits, grade of the tumor, perineural infiltration (PNI) did not influence the survival. The main factor which was found to be significant in DFS was LHR. The DFS was better for the patients who had lymphocytic infiltration of ≥ 70% (strong LHR) when compared with <70%(weak LHR) ( p = 0.037). The OS with respect to stage ( p = 0.608) and LHR ( p = 0.164) was not found to be statistically significant. Conclusion The patients with weak LHR had less DFS when compared with patients with strong LHR. Larger studies are needed to evaluate whether adding adjuvant therapy may benefit the patients with weak LHR in early stage tongue cancer.

Comparison of T1/2 Tongue Carcinoma with or without Radial Forearm Flap Reconstruction Regarding Post-Therapeutic Function, Survival, and Gender.

Flap reconstruction is commonly used in advanced tongue carcinoma in order to compensate for the loss of tongue tissue and function. Surprisingly, a large number of reconstructed early-stage tongue cancer can be found. Survival or functional benefits in these cases remain unclear. A retrospective data analysis of 384 surgically treated tongue carcinoma patients was conducted aiming to find epidemiologic and survival differences between patients with (n = 158) or without flap reconstruction (n = 226). A prospective functional analysis was performed on 55 early-stage tongue cancer patients, 33 without and 22 with radial-forearm flap reconstruction, focusing on post-therapeutic swallowing function as the primary endpoint, speech as the secondary endpoint, xerostomia, quality of life, and mouth opening. Consistent with the current literature, we demonstrated the significantly more frequent use of flap grafts in advanced tongue carcinomas. For the first time, we depicted a higher female ratio in the reconstructed group (p = 0.02). There were no significant differences in survival or functional outcomes between the groups. The none-reconstructed group showed more frequent use of adjuvant C/RT despite presenting fewer N+ stages. The higher female ratio in the reconstruction group is plausible due to the anatomically smaller oral cavity and relatively larger carcinoma in women. A higher presence of close margins in the none-reconstruction group may explain the more frequent use of adjuvant C/RT. Since we found no survival or functional differences between the groups, we propose a critical approach toward flap reconstruction in T1/2 tongue carcinoma. At the same time, proportional aspects and adequate resection margins should be taken into account.

Application value of indocyanine green fluorescence in sentinel lymph node biopsy for early-stage tongue cancer and oropharyngeal cancer.

Occult cervical lymph node metastasis is the most important reason for recurrence of early-stage tongue cancer and oropharyngeal cancer. Cervical sentinel lymph node (SLN) biopsy may help to identify them. Pigment dyes and radionuclide were used to label SLN. Both of them had shortage. This study aims to investigate the application and clinical value of indocyanine green fluorescence imaging in cervical SLN biopsy for patients with early-stage tongue cancer and oropharyngeal cancer. Retrospective analysis was conducted on 23 patients with early tongue cancer and oropharyngeal cancer, who received surgical treatment and used indocyanine green as a tracer to find SLN in Hunan Cancer Hospital from April to October 2021. The detection rate of SLN was calculated and the distribution of SLN in different regions of the neck was analyzed. SLN was successfully identified in 22 of 23 patients, with a detection rate of 95.65%. Among these 22 patients, 3 patients were found to have cancer metastasis, and the rate of occult lymph node metastasis was 13.63%. No pathologically positive lymph nodes were detected in SLN-negative patients, and thus the positive predictive rate was 100%. For patients with primary lesions located in the anterior 2/3 of the tongue, the constituent ratios of SLN in neck area I, II, III, and IV were 15.15%, 71.72%, 13.13%, and 0, respectively. For patients with primary lesions located in base of the tongue, the constituent ratios of SLN in neck area I, II, III, and IV were 0, 44.44%, 44.44%, and 11.12%, respectively. Indocyanine green fluorescence imaging has a high detection rate with accurate positive prediction in the anterior cervical SLN biopsy in patients with early-stage tongue cancer and oropharyngeal cancer. Meanwhile, it can also reflect the lymphatic drainage of tumors located at different primary sites, which has high clinical value.

The Expression of Defensin-Associated Genes May Be Correlated With Lymph Node Metastasis of Early-Stage Tongue Cancer.

We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P<0.01; fold change >2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. . Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.

Prediction of nodal metastasis based on intraoral sonographic findings of the primary lesion in early-stage tongue cancer

The aim of this study was to clarify the correlation between imaging findings obtained using intraoral ultrasonography (US) and pathological findings of tongue cancers, and to examine the predictive value of intraoral US findings with respect to occult nodal metastasis. This was a retrospective study based on the medical records of 123 patients with T1–2N0 tongue cancer. The depth of invasion (DOI) on intraoral US was positively correlated with the pathological invasion depth (PID) (ρ = 0.7080, P < 0.0001). Receiver operating characteristic analyses revealed an optimal DOI cut-off value of 4.1 mm and optimal PID cut-off value of 3.9 mm to detect nodal metastasis. Regarding the margin shape of the primary tumour on intraoral US, the incidence of nodal metastasis was significantly higher for the permeated type than for the pressure type (P < 0.001) and wedge-shaped type (P = 0.002). Furthermore, tumours with peritumoural vascularity assessed by power Doppler US had a significantly higher incidence of nodal metastasis than tumours without (P = 0.003). The sensitivity, specificity, and accuracy of the permeated type to predict nodal metastasis was 53.6%, 95.8%, and 86.2%, respectively. These results suggest that intraoral US findings closely reflect pathological findings and could be useful to predict occult nodal metastasis in patients with early-stage tongue cancer.

Ultrasound-guided microwave ablation in the treatment of early-stage tongue cancer.

BackgroundTongue cancer is a common malignant tumor of the head and neck. Its treatment methods include surgery, radiotherapy, and chemotherapy. However, these treatments have serious side effects and poor cosmetic effect, so it is urgent to find new treatment methods. We pioneered the use of microwave ablation (MWA) in the treatment of early tongue cancer and achieved good results.Case PresentationA 67-year-old woman (Han nationality) was admitted to the hospital because of progressive aggravation of tongue pain. She had a history of tongue pain of more than 1 year. Pathological biopsy showed squamous cell carcinoma; following this, radical operation of the tongue cancer was planned. The preoperative examination showed thyroid occupation in the upper mediastinum region compressing the airway; hence, the risk of general anesthesia was high. Consent was obtained from the patient and her family. Ultrasound-guided MWA was successfully performed under the lingual nerve block. The patient was followed for 1 year. She recovered well with no dysphagia and unclear articulation symptoms, and the cosmetic effect was excellent.ConclusionTo our knowledge, this is the first case of using MWA for the treatment of early-stage tongue cancer (ESTC). Ultrasound-guided MWA may be used for ESTC that can completely ablate the tumor and retain the function of the tongue, further improving the quality of life of the patient. However, it is only a case report and needs more research to verify the use of MWA in ESTC.

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.

Value of preoperative computed tomography in predicting the local staging of cancer of the tongue at primary surgery.

Preoperative staging is essential for the planning of treatment of cancer. This study was designed to evaluate the accuracy of computed tomography (CT) in predicting the local stage of tongue cancer by comparing it with the gold standard of histopathology. A total of 233 patients with newly-diagnosed tongue cancer was retrospectively reviewed, and the size of the tumour and the status of the cervical lymph node were compared between CT images and histopathological results. Patients with stage II cancer were followed up to assess the influence of inaccurate preoperative staging on prognosis. The accuracy of local staging by CT was 47.6% (111/233), with 59.7% (139/233) for tumour stage, and 70.4% (164/233) for nodal stage. The greatest dimension of the tumour on the CT image was about 2mm less than that measured by histopathology. The estimated volume of tumour was a quarter smaller. The accuracy of predicting malignant lymph nodes by CT was 68.9% (n=161). Among patients with stage II disease, simultaneous neck dissection was less likely in the understaged group than in the accurately staged one. The reoperation rate was a little higher but not significantly so. We conclude that the accuracy of CT in predicting local staging for tongue cancer was only moderate, because it underestimated the size of the tumour and needed to improve the criteria for detecting malignant lymph nodes. Understaging on CT images may influence the prognosis of patients with early stage tongue cancer.

Conformal radiotherapy in combination with cetuximab for stage Т1–2 tongue cancer with N1–2b regional metastases detected after preventive lymphadenectomy

The study objective is to analyze the experience of conformal radiotherapy in combination with cetuximab for cervical lymph node (LN) metastasis in patients with early-stage tongue cancer who had undergone multicomponent surgeries.Materials and methods. This retrospective study included 48 patients with primary squamous cell carcinoma of the tongue (Т1–2) that were treated in Nizhny Novgorod Regional Clinical Oncology Dispensary between 2012 and 2019. The experimental group comprised 25 patients who underwent hemiglossectomy with simultaneous preventive cervical lymph node dissection. The control group was composed of 23 patients who underwent hemiglossectomy alone due to the presence of concomitant somatic pathology. Before surgery, none of the patients had any signs of metastatic lesions in the cervical LNs according to the results of clinical and instrumental examinations. After surgery, 100 % of patients from the experimental group were found to have N1–2b cervical LN metastases at histological examination. Patients from the control group developed clinical signs of cervical LN metastasis within a year after operation. All patients underwent radiotherapy. The experimental group was divided into two subgroups: patients from subgroup 1 (n = 11) received cetuximab due to disease progression, whereas patients from subgroup 2 (n = 14) received cisplatin. Participants from the control group received no chemotherapy due to their concomitant somatic disorders and because regional metastasis was not confirmed.Results. In the control group, the time between surgery and patient’s death varied between 8 and 14 months. Patients from subgroups 1 and 2 survived for 12–60 months and 8–48 months respectively. So far, 9 patients from subgroup 1 and 6 patients from subgroup 2 are alive. Among them, 8 participants from subgroup 1 and 4 participants from subgroup 2 have no signs of disease progression. Three patients from subgroup 2 died of cardiovascular diseases (they had no cancer progression within 3 months after the completion of chemotherapy).Conclusion. Preventive lymph node dissection in patients with stage Т1–2 tongue cancer enables early detection of subclinical N1–2b metastases and ensures timely initiation of therapy. Our experience confirmed safety of cetuximab plus radiotherapy used to improve disease control and increase patient’s survival.

Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach

Head and neck squamous cell carcinomas (HNSCC) includes multiple subsites that exhibit differential treatment outcome, which is in turn reflective of tumor stage/histopathology and molecular profile. This study hypothesized that the molecular profile is an accurate prognostic adjunct in patients triaged based on clinico-pathological characteristics. Towards this effect, publically available micro-array datasets (n = 8), were downloaded, classified based on HPV association (n = 83) and site (tongue n = 88; laryngopharynx n = 53; oropharynx n = 51) and re-analyzed (Genespring; v13.1). The significant genes were validated in respective cohorts in The Cancer Genome Atlas (TCGA) for correlation with clinico-pathological parameters/survival. The gene entities (n = 3258) identified from HPV based analysis, when validated in TCGA identified the subset specifically altered in HPV+ HNSCC (n = 63), with three genes showing survival impact (RPP25, NUDCD2, NOVA1). Site-specific meta-analysis identified respective differentials (tongue: 3508, laryngopharynx: 4893, oropharynx: 2386); validation in TCGA revealed markers with high incidence (altered in >10% of patients) in tongue (n = 331), laryngopharynx (n = 701) and oropharynx (n = 404). Assessment of these genes in clinical sub-cohorts of TCGA indicated that early stage tongue (MTFR1, C8ORF33, OTUD6B) and laryngeal cancers (TWISTNB, KLHL13 and UBE2Q1) were defined by distinct prognosticators. Similarly, correlation with perineural/angiolymophatic invasion, identified discrete marker panels with survival impact (tongue: NUDCD1, PRKC1; laryngopharynx: SLC4A1AP, PIK3CA, AP2M1). Alterations in ANO1, NUDCD1, PIK3CA defined survival in tongue cancer patients with nodal metastasis (node+ECS-), while EPS8 is a significant differential in node+ECS- laryngopharyngeal cancers. In oropharynx, wherein HPV is a major etiological factor, distinct prognosticators were identified in HPV+ (ECHDC2, HERC5, GGT6) and HPV- (GRB10, EMILIN1, FNDC1). Meta-analysis in combination with TCGA validation carried out in this study emphasized on the molecular heterogeneity inherent within HNSCC; the feasibility of leveraging this information for improving prognostic efficacy is also established. Subject to large scale clinical validation, the marker panel identified in this study can prove to be valuable prognostic adjuncts.

Abstract 2767: Expression of defensin-associated genes may be correlated with lymph node metastasis of early stage tongue cancer

Abstract OBJECTIVES: Appropriate patient selection for elective neck dissection in N0 tongue cancer has been controversial, while there has been no genetic consideration so far. We aimed to analyze genetic difference between early and late cervical lymph node metastasis in oral tongue cancer patients using the Seoul National University Hospital (SNUH) cancer cohort and cancer genome atlas (TCGA) data, and to suggest genetic background for choosing eligible patient for elective neck dissection. METHODS: A total of 35 cases with RNAseq in SNUH cancer cohort with tongue cancer were also enrolled in this study. To investigate gene expression in early cervical lymph node metastasis, genomic data of following 2 groups was compared; 1) N0 group: T1/2 and N0, 2) N+ group: T1/2 and N+. Differentially expressed genes (DEGs) were extracted using R and limma package in bioconductor program. Gene ontology and pathway enrichment analysis were performed using DAVID online tool. Immune cell infiltration was analyzed using CIBERSORT online program. Additionally, 70 cases with matched RNAseq data of primary tumor and clinical TCGA data were analyzed to validate the role of DEGs. RESULTS: N0 and N+ groups showed no difference in age, gender, size and thickness of tumor, and nearest resection margin. In addition, there was no significant difference in 22 types of immune cell infiltration. A total of 51 DEGs were identified, and 14 genes were significantly upregulated and 37 genes were significantly downregulated (p&amp;lt;0.01, fold-change &amp;gt;2). Significant genes were PLA2G4D, NELL2, PCOLCE2, PI3, and PLA2G3. On KEGG pathway analysis, calcium, muscle contraction, and arachidonic acid metabolism-related pathway was significantly correlated. The most significant difference was found in 6 genes as follows; DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, FAM25A.DEFB which was the most significantly difference in expression was associated with ‘antibiotic’, ‘antimicrobial’, ‘beta defensing type’, defense reponse to bacterium’, and ‘defensin’. In TCGA data, DEFB4A and DEFB103B were more highly expressed in N0 group than N+ group, although it did not attain significant significance. CONCLUSIONS: Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer. Considering that defensin can be detected in saliva, simple saliva test for prediction of metastasis can be developed in the future. Note: This abstract was not presented at the meeting. Citation Format: Doh Young Lee. Expression of defensin-associated genes may be correlated with lymph node metastasis of early stage tongue cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2767.

Elective Neck Dissection Versus Wait-and-Watch Policy for Oral Cavity Squamous Cell Carcinoma in Early Stage: A Systematic Review and Meta-Analysis Based on Survival Data

Whether elective neck dissection (END) should be adopted for patients with clinically early-stage (cT1-2N0M0) oral cavity squamous cell carcinoma (OCSCC) remains debated. The aim of this systematic review was to compare the survival benefit of END with that of the wait-and-watch policy (WW) for patients with early-stage OCSCC based on survival data. According to the inclusion criteria, an exhaustive search for eligible studies was conducted. The study inclusion and data extraction were performed by 2 reviewers independently. The risk of bias was assessed in duplicate using the Risk Of Bias In Nonrandomized Studies of Interventions instrument. The hazard ratio (HR) of the time-to-event data was extracted or estimated. RevMan 5.3 and STATA 15.1 were adopted for data synthesis. Of the 35 studies that were included, only 5 were assessed as having a low risk of bias. Results of the meta-analyses showed END could significantly decrease neck recurrence (relative risk=0.45; confidence interval [CI], 0.35-0.59; P<.00001) and improve disease-free survival (HR=0.55; CI, 0.42-0.71; P<.00001), overall survival (HR=0.75; CI, 0.64-0.86; P<.0001), and disease-specific survival (HR=0.76; CI, 0.61-0.94; P=.01) compared with WW for patients with cT1-2N0. The subgroup analysis showed that END could decrease neck recurrence (P<.00001) and improve disease-free survival (P=.001) for patients with early-stage tongue cancer and that supraomohyoid neck dissection could decrease neck recurrence (P=.02). For patients with cT1N0, END could significantly decrease the proportion with neck recurrence (P=.0008) and improve disease-free survival (P=.0003), but the difference between overall survival and disease-specific survival did not achieve significance. END can decrease recurrence and improve survival time for patients with early-stage OCSCC. More high-quality studies are needed to make a solid conclusion, especially for patients with cT1N0M0.