Development of extranodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here, we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection. An institutional cohort (The University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue. OSCC data from The Cancer Genome Atlas (TCGA) were analyzed for the presence of molecular events associated with nodal and ENE status. ENE was associated with decreased overall and disease-free survival. Mutation of the gene was the most common event in ENE OSCC. The frequency of mutation in ENE tumors was higher compared with ENE tumors and wild-type (WT) TP53 was highly represented in pN0 tumors. pNENE patients had the highest proportion of high-risk mutations. Both primary tumors (PT) and lymph nodes with ENE (LN) exhibited a high rate of mutations (58.8% and 58.8%, respectively) with no significant change in allele frequency between the two tissue sites. ENE is one of the most significant markers of OSCC OS and DFS. There is a shift toward a more aggressive biological phenotype associated with high-risk mutations of the gene. Prospective clinical trials are required to determine whether mutational status can be used for personalized treatment decisions. .

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An early analysis of growth dynamics for infectious diseases, like COVID-19, is needed to dissect the crucial driving factors that result in rapid disease transmission, refine the measures taken to control the pandemic and improve disease forecast. The phenomenological models are used to identify the initial climbing growth period of COVID-19 outbreak in India and have modelled 3 major epidemic growth models: Generalized logistic growth, Logistic growth and Generalized growth, to predict the growth in the total number of positive cases, daily increase in the number of positive tested cases and the daily growth rate in confirmed positive cases, dated from Apr 10, 2020, to Apr 20, 2020. The bootstrap resampling method is applied for data prediction to process the sample data, dated from Jan 31, 2020, to Apr 10, 2020, and to calculate the 3 major growth parameters: r (Rate of growth at an early stage), K (Final epidemic size) and C(Number of aggregate cases at time t), which are used to calculate confidence inte rvals which predict the future direction of the curve and increase in the number of confirmed cases with 95% accuracy for the interval Apr 10, 2020, to Apr 20, 2020. Our models predict exponential and subexponential spread rate in the number of positive cases in India from Apr 10, 2020, to Apr 20, 2020. Our findings reveal that significant measures are needed to control the transmission rate of the virus in the community, as the models predict sub-exponential growth in India.

BACKGROUND: The treatment of advanced oral squamous cell carcinoma (OSCC) is a clinical challenge because it is unclear which therapeutic approaches are the best for this highly heterogeneous group of patients. Because TP53 mutations are the most common genetic event in these tumors, the authors investigated whether they could represent an ancillary biomarker in the management of advanced OSCC. METHODS: The TP53 gene was sequenced in 78 samples from patients with advanced OSCC who received treatment at 2 institutions located in the United States and Brazil. TP53 mutations were classified according to an in-silico impact score (the evolutionary action score of p53 [EAp53]), which identifies mutations that have greater alterations of p53 protein function (high-risk). Associations between TP53 mutation status/characteristics and clinicopathologic characteristics were investigated. The relevant findings were validated in silico by analyzing 197 samples from patients with advanced OSCC from The Cancer Genome Atlas. RESULTS: No differences in clinical outcomes were detected between patients with TP53-mutant and wild-type TP53 disease. However, patients who had tumors carrying high-risk TP53 mutations had a significantly increased risk of developing extranodal extension (ENE) compared with those who had wild-type TP53-bearing tumors. The increased chances of detecting ENE among patients who had high-risk TP53 mutations was validated among patients with advanced OSCC from The Cancer Genome Atlas cohort. CONCLUSIONS: High-risk TP53 mutations are associated with an increased chance of detecting ENE in patients with advanced OSCC. Because ENE is 1 of the major factors considered for OSCC patient management, TP53 mutation status may represent a potential ancillary biomarker for treatment decisions regarding postoperative adjuvant therapy.

<div>Abstract<p><b>Purpose:</b> Development of extranodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here, we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection.</p><p><b>Experimental Design:</b> An institutional cohort (The University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue. OSCC data from The Cancer Genome Atlas (TCGA) were analyzed for the presence of molecular events associated with nodal and ENE status.</p><p><b>Results:</b> ENE was associated with decreased overall and disease-free survival. Mutation of the <i>TP53</i> gene was the most common event in ENE⁺ OSCC. The frequency of <i>TP53</i> mutation in ENE⁺ tumors was higher compared with ENE⁻ tumors and wild-type (WT) TP53 was highly represented in pN0 tumors. pN⁺ENE⁺ patients had the highest proportion of high-risk <i>TP53</i> mutations. Both primary tumors (PT) and lymph nodes with ENE (LN) exhibited a high rate of <i>TP53</i> mutations (58.8% and 58.8%, respectively) with no significant change in allele frequency between the two tissue sites.</p><p><b>Conclusions:</b> ENE is one of the most significant markers of OSCC OS and DFS. There is a shift toward a more aggressive biological phenotype associated with high-risk mutations of the <i>TP53</i> gene. Prospective clinical trials are required to determine whether <i>TP53</i> mutational status can be used for personalized treatment decisions. <i>Clin Cancer Res; 24(7); 1727–33. ©2018 AACR</i>.</p></div>