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Objectives: The impact of positive tumor margin status and other clinicopathological factors on prognosis in early stage glottic squamous cell carcinoma (SCC) treated with transoral laser microsurgery (TLM) remains unclear. This study examined overall survival (OS) rates of patients with positive tumor margin status compared to negative tumor margin status after TLM in clinical T1-2 glottic SCC.Materials and Methods: The National Cancer Data Base (NCDB) was queried for patients who underwent resection of T1-2 glottic SCC by TLM. Patients were treated from 2004 to 2013. Overall survival was assessed with Kaplan-Meier curve analysis, and univariate and multivariate Cox proportional hazards analysis. Differences in clinicopathologic factors between positive and negative margin groups were compared using Pearson Chi-squared analysis.Results: Of 747 patients meeting inclusion criteria, 598 (80.1%) had negative margins. Median follow-up time was 48.0 months. Unadjusted 5-year OS for positive margins (80.0%) was lower compared to that of negative tumor margins (82.9%), but this was not statistically significant (P = 0.265). This persisted after multivariate analysis (P = 0.960). When tumors were stratified by T stage (647 T1, 100 T2), unadjusted 5-year OS based on margin status remained statistically insignificant for both T1 (P = 0.933) and T2 tumors (P = 0.350).Conclusion: Positive margins did not negatively impact overall survival among patients with TLM-treated early-stage glottic cancer. This finding might be useful clinically in deciding treatment modality for early stage glottic SCC. [ABSTRACT FROM AUTHOR]

Tumor cells initiate platelet activation leading to the secretion of bioactive molecules, which promote metastasis. Platelet receptors on tumors have not been well-characterized, resulting in a critical gap in knowledge concerning platelet-promoted metastasis. We identify a direct interaction between platelets and tumor CD97 that stimulates rapid bidirectional signaling. CD97, an adhesion G proteincoupled receptor (GPCR), is an overexpressed tumor antigen in several cancer types. Purified CD97 extracellular domain or tumor cell-associated CD97 stimulated platelet activation. CD97-initiated platelet activation led to granule secretion, including the release of ATP, a mediator of endothelial junction disruption. Lysophosphatidic acid (LPA) derived from platelets induced tumor invasiveness via proximal CD97-LPAR heterodimer signaling, coupling coincident tumor cell migration and vascular permeability to promote transendothelial migration. Consistent with this, CD97 was necessary for tumor cell-induced vascular permeability in vivo and metastasis formation in preclinical models. These findings support targeted blockade of tumor CD97 as an approach to ameliorate metastatic spread. [ABSTRACT FROM AUTHOR]

Objective: To compare transcervical ultrasonography (US) to standard cross-sectional imaging for the visualization of human papillomavirus-related oropharyngeal cancer (HPV-OPC).Materials and Methods: Patients with HPV-OPC and available standard imaging (CT and/or MRI) were identified in clinic and prospectively enrolled. US was performed to visualize the oropharynx and lymph nodes. Tumor characteristics across imaging modalities were evaluated (CT versus MRI, and US versus standard imaging (SI)).Results: Forty-three patients were included. The overall blinded detection rates for CT and MRI were 83% and 71%, respectively. The unblinded detection rate for US was 98%. Agreement of tumor anatomic subsite was moderate for both CT vs MRI (κ = 0.59) and US vs SI (κ = 0.47). Comparison of tumor size by CT and MRI showed statistically significant correlations in craniocaudal (CC), anteroposterior (AP), and mediolateral (ML) dimensions (RhoCC = 0.51, pCC = 0.038; RhoAP = 0.81, pAP < 0.0001; RhoML = 0.57, pML = 0.012). Tumor size estimates by US and SI showed statistically significant correlations in CC and AP, but not ML (RhoCC = 0.60, pCC = 0.003; RhoAP = 0.71, pAP < 0.0001; RhoML = 0.30, pML = 0.08). Tumor volume estimates improved correlations between US and SI (Rho = 0.66, p < 0.0001). Stratification of US patients into early and late imaging studies demonstrated an increase in correlation strength from early (Rho = 0.32, p = 0.32) to late groups (Rho = 0.77, p < 0.0001) demonstrating that ultrasound accuracy improved with experience.Conclusions: Our findings suggest that transcervical ultrasonography is a sensitive and relatively accurate adjunct to standard imaging for the evaluation of oropharyngeal tumors. Its cost, portability, and potential for in-clinic and serial imaging render US an attractive modality to further develop for imaging oropharyngeal tumors. [ABSTRACT FROM AUTHOR]

Objective: To examine reader performance in evaluating oropharyngeal anatomy on ultrasonography.Materials and Methods: Ultrasound images of the oropharynx comprising normal and malignant anatomic variants were organized into slideshows. Slideshows were administered to 6 readers blinded to participant tumor status and with varying experience reading oropharyngeal sonograms. A training slideshow oriented readers to images of the oropharynx with and without malignant lesions. Readers then evaluated images in a test slideshow for tumor presence and marked orthogonal long and short dimensions of the tumor. Results were analyzed for accuracy, sensitivity, specificity, inter-reader agreement, and measurement error relative to prospectively-identified reference measurements.Results: Eighty-seven percent of base of tongue (BOT) sonograms were identified correctly by a majority of readers. In identifying BOT tumors, median accuracy, sensitivity, specificity, and Fleiss's kappa were 79%, 73%, 85%, and 0.51, respectively. Median measurement error in the long and short axes for BOT tumors was -2.6% (range: -40% to 29%) and -2.6% (range: -56% to 156%), respectively. Eighty-four percent of palatine tonsil sonograms were identified correctly by a majority of readers. In identifying tonsil tumors, median accuracy, sensitivity, specificity, and Fleiss's kappa were 77%, 74%, 78%, and 0.41, respectively. Median measurement error in the long and short axes for tonsil tumors was 3.8% (range: -45% to 32%) and -6.5% (range: -83% to 42%), respectively.Conclusions: Overall, US has clinically useful sensitivity for identification of oropharyngeal carcinoma among readers of diverse clinical backgrounds and experience. US may be useful for the evaluation of features such as tumor dimensions. [ABSTRACT FROM AUTHOR]

This review examines the general cellular and molecular underpinnings of human papillomavirus (HPV)-related carcinogenesis in the context of head and neck squamous cell carcinoma (HNSCC) and focuses on HPV-positive oropharyngeal squamous cell carcinoma in areas for which specific data is available. It covers the major pathways dysregulated in HPV-positive HNSCC and the genome-wide changes associated with this disease. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to evaluate the efficacy of a therapeutic pathway for vestibular migraine (VM) and complex dizziness of undetermined etiology (CDUE) with caffeine cessation and pharmacotherapy. Study Design: This study is a retrospective chart review. Intervention(s): Patients were recommended to stop intake of caffeine and other putative migraine-triggering agents. Pharmacotherapy was initiated with nortriptyline or topiramate if symptoms persisted despite diet modification. Main Outcome Measure: Self-reported dizziness is the main outcome measure. Results: Vestibular migraine and CDUE were considered contributing factors to dizziness in 34 and 10, respectively, of 156 patients. Fourteen percent of patients reported improvement in symptoms upon caffeine cessation, whereas 46% of patients reported a reduction in dizziness after nortriptyline therapy (P = .007). Topiramate reduced symptoms in 25% of patients. In total, 75% of VM patients and 56% of patients with CDUE received sufficient benefit from this therapeutic pathway to not progress to other treatments. Conclusions: Vestibular migraine and CDUE can be treated effectively with a therapeutic pathway consisting of caffeine cessation followed by pharmacotherapy. [Copyright &y& Elsevier]

Introduction: Little is known regarding how human papillomavirus-positive oropharyngeal cancer (HPV-OPC) patient goals change with treatment. This study evaluates whether patient ranking of non-oncologic priorities relative to cure and survival shift after treatment as compared to priorities at diagnosis.Materials and Methods: This is a prospective study of HPV-OPC patient survey responses at diagnosis and after treatment. The relative importance of 12 treatment-related priorities was ranked on an ordinal scale (1 as highest). Median rank (MR) was compared using Wilcoxon matched-pairs signed-rank tests. Prevalence of high concern for 11 treatment-related issues was compared using paired t-test. The effect of patient characteristics on change in priority rank and concern was evaluated using linear regression.Results: Among 37 patients, patient priorities were generally unchanged after treatment compared with at diagnosis, with cure and survival persistently ranked top priority. Having a moist mouth uniquely rose in importance after treatment. Patient characteristics largely did not affect change in priority rank. Concerns decreased after treatment, except concern regarding recurrence.Discussion: Treatment-related priorities are largely similar at diagnosis and after treatment regardless of patient characteristics. The treatment experience does not result in a shift of priorities from cure and survival to non-oncologic domains over cure and survival. The rise in importance of moist mouth implies that xerostomia may have been underappreciated as a sequelae of treatment. A decrease in most treatment-related concerns is encouraging, whereas the persistence of specific areas of concern may inform patient counseling. [ABSTRACT FROM AUTHOR]

Objectives: HPV-positive oropharyngeal cancer (OPC) patients have been observed to be younger than patients with HPV-negative OPC at diagnosis. We evaluated recent trends in age at OPC diagnosis, and whether older age attenuates the survival benefit of HPV-positive tumor status.Materials and Methods: Patients diagnosed with OPC from 2004 to 2014 represented in the National Cancer Database were included. HPV tumor status was available after 2010. Trends in age by calendar year were compared using linear regression. Overall survival was compared using Cox Proportional Hazards models.Results: The mean age of OPC patients (N = 119,611) increased significantly from 2004 to 2014 (ß = 0.21 years of age per calendar year, 95% confidence interval [CI] = 0.19-0.23). The increase in age from 2010 to 2014 was similar for HPV-positive (N = 21,880; ß = 0.63, 95%CI = 0.53-0.72) and HPV-negative (N = 11,504; ß = 0.59, 95%CI = 0.45-0.74) patients. Between 2010 and 2014, the proportion of OPCs that were HPV-positive increased significantly for all age groups, including for patients ≥70 years old (from 45% to 60%, ptrend < 0.001). Although patients ≥70 years with HPV-OPC had improved survival compared to those with HPV-negative OPC (adjusted hazard ratio [aHR] = 0.65, 95%CI = 0.55-0.76), the survival benefit of HPV-positive tumor status was significantly attenuated compared to younger HPV-OPC patients (50-59 years: aHR = 0.45, 95%CI = 0.39-0.51; pinteraction < 0.001).Conclusion: The age at OPC diagnosis is increasing for both HPV-positive and HPV-negative patients, and a rising proportion of older patients have HPV-positive tumors. These findings dispel the notion that HPV-positive OPC is a disease of younger patients, identify a growing elderly population of HPV-positive OPC patients with reduced survival, and have implications for evolving treatment paradigms. [ABSTRACT FROM AUTHOR]

• There is a survival benefit to primary tumor detection regardless of HPV status. • Oropharyngeal primary tumor detection rates are increasing over time. • Female, non-white, and HPV negative patients have lower odds of primary detection. Head and neck cancer of unknown primary (CUP) poses significant therapeutic challenges. We compare CUP and oropharyngeal primary (OP) cases to identify factors associated with tumor detection. The 2004–2019 National Cancer Database was queried to identify CUP and OP cases based on clinical and pathologic TNM staging. Clinical and demographic characteristics were compared by primary detection and HPV status with descriptive statistics. Multivariable logistic regression models to characterize OP detection were constructed. Among HPV-positive and negative patients, respectively, OP and CUP patients were matched by clinical nodal disease. Cox proportional-hazards models were constructed using matched cohorts to characterize survival. 81,053 CUP and OP cases were identified; 64.3 % were HPV-positive. OP detection increased over time in HPV-positive and negative disease. HPV-positive status had higher odds of OP detection (odds ratio (OR) = 1.77, p < 0.001), while females (OR = 0.95, p = 0.008), and black (OR = 0.82, p < 0.001) and Asian (OR = 0.7, p < 0.001) patients had lower odds compared to males and whites, respectively. In HPV-positive and negative disease, OP patients had higher 2 and 5-year survival rates than CUP (p < 0.001). Primary detection status conferred lower death risk in HPV-positive (hazard ratio (HR) = 0.85, p < 0.001) and negative disease (HR = 0.87, p < 0.001) when controlling for age, sex, race, comorbidities, insurance, treatment facility, and income. In the largest cohort of CUP to date, we report a survival benefit in primary tumor detection regardless of HPV status. Groups with higher persistent CUP rates, including non-white, female, HPV-negative, and low income patients, may benefit from increased diagnostic workup to improve detection and treatment. [ABSTRACT FROM AUTHOR]

Background: Hypopharyngeal cancer is associated with poor survival. Robotic surgery is emerging as a treatment for hypopharyngeal tumors, but no rigorous data are available to assess its effect on survival.Methods: The National Cancer Database (NCDB) was used to identify patients with T1 and T2 hypopharyngeal tumors undergoing robotic surgery, laser surgery, and primary radiation with or without chemotherapy from 2010 to 2016. All adult patients with available staging and no distant metastasis were included.Results: We compared 57 patients undergoing robotic surgery, 236 undergoing laser surgery, and 5,742 undergoing primary radiation. Compared to laser surgery, patients undergoing robotic surgery were significantly more likely to have negative margins, neck dissection, lower incomes, and care at an academic center. Rates of robotic surgery also significantly increased from 2010 to 2015. After multivariate regression, robotic surgery was associated with significantly improved overall survival compared to laser surgery and primary radiation.Conclusion: Robotic surgery improves overall survival for T1 and T2 hypopharyngeal tumors compared to laser surgery and primary radiation in this NCDB cohort. This effect may be mediated by decreased positive margin rates relative to laser surgery. Rates of hypopharyngeal robotic surgery are expected to increase with wider adoption of robotic platforms and may improve overall survival rates for hypopharyngeal cancer. [ABSTRACT FROM AUTHOR]