Uchechukwu C. Megwalu

Survival Outcomes in Advanced Laryngeal Cancer

IMPORTANCE Chemoradiation therapy has become increasingly popular in the treatment of advanced laryngeal cancer as part of an organ preservation protocol. However, several studies have reported a decline in survival, possibly attributable to the increased use of radiation and chemoradiation therapy. OBJECTIVE To evaluate survival outcomes of laryngeal conservation vs surgical therapy in the treatment of advanced laryngeal cancer in the United States using a large population-based cancer database. DESIGN, SETTING, AND PARTICIPANTS Population-based, nonconcurrent cohort study of 5394 patients who received a diagnosis of stage III or IV laryngeal squamous cell carcinoma between 1992 and 2009. Data were extracted from the Surveillance, Epidemiology, and End Results 18 Database. INTERVENTIONS Surgical or nonsurgical therapy. MAIN OUTCOMES AND MEASURES Overall survival (OS) and disease-specific survival (DSS). RESULTS Patients who received surgical therapy had better 2-year and 5-year DSS (70% vs 64% and 55% vs 51%, respectively; P < .001) and 2-year and 5-year OS (64% vs 57% and 44% vs 39%, respectively; P < .001) than patients who received nonsurgical therapy. The difference in DSS and OS between treatment groups remained after stratification by year-of-diagnosis cohorts (P < .001). The survival gap consistently narrowed with subsequent year-of-diagnosis cohorts. On multivariable analysis, nonsurgical patients had worse DSS (hazard ratio [HR], 1.33 [95% CI, 1.21-1.45]) and OS (HR, 1.32 [95% CI, 1.22-1.43]) after adjustment for year of diagnosis, American Joint Committee on Cancer stage, age, sex, subsite, race, and marital status. Stage III disease (HR, 0.59 [95% CI, 0.54-0.65]), glottic subsite (HR, 0.74 [95% CI, 0.67-0.82]), 2004 to 2009 year-of-diagnosis cohort (HR, 0.79 [95% CI, 0.70-0.90]), female sex (HR, 0.80 [95% CI, 0.72-0.89]), and married status (HR, 0.68 [95% CI, 0.62-0.75]) positively affected DSS. Black race (HR, 1.17 [95% CI, 1.05-1.30]) and increased age (HR, 1.03 [95% CI, 1.02-1.03] for each year) negatively affected DSS. CONCLUSIONS AND RELEVANCE Surgical therapy leads to better survival outcomes than nonsurgical therapy for patients with advanced laryngeal cancer. Patients need to be made aware of the modest but significant survival disadvantage associated with nonsurgical therapy as part of the shared decision-making process during treatment selection.

The Effects of Melatonin on Tinnitus and Sleep

GOAL: To determine if melatonin improves tinnitus and if this improvement is related to improvement in sleep. STUDY DESIGN AND SETTING: Prospective open-label study of 24 patients with tinnitus. The patients took 3 mg of melatonin per day for 4 weeks, followed by 4 weeks of observation. The Tinnitus Handicap Inventory (THI) and the Pittsburgh Sleep Quality Index (PSQI) were administered. RESULTS: The mean THI score decreased significantly between weeks 0 and 4, and between weeks 0 and 8. The mean PSQI significantly decreased between weeks 0 and 4 (P < 0.0001), and between weeks 0 and 8 (P = 0.0003). The change in PSQI was significantly associated with the change in THI between weeks 0 and 4. The change in PSQI was not significantly associated with the change in THI between weeks 0 and 8. The change in the PSQI in the first 4 weeks was associated with the initial PSQI. There was no association between the initial THI and the change in the THI in the first 4 weeks. CONCLUSION: Melatonin use is associated with improvement of tinnitus and sleep. There was an association between the amount of improvement in sleep and tinnitus. The impact of melatonin on sleep was greatest among patients with the worst sleep quality, but its impact on tinnitus was not associated with the severity of the tinnitus. SIGNIFICANCE: Melatonin may be a safe treatment for patients with idiopathic tinnitus, especially those with sleep disturbance due to tinnitus. EBM rating: C-4

Estrogen-Mediated Angiogenesis in Thyroid Tumor Microenvironment Is Mediated Through VEGF Signaling Pathways

OBJECTIVES To explore the induction of a proangiogenic phenotype in endothelial cells in the thyroid tumor microenvironment by estrogen-treated thyroid cancer cells and to define the role of vascular endothelial growth factor (VEGF) in this interaction. DESIGN Cell-based in vitro systems analysis. SUBJECTS Thyroid tumor cell lines (BCPAP [papillary thyroid cancer] and ML-1 [follicular thyroid cancer]) were cultured with estradiol with and without an estrogen receptor (ER) inhibitor (fulvestrant or ICI) and used to treat human umbilical vein endothelial cells (HUVECs). INTERVENTIONS Immunofluorescence was used to confirm the presence of ERα and ERβ in BCPAP cells. Conditioned medium was then used to evaluate the induction of HUVEC tubulogenesis and migration. Secretion of VEGF in this medium was evaluated by Western blot analysis. The expression of phosphoinositide 3-kinase (PI3K), the initiator of a proangiogenic pathway, was evaluated with Western blot analysis of HUVEC lysates. The subsequent effects of an ER inhibitor (fulvestrant/ICI) and a neutralizing VEGF antibody were also observed. RESULTS Estrogen receptor α and ERβ are expressed in thyroid cancer cells. Estrogen-stimulated ML-1 cells secreted an increased amount of VEGF likely as a result of ER signaling. In contact with this environment, HUVECs demonstrate enhanced tubulogenesis and migration. Western blot analysis documented estrogen-mediated upregulation of PI3K in HUVECs. These effects were mitigated by an ER inhibitor (fulvestrant/ICI) and a neutralizing VEGF antibody. CONCLUSIONS Our data provide evidence that estrogen can induce a proangiogenic endothelial cell phenotype in the thyroid tumor microenvironment through ER and VEGF signaling. Our findings suggest that the effect of antiestrogenic therapy targeting tumor angiogenesis can be enhanced through VEGF inhibition.

The Impact of Demographic and Socioeconomic Factors on Major Salivary Gland Cancer Survival.

Objective This study aimed to investigate the impact of demographic and socioeconomic factors on survival in patients with major salivary gland malignancies. Study Design Population-based study using the Surveillance, Epidemiology, and End Results (SEER) cancer database. Subject and Methods The study cohort consisted of 10,735 men and women ages 20 and older who were diagnosed with major salivary gland carcinoma from 1973 to 2009. Results Kaplan–Meier analysis revealed that the overall and disease-specific survival was higher for women than for men (P < .001). Overall and disease-specific survival decreased with increasing age (P < .001) and differed by race (P < .001) and marital status (P < .001). Patients residing in counties with higher rates of high school completion had higher overall and disease-specific survival (P < .001). Patients residing in counties with higher median household incomes had better overall and disease-specific survival than patients from lower income counties (P < .001). On multivariable analysis, male sex (hazard ratio [HR] = 1.41; 95% confidence interval [CI], 1.32-1.50), increasing age, and single status (HR = 1.36; 95% CI, 1.27-1.44) had poor prognostic impact on overall survival. Male sex (HR = 1.38; 95% CI, 1.27-1.49), increasing age, and single status (HR = 1.29; 95% CI, 1.19-1.39) had poor prognostic impact on disease-specific survival. Conclusion For patients with salivary gland malignancies, there is a survival benefit for younger patients, female patients, and married patients. This highlights the significance of demographic factors on survival outcomes for patients with salivary gland malignancies and highlights areas for further research on health disparities.

Methodological and Statistical Problems in Uvulopalatopharyngoplasty Research: A Follow-up Study

OBJECTIVES To review the published literature on uvulopalatopharyngoplasty (UPPP) and assess the methodological quality of the research and compare it with a similar article published in 1995; and to determine what, if any, improvement in the methodological quality of the research resulted during the ensuing 10 years. DESIGN Methodological and statistical evaluation of the published literature on UPPP. Thirty articles representing the clinical studies on UPPP and related procedures written from January 1996 to August 2005 were reviewed. Only articles reporting polysomnography data were included. RESULTS Overall, the articles demonstrated fair methodological and statistical quality. Compared with the previous review by Schechtman et al, there was a slight increase in the number of articles that discussed statistical power and reported confidence intervals. There were increases in the mean sample size, the percentage of randomized controlled studies, the number of end points, and the use of validated subjective outcome measures; longer mean follow-up time; and more complete reporting of age and sex information. There was no increase in the percentage of published studies that used a prospective study design. None of the studies that required minimum acceptable baseline values of objective sleep parameter measures for enrollment indicated the use of separate screening and baseline assessments. There were 7 different definitions of sleep apnea and 17 different definitions of success in treatment. CONCLUSIONS There has been an overall improvement in the quality of the articles published on UPPP since 1995. Several areas still need improvement: use of more prospective studies, decrease in number of end points, use of separate screening and baseline assessments, and consensus in the definitions of sleep apnea and success.

Sociodemographic disparities in choice of therapy and survival in advanced laryngeal cancer

PURPOSE To determine if sociodemographic factors are associated with treatment choice and survival in patients with advanced stage laryngeal cancer in the U.S. DESIGN/SETTING/SUBJECTS/METHODS Population-based, non-concurrent cohort study of 5381 patients diagnosed with stage III or IV laryngeal squamous cell carcinoma from 1992-2009. Data was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. MAIN OUTCOME(S) AND MEASURES Choice of therapy (surgical vs. non-surgical) and disease-specific survival (DSS). RESULTS Age ≥60 years (odds ratio [OR]=0.78; 95% CI, 0.70-0.88) and more recent year of diagnosis (OR=0.89; 95% CI, 0.87-0.90) decreased the odds of receiving surgical therapy, while residing in a county with low median household income (OR=1.36; 95% CI, 1.17-1.57) increased the odds of receiving surgical therapy. Age ≥60 years (hazard ratio [HR]=1.45; 95% CI, 1.33-1.59) and Black race (HR=1.14; 95% CI, 1.02-1.27) were negatively associated with DSS, while female sex (HR=0.81; 95% CI, 0.72-0.90) and married status (HR=0.69; 95% CI, 0.63-0.75) were positively associated with DSS. CONCLUSIONS AND RELEVANCE For patients with advanced laryngeal cancer, younger age and residing in a low-income county increase the likelihood of receiving surgical therapy. Female sex and married status provide a survival benefit, while Black race appears to be a negative prognostic factor. This highlights the impact of sociodemographic factors on treatment strategies and outcomes and highlights areas for further research on health disparities.

Second Primaries after Major Salivary Gland Cancer

Objectives. To evaluate the risk of second primary cancers in patients with major salivary gland cancer using a large population database and to examine the effects of sex, salivary gland cancer histology, and radiation therapy on the risk of second primaries. Study Design. Population-based study using the Surveillance, Epidemiology, and End Result (SEER) cancer database. Subject and Methods. The subjects were 15,572 men and women ages 15 and above, diagnosed with cancer of the major salivary glands from 1973 to 2006. Results. There was an increased risk of oral cavity (standardized incidence ratio [SIR] = 3.48, P < .05), salivary (SIR = 9.97, P < .05), lung and bronchus (SIR = 1.60, P < .05), kidney (SIR = 1.68, P < .05), and thyroid (SIR = 2.66, P < .05) cancers. Men had an increased risk of developing kidney cancer (SIR = 1.70, P < .05) compared with women (SIR = 1.64, P > .05). Patients with mucoepidermoid carcinoma had an increased risk of a second salivary gland cancer (SIR = 8.97, P < .05) and thyroid cancer (SIR = 3.97, P < .05). Patients with adenoid cystic carcinoma had an increased risk of oral cavity (SIR = 3.76, P < .05) and nasopharyngeal (SIR = 16.88, P < .05) cancers. Patients with acinar cell carcinoma had an increased risk of salivary (SIR = 31.36, P < .05), kidney (SIR = 2.98, P < .05), and thyroid (SIR = 3.85, P < .05) cancers. Patients who received radiation therapy had a higher incidence of lung and bronchus (SIR = 2.11, P < .05), laryngeal (SIR = 3.08, P < .05), and thyroid (SIR = 2.95, P < .05) cancers compared with patients who did not receive radiation therapy (SIR = 1.18, 0.48, and 2.39, respectively; P > .05). Patients had an increased risk of developing second primaries, even 10 years after diagnosis of primary salivary gland cancer. Conclusions. Patients with major salivary gland cancers are at a risk for certain second primary cancers. This highlights the need for long-term surveillance in these patients, not only for recurrence but also for second primary cancers.

Evaluation of a laryngopharyngeal reflux management protocol

PURPOSE To evaluate the effectiveness of a protocol for management of patients with laryngopharyngeal reflux (LPR) in a multi-provider clinic. MATERIALS AND METHODS This is a retrospective cohort study of 188 patients treated for LPR. A standardized clinical protocol for diagnosis and management was instituted in 2012. Two cohorts were established: those managed according to the protocol, and those who were not. For patients managed with the LPR protocol, diagnosis was made using clinical judgment, guided by the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS). Patients were treated with proton pump inhibitors (PPI) with the goal of weaning therapy after symptom resolution. Response to therapy was rated using a global rating scale with three response levels: no response, partial response, and complete response. The primary outcome measure was complete response to therapy and the secondary outcome measures were any response (complete or partial) and successful wean off PPI therapy. RESULTS The patients treated with the LPR protocol had higher rates of complete response (p<0.001). There was no statistically significant difference in rates of any response (complete or partial) between the two groups (p=0.08). Patients treated using the LPR protocol were more likely to be successfully weaned off PPI therapy (p=0.006). CONCLUSIONS The use of an LPR protocol improved treatment effectiveness in our clinic, highlighting the role of clinical protocols in reducing variability in care, thereby improving patient outcomes.

Racial disparities in oropharyngeal cancer survival

BACKGROUND Oropharyngeal cancer is an important cause of mortality and morbidity. Several studies have revealed racial disparities in head and neck cancer outcomes. The goal of our study was to evaluate the impact of race on survival in patients with oropharyngeal cancer, using a large population-based cancer database. MATERIALS AND METHODS This was a retrospective cohort study. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 Database of the National Cancer Institute. The study cohort included patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2012. The outcomes of interest were overall survival (OS) and disease-specific survival (DSS). RESULTS After adjusting for age, sex, marital status, tumor site, and year of diagnosis, black race was associated with worse OS (HR 1.67, p<0.0001) and DSS (HR 1.67, p<0.0001). CONCLUSION Black race is associated with worse survival in patients with oropharyngeal cancer. Further research is needed to elucidate the mechanism by which race impacts survival in oropharyngeal cancer. This may reveal potential areas of opportunity for public health interventions aimed at addressing disparities in cancer outcomes.

Health Literacy Assessment in an Otolaryngology Clinic Population

Objective To assess health literacy in an adult tertiary care otolaryngology clinic population and to explore potential determinants of inadequate health literacy. Study Design Cross-sectional study. Setting Tertiary care otolaryngology clinic. Subjects and Methods The study population included all adult patients treated at 3 of Stanford University’s adult otolaryngology clinic sites between March 1 and 11, 2016. Data were collected via an anonymous questionnaire. Health literacy was assessed with the Brief Health Literacy Screen. Results Ten percent of patients had inadequate health literacy. White race (odds ratio [OR], 0.23) and having English as the primary language (OR, 0.12) were associated with adequate health literacy, while high school or lower level of education (OR, 3.2) was associated with inadequate health literacy. Age, sex, and Hispanic ethnicity were not associated with health literacy. Conclusion Our study highlights the need for health literacy screening in the otolaryngology clinic setting and identifies sociodemographic risk factors for inadequate health literacy. Further studies are needed to assess the impact of health literacy on patient outcomes and to test specific interventions to address health literacy and health outcomes.