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Objectives: To characterize the representation of women in clinical trials directing the National Comprehensive Cancer Network (NCCN) guidelines for chemotherapy use in head and neck squamous cell carcinoma (HNSCC), as well as the relationship between gender and chemotherapy administration in the definitive treatment of HNSCC in the United States.Methods: A review of all HNSCC chemotherapy clinical trials cited by the 2018 NCCN guidelines was performed. Sex-based proportions were compared with the corresponding proportions in the general U.S. population of patients with HNSCC between 1985 and 2015, derived from the Surveillance, Epidemiology, and End Results (SEER) program. A second analysis using the National Cancer Database (NCDB), identified 63,544 adult patients diagnosed with stages III-IVB HNSCC between 2004 and 2014 and treated with definitive radiotherapy or chemoradiotherapy. Univariable and multivariable logistic regression analyses were used to identify predictors of chemotherapy administration.Results: While women comprised 26.2% of U.S. patients with HNSCC between 1985 and 2015, they comprised only 17.0% of patients analyzed in U.S. NCCN-cited chemotherapy clinical trials between 1985 and 2017. On multivariable analysis, women had decreased odds of receiving chemotherapy (Odds Ratio [OR]: 0.875; 95% Confidence Interval [CI]: 0.821-0.931; p < 0.001).Conclusion: Women are underrepresented in HNSCC chemotherapy clinical trials cited by the national guidelines. Additionally, women are less likely than men to receive definitive chemoradiotherapy as oppose to definitive radiotherapy. Reasons for these disparities warrant further investigation as well as re-evaluation of eligibility criteria and enrollment strategies, in order to improve relevance of clinical trials to women with HNSCC. [ABSTRACT FROM AUTHOR]

Objectives: Studies have shown the utility of lipid-lowering agents in improving outcomes in various cancers. We aim to explore how statins affect overall survival and cancer specific survival in head and neck cancer patients using population-based datasets.Patients and Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset, we separated HNC patients into three groups: those with no hyperlipidemia (nH), those with hyperlipidemia and not taking a statin (HnS), and those with hyperlipidemia and taking a statin (H + S). Overall survival (OS) and cancer specific survival (CSS) were compared between the three groups based on disease subsite (oral cavity, oropharynx, and other) using Kaplan-Meier and multivariate Cox regression analysis (MVA), controlling for demographic, socioeconomic, staging, treatment, and comorbidity covariates. Using Pearson chi-square analysis, we also compared the incidence of cancer-related toxicity events.Results: There were 495 nH, 567 HnS, and 530 H + S patients. H + S patients had superior OS and CSS (73.0, 81.2%) relative to nH (58.6, 69.1%) and HnS groups (61.7, 69.2%) (p < 0.01). On MVA, H + S patients showed improved OS (p < 0.01) and CSS (p = 0.04) compared to nH (HR = 1.64, 1.56) and HnS (HR = 1.40, 1.37). MVA stratified by subsite yielded similar results for oral cavity and oropharyngeal disease. Toxicity-related events did not differ significantly between the groups.Conclusion: HNC patients with hyperlipidemia and taking a statin demonstrated improved outcomes compared to nH and HnS patients, further supporting statins' role as a potential adjuvant anti-neoplastic agent in HNC. Further prospective studies to investigate the impact of statins on HNC outcomes are warranted. [ABSTRACT FROM AUTHOR]

Objectives: To quantify head and neck cancer (HNC) mortality rates and identify racial and socioeconomic factors associated with 90-day mortality.Methods: The National Cancer Database (2004-2014) was queried for eligible HNC cases (n = 260,011) among adults treated with curative intent. Outcome of interest was any-cause 90-day mortality. Kaplan-Meier curves (Log-rank tests) estimated crude survival differences. A Cox proportional hazards model with further adjustments using the Šidák multiple comparison method adjusted for racial, socioeconomic and clinical factors.Results: There were 9771 deaths (90-day mortality rate = 3.8%). There were crude differences in sex, race/ethnicity, comorbidity, distance, income, and insurance (Log-rank p-value < 0.0001). In the final model, blacks (aHR = 1.10, 95% CI 1.00, 1.21) and males (aHR = 1.07; 95% CI 1.00, 1.15) had greater 90-day mortality hazard, as did those uninsured (aHR = 1.72; 95% CI 1.48, 1.99), covered by Medicaid (aHR = 1.72; 95% CI 1.53, 1.93) or Medicare (aHR = 1.40; 95% CI 1.27, 1.53). Residence in lower median income zip code was associated with greater 90-day mortality [(aHR <$30,000 = 1.30; 95% CI 1.18, 1.44); (aHR $30,000-$34,999 = 1.24; 95% CI 1.13, 1.36); (aHR $35,000-$45,999 = 1.18; 95% CI 1.08, 1.27)]; and farther travel distance for treatment was associated with decreased 90-day mortality [(aHR 50-249.9 miles = 0.86; 95% CI 0.77, 0.97); (aHR > 250 miles = 0.70; 95% CI 50, 0.99)].Conclusions: There are significant race and socioeconomic disparities among patients with HNC, and these disparities impact mortality within 90 days of treatment. [ABSTRACT FROM AUTHOR]

Objectives: Delays in the initiation of postoperative radiation have been associated with worse outcomes; however, the effect of the overall treatment package time (interval from surgery through the completion of radiation) remains undefined. The purpose of this study was to determine the impact of package time on survival and to evaluate this effect among different subgroups of head and neck cancer patients.Patients and Methods: In this observational cohort study, the National Cancer Database was used to identify 35,167 patients with resected nonmetastatic head and neck cancer who underwent adjuvant radiation from 2004 to 2014. Kaplan-Meier survival estimates and multivariate Cox regression analyses were performed to determine the effect of treatment package time on overall survival.Results: Median package time was 96 days (interquartile range, 85-112 days). After adjusting for covariates, package times of 11 weeks or less were associated with improved survival (adjusted hazard ratio (aHR), 0.90; 95% confidence interval, 0.83-0.97) compared to an interval of 12-13 weeks, whereas package times of more than 14 weeks were associated with worse survival (aHR, 1.14, 1.14, and 1.22 for 14-15, 15-17, and >17 weeks, respectively). A significant interaction was identified between package time and disease site, nodal status, and stage. Specifically, patients with oropharyngeal tumors, advanced stage (III or IV) disease, or nodal involvement experienced more pronounced increases in mortality risk with delays in treatment time.Conclusions: Treatment package time independently impacts survival. This effect may be strongest for patients with oropharyngeal tumors or advanced stage disease. [ABSTRACT FROM AUTHOR]

Purpose/objectives: The increasing survivorship of head and neck squamous cell carcinoma (HNSCC) comes with a risk of death from other causes, known as competing causes. The demographics of HNSCC are also evolving with increasing incidence of Human Papillomavirus (HPV) associated tumors. This study describes competing causes of death for the HNSCC population compared to the general population and identifies associated risk factors.Methods: Adult patients with first mucosal HNSCC (2004-2011) were identified from the Surveillance, Epidemiology and End Result database. Competing causes of death were compared to reference populations using proportion of deaths and Standardized Mortality Ratios (SMR). A multivariable competing risk survival analysis yielded subdistribution hazard ratios (HR) for competing mortality.Results: Of 64,598 HNSCC patients, 24,602 (38.1%) were deceased including 7142 deaths (29.0%) from competing causes. The most common were cardiovascular disease, lung cancer, and other cancers. All relative mortality rates were elevated, especially liver disease (SMR 38.7; 95% CI: 29.4-49.3), suicide (SMR 37.1; 95% CI: 26.1-48.6), and subsequent primary cancers (SMR 7.5; 95% CI: 6.78-8.32). Demographic and tumor factors independently increased risk of competing mortality, including age (HR per 5years 1.24; 95% CI: 1.22-1.25), sex (male HR 1.23; 95% CI: 1.16-1.32), race (Black HR 1.17; 95% CI: 1.09-1.26), insurance (uninsured HR 1.28; 95% CI: 1.09-1.50), and marital status (single HR 1.29; 95% CI: 1.21-1.37).Conclusion: Nearly one in three HNSCC patients died from competing causes. When developing long term survivorship regimens for HNSCC patients, clinicians should be familiar with this population's specific risks. [ABSTRACT FROM AUTHOR]

Objectives: The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) have proposed eight recommendations for cancer prevention, related to body fatness, diet, and physical activity. Our aim is to evaluate the role of adherence to these recommendations on head and neck cancers risk.Materials and Methods: We obtained an overall score including seven of the WCRF/AICR recommendations, and examined its relationship with head and neck cancers risk in two Italian case-control studies including 946 patients with oral cavity and pharyngeal (OCP) cancer and 2492 controls, and 689 patients with laryngeal cancer and 1605 controls.Results: Higher adherence to WCRF/AICR recommendations was associated to a reduced risk of OCP cancer (odds ratio, OR=0.45, 95% confidence interval, CI: 0.33-0.62 for a score of 4-<5, and OR=0.32, 95% CI: 0.22-0.49 for a score of ⩾5 as compared to <3). The ORs for laryngeal cancer were 0.68 (95% CI: 0.50-0.92) for a score of 3-<4, 0.39 (95% CI: 0.28-0.55) for a score of 4-<5, and 0.24 (95% CI: 0.15-0.38) for a score of ⩾5.Conclusion: Our study indicates that high adherence to the WCRF/AICR recommendations for cancer prevention is associated with a substantially decreased risk of head and neck cancers. [ABSTRACT FROM AUTHOR]

Objective: This study assesses longitudinal epidemiologic trends in the oldest head and neck cancer (HNC) patients, comparing the oropharynx to other mucosal HNC sites.Materials and Methods: Using data from the Surveillance, Epidemiology, and End Results database, trends in incidence, two-year cancer specific mortality, and percent of cases recommended for and which received surgery from 2000 to 2018 in patients ages ≥85 years were assessed using Joinpoint analysis by HNC site. Trends were quantified as annual percentage change (APC) with 95% confidence intervals (CI).Results: Among older adults, oropharyngeal cancer (OPC) incidence increased (APC = 1.80% [95% CI: 0.94-2.67]), while mortality decreased (APC = -2.01% [95% CI: -3.26--0.74]) from 2000 to 2018. At other mucosal HNC sites, incidence and mortality remained stable. Percentage of patients who received surgery significantly changed for oropharyngeal (APC = -15.34% from 2000 to 2005 [95% CI: -24.37 to -4.79]) and laryngeal (APC = -4.61% from 2000 to 2008 [95% CI -8.28 to -0.80]) cancers. Trends in recommendation for surgery varied by site with significant decreases at the larynx, oral cavity, and oropharynx.Conclusion: OPC incidence is increasing among the oldest HNC patients. An increasing proportion of HPV-associated tumors could account for associated mortality improvement. There has been a shift towards non-surgical therapy possibly due to known favorable response of HPV-associated OPC to radiation therapy and/or poor surgical candidacy in this age group. The evolving treatment approach has not been detrimental to population-level survival outcomes, but optimal treatment has yet to be established. Future studies with pathologically confirmed HPV status are needed to better understand older adult OPC burden. [ABSTRACT FROM AUTHOR]

Background: Improvements in prognosis have been reported for oral cavity squamous cell carcinoma (OCSCC) in international cohorts. We sought to quantify improvement in survival of OCSCC and to determine factors associated with survival in the United States using a large administrative database.Methods: Retrospective cohort study of 13,655 patients with OCSCC in the National Cancer Database diagnosed during time periods 1998-2003 and 2004-2006. Statistical methods included chi-square and Cox regression.Results: Patients with early (Stages I and II) and late stage (Stages III and IV) disease had improvements of 36.2% and 16.0% in three-year overall survival, respectively. Receipt of adjuvant chemoradiation increased from 8.3% to 36.4% for late stage disease, while receipt of adjuvant therapy in early stage disease remained stable. Patients with early stage disease increased from 64.1% for years 1998-2003 to 67.4% during 2004-2006 (p<.001). Being diagnosed between 2004 and 2006 was associated with decreased mortality in early and late stage disease (HR 0.67 and 0.87, p<.001, respectively). Other treatment factors associated with improved survival for patients of all stages included treatment in a high-volume center (HR 0.91, p=.002) and undergoing neck dissection (HR 0.90, p=.001).Conclusions: Three-year overall survival has increased dramatically for OCSCC patients. Advanced stage patients have been increasingly treated with chemoradiotherapy, while treatment of early stage patients has remained relatively unchanged. While other factors such as negative surgical margins and undergoing neck dissection may be partly responsible for improvements in early stage patients, further study is needed to understand the observed survival improvements. [ABSTRACT FROM AUTHOR]

Summary: Human papillomavirus (HPV) is etiologically responsible for a distinct subset of head and neck squamous cell cancers (HNSCCs). HPV-positive HNSCCs (HPV-HNSCCs) most commonly arise from the oropharynx and are responsible for the increasing incidence of oropharyngeal SCC (OSCC) in the United States (US) and abroad. HPV-positive OSCC (HPV-OSCC) has a unique demographic and risk factor profile and tumor biology. HPV-OSCC patients tend to be white, younger, and have a higher cumulative exposure to sexual behaviors as compared with HPV-negative OSCC patients. HPV-positive tumor status also significantly improves survival, and is indeed the single strongest prognostic factor for OSCC. The mechanisms that underlie the improved prognosis conferred by HPV-positive disease are unknown. The purpose of this review is to describe the clinical impact of HPV status in HNSCC, particularly in OSCC, both in terms of the unique clinic-demographic profile and prognostic implications. [ABSTRACT FROM AUTHOR]

Summary: Objectives: The epidermal growth factor receptor (EGFR) is a validated target in head and neck squamous cell carcinoma (HNSCC). In recurrent and/or metastatic (R/M) HNSCC, resistance to anti-EGFR therapy inevitably occurs. Downstream activation of the PI3K/Akt/mTOR pathway is an established resistance mechanism. Concurrent mTOR blockade may improve efficacy of anti-EGFR therapy. Materials and methods: Erlotinib 150mg daily and temsirolimus 15mg weekly were administered to patients with platinum-refractory R/M HNSCC and ECOG performance status 0–2. The primary endpoint was progression-free survival (PFS). Correlative studies determined PIK3CA and HRAS mutation status; p16, EGFR, pS6K, pAkt and PTEN expression; and pre- and post-treatment plasma levels of 20 immunomodulatory cytokines. Results: Twelve patients enrolled; six withdrew within 6weeks due to toxicity or death, prompting early closure of the trial. Grade⩾3 toxicities included fatigue, diarrhea, gastrostomy tube infection, peritonitis, pneumonia, dyspnea, and HN edema. Median PFS was 1.9months. Median overall survival was 4.0months. Six/12 tumors were p16(+), 9/11 lacked measurable PTEN expression, and 1/12 harbored a PIK3CA mutation. On exploratory analysis, high baseline plasma VEGF and interferon-gamma levels marginally associated with tumor progression. Conclusions: The combination of erlotinib and temsirolimus was poorly tolerated. Low prevalence of PTEN expression and 8% incidence of PIK3CA mutations indicate biological relevance of this pathway in R/M disease. Investigation of more tolerable combinations of EGFR and PI3K/Akt/mTOR pathway inhibitors in selected HNSCC patients is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Only one in three head and neck cancer (HNC) patients present with early-stage disease. We aimed to quantify associations between state Medicaid expansions and changes in insurance coverage rates and stage at diagnosis of HNC.Methods: Using a quasi-experimental difference-in-differences (DID) approach and data from 26,330 cases included in the Surveillance, Epidemiology, and End Results program (2011-2015), we retrospectively examined changes in insurance coverage and stage at diagnosis of adult HNC in states that expanded Medicaid (EXP) versus those that did not (NEXP).Results: There was a significant increase in Medicaid coverage in EXP (+1.6 percentage point (PP) versus) vs. NEXP (-1.8 PP) states (3.36 PP, 95% CI = 1.32, 5.41; p = 0.001), and this increase was mostly among residents of low income and education counties. We also observed a reduction in uninsured rates among HNC patients in low income counties (-4.17 PP, 95% CI = -6.84, -1.51; p = 0.002). Overall, early stage diagnosis rates were 28.3% (EXP) vs. 26.7% (NEXP), with significant increases in early stage diagnosis post-Medicaid expansion among young adults, 18-34 years (17.2 PP, 95% CI - 1.34 to 33.1, p = 0.034), females (7.54 PP, 95% CI = 2.00 to 13.10, p = 0.008), unmarried patients (3.83 PP, 95% CI = 0.30-7.35, p = 0.033), and patients with lip cancer (13.5 PP, 95% CI = 2.67-24.3, p = 0.015).Conclusions: Medicaid expansion is associated with improved insurance coverage rates for HNC patients, particularly those with low income, and increases in early stage diagnoses for young adults and women. [ABSTRACT FROM AUTHOR]

Objective: Evaluate trends in place of death for patients with head and neck cancers (HNC) in the U.S. from 1999 to 2017 based on the CDC WONDER (Wide-ranging Online Data for Epidemiologic Research) database.Materials/methods: Using patient-level data from 2015 and aggregate data from 1999 to 2017, multivariable logistic regression analyses (MLR) were performed to evaluate for disparities in place of death.Results: We obtained aggregate data for 101,963 people who died of HNC between 1999 and 2017 (25.9% oral cavity, 24.6% oropharynx/pharynx, 0.4% nasopharynx, and 49.1% larynx/hypopharynx). Most were Caucasian (92.7%) and male (87.0%). Deaths at home or hospice increased over the study period (R2 = 0.96, p < 0.05) from 29.2% in 1999 to 61.2% in 2017. On MLR of patient-level data from 2015, those who were single (ref), ages 85+ (OR 0.78; 95% CI: 0.68, 0.90), African American (OR 0.73; 95% CI: 0.65, 0.82), or Asian/Pacific Islanders (OR 0.66; 95% CI: 0.54, 0.81) were less likely to die at home or hospice. On MLR of the aggregate data (1999-2017), those who were female (OR 0.87; 95% CI: 0.83, 0.91) or ages 75-84 (OR 0.79; 95% CI: 0.76, 0.82) were also less likely to die at home or hospice. In both analyses, those who died from larynx/hypopharynx cancers were less likely to die at home or hospice.Conclusions: HNC-related deaths at home or hospice increased between 1999 and 2017. Those who were single, female, African American, Asian/Pacific Islander, older (ages 75+), or those with larynx/hypopharynx cancers were less likely to die at home or hospice. [ABSTRACT FROM AUTHOR]

Importance: United States military personnel during the Vietnam Era were potentially exposed to Agent Orange, a known carcinogen. The link between Agent Orange and head and neck cancers is largely unknown; laryngeal cancer is currently the only subsite with sufficient evidence of an Agent Orange association.Objective: We aim to determine the relationship between Agent Orange exposure and the incidence of head and neck cancers in Vietnam Era veterans as well as any relationship with head and neck cancer survival.Materials and Methods: The present study utilizes the Veterans Affairs Corporate Data Warehouse (VA CDW) to identify Vietnam Era veterans, their Agent Orange exposure status, limited demographic data, presence of head and neck cancer, and survival data.Results: Of 8,877,971 Vietnam Era veterans, 22% self-reported exposure to Agent Orange, and 54,717 had a diagnosis of head and neck cancer. Agent Orange exposure significantly predicted upper aerodigestive tract carcinoma, with a relative risk (RR) of 1.10. On subsite analysis, Agent Orange exposure (as well as race, gender, and substance use) was significantly associated with oropharyngeal (RR 1.16), nasopharyngeal (RR 1.22), laryngeal (1.11), and thyroid (1.24) cancers. Agent Orange exposure was associated with improved 10-year overall survival in upper aerodigestive tract cancer patients.Conclusions and Relevance: Self-reported Agent Orange exposure correlated with increased risks of oropharyngeal, nasopharyngeal, laryngeal, and thyroid cancers, and predicted improved survival in upper aerodigestive tract cancer patients. These findings broaden our understanding of the risks of Agent Orange exposure. [ABSTRACT FROM AUTHOR]

Objectives: HPV mediated head and neck squamous cell carcinoma (HPVmHNSCC) is increasing in prevalence in the United States, as are reports of patients with multiple HPVmHNSCCs. The prevalence, demographics, and treatment implications of this emerging clinical entity are poorly understood.Materials and Methods: We performed a multitiered assessment of patients with multiple HPVmHNSCC including: 1. systematic review of the literature, 2. query of the 2017 Surveillance, Epidemiology and End Results (SEER) database and 3. institutional level reporting at two high volume academic centers.Results: Systematic literature review: 13 articles met inclusion criteria (48 patients with multiple HPVmHNSCC). Pooled prevalence rate of multiple HPVmHNSCC was 2.64%. SEER database: 60(0.95%) patients with HPVmHNSCC had two tumors. Patients with multiple HPVmHNSCC were more likely to be younger and present with a lower T and N stage (p < 0.025 for all). The second identified tumor was more likely to be contralateral, found synchronously, of smaller size, and to occur in the tonsil (p < 0.05 for all). Institutional reporting: 17(1.69%) patients with HPVmHNSCC had two primary tumors. Similar to the SEER database, patients with multiple HPVmHNSCC were more likely to present with a low T stage and tonsil location (p < 0.007 for both).Conclusion: Multiple HPVmHNSCCs occur in a subset of HPVmHNSCC cases with distinct characteristics. Thorough interrogation of all oropharyngeal subsites should be performed as part of the initial workup for HPVmHNSCC, with consideration given to contralateral tonsillectomy at the time of surgical resection for HPV mediated tonsil cancers due to the prevalence of contralateral tonsil primaries. [ABSTRACT FROM AUTHOR]