Head And Neck Cancer Survival Research Articles

Stage of presentation and survival rates of head and neck cancer in Western Cape, South Africa

Background: The Western Cape province in South Africa has a high age-standardised mortality from cancer. Most literature reports significantly poorer access to healthcare, more advanced cancers and worse survival for rural and remote populations. This study investigates if significant disparities exist with regard to stage at presentation and overall survival of patients with head and neck cancer (HNC) between geographical areas within the Western Cape province in South Africa.Methods: A retrospective chart review was conducted on all patients managed at the Combined ENT Head and Neck Oncology clinic at Groote Schuur from January 2010 to December 2014. Ethics approval was granted by the University of Cape Town Human Research Ethics Committee (HREC, 351-2017).Results: Although we observed no significant difference in TNM clinical stages or overall survival between metropolitan and remote patients, there were statistically and clinically significant differences in terms of both stages of HNC and overall survival between some individual metropolitan and remote areas. The remote area of Eden had a median overall survival of more than 6 months less than that of the Southern subdistrict of the City of Cape Town.Conclusion: Differences in HNC stages and overall survivals between some subdistricts of the City of Cape Town and remote areas are not only statistically significant but also clinically relevant.Contribution: This article highlights the need to improve on diagnostic and referral pathways for management of patients with HNC in the Western Cape.

Abstract C010: Racial and ethnic differences in stage of presentation, comorbidity burden, and overall survival of oral cavity cancer

Abstract Background: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancer subsites. Head and neck cancer (HNC) has the third worst Black vs. White five-year survival rate of all cancers in the United States. Among the most important determinants of survival in OSCC and HNC in general are clinical factors such as stage of disease presentation and patients' comorbidity burden. It is unclear, however, how these prognostic clinical factors differ based on sex, or race and ethnicity. This study aimed to examine racial/ethnic and sex differences in stage of presentation, comorbidity burden, and overall survival in a cohort of adult patients with OSCC in the United States. Methods: We used the 2004 to 2018 data from the National Cancer Data Base (NCDB) and created a cohort of adult patients with OSCC. Our outcomes of interests were stage of disease presentation, grouped as early-stage vs late-stage, comorbidity burden (scored as 0, 1, 2, 3+), and overall survival. We used multivariable logistic regression to estimate the odds of late-stage presentation and higher comorbidity burden based on race/ethnicity and sex, while controlling for other clinical and non-clinical covariates. We also calculated the adjusted hazard ratios to estimate overall survival using Cox regression model. Results: Our final sample included 185,358 patients, with the majority of our sample comprised of males (68%), Non-Hispanic (NH) White patients (85%), 62% presenting with late-stage disease, and 78% with a comorbidity score of 0. In our final models, male patients were significantly more likely to present with late-stage disease compared to females (aOR =1.21; 95% CI:1.15,1.26). NH Black patients (aOR = 1.85;95%CI:1.68,2.04), Hispanic patients (aOR =1.56; 95% CI:1.39,1.74), and NH Other patients (aOR = 1.22; 95% CI:1.091.37) were more likely to present with late-stage disease compared to NH White patients. Regarding comorbidity burden, NH Black patients (aOR =1.60; 95%CI: 1.26,2.03) were more likely to have the highest comorbidity burden (comorbidity score 3+) compared to NH White patients. Finally, female patients had slightly higher survival odds than male patients (aHR = 0.97; 95% CI:0.96,1.00), while Hispanic patients (aHR = 1.17; 95% CI:1.10,1.24) and NH Other patients (aHR =1.32; 95% CI:1.25,1.40) had worse survival odds compared to NH White patients. Conclusion: There is significant racial/ethnic and gender disparities in stage of presentation and comorbidity burden in patients with OSCC, and racial/ethnic minorities seem to fair worse. It is important to improve outcomes for patients with OSCC and to recognize and mitigate racial and gender disparities. Citation Format: Dina K. Abouelella, Alexandra Belcastro, Shreya P. Ramkumar, Meng Chen, Rong Jiang, Melissa C. White, Oluwole A. Babatunde, Eric Adjei Boakye, Tammara L. Watts, Trinitia Y. Cannon, Nosayaba Osazuwa-Peters. Racial and ethnic differences in stage of presentation, comorbidity burden, and overall survival of oral cavity cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C010.

Subsite-specific trends in mid- and long-term survival for head and neck cancer patients in Japan: A population-based study.

Advances in diagnostic techniques and treatment modalities have impacted head and neck cancer (HNC) prognosis, but their effects on subsite-specific prognosis remain unclear. This study aimed to assess subsite-specific trends in mid- and long-term survival for HNC patients diagnosed from 1993 to 2011 using data from population-based cancer registries in Japan. We estimated the net survival (NS) for HNC by subsite using data from 13 prefectural population-based cancer registries in Japan. Changes in survival over time were assessed by multivariate excess hazard model of mortality. In total, 68,312 HNC patients were included in this analysis. We observed an overall improvement in 5-year NS for HNC patients in Japan. However, survival varied among subsites of HNC, with some, such as naso-, oro- and hypopharyngeal cancers, showing significant improvement in both 5- and 10-year NS, whereas others such as laryngeal cancer showed only a slight improvement in 5-year NS and no significant change in 10-year NS after adjustment for age, sex and stage. In conclusion, the study provides insights into changing HNC survival by site at the population level in Japan. Although advances in diagnostic techniques and treatment modalities have improved survival, these improvements are not shared equally among subsites.

The Intersectionality between Race, Ethnicity, and Residential-Level Socioeconomic Status in Disparities of Head and Neck Cancer Outcomes: A SEER Study.

Head and neck cancer (HNC) mortality differs by race, ethnicity, and socioeconomic status (SES). However, it is unclear whether the relationship between race/ethnicity and HNC-specific mortality varies according to the residence-level SES. Data from the Surveillance Epidemiology and End Results database included participants with primary HNC between 2006 and 2017 (followed through 2018) to assess the joint association of race/ethnicity and census-tract level SES Yost-index groups (quintiles) with all-cause and HNC-specific mortalities. Relative survival rates at 1, 5, and 10 years were calculated. Multivariable Cox proportional hazard regression models estimated hazard-ratios and 95% confidence intervals for all-cause mortality, and Fine-Gray subdistribution hazard models for HNC-specific mortality. Cumulative incidence curves for HNC-specific deaths were estimated. 76,095 patients were included in the analysis: 63.2% were <65 years, 73.4% male, and 11.3% non-Hispanic (NH) Black. Most patients (58.3%) were diagnosed at regional or distant stages and 20.6% died of HNC. The five-year relative survival rate increased with SES group, with 51.6% in the lowest SES group, and 74.1% in the highest SES group. NH-Black patients had higher risk of all-cause and HNC-specific mortality than NH-White patients, regardless of the SES group. NH-Asian/Pacific Islander and Hispanic patients had higher risk of HNC-specific mortality in some SES groups. NH-Black patients of all SES strata had significantly worse outcomes. Other factors, such as healthcare quality, may be associated with persistent disparities. The study highlights the persistence of significant racial disparities in HNC survival across socioeconomic categories. There is need to consider additional factors underlying these disparities.

Abstract 3535: Simultaneous inhibition of Axl and MerTK enhances anti-PDL1 efficacy and creates a pro-inflammatory tumor immune microenvironment in head and neck cancer

Abstract The tyrosine kinase receptors Axl and MerTK, known for their role on macrophages in regulating clearance of apoptotic cells, are highly overexpressed in head and neck cancer (HNC). Previous studies in our laboratory have shown that Axl is a critical driver of survival, proliferation, metastasis, and therapeutic resistance in HNC, and that MerTK is functionally redundant to Axl. In this study, we investigated the cooperative role of Axl and MerTK in creating an immunologically cold tumor immune microenvironment (TIME) by targeting both receptors simultaneously with a small molecule inhibitor of Axl and MerTK (INCB081776). Because Axl and MerTK are expressed on both macrophages and HNC cancer cells, we examined the effect of INCB081776 treatment on each cell type. In macrophages, Axl and MerTK signaling leads to M2-type polarization, an anti-inflammatory state that leads to the resolution of inflammation and, in cancer settings, promotes tumor growth. Our experiments suggest that treatment with INCB081776 can reduce M2 polarization and increase M1-type polarization, a pro-inflammatory state that promotes inflammation and tumor cell killing. Next, to determine the efficacy of INCB081776 on HNC cancer cells, mouse oral cancer (MOC) tumors were implanted in syngeneic mice and treated with INCB081776 alone or in combination with a monoclonal antibody against PDL1 (anti-PDL1), thereby mimicking current standard-of-care immune checkpoint inhibitor treatment. The results showed a marked effect of INCB081776 single-agent treatment on MOC tumor growth and an increase in several pro-inflammatory cell types (M1 macrophages, CD8+ T cells, total infiltrating leukocytes), suggesting that INCB081776 treatment can create an immunologically hot TIME. Further, in-depth analysis of tumor infiltrating leukocytes following INCB081776 treatment in both immunologically hot (MOC1) and cold (MOC2) HNC tumors suggested that INCB081776 has a greater effect in cold tumors. In cold tumors, levels of pro-inflammatory cells (CD8+ T cells, M1 macrophages, etc.) increased, and levels of anti-inflammatory cells (M2 macrophages, regulatory T cells, etc.) decreased, both to a greater extent than in hot tumors. Finally, the combination of INCB081776 and anti-PDL1 was superior to either treatment alone in slowing tumor growth. Together, these studies indicate that INCB081776 cooperates with anti-PDL1 in a syngeneic mouse model of HNC to slow tumor growth and create a pro-inflammatory environment, especially in immunologically cold tumors, thereby highlighting the potential clinical benefit of this therapeutic combination. Citation Format: Kourtney L. Kostecki, Mari Iida, Anne L. Wiley, Seungpyo Hong, Ravi Salgia, Paul M. Harari, Deric L. Wheeler. Simultaneous inhibition of Axl and MerTK enhances anti-PDL1 efficacy and creates a pro-inflammatory tumor immune microenvironment in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3535.

Enhanced recovery after surgery (ERAS) in head and neck oncologic surgery: Impact on return to intended oncologic therapy (RIOT) and survival

BackgroundEnhanced Recovery After Surgery (ERAS) pathways in head and neck cancer (HNC) have shown to improve perioperative outcomes and reduce complications. The longer term implications on adjuvant treatment and survival have not been studied. We hereby report the first study on the impact of an ERAS pathway on return to intended oncologic treatment (RIOT) and overall survival (OS) in HNC. Methods200 patients undergoing head and neck oncologic surgery on an ERAS pathway between March 1, 2016 and March 31, 2019 were matched to controls over the same interval. Demographic, tumor and adjuvant therapy-related data were collected, including time to adjuvant therapy(TAT) and treatment package time(TPT). Risk factors for TAT > 42 days and TPT ≥ 85 days were assessed. OS was compared and risk factors for inferior OS determined. ResultsBaseline characteristics including co-morbidities and tumor stage were similar. Of 179 patients planned for adjuvant treatment, there was no difference in RIOT rate (89.0% vs 87.5%, p = 0.753), proportion of TAT > 42 days of surgery (55.6% vs 59.7%, p = 0.642), or TPT ≥ 85 days (48.1% vs 57.1, p = 0.258), for the ERAS and control groups, respectively. On multivariate analysis, alcohol use (OR 3.58; 95 %CI 1.11–11.52) and recurrent disease status (OR 2.88; 95 %CI 1.40–5.93) were independently associated with prolonged TAT. Three-year OS was similar between the ERAS and control groups (73% vs 76%, p = 0.521). ConclusionERAS has not shown to improve RIOT or OS in the current study. However, its benefit for perioperative outcomes is undeniable and further studies are required on longer term quality and survival outcomes.

Cannabis Use in Patients with Head and Neck Cancer and Radiotherapy Outcomes

<h3>Purpose/Objective(s)</h3> Marijuana use in the population is increasing as states continue to allow for both medicinal and recreational use. As such, the prevalence of marijuana use among patients presenting for treatment of head and neck cancer (HNC) is likely to increase as well. Anecdotally, patients are asking about marijuana use during cancer treatment and, to date, oncology professionals treating HNC are lacking sufficient data to aid in advising their patients on use during cancer care. Further, the impact of marijuana use on survival and local control in HNC is not well understood. The current study examines the associations between marijuana use and the management and outcomes in patients with HNC squamous cell carcinoma. <h3>Materials/Methods</h3> IRB approval was obtained for a retrospective evaluation in our institutional database. Two-hundred eighty patients with detailed psychosocial and substance abuse history who were treated with either definitive or adjuvant radiotherapy between August 2018 and March 2020 were included in the analyses. Overall survival (OS) and disease-free survival (DFS) were compared between current marijuana users and non-users using Kaplan-Meier curves and log-rank tests. <h3>Results</h3> 148 patients with HNC were included (mean age=62.1 yrs, SD=9.1), 78% were male, 73% were white, 22% were black. 62% of patients had SCCa of the oropharynx, 20% SCCa of the larynx, and 14% SCCa of the oral cavity. 51% were treated with definitive chemoradiotherapy, while 32% had primary surgery. 30% were current tobacco users and 70% had ever used tobacco (mean = 43.33 PY). 15% of patients reported marijuana use at time of initial diagnosis and 34% reported a history of marijuana use. Older patients and males were more likely to be currently using marijuana (p=.005 & p=.04, respectively). Current marijuana users were more likely to require narcotic pain medications and require a greater number of types of pain medications during treatment (p=0.002 and p=0.007, respectively). There were no differences between current and historical/never users on self-reported worst pain, weight loss or enteral feeding tube use during treatment, or objective measures of treatment toxicity. Additionally, there were no other significant differences between current or historical/never users were found on cancer variables or primary treatment type. <h3>Conclusion</h3> Marijuana use in patients with HNSCCa is common and little is known about patient and oncological outcomes. There were no significant differences between current and past marijuana users and non-users on clinicopathological variables, adherence, or oncologic outcomes. Marijuana use in HNC may result in more difficulty managing pain during treatment. Further research is needed to better understand marijuana use during cancer treatment, particularly frequency and method of use (i.e., smoking vs. edibles/oils), outcomes, and quality of life.

Influence of Sex in the Molecular Characteristics and Outcomes of Malignant Tumors.

BackgroundSex is frequently underestimated as a prognostic biomarker in cancer. In this study, we evaluated a large cohort of patients and public datasets to determine the influence of sex on clinical outcomes, mutational status, and activation of immune pathways in different types of cancer.MethodsA cohort of 13,619 Oncosalud-affiliated patients bearing sex-unrelated cancers was followed over a 20-year period. Hazard ratios (HRs) for death were estimated for female vs. male patients for each cancer type and then pooled in a meta-analysis to obtain an overall HR. In addition, the mutational status of the main actionable genes in melanoma (MEL), colorectal cancer (CRC), and lung cancer was compared between sexes. Finally, a gene set enrichment analysis (GSEA) of publicly available data was conducted, to assess differences in immune processes between sexes in MEL, gastric adenocarcinoma (GC), head and neck cancer (HNC), colon cancer (CC), liver cancer (LC), pancreatic cancer (PC), thyroid cancer (TC), and clear renal cell carcinoma (CCRCC).ResultsOverall, women had a decreased risk of death (HR = 0.73, CI95: 8%–42%), with improved overall survival (OS) in HNC, leukemia, lung cancer, lymphoma, MEL, multiple myeloma (MM), and non-melanoma skin cancer. Regarding the analysis of actionable mutations, only differences in EGFR alterations were observed (27.7% for men vs. 34.4% for women, p = 0.035). The number of differentially activated immune processes was higher in women with HNC, LC, CC, GC, MEL, PC, and TC and included cellular processes, responses to different stimuli, immune system development, immune response activation, multiorganism processes, and localization of immune cells. Only in CCRCC was a higher activation of immune pathways observed in men.ConclusionsThe study shows an improved survival rate, increased activation of immune system pathways, and an enrichment of EGFR alterations in female patients of our cohort. Enhancement of the immune response in female cancer patients is a phenomenon that should be further explored to improve the efficacy of immunotherapy.

A Principal Component of Quality of Life Measures Is Associated with Survival for Head and Neck Cancer Patients Treated with Radiation Therapy.

Simple SummaryHealth-related quality of life (HRQOL) surveys describe the patient experience of disease and treatment. The relationship between post-treatment recovery of HRQOL and outcome in head and neck cancer is not well characterized. Impaired recovery of numerous individual components of HRQOL were associated with increased mortality. To obtain a better understanding how HRQOL (as a whole) impacts survival, we utilized a statistical technique called principal component analysis (PCA). PCA generated a total score of several HRQOL domains, named principal component 1 (PC1), to more accurately describe the cumulative impact of poor HRQOL recovery on outcome. PC1 was associated with survival and may be a useful tool in future studies to identify at-risk patients.Background: Health-related quality of life (HRQOL) metrics can be associated with survival in head and neck cancer (HNC); however, the impact of HRQOL recovery and the relevant HRQOL domains regarding outcome are unclear. Methods: Using a single-institution database, we retrospectively reviewed HNC patients treated with definitive or postoperative radiation therapy between 2013 and 2018. The recovery of individual HRQOL domains were determined by the ratio of the post-treatment to baseline scores. Univariate and Multivariate Cox regression were used to analyze survival outcomes. Principal component analysis was used to adjust for multicollinearity of HRQOL domains. Results: In 218 HNC patients who received radiation therapy, median follow-up was 24.8 months (interquartile range (IQR) 14.5–32.0). Principal component analysis evaluating the recovery of HRQOL domains revealed two independent principal components (PC), PC1 and PC2. PC1, which received contributions from the functional domains; physical (PF), role (RF), emotional (EF), cognitive (CF), and global health status (GQOL) was significantly associated with disease-free (HR = 0.77, 95% CI 0.61–0.98, p = 0.034) and overall survival (HR = 0.76, 95% CI 0.65–0.91, p = 0.004) on multivariate analysis and PC2, had no correlation with outcome and was mainly represented by social functioning. Unplanned hospitalization was significantly associated with lower PC1 scores (β = −0.997, Std. Error = 0.244, p < 0.001). Conclusion: Our study provides evidence that post-treatment recovery of HRQOL domains were associated with overall survival (OS) in HNC. PC1 is an attractive clinical tool to assess the recovery across multiple different HRQOL and the relationship with survival. Future prospective studies may identify patients who could benefit from additional rehabilitation based on PC1 score.

Association Between Vitamin D Exposure and Head and Neck Cancer: A Systematic Review With Meta-Analysis.

BackgroundVitamin D deficiency is a well-described preventable cause of many cancers; the association of vitamin D use with the development of head and neck cancer (HNC) is not clear. We aim to conduct a systematic review of the studies assessing the relation between vitamin D exposure and the prevention and prognosis of the HNC using meta-analysis.MethodsPubMed, EMBASE, Cochrane Library, Web of Science up to 1 January 2021, and reference lists of related studies were searched. We extracted observational studies reporting the association between vitamin D (vitamin D receptor gene polymorphisms, 25-hydroxyvitamin D concentrations, and vitamin D intake) and the outcomes of interest (HNC incidence and HNC mortality) in HNC patients aged 18 or older. Fixed effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs) by RevMan (version 5.3).ResultsSixteen studies with a total of 81,908 participants were enrolled in our meta-analysis. Based on the pooled genomic analysis, comparing with participants with the genotypes of Ff + FF or FF, the pooled odds ratio (OR) of participants with the genotype of ff was 0.77 (95% CI: 0.61 to 0.97) and 0.75 (0.58 to 0.97), respectively. A similar trend was noted when comparing tt with Tt + TT or TT, in which OR (95% CI) was 0.70 (0.55 to 0.90) and 0.72 (0.55 to 0.95). No significant association was identified between BsmI polymorphism and HNC. Furthermore, the OR of HNC incidence was 0.77 (0.65 to 0.92) for participants with vitamin D intake over the ones with a regular diet. High concentrations of circulated 25-hydroxyvitamin D (25-OHD) significantly decreased by 32% of HNC incidence (OR (95% CI): 0.68 (0.59 to 0.78)) and increased HNC survival (pooled hazard ratio 1.13, 1.05 to 1.22) during a 4–5 years follow-up. High concentrations of circulating 25-OHD in patients with HNC led to a decreased risk of mortality to 0.75 (0.60 to 0.94) as the follow-up extends to 8–12 years.ConclusionsElevated activities of vitamin D by diet intake, genomic polymorphisms, or circulated 25-OHD may protect people from HNC and improve the prognosis of patients with HNC.Systematic Review RegistrationPROSPERO, identifier CRD42020176002 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=176002).

274P Comparing comorbidity indices in predicting 90-day mortality after radical radiotherapy for head and neck cancer

Treatment of head and neck cancer (HNC) is associated with significant acute toxicity, and accurately identifying patients who will not tolerate aggressive treatment remains a challenge. Comorbidity indices are known prognostic factors for HNC survival outcomes. However, no index has been found to be superior, and their performance in predicting early outcomes in HNC patients is not known. This retrospective analysis aims to determine the role of comorbidity indices in predicting 90-day mortality after radical radiotherapy. Study population included all non-thyroid, non-metastatic HNC patients who received curative intent radiotherapy, with or without chemotherapy, from 2016-2019 in a single tertiary oncology centre. 260 patients were randomly selected for model building and comparison. Multiple logistic regression was used to analyse the performance of six comorbidity scores – the Charlson Comorbidity Index (CCI), age-adjusted CCI (ACCI), head and neck CCI (HNCCI), Simplified Comorbidity Score (SCS), Adult Comorbidity Evaluation-27 (ACE-27) and the Washington University Head and Neck Comorbidity Index (WUNHCI)– in predicting risk of 90-day mortality after radical treatment. ROC analysis was done to identify the best performing index, on which further analysis was carried out to determine the best cut-off. 46 out of a total of 958 eligible patients (4.8%) died within 90 days after radical treatment in our cohort. Four of the six comorbidity scores were independent predictors of early mortality [CCI: odds ratio (OR) 1.298, p=0.004; ACE-27: OR 2.577, p<0.001; ACCI: OR 1.324, p<0.001; HNCCI: OR 2.056, p=0.001]. From ROC analysis of the remaining four comorbidity indices, ACCI was the best performing model (AUC 0.728). Calculation of the Youden Index yielded a threshold of ACCI score > 3 as the most discriminatory cut-off in predicting 90-day mortality. ACCI >3 was associated with more than 20% mortality in our cohort. Age-adjusted CCI > 3 is associated with a higher risk of early mortality in HNC patients after radical radiotherapy. This may be taken as an easily accessible reference for discussion in the clinical setting.

Head and Neck Cancer Survival Disparities by Race and Rural-Urban Context.

This study aims to examine the relationship between race and rural-urban context in head and neck cancer (HNC) survival and determine factors that potentially drive this disparity. Using the National Cancer Database from 2004 to 2015, we identified a retrospective cohort of 146,256 patients with HNC. Kaplan-Meier survival curves and the Cox proportional hazards regression were used to calculate adjusted HRs. Median survival by patient subgroup was as follows: White urban [67 months; 95% confidence interval (CI), 66.0-67.9], White rural (59.1 months; 95% CI, 57.2-60), Black urban (43.1 months; 95% CI, 41.1-44.5), and Black rural (35.1 months; 95% CI, 31.9-39.0). The difference in 5-year survival, stratified by rural-urban context, was greater among Black patients [Δ restricted mean survival time (ΔRMST) 0.18; 95% CI, 0.10-0.27] than White patients (ΔRMST 0.08; 95% CI, 0.06-0.11). In the univariate Cox proportional hazards analysis with White urban patients as reference group, Black rural patients had the worst survival (HR, 1.45; 95% CI, 1.43-1.48; P < 0.001), followed by Black urban patients (HR, 1.29; 95% CI, 1.28-1.30; P < 0.001), and White rural patients (HR, 1.08; 95% CI, 1.07-1.09; P < 0.001). This disparity persisted when controlling for demographic, socioeconomic, and clinical factors. Black patients with HNC, specifically those living in rural areas, have decreased survival. Survival differences by rural-urban status are greater among Black patients than White patients. We have shown that race and rural-urban status impact HNC survival outcomes. Our findings will help future researchers to better frame approaches to address this disparity.

COVID-19 pandemic and health care disparities in head and neck cancer: Scanning the horizon.

The COVID‐19 pandemic has profoundly disrupted head and neck cancer (HNC) care delivery in ways that will likely persist long term. As we scan the horizon, this crisis has the potential to amplify preexisting racial/ethnic disparities for patients with HNC. Potential drivers of disparate HNC survival resulting from the pandemic include (a) differential access to telemedicine, timely diagnosis, and treatment; (b) implicit bias in initiatives to triage, prioritize, and schedule HNC‐directed therapy; and (c) the marked changes in employment, health insurance, and dependent care. We present four strategies to mitigate these disparities: (a) collect detailed data on access to care by race/ethnicity, income, education, and community; (b) raise awareness of HNC disparities; (c) engage stakeholders in developing culturally appropriate solutions; and (d) ensure that surgical prioritization protocols minimize risk of racial/ethnic bias. Collectively, these measures address social determinants of health and the moral imperative to provide equitable, high‐quality HNC care.

Returning to work after head and neck cancer.

There is a lack of evidence worldwide on return to work (RTW) in head and neck cancer (HNC), possibly because traditionally those suffering with it were typically at retirement age and survival rates were low. However, in the last 30 years, HNC survival rates have increased, resulting in more people living with the after-effects of treatment for longer, and many are of working-age. The HNC population is also changing because of a 20% increased incidence of oral and pharyngeal HNCs especially in the under 65 years of age, likely accounted for by the surge in human papilloma virus positive related HNCs. The literature suggests that people who have had treatment for HNC return to work less than other cancers. The knowledge base on RTW after HNC is emergent and conclusions are currently difficult to draw. The process of returning and remaining in work is complex, affected by multiple factors and interactions. There is little evidence about work-related experiences from the perspectives of HNC survivors. There is an urgent need for more in-depth exploration of the needs and concerns of HNC survivors returning to work after treatment, with the ultimate aim of work-related intervention development.

Impact of failure to thrive on inpatient mortality and resource utilization in patients with head and neck cancer: A nationwide analysis.

e18531 Background: Failure to thrive (FTT), encompassing malnutrition and cachexia, is a common comorbidity afflicting Head and Neck cancer (HNC), brought about either by progression of disease or complications of treatment. FTT can exacerbate infections or cytopenias and delay wound healing, and has shown to affect survival in HNC. This study aims to explore the effects of FTT on mortality and resource utilization among hospitalized patients with HNC. Methods: Adult patients with HNC admitted from 2012-2017 were identified from the Nationwide Inpatient Sample database. Temporal trends of resource utilization across six years were evaluated. Multivariable logistic regression was used to evaluate risk factors for malnutrition and mortality in patients with HNC. Results: A total of 448,255 patients met inclusion criteria, of which 27.2% had FTT. Mean age was 66.3 years. Patients were predominantly male (71.8%) and white (70.4%). Patients with FTT had higher mortality (6.3% vs. 3.6%, p&lt;0.0001), longer hospital stay (9.1 vs. 5.7 days, p&lt;0.0001) and higher hospital charges ($23k vs. $18k, p&lt;0.0001). On multivariate analysis, risk factors for FTT included male sex, African American (AA) race and higher comorbidity burden. After adjusting for confounders, patients with FTT had higher inpatient mortality (OR 1.71, 95% CI 1.60-1.83, p&lt;0.001). There is an increasing trend of FTT in HNC over the years, from 22.7% to 32.6% (p trend &lt;0.001). Temporal trends in mortality, length of stay and hospital charges in those with FTT did not change significantly. Conclusions: Patients with HNC and FTT had higher inpatient mortality than those without FTT. AA patients especially were at higher risk of FTT. Inpatients with HNC and FTT had longer mean hospital stay by 3 days incurring higher healthcare costs. The study highlights an under acknowledged paradigm in HNC care and warrants further steps towards more vigilant nutritional surveillance and interventions, such as early/prophylactic enteral feeding in HNC patients. This could greatly improve quality of life and objective outcomes in HNC patients. [Table: see text]

Identifying potential prognostic biomarkers in head and neck cancer based on the analysis of microRNA expression profiles in TCGA database.

The present study aimed to identify sensitive, specific and independent prognostic biomarkers in head and neck cancer (HNC) based on microRNA expression profiles and other high‑throughput sequencing data in The Cancer Genome Atlas (TCGA) database. Identification of such prognostic biomarkers could provide insight into HNC diagnosis and treatment. The differential expression profiles of microRNAs between HNC tissues and adjacent cancer tissues in the TCGA database were analyzed (log fold‑change >2; P<0.01). Univariate and multivariate Cox regression analyses of the differentially expressed microRNAs were performed to determine those significantly related to the survival of patients with HNC. The identified microRNAs were verified by survival and receiver operating characteristic curve analyses. To better predict prognosis, a combined prognostic model (risk equation) was established based on the risk coefficient of each microRNA, calculated by a multivariate Cox regression analysis, and the risk score was calculated. To explore the signaling pathways related to prognosis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on the differentially expressed genes between the high‑risk and low‑risk groups, grouped according to the median risk score. A total of 89 differentially expressed microRNAs between HNC and adjacent cancer tissues were screened, 11 of which were identified as risk factors related to HNC survival by the univariate Cox regression analysis (P<0.05). The multivariate Cox regression analysis showed that three of the 11 microRNAs, hsa‑miR‑99a, hsa‑miR‑499a and hsa‑miR‑1911 (all P<0.01), were identified as independent risk factors significantly related to patient survival. The risk equation used was as follows: Risk score=(‑0.1597xhsa‑miR‑99a) + (0.1871 x hsa‑miR‑499a) + (0.1033 x hsa‑miR‑1911). KEGG and GO analyses showed that the JAK‑STAT signaling pathway and some metabolic pathways were associated with HNC prognosis. The present study suggested that hsa‑miR‑99a, hsa‑miR‑499a and hsa‑miR‑1911 may serve as potential prognostic biomarkers in HNC.

Patterns of Immune Infiltration in HNC and Their Clinical Implications: A Gene Expression-Based Study

Background: Immune infiltration of head and neck cancer (HNC) highly correlated with the patient's prognosis. However, previous studies failed to explain the diversity of different cell types that make up the function of the immune response system. The aim of the study was to uncover the differences in immune phenotypes of the tumor microenvironment (TME) between HNC adjacent tumor tissues and tumor tissues using CIBERSORT method and explore their therapeutic implications.Method: In current work, we employed the CIBERSORT method to evaluate the relative proportions of immune cell profiling in 11 paired HNC and adjacent samples, and analyzed the correlation between immune cell infiltration and clinical information. The tumor-infiltrating immune cells of TCGA HNC cohort was analyzed for the first time. The fractions of LM22 immune cells were imputed to determine the correlation between each immune cell subpopulation and survival and response to chemotherapy. Three types of molecular classification were identified via “CancerSubtypes” R-package. The functional enrichment was analyzed in each subtype.Results: The profiles of immune infiltration in TCGA HNC cohort significantly vary between paired cancer and para-cancerous tissue and the variation could reflect the individual difference. Total Macrophage, Macrophages M0 and NK cells resting were elevated in HNC tissues, while total T cells, total B cells, T cells CD8, B cell navie, T cell follicular helper, NK cells activated, Monocyte and Mast cells resting were decreased when compared to paracancerous tissues. Among each cell immune subtype, T cells regulatory Tregs, B cells naïve, T cells follicular helper, and T cells CD4 memory activated was significantly associated with HNC survival. Three clusters were observed via Cancer Subtypes R-package. Each cancer subtype has a specific molecular classification and subtype-specific immune cell characterization.Conclusions: Our data suggest a difference in immune response may be an important driver of HNC progression and response to treatment. The deconvolution algorithm of gene expression microarray data by CIBERSOFT provides useful information about the immune cell composition of HNC patients.

Abstract 614: Cytomegalovirus (CMV) reactivation and patient survival in head and neck cancer

Abstract There is building evidence that cytomegalovirus (CMV) may contribute to the development of solid tumors, however to date this has not been investigated in head and neck cancer (HNC). CMV is a highly prevalent, latent herpesvirus infecting over 50% of the population. CMV maintains latency in CD34+ cells, and recent work has demonstrated these latently infected cells preferentially differentiate into immunosuppressive monocytes. However, CMV is not solely immune suppressive as highly cytotoxic adaptive natural killer (NK) cells arise specifically in response to CMV reactivation. Here, we have investigated whether biomarkers of CMV reactivation are associated with patient survival in non-smoking HNC (n=184). CMV DNAemia was assessed using digital PCR, and a threshold of 1000 copies/mL serum was defined as reactivation; 22% of patients met this definition of CMV reactivation, however they did not have significantly worse survival than those without CMV reactivation (HR 1.5 (95% CI 0.7 - 3.0)). Monocytes that mobilize to the cancer site contribute to tumor-associated inflammation. Therefore, we explored whether a biomarker of inflammation, CRP, modified the association of CMV reactivation and HNC patient survival. In the absence of inflammation, there was no association between CMV reactivation and patient survival (HR 0.90 (95% CI 0.30 - 2.71)). However, those with both CMV reactivation and high inflammation had dramatically worse survival (HR 8.86 (95% CI 3.63 - 21.64)). These data are consistent with the recent report that CMV infected monocytes are immunosuppressive and suggest that stimulation of these monocytes to the tumor site may negatively impact patient survival. Future work should address the generalizability of this finding to other cancer types and determine whether CMV infected myeloid cells are present in the tumor microenvironment. Citation Format: Heather H. Nelson, Jeffrey S. Miller, DeVon Hunter-Schlichting, Rondi A. Butler, Karl T. Kelsey. Cytomegalovirus (CMV) reactivation and patient survival in head and neck 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 614.

What's Love Got to do with it? Marital status and survival of head and neck cancer.

To determine whether marital status independently predicts survival in a head and neck cancer (HNC) survivor population. In this retrospective cohort study, we analysed data from 460 adult patients (59.31±11.42) years diagnosed with HNC at an academic tertiary referral centre between 1997 and 2012. Cox proportional hazards model estimated the effect of marital status on survival. Our study had 73% men, and 82.2% were Whites. We found an association between marital status and HNC survival. Unmarried HNC patients had a 66% increase in hazard of death compared to married patients (aHR=1.66, 95% CI=1.23-2.23). This was after controlling for sociodemographic variables (age, race, sex and health insurance status), social habits (tobacco and alcohol), primary anatomical subsite (oral cavity, oropharyngeal, laryngeal and others), stage at presentation (early vs. late stage) and treatment modality (surgery, surgery with adjuvant therapies, other single modality therapy and palliative care). Being married confers survival advantage for HNC survivors. Our finding underscores the need to recognise this aspect of survivorship. Social support should be considered part of standard care for managing HNC. There may also be need to develop other support mechanisms, especially for unmarried HNC survivors.

Metformin exposure and survival in head and neck cancer: A large population-based cohort study.

Observational clinical studies of metformin for prevention and treatment of several cancer types have reported mixed findings. Although preclinical studies have suggested metformin may reduce head and neck cancer (HNC) proliferation, clinical evidence is limited. The objective of this large population-based study was to evaluate the relationship between metformin exposure following HNC diagnosis and all-cause mortality. We conducted a retrospective cohort study using the Italian Emilia-Romagna Regional administrative healthcare database, which includes demographic, hospital and outpatient prescription information for ~4.5million residents. Included patients were followed from the first hospital discharge (index) during the study period (01/2003-12/2012) with a diagnosis of HNC. Metformin exposure and select covariates were operationalized in a time-dependent manner during follow-up. Cox proportional hazards models estimated the covariate-adjusted time-dependent association between metformin exposure and all-cause mortality. Among 7872 patients diagnosed with HNC, 708 (9.0%) were exposed to metformin after HNC diagnosis, and 3626 (46.1%) died during follow-up (median follow-up: 35.2months). In the covariate-adjusted model, the all-cause mortality rate appeared lower (HR: 0.81, 95% CI: 0.61-1.09) among metformin exposed patients during the 2years post-diagnosis, while the all-cause mortality rate appeared higher (HR: 1.20, 95% CI: 0.94-1.53) among exposed patients after 2years post-diagnosis. Metformin was protective among patients ≤60years of age (HR for the period of 0-2years post-diagnosis: 0.22, 95% CI 0.09-0.56; HR for the period ≥2years post-diagnosis: 0.56, 95% CI 0.26-1.22) but not in those >60years. In this population-based study of metformin in HNC, we found a modest protective association between metformin exposure and all-cause mortality in the 2-year post-diagnosis period. Age appeared to modify the association between metformin and HNC survival.