Head And Neck Cancer Outcomes Research Articles

Disparities in head and neck cancer (HNC): An insight of the National Inpatient (NIS) database.

e13730 Background: Despite the decline in tobacco use, the incidence of head and neck cancers continues to increase in part due to HPV. HNC accounts for 4% of all cancers in the United States (USA), with particularly high morbidity in oncology. There is a complex interplay of factors that contributes to the incidence and prevalence of HNC; among these, sociodemographic characteristics and net income are notably linked to poorer outcomes within African American and Latino communities. Interestingly, despite a higher incidence in the White population, disparities persist. Consequently, there is a pressing need for a more nuanced characterization to comprehensively grasp the impact of sociodemographic factors on HNC outcomes. Methods: This was a retrospective cohort analysis of adults admitted to hospitals in the USA between 2016 and 2020 with a primary diagnosis of HNC. Data was obtained from the NIS Database, the largest publicly available inpatient database in USA, with over 7 million in-hospital stays per year. The primary outcome was to describe the trends of HNC, comparing sociodemographic characteristics. Secondary outcomes included the impact of being cared for in Teaching Hospitals (TH) vs. nonteaching hospitals (NTH) and length of stay (LoS). Hypothesis testing for categorical variables was tested with Chi-Square. Continuous variables were tested with a Student's t-test. Statistical significance was defined as a two-tailed P value of <0.05. Results: 191,740 patients met inclusion criteria: patients admitted between January 2016 and December 2020 under the primary diagnosis of HNC, corresponding to the billable code of the International Classification of Diseases 10th Revision, and patients 18 and older. Of all patients, 159,985 were admitted to TH and 31,755 in NTH. The most common geographic locations were the south region, 34% vs 46%, and the central region, 24% vs 20% for TH and NTH, respectively. The mean patient age was 62 in TH and 65.4 in NTH (p<0.001). The most affected sex was male. Hospitalization LoS (median) was 6.3 days in TH and 5.4 days in NTH (p<0.001). Furthermore, mortality was higher in NTH 7.51% vs 4.87% in TH (p<0.001). Most patients had a lower income: 50% in TH vs 62% in NTH had an income under the 50 bracket (p<0.001). White was the most common race among admitted patients (p<0.001). Chronic kidney disease, obesity, and coronary artery disease were significantly associated comorbidities (p<0.001). The two most commonly described complications during admission were AKI (p= 0.58) and mechanical ventilation (p=0.55). Conclusions: Low income is associated with higher mortality in patients with HNC. Socioeconomic determinants of health have been shown to have a predominant influence on outcomes over classic risk factors. Despite a greater LoS in teaching hospitals, this was inversely related to mortality, which could be associated with a more comprehensive diagnostic process and cancer-related care.

Effect of Rurality in Head and Neck Cancer: A Scoping Review.

This scoping review sought to evaluate the current literature regarding the following outcomes in relation to rurality: stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes of head and neck cancer (HNC). A literature search was performed using PubMed (MEDLINE), Science Direct, EMBASE, SCOPUS, and Web of Science databases. A 20-year study cutoff from the initial search was used to increase the comparability of the studies regarding population and standards of clinical care. These searches were designed to capture all primary studies reporting HNC incidence, presenting characteristics, treatments, and treatment outcomes. Two reviewers independently screened abstracts, selected articles for exclusion, extracted data, and appraised studies. Critical appraisal was done according to the Joanna Briggs Institute Quality Assessment Tool for Cohort Studies. Twenty eligible original articles were included. Stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes were measured. Our review indicates that although this relationship is unclear, there may be variations in treatment choice for laryngeal cancer based on geographic location and rural residency status. The studies assessing HNC outcomes related to stage at diagnosis, clinical characteristics, treatment characteristics, and overall survival demonstrated conflicting findings, indicating a need for further research examining HNC outcomes with a focus on rurality as the main exposure. The relationship between HNC and rural-urban status remains unclear. More studies are needed, along with a consistent metric for measuring rurality and recruitment of comparable populations from both rural and urban areas. Laryngoscope, 2024.

Abstract 4845: Evaluating racial disparities in immune checkpoint inhibitor survival and autoimmunity

Abstract Introduction: In recent years, immune checkpoint inhibitors (ICI) have revolutionized the landscape of treatment across a variety of cancers. Potential concerns regarding racial disparities in ICI access and therapeutic efficacy have been well documented. Recent studies have indicated improved ICI access and response outcomes in White patients compared to minority groups with head and neck cancer (HNC) and melanoma patients. In contrast, patients diagnosed with lung cancer have been mixed, with some research suggesting black patients may fare better with ICI therapy. Existing literature is largely limited to retrospective studies with small population sizes, and lacks comparisons of racial disparities across malignancies. We aim to describe and compare racial inequities in ICI outcomes in HNC, melanoma, and lung cancer. Methods: The TriNetX US Collaborative Network database was queried for patients >18 years-old with a diagnosis of head and neck cancer, melanoma or lung cancer that were treated with ICIs. Malignancy cohorts were defined by race: non-Hispanic White (NHW) and Black. Race cohorts were 1:1 propensity score matched (PSM) for comorbidities, oncologic stage, and chemoradiation treatment. Demographic differences in cohorts were evaluated prior to matching. Following PSM, overall survival and rates of autoimmunity were assessed at 5 years. Results: 19,443 NHW and 2,827 Black patients treated with ICI were identified. At a baseline, the Black patient cohorts had significantly higher rates of comorbidies (p<0.02). Across all malignancies, the geographic distribution of NHW patients was more equally distributed compared to Black patients (majority south). With PSM, black HNC patients had significantly lower survival rates compared to NHW [HR: 1.4 (1.2, 1.6), p=0.0002]. In melanoma, the same trend was present, though not significant [HR: 1.3 (0.95, 1.7), p=0.1]. In contrast, in lung cancer, Black patients had significantly higher survival rates compared to NHW patients [HR 0.78 (0.70, 0.86), p<0.0001]. In HN and lung cancer, NHW patients had significantly higher rates of autoimmune conditions after ICI therapy compared to Black [OR: 2.0 (1.4,2.8), 1.2 (1.0, 1.4), respectively]. Conclusion: This study represents the most extensive analysis of racial disparities on ICI outcomes across malignancies. This study found that black patients treated with ICIs had decreased survival rates at 5 years compared to NHW patients in HNC and melanoma, but increased survival rate in lung cancer. This disparity persisted following PSM, matching cohorts for comorbidities, oncologic stage and adjuvant therapy. Black patients also had significantly lower rates of autoimmunity in HN and lung cancer. Noted differences in survival may be a reflection of geographic practice differences, access to care and/or socioeconomic status. Further investigation is required to elucidate the underlying etiologies of these trends. Citation Format: Kathryn L. Nunes, Pablo Llerena, Praneet Kaki, Shreya Mandloi, Annie Moroco, Eric Mastrolonardo, David M. Cognetti, Adam J. Luginbuhl, Joseph M. Curry. Evaluating racial disparities in immune checkpoint inhibitor survival and autoimmunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4845.

Five-Year Mortality Outcomes for Eating As Treatment (EAT), a Health Behavior Change Intervention to Improve Nutrition in Patients With Head and Neck Cancer: A Stepped-Wedge, Randomized Controlled Trial

BackgroundMalnutrition affects up to 80% of patients with head and neck cancer (HNC), and is associated with higher burden of disease, poorer treatment outcomes, and greater mortality. The Eating As Treatment (EAT) intervention is a behavioural intervention, previously demonstrated to be effective for improved nutritional status, depression and quality of life, in patients with HNC. This paper examines the impacts of the EAT intervention on five-year mortality among participants. MethodsA multi-centre stepped-wedge randomised controlled trial was conducted in five Australian hospitals. Dietitians were trained to deliver EAT, a combination of motivational interviewing and cognitive behaviour therapy strategies, to patients with HNC receiving radiation therapy. This paper describes secondary analyses of survival benefit on an intention to treat basis. Differences in proportions of 5-year all-cause mortality between control and EAT intervention arms were analysed using multivariable logistic regression and 5-year survival rates were analysed using Cox proportional hazard regression. Analyses controlled for temporal effects (study time), hospital site (clustering), and baseline nutritional status differences. ResultsOverall, there were 64 deaths in the 5 years following enrolment; 36 (24%) among those assigned to the control condition and 28 (18%) among those assigned to EAT. Logistic regression showed statistically significant reduced odds in favour of EAT (OR= 0.33, 95%CI 0.11-0.96), with an absolute risk reduction of 17%(0.01 to 0.33%), a relative risk reduction of 55% (0.22-0.92), resulting in the number needed to treat of 6 (4 -13). Survival analysis found that risk of death was significantly reduced by the EAT intervention (Hazard Ratio 0.39, 0.16-0.96). ConclusionsEAT showed a statistical and clinically meaningful survival benefit, probably via improved nutrition during radiotherapy. This survival benefit strengthens the finding of the main trial showing that a behavioural intervention focussed on nutrition could improve HNC outcomes. Replication studies using stepped-wedge designs for implementation into clinical practice may be warranted.

Aspirin use and head and neck cancer survival and recurrence.

Head and neck cancer (HNC) has low 5-year survival, and evidence-based recommendations for tertiary prevention are lacking. Aspirin improves outcomes for cancers at other sites, but its role in HNC tertiary prevention remains understudied. HNC patients were recruited in the University of Michigan Head and Neck Cancer Specialized Program of Research Excellence (SPORE) from 2003 to 2014. Aspirin data were collected through medical record review; outcomes (overall mortality, HNC-specific mortality, and recurrence) were collected through medical record review, Social Security Death Index, or LexisNexis. Cox proportional hazards models were used to evaluate the associations between aspirin use at diagnosis (yes/no) and HNC outcomes. We observed no statistically significant associations between aspirin and cancer outcome in our HNC patient cohort (n = 1161) (HNC-specific mortality: HR = 0.91, 95% CI = 0.68-1.21; recurrence: HR = 0.94, 95% CI = 0.73-1.19). In analyses stratified by anatomic site, HPV status, and disease stage, we observed no association in any strata examined with the possible exception of a lower risk of recurrence in oropharynx patients (HR = 0.60, 95% CI 0.35-1.04). Our findings do not support a protective association between aspirin use and cancer-specific death or recurrence in HNC patients, with the possible exception of a lower risk of recurrence in oropharynx patients.

The interplay between tumor and nodal microenvironments for the formation of nodal premetastatic niche in head and neck cancer.

Head and neck cancer (HNC) encompasses a number of malignancies originating in the head and neck area. In patients with HNC, cervical lymph nodes constitute metastatic sites for cancer cells that escape primary tumors. The premetastatic niche (PMN) is a crucial concept in understanding metastatic disease. PMN refers to the microenvironment resulting mainly from primary tumor cells to foster metastatic tumor cell growth at a distant organ. Tumor microenvironment (TME) plays an important part in the pathogenesis of PMN. A significant prognostic factor is the close association between metastases of lymph nodes and organ dissemination in many different malignancies. The nodal premetastatic niche (NPMN) is a particular type of PMN located within the lymph nodes. NPMN formation is specifically important in HNC as regional lymph node metastasis commonly occurs. The formation happens when tumor cells create a supportive microenvironment within lymph nodes, facilitating their survival, growth, spread, and invasion. This complex mechanism involves multiple steps and cellular interactions between the primary tumor and tumor microenvironment. Several extracellular matrix (ECM) macromolecules, cytokines, and growth factors are implicated in this process. The aim of this article is to present the most recent data on the regulation of the lymph node PMN at molecular and cellular levels in HNC, as well as insights with respect to the relationship between primary tumor cells and the microenvironment of lymph nodes, and the formation of NPMN. We also critically discuss on potential targets for preventing or disrupting nodal metastases and identify potential biomarkers for predicting HNC outcomes.

Pre-rehabilitation interventions for patients with head and neck cancers: A systematic review and meta-analysis.

To investigate the effect of pre-rehabilitation interventions such as nutrition and exercise for patients with head and neck cancer (HNC). Web of Science, PubMed, Scopus, Google Scholar, and Cochrane databases were searched up to December 2022. Quality of life, length of hospital stay, postoperative complications, change in body mass index or muscle mass, and functional assessments were the primary outcomes. PRISMA guidelines were adhered to, and the study was registered on PROSPERO. The Cochrane Collaboration tool and Newcastle Ottawa scale assessed the quality of included studies. Pooled data are presented as odds ratios (OR) and 95% confidence intervals (CI). Analysis was conducted using RevMan5.4. A total of 31 articles were included for quantitative analysis and 15 for qualitative synthesis. Nutrition alone resulted in significant weight retention (2.60; 2.32, 2.88, p < 0.00001), length of stay (-4.00; -6.87, -1.13), p = 0.0006) and complications (0.64; 0.49, 0.83, p = 0.0009). Nutrition and psychoeducation resulted in a significant reduction in mortality rate (0.70; 0.49, 1.00, p = 0.05 and 0.60; 0.48, 0.74, p < 0.00001), and exercise resulted in a significant reduction in dysphagia (0.55; 0.35, 0.87, p = 0.01). Exercise with nutrition resulted in significant improvements in weight loss, length of stay, complications, and dysphagia. Randomized controlled trials (RCTs) had a moderate risk of bias and cohort studies were of fair to good quality. Prehabilitation programs based on exercise, nutrition, or psychoeducation demonstrated improved post-interventional outcomes in HNC, such as quality of life, and mortality and morbidity. Studies with longer follow-ups and larger sample sizes, and investigations comparing nutritional supplements with exercise programs are needed.

Differential Response to Radiation Fractionation in Head and Neck Cancer Patient-Derived Xenografts

Despite optimal management with conventionally fractionated radiotherapy, head and neck cancer (HNC) mortality is driven by locoregional failure. With the increasing development of hypofractionated regimens in other malignancies, we sought to investigate the sensitivity of patient HNC to radiation fractionation using murine patient-derived xenografts (PDXs). We developed PDXs from three HNC patients who underwent primary surgical resection and enrolled on our IRB-approved (PRO00040992) prospective HNC tumor bank by implanting freshly resected tumors subcutaneously in the flank of NSG-SGM3 mice. PDXs from each patient were randomized to receive no radiation, 2 Gy x 5 fractions delivered daily (conventional arm) or 10 Gy in a single fraction (hypofractionation arm). Tumor volume was measured until 15 days post-RT, when mice were sacrificed. Bulk RNA sequencing analysis was performed on PDX tumors after intervention. Three PDX tumors from three unique patients (P006, P010 and P016) were successfully developed and irradiated per protocol. Unique responses to radiation were seen with each tumor: P010 showed equal sensitivity to both the conventional and hypofractionated regimens; P006 showed intermediate sensitivity to the conventional regimen with high sensitivity to hypofractionation, and P016 was resistant to conventional fractionation but showed sensitivity to hypofractionation. Concurrent with the patient-specific PDX response to fractionation, principal component analysis demonstrated that each patient PDX had a unique signature of differentially expressed genes in response to the conventional and hypofractionated regimens. HNC PDXs show differential tumor and genomic response to radiation fractionation regimens. A precision approach to radiation fractionation for HNC may improve tumor control outcomes in HNCs.

Exploring Olfactory Dysfunction as a Marker of Frailty and Postoperative Outcomes in Head and Neck Cancer

Olfactory dysfunction (OD) is increasingly recognized as a robust marker of frailty and mortality. Despite broad recognition of frailty as a critical component of head and neck cancer (HNC) care, there is no standardized frailty assessment. To assess the prevalence of OD and its association with frailty and postoperative outcomes in HNC. In this prospective cohort study with enrollment between February 17, 2021, to September 29, 2021, at a tertiary academic medical center, 85 eligible adult patients with primary, treatment-naive HNC of mucosal or cutaneous origin were included. Patients with a history of COVID-19, neurocognitive, or primary smell/taste disorders were excluded. Prospective olfactory assessments (self-reported, visual analog scale [VAS] and psychophysical, University of Pennsylvania Smell Identification Test [UPSIT]) with concurrent frailty assessment (Risk Analysis Index [RAI]) were used. Olfactory-specific quality of life (QOL) was examined with brief Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). The primary outcome was the prevalence of OD as assessed by VAS (0-10, no to normal smell) and UPSIT (0-40, higher scores reflect better olfaction) and its association with frailty (RAI, 0-81, higher scores indicate greater frailty). For surgical patients, secondary outcomes were associations between OD and postoperative length of stay (LOS), 30-day postoperative outcomes, and QOD-NS (0-21, higher scores indicate worse QOL). Among 51 patients with HNC (mean [SD] age, 63 [10] years; 39 [77%] male participants; 41 [80%] White participants), 24 (47%) were frail, and 4 (8%) were very frail. Despite median (IQR) self-reported olfaction by VAS of 9 (8-10), 30 (59%) patients demonstrated measured OD with psychophysical testing. No meaningful association was found between self-reported and psychophysical testing (Hodges-Lehmann, <0.001; 95% CI, -2 to 1); a total of 46 (90%) patients did not report decreased olfaction-specific QOL. Median UPSIT scores were lower in frail patients (Hodges-Lehmann, 6; 95% CI, 2-12). Multivariate modeling demonstrated severe microsmia/anosmia was associated with 1.75 (95% CI, 1.09-2.80) times odds of being frail/very frail and approximately 3 days increased LOS (β, 2.96; 95% CI, 0.29-5.62). Although patients with HNC are unaware of olfactory changes, OD is common and may serve as a bellwether of frailty. In this prospective cohort study, a dose-dependent association was demonstrated between increasing degrees of OD and frailty, and the potential utility of olfaction was highlighted as a touchstone in the assessment of HNC frailty.

Association of molecular profiles of head and neck squamous cell carcinoma with heterogeneity across racial/ethnic groups in the United States.

e18036 Background: Significant disparities exist across the head and neck cancer (HNC) care continuum in presentation, treatment, and survival. Along with demographic factors such as race or ethnicity, tumor-specific molecular signatures may play a role in these differences. In the United States, the current body of literature mainly highlights molecular contrasts between Black and White patients. Here, we further investigate the molecular profiles of Black and White patients with HNC and add to the literature by comparing additional racial/ethnic groups in a large, real-world cohort. Methods: De-identified records of patients with a primary diagnosis of HNC who underwent Tempus xT testing (Tempus Labs, Chicago, IL) were selected from the Tempus Database. Those with squamous cell histology and self-reported race were selected for retrospective analysis. Briefly, Tempus xT is a targeted, tumor/normal-matched panel that detects single-nucleotide variants, insertions and/or deletions, and copy number variants in 648 genes, as well as chromosomal rearrangements in 22 genes with high sensitivity and specificity. Tumor mutational burden (TMB) was calculated by dividing the number of nonsynonymous mutations by the megabase size of the panel. Results: Among the 749 patients included, most identified as Non-Hispanic/Latino (NHL) White (n = 570), while 62 identified as NHL Black, 44 as NHL Asian/Pacific Islander (API), 21 as NHL of other races, and 52 as Hispanic/Latino of any race. Age at diagnosis differed between races ( P= 0.009). Oral cavity was the most common subsite in our cohort (N = 306, 41%). TMB also differed among races ( P= 0.018), with Black patients demonstrating the highest TMB (median = 4.6 mut/Mb [3.0-6.2]) and API the lowest (median = 2.3 mut/Mb [1.5-4.2]). Black patients had higher proportions of TP53 (76%), KMT2D (24%), and CTTN (15%) alterations (not significant across races). There were differences in the frequencies of OR4G11P (q = 0.031) and OR4F5 (q = 0.014) aberrations between races, with Black patients showing the highest frequencies (16% and 15%, respectively). The API population demonstrated higher frequencies of RASA1 (16%), MTAP (11%), CDKN2B (32%), and ERCC3 (11%) mutations (not significant across races). Additionally, there were differences in TERT mutations between races (q = 0.01), with API harboring the highest proportion of TERT co-mutations (52%). Conclusions: Overall, these results demonstrate that molecular profiles are heterogeneous across multiple racial/ethnic groups. Many of the alterations described here have been previously associated with outcomes in HNC. Accordingly, future investigations should aim to understand the effects of the activated pathways for clinical utility and investigate biomarkers to drive individualized treatment plans that result in equitable care.

Baseline gut microbiota composition is associated with oral mucositis and tumour recurrence in patients with head and neck cancer: a pilot study.

Mounting evidence suggests thatthe gut microbiome influences radiotherapy efficacy and toxicity by modulating immune signalling. However, its contribution to radiotherapy outcomes in head and neck cancer (HNC) is yet to be investigated. This study, therefore, aimed to uncover associations between an individual's pre-therapy gut microbiota and (i) severity of radiotherapy-induced oral mucositis (OM), and (ii) recurrence risk in patients with HNC. In this prospective pilot study, 20 patients with HNC scheduled to receive radiotherapy or chemoradiotherapy were recruited. Stool samples were collected before treatment and microbial composition was analysed using 16S rRNA gene sequencing. OM severity was assessed using the NCI-CTCAE scoring system. Patients were also followed for 12 months of treatment completion to assess tumour recurrence. Overall, 80% of the patients were male with a median age of 65.5 years. Fifty-three percent experienced mild/moderate OM while 47% developed severe OM. Furthermore, 18% experienced tumour relapse within 1 year of treatment completion. A pre-treatment microbiota enriched of Eubacterium, Victivallis, and Ruminococcus was associated with severe OM. Conversely, a higher relative abundance of immunomodulatory microbes Faecalibacterium, Prevotella, and Phascolarctobacterium was associated with a lower risk of tumour recurrence. Our results indicate that a patient's gut microbiota composition at the start of treatment is linked to OM severity and recurrence risk. We now seek to validate these findings to determine their ability to predict treatment outcomes in HNC, with the goal of using this data to inform second-generation microbial therapeutics to optimise treatment outcomes for patients with HNC.

Differential Outcomes Among Survivors of Head and Neck Cancer Belonging to Racial and Ethnic Minority Groups

Approximately 1 in 5 new patients with head and neck cancer (HNC) in the US belong to racial and ethnic minority groups, but their survival rates are worse than White individuals. However, because most studies compare Black vs White patients, little is known about survival differences among members of racial and ethnic minority groups. To describe differential survival and identify nonclinical factors associated with stage of presentation among patients with HNC belonging to racial and ethnic minority groups. This population-based retrospective cohort study used data from the 2007 to 2016 Surveillance, Epidemiology, and End Results (SEER) database and included non-Hispanic Black, Asian Pacific Islander, American Indian/Alaska Native, and Hispanic patients with HNC. The data were analyzed from December 2020 to May 2021. Outcomes were time to event measures: (HNC-specific and all-cause mortality) and stage of presentation. Covariates included nonclinical (age at diagnosis, sex, race and ethnicity, insurance status, marital status, and a composite socioeconomic status [SES]) and clinical factors (stage, cancer site, chemotherapy, radiation, and surgery). A Cox regression model was used to adjust associations of covariates with the hazard of all-cause death, and a Fine and Gray competing risks proportional hazards model was used to estimate associations of covariates with the hazard of HNC-specific death. A proportional log odds ordinal logistic regression identified which nonclinical factors were associated with stage of presentation. There were 21 966 patients with HNC included in the study (mean [SD] age, 56.02 [11.16] years; 6072 women [27.6%]; 9229 [42.0%] non-Hispanic Black, 6893 [31.4%] Hispanic, 5342 [24.3%] Asian/Pacific Islander, and 502 [2.3%] American Indian/Alaska Native individuals). Black patients had highest proportion with very low SES (3482 [37.7%]) and the lowest crude 5-year overall survival (46%). After adjusting for covariates, Hispanic individuals had an 11% lower subdistribution hazard ratio (sdHR) of HNC-specific mortality (sdHR, 0.89; 95% CI, 0.83-0.95), 15% lower risk for Asian/Pacific Islander individuals (sdHR, 0.85; 95% CI, 0.78-0.93), and a trending lower risk for American Indian/Alaska Native individuals (sdHR, 0.85; 95% CI, 0.71-1.01), compared with non-Hispanic Black individuals. Race, sex, insurance, marital status, and SES were consistently associated with all-cause mortality, HNC-specific mortality, and stage of presentation, with non-Hispanic Black individuals faring worse compared with individuals of other racial and ethnic minority groups. In this cohort study that included only patients with HNC who were members of racial and ethnic minority groups, Black patients had significantly worse outcomes that were not completely explained by stage of presentation. There may be unexplored multilevel factors that are associated with social determinants of health and disparities in HNC outcomes.

Head and Neck Cancer among American Indian and Alaska Native Populations in California, 2009-2018.

Simple SummaryIn the United States, it is estimated there will be 54,000 new cases of oral cavity and pharyngeal cancer in 2021. Tobacco exposure and drinking alcohol are the main causes of head and neck cancer (HNC). Human Papilloma Virus (HPV) is now increasing in prevalence and is the most common cause of oropharyngeal cancer in the United States. This study assessed the incidence of HNC and HPV status in American Indian/Alaska Native (AI/AN) populations in California and determined if incidence was higher among AI/ANs compared to other ethnicities. We found that AI/AN and White patients had the highest burden of late-stage HNC and HPV+ lip, oral cavity, and pharynx cancer compared to other ethnicities. In addition, AI/ANs had a decreased survival rate compared to White patients. These findings reveal ethnic or racial differences in incidence, presentation, and survival, and should inform future preventative care measures for the AI/AN population.The purpose of this study was to determine the incidence of HPV-positive (HPV+) and HPV-negative (HPV-) head and neck cancer (HNC) in the American Indian/Alaska Native (AI/AN) population in California to assess whether incidence is higher among AI/ANs compared to other ethnicities. We analyzed data from the California Cancer Registry, which contains data reported to the Cancer Surveillance Section of the Department of Public Health. A total of 51,289 HNC patients were identified for the years 2009–2018. Outcomes of interest included sex, stage at presentation, 5-year survival rate, tobacco use, and HPV status. AI/AN and White patients had the highest burden of late stage HNC (AI/AN 6.3:100,000; 95% CI 5.3–7.4, White 5.8:100,000; 95% CI 5.7–5.9) compared to all ethnicities or races (Black: 5.2; 95% CI 4.9–5.5; Asian/Pacific Islander: 3.2; 95% CI 3–3.3; and Hispanic: 3.1; 95% CI 3–3.2 per 100,000). Additionally, AI/AN and White patients had the highest burden of HPV+ lip, oral cavity, and pharynx HNC (AI/AN 0.9:100,000; 95% CI 0.6–1.4, White 1.1:100,000; 95% CI 1–1.1) compared to all ethnicities or races (Black: 0.8:100,000; 95% CI 0.7–0.9; Asian/Pacific Islander: 0.4; 95% CI 0.4–0.5; and Hispanic: 0.6; 95% CI 0.5–0.6). AI/ANs had a decreased 5-year survival rate compared to White patients (AI/AN 59.9%; 95% CI 51.9–67.0% and White 67.7%; 95% CI 67.00–68.50%) and a higher incidence of HNC in former and current tobacco users. These findings underscore the disparities that exist in HNC for California AI/AN populations. Future studies should aim to elucidate why the unequal burden of HNC outcomes exists, how to address increased tobacco usage, and HPV vaccination patterns to create culturally and community-based interventions.

Health-related quality of life in head and neck cancer survivors: Evaluating the rural disadvantage.

Head and neck cancer (HNC) survivors often experience distress and health-related quality of life (HRQOL) impairment. Research suggests that rural cancer patients may have poorer outcomes than urban patients. This study examined whether HNC patient emotional and HRQOL outcomes differ in those living in a rural versus urban location at 6 and 12 months postdiagnosis. A total of 261 HNC patients were included from a longitudinal study of HNC outcomes. The majority were diagnosed with advanced stage cancer (51.3%); the most common cancer site was oral cavity (41.0%). Rurality was measured using the US Department of Agriculture Rural Urban Commuting Area codes. Depression was measured using the Beck Depression Inventory (BDI), general HRQOL using the Short Form-36 (SF-36), and HNC-specific HRQOL using the Head and Neck Cancer Inventory (HNCI). Analyses were 2 (group) × 3 (assessment) repeated measures ANCOVAs, controlling for demographic and clinical characteristics. Approximately 45% of the sample lived in a rural location. Follow-up comparisons of significant overall models indicated that rural patients reported significantly more nonsomatic depression symptoms at 6-month follow-up. Rural patients were also more likely to report significantly poorer general mental HRQOL at 12-month follow-up, significantly poorer HNC-specific HRQOL related to eating at 6- and 12-month follow-up, and marginally worse aesthetics at 12-month follow-up. These findings are consistent with suggestions that rural HNC patients may be at heightened risk for depression symptoms and decrements in HRQOL. Patients should be screened and regularly monitored for issues with depression and HNC-specific HRQOL throughout the survivorship period.

Head and neck cancer and non-steroidal anti-inflammatory drugs: Systematic review and meta-analysis.

The objective was to assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on head and neck cancer (HNC) outcomes. A systematic review was conducted following the PRISMA guidelines. The MEDLINE and the Cochrane Central Register databases were searched. Risk of bias was assessed by the Cochrane Collaboration's tool and by the Newcastle-Ottawa Scale. Meta-analyses were performed with the RevMan software. Seventeen articles met the inclusion criteria. Quality scores for observational studies ranged between 5 and 8 stars and the RCT was assessed as high risk of bias. NSAIDs use was associated with a 13% risk reduction of HNC (OR: 0.87 95% CI 0.77-0.99). NSAIDs use was associated with a 30% reduced cancer-specific mortality and with a 40% decreased risk on disease-recurrence. NSAIDs may have a modest protective effect on HNC risk and a positive impact on cancer-specific survival and disease-recurrence. The findings do not support a protective role of aspirin on HNC outcomes.

Study of association of age at presentation with outcome in patients with head-and-neck cancer

Background: Elderly patients with head-and-neck cancer (HNC) are increasing in number. Outcome of HNC with relation to age is controversial.Methods: In this hospital-based retrospective study, medical records of 76 patients of HNC who were treated with surgery followed by radiotherapy or radiotherapy with or without chemotherapy were analysed. The patients were divided into two age groups: Group I patients ≥55 years and Group II patients <55 years. Patient characteristics, treatment and toxicities were evaluated. They were followed-up clinically and radiologically up to a median time of 16 months.Results: Complete response was 94.4% and 80.05% in Group I and II, respectively. Disease-free survival (DFS) was 53.67% and 47.8% in Group I and II, respectively (P = 0.332), whereas overall survival (OS) was 67.34% and 49.42% in two groups, respectively (P = 0.234); hence, DFS and OS are not statistically significant.Conclusion: Complete response was more frequently among patients older than 55 years in comparison to patients younger than 55 years, even though the dose delivered to them is lower. There was no statistically significant difference in both groups with respect to DFS and OS. Haematological toxicities were found more in older patients in comparison to patients younger than 55 years.

Is Frailty Associated With Worse Outcomes After Head and Neck Surgery? A Narrative Review.

Frailty has emerged as an important determinant of many health outcomes across various surgical specialties. We examined the published literature reporting on frailty as a predictor of perioperative outcomes in head and neck cancer (HNC) surgery. Narrative review with limited electronic database search and cross-referencing of included studies. PubMed was searched from inception until June 2019 to capture studies evaluating an association between frailty and perioperative outcomes among patients undergoing HNC surgery. Primary outcomes included mortality and morbidity, whereas secondary outcomes included in-hospital cost, length of stay, readmission, and discharge disposition. We identified nine series examining frailty as a predictor of outcomes in HNC. The majority of studies (77%) identified patients using a large population-based database such as the National Surgical Quality Improvement Project or National Inpatient Sample. Frailty measures applied in the HNC surgery literature include the modified frailty index, Groningen Frailty Indicator, and John Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. Most studies demonstrated a significant association between frailty and perioperative outcomes, including mortality, perioperative complications, and Clavien-Dindo grade IV complications. Furthermore, frailty was associated with greater length of hospital stay, readmission rate, and likelihood of discharge to short-term or skilled nursing facilities. The current literature demonstrates the utility of frailty as a predictor of perioperative mortality and morbidity. Further research is needed to develop frailty screening measures in order to risk-stratify patients and optimize modifiable factors preoperatively. Laryngoscope, 130:1436-1442, 2020.

Radiation Therapy in Head and Neck Cancer Clinical Research – Is there Room to Exploit Radiation-Specific Principles in Clinical Trial Design with or without Systemic Therapy?

Much of the progress in the definitive treatment of head and neck cancer (HNC) has come with combining radiation therapy (RT) and systemic therapy (ST). Yet RT-specific advances that draw upon radiobiologic principles (dose and fractionation) and technology (e.g. IMRT) have also led to improvements in HNC outcome. We aimed to characterize current HNC clinical trials, focusing on the role of RT to determine how often RT-specific hypotheses are tested. A web query of all open interventional trials on www.ClinicalTrials.gov was performed on 6/27/2017 using search terms “head and neck cancer” and specific HNC subsites. The details of each trial were characterized including the type of modality utilized (RT, drug, surgery, or other), principal investigator (PI) specialty, study funding, and whether the study tested a RT-modality specific hypothesis (focused on comparing RT dose, fractionation, techniques, use of any RT, or other). There were 841 open HNC trials identified including definitive (47.6%) and recurrent/metastatic (41.9%) populations. Most trials were phase I or non-randomized phase II studies (71.7%), rather than phase III or randomized phase II (28.3%). Among phase III and randomized phase II trials, most trials tested the combination of RT with ST (49.8%), while only 11.1% tested an RT-specific hypothesis such as dose, fractionation, modality (e.g. SBRT, protons, etc.), (p < 0.001). More trials tested an RT-specific hypothesis if one of the study PIs was a radiation oncologist (20.9% vs 6.0%, p < 0.001). Among RT-only trials, most early-phase studies tested novel treatment modalities (e.g. stereotactic radiation or proton therapy), while most later-phase studies tested dose and fractionation. RT-specific trials had low rates of federal (10.4%) or industry (2.6%) funding. RT modality-specific research hypotheses are a minority of phase II-III HNC trials, which mostly focus on incorporating ST in the definitive or recurrent/metastatic setting. Radiation oncologist PI leadership is likely to be an important factor in ensuring that radiobiologic, technologic, and other RT-specific hypotheses are incorporated into trial design to maximally exploit the potential for RT to improve HNC outcomes whether alone or in combination with ST.

Investigating the impact of self-management behaviours on quality of life and fear of recurrence in head and neck cancer survivors: A population-based survey.

Emerging cancer-survivorship research suggests that self-management can lead to improved outcomes. However, research examining the impact of self-management behaviours on quality of life (QoL) and fear of recurrence (FoR) in cancer survivors is lacking. This study investigated the relationship between self-management behaviours and QoL and FoR following treatment for head and neck cancer (HNC). Postal surveys were sent to 734 eligible HNC survivors (ICD10 C01-C14; C32) in the Republic of Ireland who were 12- to 60-months post diagnosis. QoL and FoR were measured using the Functional Assessment of Cancer Therapy (FACT-G and Head and Neck Cancer Subscale) measure and Fear of Relapse/Recurrence Scale, respectively. Seven self-management behaviours were measured using the Health Education Impact Questionnaire. Three hundred and ninety-five HNC survivors completed surveys (50.3% response rate). After controlling for sociodemographic and clinical characteristics, self-management behaviours accounted for 20% to 39.4% of the variance in QoL and FoR. Higher scores on positive and active engagement in life, constructive attitudes and approaches, and skill and technique acquisition were significantly associated with higher global QoL and lower FoR, whilst higher scores on positive and active engagement in life and constructive attitudes and approaches only were significantly associated with higher HNC-specific QoL. Additionally, lower scores on self-monitoring and insight were significantly associated with higher HNC-specific and global QoL and lower FoR. The findings highlight the potential utility of self-management interventions promoting active problem solving, positive self-talk, and skill acquisition amongst cancer survivors. However, increased self-monitoring may relate to negative outcomes in HNC, a finding that warrants further investigation.

The prognostic significance of circulating tumor cells in head and neck and non-small-cell lung cancer.

Tumor biopsy is the gold standard for the assessment of clinical biomarkers for treatment. However, tumors change dynamically in response to therapy, and there remains a need for a more representative biomarker that can be assayed over the course of treatment. Circulating tumor cells (CTCs) may provide clinically important and comprehensive tumoral information that is predictive of treatment response and outcome. Blood samples were processed for CTCs from 56 patients using the ClearCell FX system. Captured cells were phenotyped for CTC clusters and markers for immunotherapy (PD‐L1) CTC chromosomal architecture (ALK, EGFR). CTCs were isolated in 11/23 (47.8%) of head and neck cancer (HNC) patients and 17/33 (51.5%) of non‐small‐cell lung cancer (NSCLC) patients. CTCs were determined to be PD‐L1‐positive in 6/11 (54.4%) HNC and 11/17 (64.7%) NSCLC cases, respectively. 3D chromosomal DNA FISH for ALK and EGFR molecular targets showed better resolution than in 2D when imaging CTCs. HNC CTC‐positive patients had shorter progression‐free survival (PFS) (hazard ratio[HR]: 4.946; 95% confidence internal[CI]:1.571‐15.57; P = 0.0063), and PD‐L1‐positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011‐26.33; P = 0.0485). In the advanced stage NSCLC patient cohort, PFS was not found to be associated with CTCs prior to therapy ([HR]:2.246; 95% [CI]:0.9565‐5.273; P = 0.0632), nor the presence of PD‐L1 expression ([HR]:1.646; 95% [CI]:0.5128‐5.283; P = 0.4023). This study demonstrated that CTCs are predictive of poorer outcomes in HNC and provides distinct and separate utility for CTCs in HNC and NSCLC, which may be more representative of the disease burden and overall survival than the parameters used to measure them.