Depth of Invasion Assessment in Laryngeal Glottic Carcinoma: A Preoperative Imaging Approach for Prognostication.

OBJECTIVE: The prognostic value of depth of invasion (DOI) in oral squamous cell cancer carcinoma and cutaneous melanoma is well established, while there is a lack of reports investigating the role of DOI in laryngeal cancer. This study aims to explore the association of glottic cancer DOI with other established pathological risk factors and nodal metastasis and evaluate the feasibility of measuring DOI preoperatively using tomographic imaging. METHODS: The medical records of glottic cancer patients treated between 2015 and 2020 in a single tertiary referral center were screened retrospectively. Pathologically measured DOI (pDOI) value was also reviewed and registered. Preoperative computer tomography (CT) was used to obtain the radiological DOI (rDOI) measured by two dedicated radiologists. Their inter-rated agreement was assessed and the correlation between pDOI and rDOI was calculated. pDOI association with the main pathology report features was assessed with univariable analysis. Cox univariable and multivariable models were used to explore the role of pDOI on survival. RESULTS: Ninety-one patients had pDOI data available, of which 59 also had rDOI data. A strong concordance between the two radiologists was found (concordance correlation coefficient = 0.96); rDOI and pDOI were highly and significantly correlated (R = 0.85; p < 0.001). pDOI was significantly higher in patients with perineural invasion (PNI; p < 0.001), lymphovascular invasion (LVI; p < 0.001), and nodal metastasis (p < 0.001). pDOI was associated with disease-free survival at univariable analysis (p = 0.04) while it did not show a significant impact (p = 0.10) at multivariable analysis. CONCLUSION: Glottic carcinoma DOI correlates with PNI, LVI, and nodal metastasis and it can be reliably assessed in a preoperative setting using CT imaging. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3230-3237, 2024.

Variations in disease burden of laryngeal cancer attributable to alcohol use and smoking in 204 countries or territories, 1990-2019.

BACKGROUND: Alcohol consumption and smoking are the leading risk factors for laryngeal cancer (LC). Understanding the variations in disease burden of LC attributable to alcohol use and smoking is critical for LC prevention. METHODS: Disease burden data of LC were retrieved from the Global Burden of Disease Study 2019. We used estimated average percentage change (EAPC) to measure the temporal trends of the age-standardized mortality rate (ASMR) of LC. RESULTS: Globally, while the ASMR of LC decreased by 1.49% (95% CI, 1.41-1.57%) per year between 1990 and 2019, the number of deaths from LC has increased 41.0% to 123.4 thousand in 2019. In 2019, 19.4 and 63.5% of total LC-related deaths were attributable to alcohol use and smoking worldwide, respectively. The ASMR of alcohol- and smoking-related LC decreased by 1.78 and 1.93% per year, whereas the corresponding death number has increased 29.2 and 25.1% during this period, respectively. The decreasing trend was more pronounced in developed countries. In some developing countries, such as Guinea and Mongolia, the LC mortality has shown an unfavorable trend. CONCLUSION: The ubiquitous decrease in LC mortality was largely attributed to the smoking control and highlighted the importance of smoking control policies. However, the disease burden of LC remained in increase and more effective strategies are needed to combat the global increase of alcohol consumption.

Does insurance type influence overall survival in patients with laryngeal squamous cell carcinoma?

OBJECTIVE: Patients with head and neck cancer with Medicaid or no insurance present at a more advanced stage and have lower survival. This study is one of the first to examine the relationship between specific insurance types and overall survival for laryngeal squamous cell carcinoma patients. STUDY DESIGN: Retrospective chart review. SETTING: Henry Ford Cancer Institute. SUBJECTS AND METHODS: A retrospective database review was performed using the Henry Ford Virtual Data Warehouse Tumor Registry. Six hundred and fifty patients diagnosed with laryngeal squamous cell carcinoma were identified. Insurance groups analyzed were fee for service, health maintenance organization, Henry Ford Medical Group - a managed care type insurance, Medicare and Medicaid/uninsured. Cox proportional hazards and Kaplan-Meier curves were generated to analyze overall survival and display survival differences respectively. RESULTS: The uninsured group had the lowest median survival time of 29.8 months (95% CI: 20.3-44.8) and the highest HR of 1.85 (95% CI 1.16-2.93) as compared to the HMO group at p < 0.001. Patients with fee for service insurance had longer overall survival compared to the other insurance types. Patients with fee for service insurance also had a high proportion of patients with advanced stage disease, but a younger mean age. Henry Ford Medical Group had a higher mean age and no statistically significant difference in survival when compared to fee for service. (p = 0.999) After controlling for socioeconomic status, insurance type remains a significant predictor of overall survival. CONCLUSIONS: Fee for service had the highest overall survival of the different insurance types, but it was only statistically significant when compared to the Medicaid/uninsured group.

Disparities in Mortality from Larynx Cancer: Implications for Reducing Racial Differences.

OBJECTIVE: Race predicts overall mortality (OM) of laryngeal squamous cell carcinoma (LSCC) in the United States (US). We assessed whether racial disparities affect cancer-specific mortality (CSM) using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Adults with LSCC from 2004 to 2015 were selected. Univariable and multivariable Cox proportional hazards and Fine-Gray competing-risks regression analysis adjusted for clinicodemographic factors defined hazard ratios (aHR). RESULTS: We identified 14,506 patients. The median age was 63 years. Most were male (11,725, 80.8%) and white (11,653, 80.3%), followed by Black (2294, 15.8%). Most had early-stage disease (7544, 52.0%) and received radiotherapy only (4107, 28.3%), followed by chemoradiation (3748, 25.8%). With median follow-up of 60 months, overall 3- and 5-year OM were 34.0% and 43.2%; CSM were 16.0% and 18.9%, respectively. Black patients had higher OM than white patients on univariable (HR 1.35, 95% CI, 1.26-1.44, P < .001) and multivariable (aHR 1.10, 95% CI, 1.02-1.18, P = .011) analyses. Black patients had higher CSM on univariable analysis (HR 1.22, 95% CI, 1.09-1.35, P < .001) but not on multivariable CSM analysis (aHR 1.01, 95% CI, 0.90-1.13, P = .864). On multivariable analysis, year of diagnosis, age, disease site, stage, treatment, nodal metastasis, marital status, education, and geography significantly predicted CSM. CONCLUSION: On multivariable analyses controlling for sociodemographic, clinical, and treatment characteristics, Black and white patients differed in OM but not in CSM. However, Black patients presented with greater proportions of higher stage cancers and sociodemographic factors such as income and marital status that were associated with worse outcomes. Efforts to target sociodemographic disparities may contribute to the mitigation of racial disparities in LSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1147-E1155, 2021.

Gender and race interact to influence survival disparities in head and neck cancer.

Gender and race disparities in head and neck squamous cell carcinoma (HSNCC) survival are independently well documented, but no prior studies have examined the joint effect of these factors on HSNCC outcomes. We aim to comprehensively estimate the effect of gender and race on overall survival in HNSCC. We constructed a retrospective cohort from the National Cancer Database for primary HNSCC of the larynx, hypopharynx, oral cavity, and oropharynx from 2010 to 2015. We used Kaplan-Meier curves and Cox proportional hazards regressions to calculate hazard ratios adjusting for treatment type, age, insurance, staging classifications, and comorbidities. Oral cavity cancer was significantly more common among Hispanic and White females compared to other sites. Female non-oropharyngeal HNSCC cases had better five-year overall survival than males (56.3% versus 54.4%, respectively), though Black females (52.8%) had poorer survival than both White (56.2%) and Hispanic (57.9%) males. There were significant differences in oropharyngeal cancer by HPV status. Notably, Black females with HPV-positive oropharyngeal OPSCC had far worse survival than any other race and gender group. These results persisted even when adjusting for potential mediating factors. Clearly gender is a significant prognosticator for HNSCC and has meaningful interactions with race. The distinct site distributions across gender and race reveal important insights into HNSCC among females. Taking into account these gender disparities while considering race is essential to providing appropriate care to head and neck patients and accurately counselling these individuals on prognosis and outcomes.

Assessment of HPV 16, HPV 18, p16 expression in advanced stage laryngeal cancer patients and prognostic significance / Avaliação da expressão do HPV 16, HPV 18, e p16 em pacientes com câncer de laringe em estágio avançado e significado prognóstico

Abstract Introduction: Human papilloma virus is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. The developmental mechanisms of laryngeal carcinomas are quite complex and controlled by various factors. Smoking and alcohol are most important risk factors. Recent studies indicate that HPV infection also plays an important role in larynx carcinomas. HPV related laryngeal carcinomas especially occur at the supraglottic region of larynx. Objective: We aimed to determine the frequency of HPV/protein16 positivity in patients with laryngeal carcinoma and association of HPV and/or p16 positivity with variables such as age, sex, smoking habits, tumor localization, lymph node metastasis, recurrence and survival in advanced stage laryngeal carcinoma in our study. Methods: This retrospective study included 90 patients with advanced laryngeal carcinoma. The Control group was 10 normal larynx mucosa specimens. The presence of HPV was investigated polyclonally by polymerase chain reaction, and protein16 with immunohistochemical method. In HPV positive cases, the presence of HPV types 16, 18 were evaluated by polymerase chain reaction. Demographic features of patients were noted. Patient survival and association with HPV/protein16 was determined. Results: Polyclonal HPV positivity was detected in 11 (12.2%) of 90 cases. Out of these 11 cases, HPV 16 was positive in 6, HPV 18 in 4, and both HPV 16 and 18 were positive in 1. In 18 (20%) of the cases, p16 was positive. Six of the cases (6.6%) had both HPV and protein16 positivity. In cases where protein16 alone or HPV and protein16 were co-positive, alcohol use was less and the tumor was found more likely to be localized in the supraglottic area. These ratios were statistically significant. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant (p= 0.011). 55.6% of protein16 positive cases was located in the supraglottic region, 33.3% was glottic and 11.1% was transglottic. Although life expectancy over 5 years were numerically higher in HPV and protein16 positive cases, this was not found to be statistically significant. There was no statistically significant relationship between HPV positivity and mean age, differentiation, smoking and alcohol use, tumor progression, lymph node metastasis, localization, recurrence, cause of mortality and treatment methods in our study. The mean follow-up period of our patients was 6.7 years. Conclusion: The close relationship between HPV and oropharyngeal squamous cell carcinoma could not be shown in larynx malignancy in many studies, including our study. Our findings support a limited role of HPV in laryngeal carcinogenesis. Protein16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant. There is a need for more populated clinical trials, where neoplastic proliferation is better demonstrated and the accuracy of the results obtained is supported by different techniques.

Resumo Introdução: O papilomavírus humano é um fator de risco etiológico para um subconjunto de carcinoma espinocelular de cabeça e pescoço. Tem sido demonstrado que o HPV é um poderoso biomarcador prognóstico para o câncer de orofaringe, mas seu papel na laringe ainda não foi explorado em profundidade. Os mecanismos de desenvolvimento dos carcinomas de laringe são bastante complexos e controlados por vários fatores. Tabagismo e álcool são os fatores de risco mais importantes. Estudos recentes indicam que a infecção pelo HPV também desempenha um papel importante nos carcinomas da laringe. Os carcinomas laríngeos relacionados ao HPV ocorrem especialmente na região supraglótica. Objetivo: Nosso objetivo foi determinar a frequência da positividade para o HPV / proteína 16 em pacientes com carcinoma da laringe e a associação da positividade para o HPV e /ou proteína 16 com variáveis como idade, sexo, tabagismo, localização do tumor, metástase linfonodal, recidiva e sobrevivência de carcinoma da laringe em estágio avançado em nosso estudo. Método: Este estudo retrospectivo incluiu 90 pacientes com carcinoma laríngeo avançado. O grupo controle incluiu 10 amostras de mucosa laríngea normal. A presença de HPV foi inves-tigada por anticorpo policlonal através de reação de polimerase em cadeia e a proteína 16 por método imunohistoquímico. Nos casos positivos para o HPV, a presença dos tipos 16 e 18 do foi avaliada por reação de polimerase em cadeia. As características demográficas dos pacientes foram observadas. A sobrevida dos pacientes e a associação com HPV / proteína 16 foram determinadas. Resultados: A positividade com anticorpo policlonal do HPV foi detectada em 11 (12,2%) dos 90 casos. Desses 11 casos, o HPV 16 foi positivo em 6, o HPV 18 em 4 e o HPV 16 e 18 foram positivos em 1. Em 18 (20%) dos casos, a proteína 16 foi positiva. Seis dos casos (6,6%) apresentaram positividade para HPV e proteína16. Nos casos positivos apenas para a proteína 16 ou quando HPV e a proteína 16 foram co-positivos, a ingestão de álcool foi menor e o tumor apresentou maior probabilidade de estar localizado na área supraglótica. Essas proporções foram estatisticamente significantes. A localização supraglótica do tumor foi maior em casos positivos para proteína 16. A correlação entre positividade para proteína 16 e localização da área supraglótica foi estatisticamente significante (p = 0,011). Dos casos positivos para proteína 16, 55,6% foram supraglóticos, 33,3% glóticos e 11,1% transglóticos. Embora a expectativa de vida acima de 5 anos tenha sido numericamente maior nos casos positivos para HPV e proteína 16, isso não foi estatisticamente significante. Não houve relação estatisticamente significante entre positividade do HPV e média de idade, diferenciação, tabagismo e uso de álcool, progressão tumoral, metástase linfonodal, localização, recidiva, causa de mortalidade e métodos de tratamento em nosso estudo. O período médio de seguimento de nossos pacientes foi de 6,7 anos. Conclusão: A estreita relação entre HPV e carcinoma espinocelular orofaríngeo não pôde ser demonstrada na laringe em muitos estudos, inclusive no nosso estudo. Nossos achados confirmam um papel limitado do HPV na carcinogênese da laringe. A proteína 16 não é um substituto confiável para o status do HPV nos cânceres de laringe e não é preditor da sobrevida do câncer de laringe. A localização supraglótica do tumor foi maior em casos positivos para proteína16. A correlação entre positividade para proteína 16 e localização na área supraglótica foi determinada como estatisticamente significante. Há necessidade de ensaios clínicos com amostras maiores, nos quais a proliferação neoplásica seja melhor demonstrada e a precisão dos resultados obtidos seja apoiada por diferentes técnicas.

Assessment of HPV 16, HPV 18, p16 expression in advanced stage laryngeal cancer patients and prognostic significance.

INTRODUCTION: Human papilloma virus is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. The developmental mechanisms of laryngeal carcinomas are quite complex and controlled by various factors. Smoking and alcohol are most important risk factors. Recent studies indicate that HPV infection also plays an important role in larynx carcinomas. HPV related laryngeal carcinomas especially occur at the supraglottic region of larynx. OBJECTIVE: We aimed to determine the frequency of HPV/protein16 positivity in patients with laryngeal carcinoma and association of HPV and/or p16 positivity with variables such as age, sex, smoking habits, tumor localization, lymph node metastasis, recurrence and survival in advanced stage laryngeal carcinoma in our study. METHODS: This retrospective study included 90 patients with advanced laryngeal carcinoma. The Control group was 10 normal larynx mucosa specimens. The presence of HPV was investigated polyclonally by polymerase chain reaction, and protein16 with immunohistochemical method. In HPV positive cases, the presence of HPV types 16, 18 were evaluated by polymerase chain reaction. Demographic features of patients were noted. Patient survival and association with HPV/protein16 was determined. RESULTS: Polyclonal HPV positivity was detected in 11 (12.2%) of 90 cases. Out of these 11 cases, HPV 16 was positive in 6, HPV 18 in 4, and both HPV 16 and 18 were positive in 1. In 18 (20%) of the cases, p16 was positive. Six of the cases (6.6%) had both HPV and protein16 positivity. In cases where protein16 alone or HPV and protein16 were co-positive, alcohol use was less and the tumor was found more likely to be localized in the supraglottic area. These ratios were statistically significant. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant (p =  0.011). 55.6% of protein16 positive cases was located in the supraglottic region, 33.3% was glottic and 11.1% was transglottic. Although life expectancy over 5 years were numerically higher in HPV and protein16 positive cases, this was not found to be statistically significant. There was no statistically significant relationship between HPV positivity and mean age, differentiation, smoking and alcohol use, tumor progression, lymph node metastasis, localization, recurrence, cause of mortality and treatment methods in our study. The mean follow-up period of our patients was 6.7 years. CONCLUSION: The close relationship between HPV and oropharyngeal squamous cell carcinoma could not be shown in larynx malignancy in many studies, including our study. Our findings support a limited role of HPV in laryngeal carcinogenesis. Protein16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant. There is a need for more populated clinical trials, where neoplastic proliferation is better demonstrated and the accuracy of the results obtained is supported by different techniques.

Observed-to-expected ratio for adherence to treatment guidelines as a quality of care indicator for laryngeal cancer.

OBJECTIVES/HYPOTHESIS: To examine associations between survival and adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines using an observed-to-expected (O/E) ratio for greater adherence as a risk-adjusted hospital measure of quality care in elderly patients treated for larynx cancer. STUDY DESIGN: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data. METHODS: Patients diagnosed with larynx cancer from 2004 to 2007 were evaluated using multivariate regression and survival analysis. A fit logistic regression model was used to calculate an O/E ratio for guideline adherence for each hospital using quality indicators derived from NCCN guidelines for recommended treatment and stratified by hospital volume. RESULTS: Of 1,721 patients treated at 395 hospitals, 43.0% of patients received NCCN guideline-adherent care. Low-volume hospitals (N = 295) treating six or fewer cases treated 765 patients (44.5%), with a mean O/E of 0.96 ± 0.45. Hospitals treating more then six cases with an O/E <1 (N = 32) treated 284 patients (16.5%), with a mean O/E of 0.77 ± 0.18. Hospitals treating more than six cases with an O/E ≥1 (N = 68) treated 672 patients (39.1%), with a mean O/E of 1.17 ± 0.11. Treatment at hospitals with an O/E ≥1 was associated with improved survival (hazard ratio [HR] = 0.83 [95% confidence interval [CI]: 0.70 to 0.98]) and lower mean incremental treatment-related costs (-$3,009 [-$5,226 to -$791]) compared with hospitals with an O/E <1 (HR = 1.00 [0.80 to 1.24]) and the reference group of low-volume hospitals. CONCLUSIONS: A hospital-specific O/E for NCCN treatment guideline adherence, combined with a minimum case volume criterion, is associated with survival and treatment-related costs in elderly patients with larynx cancer, and may be a feasible measure of larynx cancer quality of care. LEVEL OF EVIDENCE: NA Laryngoscope, 130:672-678, 2020.

Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy.

OBJECTIVES: Ambiguous results have been reported on the predictive value of the Ki-67 proliferation index (Ki-67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early-stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut-off values are attributing factors. Our aim was to elucidate the predictive value of the Ki-67 PI for LC and disease-specific survival (DSS) using a well-defined series of T1-T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA). METHODS: A consecutive and well-defined cohort of 208 patients with T1-T2 LSCC treated with primary RT was selected. The Ki-67 PI was determined using DIA. Mann-Whitney U-tests, logistic and Cox regression analyses were performed to assess associations between Ki-67 PI, clinicopathological variables, LC and DSS. RESULTS: In multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06-4.59, P = .04) and alcohol use (HR 2.84, 95% CI 1.20-6.71; P = .02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16-8.64; P = .03). Ki-67 PI was not associated with LC (HR 1.59; 95% CI 0.89-2.81; P = .11) or DSS (HR 0.98; 95% CI 0.57-1.66; P = .97). In addition, continuous Ki-67 PI was not associated with LC (HR 2.03; 95% CI 0.37-11.14, P = .42) or DSS (HR 0.62; 95% CI 0.05-8.28; P = .72). CONCLUSION: The Ki-67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment-related decision-making for LSCC.

Association of Hospital Volume With Laryngectomy Outcomes in Patients With Larynx Cancer.

Importance: A volume-outcome association exists for larynx cancer surgery, but to date it has not been investigated for specific surgical procedures. Objectives: To characterize the volume-outcome association specifically for laryngectomy surgery and to identify a minimum hospital volume threshold associated with improved outcomes. Design, Setting, and Participants: In this cross-sectional study, the Nationwide Inpatient Sample was used to identify 45 156 patients who underwent laryngectomy procedures for a malignant laryngeal or hypopharyngeal neoplasm between January 2001 and December 2011. The analysis was performed in 2018. Hospital laryngectomy volume was modeled as a categorical variable. Main Outcomes and Measures: Associations between hospital volume and in-hospital mortality, complications, length of hospitalization, and costs were examined using multivariate logistic regression analysis. Results: Among 45 156 patients (mean age, 62.6 years; age range, 20-96 years; 80.2% male) at 5516 hospitals, higher-volume hospitals were more likely to be teaching hospitals in urban locations; were more likely to treat patients who had hypopharyngeal cancer, were of white race/ethnicity, were admitted electively, had no comorbidity, and had private insurance; and were more likely to perform flap reconstruction or concurrent neck dissection. After controlling for all other variables, hospitals treating more than 6 cases per year were associated with lower odds of surgical and medical complications, with a greater reduction in the odds of complications with increasing hospital volume. High-volume hospitals in the top-volume quintile (>28 cases per year) were associated with decreased odds of in-hospital mortality (odds ratio, 0.45; 95% CI, 0.23-0.88), postoperative surgical complications (odds ratio, 0.63; 95% CI, 0.50-0.79), and acute medical complications (odds ratio, 0.63; 95% CI, 0.48-0.81). A statistically meaningful negative association was observed between very high-volume hospital care and the mean incremental length of hospitalization (-3.7 days; 95% CI, -4.9 to -2.4 days) and hospital-related costs (-$4777; 95% CI, -$9463 to -$900). Conclusions and Relevance: Laryngectomy outcomes appear to be associated with hospital volume, with reduced morbidity associated with a minimum hospital volume threshold and with reduced mortality, morbidity, length of hospitalization, and costs associated with higher hospital volume. These data support the concept of centralization of complex care at centers able to meet minimum volume thresholds to improve patient outcomes.

Assessment of Oropharyngeal and Laryngeal Cancer Treatment Delay in a Private and Safety Net Hospital System.

Objective To examine the impact of treatment setting and demographic factors on oropharyngeal and laryngeal cancer time to treatment initiation (TTI). Study Design Retrospective case series. Setting Safety net hospital and adjacent private academic hospital. Subjects and Methods Demographic, staging, and treatment details were retrospectively collected for 239 patients treated from January 1, 2014, to June 30, 2016. TTI was defined as days between diagnostic biopsy and initiation of curative treatment (defined as first day of radiotherapy [RT], surgery, or chemotherapy). Results On multivariable analysis, safety net hospital treatment (vs private academic hospital treatment), initial diagnosis at outside hospital, and oropharyngeal cancer (vs laryngeal cancer) were all associated with increased TTI. Surgical treatment, severe comorbidity, and both N1 and N2 status were associated with decreased TTI. Conclusion Safety net hospital treatment was associated with increased TTI. No differences in TTI were found when language spoken and socioeconomic status were examined in the overall cohort.

Risk assessment for metalworking fluids and cancer outcomes.

BACKGROUND: Metalworking fluids (MWF) are complex mixtures with dermal and inhalation exposure. Published reports reveal excess cancer risk. METHODS: Using published findings exposure response was derived for each attributable cancer site. Aggregate excess lifetime risk was estimated by applying a lifetable calculation. RESULTS: Cancer sites contributing the most attributable cases were larynx, esophagus, brain, female breast, and uterine cervix. With constant workplace MWF exposure of 0.1 mg/m3 over a 45 years working life, the risk of attributable cancer was 3.7% or, excluding the less certain female cancers, 3.1%. CONCLUSION: Substantial cancer risks occurred at 0.1 mg/m3 MWF, one fourth of the current NIOSH recommended exposure limit for MWF total particulate. Because ingredients in current MWF remain from earlier formulations, it is likely that some MWF carcinogenicity persists today. Although important changes have occurred, newer agents are being continually introduced with little or no knowledge of chronic health risks.

Assessment of laryngeal cancer in patients younger than 40 years.

OBJECTIVES/HYPOTHESIS: To assess the differences between patients with laryngeal squamous cell carcinoma under 40 years old and those 40 years old or older. A secondary objective was to compare survival outcome between these cohorts. STUDY DESIGN: Retrospective chart review. METHODS: We reviewed the medical charts of all patients treated in our tertiary referral center for laryngeal squamous cell carcinoma from 2005 to 2014. Patients aged < 40 years at diagnosis were compared to older patients. RESULTS: The study group comprised 160 patients. Of them, 13 were aged < 40 years at diagnosis. Mean age was 35 ± 3.9 years and 64.4 ± 11 years for the two groups. Among the younger patients, 38% were smokers (mean pack/day, 2.2) versus 71% in the older group (mean pack/day, 3). The younger group typically had a more advanced stage than the older group at presentation; eight young patients (62%) had stage III or IV versus 49 (33%) in the older group (P = .042). Mean overall survival was 6.7 ± 1 years for those under 40 years old and 7.7 ± 0.2 years for the older patients (P = .2). The 5-year survival rate was 69% for young patients and 90% for the older group (P = .04). However, there was no significant between-group difference in overall survival or 5-year survival rate when stratified for early- and late-stage disease. CONCLUSIONS: There is a lower prevalence of classic risk factors in younger patient with laryngeal carcinoma in this study, suggesting a different etiology compared to our older cohort. The under-40 cohort presented with more advanced disease and had a worse 5-year survival; however, when stratified for early- versus late-stage disease, there was no significant difference in overall or 5-year survival between the groups. This may suggest that, despite a different etiology, laryngeal cancer behaves similarly in older and younger patients. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1602-1605, 2018.

Site-specific Solid Cancer Mortality After Exposure to Ionizing Radiation: A Cohort Study of Workers (INWORKS).

BACKGROUND: There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS: Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation-mortality associations were estimated using a maximum-likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS: The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS: The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

Patterns of Care for Patients With Early-Stage Glottic Cancer Undergoing Definitive Radiation Therapy: A National Cancer Database Analysis.

PURPOSE: To characterize practice patterns, including temporal trends, in fractionation schedules among patients in the United States undergoing definitive radiation therapy for early-stage glottic cancer and to compare overall survival outcomes between fractionation schedules. METHODS AND MATERIALS: We queried the National Cancer Database for patients with TisN0M0, T1N0M0, or T2N0M0 squamous cell carcinoma of the glottic larynx diagnosed between 2004 and 2012 and undergoing definitive radiation therapy. Dose per fraction was calculated to define cohorts undergoing conventional fractionation (CFxn) and hypofractionation (HFxn). Logistic regression was performed to identify predictors of receiving HFxn, and Cox regression was used to determine predictors of death. One-to-one propensity score matching was then used to compare survival between fractionation schedules. RESULTS: The study included 10,539 patients, with 6576 undergoing CFxn and 3963 undergoing HFxn. Patients with T1 disease comprised a majority of each cohort. Use of HFxn increased significantly over the period studied (P<.001), but even in the final year, nearly one-half of patients continued to receive CFxn. Receipt of HFxn was also independently associated with higher income and facility types other than community cancer programs on logistic regression. On multivariate Cox regression, HFxn was associated with improved survival (hazard ratio [HR] for death, 0.90; 95% confidence interval [CI], 0.83-0.97; P=.008), a finding redemonstrated on univariate Cox regression among a well-matched cohort after propensity score matching (HR, 0.88; 95% CI, 0.80-0.96; P=.003). Subgroup Cox multivariate analysis demonstrated a significant survival advantage with HFxn among patients with T1 disease (HR, 0.90; 95% CI, 0.81-0.99; P=.042) but a nonsignificant benefit among those with Tis (HR, 0.86; 95% CI, 0.57-1.30; P=.472) or T2 (HR, 0.88; 95% CI, 0.76-1.02; P=.099) disease. CONCLUSIONS: Use of HFxn is increasing and is associated with improved survival over CFxn. Our findings support the broadened use of HFxn for patients with early-stage glottic cancer undergoing definitive radiation therapy.

Estimating cross-validatory predictive p-values with integrated importance sampling for disease mapping models.

An important statistical task in disease mapping problems is to identify divergent regions with unusually high or low risk of disease. Leave-one-out cross-validatory (LOOCV) model assessment is the gold standard for estimating predictive p-values that can flag such divergent regions. However, actual LOOCV is time-consuming because one needs to rerun a Markov chain Monte Carlo analysis for each posterior distribution in which an observation is held out as a test case. This paper introduces a new method, called integrated importance sampling (iIS), for estimating LOOCV predictive p-values with only Markov chain samples drawn from the posterior based on a full data set. The key step in iIS is that we integrate away the latent variables associated the test observation with respect to their conditional distribution without reference to the actual observation. By following the general theory for importance sampling, the formula used by iIS can be proved to be equivalent to the LOOCV predictive p-value. We compare iIS and other three existing methods in the literature with two disease mapping datasets. Our empirical results show that the predictive p-values estimated with iIS are almost identical to the predictive p-values estimated with actual LOOCV and outperform those given by the existing three methods, namely, the posterior predictive checking, the ordinary importance sampling, and the ghosting method by Marshall and Spiegelhalter (2003). Copyright © 2017 John Wiley & Sons, Ltd.

Readmission following primary surgery for larynx and oropharynx cancer in the elderly.

OBJECTIVE: To examine 30-day readmission rates and associations with risk factors, survival, length of hospitalization, and costs in elderly patients with laryngeal and oropharyngeal squamous cell cancer (SCC). STUDY DESIGN: Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We evaluated 1,518 patients diagnosed with laryngeal or oropharyngeal SCC from 2004 to 2007 who underwent primary surgery using cross-tabulations, multivariate regression modeling, and survival analysis. RESULTS: Thirty-day readmission occurred in 14.1% of hospitalizations. Readmission was more likely in patients with postoperative complications during initial hospitalization (24.8% vs. 4.5%, P < 0.001), and was associated with an increased 30-day mortality incidence rate (5.1% vs. 0.9%; P < 0.001). On multivariate analysis, 30-day readmission was significantly associated with advanced stage (odds ratio [OR] = 1.81 [1.13-2.90]), comorbidity (OR = 2.69 [1.65-4.39]), divorced/separated marital status (OR = 2.00 [1.19-3.38]), preoperative tracheostomy (OR = 3.39 [1.55-7.44]), major surgical procedures (OR = 2.58 [1.68-3.97]), greater length of initial hospitalization (OR = 1.72 [1.09-2.71]), pneumonia (OR = 2.86 [1.28-6.40]), postoperative dysphagia (OR = 5.97 [2.48-15.83]), and cardiovascular events (OR = 5.84 [1.89-17.96]). Thirty-day readmission was significantly associated with 30-day mortality (OR = 5.89 [2.21-15.70) and higher 1-year mortality (68.0% vs. 89.2%, P < 0.001). The mean incremental costs of surgical care were significantly greater for patients with unplanned readmission ($15,123 [$10,514-$19,732]), after controlling for all other variables. CONCLUSION: Unplanned readmissions are associated with increased short- and long-term mortality and costs. Elderly patients with advanced disease, advanced comorbidity, lack of spousal support, pretreatment organ dysfunction, more extensive surgery, postoperative pneumonia, postoperative dysphagia, and prolonged hospitalization are at increased risk of 30-day readmission. These findings suggest a need for targeted interventions before, during, and after hospitalization to reduce morbidity, mortality, and excess costs in this high-risk population. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:631-641, 2017.

Transoral laser microsurgery versus radiation therapy in the management of T1 and T2 laryngeal glottic carcinoma: which modality is cost-effective within the UK?

OBJECTIVES: To identify the most cost-effective treatment strategy in patients with early stage (T1 and T2) cancers of the laryngeal glottis. DESIGN: A Markov decision model populated using data from updated systematic reviews and meta-analyses, with attributable costs from NHS sources. Data on local control and mortality were obtained from updates of existing systematic reviews conducted for the NICE guideline on cancer of the upper aerodigestive tract. Procedure costs were sourced from NHS reference costs 2013/14 by applying tariffs associated with the appropriate health resource group code SETTING: The UK National Health Service. POPULATION: Patients with early stage (T1 and T2) cancers of the laryngeal glottis. INTERVENTIONS: Transoral laser microsurgery (TLM) and radiation therapy (RT). MAIN OUTCOME MEASURES: Total costs, incremental costs and quality adjusted life years (QALYs) over a 10-year time horizon. RESULTS: Radiation therapy as the initial treatment strategy was found to be more expensive (£2654 versus £623) and less effective (QALY reduction of 0.141 and 0.04 in T1a and T1b-T2 laryngeal cancers, respectively) than TLM. The dominance of TLM for T1a cancers was unchanged in most scenarios modelled in sensitivity analysis. For T1b-T2 laryngeal cancers, the result changed in numerous scenarios. In probabilistic sensitivity analysis, TLM was found to have a 71% and 58% probability of being cost-effective in T1a and T1b-T2 laryngeal cancers, respectively. CONCLUSIONS: Transoral laser microsurgery is a cost-effective strategy to adopt in the management of T1a laryngeal cancers. Uncertainty remains over the optimal strategy to adopt in T1b-T2 laryngeal cancers.

Laryngeal Preservation in Glottic Cancer: A Comparison of Hospital Charges and Morbidity among Treatment Options.

OBJECTIVE: When total laryngectomy is not required, organ preservation surgery or radiotherapy is considered the standard of care for primary glottic cancer. These accepted treatment options are available for early and advanced glottic cancers due to equivalent locoregional control and survival rates. However, in today's climate of accountable care, the financial burden of treatment choices continues to increase in significance. We therefore compared hospital charges and treatment-related morbidity between organ-preserving surgery and radiation with or without chemotherapy-herein, (chemo)radiation-in the primary treatment of glottic cancer. STUDY DESIGN: Nationwide Inpatient Sample Database was analyzed to assess clinical and financial information. SETTING: Population-based analysis. SUBJECTS: Patients (N = 5499) with primary glottic cancer undergoing treatment with laryngeal preservation strategies. METHODS: Patients were subdivided by ICD-9 codes into 3 treatment groups: endoscopic resection, open partial laryngectomy, and (chemo)radiation. Treatment-related outcomes, charges, and length of hospitalization were analyzed among treatment groups. RESULTS: When adjusting for sex, age, race, comorbidity, and primary payer, (chemo)radiotherapy was associated with increased direct charges (P < .001; coefficient, $23,658.99; 95% confidence interval [95% CI]: $10,227.15-$37,090.84) and length of hospitalization (P < .001; hazard ratio, 0.593; 95% CI: 0.502-0.702) when compared with endoscopic surgery. As compared with open surgery, endoscopic surgery was associated with reduced hospital charges (P = .012; coefficient, $11,967.01; 95% CI: $2,784.17-$21,249.85) and duration of hospitalization (P < .001; hazard ratio, 0.749; 95% CI: 0.641-0.876). CONCLUSIONS: This analysis suggests that increased utilization of endoscopic surgery in patients with primary glottic cancer not requiring total laryngectomy may lead to reduced financial burden and duration of hospitalization when compared with open surgery or (chemo)radiation therapy.

Effect of Payer Status on Relative Survival of Patients with Laryngeal Cancer.

BACKGROUND: Relative survival (RS) for patients with laryngeal cancer in the US population has yet to be described. Additionally, survival of patients with laryngeal cancer has demonstrated socioeconomic and racial disparities which have not been previously examined through the lens of RS. MATERIALS AND METHODS: Data on 58,814 patients with laryngeal cancer were obtained from the National Cancer Database. Patients were diagnosed between 1998 and 2006, and had at least 5 years of follow-up. Birth-, year-, age-, sex- and race-specific matched life expectancies were used to estimate expected survival. Stage-stratified RS rates were calculated with multiple factors assessed for significance. Excess mortality ratios were estimated in multivariate analysis utilizing Poisson regression. RESULTS: Younger age, African-American race, uninsured or Medicaid insurance, and treatment at an academic center were all significantly associated with stage IV disease. Uninsured and Medicaid patients demonstrated decreased RS when compared to privately insured individuals. Excess mortality was markedly pronounced in the first year for patients over 50 years old with stage II-IV disease, especially for the over 75-year-old cohort. CONCLUSION: Survival disparities for uninsured and Medicaid populations were found, with these patients exhibiting increased excess mortality. Additionally, RS calculations highlight the negative effects of increasing age on survival of patients with laryngeal cancer.