Integrated Biomarkers for the Management of Indeterminate Pulmonary Nodules.

Rationale: Patients with indeterminate pulmonary nodules (IPNs) at risk of cancer undergo high rates of invasive, costly, and morbid procedures. Objectives: To train and externally validate a risk prediction model that combined clinical, blood, and imaging biomarkers to improve the noninvasive management of IPNs. Methods: In this prospectively collected, retrospective blinded evaluation study, probability of cancer was calculated for 456 patient nodules using the Mayo Clinic model, and patients were categorized into low-, intermediate-, and high-risk groups. A combined biomarker model (CBM) including clinical variables, serum high sensitivity CYFRA 21-1 level, and a radiomic signature was trained in cohort 1 (n = 170) and validated in cohorts 2-4 (total n = 286). All patients were pooled to recalibrate the model for clinical implementation. The clinical utility of the CBM compared with current clinical care was evaluated in 2 cohorts. Measurements and Main Results: The CBM provided improved diagnostic accuracy over the Mayo Clinic model with an improvement in area under the curve of 0.124 (95% bootstrap confidence interval, 0.091-0.156; P < 2 × 10-16). Applying 10% and 70% risk thresholds resulted in a bias-corrected clinical reclassification index for cases and control subjects of 0.15 and 0.12, respectively. A clinical utility analysis of patient medical records estimated that a CBM-guided strategy would have reduced invasive procedures from 62.9% to 50.6% in the intermediate-risk benign population and shortened the median time to diagnosis of cancer from 60 to 21 days in intermediate-risk cancers. Conclusions: Integration of clinical, blood, and image biomarkers improves noninvasive diagnosis of patients with IPNs, potentially reducing the rate of unnecessary invasive procedures while shortening the time to diagnosis.

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

OBJECTIVE: To determine whether marital status independently predicts survival in a head and neck cancer (HNC) survivor population. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Survival differences in nasopharyngeal carcinoma among racial and ethnic minority groups in the United States: A retrospective cohort study.

OBJECTIVE: The literature on nasopharyngeal carcinoma survival in the United States has focused mostly on Whites or Asians and not much is known about survivorship in other minority racial and ethnic groups. We aimed to determine the disease-specific survival rate and prognostic factors for nasopharyngeal carcinoma survival across the minority United States population. DESIGN: A retrospective cohort study. SETTING: The Surveillance, Epidemiology and End Results (SEER) 13 database from 1992 to 2014 was queried for adult cases of nasopharyngeal carcinoma (n = 2549). PARTICIPANTS: Eligible cases were Blacks, Hispanics, Asians/Pacific Islanders, American Indians/Alaska Natives; White patients were excluded. MAIN OUTCOMES MEASURE: A multivariable competing risk survival analysis yielded hazard ratios (HR) for competing mortality and was used to identify independent prognostic factors for survival. RESULTS: Non-Hispanic American Indians/Alaska Natives consistently had the worst cause-specific survival of any group and that non-Hispanic Asians/Pacific Islanders consistently had the best survival (P < 0.001). Even after adjusting for other poor prognostic factors in the study, including older age, keratinising histology, and lack of radiation treatment, non-Hispanic American Indians/Alaska Natives had more than double hazards of death from nasopharyngeal cancer compared with non-Hispanic Asians/Pacific Islanders (aHR = 2.63, 95% CI 1.67, 4.13). CONCLUSIONS: There are disparities in nasopharyngeal carcinoma survival among racial and ethnic minority groups in the United States, with American Indians/Alaskan Natives faring worst. It is critical that future research focuses on nasopharyngeal carcinoma among this population to improve survivorship and mitigate cancer-related health disparities.

Impact of treatment modality on quality of life of head and neck cancer patients: Findings from an academic medical institution.

PURPOSE: The objective of this pilot study was to determine how different treatment modalities (surgery, radiation, and chemotherapy) impact quality of life (QOL) in a population of head and neck cancer (HNC) survivors. METHODS: Fifty-nine newly diagnosed, biopsy-confirmed HNC patients were recruited between 2007-2012. They completed the EORTC Quality of Life Questionnaire and Head & Neck Module at 5 intervals pre- and post-treatment. Participants were grouped into four categories based on modality: surgery only, surgery/radiation, chemoradiation, or surgery/chemoradiation. Repeated measures ANOVA examined effect of treatment modality on QOL over time. RESULTS: Xerostomia symptoms were significantly associated with chemoradiation (F(2.47, 59.27)=3.57, p=0.03), lowest at pretreatment and highest 6 months post-treatment. Time was significantly associated with head and neck pain, F(2.95,67.89)=3.39, p=0.02. CONCLUSIONS: HNC survivors exhibit different QOL related symptoms depending on combined treatment modalities, and time post-treatment. It is important to understand QOL differences based upon treatment modalities when developing treatment plans for HNC patients.

Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging.

Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 ± 11.5 vs. -74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.

Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: a meta-analysis.

IMPORTANCE: Positron emission tomography (PET) combined with fludeoxyglucose F 18 (FDG) is recommended for the noninvasive diagnosis of pulmonary nodules suspicious for lung cancer. In populations with endemic infectious lung disease, FDG-PET may not accurately identify malignant lesions. OBJECTIVES: To estimate the diagnostic accuracy of FDG-PET for pulmonary nodules suspicious for lung cancer in regions where infectious lung disease is endemic and compare the test accuracy in regions where infectious lung disease is rare. DATA SOURCES AND STUDY SELECTION: Databases of MEDLINE, EMBASE, and the Web of Science were searched from October 1, 2000, through April 28, 2014. Articles reporting information sufficient to calculate sensitivity and specificity of FDG-PET to diagnose lung cancer were included. Only studies that enrolled more than 10 participants with benign and malignant lesions were included. Database searches yielded 1923 articles, of which 257 were assessed for eligibility. Seventy studies were included in the analysis. Studies reported on a total of 8511 nodules; 5105 (60%) were malignant. DATA EXTRACTION AND SYNTHESIS: Abstracts meeting eligibility criteria were collected by a research librarian and reviewed by 2 independent reviewers. Hierarchical summary receiver operating characteristic curves were constructed. A random-effects logistic regression model was used to summarize and assess the effect of endemic infectious lung disease on test performance. MAIN OUTCOME AND MEASURES: The sensitivity and specificity for FDG-PET test performance. RESULTS: Heterogeneity for sensitivity (I2 = 87%) and specificity (I2 = 82%) was observed across studies. The pooled (unadjusted) sensitivity was 89% (95% CI, 86%-91%) and specificity was 75% (95% CI, 71%-79%). There was a 16% lower average adjusted specificity in regions with endemic infectious lung disease (61% [95% CI, 49%-72%]) compared with nonendemic regions (77% [95% CI, 73%-80%]). Lower specificity was observed when the analysis was limited to rigorously conducted and well-controlled studies. In general, sensitivity did not change appreciably by endemic infection status, even after adjusting for relevant factors. CONCLUSIONS AND RELEVANCE: The accuracy of FDG-PET for diagnosing lung nodules was extremely heterogeneous. Use of FDG-PET combined with computed tomography was less specific in diagnosing malignancy in populations with endemic infectious lung disease compared with nonendemic regions. These data do not support the use of FDG-PET to diagnose lung cancer in endemic regions unless an institution achieves test performance accuracy similar to that found in nonendemic regions.

Determining the Efficacy of Surgical Versus Non-Surgical Management in T3M0 Laryngeal Cancer With Cord Fixation.

OBJECTIVE: Survival of laryngeal cancer is decreasing; thus, optimal treatment selection is paramount. Specifically, T3 disease survival appears similar with surgical or non-surgical management; however, the implications of vocal cord fixation on treatment selection and survival are unknown. This study seeks to determine if surgical treatment of patients with T3M0 laryngeal cancer with vocal cord fixation is associated with superior survival compared to non-surgical treatment. METHODS: The National Cancer Database (NCDB) was queried for all T3M0 laryngeal carcinoma cases from 2004 to 2015, whose treatment included surgery or radiation therapy. Cases were stratified by cord fixation status and overall survival was compared using multivariable methods based on surgical versus non-surgical management. RESULTS: Non-surgical management was more common, regardless of cord fixation status (84% in fixed and 79% in mobile). Cord fixation itself did not influence survival; however, surgical management had a significant survival benefit in the fixed cohort (HR = 0.843; 95% CI: 0.738, 0.962). CONCLUSION: In this large observational cohort study of T3M0 laryngeal cancer, those with fixed cords had superior survival when managed surgically.

Association of adjuvant radiation and survival in human papilloma virus-positive oropharynx squamous cell carcinoma with lymphovascular invasion as the sole adverse pathologic feature.

BACKGROUND: Postoperative radiotherapy radiation therapy (PORT) for early-stage human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) with positive lymphovascular invasion (LVI) has an unclear association with overall survival (OS). METHODS: This retrospective cohort study queried the National Cancer Database for surgically treated, T1-2, N0-1 HPV+ OPSCC from 2010 to 2019. Primary exposures were LVI and PORT, and the main outcome was 5-year OS. Odds ratios and hazard ratios (HR) with 95% confidence intervals (CIs) were generated using multivariable models and Cox proportional hazard models, respectively. RESULTS: Of 2768 patients, average age was 59.3 years, 2207 (79.7%) were male, and 386 (13.9%) had LVI. Of patients with LVI as their sole adverse pathologic feature, 220 (57.0%) received PORT, which was not associated with 5-year OS (HR, 1.13; CI, 0.65-1.19). CONCLUSIONS: Patients with surgically treated, early-stage HPV+ OPSCC and positive LVI as their only pathologic adverse feature may not require PORT.

Association Between Antibiotic Prescribing and Time to Diagnosis of Head and Neck Cancer.

Importance: Diagnostic delay can negatively affect patient outcomes in head and neck cancer (HNC). Neck mass and other symptoms of undiagnosed HNC may be treated with antibiotics, delaying diagnosis and treatment, despite current clinical practice guidelines. Objective: To investigate temporal trends, associated factors, and time from symptom onset to antibiotic prescribing before an HNC diagnosis. Design, Setting, and Participants: A retrospective cohort study was conducted using data obtained from a deidentified electronic health records data set from January 1, 2011, to December 31, 2018. Patients with HNC enrolled in the data set for at least 1 year before diagnosis date determined by either 1 inpatient encounter or first of 2 outpatient encounters within 6 months were included. Data analysis was conducted from May 1 to November 9, 2022. Exposure: Antibiotic prescription within 3 months before HNC diagnosis date. Main Outcomes and Measures: The primary outcome was days from the first documented symptom to HNC diagnosis. Results: The cohort included 7811 patients with HNC (4151 [53.1%] men, mean [SD] age, 60.2 [15.8] years). At least 1 antibiotic was prescribed for 1219 patients (15.6%) within 3 months before HNC diagnosis. This represented an increase over the 8.9% prescribing rate during the baseline period 12 to 9 months before diagnosis. The rate of antibiotic prescribing within 3 months before diagnosis did not change significantly over time (quarterly percent change, 0.49%; 95% CI, -3.06% to 4.16%). Patients receiving an antibiotic prescription within 3 months of an HNC diagnosis had a 21.1% longer time between symptom onset and HNC diagnoses (adjusted rate ratio [ARR], 1.21; 95% CI, 1.14-1.29). Compared with diagnosis by otolaryngologists, primary care/internal medicine physicians were most likely to prescribe antibiotics for patients who were diagnosed with a presenting symptom (adjusted prevalence ratio, 1.60; 95% CI, 1.27-2.02). In patients presenting with neck mass/swelling, those presenting with other symptoms were more likely to have longer intervals from symptom onset to diagnosis (ARR, 1.31; 95% CI, 1.08-1.59). Conclusions and Relevance: The findings of this cohort study suggest there is an increased rate of antibiotic prescription in the 3 months before HNC diagnosis, which is associated with an increased time to diagnosis. These findings identify an area for improvement in HNC care and guidelines.

Practice Patterns and Career Satisfaction in Recent Head and Neck Oncology Fellowship Graduates.

Objective: Examine the characteristics of recent head and neck (H&N) oncology fellowship graduates and assess their current perceptions of career alignment and satisfaction. Methods: H&N fellowship graduates from American Head and Neck Society-accredited programs between 2015 to 2020 were surveyed. Two-sample t tests and analysis of variance tests were used to determine the effect of respondents' demographics, fellowship characteristics, career preferences, and current practice on their degree of career alignment with expectations and overall job satisfaction. Results: Fifty-eight fellowship graduates completed the cross-sectional survey. Of all respondents, 52 (89.7%) primarily preferred an academic job, of whom 5 (9.6%) went into private practice. Respondents in private practice, those treating general otolaryngology patients, and those who do not work with residents demonstrated significantly poorer job alignment and career satisfaction as compared with those in academic medicine, those treating only H&N patients, and those working with residents, respectively. Discussion: The majority of graduating H&N fellows prefer a job in academic medicine; however, there may be an insufficient number of desirable academic positions available each year to meet such demand. Implications for Practice: By setting realistic career expectations, preparing for a mixed scope of practice, and integrating resident involvement into private practice groups, H&N providers may ultimately find more fulfillment in their work. These findings could also be valuable to the American Head and Neck Society and fellowship programs in designing training and in planning for the number of available fellowship positions each year.

18F-FSPG PET imaging for the evaluation of indeterminate pulmonary nodules.

BACKGROUND: 18F-fluorodeoxyglucose (FDG) PET/CT is recommended for evaluation of intermediate-risk indeterminate pulmonary nodules (IPNs). While highly sensitive, the specificity of FDG remains suboptimal for differentiating malignant from benign nodules, particularly in areas where fungal lung diseases are prevalent. Thus, a cancer-specific imaging probe is greatly needed. In this study, we tested the hypothesis that a PET radiotracer (S)-4-(3-[18F]-fluoropropyl)-L-glutamic acid (FSPG) improves the diagnostic accuracy of IPNs compared to 18F-FDG PET/CT. METHODS: This study was conducted at a major academic medical center and an affiliated VA medical center. Twenty-six patients with newly discovered IPNs 7-30mm diameter or newly diagnosed lung cancer completed serial PET/CT scans utilizing 18F-FDG and 18F-FSPG, without intervening treatment of the lesion. The scans were independently reviewed by two dual-trained diagnostic radiology and nuclear medicine physicians. Characteristics evaluated included quantitative SUVmax values of the pulmonary nodules and metastases. RESULTS: A total of 17 out of 26 patients had cancer and 9 had benign lesions. 18F-FSPG was negative in 6 of 9 benign lesions compared to 7 of 9 with 18F-FDG. 18F-FSPG and 18F-FDG were positive in 14 of 17 and 12 of 17 malignant lesions, respectively. 18F-FSPG detected brain and intracardiac metastases missed by 18F-FDG PET in one case, while 18F-FDG detected a metastasis to the kidney missed by 18F-FSPG. CONCLUSION: In this pilot study, there was no significant difference in overall diagnostic accuracy between 18F-FSPG and 18F-FDG for the evaluation of IPNs and staging of lung cancer. Additional studies will be needed to determine the clinical utility of this tracer in the management of IPNs and lung cancer.

F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma.

F18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a powerful tool to investigate the role of tumor metabolic activity and its suppression by therapy for cancer survival. As part of Total Therapy 3 for newly diagnosed multiple myeloma, metastatic bone survey, magnetic resonance imaging, and FDG-PET scanning were evaluated in 239 untreated patients. All 3 imaging techniques showed correlations with prognostically relevant baseline parameters: the number of focal lesions (FLs), especially when FDG-avid by PET-computed tomography, was positively linked to high levels of beta-2-microglobulin, C-reactive protein, and lactate dehydrogenase; among gene expression profiling parameters, high-risk and proliferation-related parameters were positively and low-bone-disease molecular subtype inversely correlated with FL. The presence of more than 3 FDG-avid FLs, related to fundamental features of myeloma biology and genomics, was the leading independent parameter associated with inferior overall and event-free survival. Complete FDG suppression in FL before first transplantation conferred significantly better outcomes and was only opposed by gene expression profiling-defined high-risk status, which together accounted for approximately 50% of survival variability (R(2) test). Our results provide a rationale for testing the hypothesis that myeloma survival can be improved by altering treatment in patients in whom FDG suppression cannot be achieved after induction therapy.

The utility of intra-oral ultrasound in improving deep margin clearance of oral tongue cancer resections.

OBJECTIVES: To investigate the potential utility of intra-oral ultrasound (IOUS) in guiding deep margin clearance and measuring depth of invasion (DOI) of oral tongue carcinomas (OTC). MATERIALS AND METHODS: Retrospective chart review of consecutive patients with T1-T3 OTC who underwent intraoperative ultrasound-guided resection and a comparator group that had undergone resection without the use of IOUS both by a single surgeon. Data was extracted from operative, pathology and radiology reports. Deep margins and DOI were reviewed by a dedicated head and neck pathologist. Correlation between histologic and ultrasound DOI was assessed using Pearson correlation. RESULTS: A total of 23 patients were included in the study cohort with a comparator group of 21 patients in the control group. None of the patients in the study cohort had a positive (cut-through) deep margin and the mean deep margin clearance was 8.5 ± 4.9 and 6.7 ± 3.8 for the IOUS and non-IOUS groups respectively (p-value 0.18) showing a non-significant improvement in the IOUS group. As a secondary outcome, there was a strong correlation between histologic and ultrasound DOI (0.9449). CONCLUSION: Ultrasound appears to be a potentially effective tool in guiding OTC resections. In this small series, IOUS facilitated deep margin clearance and resulted in a non-statistically significant increase in deep margin clearance. Intraoral ultrasound can accurately measure lesional DOI.

Establishing a Cohort and a Biorepository to Identify Biomarkers for Early Detection of Lung Cancer: The Nashville Lung Cancer Screening Trial Cohort.

Rationale: A prospective longitudinal cohort of individuals at high risk of developing lung cancer was established to build a biorepository of carefully annotated biological specimens and low-dose computed tomography (LDCT) chest images for derivation and validation of candidate biomarkers for early detection of lung cancer.Objectives: The goal of this study is to characterize individuals with high risk for lung cancer, accumulating valuable biospecimens and LDCT chest scans longitudinally over 5 years.Methods: Participants 55-80 years of age with a 5-year estimated risk of developing lung cancer >1.5% were recruited and enrolled from clinics at the Vanderbilt University Medical Center, Veteran Affairs Medical Center, and Meharry Medical Center. Individual demographic characteristics were assessed via questionnaire at baseline. Participants underwent an LDCT scan, spirometry, sputum cytology, and research bronchoscopy at the time of enrollment. Participants will be followed yearly for 5 years. Positive LDCT scans are followed-up according to standard of care. The clinical, imaging, and biospecimen data are collected prospectively and stored in a biorepository. Participants are offered smoking cessation counseling at each study visit.Results: A total of 480 participants were enrolled at study baseline and consented to sharing their data and biospecimens for research. Participants are followed with yearly clinic visits to collect imaging data and biospecimens. To date, a total of 19 cancers (13 adenocarcinomas, four squamous cell carcinomas, one large cell neuroendocrine, and one small-cell lung cancer) have been identified.Conclusions: We established a unique prospective cohort of individuals at high risk for lung cancer, enrolled at three institutions, for whom full clinical data, well-annotated LDCT scans, and biospecimens are being collected longitudinally. This repository will allow for the derivation and independent validation of clinical, imaging, and molecular biomarkers of risk for diagnosis of lung cancer.Clinical trial registered with ClinicalTrials.gov (NCT01475500).

Mimosa pudica: Electrical and mechanical stimulation of plant movements.

Thigmonastic movements in the sensitive plant Mimosa pudica L., associated with fast responses to environmental stimuli, appear to be regulated through electrical and chemical signal transductions. The thigmonastic responses of M. pudica can be considered in three stages: stimulus perception, electrical signal transmission and induction of mechanical, hydrodynamical and biochemical responses. We investigated the mechanical movements of the pinnae and petioles in M. pudica induced by the electrical stimulation of a pulvinus, petiole, secondary pulvinus or pinna by a low electrical voltage and charge. The threshold value was 1.3-1.5 V of applied voltage and 2 to 10 microC of charge for the closing of the pinnules. Both voltage and electrical charge are responsible for the electro-stimulated closing of a leaf. The mechanism behind closing the leaf in M. pudica is discussed. The hydroelastic curvature mechanism closely describes the kinetics of M. pudica leaf movements.

Comorbidity burden and nonclinical factors associated with sinonasal cancer all-cause mortality.

OBJECTIVE: To describe comorbidity burden and nonclinical factors associated with all-cause mortality of sinonasal cancer in the United States. METHODS: The National Cancer Database (2004-2013) was queried for adult cases of sinonasal cancer (n = 10,518). Outcome of interest was all-cause mortality. Independent variables included comorbidity score and nonclinical factors such as age, gender, race, facility type, distance to facility, insurance, and income. Survival analysis was conducted via multivariable extended Cox regression with Heaviside adjustments. RESULTS: Patients were mostly (79%), male (61%), and mean age of diagnosis was 63.5 years. Approximately one in five patients (18.7%) had a major comorbid condition (Charlson-Deyo score ≥ 1) at diagnosis. After adjusting for clinical factors, increasing comorbidity score was associated with a corresponding increase in hazard of mortality (aHR comorbidity score of 1 = 1.25; 95% CI, 1.16, 1.35), (aHR score of 2+ = 1.61; 95%, CI 1.41, 1.83). Hazard of mortality was also associated with being male (aHR = 1.11; 95% CI, 1.04, 1.17); black (aHR = 1.13, 95% CI, 1.03, 1.24); uninsured (aHR = 1.45; 95% CI, 1.25, 1.68) or on Medicaid (aHR = 1.50; 95% CI, 1.33, 1.69); residence in zip codes with lower median income quartile (aHR < $30,000 = 1.17; 95% CI, 1.06, 1.29); and treatment at community cancer programs (aHR = 1.14, 95% CI 1.01, 1.28). CONCLUSION: Comorbid disease is associated with all-cause sinonasal cancer mortality, and after accounting for known clinical factors, significant differences in mortality persist based on disparity-driven, nonclinical factors. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1443-1449, 2020.

Basaloid Squamous Cell Carcinoma of the Larynx: A National Cancer Database Analysis.

OBJECTIVE: Basaloid squamous cell histology is a rare variant that accounts for about 2% of all head and neck squamous cell laryngeal carcinomas. The purpose of this study was to examine overall survival rates of patients according to treatment, stage, and laryngeal subsite. STUDY DESIGN: Retrospective analysis. SETTING: National Cancer Database (NCDB). SUBJECTS AND METHODS: The NCDB was queried for patients with basaloid squamous cell carcinoma (BSCC) who were treated from 2004 to 2014. Five-year overall survival rates were determined by the Kaplan-Meier method. Univariate and multivariate analysis was used to identify factors correlated with 5-year overall survival. RESULTS: The NCDB identified 440 patients meeting inclusion criteria. Median follow-up time was 31.2 months. On univariate analysis, the treatment modalities assessed (surgery alone, surgery with radiotherapy, surgery with chemoradiotherapy, radiotherapy, chemoradiotherapy) did not differ in their survival benefit. On multivariate analysis, only chemoradiotherapy (hazard ratio, 0.587; 95% CI, 0.37-0.93; P = .022) was associated with improved survival. All treatment modalities performed similarly between stage I and II tumors ( P = .340) and stage III and IV tumors ( P = .154). CONCLUSION: This study represents the largest laryngeal BSCC series to date. We found that chemoradiotherapy was associated with improved 5-year overall survival of laryngeal BSCC on multivariate analysis.

Does anatomic subsite influence oral cavity cancer mortality? A SEER database analysis.

OBJECTIVE: To determine if there are differences in mortality from oral cavity squamous cell carcinoma (OCSCC) based on oral cavity (OC) subsites. METHODS: Using the Surveillance, Epidemiology, and End Results Program (SEER) 9 database, patients with sequence number 0 or 1 squamous cell OCSCC were analyzed by OC subsite for 5-year cause-specific mortality (CSM) from OCSCC. Proportional hazards regression determined the association between 5-year CSM and OC subsites while controlling for treatment modality, stage, and demographic characteristics using hazard ratios. Significance was set at alpha = 0.05. RESULTS: 20,647 OC patients were included in the regression analysis. The most commonly diagnosed sites were floor of mouth (34.4%) and oral tongue (34.3%). Floor of mouth, upper gum, and retromolar trigone were associated with lower CSM compared to oral tongue. Not receiving surgery and receiving radiation were associated with increased CSM, and CSM increased with cancer staging when distant or regional disease was compared to localized disease. Also, patients diagnosed at 60 years or older and black patients had increased CSM. CONCLUSION: Among OCSCC patients, those with oral tongue cancer are more likely to experience CSM than patients with floor of mouth, upper gum, and retromolar trigone cancer. It is important to understand these mortality related differences in the management of OCSCC patients. Understanding subsite-specific mortality may benefit prognosis counseling of OCSCC patients and elicit subsite-directed research as a means to improve outcomes. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1400-1406, 2019.

Prognostic significance of surgical margins after transoral laser microsurgery for early-stage glottic squamous cell carcinoma.

OBJECTIVES: The impact of positive tumor margin status and other clinicopathological factors on prognosis in early stage glottic squamous cell carcinoma (SCC) treated with transoral laser microsurgery (TLM) remains unclear. This study examined overall survival (OS) rates of patients with positive tumor margin status compared to negative tumor margin status after TLM in clinical T1-2 glottic SCC. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was queried for patients who underwent resection of T1-2 glottic SCC by TLM. Patients were treated from 2004 to 2013. Overall survival was assessed with Kaplan-Meier curve analysis, and univariate and multivariate Cox proportional hazards analysis. Differences in clinicopathologic factors between positive and negative margin groups were compared using Pearson Chi-squared analysis. RESULTS: Of 747 patients meeting inclusion criteria, 598 (80.1%) had negative margins. Median follow-up time was 48.0 months. Unadjusted 5-year OS for positive margins (80.0%) was lower compared to that of negative tumor margins (82.9%), but this was not statistically significant (P = 0.265). This persisted after multivariate analysis (P = 0.960). When tumors were stratified by T stage (647 T1, 100 T2), unadjusted 5-year OS based on margin status remained statistically insignificant for both T1 (P = 0.933) and T2 tumors (P = 0.350). CONCLUSION: Positive margins did not negatively impact overall survival among patients with TLM-treated early-stage glottic cancer. This finding might be useful clinically in deciding treatment modality for early stage glottic SCC.

Comparison of the Financial Burden of Survivors of Head and Neck Cancer With Other Cancer Survivors.

IMPORTANCE: Head and neck cancer (HNC) is more common among socioeconomically disenfranchised individuals, making financial burden particularly relevant. OBJECTIVE: To assess the financial burdens of HNC compared with other cancers. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective review of nationally representative, publicly available survey, data from the Medical Expenditure Panel Survey were extracted from January 1, 1998, to December 31, 2015. A total of 444 867 adults were surveyed, which extrapolates to a population of 221 503 108 based on the weighted survey design. Data analysis was performed from April 18, 2018, to August 20, 2018. EXPOSURES: Of 16 771 patients with cancer surveyed (weighted count of 10 083 586 patients), 489 reported HNC (weighted count of 261 631). MAIN OUTCOMES AND MEASURES: Patients with HNC were compared with patients with other cancers on demographics, income, employment, and health. Within the HNC group, risk factors for total medical expenses and relative out-of-pocket expenses were assessed with regression modeling. Complex sampling methods were accounted for with weighting using balanced repeated replication. RESULTS: A total of 16 771 patients (mean [SD] age, 62.3 [18.9] years; 9006 [53.7%] female) with cancer were studied. Compared with patients with other cancers, patients with HNC were more often members of a minority race/ethnicity, male, poor, publicly insured, and less educated, with lower general and mental health status. Median annual medical expenses ($8384 vs $5978; difference, $2406; 95% CI, $795-$4017) and relative out-of-pocket expenses (3.93% vs 3.07%; difference, 0.86%; 95% CI, 0.06%-1.66%) were higher for patients with HNC than for patients with other cancers. Among patients with HNC, median expenses were lower for Asian individuals compared with white individuals ($5359 vs $10 078; difference, $4719; 95% CI, $1481-$7956]), Westerners ($8094) and Midwesterners ($5656) compared with Northwesterners ($10 549), and those with better health status ($16 990 for those with poor health vs $6714 for those with excellent health). Higher relative out-of-pocket expenses were associated with unemployment (5.13% for employed patients vs 2.35% for unemployed patients; difference, 2.78%; 95% CI, 0.6%-4.95%), public insurance (5.35% for those with public insurance vs 2.87% for those with private insurance; difference, 2.48%; 95% CI, -0.6% to 5.55%), poverty (13.07% for poor patients vs 2.06% for high-income patients), and lower health status (10.2% for those with poor health vs 1.58% for those with excellent health). CONCLUSIONS AND RELEVANCE: According to this study, HNC adds a substantial, additional burden to an already financially strained population in the form of higher total and relative expenses. The financial strain on individuals, assessed as relative out-of-pocket expenses, appears to be driven more by income than by health factors, and health insurance does not appear to be protective.