Independent Validation of the International Grading System for Medullary Thyroid Carcinoma: A Single Institution Experience.

Medullary thyroid carcinoma (MTC), an uncommon C cell thyroid malignancy, accounts for a disproportionate number of thyroid cancer deaths. To predict MTC clinical behavior, the recent international MTC grading system (IMTCGS) was published combining features from the Memorial Sloan Kettering Cancer Center and Royal North Shore Hospital grading systems that incorporates mitotic count, necrosis, and Ki67 proliferative index (Ki67PI). The IMTCGS appears promising, but independent validation data are limited. Here, we applied the IMTCGS to our institutional MTC cohort and assessed its ability to predict clinical outcomes. Our cohort comprised 87 MTCs (30 germline and 57 sporadic). Slides for each case were reviewed by 2 pathologists and histologic features recorded. Ki67 immunostaining was performed on all cases. Each MTC was graded with the IMTCGS based on tumor necrosis, Ki67PI, and mitotic count. Cox regression analysis was performed to assess the impact of various clinical and pathological data on disease outcomes, including overall survival (OS), disease-free survival, disease-specific survival (DSS), and distant metastasis-free survival. In our MTC cohort, 18.4% (n = 16/87) were IMTCGS high grade. IMTCGS grade was strongly prognostic for OS, disease-free survival, DSS, and distant metastasis-free survival on univariate analysis and multivariable analysis in both the entire MTC cohort and in the sporadic subset. Among the individual IMTCGS parameters, while all 3 were associated with poorer survival outcomes on univariate analysis, necrosis had the strongest association with all survival parameters on multivariable analysis, whereas Ki67PI or mitotic count was associated only with OS and DSS. This retrospective study independently demonstrates that the IMTCGS is valid for grading MTCs. Our findings support incorporating IMTCGS into routine pathology practice. IMTCGS grading may help clinicians to better predict the prognosis of MTC. Future studies may shed light on how MTC grading should impact treatment protocols.

Current Trainee and Workforce Patterns for Thyroid and Parathyroid Surgery in the United States.

OBJECTIVE: Thyroid and parathyroid surgery is performed by both general surgeons and otolaryngologists. We describe the proportion of surgeries performed by specialty, providing data to support decisions about when and to whom to direct research, education, and quality improvement interventions. METHODS: We tabulated case numbers for privately insured patients undergoing thyroid and parathyroid surgery in Marketscan: 2010-2016 and trainee case logs for residents and fellows in general surgery and otolaryngology. Summary statistics and tests for trends and differences were calculated. RESULTS: Marketscan data captured 114 500 thyroid surgeries. The proportion performed by each specialty was not significantly different. Otolaryngologists performed 58 098 and general surgeons performed 56 402. Otolaryngologists more commonly performed hemithyroidectomy (n = 25 148, 43.29% of all thyroid surgeries performed by otolaryngologists) compared to general surgeons (n = 20 353, 36.09% of all thyroid surgeries performed by general surgeons). Marketscan data captured 21 062 parathyroid surgeries: 6582 (31.25%) were performed by otolaryngologists, and 14 480 (68.75%) were performed by general surgeons. The case numbers of otolaryngology and general surgery trainees completing residency and fellowship varied 6- to 9-fold across different sites. The wide variation may reflect both the level of exposure a particular training program offers and trainee level of interest. CONCLUSION: Thyroid surgical care is equally provided by general surgeons and otolaryngologists. Both specialties contribute significantly to parathyroid surgical care. Both specialties should provide input into and be targets of research, quality, and education interventions.

Betel Quid Use and Oral Cancer in a High-Risk Refugee Community in the USA: The Effectiveness of an Awareness Initiative.

Betel nut (BN) is a psychoactive oral carcinogen that is commonly used among Asian communities. This study aims to investigate BN usage patterns and the effectiveness of a visually guided educational initiative in a high-risk refugee population. All adult patients presenting to a private practice clinic, free community clinic, or health fair in the refugee community of Clarkston, Georgia during days when survey staff were present were approached for the study. Participants were first categorized into a familiar and unfamiliar cohort depending on participant-reported familiarity with BN. Depending on familiarity, subjects were then administered a pre-intervention test surveying health awareness for BN and usage patterns where relevant; subsequently, a visually guided educational brochure was reviewed, and a post-intervention test was administered. Results were statistically analyzed (STATA 12). Forty-eight participants were surveyed for the familiar cohort and 25 for the unfamiliar cohort. Among the familiar cohort, South and Southeast Asians comprised 91% of participants. On frequency of use, 42.8% reported social, 28.6% reported usage during celebrations only, and 28.6% reported daily. The most common reasons for use were for taste (40.9%), enjoyment (38.6%), and addiction (25%). Among the familiar cohort, 75% believed BN was harmful for health compared to 8% among the unfamiliar (p < 0.0001). In the familiar cohort, 52.3% believed BN alone could cause cancer compared to 4% among the unfamiliar (p < 0.0001). Following the educational intervention, 100% of participants believed BN mastication is harmful in both cohorts (p < 0.01), while 87.5% of participants in both cohorts recognized that BN alone could cause cancer (p < 0.0007). This study illustrates gaps in understanding regarding oral cancer and the health consequences of chronic BN mastication, as well as the efficacy of a visually guided educational brochure to improve participant knowledge among a high-risk refugee population.

Treatment and survival vary by race/ethnicity in patients with anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is the rarest type of thyroid cancer and has the lowest overall survival. To the authors' knowledge, the impact of socioeconomic status and race/ethnicity has not yet been described. METHODS: Data regarding 719 patients diagnosed with their first primary malignant ATC from January 1, 1998 to December 31, 2011 in the Surveillance, Epidemiology, and End Results program registries were examined. Differences in receipt of thyroidectomy, radiotherapy, and lymph node examination were examined by race/ethnicity. Survival also was examined by race/ethnicity. RESULTS: Nearly 70% of patients were non-Hispanic white, and 55.4% of patients received treatment. Tumor size (P = .13), lymph node involvement (P = .60), and residence in high poverty neighborhoods (P = .08) did not vary by race/ethnicity. Nonwhite patients were more likely to receive no treatment (adjusted odds ratio, 0.29; 95% confidence interval [95% CI], 0.16-0.54). When receipt of radiotherapy was adjusted for, nonwhite patients had a higher risk of overall death (adjusted hazards ratio [aHR], 1.24; 95% CI, 1.01-1.54), although not disease-specific death (aHR, 1.14; 95% CI, 0.92-1.42). Patients living in areas of high poverty had lower overall survival (aHR, 1.54; 95% CI, 1.09-2.18) and disease-specific survival (aHR, 1.68; 95% CI, 1.19-2.36). CONCLUSIONS: In this population-based study of patients with ATC, nonwhite patients were found to be less likely to receive treatment. Furthermore, nonwhite patients had poorer overall survival, and patients living in areas of high poverty had both worse overall and disease-specific survival. Racial/ethnic and socioeconomic disparities appear to exist in the treatment and survival of patients with ATC. Cancer 2018;124:1780-90. © 2018 American Cancer Society.

Bullous diaper dermatitis with cloth diaper use.

Irritant diaper dermatitis occurs at a higher frequency with cloth diaper use than disposable diapers. We present four cases of vesiculobullous, erosive diaper dermatitis occurring in older infants and toddlers with cloth diaper use that resolved completely after transitioning to disposable diapers. This is the first report of vesicles and bullae as a type of irritant diaper dermatitis.

Comparative effectiveness of surgical and nonsurgical therapy for advanced laryngeal cancer.

BACKGROUND: The treatment of patients with advanced stage laryngeal cancer includes surgery or concurrent chemoradiation (CRT). Although CRT has become more common in recent years, to the authors' knowledge, the effectiveness of complete CRT in improving survival over surgery has not been studied. METHODS: The authors examined patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare claims-linked data set with locoregional laryngeal cancer who were diagnosed between 1997 and 2007. Multivariate Cox proportional hazard analyses were conducted to compare overall and cause-specific 5-year survival rates between treatment modalities, adjusting for patient sociodemographic and clinical characteristics. A propensity score-matched subcohort also was used to compare survival. RESULTS: Of the 3212 patients in the study cohort, 42% underwent surgery and 18% underwent CRT. Only approximately one-quarter of patients who were treated with CRT completed the courses. In adjusted analyses, the authors were unable to reject the null hypothesis of no difference in 5-year all-cause or cause-specific mortality risk between patients treated with surgery and patients undergoing complete CRT (hazards ratio, 1.25 [95% confidence interval, 0.91-1.71; P = .16] and hazard ratio, 1.41 [95% confidence interval, 0.9-2.2; P = .14], respectively). Older age, not currently married, Medicaid eligibility, and prior cancer history were found to be associated with a higher risk of mortality (P<.05). CONCLUSIONS: Patients with advanced laryngeal cancer who underwent complete CRT were found to have overall and cause-specific survival rates similar to those of patients undergoing surgery. However, a substantial percentage of patients who initiated CRT did not complete the course. Although CRT provides organ preservation, the benefits and trade-offs of CRT and total laryngectomy should be discussed fully with patients. The importance of completing the full course of CRT should be emphasized. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2845-2856. © 2016 American Cancer Society.

The importance of margins in head and neck cancer.

An estimated 200,000 deaths each year worldwide are due to cancer of the head and neck, mostly mucosal squamous cell carcinoma and nonmelanoma skin cancer. The status of surgical margins is important for prognosis and need for adjuvant therapy. We will discuss how margin status impacts outcomes and therapy, and the conundrum of determining margin status.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: THE INCREASING INCIDENCE OF THYROID CANCER.

OBJECTIVE: (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action. METHODS: Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013. RESULTS: The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease. CONCLUSION: Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers.

Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Platinum-based therapy combined with cetuximab is standard first-line therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Preclinical studies have suggested that mammalian target of rapamycin inhibitors may overcome resistance to epidermal growth factor receptor blockers and may augment cetuximab antitumor activity. We conducted a phase 1b trial of carboplatin, cetuximab, and everolimus for untreated RMSCCHN. METHODS: Patients received carboplatin (area under the curve = 2 mg/ml/min; 3 weeks on, 1 week off), cetuximab (with a loading dose of 400 mg/m(2) and then 250 mg/m(2) weekly), and dose-escalating everolimus (2.5, 5.0, 7.5, and 10 mg/day) with a 3+3 design. After 4 cycles, patients without progression continued cetuximab/everolimus until progression or intolerable toxicity. Patients (age ≥ 18 years) had previously untreated, unresectable RMSCCHN not amenable to radiotherapy and an Eastern Cooperative Oncology Group performance status of 0 to 2. RESULTS: The study enrolled 20 patients (male/female = 18/2) with RMSCCHN; the median age was 65 years (44-75 years). Thirteen patients received everolimus (male/female = 92%). Two of 6 patients receiving 2.5 mg/day experienced dose-limiting toxicity (DLT) with grade 3 hyponatremia and nausea. In 7 patients receiving de-escalated everolimus (2.5 mg every other day), grade 3 hyperglycemia produced DLT in 1 of 6 patients. The objective response rate (RR) was 61.5% (all partial responses). Progression-free survival (PFS) was 8.15 months. The pharmacokinetics of everolimus was described with a 2-compartment mixed-effects model. There was a significant correlation between tumor p-p44/42 staining and response (P = .044) and a marginally significant correlation between phosphorylated mammalian target of rapamycin and overall survival. CONCLUSIONS: The maximum tolerated dose of everolimus with cetuximab and carboplatin was 2.5 mg every other day. The regimen was associated with an encouraging RR and PFS, and this suggested possible clinical efficacy in a select group of patients with squamous cell carcinoma of the head and neck.

Current treatment of head and neck squamous cell cancer.

Head and neck cancer is a heterogenous group of cancers involving the upper aerodigestive tract. In this review article, the most common sites will be discussed, including the oral cavity, oropharynx, hypopharynx, and larynx. Etiology and epidemiology will be discussed followed by staging, treatment, and survival.

Polarized hyperspectral microscopic imaging system for enhancing the visualization of collagen fibers and head and neck squamous cell carcinoma.

Significance: Polarized hyperspectral microscopes with the capability of full Stokes vector imaging have potential for many biological and medical applications. Aim: The aim of this study is to investigate polarized hyperspectral imaging (PHSI) for improving the visualization of collagen fibers, which is an important biomarker related to tumor development, and improving the differentiation of normal and tumor cells on pathologic slides. Approach: We customized a polarized hyperspectral microscopic imaging system comprising an upright microscope with a motorized stage, two linear polarizers, two liquid crystal variable retarders (LCVRs), and a compact SnapScan hyperspectral camera. The polarizers and LCVRs worked in tandem with the hyperspectral camera to acquire polarized hyperspectral images, which were further used to calculate four Stokes vectors: S0, S1, S2, and S3. Synthetic RGB images of the Stokes vectors were generated for the visualization of cellular components in PHSI images. Regions of interest of collagen, normal cells, and tumor cells in the synthetic RGB images were selected, and spectral signatures of the selected components were extracted for comparison. Specifically, we qualitatively and quantitatively investigated the enhanced visualization and spectral characteristics of dense fibers and sparse fibers in normal stroma tissue, fibers accumulated within tumors, and fibers accumulated around tumors. Results: By employing our customized polarized hyperspectral microscope, we extract the spectral signatures of Stokes vector parameters of collagen as well as of tumor and normal cells. The measurement of Stokes vector parameters increased the image contrast of collagen fibers and cells in the slides. Conclusions: With the spatial and spectral information from the Stokes vector data cubes (S0, S1, S2, and S3), our PHSI microscope system enhances the visualization of tumor cells and tumor microenvironment components, thus being beneficial for pathology and oncology.

An Ensemble Learning Method for Detection of Head and Neck Squamous Cell Carcinoma Using Polarized Hyperspectral Microscopic Imaging.

Head and neck squamous cell carcinoma (HNSCC) has a high mortality rate. In this study, we developed a Stokes-vector-derived polarized hyperspectral imaging (PHSI) system for H&E-stained pathological slides with HNSCC and built a dataset to develop a deep learning classification method based on convolutional neural networks (CNN). We use our polarized hyperspectral microscope to collect the four Stokes parameter hypercubes (S0, S1, S2, and S3) from 56 patients and synthesize pseudo-RGB images using a transformation function that approximates the human eye's spectral response to visual stimuli. Each image is divided into patches. Data augmentation is applied using rotations and flipping. We create a four-branch model architecture where each branch is trained on one Stokes parameter individually, then we freeze the branches and fine-tune the top layers of our model to generate final predictions. Our results show high accuracy, sensitivity, and specificity, indicating that our model performed well on our dataset. Future works can improve upon these results by training on more varied data, classifying tumors based on their grade, and introducing more recent architectural techniques.

Effects of socioeconomic status on enrollment in clinical trials for cancer: A systematic review.

BACKGROUND: To achieve equitable access to cancer clinical trials (CCTs), patients must overcome structural, clinical, and attitudinal barriers to trial enrollment. The goal of this systematic review was to study the relationship between socioeconomic status (SES), assessed either by direct or proxy measures, and CCT enrollment. METHODS: The review team and medical librarian developed search strategies for each database to identify studies for this systematic review, which was conducted according to PRISMA guidelines. Inclusion criteria were as follows: studies published in relevant scientific journals between January 2000 and July 2022, primary sources, English literature, and studies conducted in the US. Sixteen studies fulfilled the inclusion criteria and were reviewed. The risk of bias assessment was conducted independently by two reviewers using the Newcastle Ottawa scale. RESULTS: The initial search yielded 4070 citations, and 16 studies were included in our review. Four of the studies included used patient reported annual income as a measure of SES, while the remaining 12 studies used patient zip code as a proxy measurement of SES. Consistent with our hypothesis, 13 studies showed a positive association between high SES (patient-reported or proxy measurement) and CCT enrollment. Two studies showed a negative association, and one study showed no relationship. CONCLUSIONS: The existing literature suggests that low SES is associated with lower participation in CCT. The small number of studies identified on this topic highlights the need for additional research on SES and other barriers to CCT participation.

CD28-CD57+ T cells from head and neck cancer patients produce high levels of cytotoxic granules and type II interferon but are not senescent.

T lymphocytes expressing CD57 and lacking costimulatory receptors CD27/CD28 have been reported to accumulate with aging, chronic infection, and cancer. These cells are described as senescent, with inability to proliferate but enhanced cytolytic and cytokine-producing capacity. However, robust functional studies on these cells taken directly from cancer patients are lacking. We isolated these T cells and their CD27/28+ counterparts from blood and tumor samples of 50 patients with previously untreated head and neck cancer. Functional studies confirmed that these cells have enhanced ability to degranulate and produce IFN-γ. They also retain the ability to proliferate, thus are not senescent. These data suggest that CD27/28-CD57+ CD8+ T cells are a subset of highly differentiated, CD45RA+ effector memory (TEMRA) cells with retained proliferative capacity. Patients with > 34% of these cells among CD8+ T cells in the blood had a higher rate of locoregional disease relapse, suggesting these cells may have prognostic significance.

Coffee, tea, and fatal oral/pharyngeal cancer in a large prospective US cohort.

Epidemiologic studies suggest that coffee intake is associated with reduced risk of oral/pharyngeal cancer. The authors examined associations of caffeinated coffee, decaffeinated coffee, and tea intake with fatal oral/pharyngeal cancer in the Cancer Prevention Study II, a prospective US cohort study begun in 1982 by the American Cancer Society. Among 968,432 men and women who were cancer free at enrollment, 868 deaths due to oral/pharyngeal cancer occurred during 26 years of follow-up. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risk. Intake of >4 cups/day of caffeinated coffee was associated with a 49% lower risk of oral/pharyngeal cancer death relative to no/occasional coffee intake (relative risk = 0.51, 95% confidence interval: 0.40, 0.64) (1 cup/day = 237 ml). A dose-related decline in relative risk was observed with each single cup/day consumed (P(trend) < 0.001). The association was not modified by sex, smoking status, or alcohol use. An inverse association for >2 cups/day of decaffeinated coffee intake was suggested (relative risk = 0.61, 95% confidence interval: 0.37, 1.01). No association was found for tea drinking. In this large prospective study, caffeinated coffee intake was inversely associated with oral/pharyngeal cancer mortality. Research is needed to elucidate biologic mechanisms whereby coffee might help to protect against these often fatal cancers.

Paranasal sinus squamous cell carcinoma incidence and survival based on Surveillance, Epidemiology, and End Results data, 1973 to 2009.

BACKGROUND: Paranasal sinus squamous cell carcinomas (PNSSCC) account for 3% of all head and neck malignancies. There has been little information on the trends in incidence and survival, and no randomized trials have been conducted to guide therapy. METHODS: Patients with PNSSCC reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1973 through 2009 were categorized by sex, age, year of diagnosis, primary site, stage, and treatment. The incidence and survival were then compared across different demographic and disease-related categories by calculating rate ratios (RRs) and mortality hazard ratios along with the corresponding 95% confidence intervals (CIs). RESULTS: In total, 2553 patients with PNSSCC were identified. While incidence of PNSSCC showed a gradual decline, survival remained largely unchanged. The proportion of patients with advanced disease decreased from 14.7% during the period from 1983 to 1992 to 12.4% during 1993-2002 and to 9.5% during 2003-2009. Compared with whites, incidence was higher among African Americans (RR 1.63; 95% CI, 1.39, 1.90) and among all other racial groups (RR, 1.78; 95% CI: 1.53-2.07). After adjusting for age, sex, disease stage, tumor site, and treatment, mortality among African American patients also was increased (hazard ratio, 1.22; 95% CI, 1.04-1.43). Among patients with localized disease, the relation between race and mortality was no longer evident once the results were controlled for tumor classification. CONCLUSIONS: The current findings point to racial disparities in the incidence of PNSSCC and, to a lesser extent, in the outcome of patients with PNSSCC. Although there has been a decline in the proportion of patients presenting with advanced PNSSCC, the overall survival remained stable over time.

Validation and application of the M.D. Anderson Dysphagia Inventory in patients treated for head and neck cancer in Brazil.

Analysis of quality of life (QOL) has revealed that preservation of swallowing, speech, and breathing functions has a direct impact on QOL and that these functions are important patient-reported outcomes. The purposes of this study were to adapt and culturally validate the M.D. Anderson Dysphagia Inventory (MDADI) to the Brazilian Portuguese language and to evaluate QOL related to dysphagia in patients treated for head and neck cancer. This was a cross-sectional study that included 72 adult patients with a mean age of 63 years who were treated for head and neck cancer. Construct validity and reliability analyses were performed through the comparison of the MDADI with three other health-related QOL questionnaires administered at the time of enrollment and MDADI application 2 weeks thereafter, respectively. Reliability was established by assuring both internal consistency (Cronbach's α) and test-retest reliability (intraclass correlation coefficient, ICC). Test-retest reliability for the total score in the MDADI had an ICC greater than 0.795 (p < 0.001). The MDADI had significant statistical correlations with the other questionnaires. Patients treated for head and neck cancer had a mean total score of 83 on the MDADI, which is indicative of minimal limitation in overall QOL. In conclusion, the present study validates the adaptation of the MDADI to the Brazilian Portuguese language and provides another tool to evaluate the impact of dysphagia on the QOL of head and neck cancer patients.

Adenoid cystic carcinoma of the head and neck: Incidence and survival trends based on 1973-2007 Surveillance, Epidemiology, and End Results data.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the head and neck (ACCHN) is a rare tumor of minor salivary, parotid, and submandibular glands. The biologic behavior of the disease is poorly understood, and nonsurgical treatment strategies have yet to be standardized. The long-term prognosis continues to be guarded, with an estimated 10-year survival of <60%. Population-based studies examining ACC are scarce. The authors aimed to analyze incidence rates and survival outcomes for patients diagnosed with ACCHN using national population-based data. METHODS: Data were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Newly diagnosed ACCHN cases reported to SEER from 1973 through 2007 were categorized according to their sex, race, age, year of diagnosis, marital status, treatment interventions, primary tumor site, and disease stage. Incidence of ACCHN and postdiagnosis survival were examined over time and compared across different demographic and disease-related categories. RESULTS: The authors identified 3026 patients with ACCHN. The mean age at diagnosis among those cases was 57.4 years (range, 11-99 years). Analyses of incidence data demonstrated a decline in ACCHN rates between 1973 and 2007, noted across all sexes and races with no detectable inflexion points. The overall 5-year, 10-year, and 15-year survival outcomes for ACCHN patients were 90.3%, 79.9%, and 69.2%, respectively. Females, patients with localized disease, and younger patients were found to have significantly better survival across all time periods (all comparison-specific log-rank P values <0.001). Multivariate analyses revealed better prognosis among women compared with men (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65-0.82), among married compared with unmarried individuals (HR, 0.81; 95% CI, 0.71-0.91), with certain sites of origin and stage of disease (HR, 2.788; 95% CI, 2.36-3.29), and in those who had surgery of the primary tumor site (HR, 0.45; 95% CI, 0.37-0.54). CONCLUSIONS: The overall incidence of ACC is declining. The noted differences in survival based on sex, marital status, site of origin, and treatment intervention require further investigation.