Inequities in Time to Treat Thyroid Cancer.

BACKGROUND/AIM: The purpose of this study was to determine socioeconomic and demographic factors which may contribute to inequities in time to treat thyroid cancer. PATIENTS AND METHODS: We used data from the National Cancer Database, 2004-2019, to conduct an analysis of thyroid cancer patients. All (434,083) patients with thyroid cancer, including papillary (395,598), follicular (23,494), medullary (7,638), and anaplastic (7,353) types were included. We compared the wait time from diagnosis to first treatment, surgery, radiotherapy, and chemotherapy for patients based on age, race, sex, location, and socioeconomic status (SES). RESULTS: A total of 434,083 patients with thyroid cancer were included. Hispanic patients had significantly longer wait times to all treatments compared to non-Hispanic patients (first treatment 33.44 vs. 20.45 days, surgery 40.06 vs. 26.49 days, radiotherapy 114.68 vs. 96.42 days, chemotherapy 92.70 vs. 58.71 days). Uninsured patients, patients at academic facilities, and patients in metropolitan areas also had the longest wait times to treatment. CONCLUSION: This study identified multiple disparities related to SES and demographics that correspond to delays in time to treatment. It is crucial that this topic is investigated further to help mitigate these incongruities in thyroid cancer care in the future.

The Association of Socioeconomic Factors and Well-Differentiated Thyroid Cancer.

INTRODUCTION: Well-differentiated thyroid cancer (WDTC) is the most common thyroid malignancy, and the worldwide incidence is increasing. Early stage disease is curable with surgery. We hypothesized that patients who live at greater distances from health care institutions or have complicating socioeconomic barriers may present with more advanced diseases and have worse outcomes. METHODS: The National Cancer Database (NCDB) was used to identify patients who were diagnosed with WDTC between 2004 and 2018. Race, ethnicity, insurance status, income status, and distance from residence to health care clinic of diagnosis (great circle distance [GCD]) were analyzed with respect to the severity of disease at presentation (stage) and outcomes. Binary logistic regression and Cox regression were used to determine associations between socioeconomic variables and tumor stage or survival. RESULTS: The Hispanic (OR: 1.49, CI: 1.45-1.54, P < 0.001) and Asian (OR: 1.49, CI: 1.43-1.55, P < 0.001) populations had higher odds of developing an advanced disease when compared to the White population separately. Patients without insurance displayed higher odds of developing an advanced disease at diagnosis compared to those with insurance (OR: 1.39, CI: 1.31-1.47, P < 0.001). Adjusted-Cox regression analysis of survival revealed that Black patients had detrimental survival outcomes when compared to White patients (HR: 1.24, P < 0.001), and patients with private insurance had improved survival outcomes when compared to those without insurance (HR: 0.58, P < 0.001). CONCLUSIONS: Hispanic and Asian patients were found to be more likely to present with an advanced disease but also displayed greater overall survival when compared to the White population. The Black population, patients without insurance, and patients with lower income status exhibited worse survival outcomes.

Comparing surgical thoroughness and recurrence in thyroid cancer patients across race/ethnicity.

BACKGROUND: For patients with differentiated thyroid cancer who will receive postoperative radioactive iodine, thyroid remnant uptake can be calculated and may point to the thoroughness of the surgical resection. In the United States, outcome disparities exist among ethnic/racial minorities with differentiated thyroid cancer. Data about surgical thoroughness and recurrence rates across races/ethnicities do not exist. This study compared the amount of thyroid remnant uptake and cancer recurrence rates across race/ethnicity. METHODS: This was a retrospective analysis of adult patients with differentiated thyroid cancer who had postoperative radioactive iodine in 2017 and 2018 and were followed to 2020. We collected thyroid bed remnant uptake from postoperative radioactive iodine scans and analyzed it as a ratio of percent of uptake to dose of radioactive iodine received to control for varying radioactive iodine doses. Thyroid remnant, uptake to dose of radioactive iodine received, and recurrence were evaluated across race/ethnicity. RESULTS: Of 218 patients: 61% were White, 21% Black, 11% Asian, and 7% Hispanic; 72% were female. Seventy-one percent of patients had their surgery done by a high-volume surgeon, although volume data were not available for all. In White, Black, Asian, and Hispanic patients, median uptake was 0.68%, 0.44%, 1.5%, and 0.8%, respectively (P = .13). We did not observe differences in median uptake to dose of radioactive iodine received across groups (P = .41). Recurrence rate was 17.0% among White patients, 16.7% among Black patients, 17.6% among Asian patients, and 16.7% among Hispanic patients (P = 1.00). CONCLUSION: We did not observe differences across race/ethnicity in surgical thoroughness or rate of recurrence. These findings suggest that disparities may be mitigated when ethnic/racial minorities have similar access to quality surgical care.

Racial/Ethnic Disparities in Use of High-Quality Hospitals Among Thyroid Cancer Patients.

This study examined racial/ethnic differences in the use of high-quality hospitals among thyroid cancer patients. The study included adult patients diagnosed between 2004 and 2015 identified in the California Cancer Registry linked with hospital discharge records. Hospital quality was defined using a composite thyroid cancer-specific hospital quality score. Black (risk ratio [RR] 0.75, 95% CI 0.70-0.80), Hispanic (RR 0.73, 95% CI 0.71-0.75), and Asian/Pacific Islander patients (RR 0.86, 95% CI 0.84-0.89) were less likely to be treated in high-quality hospitals than non-Hispanic White patients. This disparity persisted after adjusting for insurance status and socioeconomic status.

Analysis of the association of BRAFV600E mutation and Ki-67 overexpression with clinical and pathological characteristics in papillary thyroid cancer.

In recent years, many studies were dedicated to the search for genetic markers in thyroid malignancies, including papillary thyroid cancer. This study was designed to investigate the prevalence of BRAFV600E mutation in the PTC in the Kazakh population, to evaluate the relationship between BRAF V600E mutation status and the clinicopathological features of PTC. Besides, we aimed at assessing of the relationship between the high proliferation index and the clinicopathological features of PTC and also between the concomitant coexistence of BRAFV600E and the high proliferative index with clinicopathological features of PTC. We carried out a cross-sectional study on 123 patients with PTC of Kazakh ethnicity and analyzed their clinical, laboratory, and genetic findings. The study groups were pooled based on the presence of mutated or wild-type BRAFV600E and quantitative assessment of Ki-67 marker expression. In the course of our study, we found that the age of patients from the group of BRAF gene mutation was significantly higher than that of patients from the wild-type group (48.63 ± 14.07 years versus 40.23 ± 14.34 years) (t = - 3.257; p = 0.001). Correlation analysis between BRAF mutation, Ki-67 expression, their combination and various clinical and pathological parameters in PTC patients showed that older age was positively correlated with higher frequency of mutant BRAF gene (r = 0.284; p < 0.001), while more advanced stage of tumor was positively correlated with higher expression of Ki-67 (r = 0.307; p < 0.001). To understand the significance of detecting the BRAFV600E mutation and an increased level of Ki-67 expression in the choice of patient therapy tactics, larger studies are required with patient survival as one of the primary outcomes.

Unmet Information Needs Among Hispanic Women with Thyroid Cancer.

CONTEXT: Thyroid cancer is the second most common cancer in Hispanic women. OBJECTIVE: To determine the relationship between acculturation level and unmet information needs among Hispanic women with thyroid cancer. DESIGN: Population-based survey study. PARTICIPANTS: Hispanic women from Los Angeles Surveillance Epidemiology and End Results registry with thyroid cancer diagnosed in 2014-2015 who had previously completed our thyroid cancer survey in 2017-2018 (N = 273; 80% response rate). MAIN OUTCOME MEASURES: Patients were asked about 3 outcome measures of unmet information needs: (1) internet access, (2) thyroid cancer information resources used, and (3) ability to access information. Acculturation was assessed with the Short Acculturation Scale for Hispanics (SASH). Health literacy was measured with a validated single-item question. RESULTS: Participants' median age at diagnosis was 47 years (range 20-79) and 48.7% were low-acculturated. Hispanic women were more likely to report the ability to access information "all of the time" if they preferred thyroid cancer information in mostly English compared to mostly Spanish (88.5% vs 37.0%, P < 0.001). Low-acculturated (vs high-acculturated) Hispanic women were more likely to have low health literacy (47.2% vs 5.0%, P < 0.001) and report use of in-person support groups (42.0% vs 23.1%, P = 0.006). Depending on their level of acculturation, Hispanic women accessed the internet differently (P < 0.001) such that low-acculturated women were more likely to report use of only a smartphone (34.0% vs 14.3%) or no internet access (26.2% vs 1.4%). CONCLUSIONS: Low-acculturated (vs high-acculturated) Hispanic women with thyroid cancer have greater unmet information needs, emphasizing the importance of patient-focused approaches to providing medical information.

Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium.

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.

Initial treatment of patients with thyroid cancer: Outcomes and factors associated with care at academic versus nonacademic cancer centers.

BACKGROUND: Factors associated with receiving initial care for thyroid cancer (TC) at academic centers (ACs) versus nonacademic centers (NACs) and their impact on patient outcomes have not been reported. METHODS: The National Cancer Database with TC cases from 2004 to 2013 was evaluated for association of type of center for initial care with socioeconomic factors and disease and treatment characteristics, as well as overall survival (OS; all-cause mortality). RESULTS: The patients with TC (n = 200,824) included were predominantly women (74%), non-Hispanic Whites (85%), and from metro areas (84%). Sixty percent received initial care at a NAC. There were no significant differences between treatment groups by age or gender. Among those treated at an AC, a higher proportion belonged to racial/ethnic minorities (16.5%) versus at a NAC (11.6%). Hormone therapy was used more in an AC versus a NAC (60% vs 47%). Patients with all TC pathologies combined had a lower likelihood of death when they received initial care at an AC (hazard ratio [HR], 0.948; P = .0006). Among individual pathologic subtypes, a lower likelihood of death was noted when initial care was received at an AC for follicular (HR, 0.828, P = .0010) and Hurthle cell cancers (HR, 792; P = .0008), as well as stage II papillary thyroid cancer (HR, 0.828; P = .0026), but not for other histopathologic subtypes. CONCLUSIONS: Initial care at an AC was associated with lower likelihood of death for patients with TC, especially for those with follicular or Hurthle cell subtypes. Optimal resource use with consideration of patients' socioeconomic and demographic factors is imperative to ensure the most appropriate management of patients with TC in various treatment settings.

Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. METHODS: Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. RESULTS: The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. CONCLUSIONS: This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

Factors affecting online health community participation behavior in patients with thyroid cancer.

Globally, cancer patients obtain much of their disease information online. Online health communities allow patients to share questions and information about diseases. However, there have been few studies on the factors affecting online health community participation behavior in cancer patients. Online social networking is associated with mental health problems, and patients with thyroid cancer experience high levels of distress, anxiety and depression. The purpose of this study was to investigate factors associated with use of online health communities by patients with thyroid cancer to understand the characteristics of patients participating in such online communities. A questionnaire survey was completed by 114 thyroid cancer patients admitted for surgery at a general hospital in Seoul, Korea. General characteristics, clinical characteristics, attitude toward cancer, distress, and anxiety and depression scores of patients who joined an online health community (user group) and patients who did not (non-user group) were compared. The factors affecting online health community participation were education (p = 0.049), tumor size (p = 0.010), attitude toward cancer (p = 0.022), and anxiety and depression (p = 0.021). The average score of satisfaction with the online health community was 4.25 of 5. The user group had larger tumors, a high awareness of the risk of thyroid cancer, and high levels of anxiety and depression. Patients who actively used the online health community have relatively larger cancer size and had higher levels of mental stress. As such patients are often very anxious and depend heavily on the gathered information, the quality of this information is important. Healthcare professionals need to develop appropriate interventions for patients participating in the online health community.

Disparities Research in Thyroid Cancer: Challenges and Strategies for Improvement.

Until recently, thyroid cancer was one of the most rapidly increasing cancers in the United States. Disparities exist in many aspects of thyroid cancer care as a result of the multifactorial interplay of systemic, patient, and physician factors. To better understand the management of thyroid cancer in populations at risk for health disparities and subsequently implement changes that will lead to health equity for all patients with thyroid cancer, health services research with innovative approaches is necessary.

Patient Report of Recurrent and Persistent Thyroid Cancer.

Background: Despite the excellent survival of most patients with differentiated thyroid cancer (DTC), recurrent and persistent disease remain major concerns for physicians and patients. However, studies on patient report of recurrent and persistent disease are lacking. Methods: Between February 1, 2017, and October 31, 2018, we surveyed eligible patients who were diagnosed with DTC between 2014 and 2015 from the Georgia and Los Angeles Surveillance, Epidemiology, and End Results cancer registries (N = 2632; response rate, 63%). Patients who reported current disease status were included in this study (n = 2454). Patient-reported data were linked to registry data. A multivariable, multinomial logistic regression analysis was conducted to determine patient and tumor characteristics associated with recurrent and persistent thyroid cancer. Quality of life was evaluated using the Patient-Reported Outcomes Measurement Information System-Global Health v1.2 questionnaire. Meaningful change in global health was defined as a minimal difference of a half standard deviation or 5 points compared with the mean (T score = 50) of a sample population matching the United States 2000 General Census. Results: Of the 2454 patients completing the survey, 95 (4.1%) reported recurrent disease and 137 (5.8%) reported persistent disease. In multinomial analyses, T3/T4 classification and cervical lymph node involvement (N1) were associated with both report of recurrent (adjusted relative risk ratio [RRR] 1.99, 95% confidence interval [CI 1.16-3.42]; adjusted RRR 2.03 [CI 1.29-3.21], respectively) and persistent disease (adjusted RRR 3.48 [CI 1.96-6.20]; adjusted RRR 3.56 [CI 2.41-5.24], respectively). Additionally, Hispanic ethnicity was associated with report of recurrent disease (adjusted RRR 1.99 [CI 1.23-3.24]). Regarding quality of life, the median scores in patients with persistent disease met criteria for meaningful change in global physical health (T-score = 44.9) and global mental health (T-score = 43.5) when compared with the general population norms. Median scores in patients with cured or recurrent disease did not meet criteria for meaningful change. Conclusions: Patient report is a reasonable method of assessing recurrent and persistent disease. Impact on quality of life is more marked for patients with reported persistent disease. Our findings will help personalize treatment and long-term follow-up in these patients.

BRAFV600E hot spot mutation in thyroid carcinomas: first Moroccan experience from a single-institution retrospective study.

BACKGROUND: The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAFV600E mutation is described to be associated with a worse prognostic of thyroid carcinomas, as well as extrathyroidal invasion and increased mortality. OBJECTIVE: To our knowledge, there are no reported studies neither from Morocco nor from other Maghreb countries regarding the prevalence of BRAFV600E mutation in thyroid carcinomas. Here we aim to evaluate the frequency of BRAFV600E oncogene in Moroccan thyroid carcinomas. METHODS: In this Single-Institution retrospective study realized in the Anatomic Pathology and Histology Service in the Military Hospital of Instruction Mohammed V 'HMIMV' in Rabat, we report, using direct genomic sequencing, the assessment of BRAFV600E in 37 thyroid tumors. RESULTS: We detected BRAFV600E mutation exclusively in Papillary Thyroid Carcinomas 'PTC' with a prevalence of 28% (8 PTC out 29 PTC). Like international trends, Papillary Thyroid Carcinomas 'PTC' is more frequent than Follicular Thyroid Carcinomas 'FTC' and Anaplastic Thyroid Carcinomas 'ATC' (29 PTC, 7 FTC and 1 ATC). CONCLUSION: Our finding gives to the international community the first estimated incidence of this oncogene in Morocco showing that this prevalence falls within the range of international trends (30% to 90%) reported in distinct worldwide geographic regions.

Unexpected high-risk pathologic features following thyroidectomy in the chinese immigrant population.

OBJECTIVE: To compare rates of unexpected high-risk pathologic features between Chinese and non-Asian patients who underwent thyroidectomy for papillary thyroid cancer. METHODS: This was a retrospective cohort study at a tertiary academic urban medical center. Patients who underwent thyroidectomy for papillary carcinoma from 2015 to 2017 were included. Patient demographics, tumor characteristics, and tumor histopathology were analyzed. Primary outcome was the presence of adverse histopathologic features such as lymphovascular invasion (LVI) or microscopic/minimal extrathyroidal extension (mETE). Differences between the groups were analyzed using multivariate logistical regression analysis and propensity score-weighted analysis. RESULTS: One hundred seventy-nine patients were included: 58 Chinese-born and 121 non-Asian. The median age of the cohort was 47 years old (36-58). Twenty-nine percent of patients were male, and 71% were female. There was no statistically significant difference between the two cohorts in rates of LVI, multifocality, extent of surgery, or presence of thyroiditis. Patients with mETE were more likely to have larger tumors (P = 0.00247). Both the multivariate and propensity-weighted models demonstrated that Chinese ancestry was independently associated with an increased rate of unexpected mETE (adjusted prevalence ratio, 2.52; 95% confidence interval, 1.82-3.48). CONCLUSION: mETE is significantly higher in the immigrant Chinese compared to the non-Asian population. Given the high prevalence of unexpected mETE in the Chinese population, the added risk of this finding should be brought into the discussion during initial surgical planning. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:1844-1849, 2020.

Incidence of thyroid cancer in Puerto Rico and the US by racial/ethnic group, 2011-2015.

BACKGROUND: Puerto Rico has the highest incidence rate of thyroid cancer (TC) in the Americas and the third highest rate worldwide. The purpose of this study was to compare the burden of TC between the population of PR and United States (US) non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and US Hispanics (USH) during the period 2011-2015. METHODS: TC data for the period 2011-2015 was obtained from the Puerto Rico Central Cancer Registry (PRCCR) and the Surveillance Epidemiology and Ends Results Program (SEER) 18 Registries Research Data. TC was categorized in: papillary carcinoma (PTC), and other TC histologic types. Data was analyzed by sex, age groups, and histologic type. Racial/ethnic differences by sex, age, and histologic types were assessed using the Standardized Rate Ratio (SRR) and its 95% CI. RESULTS: During the period 2011-2015 there were 5175 and 65,528 cases of TC diagnosed in PR and the US, respectively. The overall age-adjusted incidence rate of PTC was almost two-fold higher in PR than in the US (25.8/100,000 vs. 12.9/100,000). Among PR women, the incidence rate of PTC was 40.0/100,000 compared to 19.4/100,000 in US. PR women had 83% increased risk of being diagnosed with PTC than NHW women, a 2.25-fold increased risk than USH, and 3.45-fold increased risk than NHB women. For men, PR had 34% increased risk of being diagnosed with PTC than NHW men, 2.2-fold increased risk than USH men, and 3.2-fold higher risk than in NHB men. CONCLUSION: Further research is needed to understand this disparity in the island. This research should address the extent of overdiagnosis in PR, the role of health insurance status and insurance type, characteristics of the healthcare delivery system as well as the role of patient and environmental factors.

Influence of CYP3A4/5 and ABC transporter polymorphisms on lenvatinib plasma trough concentrations in Japanese patients with thyroid cancer.

Lenvatinib is a substrate of cytochrome P450 (CYP) 3A and ATP-binding cassette (ABC) transporters. In this study, we aimed to evaluate how CYP3A4/5 and ABC transporter polymorphisms affected the mean steady-state dose-adjusted plasma trough concentrations (C0) of lenvatinib in a cohort of 40 Japanese patients with thyroid cancer. CYP3A4 20230G > A (*1G), CYP3A5 6986A > G (*3), ABCB1 1236C > T, ABCB1 2677G > T/A, ABCB1 3435C > T, ABCC2 -24C > T, and ABCG2 421C > A genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. In univariate analysis, there were no significant differences in the mean dose-adjusted C0 values of lenvatinib between the ABCB1, ABCG2, and CYP3A5 genotypes. However, the mean dose-adjusted C0 values of lenvatinib in patients with the CYP3A4*1/*1 genotype and ABCC2 -24T allele were significantly higher than those in patients with the CYP3A4*1G allele and -24C/C genotype, respectively (P = 0.018 and 0.036, respectively). In multivariate analysis, CYP3A4 genotype and total bilirubin were independent factors influencing the dose-adjusted C0 of lenvatinib (P = 0.010 and 0.046, respectively). No significant differences were found in the incidence rates of hypertension, proteinuria, and hand-foot syndrome following treatment with lenvatinib between the genotypes of CYP3A4/5 and ABC transporters. Lenvatinib pharmacokinetics were significantly influenced by the CYP3A4*1G polymorphism. If the target plasma concentration of lenvatinib for efficacy or toxicity is determined, elucidation of the details of the CYP3A4*1G genotype may facilitate decision-making related to the appropriate initial lenvatinib dosage to achieve optimal plasma concentrations.

Trends in pediatric thyroid cancer incidence in the United States, 1998-2013.

BACKGROUND: Pediatric differentiated thyroid cancer (DTC) rates have increased over time in the United States and worldwide. Improvements in imaging for the diagnosis of DTC have been hypothesized as a potential driver of these increases. This study stratifies temporal trends in pediatric DTC by stage and tumor size to assess whether rates of large, late-stage cancers, which are likely to be clinically meaningful, are increasing over time. METHODS: Age-standardized incidence rates (ASRs) of DTC and annual percent changes (APCs) in primary DTC rates were estimated for 0- to 19-year-olds with data from 39 US cancer registries during 1998-2013. RESULTS: During 1998-2013, 7296 cases of DTC were diagnosed (6652 papillary cases and 644 follicular cases). APCs of pediatric DTCs significantly increased by 4.43%/y [95% CI, 3.74%/y-5.13%/y], primarily because of increases in papillary histologies. Increasing trends were observed for children aged 10 to 19 years for both sexes and for non-Hispanic whites, non-Hispanic blacks, and Hispanics. Rates increased significantly over the time period for all tumor stages (APClocalized , +4.06%/y [95% CI, 2.84%/y-5.29%/y]; APCregional , +5.68%/y [95% CI, 4.64%/y-6.73%/y]; APCdistant , +8.55%/y [95% CI, 5.03%/y-12.19%/y]) and across tumor sizes (APC<1 cm , +9.46%/y [95% CI, 6.13%/y-12.90%/y]; APC1-2 cm , +6.92%/y [95% CI, 4.31%/y-9.60%/y]; APC>2 cm , +4.69%/y [95% CI, 2.75%/y-6.67%/y]). CONCLUSIONS: Significantly increasing rates of DTC over time among 10- to 19-year-olds in the United States are unlikely to be entirely explained by increases in medical surveillance during childhood because rates of large and late-stage DTC are increasing over time. Future studies should examine environmental and other factors that may be contributing to rising DTC rates.

Significant racial differences in the incidence and behavior of the follicular variant of papillary thyroid carcinoma.

BACKGROUND: Increased detection of papillary thyroid cancer (PTC) has led to overtreatment of the largely indolent follicular variant (fvPTC). To guide management of non-aggressive lesions, we investigated whether race predicts PTC variant and tumor behavior. METHODS: Analysis of 258 973 patients from the National Cancer Database diagnosed with PTC in 2004-2014. Clinical and tumor information was compared by race. Multivariate logistic regression was used to predict fvPTC, extrathyroidal extension (ETE), and lymph node metastasis (LNM) of fvPTC. RESULTS: Blacks had the highest fvPTC rate (40% vs white 30%, Hispanic 26%, Asian 25%, P < .001). Blacks had higher odds of fvPTC (aOR = 1.33, 95% CI: 1.28-1.37) and lower odds of ETE than whites (aOR = 0.90, 95% CI: 0.82-0.99) (P < .001). Hispanics and Asians had lower odds of fvPTC (aOR = 0.89, 95% CI: 0.86-0.92 and aOR = 0.81, 95% CI: 0.79-0.84) and higher odds of LNM and ETE than whites (P < .001). CONCLUSIONS: Racial disparities in fvPTC incidence and behavior should be considered to optimize diagnosis and treatment planning.

Risk Haplotypes Uniquely Associated with Radioiodine-Refractory Thyroid Cancer Patients of High African Ancestry.

BACKGROUND: Thyroid cancer patients with radioiodine-refractory (RAI-R) disease, resulting from insufficient RAI delivery and/or RAI resistance, have increased mortality and limited treatment options. To date, studies have largely focused on tumor mutations associated with different stages of disease, which could provide prognostic value for RAI-R disease. It was hypothesized that germline variants contributing to intrinsic differences in iodine metabolism, tumor microenvironment, and/or immune surveillance are associated with RAI-R disease. METHODS: Whole-genome genotyping data analysis was performed on 1145 Caucasian (CAU) patients, 244 of whom were RAI-R, and 55 African American (AA) patients, nine of whom were RAI-R. Germline-variant association studies were conducted using candidate genes involved in iodine metabolism or DNA-damage repair, as well as genome-wide association analysis. Initial data indicated several notable variants in a small number of patients (n = 7), who were later determined to be AA patients of >80% African ancestry (n = 37). This led to the study focusing on germline single nucleotide polymorphisms uniquely associated with RAI-R AA patients. Sanger sequencing was performed to validate risk alleles and identify the incidence of the common somatic mutations BRAFV600E, NRASQ61R, and HRASQ61R in AA patients whose primary tumor samples were available (28/55). RESULTS: TG, BRCA1, and NSMCE2 haplotypes were identified as being uniquely associated with RAI-R AA patients of >80% African ancestry. All patients with the TG haplotype (n = 4) had a biochemical incomplete response to RAI therapy. Patients with the NSMCE2 haplotype (n = 4) were diagnosed at a young age (13, 17, 17, and 26 years old) with distant metastatic disease at initial diagnosis. The BRCA1 haplotype co-occurred in three out of four patients with the NSMCE2 haplotype. The incidence of BRAFV600E appears lower in papillary thyroid carcinomas from AA patients of >80% African ancestry (3/14; 21%) than in AA patients of <80% African ancestry (6/9; 67%), albeit only just approaching statistical significance (p = 0.077). The tumors available from three RAI-R AA patients were negative for BRAFV600E, NRASQ61R, and HRASQ61R. CONCLUSIONS: The identification of candidate RAI-R risk haplotypes may allow early stratification of clinical manifestations of RAI-R disease followed by early intervention and personalized treatment strategies. Functional annotation of candidate RAI-R risk haplotypes may provide insights into the mechanisms underlying RAI-R disease.