Differences Between Cancer-Specific Survival of Patients With Anaplastic and Primary Squamous Cell Thyroid Carcinoma and Factors Influencing Prognosis: A SEER Database Analysis.

Purpose: Anaplastic thyroid carcinoma (ATC) and primary squamous cell carcinoma of the thyroid (PSCCTh) have similar histological findings and are currently treated using the same approaches; however, the characteristics and prognosis of these cancers are poorly researched. The objective of this study was to determine the differences in characteristics between ATC and PSCCTh and establish prognostic models. Patients and Methods: All variables of patients with ATC and PSCCTh, diagnosed from 2004-2015, were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Percentage differences for categorical data were compared using the Chi-square test. Kaplan-Meier curves, log-rank test, and Cox-regression for survival analysis, and C-index value was used to evaluate the performance of the prognostic models. Results: After application of the inclusion and exclusion criteria, a total of 1164 ATC and 124 PSCCTh patients, diagnosed from 2004 to 2015, were included in the study. There were no differences in sex, ethnicity, age, marital status, or percentage of proximal metastases between the two cancers; however, radiotherapy, chemotherapy, incidence of surgical treatment, and presence of multiple primary tumors were higher in patients with ATC than those with PSCCTh. Further cancer-specific survival (CSS) of patients with PSCCTh was better than that of patients with ATC. Prognostic factors were not identical for the two cancers. Multivariate Cox model analysis indicated that age, sex, radiotherapy, chemotherapy, surgery, multiple primary tumors, marital status, and distant metastasis status are independent prognostic factors for CSS in patients with ATC, while for patients with PSCCTh, the corresponding factors are age, radiotherapy, multiple primary tumors, and surgery. The C-index values of the two models were both > 0.8, indicating that the models exhibited good discriminative ability. Conclusion: Prognostic factors influencing CSS were not identical in patients with ATC and PSCCTh. These findings indicate that different clinical treatment and management plans are required for patients with these two types of thyroid cancer.

Primary Versus Secondary Anaplastic Thyroid Carcinoma: Perspectives from Multi-institutional and Population-Level Data.

Primary (or de novo) anaplastic thyroid carcinoma (ATC) is ATC without pre-existing history of differentiated thyroid carcinoma (DTC) and no co-existing DTC foci at the time of diagnosis. Secondary ATC is diagnosed if the patient had a history of DTC or co-existing DTC components at time of diagnosis. This study aimed to investigate the incidence, clinical presentations, outcomes, and genetic backgrounds of primary versus secondary ATCs. We searched for ATCs in our institutional databases and the Surveillance, Epidemiology, and End Result (SEER) database. We also performed a systematic review and meta-analysis to analyze the genetic alterations of primary and secondary ATCs. From our multi-institutional database, 22 primary and 23 secondary ATCs were retrieved. We also identified 620 and 24 primary and secondary ATCs in the SEER database, respectively. Compared to primary ATCs, secondary ATCs were not statistically different in terms of demographic, clinical manifestations, and patient survival. The only clinical discrepancy between the two groups was a significantly larger tumor diameter of the primary ATCs. The prevalence of TERT promoter, PIK3CA, and TP53 mutations was comparable between the two subtypes. In comparison to primary ATCs, however, BRAF mutations were more prevalent (OR = 4.70; 95% CI = 2.84-7.78) whereas RAS mutations were less frequent (OR = 0.43; 95% CI = 0.21-0.85) in secondary tumors. In summary, our results indicated that de novo and secondary ATCs might share many potential developmental steps, but there are other factors that suggest distinct developmental pathways.

Decreasing trends in thyroid cancer incidence in South Korea: What happened in South Korea?

BACKGROUND: South Korea has the highest incidence of thyroid cancer in the world. Our study examined the trends in thyroid cancer incidence by the histologic type, cancer stage, and age group and explored possible factors that affected thyroid cancer trends. METHODS: We conducted a descriptive epidemiological study using the national cancer registry data and cause of death data from 1999 to 2016 in South Korea. Age-standardized rates were calculated using Segi's world standard population. Joinpoint regression analysis was applied to determine the changing point of thyroid cancer trends according to histologic type; Surveillance, Epidemiology, and End Results (SEER) summary stage; and age groups by sex. RESULTS: The age-standardized incidence of thyroid cancer in both men and women increased from 6.3 per 100,000 people in 1999 to 63.4 per 100,000 in 2012 but declined from 2012 to 2016, before the debates for over diagnosis of thyroid cancer began in 2014. The age-standardized mortality rate of thyroid cancer, incidence of distant thyroid cancer, and incidence of regional and localized thyroid cancer started to decline since early 2000, 2010, and 2012, respectively. In addition, thyroid cancer prevalence in thyroid nodules showed decreasing trends from 1999-2000 to 2013-2014. CONCLUSIONS: The incidence of thyroid cancer began declining from 2012, before the debates for over diagnosis of thyroid cancer began in 2014. Changes in guidelines for thyroid nodule examinations may have affected this inflection point. Moreover, the debates for over diagnosis of thyroid cancer may have accelerated the decline in thyroid cancer.

Treatment of anaplastic thyroid cancer with tyrosine kinase inhibitors targeted on the tumor vasculature: initial experience in clinical practice.

Anaplastic thyroid cancer (ATC) is a rarely occurring refractory disease. While recent clinical trials have demonstrated the efficacy of tyrosine kinase inhibitor (TKI) therapy for ATC, evidence is scarce in clinical practice. In this study, we reviewed our initial experiences with TKI treatment in ATC patients with the aim of revealing the efficacy and safety of the same in clinical practice. We retrospectively reviewed our experiences with TKI treatment use in ATC patients diagnosed at our institute from 2014 to 2019. Changes in the patients' neutrophil-to-lymphocyte ratio (NLR) by TKI therapy introduction as well as their clinical factors to indicate the efficacy were examined. Seven patients showed no indication for TKI treatment, while 13 (65%) received treatment. The median duration of TKI treatment was 1.9 months. All patients died, and the overall survival period from diagnosis was 4.7 (95% confidence interval: 2.0-11.5) months. Adverse events ≥Grade 3 were observed commonly (92.3%), and resulted in the termination of TKI treatment in six cases (46.1%). Existence of multiple unfavorable characteristics (higher Prognostic Index) was associated with poor survival. The NLR decreased after the introduction of TKIs and increased again when treatment failed. The response rate to TKI among the ATC patients were approximately 30% in practice. Although the duration of the response was short, several patients demonstrated long survival durations when TKI treatment was provided after successful multidisciplinary treatment to control local disease. Decreases in high NLR values during treatment may suggest the continued effect of TKIs.

Anaplastic thyroid carcinoma: Updates on WHO classification, clinicopathological features and staging.

Anaplastic thyroid carcinoma is an uncommon carcinoma representing 1 to 4% of all thyroid cancers. The carcinoma is most common in females of the eight decades. It is a locally advanced cancer with frequent infiltration of surrounding organs, blood vessels and skin of neck. Paraneoplastic manifestations could occur. Approximately half of the patients with anaplastic thyroid carcinoma had distant metastasis with lung and brain as the most frequent sites of metastasis. The median survival of patients with anaplastic thyroid carcinoma reported was from 1 to 6 months. The terminology of the cancer in World Health Organization is "anaplastic thyroid carcinoma" rather than "undifferentiated thyroid carcinoma". In the latest American Joint Committee on Cancer (AJCC) TNM staging system for anaplastic thyroid carcinoma, there are updates on T and N categories. To conclude, updated knowledge of clinicopathological features, classification, pathological staging will improve our understanding of the cancer and will help in the management of the patients with this aggressive cancer.

Evaluation of Overall Survival in Patients With Anaplastic Thyroid Carcinoma, 2000-2019.

Importance: Anaplastic thyroid carcinoma (ATC) historically has a 4-month median overall survival (OS) from time of diagnosis, with disease-specific mortality approaching 100%. The association between recent major advancements in treatment and OS has yet to be evaluated. Objective: To evaluate rates of OS in patients with ATC over the last 2 decades. Design, Setting, and Participants: Retrospective cohort study in a single tertiary care institution. Patients with histopathological confirmation of ATC from January 2000 to October 2019 were included and divided into 3 groups according to date of presentation: 2000-2013, 2014-2016, and 2017-2019. Main Outcomes and Measures: Overall survival compared among different treatment eras and differing therapies, including targeted therapy, immunotherapy, and surgery. Results: Of 479 patients (246 men [51%]; median age, 65.0 [range, 21.1-92.6] years) with ATC evaluated, 52 (11%) were stage IVA, 172 (36%) stage IVB, and 255 (53%) stage IVC at presentation. The median OS of the entire cohort was 0.79 years (9.5 months), ranging from 0.01 to 16.63. The OS at 1 and 2 years was 35% (95% CI, 29%-42%) and 18% (95% CI, 13%-23%) in the 2000-2013 group (n = 227), 47% (95% CI, 36%-56%) and 25% (95% CI, 17%-34%) in the 2014-2016 group (n = 100), and 59% (95% CI, 49%-67%) and 42% (95% CI, 30%-53%) in the 2017-2019 group (n = 152), respectively (P < .001). The hazard ratio was 0.50 (95% CI, 0.38-0.67) for the 2017-2019 group compared with the 2000-2013 patients (P < .001). Factors associated with improved OS included targeted therapy (hazard ratio, 0.49; 95% CI, 0.39-0.63; P < .001), the addition of immunotherapy to targeted therapy (hazard ratio, 0.58; 95% CI, 0.36-0.94; P = .03), and surgery following neoadjuvant BRAF-directed therapy (hazard ratio, 0.29; 95% CI, 0.10-0.78; P = .02). Patients undergoing surgery following neoadjuvant BRAF-directed therapy (n = 20) had a 94% 1-year survival with a median follow-up of 1.21 years. Conclusion and Relevance: In this large single-institution cohort study spanning nearly 20 years, changes in patient management appear to be associated with significant increase in survival. The era of untreatable ATC is progressively being replaced by molecular-based personalized therapies, with integration of multidisciplinary therapies including surgery and radiation therapy.

Anaplastic thyroid carcinoma: a nationwide cohort study on incidence, treatment and survival in the Netherlands over 3 decades.

OBJECTIVE: To perform a nationwide population based study in ATC on incidence, treatment and survival. DESIGN: Retrospective cohort study. METHODS: All patients with primary ATC between 1989 and 2016 were identified in the Netherlands Cancer Registry (NCR). Of all these patients excerpts from the pathology reports from PALGA: Dutch Pathology registry were linked to the data of the NCR. Standardized incidences were calculated, survival was estimated using Kaplan-Meier method and univariable statistically significant factors were included in a multivariable regression model. RESULTS: In total, 812 patients were included. Mean standardized incidence rates were 0.18/100 000 (range 0.11-0.27/100 000) with a significant trend over the years with an estimated annual percentage change of 1.3% per year (95% CI 0.4-2.1%). Median overall survival was 2.2 months, and estimated 1-year survival was 12%. Patients without distant metastases at diagnosis had an estimated 1-year survival of 21.6%. Prognostic factors for prolonged survival were double or triple therapy, age below 65 years, M0-status and absence of bilateral lymph node metastases. CONCLUSIONS: ATC is rare, but often lethal, form of thyroid cancer, with a median survival of 2 months and 1-year survival of approximately 10%. The incidence is slightly rising in the Netherlands over the past 3 decades. There appears to be a subgroup of patients that survive longer, mainly those with relatively limited disease who underwent double or triple therapy. Further research is needed to define these patients more distinctively.

Dietary iodine intake, therapy with radioiodine, and anaplastic thyroid carcinoma.

Background Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors. The aim of the study was to determine the correlation between a higher dietary intake of iodine, frequency of ATC and the characteristics of ATC, and to find out how often patients with ATC had a history of radioiodine (RAI) therapy. Patients and methods This retrospective study included 220 patients (152 females, 68 males; mean age 68 years) with ATC who were treated in our country from 1972 to 2017. The salt was iodinated with 10 mg of potassium iodide/ kg before 1999, and with 25 mg of potassium iodide/kg thereafter. The patients were assorted into 15-year periods: 1972-1986, 1987-2001, and 2002-2017. Results The incidence of ATC decreased after a higher iodination of salt (p = 0.04). Patients are nowadays older (p = 0.013) and have less frequent lymph node metastases (p = 0.012). The frequency of distant metastases did not change over time. The median survival of patients in the first, second, and third periods was 3, 4, and 3 months, respectively (p < 0.05). The history of RAI therapy was present in 7.7% of patients. Conclusions The number of patients with a history of RAI therapy did not change statistically over time. The incidence of ATC in Slovenia decreased probably because of higher salt iodination.

Anaplastic thyroid carcinoma with leucocytosis.

BACKGROUND: Anaplastic thyroid carcinoma is a high-grade tumour with poor prognosis. Most of the cases are easily diagnosed on cytology and some of these are associated with increased neutrophils in cytology specimen as well as in the blood. The objective of the study is to determine the frequency of neutrophilia with fever in anaplastic thyroid carcinoma. METHODS: This descriptive cross-sectional study was performed in the Department of Pathology Ayub Teaching Hospital Abbottabad as well as in association with Advance lab Abbottabad. All the cases diagnosed as anaplastic thyroid carcinoma on cytology were included, histopathological examination was done only in 5 cases. The duration of study was from October 2016 to October 2019 were included in the study. RESULTS: Out of 150 cases of thyroid cytology 09 were diagnosed as anaplastic thyroid carcinoma. The mean age of patients was 65.7±6.96. Gender distribution was 5/9 (55.6%) males and 4/9 (44.4%) were females. Out of which 05 were confirmed on histopathology 3 patients died within a month and 1 patient refused a biopsy. All of these cases were associated with an increased number of neutrophils on cytology and WBC count is 04 cases showed leucocytosis. All of them presented with rapidly growing mass in long-standing goitre with a median duration of 2 months. Weight loss was seen in 4/9 (44.44%), 3/9 (33.33%) presented with hoarseness of voice while only 1/9 (11.1%) patient presented with superior vena caval syndrome. CONCLUSION: In long-standing goitre rapid increase in size with fever and leucocytosis are suggestive of anaplastic thyroid carcinoma which should be investigated promptly.

Poorly Differentiated Carcinoma of the Thyroid Gland: Current Status and Future Prospects.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) is a rare but clinically highly significant entity because it accounts for most fatalities from non-anaplastic follicular cell-derived thyroid cancer. Due to the relative rarity of the disease and heterogeneous diagnostic criteria, studies on PDTC have been limited. In light of the evolution of ultra-deep next-generation sequencing technologies and through correlation of clinicopathologic and genomic characteristics of PDTC, an improved understanding of the biology of PDTC has been facilitated. Here, the diagnostic criteria, clinicopathologic characteristics, management, and outcomes in PDTC, as well as genomic drivers in PDTC reported in recent next-generation sequencing studies, are reviewed. In addition, future prospects in improving the outcomes in PDTC patients are reviewed. SUMMARY: PDTC patients tend to present with adverse clinicopathologic characteristics: older age, male predominance, advanced locoregional disease, and distant metastases. Surgery with clearance of all gross disease can achieve satisfactory locoregional control. However, the majority of PDTC patients die of distant disease. Five-year disease-specific survival for PDTC patients has been reported at 66%. On multivariate analysis, reported predictors of poor survival in PDTC patients have been older age (>45 years), T4a pathological stage, extrathyroidal extension, high mitotic rate, tumor necrosis, and distant metastasis at presentation. BRAFV600E or RAS mutations (27% and 24% of cases, respectively) remain mutually exclusive main drivers in PDTC. TERT promoter mutations represent the most common alteration in PDTC (40%). Mutation in translation initiation factor EIF1AX (11%) and tumor suppressor TP53 (16%) have also been reported in PDTC. High rates of novel mutations (MED12 and RBM10) have been reported in fatal PDTC (15% and 12%, respectively). Chromosome 1q gains represent the most common arm-level alterations in PDTC, and those patients show worse survival rates. Chromosome 22q losses are also found in PDTC and show strong association with RAS mutation. CONCLUSIONS: These new insights into the clinicopathologic and molecular characteristics of PDTC, together with further advancement in ultra-deep sequencing technologies, will be conducive in narrowing the focus in order to develop novel targeted therapies and improve the outcomes in PDTC patients.

County Median Family Income Is an Independent Prognostic Factor for Stage IV Anaplastic Thyroid Cancer.

BACKGROUND/AIM: Advanced anaplastic thyroid cancer (ATC) is a rare, but highly aggressive malignancy, and its prognostic factors need to be further explored. We examined socioeconomic factors' predictive effect for survival performance in stage IV ATC patients. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, we collected 1,048 cases with stage IV anaplastic thyroid cancer (ATC) from 2004 to 2015. Demographic, clinical, and socioeconomic factors were evaluated using univariate and multivariate analyses. RESULTS: Median family income showed a significant effect on overall survival (OS) and cancer-specific survival (CSS) in univariate analysis. Median family income level was found to be an independent prognostic factor for OS after multivariate adjustment Multivariate analysis for CSS showed similar results. CONCLUSION: Family income level is an independent prognostic factor for stage IV ATC.

Anaplastic thyroid carcinoma: an epidemiologic, histologic, immunohistochemical, and molecular single-institution study.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive form of thyroid cancer. A single-institution thyroid cancer cohort of ATC was identified within the last 10 years at our institution. Retrospective analysis revealed that the frequency of ATC was 0.5% (11/2106 thyroid carcinomas). The average age at diagnosis of ATC was 74 years, and the female-to-male ratio was 1.2:1. ATC presented as a rapidly enlarging neck mass involving predominantly the left thyroid lobe (7/11; 64%). Cervical adenopathy was present in 7 (64%) of 11 cases. Fifty-five percent (6/11) of patients had distant metastases at the time of diagnosis. Histologically, ATC closely simulated a large variety of soft tissue sarcomas; osteoclast-like giant cell-rich tumors; squamous cell, spindle cell, and small cell carcinomas; and anaplastic/large cell lymphomas. Four tumors (4/11; 36%) showed heterologous elements, including rhabdoid and chondroid differentiation. Immunohistochemical studies showed that all ATCs lost TTF-1 and thyroglobulin expression, whereas PAX-8 expression was identified in 36% (4/11) of tumors. Intense and extensive nuclear staining of p53 (>50%) and high Ki-67 proliferative rate (>30%) were seen in all ATCs (11/11; 100%). Next-generation sequencing revealed recurrent BRAF V600E and TP53 gene mutations. Individual examples of a BRAF G469A mutation in ATC with follicular carcinoma component, EGFR, PTEN, PIK3CA, and FGFR3 mutations, were also identified, whereas 1 case of ATC showed wild-type sequencing with no identifiable alterations.

Anaplastic thyroid carcinoma in Denmark 1996-2012: A national prospective study of 219 patients.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the least common but most malignant thyroid cancer. We aimed to examine the characteristics as well as evaluate the incidence, prognostic factors, and if introduction of a fast track cancer program might influence survival in a cohort of ATC patients. METHODS: A cohort study based on prospective data from the national Danish thyroid cancer database DATHYRCA and the national Danish Pathology Register including 219 patients diagnosed from 1996 to 2012, whom were followed until death or through September 2014. RESULTS: We found the median age in the 7th decade, the majority of patients being women presenting with a growing mass at the neck, diagnosed with stage T4b disease. At diagnosis, 56% of the patients had lymph node metastasis and 38% distant metastasis. We observed one- and five-year survival of 20.7% and 11.0%, respectively. Both univariate and multivariate analyses showed age (above 73.6 years), respiratory impairment, T4b stage, and distant metastasis at diagnosis to be significant prognostic factors. Further, introduction of a national fast track cancer program increased survival nearly two-fold. CONCLUSION: As new information, our study adds "respiratory impairment at diagnosis" and "introduction of a national fast track cancer program" to the list of already established prognostic indicators for ATC.

Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years (AU)

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Consensus on management of advanced medullary thyroid carcinoma on behalf of the Working Group of Thyroid Cancer of the Spanish Society of Endocrinology (SEEN) and the Spanish Task Force Group for Orphan and Infrequent Tumors (GETHI)

Background: Of all thyroid cancers,< 5 % are medullary (MTC). It is a well-characterized neuroendocrine tumor arising from calcitonin-secreting C cells, and RET gene plays a central role on its pathogeny. Methods: The electronic search was conducted using MEDLINE (PubMed), EMBASE and Cochrane Central Register of Controlled Trials. Quality assessments of selected current articles, guidelines and reviews of MTC were performed. Results: This consensus updates and summarizes biology, treatment and prognostic considerations of MTC. Conclusions: Multidisciplinary teams and specialized centers are recommended for the management of MTC patients. In the metastatic setting, those patients with large volume of disease are candidates to start systemic treatment mainly if they are symptomatic and the tumor has progressed in the last 12-14 months. Wait and see strategy should be offered to patients with: disseminated disease with only high levels of calcitonin and no macroscopic structural disease, low burden and absence of progression (AU)

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The changing incidence of thyroid cancer.

During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be attributable both to the growing use of diagnostic imaging and fine-needle aspiration biopsy, which has led to enhanced detection and diagnosis of subclinical thyroid cancers, and environmental factors. The latest American Thyroid Association (ATA) practice guidelines for the management of adult patients with thyroid nodules and differentiated thyroid cancer differ substantially from the previous ATA guidelines published in 2009. Specifically, the problems of overdiagnosis and overtreatment of a disease that is typically indolent, where treatment-related morbidity might not be justified by a survival benefit, now seem to be acknowledged. As few modifiable risk factors for thyroid cancer have been established, the specific environmental factors that have contributed to the rising incidence of thyroid cancer remain speculative. However, the findings of several large, well-designed epidemiological studies have provided new information about exposures (such as obesity) that might influence the development of thyroid cancer. In this Review, we describe the changing incidence of thyroid cancer, suggest potential explanations for these trends, emphasize the implications for patients and highlight ongoing and potential strategies to combat this growing clinical and public health issue.

El aumento de la incidencia del cáncer diferenciado de tiroides no se relaciona con un incremento en la detección de microcarcinomas incidentales / Rise in differentiated thyroid cancer incidence in our hospital is not related with an increased incidental microcarcinoma detection

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Concept and design of a nationwide prospective feasibility/efficacy/safety study of weekly paclitaxel for patients with pathologically confirmed anaplastic thyroid cancer (ATCCJ-PTX-P2).

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, often demonstrating resistance to multimodal therapeutic approaches. The median survival of ATC patients after initial diagnosis was reported to be <6 months due to the rapid progression of disease by dissemination and/or invasion. There have been several reports describing possible effective chemotherapies, but these studies might be biased by the nature of retrospective accumulations of clinical experiences, and thus reliable data concerning the efficacies of the treatment efforts are required. DESIGN: In 2009, we established the research organization Anaplastic Carcinoma Research Consortium Japan (ATCCJ) to investigate this highly malignant disease. Using this nationwide organization, we conducted a prospective clinical study to investigate the feasibility, safeness, and efficacy of chemotherapy with weekly paclitaxel for ATC patients. This trial is registered on the clinical trials site of the University Hospital Medical Information Network Clinical Trials Registry Web site (UMIN000008574). The study was started in 2012, and enrollment was closed in March 2014 after accumulating 71 patients from 28 registered institutes. The follow-up data will be available in April 2015. DISCUSSION: Important information concerning the management of this disease is expected to be revealed by this study. The concept and design of the study are described herein.

Geospatial and Temporal Analysis of Thyroid Cancer Incidence in a Rural Population.

BACKGROUND: The increasing incidence of thyroid cancer has resulted in the rate tripling over the past 30 years. Reasons for this increase have not been established. Geostatistics and geographic information system (GIS) tools have emerged as powerful geospatial technologies to identify disease clusters, map patterns and trends, and assess the impact of ecological and socioeconomic factors (SES) on the spatial distribution of diseases. In this study, these tools were used to analyze thyroid cancer incidence in a rural population. METHODS: Thyroid cancer incidence and socio-demographic factors in Vermont (VT), United States, between 1994 and 2007 were analyzed by logistic regression and geospatial and temporal analyses. RESULTS: The thyroid cancer age-adjusted incidence in Vermont (8.0 per 100,000) was comparable to the national level (8.4 per 100,000), as were the ratio of the incidence of females to males (3.1:1) and the mortality rate (0.5 per 100,000). However, the estimated annual percentage change was higher (8.3 VT; 5.7 U.S.). Incidence among females peaked at 30-59 years of age, reflecting a significant rise from 1994 to 2007, while incidence trends for males did not vary significantly by age. For both females and males, the distribution of tumors by size did not vary over time; ≤1.0 cm, 1.1-2.0 cm, and >2.0 cm represented 38%, 22%, and 40%, respectively. In females, papillary thyroid cancer (PTC) accounted for 89% of cases, follicular (FTC) 8%, medullary (MTC) 2%, and anaplastic (ATC) 0.6%, while in males PTC accounted for 77% of cases, FTC 15%, MTC 1%, and ATC 3%. Geospatial analysis revealed locations and spatial patterns that, when combined with multivariate incidence analyses, indicated that factors other than increased surveillance and access to healthcare (physician density or insurance) contributed to the increased thyroid cancer incidence. Nine thyroid cancer incidence hot spots, areas with very high normalized incidence, were identified based on zip code data. Those locations did not correlate with urban areas or healthcare centers. CONCLUSIONS: These data provide evidence of increased thyroid cancer incidence in a rural population likely due to environmental drivers and SES. Geospatial modeling can provide an important framework for evaluation of additional associative risk factors.