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      Replication of newly proposed TNM staging system for medullary thyroid carcinoma: a nationwide study

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          Abstract

          A recent study proposed new TNM groupings for better survival discrimination among stage groups for medullary thyroid carcinoma (MTC) and validated these groupings in a population-based cohort in the United States. However, it is unknown how well the groupings perform in populations outside the United States. Consequently, we conducted the first population-based study aiming to evaluate if the recently proposed TNM groupings provide better survival discrimination than the current American Joint Committee on Cancer (AJCC) TNM staging system (seventh and eighth edition) in a nationwide MTC cohort outside the United States. This retrospective cohort study included 191 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. In multivariate analysis, hazard ratios for overall survival under the current AJCC TNM staging system vs the proposed TNM groupings with stage I as reference were 1.32 (95% CI: 0.38–4.57) vs 3.04 (95% CI: 1.38–6.67) for stage II, 2.06 (95% CI: 0.45–9.39) vs 3.59 (95% CI: 1.61–8.03) for stage III and 5.87 (95% CI: 2.02–17.01) vs 59.26 (20.53–171.02) for stage IV. The newly proposed TNM groupings appear to provide better survival discrimination in the nationwide Danish MTC cohort than the current AJCC TNM staging. Adaption of the proposed TNM groupings by the current AJCC TNM staging system may potentially improve accurateness in survival discrimination. However, before such an adaption further population-based studies securing external validity are needed.

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          Most cited references29

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          The Danish Pathology Register.

          The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established. DPR contains patient, pathology, and workload data. All records are subject to error tracing. The DPR covers all pathology data in Denmark. The data is used by the pathologists in the daily diagnostic process. The National Board of Health uses the data in the Danish Cancer Registry and DPR is unique for research as data can be linked to tissue biobanks and clinical databases.
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            Prognostic factors for thyroid carcinoma. A population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program 1973-1991.

            A number of prognostic factors for thyroid carcinoma have been identified, including sociodemographic characteristics, such as age and gender, and tumor characteristics, such as histology and stage. The relative importance of these factors as independent predictors of survival for patients with papillary, follicular, anaplastic, and medullary thyroid carcinoma has been extensively studied but remains uncertain. The authors used data collected by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute between 1973 and 1991 to investigate prognostic factors for each of the major histologic types of thyroid carcinoma in a population-based patient series and to assess the effect of these factors as predictors of survival. Both tumor and sociodemographic characteristics were independently associated with survival. Patients with papillary carcinoma had the highest 10-year relative survival (0.98), followed by those with follicular carcinoma (0.92) and medullary carcinoma (0.80). Anaplastic tumors had the lowest 10-year relative survival (0.13). Stage at diagnosis and differentiation status were strong independent prognostic factors for each histologic type. Advanced stage at diagnosis was a stronger prognostic factor for medullary carcinoma than for other histologic types. Increasing age was associated with lower relative survival for each histologic type. Gender, marital status, and ethnicity were significant, but weaker, predictors of survival. Survival varied markedly among patients with different histologic types of thyroid carcinoma. Stage at diagnosis and tumor differentiation were important prognostic factors for each histologic type. Age at diagnosis was a stronger predictor of survival for patients with follicular and medullary carcinoma than for patients with papillary carcinoma.
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              Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'étude des tumeurs à calcitonine.

              Prognostic factors of sporadic or inherited medullary thyroid carcinoma (MTC) are still controversial and have been assessed in old and small series. A better knowledge of these factors would improve patient management. To evaluate factors involved in the prognosis of MTC in a large series of cases, using uni- and multivariate analysis. Clinical, biological, surgical and epidemiological data on 899 MTC patients, diagnosed between 1952 and 1996, were collected by the French Calcitonin Tumors Study Group (GETC) with a standardized questionnaire, and processed in a national database. Survival and biochemical cure (i.e. normal basal post-operative serum calcitonin levels) were analysed with Kaplan and Meier and log-rank test statistical procedures. Data are presented as adjusted rather than observed survival, to consider only patients who died of MTC. Cox's forward-stepping proportional hazard model was used to analyse factors with a significant influence on survival by univariate analysis. Apart from the large proportion of familial forms (43%), the general characteristics of our population were similar to those in other studies: mean age at surgery = 43.4 years; sex ratio = 1 male/1.35 female; stage I = 20.8%; stage II = 21.2%; stage III = 46.5% and stage IV = 11.5%. 863 (96%) patients underwent surgery; 43% of operated patients were biochemically cured. Adjusted survival was 85.7 +/- 1.5% at 5 years and 78.4 +/- 2.1% at 10 years. Multivariate analysis showed that age and stage were independent predictive factors of survival. Gender, type of surgery, type of familial form were predictive only in univariate analysis. Biochemical cure predicts a survival rate of 97.7% at 10 years. Authentic recurrence, that is subsequent elevation of calcitonin (CT) after post-operative normalization, was found in 4.9%. In non-cured patients (57%), survival was still good: 80.2% (+/- 2.2%) and 70.3% (+/- 2.9%) at 5 and 10 years, respectively. Similarly, prediction of biochemical cure was solely dependent on stage. Survival of these medullary thyroid carcinoma patients appears better than expected even in non-cured patients. Considering the strong impact of stage, the necessity for pre-operative diagnosis of MTC is obvious.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                January 2019
                14 December 2018
                : 8
                : 1
                : 1-7
                Affiliations
                [1 ]Department of ORL Head & Neck Surgery and Audiology , Odense University Hospital, Odense, Denmark
                [2 ]Department of Clinical Research , University of Southern Denmark, Odense, Denmark
                [3 ]Department of Clinical Medicine and Endocrinology , Aalborg University Hospital, Aalborg, Denmark
                [4 ]Steno Diabetes Center North Jutland , Aalborg, Denmark
                [5 ]Department of Internal Medicine and Endocrinology , Aarhus University Hospital, Aarhus, Denmark
                [6 ]Department of Medical Endocrinology , Copenhagen University Hospital, Copenhagen, Denmark
                [7 ]Department of ORL Head & Neck Surgery , Aarhus University Hospital, Aarhus, Denmark
                [8 ]Department of ORL Head & Neck Surgery , Aalborg University Hospital, Aalborg, Denmark
                [9 ]Department of ORL Head & Neck Surgery , Copenhagen University Hospital, Copenhagen, Denmark
                [10 ]Department of Oncology , Herlev Hospital, Herlev, Denmark
                [11 ]Odense Patient data Explorative Network (OPEN) , Odense University Hospital, Odense, Denmark
                [12 ]Department of Molecular Medicine , Aarhus University Hospital, Aarhus, Denmark
                [13 ]Center for Genomic Medicine , Copenhagen University Hospital, Copenhagen, Denmark
                Author notes
                Correspondence should be addressed to J S Mathiesen: jes_mathiesen@ 123456yahoo.dk
                Article
                EC-18-0494
                10.1530/EC-18-0494
                6330714
                30550378
                c8fa4ab8-59b5-42e6-b7f8-da7d9aca7c67
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 23 November 2018
                : 14 December 2018
                Categories
                Research

                thyroid,endocrine cancers,rare diseases/syndromes
                thyroid, endocrine cancers, rare diseases/syndromes

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