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      Serum calcitonin nadirs to undetectable levels within 1 month of curative surgery in medullary thyroid cancer

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          ABSTRACT

          Objective:

          Because serum calcitonin (CT) is a reliable marker of the presence, volume, and extent of disease in medullary thyroid cancer (MTC), both the ATA and NCCN guidelines use the 2-3 month post-operative CT value as the primary response to therapy variable that determines the type and intensity of follow up evaluations. We hypothesized that the calcitonin would nadir to undetectable levels within 1 month of a curative surgical procedure.

          Subjects and methods:

          This retrospective review identified 105 patients with hereditary and sporadic MTC who had at least two serial basal CT measurements done in the first three months after primary surgery.

          Results:

          When evaluated one year after initial surgery, 42 patients (42/105, 40%) achieved an undetectable basal calcitonin level without additional therapies and 56 patients (56/84, 67%) demonstrated a CEA within the normal reference range. In patients destined to have an undetectable CT as the best response to initial therapy, the calcitonin was undetectable by 1 month after surgery in 97% (41/42 patients). Similarly, in patients destined to have a normalize their CEA, the CEA was within the reference range by 1 month post-operatively in 63% and by 6 months in 98%. By 6 months after curative initial surgery, 100% of patients had achieved a nadir undetectable calcitonin, 98% had reached the CEA nadir, and 97% had achieved normalization of both the calcitonin and CEA.

          Conclusion:

          The 1 month CT value is a reliable marker of response to therapy that allows earlier risk stratification than the currently recommended 2-3 month CT measurement.

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          Most cited references22

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          Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.

          The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association.
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            Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

            The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial. The study group consisted of 104 patients with MTC or C-cell hyperplasia managed at the hospitals of the University of California, San Francisco, between January 1960 and December 1998. Patients were classified as having sporadic MTC, familial non-multiple endocrine neoplasia (MEN) MTC, MEN 2A, or MEN 2B. The TNM, European Organization for Research and Treatment of Cancer (EORTC), National Thyroid Cancer Treatment Cooperative Study (NTCTCS), and Surveillance, Epidemiology, and End Results (SEER) extent-of-disease stages were determined for each patient. The predictive values of these staging or prognostic scoring systems were compared by calculating the proportion of variance explained (PVE) for each system. Fifty-six percent of the patients had sporadic MTC, 22% had familial MTC, 15% had MEN 2A, and 7% had MEN 2B. The overall average age at diagnosis was 38 years, and patients with sporadic MTC presented at an older age (P < 0.05). Thirty-two percent of the patients with hereditary MTC were diagnosed by screening (genetic and/or biochemical). These patients had a lower incidence of cervical lymph node metastasis (P < 0.05) and 94.7% were cured at last follow-up (P < 0.0001) compared with patients not screened. Patients with sporadic MTC who had systemic symptoms (diarrhea, bone pain, or flushing) had widely metastatic MTC and 33.3% of those patients died within 5 years. Overall, 49.4% of the patients were cured, 12.3% had recurrent MTC, and 38.3% had persistent MTC. The mean follow-up time was 8.6 years (median, 5.0 years) with 10.7% (n=11) and 13.5% (n=14) cause specific mortality at 5 and 10 years, respectively. Patients with persistent or recurrent MTC who died of MTC lived for an average of 3.6 years (ranging from 1 month to 23.7 years). Patients who had total or subtotal thyroidectomy were less likely to have persistent or recurrent MTC (P < 0.05), and patients who had total thyroidectomy with cervical lymph node clearance required fewer reoperations for persistent or recurrent MTC (P < 0.05) than patients who underwent lesser procedures. In univariate analysis, age, gender, clinical presentation, TNM stage, sporadic/hereditary MTC, distant metastasis, and extent of thyroidectomy were significant prognostic factors. Only age and stage, however, remained independent prognostic factors in multivariate analysis. The TNM, EORTC, NTCTCS, and SEER staging systems were all accurate predictors of survival, but the EORTC prognostic scoring system had the highest PVE in this cohort. Screening for MTC and early treatment (total thyroidectomy with central neck lymph node clearance) had nearly a 100% cure rate. Patients with postoperative hypercalcitoninemia without clinical or radiologic evidence of residual tumor after apparently curative surgery may enjoy long term survival but have occult MTC. Only patient age at presentation and TNM stage were independent predictors of survival. The EORTC criteria, which included the greatest number of significant prognostic factors in our cohort, had the highest predictive value. Copyright 2000 American Cancer Society.
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              Medullary thyroid carcinoma.

              Medullary thyroid carcinoma (MTC) accounts for 5-8% of all thyroid cancers. MTC is mainly sporadic in nature, but an hereditary pattern [multiple endocrine neoplasia type 2 (MEN 2)] is present in 20-30% of cases, transmitted as an autosomal-dominant trait due to germline mutations of the RET proto-oncogene. About 98% of patients with MEN 2 have germline mutations in exons 5, 8, 10, 11, 13, 14, 15 or 16 of the RET gene. The primary treatment of both hereditary and sporadic forms of MTC is total thyroidectomy and removal of all neoplastic tissue present in the neck. The therapeutic option for lymph node surgery should be dictated by the results of presurgical evaluation. After total thyroidectomy, measurements of serum calcitonin (CT) and carcinoembryonic antigen are of paramount importance in the postsurgical follow-up of patients with MTC as they reflect the presence of persistent or recurrent disease. Complete remission is demonstrated by undetectable and stimulated serum CT measurement. On the contrary, if serum CT is detectable under basal conditions or becomes detectable after stimulation, the patient is probably not cured, but imaging techniques will not demonstrate any disease until serum CT approaches levels >150 pg/ml. The tumour metastasises early to both paratracheal and lateral cervical lymph nodes. Metastases outside the neck may occur in the liver, lungs, bones and, less frequently, brain and skin. Surgery is the main treatment for local and distant metastases whenever feasible. Systemic chemotherapy with dacarbazine, 5-fluorouracil and doxorubicin (alone or in combination) has shown very limited efficacy, achieving only partial responses in the range of 10-20% and of short duration. Several kinase inhibitors are currently under evaluation and preliminary results are promising. Familial cases must be identified by searching for RET proto-oncogene mutations in the proband and in family members. Carriers of the RET gene are candidates for prophylactic thyroidectomy at different ages depending on the risk associated with the specific RET mutations. Copyright (c) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Arch Endocrinol Metab
                Arch Endocrinol Metab
                aem
                Archives of Endocrinology and Metabolism
                Sociedade Brasileira de Endocrinologia e Metabologia
                2359-3997
                2359-4292
                18 March 2019
                Mar-Apr 2019
                : 63
                : 2
                : 137-141
                Affiliations
                [1 ] normalizedInstituto Nacional de Câncer orgnameInstituto Nacional de Câncer orgdiv1Endocrinology Service orgdiv2Department of Medicine Rio de Janeiro RJ Brasil originalDepartment of Medicine, Endocrinology Service, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brasil
                [2 ] normalizedUniversité de Montréal orgnamel’Université de Montréal orgdiv1Center Hospitalier Montreal Canadá originalCenter Hospitalier de l’Université de Montréal, Medicine Endocrinology, Montreal, Canadá
                [3 ] orgnameMemorial Sloan-Kettering Cancer Center orgdiv1Department of Medicine New York NY USA originalDepartment of Medicine, Endocrinology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
                [4 ] orgnameMemorial Sloan-Kettering Cancer Center orgdiv1Department of Surgery, Head and Neck Cancer New York NY USA originalDepartment of Surgery, Head and Neck Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
                Author notes
                Correspondence to: Fernanda Accioly de Andrade, Departamento de Endocrinologia, Instituto Nacional de Câncer José Alencar Gomes da Silva Praça da Cruz Vermelha, 23, 8º andar, 20230-130 – Rio de Janeiro, RJ, Brasil andrade.clinica@ 123456gmail.com

                Disclosure: no potential conflict of interest relevant to this article was reported.

                Article
                2359-3997000000112
                10.20945/2359-3997000000112
                6639090
                30916162
                f8047cdf-1824-4562-b520-06dd65035ee2

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 June 2018
                : 12 December 2018
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 19, Pages: 5
                Categories
                Original Article

                calcitonin,medullary thyroid cancer,risk stratification,curative surgery,prognostic

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