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      The role of postoperative adjuvant radiotherapy in local recurrence risk in medullary thyroid carcinoma


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          The value of postoperative radiotherapy in the treatment of medullary thyroid carcinoma (MTC) has not been unequivocally demonstrated. Therefore our study aimed to answer the question of whether adjuvant radiotherapy showed any impact on the risk of local recurrence and whether there were any differences in response to radiotherapy between hereditary and sporadic MTC.


          A retrospective analysis involved 254 MTC patients, among them 73 patients with a hereditary disease. Two hundred and twenty-four patients, including 43 persons at a high risk of local relapse, underwent only initial surgery; 18 other patients were operated due to MTC recurrences, whereas the remaining 12 patients had cytoreductive procedure or were not amenable for surgery. Radiotherapy was carried out in 132 patients. One hundred and twenty patients underwent adjuvant radiotherapy, among them 102 patients after initial surgery. The median follow-up was 10 years (range 0.5–29 years).


          Local recurrence occurred in 107/254 patients, among them in 63 subjects after prior radiotherapy. The frequency of relapse showed significantly increasing trend toward higher MTC stages ( P <0.001). More relapses occurred in patients with lymph node metastases present at MTC onset. Adjuvant radiotherapy was associated with a lower risk of nodal recurrence only in high-risk patients, particularly if lymph node metastases were present at MTC diagnosis. The differences between hereditary and sporadic subgroups were not significant.


          Adjuvant radiotherapy has a limited importance in MTC treatment. It should be considered in high-risk MTC patients. The presence of RET mutation does not influence the response to radiation.

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          Medullary thyroid carcinoma.

          Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells that produce calcitonin (CT), and accounts for 5-10% of all thyroid cancers. MTC is hereditary in about 25% of cases. The discovery of a MTC in a patient has several implications: disease extent should be evaluated, phaeochromocytoma and hyperparathyroidism should be screened for and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. In this review, pathological characteristics, tumour markers and genetic abnormalities in MTC are discussed. The diagnostic and therapeutic modalities applied to patients with clinical MTC and those identified with preclinical disease through familial screening are also described. Progresses concerning genetics, initial treatment, follow-up, screening and treatment of pheochromocytoma have permitted an improvement in the long-term outcome. However, there is no effective treatment for distant metastases, and new therapeutic modalities are urgently needed.
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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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              Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control.

              Records of 73 patients with medullary thyroid cancer were reviewed to assess prognostic factors and the role of external beam radiation therapy. Patients were treated between 1954 and 1992. The median age was 49 years (range 15-85), M:F ratio 1.6:1, and the median follow-up was 7.9 years. (2.5-34.6). The primary tumor size was 4 cm in 37%. Multifocality was noted in 32%, and 23% had metastasis at presentation. Eight patients presented with inoperable tumors, 40% had gross, and 37% microscopic residual disease postthyroidectomy. Extraglandular extension was present in 56%, and 74% had pathologically involved lymph nodes. Treatment was by total or near total thyroidectomy in 41 patients; 37 had a lymph node dissection. Forty-six patients were irradiated, the dose of radiation ranging from 20 to 75.5 Gy; median was 40 Gy, treatment time median was 28 days and the median number of fractions was 20. The overall cause specific survival (CSS) was 70% and 57% at 5 and 10 years, respectively. In a univariate analysis, the following factors predicted for lower CSS: age as a continuous variable (p = 0.003), male gender (p = 0.008), presence of distant metastasis (p 4 cm (p = 0.05), extraglandular invasion (p < 0.004), vascular invasion (p = 0.007), diarrhea (p < .0007), and abnormal postoperative calcitonin (p = 0.02). On multivariate analysis only two factors were significant: the presence of extraglandular invasion, and postoperative gross residual disease. There was no difference in local/regional relapse free rate between patients receiving external radiation and those that did not, but in 40 high risk patients (microscopic residual disease, extraglandular invasion, or lymph node involvement), the local/regional relapse free rate was 86% at 10 years with postoperative external beam radiation (25 patients), and 52% for those with no postoperative external radiation (p = 0.049). To optimize local/regional tumor control, we therefore continue to advise external beam radiation in patients at high risk of local/regional relapse.

                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                January 2020
                28 November 2019
                : 9
                : 1
                : 1-8
                [1 ]Nuclear Medicine and Endocrine Oncology Department , M. Sklodowska-Curie Institute – Oncology Center, Gliwice Branch, Gliwice, Poland
                [2 ]Radiotherapy Department , M. Sklodowska-Curie Institute – Oncology Center, Gliwice Branch, Gliwice, Poland
                [3 ]Department of Epidemiology and Silesia Cancer Registry , M. Sklodowska-Curie Institute – Oncology Center, Gliwice Branch, Gliwice, Poland
                Author notes
                Correspondence should be addressed to J Krajewska: jolanta.krajewska@ 123456io.gliwice.pl
                © 2020 The authors

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

                : 07 November 2019
                : 28 November 2019

                medullary thyroid carcinoma,adjuvant radiotherapy,postoperative radiotherapy,radiation treatment


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