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      Prognosis of radiotherapy in medullary thyroid carcinoma patients without distant metastasis

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          Abstract

          Background

          Medullary thyroid carcinoma (MTC) is an advanced disease with a poor prognosis. Although radiotherapy is widely utilized to treat MTC, it is still controversial. MTC patients without distant metastases have not been investigated to explore indications for adjuvant radiotherapy. This study aims to investigate the impact of radiotherapy on the survival of MTC patients without distant metastases.

          Methods

          Data of MTC patients without distant metastasis who underwent total thyroidectomy between 2010 and 2015 were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Propensity score matching was performed to analyze the relationship between radiotherapy and cancer-specific survival (CSS).

          Results

          Seventy-four of 718 MTC patients without distant metastases received radiotherapy and underwent total thyroidectomy. A total of 148 patients were screened via propensity score matching analysis. Multivariate Cox regression indicated that factors including age, sex, radiotherapy and chemotherapy were independent predictors of CSS. Based on these factors, MTC patients without distant metastasis were classified into two risk groups using a nomogram and risk classification system. The C-index of the nomogram was 0.791. The calibration curves showed good consistency of CSS between the actual observation and the nomogram prediction, and decision curve analysis (DCA) showed great clinical usefulness of the nomogram. The three-year CSS of the radiotherapy group was 85.3%, and that of the surgery group was 95%. Particularly, compared with the surgery group, the three-year CSS of subgroups of the radiotherapy group, including male patients and those aged >48 years, was decreased.

          Conclusions

          Radiotherapy results in worse CSS for MTC patients without distant metastases. To maximize benefits, decisions about individual radiotherapy should weigh its advantages and disadvantages.

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          Most cited references31

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

          Samuel A Wells, Sylvia L Asa, Henning Dralle … (2015)
          The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association.
          Article 0 comments Cited 369 times – based on 0 reviews     Review now
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            Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives

            Lucieli Ceolin, Marta Duval, Antônio Felippe Benini … (2019)
            Medullary thyroid carcinoma (MTC) is a rare type of tumor that originates from thyroid C cells and accounts for 2–4% of all malignant thyroid neoplasms. MTC may occur sporadically or be inherited, as part of the MEN 2 syndrome. Germline mutations of the RET (REarranged during Transfection) proto-oncogene cause hereditary cancer, whereas somatic RET mutations and, less frequently, RAS mutations have been described in sporadic MTC samples. Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC. Nevertheless, despite recent advances, the management of advanced, progressive MTC remains challenging. The multikinase inhibitors (MKI), vandetanib and cabozantinib, were approved for the treatment of progressive or symptomatic MTC, and several other compounds have exhibited variable efficacy. Although these drugs have been shown to improve progression-free survival, no MKI has been shown to increase the overall survival. As these drugs are nonselective, significant off-target toxicities may occur, limiting achievement of the required TK-specific inhibition. Recently, next-generation small-molecule TKI has been developed. These TKI are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. Here, we summarize the current understanding of the intracellular signaling pathways involved in MTC pathogenesis as well as the therapeutic approaches and challenges for the management of advanced MTC, focusing on targeted molecular therapies.
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              Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control.

              Kenneth W. Simpson, Jane S. Sutcliffe, J Brierley … (1996)
              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.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transl Cancer Res
                Journal ID (iso-abbrev): Transl Cancer Res
                Journal ID (publisher-id): TCR
                Title: Translational Cancer Research
                Publisher: AME Publishing Company
                ISSN (Print): 2218-676X
                ISSN (Electronic): 2219-6803
                Publication date (Print and electronic): November 2021
                Publication date (Print): November 2021
                Volume: 10
                Issue: 11
                Pages: 4714-4726
                Affiliations
                [1]deptDepartment of Endocrinology, Zhujiang Hospital , Southern Medical University , Guangzhou, China
                Author notes

                Contributions: (I) Conception and design: S Huang, J Zhong; (II) Administrative support: H Chen; (III) Provision of study materials or patients: Z Zhang; (IV) Collection and assembly of data: R Chen, J Li; (V) Data analysis and interpretation: S Huang, J Zhong, J Sun; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Hong Chen; Jia Sun. No. 253, Industrial Avenue Middle, Haizhu District, Guangzhou 510282, China. Email: chenhong123@ 123456smu.edu.cn ; sunjia@ 123456smu.edu.cn .
                Article
                Publisher ID: tcr-10-11-4714
                DOI: 10.21037/tcr-21-1179
                PMC ID: 8798267
                PubMed ID: 35116326
                SO-VID: 0c0ed14d-f9c5-4cd8-898d-ed7dfb38c6c7
                Copyright © 2021 Translational Cancer Research. All rights reserved.
                License:

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                Date received : 05 July 2021
                Date accepted : 16 September 2021
                Funding
                Funded by: the National Natural Science Foundation of China
                Award ID: Grant No. 81770835
                Funded by: the Key-Area Research and Development Program of Guangdong Province
                Award ID: Grant No. 2019B020230001
                Categories
                Subject: Original Article

                Keywords: medullary thyroid cancer (mtc),radiotherapy,prognosis,propensity score matching,the surveillance epidemiology and end results database (seer database)
                Data availability:
                Keywords: medullary thyroid cancer (mtc), radiotherapy, prognosis, propensity score matching, the surveillance epidemiology and end results database (seer database)

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