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      MON-LB015 Sporadic MTC in Children: Characterization of a Rare Disease

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          Abstract

          INTRODUCTION: Medullary thyroid carcinoma (MTC) is rare in children and is hereditary (hMTC), caused by germline mutations in the RET proto-oncogene, in about 95% of cases. Very little is known about sporadic MTC (sMTC) when diagnosed in children/young adults. Our aim was to study the clinical presentation and long-term outcomes of a large cohort of sMTC seen at a tertiary cancer center and to compare sMTC with hMTC in young patients (pts).

          METHODS: Through a review of institutional databases, we identified pts diagnosed with MTC ≤ age 21 years (y.). Charts were retrospectively reviewed and data abstracted. The diagnosis of sMTC vs hMTC was determined based on germline RET testing and family history.

          RESULTS: We identified 146 pts (53% female), of whom 20 (14%) had sMTC and 126 (86%) had hMTC (80 MEN2a and 46 MEN2b), with a median follow-up of 10 y. (range: 0.08-58, IQR 4.8-18). In pts with sMTC, the stage at diagnosis was I-II in 3/15 (20%) and stage III-IV in 12/15 (80%). Somatic mutations were identified in 11/12 tumors tested (6 RET p.M918T, 1 RET p.G691S, 2 RET deletions p.L629_L633del and p.E632_L633del, 1 RET c.2698_2710delinsC, and 1 CCDC6- ALK fusion). In contrast to hMTC, pts with sMTC were diagnosed at an older age [mean 18.0 y. ± 3.4 (range: 10-21) vs 12.9 y. ± 5.4 (range: 1.5-21), p<0.001], had higher calcitonin [median 889 (IQR 528-2634) vs 16 (IQR 3-117) x Upper Limit of Normal, p<0.001] and CEA levels [median 186 (IQR 46-468) vs 11 (IQR 4-16) x Upper Limit of Normal, p<0.001], larger tumors [median 2.5 cm (IQR 2-3.7) vs. 0.8 cm (IQR 0.4-1.9), p<0.001], and were more likely to be stage IV at diagnosis [73% vs 28%, p<0.001]. sMTC pts were less likely to have bilateral tumors [27% vs 81%, p<0.001] and, at last follow-up, had more persistent structural disease [79% vs 46%, p=0.007] and distant metastases [74% vs 37%, p=0.005]. Death from MTC occurred in 15% of pts with sMTC vs 6% pts with hMTC; median overall survival was not significantly different [30.6 y. in sMTC vs 39.3 y. in hMTC].

          CONCLUSION: In this largest reported series of MTC in children/young adults, and the only study to look at sMTC in this population, we identified sMTC in 14% of MTC cases, a higher prevalence than is traditionally recognized but one that is possibly confounded by a referral bias. Somatic mutations were identified in 92% of samples tested, allowing for targeted therapy in those with distant metastases if needed. Compared with hMTC, patients with sMTC presented at an older age with higher tumor markers, larger tumors, and more unilateral disease. At last follow-up, persistent structural disease and distant metastases were more common in sMTC. The differences in clinical presentation and long-term outcomes likely reflect a variable path to MTC diagnosis. In conclusion, sMTC in pts ≤ age 21 y. presents at an older age with more advanced disease, frequently has an actionable driver mutation, and may be more common than previously thought.

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          Author and article information

          Journal
          J Endocr Soc
          J Endocr Soc
          jes
          Journal of the Endocrine Society
          Oxford University Press (US )
          2472-1972
          08 May 2020
          08 May 2020
          08 May 2020
          : 4
          : Suppl 1 , ENDO 2020 ABSTRACTS SCHEDULED FOR THE ANNUAL MEETING OF THE ENDOCRINE SOCIETY – MARCH 28 – 31, 2020 - SAN FRANCISCO, CALIFORNIA (CANCELLED)
          : MON-LB015
          Affiliations
          [1 ] Baylor College of Medicine , Houston, TX, USA
          [2 ] University of Texas MD Anderson Cancer Center , Houston, TX, USA
          Article
          bvaa046.2101
          10.1210/jendso/bvaa046.2101
          7208739
          8f204124-36a3-4f4e-8e8f-7845a1109b14
          © Endocrine Society 2020.

          This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

          History
          Page count
          Pages: 1
          Categories
          Pediatric Endocrinology
          Pediatric Obesity, Thyroid, and Cancer
          AcademicSubjects/MED00250

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