Significant difference in aggressiveness of medullary thyroid carcinoma in rare RET mutations (codons 790, 791, 804)

ObjectiveRadioactive iodine (RAI) therapy in medullary thyroid carcinoma (MTC) is applied in some centers, based on the assumption that cross-irradiation from thyroid follicular cells may be beneficial. However, no systematic studies on the effect of RAI treatment in MTC have been performed. The aim of this study was to analyze the effect of RAI treatment on survival in MTC patients.DesignRetrospective multicenter study in eight University Medical Centers in The Netherlands.MethodsTwo hundred and ninety three MTC patients without distant metastases who had undergone a total thyroidectomy were included between 1980 and 2007. Patients were stratified by clinical appearance, hereditary stage, screening status, and localization. All patients underwent regular surgical treatment with additional RAI treatment in 61 patients. Main outcome measures were disease-free survival (DFS) and disease-specific survival (DSS). Cure was defined as biochemical and radiological absence of disease.ResultsIn multivariate analysis, stratification according to clinical appearance (P=0.72), hereditary stage (P=0.96), localization (P=0.69), and screening status (P=0.31) revealed no significant effects of RAI treatment on DFS. Multivariate analysis showed no significant difference in DSS for the two groups stratified according to clinical appearance (P=0.14). Owing to limited number of events, multivariate analysis was not possible for DSS in the other groups of stratification.ConclusionsBased on the results of the present analysis, we conclude that RAI has no place in the treatment of MTC.

Download Full-text

Comparison Between Clinicopathological Characteristics, BRAF V600E and TERT Promoter Mutation of Familial Non-Medullary Thyroid Carcinomas, and Sporadic Case

Frontiers in Oncology ◽

10.3389/fonc.2021.616974 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tian Yang ◽

Longsheng Huang ◽

Chang Chen ◽

Han Luo ◽

Yong Jiang

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Nodular Goiter ◽

Sporadic Case ◽

Clinicopathological Characteristics ◽

Braf V600e ◽

Biological Behavior ◽

Promoter Mutation ◽

Medullary Thyroid ◽

Significant Difference

BackgroundIt has been debated whether familial non-medullary thyroid carcinoma (FNMTC) is more aggressive and has a worse prognosis than sporadic non-medullary thyroid carcinoma (SNMTC). Our aim was to compare the invasiveness and prognosis of FNMTC and SNMTC by their biological behavior and molecular changes.Method and MaterialOur group mainly compared 106 patients with FNMTC whom have complete clinicopathological data during 2011–2019 in West China Hospital, Sichuan University, and 212 randomly selected cases with SNMTC were included to compare their biological behavior, recurrence and mortality, and molecular expression of BRAF V600E and TERT promoter. At the same time, FNMTC cases were divided into four subgroups, namely, two affected members group, three or more affected members, parent/offspring group, and sibling group, and they were compared with SNMTC separately to analyze the difference in their invasiveness and prognosis.ResultsWe found that the mean tumor size of FNMTC (0.96 ± 0.53cm) was smaller than that of SNMTC (1.15 ± 0.72 cm) (p = 0.020), while no significant difference in the incidence of other clinicopathological factors, including bilateral growth, capsular invasion, with thyroid nodular goiter or not, multifocality, lymph node metastasis, extrathyroidal extension, iodine 131 treatments, T stage, and American Joint Committee on Cancer (AJCC) stage, was observed between FNMTC and SNMTC (p > 0.05), between each FNMTC subgroup (p > 0.05), and between each FNMTC subgroup and SNMTC (p > 0.05). There was no significant difference in recurrence, mortality, and BRAF V600E and TERT promoter mutation between FNMTC and SNMTC, among which 50/60 (83.33%) of FNMTC patients had BRAF V600E mutation and 1/32 (3.13%) had TERT promoter mutation, while the mutation rates of SNMTC were 93/108 (86.11%) and 3/64 (4.69%) (p > 0.05).ConclusionThere was no significant difference in invasiveness and prognosis between FNMTC and SNMTC by biological behavior, patient survival, and molecular level comparison.

Download Full-text

The Diagnostic Value of Ultrasound in Medullary Thyroid Carcinoma: A Comparison With Computed Tomography

Technology in Cancer Research & Treatment ◽

10.1177/1533033820905832 ◽

2020 ◽

Vol 19 ◽

pp. 153303382090583

Author(s):

Liang Wang ◽

Hongju Kou ◽

Wei Chen ◽

Mingdong Lu ◽

Lingling Zhou ◽

...

Keyword(s):

Computed Tomography ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Gold Standard ◽

Diagnostic Value ◽

Benign Lesions ◽

Clinical Value ◽

Medullary Thyroid ◽

Significant Difference ◽

Enhanced Computed Tomography

Purpose: To explore the clinical value of ultrasound in the diagnosis of medullary thyroid carcinoma by comparing with enhanced computed tomography. Methods: This retrospective study was performed on 62 patients with pathologically confirmed medullary thyroid carcinoma. All patients underwent ultrasound and enhanced computed tomography examinations before surgery. The findings of the pathologic examination of resected specimens were considered as gold standard and were compared with the results of these 2 methods. Results: There were 73 medullary thyroid carcinoma lesions and 29 benign lesions in 62 patients. In all, 55 of 73 medullary thyroid carcinoma lesions and 27 of 29 benign lesions were correctly diagnosed by ultrasound; and 45 of 73 medullary thyroid carcinoma lesions and 24 of 29 benign lesions were correctly diagnosed by enhanced computed tomography. The accuracy of ultrasound and enhanced computed tomography was 80.4% and 67.6%, respectively. There was significant difference between 2 methods ( P < .05). Conclusions: Ultrasound can be used to observe the location, number, size, shape, border, internal echo, calcification, and blood flow of the lesion. It is a convenient, inexpensive, and nonradiative method with higher accuracy than enhanced computed tomography.

Download Full-text

Medullary Thyroid Carcinoma in MEN2A: ATA Moderate- or High-Risk RET Mutations Do Not Predict Disease Aggressiveness

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-00317 ◽

2017 ◽

Vol 102 (8) ◽

pp. 2807-2813 ◽

Cited By ~ 33

Author(s):

Rachel K Voss ◽

Lei Feng ◽

Jeffrey E Lee ◽

Nancy D Perrier ◽

Paul H Graham ◽

...

Keyword(s):

High Risk ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Multivariable Analysis ◽

Disease Onset ◽

Moderate Risk ◽

Medullary Thyroid ◽

Ret Mutation ◽

Significant Difference ◽

Risk Patients

Abstract Context High-risk RET mutations (codon 634) are associated with earlier development of medullary thyroid carcinoma (MTC) and presumed increased aggressiveness compared with moderate-risk RET mutations. Objective To determine whether high-risk RET mutations are more aggressive. Design Retrospective cohort study using institutional multiple endocrine neoplasia type 2 registry. Setting Tertiary cancer care center. Patients Patients with MTC and moderate- or high-risk germline RET mutation. Intervention None (observational study). Main Outcome Measures Proxies for aggressiveness were overall survival (OS) and time to distant metastatic disease (DMD). Results A total of 127 moderate-risk and 135 high-risk patients were included (n = 262). Median age at diagnosis was 42.3 years (range, 6.4 to 86.4 years; mean, 41.6 years) for moderate-risk mutations and 23.0 years (range, 3.7 to 66.8 years; mean, 25.6 years) for high-risk mutations (P < 0.0001). Moderate-risk patients had more T3/T4 tumors at diagnosis (P = 0.03), but there was no significant difference for N or M stage and no significant difference in OS (P = 0.40). From multivariable analysis for OS, increasing age [hazard ratio (HR), 1.05/y; 95% confidence interval (CI), 1.03 to 1.08], T3/T4 tumor (HR, 2.73; 95% CI, 1.22 to 6.11), and M1 status at diagnosis (HR, 3.93; 95% CI, 1.61 to 9.59) were significantly associated with worse OS but high-risk mutation was not (P = 0.40). No significant difference was observed for development of DMD (P = 0.33). From multivariable analysis for DMD, only N1 status at diagnosis was significant (HR, 2.10; 95% CI, 1.03 to 4.27). Conclusions Patients with high- and moderate-risk RET mutations had similar OS and development of DMD after MTC diagnosis and therefore similarly aggressive clinical courses. High-risk connotes increased disease aggressiveness; thus, future guidelines should consider RET mutation classification by disease onset (early vs late) rather than by risk (high vs moderate).

Download Full-text

Calcitonin release from medullary thyroid carcinoma by thyrotropin-releasing hormone: comparison with calcium injection

Acta Endocrinologica ◽

10.1530/acta.0.1260325 ◽

1992 ◽

Vol 126 (4) ◽

pp. 325-328 ◽

Cited By ~ 4

Author(s):

Seiichi Oishi ◽

Jouji Yamauchi ◽

Yasuko Fujimoto ◽

Shinichiro Hamasaki ◽

Teruhisa Umeda ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Normal Subjects ◽

Thyrotropin Releasing Hormone ◽

Medullary Thyroid ◽

Releasing Hormone ◽

Significant Difference ◽

Calcium Infusion ◽

Calcium Injection ◽

Peak Value

The effects of thyrotropin-releasing hormone on the release of calcitonin were investigated in 15 normal subjects and 12 patients with medullary thyroid carcinoma. The present study also compared the effect of TRH stimulation with calcium infusion test on calcitonin release in patients with medullary thyroid carcinoma. In normal subjects, calcitonin increased from a basal value of 7.5±2.5 pmol/l to a peak value of 9.4±3.0 pmol/l (p<0.01) after iv injection of synthetic TRH (500 μg). Basal calcitonin values in patients with medullary thyroid carcinoma were high (1216±2230 pmol/l, p<0.05), and TRH induced a further increase in calcitonin to 1 842±3149 pmol/l in all the patients (p< 0.05). They had a peak value of 7891±13 528 pmol/l after the calcium infusion, which was significantly higher than the basal value of 1463±2630 pmol/l (p<0.05). All medullary thyroid carcinoma patients displayed a marked calcitonin increase after TRH and calcium stimulation. Although the increase in serum calcitonin after TRH injection was lower than that after calcium injection (1.6-fold vs 5.4-fold, p <0.05), there was no significant difference in mean peak calcitonin value following TRH and calcium injection in patients with medullary thyroid carcinoma. These results indicated that TRH could stimulate calcitonin release from the thyroid C-cells in both normal subjects and patients with medullary thyroid carcinoma.

Download Full-text

Association between calcitonin and efficacy of anlotinib in medullary thyroid carcinoma: An analysis based on the ALTER01031 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.6526 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 6526-6526

Author(s):

Ming Gao ◽

Yihebali Chi ◽

Pingzhang Tang ◽

Zhengang Xu ◽

Xiangqian Zheng ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Response Rate ◽

Objective Response ◽

Target Lesion ◽

Medullary Thyroid ◽

Lower Baseline ◽

Significant Difference ◽

The Relationship ◽

Clinical Trial Information

6526 Background: Calcitonin (Ct) is the most important biomarker for medullary thyroid carcinoma (MTC). In a randomized, placebo-controlled phase IIb trial (ALTER01031, NCT02586350) for MTC, anlotinib exhibited a strong capability not only in PFS prolongation but also in decreasing Ct level. This subanalysis explored the relationship between Ct level and anlotinib efficacy in this trial. Methods: Serum Ct of patients (pts) were tested at baseline and on week 6 (after 2 treatment cycles). Correlation between changes in Ct level and changes in target lesion diameters was explored. The influence of baseline Ct level on median PFS for anlotinib treated pts was estimated. Finally, pts in anlotinib arm were divided into two subgroups based on the percentage decline of Ct levels (> 50% vs. ≤50%) at week 6. Median PFS (mPFS), median OS (mOS) and objective response rate (ORR) of two groups were compared. Results: 86 of 91 enrolled pts (58 in anlotinib arm and 28 in placebo arm) were recorded their serum Ct levels at baseline and no significant difference was observed between two arms (7990.0 ng/L vs. 10891.5 ng/L, P = 0.192). After 2 treatment cycles, the Ct level decreased to 4597.5 ng/L in anlotinib arm (n = 50) while increased slightly in placebo arm (12640.0 ng/L, n = 24, P = 0.006). For 49 pts in anlotinib arm who had complete assessments at baseline and week 6, roughly linear relationship was observed between Ct levels (X-axis) and target lesion diameters (Y-axis) in percent changes from baseline to week 6 (y = 0.175x – 0.049; r = 0.352, P = 0.016, excluding 3 outliers). Pts with less baseline Ct level (≤ median value vs. > median value) did not show more PFS benefit (17.7 vs. 22.4 months, P = 0.802). However, after 2 treatment cycles, a trend of better survival and higher response was observed in pts with high percentage decline of Ct level (> 50%, n = 25) than those with low percentage decline (≤50%, n =25) although without statistical difference (data presented in the table below). Conclusions: In ALTER01031, anlotinib showed a strong capability in rapidly decreasing serum Ct. Lower baseline Ct level does not mean better prognosis while a rapid Ct decrease may predict improved survival and treatment response to MTC pts received anlotinib. Clinical trial information: NCT02586350 . [Table: see text]

Download Full-text