Diagnostic and surgical dilemmas in hereditary medullary thyroid carcinoma

10014 Background: Mutations in the RET protooncogenecause hereditary medullary thyroid carcinoma (MTC) including Multiple Endocrine Neoplasia (MEN) Type 2A, Type 2B and familial MTC. Vandetanib inhibits VEGFR, EGFR, and RET tyrosine kinases and is active in adults with hereditary MTC. Methods: We are conducting a trial of vandetanib in children and adolescents with RET mutations and MTC. Safety is evaluated at each dose level in adolescents (13–18 years) prior to enrolling children (5–12 years). In the absence of dose limiting toxicity (DLT), intrapatient dose escalation is permitted after cycle 2. To assess bone toxicity, growth plate volume is measured using MRI. Response is monitored using tumor measurements (RECIST), serum biomarkers, calcitonin (CTN), and carcinoembryonic antigen (CEA). Results: Five adolescents and 2 children were enrolled at the 100 mg/m2 dose level, 3 adolescents were dose escalated to 150 mg/m2. Six have MEN2B (M918T RET mutation). Median (range) baseline CTN was 12,200 pg/mL (2,300–67,000) and CEA was 104 mcg/L (5–325). Dose limiting diarrhea was observed in 1/5 adolescents at the 100 mg/m2 and 1/3 adolescents escalated to 150 mg/m2. No DLTs were observed in children receiving 100 mg/m2. Non-DLT included elevated TSH (n = 6), rash (n = 5), anorexia (n = 3), diarrhea (n = 2), hypertension (n = 1), and fatigue (n = 1). Median (range) percent change in growth plate volume during therapy was -18% (-44% to + 50%). All patients had linear growth during therapy. Serum CTN and CEA decreased by ≥ 50% in 6/7 and 2/7 patients, respectively. Tumor size decreased in 6/6 patients with M918T RET mutations; 2 achieved RECIST partial response after 6 and 12 cycles. Conclusions: Preliminary results suggest that vandetanib has activity in children and adolescents with MEN2B associated MTC. Vandetanib 100 mg/m2 was well tolerated. Linear growth was not impaired. [Table: see text]

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Ergebnisse der EUROMEN-Studie zur prophylaktischen Thyreoidektomie beim hereditären Schilddrüsenkarzinom / Early Thyroidectomy in Hereditary Medullary Thyroid Carcinoma: Results of the EUROMEN Study in 212 Patients

Deutsche Gesellschaft für Chirurgie - Panta Rhei — Umdenken — ◽

10.1007/978-3-642-56458-1_64 ◽

2001 ◽

pp. 221-221

Author(s):

J. Ukkat ◽

O. Grimm ◽

H. Dralle

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Medullary Thyroid ◽

Hereditary Medullary Thyroid Carcinoma

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Similar stage-dependent survival and outcome in sporadic and hereditary medullary thyroid carcinoma

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab326 ◽

2021 ◽

Author(s):

Friedhelm Raue ◽

Thomas Bruckner ◽

Karin Frank-Raue

Keyword(s):

Observational Study ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Residual Disease ◽

Disease Specific Survival ◽

Medullary Thyroid ◽

Hereditary Medullary Thyroid Carcinoma ◽

Similar Stage ◽

Disease Specific

Abstract Context Long-term data are scarce on large cohorts with sporadic (sMTC) and hereditary medullary thyroid carcinoma (hMTC). Objectives To compare long-term disease-specific survival (DSS) and outcomes between sMTC and hMTC groups. Design Retrospective analysis Setting German tertiary referral center Patients 673 patients with MTC that underwent surgery from January 1974 to July 2019 Intervention None (observational study) Main Outcome Measure Differences between sMTC and hMTC in long-term, stage-dependent survival and outcomes Results Surgery was performed at median ages of 49 years for sMTC (n=477, 44% male) and 29 years for hMTC (n=196, 43% male; p<0.0001). The mean follow-up times were 9.2±8.0 (sMTC) and 14.6±10.3 years (hMTC). Age and tumor stage at diagnosis were significantly different between the two groups (p<0.0001). The sMTC and hMTC groups had different overall DSS (log rank, p=0.0183), but similar stage-dependent DSS (log rank, p=0.1242 to 0.8981). In a multivariate analysis, sMTC and hMTC did not differ in DSS (HR=1.56, 95%CI=0.94-2.57), but in both groups, a worse DSS was significantly associated with age at diagnosis (HR=1.04, 95%CI=1.02-1.05), male sex (HR=0.49, 95%CI=0.32-0.76), and stages III and IV at diagnosis (HR=20.00, 95%CI=2.74-145.91 and HR=97.47, 95%CI=13.07-726.67, respectively). The groups had significantly different (p<0.0001) outcomes (i.e., cured, minimal residual disease, structural detectable disease, and death), but similar stage-dependent outcomes (p=0.9449 to 0.0511), except for stage III (p=0.0489). Conclusion Patients with sMTC and hMTC had different ages of onset, but similar stagedependent DSS and outcomes after the MTC diagnosis. This finding suggested that tumor behavior was similar in sMTC and hMTC. Précis This observational study of 673 patients with sporadic (n=477) and hereditary MTC (n=196) revealed similar disease-specific survival rates and outcomes, which suggested similar tumor behavior.

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