Subsequent thyroid carcinomas in children and adolescents registered in the German MET consortium (1997–2023)

Kunstreich M; Ronckers CM; Lorenz K; Wolf SH; essel L; Rohrer TR; Vokuhl C; Schmid KW; Luster M; Fruhwald MC; Vorwerk P; Redlich A; Kuhlen M

doi:10.1530/ey.22.9.9

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ESPE Yearbook of Paediatric Endocrinology (2025) 22 9.9 | DOI: 10.1530/ey.22.9.9

ESPEYB25 9. Oncology and Chronic Disease Secondary Thyroid Cancer (2 abstracts)

9.9. Subsequent thyroid carcinomas in children and adolescents registered in the German MET consortium (1997-2023)

Kunstreich M , Ronckers CM , Lorenz K , Wolf SH , Lessel L , Rohrer TR , Vokuhl C , Schmid KW , Luster M , Frühwald MC , Vorwerk P , Redlich A & Kuhlen M

Thyroid. 2025 Jan;35(1):18-30. PMID: 39699646. doi: 10.1089/thy.2024.0312. [email protected]

Brief summary: This retrospective multicenter cohort study compared clinical characteristics and outcomes of subsequent differentiated thyroid carcinoma (DTC) in childhood cancer survivors with first primary DTC. It also compared cases of subsequent DTC in patients treated with chemotherapy alone to those treated with both chemotherapy and radiotherapy.

The study analyzed 505 cases of childhood DTC reported to the German Malignant Endocrine Tumour (MET) registry (1997–2023), of which 66 (13.1%) were subsequent DTCs arising after childhood cancer or hematopoietic stem-cell transplant (HSCT). These subsequent DTCs presented at median age 12.7 years, following a median latency period 7.3 years. Compared to primary DTCs, subsequent DTCs were less frequent in females, were smaller (median 1.1 cm vs. 2.2 cm), yet more often multifocal, and were usually detected through surveillance rather than symptoms; however, stage distribution and long-term outcomes did not differ. Among subsequent DTC cases, tumours arising after chemotherapy alone appeared earlier (median age 11.5 years), with a shorter latency (6.2 years) and were of a larger size (1.86 cm) than those following chemo + radiotherapy.

These findings support chemotherapy as an independent risk factor for treatment-related paediatric DTC, likely through DNA damage, genomic instability and treatment-induced mutations or chromosomal aberrations.

Comment: This series represents the largest published cohort of subsequent DTC in children aged 5–18-year-old. It addresses a key knowledge gap left by studies that focused on older adolescents and young adults. Even if DTC is typically associated with radiation exposure, this study shows that survivors treated with chemotherapy alone are also at risk of developing larger thyroid tumors at younger ages and after shorter latency periods. This highlights chemotherapy as an independent risk factor for subsequent DTC. Follow-up protocols should be changed to include customized, ultrasound-based care based on the patient’s treatment history and individual risk.