Objective Childhood cancer survivors (CCS) are at increased risk to develop differentiated thyroid cancer predominantly after radiotherapy (subsequent DTC). It is insufficiently known whether subsequent DTC in CCS has a different presentation or outcome than sporadic DTC. Methods Patients with subsequent DTC (n= 31) were matched to patients with sporadic DTC (n= 93) on gender, age and year of diagnosis to compare presentation and DTC outcomes. Clinical data were collected retrospectively. Results Among the CCS with subsequent DTC, all but one had received chemotherapy for their childhood cancer; 19 (61.3%) had received radiotherapy including the thyroid region; 3 (9.7%) 131I-MIBG and 8 (25.8%) had received treatment with chemotherapy only. Subsequent DTC was detected by surveillance through neck palpation (46.2%), as a self-identified mass (34.6%), or by chance. Among sporadic DTC patients, self detection predominated (68.8%). CCS with subsequent DTC tended to have on average smaller tumors (1.9 vs. 2.4 cm respectively, (p=0.051), and more often bilateral (5/25 (60.0%) vs. 28/92 (30.4%), p=0.024). There were no significant differences in the occurrence of surgical complications, recurrence rate or disease-related death. Conclusion When compared to patients with sporadic DTC, CCS with subsequent DTC seem to present with smaller tumors and more frequent bilateral tumors. Treatment outcome seems to be similar. The finding that one third of subsequent DTC cases had been treated with chemotherapy only needs further investigation. These results are important for the development of surveillance programs for CCS at risk for DTC and for treatment guidelines of subsequent DTC.

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