Bridging the gap between thyroidology & pediatric oncology

Abstract

Part I. Differentiated thyroid carcinoma in children Thyroid carcinoma is the most common endocrine malignancy in children, with a worldwide rising incidence. In chapter 2 the incidence and survival rates of differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma in Dutch children, adolescents, and young adults (0-24 years) over a 30-year life span are described. We found an increased incidence DTC over time, while the incidence rate of MTC had decreased.

In chapter 3 we summarized literature on DTC in children with PTEN hamartoma tumor syndrome (PHTS). No evidence was found for different clinical behavior of DTC in PHTS versus sporadic DTC. Consensus was reached to recommend surveillance for DTC in all children with PHTS by means of annual neck palpation and triennial neck ultrasound from the age of 10 years onwards.

Because DTC is a rare disease, national and international harmonization of care for children with DTC is necessary to improve the outcome. Up till now neither Dutch nor European pediatric recommendations for thyroid nodules and DTC were available. In chapter 4 and 5 the first national and European recommendations for the treatment of pediatric DTC are presented.

In chapter 6 we investigated the value of routine cervical US surveillance in follow-up of pediatric DTC after total thyroidectomy and we assessed the contribution of cervical US findings to the identification of structural residual or recurrent disease as compared to other surveillance modalities. Based on our findings we suggest that, in children with undetectable or low-detectable thyroglobulin concentrations during subsequent follow-up, without elevated TgAbs, it may be reasonable to restrict subsequent surveillance to a ‘Tg-first’ approach (chapter 6).

In chapter 7 we retrospectively evaluated the results of FDG PET/CT imaging as a first-line nuclear imaging modality in adult patients suspected of residual or recurrent DTC without first performing a radioactive iodine whole body scan (RAI WBS). In this case series we showed that FDG PET/CT imaging might be of additional value to detect residual or recurrent DTC in adult patients with low detectable Tg. However, DTC cannot be ruled out when no lesions are found on FDF PET/CT imaging.

In chapter 8 we investigated the clinical presentation, treatment, and outcome of subsequent DTC among childhood cancers survivors (CCS) in The Netherlands. In accordance with previous studies, we found that subsequent DTC seems to present with smaller tumors and more frequent bilateral disease. Tumor behavior and outcome of DTC in CCS does not seem to differ significantly from sporadic DTC.

Part II. Thyroid dysfunction during childhood cancer treatment Thyroid dysfunction is known to occur as late effect in childhood cancer survivors. Thyroid dysfunction during childhood cancer treatment has not been studied extensively so far, however. In chapter 9 we systematically reviewed all current available studies on thyroid dysfunction during treatment with systemic antineoplastic therapy for childhood cancer. In chapter 10 and 11 we present the first results of a prospective cohort study in the largest European pediatric oncology center: the THYRO-Dynamics study.