Context: Denosumab is an effective treatment for many receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated disorders but there are potential safety considerations and limited data to guide its use in children and adolescents. Objective: This document seeks to summarize the evidence and provide expert opinion on safe and appropriate use of denosumab in pediatric RANKL-mediated disorders. Participants: Ten experts in pediatric bone and mineral medicine from 6 countries with experience in the use of denosumab participated in the creation of this document. Evidence: Data were sourced from the published literature, primarily consisting of case reports/series and review articles because of the lack of higher level evidence. Expert opinion of the authors was used substantially when no published data were available. Conclusion: Denosumab is an effective treatment for RANKL-mediated disorders in children and adolescents but is often not curative and, in some cases, is best used in conjunction with surgical or other medical treatments. Careful multidisciplinary planning is required to define the goals of treatment and expert oversight needed to manage the risk of mineral abnormalities. Substantive, collaborative research efforts are needed to determine optimal treatment regimens and minimize risks.

Purpose of Review: Paediatric thyroid cancer management traditionally relied on extrapolation from adult data and, despite good survival outcomes, often involved extensive surgical approaches and radioactive iodine (RAI) therapy with potentially life‐long complications. Increasing understanding of paediatric diagnostic techniques, molecular tumour drivers and targeted therapies will allow a more nuanced, disease‐specific comprehensive model of care. This review summarises recent developments in paediatric thyroid cancer biology, diagnosis and models of care.Methods: Review of relevant literature from the last 5 years to inform a narrative summary by a multidisciplinary team of clinician experts in paediatric thyroid cancer management.Findings: Standardised risk scoring systems will likely improve the objectivity and accuracy of paediatric thyroid nodule risk stratification on ultrasound, but further studies are needed to validate these. Identification of somatic and germline gene variants is playing a rapidly increasing role in paediatric thyroid cancer diagnosis and planning of surgical approaches and neoadjuvant and adjuvant therapies. There is growing recognition that lobectomy may achieve comparable outcomes, with reduced risk of complications, to total thyroidectomy in patients with low‐risk disease. Molecularly targeted therapies are now available for the management of advanced disease as an adjuvant, and likely neo‐adjuvant, therapy for medical debulking of large tumours and resensitisation of RAI‐resistant disease.Conclusions: The management pathways for paediatric thyroid cancer are rapidly evolving due to the increasing availability of paediatric‐specific data. As management options become more complex, interdisciplinary collaboration and shared decision‐making are ever more important.

Background: The understanding of the molecular basis of paediatric thyroid carcinoma has expanded rapidly in the last decade. Most carcinomas are associated with de novo somatic gene alterations that confer distinct clinicopathological characteristics. In comparison to adults, paediatric carcinomas are less commonly associated with point mutations and more commonly with gene fusions, which are characterised by more-invasive disease. Cancer predisposition genes play an important role in a small percentage of tumours, and the family history and the recognition of other syndromic features are key to identifying these patients. Molecular testing platforms for clinical use have been developed and validated in adults, and their use is becoming established in the management of indeterminate thyroid nodules, where they significantly reduce the rates of diagnostic lobectomy. Paediatric data are more limited than adult data, and the role of molecular testing in paediatric thyroid carcinoma management is evolving. Methods: This review describes the current knowledge of molecular alterations in paediatric thyroid carcinomas, evidence supporting molecular testing in clinical practice, and future directions for research. Results and Conclusions: A molecular diagnosis enables the use of molecularly targeted therapies for children and adolescents with advanced or radioiodine-refractory disease. There is also great potential for molecular testing to improve the accuracy of the risk-stratification of paediatric thyroid nodules, reducing surgical intervention and complications without negatively impacting outcomes, and data to support such an approach are emerging.