Citations

Background: The incidence of pediatric thyroid cancer has been increasing, and care varies due to socioeconomic disparities or differing practice patterns. Clinical guidelines call for care in multidisciplinary teams to minimize variance and provide protocols. Based on expert opinion, we hope to describe the form and function of such multidisciplinary teams for pediatric thyroid programs. Methods: A modified Delphi method to reach consensus statements over two rounds. Twenty-one experts with varying backgrounds responded to each statement on a 9-point Likert scale. Upon completion of the survey, the panel reviewed and shared the results and comments from participants and modified the statements accordingly. This process was repeated such that statements reached consensus, were deemed no consensus, or had no change in the mean. Results: There was an 88% and 83% completion rate for Rounds 1 and 2, respectively. A consensus was observed that there is a distinct definable model of care for pediatric thyroid patients. No consensus was reached for the age range of patients, but programs should care for children with medullary thyroid cancer, differentiated thyroid cancer, and patients with genetic predisposition syndromes. A comprehensive team includes, but is not limited to, a thyroid surgeon, a pediatric endocrinologist, a high-volume fine-needle aspiration (FNA) proceduralist, an oncologist, a nuclear medicine physician, a pediatric pathologist, a pediatric radiologist, and a nurse coordinator. Necessary support services involve care coordination, access to a multidisciplinary tumor board, ability to perform ultrasound-guided FNA, and access to molecular testing. The panel emphasized cross-institutional collaborative research prioritizing guidelines development, disease-specific outcomes, treatment toxicity, and the molecular landscape of thyroid cancer. Conclusions: These consensus statements can be beneficial in improving multidisciplinary care, by describing which elements of pediatric thyroid programs should be consistent across institutions. Overall, the panel agreed that pediatric thyroid centers should provide integrated care with defined team members, services, resources, and research priorities. This model has the potential to standardize various aspects of clinical care and enhance our ability to study patient outcomes, improve health care delivery, and increase scholarly collaboration.

Tumor-initiating cells (TIC) are dynamic cancer cell subsets that display enhanced tumor functions and resilience to treatment but the mechanism of TIC induction or maintenance in lung cancer is not fully understood. In this study, we show the calcium pathway transcription factor NFATc2 is a novel regulator of lung TIC phenotypes, including tumorspheres, cell motility, tumorigenesis, as well as in vitro and in vivo responses to chemotherapy and targeted therapy. In human lung cancers, high NFATc2 expression predicted poor tumor differentiation, adverse recurrence-free and cancer-specific overall survivals. Mechanistic investigations identified NFATc2 response elements in the 3’ enhancer region of SOX2, and NFATc2/SOX2 coupling upregulates ALDH1A1 by binding to its 5’ enhancer. Through this axis, oxidative stress induced by cancer drug treatment is attenuated, leading to increased resistance in a mutation-independent manner. Targeting this axis provides a novel approach for the long-term treatment of lung cancer through TIC elimination.