Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects £ 18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided.

Background Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide (I/T) has activity in these patients, and the toxicity profile of I/T makes it an excellent backbone for study of new agents. Temsirolimus (TEM) and dinutuximab (DIN) were selected for testing with I/T in subjects with relapsed or refractory neuroblastoma. Methods Children’s Oncology Group (COG) ANBL1221, a randomised Phase II selection design trial, compared response and toxicity in subjects treated with I/T and either temsirolimus (I/T/TEM) or dinutuximab with granulocyte-macrophage colony stimulating factor (I/T/DIN). Patients were eligible at first relapse/progression or first designation of refractory disease, provided organ function requirements were met. Patients had to have histologic verification of neuroblastoma and/or demonstration of tumour cells in bone marrow with increased urinary catecholamines at diagnosis. Patients were eligible at first designation of relapse (defined as recurrence after response to treatment), or first designation of refractory disease (defined as inadequate response to treatment that included at least 4 cycles of ≥2 chemotherapeutic agents, including an alkylator and a platinum-containing compound. Patients previously treated for refractory or relapsed disease were ineligible. Computer-based randomisation with sequence generation defined by permuted block randomisation, with blocks of size 2, was used to assign patients 1:1 to I/T/TEM or I/T/DIN. Randomisation was stratified to ensure equal distribution of disease category (measurable vs. evaluable), prior exposure to anti-GD2 antibody therapy, and tumour MYCN amplification status. Patients on both regimens received oral temozolomide (100 mg/m2/dose) and intravenous (IV) irinotecan (50 mg/m2/dose) on days 1–5 of 21-day cycles. TEM (35 mg/m2/dose IV) was given on days 1 and 8. DIN (17·5 or 25 mg/m2/day IV) was administered on days 2–5. The primary endpoint was objective (complete or partial) response; responses were centrally reviewed by an independent panel of radiologists. Response was analysed on an intent-to-treat basis. Toxicity was assessed in all participants who received at least one dose of protocol therapy. Follow up of the initial cohort is ongoing. This study is registered at ClinicalTrials.gov (NCT01767194). Findings Thirty-five eligible subjects were enrolled from February 22, 2013-March 23, 2015. Median age was 5.7 years (range 2·1–16·2 years; interquartile range (IQR) 4·5–9·1 years). Among 18 subjects randomised to I/T/TEM, 1 PR was observed (5·6%, 95% confidence interval (CI): [0·0%, 16·1%]). Among 17 patients randomised to I/T/DIN, 9 (53%, 95% CI: [29·2%, 76·7%]) had objective responses (4 PR, 5 CR), including responses in 5/10 patients with relapsed/progressive disease and 4/7 with refractory disease. I/T/DIN met protocol-defined criteria for selection as the combination meriting further study. The most common ≥Grade 3 toxicities among I/T/TEM patients were neutropenia ...

Radiolabeled metaiodobenzylguanidine (mIBG) is a highly sensitive and specific marker for detecting neuroblastoma. A semiquantitative mIBG score (Curie score [CS]) was assessed for utility as a prognostic indicator for a cohort of patients with highrisk metastatic disease. Methods mIBG scans from 280 patients with mIBG-avid, stage 4 neuroblastoma enrolled on the Children’s Oncology Group (COG) protocol A3973 were evaluated at diagnosis (n = 280), after induction chemotherapy (n = 237), and after an autologous stem cell transplantation (n = 178). Individual mIBG scans were evaluated at 10 different anatomic regions, with the scoring of each site (0–3) based on the extent of disease at that anatomic region. Results There was no correlation between CS at diagnosis and subsequent treatment outcome. Patients with a CS > 2 after induction therapy had a significantly worse event-free survival (EFS) than those with scores ≤ 2 (3-y EFS: 15.4% ± 5.3% vs. 44.9% ± 3.9%, respectively; P < 0.001). A postinduction CS > 2 identified a cohort of patients at greater risk for an event, independent of other known neuroblastoma factors, including age, MYCN status, ploidy, mitosis-karyorrhexis index, and histologic grade. For MYCN-amplified tumors, the presence (CS > 0) versus absence (CS = 0) of residual mIBG avidity after induction was associated with a significantly worse outcome (3-y EFS: 11.8% ± 7.8% vs. 49.6% ± 7.7%, respectively; P = 0.003). After transplantation, patients with a CS > 0 had an EFS inferior to that of patients with a CS of 0 (3-y EFS: 28.9% ± 6.8% vs. 49.3% ± 4.9%, respectively [n = 133]; P = 0.009). Conclusion Curie scoring carries prognostic significance in the management of patients with high-risk neuroblastoma. In particular, patients with CSs > 2 after induction have extremely poor outcomes and should be considered for alternative therapeutic strategies.