Long-Term Thyroid Toxicity Burden in Children Who Received Treatment for High-Risk Neuroblastoma.
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BACKGROUND: Multimodal treatment, including both conventional and myeloablative chemotherapy (MAT), radiotherapy, surgery, immunotherapy, and differentiating therapy, has increased survival for children affected by high-risk neuroblastoma (HRNB) at the potential cost of long-term endocrine morbidities. In this retrospective single-center study we investigate the long-term thyroid toxicity in neuroblastoma survivors. METHODS: This is a retrospective, single-center cohort study. HRNB survivors were followed in outpatient clinic with a scheduled long-term follow-up program; for this report, we considered patients alive on June 1, 2023 at least 5 years from diagnosis treated during 1996-2018 period. Data were obtained from a chart review and were evaluated as risk factors for long-term toxicity occurrence. RESULTS: Forty-five patients with a median follow-up from diagnosis of 10.6 years (range 5-25.8 years) were evaluated. Long-term thyroid toxicities were reported in 24/45 (53%) patients at a median time of 7.5 years (range 1.2-18.2; interquartile range 3-12) from diagnosis; hypothyroidism was the most common toxicity (12/24, 50% of patients). The probability of being free from thyroid toxicity at 10 years was 62% (CI: 44-75%). Analyzing children's exposure to different treatments, the probability was 0% in patients who have undergone molecular radiotherapy and 72% (CI: 53-85%) in those who did not (p < 0.001); 30% (CI: 6-59%) in those who received immunotherapy and 78% (CI: 65-90%) in those who did not (p = 0.008); 37% (CI: 12-64%) in patients treated with tandem MAT and 71% (CI: 49-85%) in children who underwent single MAT (p = 0.016); and 86% in patients who did not receive Busulfan (CI: 39-98%) and 55% (CI: 35-71%) in those who did receive Busulfan (p = 0.002). Patients undergoing immunotherapy, 131I-meta-iodobenzylguanidine therapy or Busulfan experienced thyroid toxicity significantly earlier than those who did not (p = 0.047). CONCLUSIONS: The high cumulative treatment burden in this population results in a substantial risk of thyroid toxicity, even many years after therapy. Therefore, long-term endocrine follow-up should be considered also during adulthood.