Carga a Largo Plazo de Toxicidad Tiroidea en Niños que Recibieron Tratamiento para Neuroblastoma de Alto Riesgo

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.

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.

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).

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.