Long-Term Thyroid Toxicity Burden in Children Who Received Treatment for High-Risk Neuroblastoma

Abstract

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.