ESPE Abstracts

Background: Medulloblastoma is the most common malignant pediatric brain tumor. Although survival has improved with oncological therapy, late effects such as endocrine consequences are common, especially growth failure and thyroid dysfunction.

Methods: Children diagnosed with medulloblastoma in a pediatric hospital between 2004 and 2014 were studied and followed until 2019. Statistical analysis was performed to estimate the effect of radiotherapy (RT) on growth and thyroid disorders.

Results: Fifty-six patients (39 boys, 17 girls) were reviewed. The mean age at diagnosis was 5.2 years (IQR:3.0-8.1). Forty-three were assessed by pediatric endocrinologists for 3.5 years (IQR:0.6-7.3), of which 14 are still being followed in our department.

Forty-five patients received RT and endocrine alterations were significantly more frequent afterwards(P=0.03), especially for growth hormone (GH) and thyroid function disorders (P<0.05). The mean dose to the posterior fossa was 54.3 Gy (IQR:54-60) and to the craniospinal region 30.9 Gy (IQR: 23.4-36). Median age at the time of radiotherapy was 5.8 years (IQR:4.2-9.1).

GH deficiency was the most common sequelae (21 patients) after a mean of 3.8 years of RT (IQR:3.0-5.8), followed by hypothyroidism (14=primary, 5=secondary) after 3.0 years of age (IQR:1.5-5.1). Patients who received RT and developed hypothyroidism also presented ultrasound alterations: 48% with reduced size of thyroid and 31% with altered echogenicity. There was a strong association between radiotherapy and hypothyroidism, P=0.01.

Only 12 patients received GH treatment (12/21). The mean GH peak after clonidine and insulin tolerance test was 2.5 µg/L (IQR:0.7-3.5) and 1.2 µg/L (IQR:0.5-3.5), respectively. GH therapy was stopped after a mean of 3.2 years (IQR:2.0-5.0) of finalizing oncological therapy and at 12.1 years of age (IQR:9.1-12.6); only 45.5% were prepubertal. Growth velocity before GH replacement was -3.7 SDS (IQR:-4.4,-1.8) and after one year of treatment +1.0 SDS (IQR:-0.3,+2.3). Mean time of treatment was 2.4 years (IQR:1.0-4.5). Six achieved final height -2.2 SDS (IQR:-3.3,-1.6); -2.0 SDS (IQR:-2.7,-0.8) corrected for their target height.

Conclusions: 1. Radiotherapy is significantly linked to hormonal deficiencies. Long-term follow up is essential especially in the first years after radiotherapy.

2. Hypothyroidism is correlated to radiotherapy and the volume of the gland is reduced in almost half of these patients.

3. Not only radiotherapy may have a role in incomplete catch-up growth, but also other oncological therapies.