SAT-457 Hypothalamic-Pituitary Disorders after Conformal Radiation Therapy for Childhood and Young Adult Low-Grade Glioma or Ependymoma

Purpose To describe the prevalence, risk factors, latency time and adverse health outcomes of hypothalamic-pituitary (HP) disorders among children and young adults who received focal conformal radiation therapy (RT) for brain tumors. Methods Cohort study of 355 patients, aged ≤ 25 years at diagnosis, treated with high-dose (54-59.4 Gy) RT using photons between 1996 and 2016 for low-grade glioma or ependymoma. Patients (median age, 6.4 years at RT exposure) received systematic endocrine follow-up for a median of 10.1 years (range 0.1-19.6). Associations between HP disorders and risk factors, as well as adverse health outcomes were determined using multivariable regression analysis. Results The prevalence was 37.2% (95% CI 32.1%-42.4%) for growth hormone (GH) deficiency (GHD), 17.7% (95% CI 13.2%-23.0%) for luteinizing hormone/follicle-stimulating hormone deficiency (LH/FSHD), 14.9% (95% CI 11.2%-19.2%) for thyroid-stimulating hormone deficiency (TSHD), 10.3% (95% CI 7.3%-14.1%) for adrenocorticotropic hormone deficiency (ACTHD), and 12.6% (95% CI 8.8%-17.2%) for central precocious puberty (CPP). Tumor involvement in the HP region and shorter follow-up time were significantly associated with GHD, LH/FSHD, TSHD and ACTHD. CPP primarily occurred in patients with HP tumor involvement. GHD, treated in 84 (63.6%) patients, was associated with a higher odds of short stature (OR 2.77; 95% CI 1.34-5.70) and low bone mineral density (BMD) (OR 3.47; 95% CI 1.16-10.40), while TSHD demonstrated an independent association with dyslipidemia (OR 5.54; 95% CI 1.66-18.52). TSHD (P = 0.02), ACTHD (P = 0.0002), LH/FSHD (P = 0.01) and CPP (P = 0.002) were associated with lower intelligence quotient scores; GHD (P = 0.02), ACTHD (P = 0.01), LH/FSHD (P = 0.01) and CPP (P = 0.04) with worse attention scores; GHD (P = 0.0003), ACTHD (P = 0.02) and LH/FSHD (P = 0.02) with lower memory scores. GH treatment was associated with a higher risk for secondary tumors (OR 2.22; 95% CI 1.05-4.67), but did not increase the risk for tumor recurrence or mortality. Conclusion HP disorders occur frequently during follow-up in patients exposed to high-dose RT and may have a significant impact on physical and neurocognitive well-being. Whether further optimization of endocrine management could allow better outcomes, requires additional investigation.