Correlating measured radiotherapy dose with patterns of endocrinopathy: The importance of minimising pituitary dose.

Abstract

Pituitary insufficiency is a common toxicity of cranial radiotherapy received in childhood for central nervous system, head and neck and haematological malignancies. There is a recognised deficiency pattern and correlation with prescribed radiotherapy dose, however correlation with measured pituitary dose (which can be minimised with modern radiotherapy techniques) has not previously been assessed. Retrospective analysis of measured pituitary dose and endocrine outcomes of patients receiving cranial, total body or head and neck photon beam radiotherapy at a tertiary centre July 2008 - October 2019. Complete data for 102 patients were available. Median (IQR) age at radiotherapy was 9.0(6.0;12.0) and follow-up 5.7 years (3.5-9.1). Most patients received focal brain radiotherapy (36.3%) or TBI (32.4%); most frequent diagnoses were ALL (25.5%) and medulloblastoma (17.6%). The majority developed pituitary insufficiency (64; 62.7%); 41% had one and 38% two hormone deficiencies. GHD (58; 56.9%), and TSHD (32; 31.4%) were most common. Patients who developed pituitary insufficiency received higher maximum pituitary dose - median (IQR)Gy, 44.0(20.4-54.0) vs 18.2(14.4-52.6); p = 0.008. Doses of 40-49Gy or >50Gy led to higher cumulative incident rate than <20Gy (HR4.07, p<0.001 and HR3.04, p<0.001 respectively). However even at lower dose bands, levels of pituitary insufficiency were significant with five-year cumulative incidence of GHD for <20Gy and TSHD for 20-29Gy reaching >30%. Our findings confirm correlation between measured pituitary dose and risk of insufficiency even at lower doses, despite modern radiotherapy techniques. These data highlight importance of minimising pituitary dose and early specialist Endocrine follow-up. This article is protected by copyright. All rights reserved.