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

Abstract

Background Pituitary insufficiency is a common toxicity of cranial radiotherapy received in childhood for central nervous system, head and neck, and hematological malignancies. There is a recognized deficiency pattern and correlation with prescribed radiotherapy dose; however, correlation with measured pituitary dose (which can be minimized with modern radiotherapy techniques) has not previously been assessed. Procedure Retrospective analysis was carried out of measured pituitary dose and endocrine outcomes of patients receiving cranial, total body, or head and neck photon beam radiotherapy at a tertiary center from July 2008 to October 2019. Results 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 total body irradiation (32.4%); most frequent diagnoses were acute lymphoblastic leukemia (25.5%) and medulloblastoma (17.6%). The majority developed pituitary insufficiency (64; 62.7%); 41% had one and 38% had two hormone deficiencies. Growth hormone deficiency (GHD) (58; 56.9%) and thyroid‐stimulating hormone deficiency (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 40‐49 Gy or >50 Gy led to a higher cumulative incident rate than <20 Gy (HR 4.07, P < 0.001 and HR 3.04, P < 0.001, respectively). However, even at lower dose bands, levels of pituitary insufficiency were significant with a five‐year cumulative incidence of GHD for <20 Gy and TSHD for 20‐29 Gy reaching >30%. Conclusions Our findings confirm a correlation between measured pituitary dose and risk of insufficiency even at lower doses, despite modern radiotherapy techniques. These data highlight the importance of minimizing pituitary dose and early specialist endocrine follow‐up.

Time to first remission and survival in patients with acromegaly: Evidence from the UK Acromegaly Register Study (UKAR)

“…26 Pituitary radiotherapy has also been reported with stroke 27 and increased risk of intracranial neoplasm 28 and other endocrinopathies. 29 The excess mortality with pituitary radiotherapy should be interpreted cautiously in these observational studies. It is possible that those who receive radiotherapy may have advanced diseases and other comorbidities associated with an increased risk of mortality independent of radiotherapy.…”