Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance

Background Radiotherapy is a valuable treatment in the management algorithm of pituitary adenomas and craniopharyngiomas. However, the risk of second brain tumour following radiotherapy is a major concern. We assessed this risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls. Methods In this multicentre, retrospective cohort study, 4292 patients with pituitary adenoma or craniopharyngioma were identified from departmental registries at six adult endocrine centres (Birmingham, Oxford, Leeds, Leicester, and Bristol, UK and Ferrara, Italy). Patients with insufficient clinical data, known genetic predisposition to or history of brain tumour before study entry (n=532), and recipients of proton beam or stereotactic radiotherapy (n=81) were excluded. Data were analysed for 996 patients exposed to 2-dimensional radiotherapy, 3-dimensional conformal radiotherapy, or intensity-modulated radiotherapy, and compared with 2683 controls. Findings Over 45 246 patient-years, second brain tumours were reported in 61 patients (seven malignant [five radiotherapy, two controls], 54 benign [25 radiotherapy, 29 controls]). Radiotherapy exposure and older age at pituitary tumour detection were associated with increased risk of second brain tumour. Rate ratio for irradiated patients was 2.18 (95% CI 1.31-3.62, p<0.0001). Cumulative probability of second brain tumour was 4% for the irradiated and 2.1% for the controls at 20 years. Interpretation Irradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

Automated summary

Radiotherapy is a valuable treatment for pituitary adenomas and craniopharyngiomas, but the risk of developing a second brain tumor after radiotherapy is a major concern. This study assessed the risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls. The results showed that irradiated patients had an increased risk of second brain tumors, although the risk was lower than previously reported in studies using general population controls without imaging surveillance.