Second brain tumours after pituitary irradiation: lower risk than once thought

Abstract

Since its first proposal in the treatment of pituitary tumours more than a century ago, indications for cranial radiotherapy have notably evolved. In rare pituitary carcinomas, indication of radiotherapy remains undisputable after surgical treatment in case of remnant tumour or recurrence. Until the availability of effective medical treatment, radiotherapy was the second-line treatment for many secreting pituitary adenomas after surgery. Thanks to the use of cabergoline, which controls prolactin secretion and is able to shrink even giant macroprolactinomas, nowadays, radiotherapy is hardly ever proposed. 1 Chanson P Maiter D Prolactinoma. in: Melmed S The pituitary. 5th ed. Academic Press, London2022: 495-543 Google Scholar In patients with acromegaly, with the availability of somatostatin receptor ligands and growth hormone receptor antagonists, the indication of radiotherapy in patients in whom surgery was unable to achieve cure of the disease, has also clearly decreased over time. 2 Maione L Chanson P National acromegaly registries. Best Pract Res Clin Endocrinol Metab. 2019; 33101264 Crossref PubMed Scopus (37) Google Scholar In patients with non-functioning pituitary adenomas, indications for radiotherapy have also evolved—while it was routinely administered after surgery some decades ago, it is now reserved to patients with a postoperative remnant, with its timing, immediately after, or only in case of remnant regrowth, being a matter of debate. 3 Chanson P Dormoy A Dekkers OM Use of radiotherapy after pituitary surgery for non-functioning pituitary adenomas. Eur J Endocrinol. 2019; 181: 1-13 Crossref PubMed Scopus (15) Google Scholar Indeed, even if the efficacy of radiotherapy is remarkable for achieving local control of pituitary tumours (roughly 90% of cases), 4 Loeffler JS Shih HA Radiation therapy in the management of pituitary adenomas. J Clin Endocrinol Metab. 2011; 96: 1992-2003 Crossref PubMed Scopus (151) Google Scholar the issue of side effects and particularly late toxicities long after radiation exposure has somewhat dampened the enthusiasm for this technique. The main adverse effect of radiotherapy is the occurrence of anterior pituitary hormone deficiency in about 30% of individuals at 5 years and 50% at 10 years after fractionated radiotherapy, respectively. 3 Chanson P Dormoy A Dekkers OM Use of radiotherapy after pituitary surgery for non-functioning pituitary adenomas. Eur J Endocrinol. 2019; 181: 1-13 Crossref PubMed Scopus (15) Google Scholar , 5 Fernandez A Brada M Zabuliene L Karavitaki N Wass JA Radiation-induced hypopituitarism. Endocr Relat Cancer. 2009; 16: 733-772 Crossref PubMed Scopus (68) Google Scholar Whether or not radiotherapy technical refinement (eg, use of fractionated stereotactic radiotherapy or radiosurgery) will decrease this rate remains to be determined. Optic neuropathy, another side effect of radiotherapy, is nowadays quite rare, thanks to the limited radiation dose administered to the optic chiasm, as a result of improvements in radiotherapy techniques. But one of the main concerns with radiotherapy was the potential occurrence of secondary brain tumours, 6 Yamanaka R Abe E Sato T Hayano A Takashima Y Secondary intracranial tumors following radiotherapy for pituitary adenomas: a systematic review. Cancers (Basel). 2017; 9: 103 Crossref Scopus (27) Google Scholar some being devastating (eg, glioblastomas) when radiotherapy had been used in these patients for treating a benign condition. However, in clinical practice, this adverse effect seemed to be much more exceptional than previously reported. Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillanceIrradiated 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. Full-Text PDF Open Access