Radiotherapy of pituitary/sellar lesions tied to increased risk of brain tumors

By Will Boggs MD

NEW YORK (Reuters Health) – Radiotherapy of pituitary/sellar lesions are associated with an increased risk of de novo brain tumors, especially when treatment takes place at younger ages.

"The key finding of this study is the marked relation between a younger age at radiotherapy (less than 30 years) and the risk for developing a brain tumor,” Dr. Pia Burman from Skanes University Hospital, University of Lund, in Malmo, Sweden, told Reuters Health by email.

“What was surprising was that patients who had been treated with radiotherapy during the last 10 years seemed to have a similar risk as patients treated a longer time ago,” she said. “This was unexpected, as it has been assumed that modern treatment methods are safer, because the brain tissue that surrounds the pituitary tumor is exposed to lower doses of radiation with such techniques.”

Identifying risk factors for secondary brain tumors in individuals with pituitary/sellar tumors has been challenging, because the incidence of de novo tumors is low and they mostly occur decades after treatment.

Dr. Burman's team investigated the incidence of de novo brain tumors in more than 8,900 patients with pituitary tumors in the Pfizer International Metabolic database treated with (n=3,236) and without (n=4,927) radiotherapy between 1994 and 2012.

Overall, there were 17 malignant brain tumors reported in the database (versus 5.01 expected in the general population). The excess incidence was statistically significant in the radiotherapy group (13 observed versus 2.16 expected cases), but not in the no-radiotherapy group (four cases versus 2.84 expected).

Brain tumors occurred at an earlier age in the radiotherapy group than in the no-radiotherapy group (median, 57.2 vs. 66.9 years), the researchers report in The Journal of Clinical Endocrinology & Metabolism, online January 13.

Meningiomas also occurred with greater frequency (0.98 cases vs. 0.18 cases/1,000 patient-years) and at a younger age (median, 51.6 vs. 54 years) in the radiotherapy group, and more commonly in women than in men.

Younger age at exposure to radiotherapy was associated with a significantly greater risk of subsequent brain tumor, with each year linked with an 8.2% increase in the risk of malignant brain tumor and a 4.6% increase in the risk of meningioma.

The incidence of brain tumors did not differ with radiotherapy type (external and stereotactic), although there was only one brain tumor among patients treated with a combination of gamma knife and radioactive implants.


Growth hormone doses did not differ significantly between patients who did and did not develop secondary brain tumors.

Dr. Burman noted two clinical implications of these findings: “Firstly, physicians who treat patients with pituitary tumors must be aware of this risk and carefully select patients that will require radiotherapy. In some cases, medications could be an alternative. Secondly, patients who have been treated with radiotherapy should be under medical supervision life-long.”

“Physicians are used to weighing benefits and risks with all treatments and selecting the best alternative for the individual patient,” she said. “Our report will hopefully remind colleagues that radiotherapy can cause brain tumors, and to carefully consider if there is an alternative.”

Dr. Burman added, “The study underlines the need for establishing international registries for patients treated with radiotherapy to accumulate and analyze treatment outcomes, so that we can learn more about side effects and how to minimize these in the future.”

Two of the five authors are employees of Pfizer Inc., and the other three authors have various relationships with the company.


J Clin Endocrinol Metab 2017.

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