The Incidence of Stroke in Pituitary Adenoma Patients Treated with Postoperative Radiotherapy vs. Surgery Alone

Abstract

To assess and compare the incidence of stroke in pituitary adenoma patients treated with postoperative radiotherapy (PORT) or surgery alone. PORT results in excellent local tumor control and improvement of excessive hormonal secretion where (repeated) surgery was unsuccessful. Nevertheless, concerns related to possible long-term side effects are often quoted to delay or reject this treatment. In previous studies, the incidence of stroke in PORT patients was compared with a normal reference population. However, such comparisons are biased by imbalances in the presence of other stroke risk factors that are related to pituitary adenoma disease and surgery. A cohort of 462 pituitary adenoma patients (non-functioning adenoma n = 256, growth-hormone secreting n = 139 and adrenocorticotropic-hormone secreting adenoma n = 67) treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. PORT was administered in 236 patients. Most patients received a total radiation dose of 45 Gy in 25 fractions of 1.8 Gy in 5 weeks. Stroke was classified into hemorrhagic and ischemic stroke. The TOAST and Oxfordshire classification methods were used to compare differences of causative mechanism and anatomic distribution of ischemic infarcts. Age at pituitary adenoma diagnosis was transformed to median life expectancy (MLE) using the annual life tables of the Central Office of Statistics according to gender. MLE was used in order to account for differences in life expectancy due to differences in follow-up, gender and birth cohort effects. The data were analyzed by log-rank test for investigating the risk of stroke in patients treated with PORT vs. surgery alone. Stroke risk factors were analyzed in univariate-and multivariate analysis by log-rank test. The median follow-up time was 14 years (range, 1 – 49 years) in patients treated with PORT and 6 years (range, 1 – 34 years) in patients treated with surgery alone. Thirteen PORT patients (5.5%) were diagnosed with a stroke (ischemic n = 10) compared to 12 patients (5.3%; ischemic n = 10) treated with surgery alone (univariate RR, 0.62; 95% CI, 0.28 – 1.35; p = 0.23). Stroke risk factors were coronary-and peripheral artery disease (univariate and multivariate RR, 10.4; 95% CI, 4.7 – 22.8; p < 0.001) and hypertension (univariate RR, 3.9; 95% CI, 1.6 – 9.8; p = 0.002). No difference was seen in TOAST and Oxfordshire classification of ischemic stroke between the two treatment groups. Postoperative radiotherapy in pituitary adenoma patients was not associated with an increased incidence or causative mechanism of stroke compared to patients treated with surgery alone. Coronary and peripheral artery disease on the other hand was associated with higher risk of stroke.