Cognitive performance and the hippocampus in patients with postoperative pituitary radiotherapy: A detailed dosimetric study

Context and objective: We showed previously that postoperative radiotherapy (RT) for nonfunctioning pituitary macroadenoma (NFA) is unlikely to have a major effect on cognition. However, a small effect could not be excluded. Radiation dosimetry offers the possibility to relate radiation exposure of brain areas of interest to cognitive performance, thereby detecting smaller effects potentially induced by RT. The hippocampus has a crucial role in memory and information processing and is known to be sensitive to radiotherapy. Here, we studied the effects of various pituitary RT techniques by relating detailed dosimetry of the hippocampus to cognitive performance.

Design: Aspects of verbal memory and problem solving were assessed by using standardized neuropsychological test procedures that have been shown to be sensitive to the effects of brain surgery and radiation. We compared dosimetric data of 3 different RT techniques (3-fields, 4-fields and 5-fields technique) and a non-irradiated patient group. A reconstruction was made of the different radiation techniques used and the mean left and right hippocampi doses were calculated.

Patients: 75 patients (61±10 year) underwent transsphenoidal surgery as primary treatment. Irradiated patients (n=30) were divided into 3 groups; 3-fields technique n=10; 4-fields technique n=15; 5-fields technique n=5. All patients received 45 gray (Gy), given in 25 fractions of 1.8 Gy. Cognitive performance data from the different irradiated patients groups and the non-irradiated patient group (n=45) were compared.

Results: Mean (SD) cumulative dose for the left hippocampus irradiated with the 3-, 4-, and 5-fields techniques were respectively 13.82 (15.11), 18.46 (10.09), and 12.48 (12.41) Gy. Mean cumulative dose for the right hippocampus with the 3-, 4-, and 5-fields techniques were 15.55 (16.61), 22.27 (12.05), and 13.82 (14.48) Gy. No significant differences were found for the different RT techniques and the non-irradiated patients for cognitive tests, particularly memory and information processing which has its anatomical substrate in the hippocampus (Verbal memory, P=0.337). No radiation dose- cognitive response relationship was detected.

Conclusion: Postopertive pituitary RT has no effect on cognitive performance involving the hippocampus in NFA patients. No dose response relationship could be established, confirming that these RT techniques and fractionated radiation dose regimens are safe with regard to cognition.