Cognitive performance after postoperative pituitary radiotherapy: a dosimetric study of the hippocampus and the prefrontal cortex

Abstract

Objective: The hippocampus and prefrontal cortex (PFC) are important for memory and executive functioning and are known to be sensitive to radiotherapy (RT). Radiation dosimetry relates radiation exposure to specific brain areas. The effects of various pituitary RT techniques were studied by relating detailed dosimetry of the hippocampus and PFC to cognitive performance. Methods: In this cross-sectional design, 75 non-functioning pituitary macroadenoma (NFA) patients (61G10 years) participated and were divided into irradiated (RTC, nZ30) and non-irradiated (RTK, nZ45) groups. The RTC group (who all received 25 fractions of 1.8 Gy; total dose: 45 Gy) consisted of three RT technique groups: three-field technique, nZ10; four-field technique, nZ15; and five-field technique, nZ5. Memory and executive functioning were assessed by standardized neuropsychological tests. A reconstruction of the dose distributions for the three RT techniques was made. The RT doses on 30, 50, and 70% of the volume of the left and right hippocampus and PFC were calculated. Results: Cognitive test performance was not different between the four groups, despite differences in radiation doses applied to the hippocampi and PFC. Age at RT, time since RT, and the use of thyroid hormone varied significantly between the groups; however, they were not related to cognitive performance. Conclusion: This study showed that there were no significant differences on cognitive performance between the three-, four-, and five-field RT groups and the non-irradiated patient group. A doseresponse relationship could not be established, even with a radiation dose that was higher on most of the volume of the hippocampus and PFC in case of a four-field RT technique compared with the three-and five-field RT techniques.

Long-term Outcome After Fractionated Radiotherapy for Pituitary Adenoma

“…Few studies attempt to evaluate the cognitive effects of RT in this setting, but the best study on this subject showed no detrimental effect. 12 In our series, 30 patients (26%) with clinical tumor control developed a pituitary hormone deficiency requiring medical management. It is difficult to separate the influence of RT from surgery and the influence of the tumor, but it is reasonable to assume that RT compromises pituitary function.…”

Brain abnormalities on MRI in non-functioning pituitary adenoma patients treated with or without postoperative radiotherapy

“…WMLs and cerebral atrophy) are unknown and have not yet been investigated. Nevertheless, several studies reported on cognitive function [8][9][10]. Previously, we found no major influence of RT on cognition in NFA patients treated with RT compared to those treated with surgery-alone [8,9].…”

“…Previously, we found no major influence of RT on cognition in NFA patients treated with RT compared to those treated with surgery-alone [8,9]. Furthermore, a dose-response relationship, by relating detailed radiation dosimetry to the temporal lobes, hippocampi and the prefrontal cortex, with cognition could not be established [10]. In addition, we showed that postoperative RT was not associated with an increased incidence of second tumours, stroke or mortality compared to pituitary adenoma patients treated with surgery-alone [11,12].…”

Fractionated stereotactic radiotherapy for large and invasive non-functioning pituitary adenomas: long-term clinical outcomes and volumetric MRI assessment of tumor response

“…Gondi et al (47) demonstrated that biologically equivalent doses in 2-Gy fractions (EQD2) delivered to 40% of the bilateral hippocampi (D40%) O7.3 Gy (assuming an a/b ratio of 2 Gy) were associated with long-term impairment in list-learning delayed verbal recall in 18 patients receiving FSRT for benign brain tumors. In contrast, Brummelman et al (48) found no significant differences in cognitive performance among 30 patients who received radiotherapy for NFPA when mean doses up to 15.2 Gy were given to 50% of the hippocampal volume. Delivering a mean dose of 10 Gy to the bilateral hippocampi, we observed no clinically apparent neurocognitive deterioration over time; however, the lack of formal neurocognitive testing and the relatively short follow-up do not allow a definitive conclusion to be drawn.…”