We found no negative outcomes and even some limited positive effects in the perception of mental and physical health after RT in a large cohort of patients with NFA.
Health-related quality of life was measured in this study with the RAND 36 questionnaire, which has been shown to be a reliable and valid instrument with good internal consistency. Results were compared with age-adjusted normative data for the Dutch population19. We found that social functioning, vitality, and general health perception (three domains of RAND 36) were significantly lower in the group that did not receive RT when compared with the reference population. In contrast, in patients who underwent RT only general health perception was worse than in the age-matched control population, whereas physical functioning, pain (RAND 36), and anxiety (HADS) were not adversely affected, and their score was even slightly better. The group of patients that underwent RT reported significantly higher levels of vitality and less depressive symptoms and physical and mental fatigue, with effect sizes ranging from 0.47 to 0.56, indicating a clinically relevant medium size effect. This suggests that RT may be bene-ficial to self-perceived health. Our results are in contrast to those found by Page et al.27. They used the SF36 questionnaire, identical to the RAND 36, and reported that patients treated with RT for nonfunctioning pituitary tumors were more depressed and anxious than those who underwent mastoid surgery. However, this study group of patients with NFA was smaller than ours, and only 18 patients had received RT after surgery. Further, it is not clear from their report whether they properly corrected for age in each individual patient. Noad et al.28 recently reported data on the effects of RT on cognitive function and quality of life in patients with pituitary disease. Of the 71 patients who were assessed, 33 had nonfunctioning adenomas, 15 of whom underwent RT. It was concluded from data of their entire group that patients who had received RT had no significant change in the quality of life as measured by the physical and mental health composite of the SF36. Recently, Dekkers et al.29 reported on the diminished quality of life in patients with nonfunctioning pituitary macroadenomas. Although RT was very infrequently applied in this study, a small subanalysis by means of linear regression revealed that RT was not an independent predictor for reduced quality of life. Thus, results from smaller studies on the effects of RT on quality of life are in accordance with our findings.
We extensively looked for a selection bias but did not find one. Age at surgery and duration of follow-up are potential candidates. However, both in univariate and multivariate analysis, RT remained a strong and independent predictor for quality of life, and neither age at surgery nor duration of follow-up were of any importance. Socioeconomic status and comorbidity also did not differ between groups. Further, RT was given to patients with tumors that were larger or growing more aggressively. The RT group even needed more hormone substitution therapy and more often underwent a craniotomy. Therefore, we believe that a selection bias toward a better quality of life for patients who underwent RT is unlikely.
We found higher scores for depression in the group that did not receive RT. Scores for anxiety were similar between both groups. Noad et al.28 also used the HADS and found no treatment effect for RT. However, as mentioned earlier, their group size of NFA patients was very small. A report from Peace et al.16 is in accordance with our findings. They used the Beck Depression Inventory and the State-Trait Anxiety Inventory to assess self-reported mood and found that RT exerted a mild protective effect on depression.
Several studies suggest that patients with pituitary tumors may continue to suffer from cognitive impairment even after treatment of their disease11,15,17,30. McCord et al.14 suggested that RT for pituitary tumors may be associated with cognitive impairment. However, their assessment contained no formal, objective measures of cognitive impairment and relied entirely on self-report. Grattan-Smith et al.30 performed neuro-psychological testing in a group of patients with pituitary adenoma and reported memory and executive function impairments in these patients when compared with a control group. In this study, no specific cause of the neuropsychological impairment was found, and patients treated with RT performed equally when compared with those who did not receive RT. Peace et al.15 found deficits primarily on test of executive function, but they found them in response to surgery and not RT. Anterograde memory deficits were found by Guinan et al.11 in patients with pituitary tumors. However, there was no negative treatment effect of pituitary RT. In accordance with the lack of evidence of reduced cognitive performance associated with RT, we also found no indications of cognitive impairment as a consequence of RT.
In conclusion, no negative outcomes and even some limited positive effects in the perception of mental and physical health after RT were found in a large cohort of patients with NFA. Our results are reassuring and raise no concern that RT applied after surgery in the treatment of NFA leads to reduced quality of life or impaired cognition.