Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up.
BACKGROUND
Our previous study on cognitive functioning among 195 patients with low-grade glioma (LGG) a mean of 6 years after diagnosis suggested that the tumour itself, rather than the radiotherapy used to treat it, has the most deleterious effect on cognitive functioning; only high fraction dose radiotherapy (>2 Gy) resulted in significant added cognitive deterioration. The present study assesses the radiological and cognitive abnormalities in survivors of LGG at a mean of 12 years after first diagnosis.


METHODS
Patients who have had stable disease since the first assessment were invited for follow-up cognitive assessment (letter-digit substitution test, concept shifting test, Stroop colour-word test, visual verbal learning test, memory comparison test, and categoric word fluency). Compound scores in six cognitive domains (attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed) were calculated to detect differences between patients who had radiotherapy and patients who did not have radiotherapy. White-matter hyperintensities and global cortical atrophy were rated on MRI scans.


RESULTS
65 patients completed neuropsychological follow-up at a mean of 12 years (range 6-28 years). 32 (49%) patients had received radiotherapy (three had fraction doses >2 Gy). The patients who had radiotherapy had more deficits that affected attentional functioning at the second follow-up, regardless of fraction dose, than those who did not have radiotherapy (-1.6 [SD 2.4] vs -0.1 [1.3], p=0.003; mean difference 1.4, 95% CI 0.5-2.4). The patients who had radiotherapy also did worse in measures of executive functioning (-2.0 [3.7] vs -0.5 [1.2], p=0.03; mean difference 1.5, 0.2-2.9) and information processing speed (-2.0 [3.7] vs -0.6 [1.5], p=0.05; mean difference 0.8, 0.009-1.6]) between the two assessments. Furthermore, attentional functioning deteriorated significantly between the first and second assessments in patients who had radiotherapy (p=0.25). In total, 17 (53%) patients who had radiotherapy developed cognitive disabilities deficits in at least five of 18 neuropsychological test parameters compared with four (27%) patients who were radiotherapy naive. White-matter hyperintensities and global cortical atrophy were associated with worse cognitive functioning in several domains.


CONCLUSIONS
Long-term survivors of LGG who did not have radiotherapy had stable radiological and cognitive status. By contrast, patients with low-grade glioma who received radiotherapy showed a progressive decline in attentional functioning, even those who received fraction doses that are regarded as safe (</=2 Gy). These cognitive deficits are associated with radiological abnormalities. Our results suggest that the risk of long-term cognitive and radiological compromise that is associated with radiotherapy should be considered when treatment is planned.


BACKGROUND
Kaptein Fonds; Schering Plough.
Douw
Linda
L
Department of Neurology, VU University Medical Center, Amsterdam, Netherlands. l.douw@vumc.nl
Klein
Martin
M
Fagel
Selene Saa
SS
van den Heuvel
Josje
J
Taphoorn
Martin Jb
MJ
Aaronson
Neil K
NK
Postma
Tjeerd J
TJ
Vandertop
W Peter
WP
Mooij
Jacob J
JJ
Boerman
Rudolf H
RH
Beute
Guus N
GN
Sluimer
Jasper D
JD
Slotman
Ben J
BJ
Reijneveld
Jaap C
JC
Heimans
Jan J
JJ
D000328:Adult; D001284:Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001288:Attention / Q000502:physiology / Q000528:radiation effects; D001921:Brain / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D009483:Neuropsychological Tests; D011829:Radiation Dosage; D011878:Radiotherapy / Q000009:adverse effects* / Q000379:methods / Q000706:statistics & numerical data; D012189:Retrospective Studies; D018570:Risk Assessment; D013995:Time