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. FINDINGS: 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. INTERPRETATION: 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 (

Radiotherapy for partially resected spinal ependymomas: a retrospective study of 60 cases.

Ependymomas (Es) and myxopapillary ependymomas (mpEs) are the most common primary tumours of the spinal cord. Recurrence-free survival depends on local control of the tumour. The value of additional radiotherapy (RT) is still a matter of debate. The aim of this retrospective study was to analyse radiotherapy, surgery and the preoperative state with regard to recurrence rate and long-term neurological outcome. Sixty patients with spinal Es (40) and spinal mpEs (20) were included. According to local policy, 14 patients who underwent total resection and 20 patients with incomplete resection were irradiated postoperatively. Total resection was achieved in 34 of the 60 tumours. Preoperative state and long-term outcome was assessed according to a previously published scale. When postoperative RT was applied after partial resection, only 3 of 11 Es and 1 of 9 mpEs recurred. All partially resected non-radiated Es (n=3) and 2 of the 3 partially resected non-radiated mpEs recurred. There was no recurrence after total resection. Only one of 6 patients with disseminated mpEs had clinical symptoms caused by the disseminated tumour. Long-term neurological outcome was related to preoperative conditions with no difference between partially and totally resected tumours. Our study shows that RT is only beneficial for partially resected Es and mpEs. Local recurrence-free survival of spinal Es and mpEs is obtained by total resection. Long-term neurological outcome is related to preoperative conditions. Seeding is seen in mpEs and does not cause clinical symptoms in most of the patients.

Chromosomal imbalances in primary oligodendroglial tumors and their recurrences: clues about malignant progression detected using comparative genomic hybridization.

OBJECT: Despite the rapid increase in knowledge concerning the genetic basis of malignant progression in astrocytic tumors, progression of oligodendroglial tumors (including both pure oligodendrogliomas and mixed oligoastrocytomas) is still poorly understood. The aim of the present study is the elucidation of chromosomal imbalances involved in the progression of oligodendroglial tumors toward malignancy. METHODS: Using comparative genomic hybridization (CGH) on snap-frozen tumor tissue, the tumor genomes of five primary oligodendroglial tumors and associated recurrent tumors were screened for chromosomal imbalances. This information was correlated with clinical data (including follow-up data) and histopathological malignancy grade. In all cases an increase in chromosomal imbalances was detected in the recurrent tumor, indicating genetic progression. In three of the five cases this correlated with malignant progression detected at the histopathological level. The results indicate that, similar to what occurs in astrocytic tumors, chromosomal imbalances harboring genes involved in the cell proliferation control mechanism at the G1-S border are involved in the progression of oligodendroglial tumors. Additionally, although gains of genetic material on chromosome 7 and losses on chromosome 10 are most frequently detected in the course of malignant progression of astrocytic tumors, either or both of these can also occur during malignant progression of typical oligodendroglial tumors that contain losses involving chromosome 1p and/or chromosome 19q. CONCLUSIONS: When performed on optimally preserved material from a small set of primary oligodendroglial tumors and associated recurrent tumors, CGH detects chromosomal aberrations that potentially play a mechanistic role in the malignant progression of these tumors.