- Explain to interested patients that radiotherapy has been associated with long-term cognitive decline in patients with low-grade gliomas.
- Note that the study was not randomized and that the authors and commentators cautioned that the results should not be considered definitive.
- Also point out that the treatment period started in the late 1970s and some of the techniques used are outdated, and patients were treated with what are now considered to be excessive volumes and doses of radiation.
Even doses of radiotherapy generally regarded in the past
as safe may contribute to cognitive decline in patients with low-grade gliomas, the most common type of brain cancer, researchers found.
More than half of low-grade glioma patients (53%) had cognitive deficits 12 years after radiotherapy, compared with only 27% of patients who had not received radiation, according to the study published online Aug. 9 in Lancet Neurology.
"These cognitive deficits are associated with radiological abnormalities," Linda Douw, of the VU University Medical Center in Amsterdam and colleagues wrote. "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."
The researchers had previously conducted a study in 195 patients that found that, six years after treatment, radiotherapy was associated with cognitive disability only in the low-grade glioma patients who had had high-dose radiotherapy.
However, the effects in long-term survivors remained unknown. So the researchers performed a 12-year follow-up cognitive assessments on 65 of the participants of their earlier study.
About half of the patients had received radiotherapy and three had received high-dose radiation, which was defined as a fractional dose of greater than 2 gray units (Gy).
The researchers tested patients for attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed. They also used magnetic resonance imaging to look for brain abnormalities, specifically white matter hyperintensities and cortex atrophy, which are associated with poor cognitive performance.
The mean total radiation dose among the patients was 56.6 Gy in a mean of 30.6 fractions of 1.6 to 2.5 Gy per fraction, and the mean absorbed dose per fraction was 1.9 Gy.
The study found that patients who had radiotherapy did worse than those who did not on tests of three of the six cognitive domains:
- Executive functioning (mean score –2.0 compared with –0.5, P=0.03; mean difference 1.5, 95% CI 0.2 to 2.9)
- Information processing speed (–2.0 [3.7] versus –0.6 [1.5], P=0.05; mean difference 0.8, 0.009 to 1.6)
- Attention (–1.6 [2.4] compared with –0.1 [1.3], P=0.003; mean difference 1.4, 0.5 to 2.4)
Attentional functioning had also deteriorated significantly between the previous study and current study in patients who had had radiation (P=0.25).
Radiotherapy patients had slightly more white matter hyperintensities at the 12-year assessment than at the six-year assessment, regardless of whether the three patients who had received high doses were included. This increase in radiological abnormalities was associated with the decline in cognitive performance.
"By contrast with the results of our earlier study, the current results indicate that radiotherapy is associated with long-term cognitive deterioration, regardless of fraction dose," the authors wrote.
They suggested that the risk of long-term cognitive and radiological compromise associated with radiotherapy should be considered when treatment is planned.
The authors noted that theirs was not a randomized study and that further prospective studies are needed to firmly establish whether the cognitive deterioration was the direct result of radiotherapy.
In an accompanying editorial, Paul D. Brown, MD, and Jane H. Cerhan, PhD, LP, of the Mayo Clinic, also urged caution in interpreting the results.
They noted that the radiotherapy received by participants in the study is now considered outdated and that the doses are excessive by current standards.
They also pointed out that the lack of randomization induced bias and "more of the patients who had aggressive tumors were treated with radiotherapy compared with those who were treated with surgery."
They also noted that large prospective studies are in the works that might better answer the questions posed by this study.
"Until the results of these trials are available, any questions about the effect of radiotherapy on cognition (i.e., is it the same, better, or worse after treatment?) in patients with low-grade glioma will remain unanswered," Brown and Cerhan said.
The study was funded by Kaptein Fonds and Schering Plough.
The authors reported that they had no financial conflicts of interest.
The editorialists also said that they had no conflicts of interest.