Brain damage following prophylactic cranial irradiation in lung cancer survivors

Abstract

Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population.

Longitudinal Brain Changes Associated with Prophylactic Cranial Irradiation in Lung Cancer

“…46 This explanation is also supported by the fact that similar WM changes are seen in long-term SCLC survivors. 32 Interestingly, these chemotherapy-related changes did not appear after platinum-based chemotherapy in the NSCLC group. We speculate that this distinct response to chemotherapy might be related to an increased susceptibility of SCLC to platinum-based toxicity.…”

“…On the basis of our results, patients with SCLC should be informed about the survival benefits of PCI and about the potential minor, but negative, effects of this therapy on cognitive functioning, with emphasis on their limited impact on quality of life. However, because of the permanent long-term cognitive and structural brain effects observed in our previous study of SCLC survivors treated with PCI, 32 we think that it is crucial to better identify upfront those patients in whom brain metastases will develop and those patients in whom they will not, so that we can safely avoid PCI in specific subgroups of patients and thereby elude the brain-toxic effects.…”

“…36 Recent neuroimaging studies using DTI both in patients with brain tumors and in the SCLC population showed decreased FA in the CC after radiation. 32,37 In fact, the CC has recently been described as one of the most radiation-sensitive structures of the brain, 38 and the amount of microstructural damage to the WM fibers of the CC has been directly related to the cognitive deterioration found in long-term SCLC survivors. 32 Hence, the WM changes in the CC exhibited in the present study provide evidence that the damage to WM microstructure seen in long-term SCLC survivors occurs as early as 3 months after radiation therapy, and that these WM changes also correlated with cognitive deficits in processing speed.…”

“…The methodology used was similar to that used in our previous works. 29,[31][32][33] Morphometric analysis was carried out using the longitudinal processing stream in the Voxel-Based Morphometry 8 (VBM8) toolbox (http://dbm. neuro.uni-jena.de/vbm/) under the Statistical Parametric Mapping 8 (SPM8) software package (Version 8, Wellcome Department of Imaging Neuroscience, London, UK) and MATLAB (Version 7, Mathworks, Inc., Natick, MA).…”

Regional Changes in Brain 18F-FDG Uptake After Prophylactic Cranial Irradiation and Chemotherapy in Small Cell Lung Cancer May Reflect Functional Changes

“…Additionally, cognitive impairment has been observed after chemotherapy, especially after combined whole-brain radiation therapy (8,9). An MRI study on patients with SCLC who received chemotherapy and PCI showed an association between long-term cognitive effects and structural brain changes (10).…”