Systemic chemotherapy decreases brain glucose metabolism

Abstract

ObjectiveCancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-based chemotherapy on glucose metabolism in the brain of cancer patients.MethodsUsing sequential FDG-PET/CT imaging prior to and after administration of chemotherapy, we retrospectively characterized the effects of intravenously administered chemotherapy on brain glucose metabolism in a total of 24 brain regions in a homogenous cohort of 10 patients with newly diagnosed non-small-cell lung cancer.ResultsSignificant alterations of glucose metabolism were found in response to chemotherapy in all gray matter structures, including cortical structures, deep nuclei, hippocampi, and cerebellum. Metabolic changes were also notable in frontotemporal white matter (WM) network systems, including the corpus callosum, subcortical, and periventricular WM tracts.InterpretationOur data demonstrate a decrease in glucose metabolism in both gray and white matter structures associated with chemotherapy. Among the affected regions are those relevant to the maintenance of brain plasticity and global neurologic function. This study potentially offers novel insights into the spatial and temporal effects of systemic chemotherapy on brain metabolism in cancer patients.

Global and regional brain glucose metabolism decline after systemic chemotherapy

“…1) [3]. In line with these findings in a recent paper by Sorokin et al [4], we reported a significant decline in global brain function as measured by the degree of FDG uptake following chemotherapy.…”

“…Regional semiquantitative indices showed decreased glucose metabolic function in almost all brain areas (SUV max declines vary from 9 to 24 % and SUV mean declines vary from 6 to 26 % in different areas). Comparing baseline to posttreatment images, they found a mean overall decrease of 22 % (SUV mean ) in glucose metabolism in the gray matter and also significant reduction of metabolism in the white matter and germinal zones [3].…”

“…ROIs were placed around target brain area of coregistered MRI/PET images using 3D Slicer. Investigators measured SUV max and SUV mean of cerebellar cortex (1, 2), hippocampus and medial temporal lobe (3,4), olfactory gyrus and orbitofrontal cortex (5, 6), subventricular (anterior and posterior zones) (7, 8), caudate nucleus (9, 10), thalamus (11, 12), periventricular white matter (13, 14), frontal cortex (16, 17), and subcortical white matter (18,19) in each hemisphere and also corpus callosum (splenium) (15). Parietal cortex, corpus callosum (genu), posterior cingulate, and cerebellar white matter were measured with the same methodology but are not shown in this image.…”

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

“…Horky et al found decreased glucose metabolism in both gray and white matter structures associated with chemotherapy for SCLC, and the frontal cortex was more affected (11). In breast cancer patients, Silverman et al used a combination of 15 O-water and 18 F-FDG PET to reveal changes in the activity of the frontal cortex 5-10 y after completion of chemotherapy (12).…”

Cytokine‐mediated blood brain barrier disruption as a conduit for cancer/chemotherapy‐associated neurotoxicity and cognitive dysfunction

“…Neurotoxicity and its associated cognitive manifestations are poorly characterized, dose‐limiting side effects of chemotherapy treatment . Clinically, the impact of chemotherapy on cognition has been most extensively studied in breast cancer patients, however it is becoming increasingly recognized that cognitive symptoms affect a large portion of patients with varying malignancies and treatments . Despite its prevalence, cognitive dysfunction, often referred to as chemobrain, remains an under‐reported and ill‐defined complication of anti‐cancer treatment.…”