Let me first walk you through really briefly on some of what may be considered as key drivers of CRCI. First of all, for a small proportion of patients, there is a genuine genetic predisposition. So, some individuals are more prone to developing CRCI because of their genes. Second, it’s cancer itself and the stress related to cancer. We know that chronic inflammation and mitochondrial dysfunction are considered hallmarks of cancer...
Let me first walk you through really briefly on some of what may be considered as key drivers of CRCI. First of all, for a small proportion of patients, there is a genuine genetic predisposition. So, some individuals are more prone to developing CRCI because of their genes. Second, it’s cancer itself and the stress related to cancer. We know that chronic inflammation and mitochondrial dysfunction are considered hallmarks of cancer. And these two processes are the key, let’s say, drivers of CRCI at the biologic level. Having said that, we know that treatment itself, like surgery, radiotherapy, immunotherapy, or even chemotherapy, can induce CRCI. We know that chemotherapy has direct neurotoxic effects on the neurons on the prefrontal cortex, which is, we know, essential in decision-making and executive functioning. Beyond that, the drugs we use to manage symptoms like anti-nausea or opioids, this can contribute to CRCI. And we also have aging, we have insomnia, we have anxiety disorders, we have depression, we have, let’s say, a lack of exercise. All of these factors contribute to CRCI. But in the context of our study, we tried to minimize, you know, confounding. And we did that by using certain exclusion criteria and certain groups, study groups, so control groups. So patients with pre-existing dementia, anxiety disorders, anemia were excluded from the study. Patients aged 65 or above underwent CGA, comprehensive geriatric assessment. So only older, fit older patients were included in this study. Moreover, we used control groups with patients not receiving chemotherapy, cancer patients not receiving chemotherapy, and also age-matched healthy individuals. So in this setting, in the setting of our study, chemotherapy exposure might be the key driver of CRCI. As far as high-risk patients, if we could identify them, I would, of course, include older patients, patients with lower cognitive reserves, patients with pre-existing dementia, with pre-existing anxiety disorders, patients who develop grade 3 or greater anemia during the course of treatment. All of these patients are at greater risk of developing CRCI. Having said that, our study shows that CRCI is not confined only to these patient groups. So cognitive assessment tools should be implemented broadly.
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