Not just a bit of ‘chemobrain’: Barriers persist to treating cancer-related cognitive impairment

Cancer-related cognitive impairment (CRCI) is a common disorder that can significantly affect a patient's quality of life (Qol) and well-being. However, it is currently challenging to diagnose and difficult to treat, according to researchers at Yale University. They have developed a practical guide for oncologists to effectively screen and manage CRCI in the office setting.“The first step we can take is to start discussing this in the clinic and acknowledging that this is a real condition that patients with cancer are experiencing. Unfortunately, we still have a lot of gaps in knowledge regarding what are the best diagnostic tests for diagnosing CRCI and there is a lack of evidence-based methods of how to best manage CRCI,” said lead study author Dr. Yu Zhang, who is an assistant professor at Yale School of Medicine.Treatments linked to CRCI include chemotherapy, radiation therapy, surgery, hormonal therapy, targeted therapy with antibodies and small molecule inhibitors, along with immunotherapy. CRCI may affect 60%-to-75% or more of patients with cancer, according to the authors. Further, it is associated with decreased Qol and overall survival. “Cancer-related cognitive impairment is super important and has a significant negative impact on multiple aspects of a patient's life including the patient's ability to work. Many of our cancer patients are on disability,” Dr. Zhang said in an email to the Medical Post. “Tracking it and addressing it at oncology visits is so vital as it can make a huge difference to a patient's experience.”Measurable syndrome based on clinical findingsMultiple studies have shown that diverse cancer therapies directly contribute to glial and neuronal cell injury, leading to a cascade of events. Image studies of CRCI in patients have demonstrated structural and functional brain changes related to cancer treatments. “I think the landscape is changing, but not fast enough. Previously, the existence of cancer-related cognitive impairment had been controversial and was debated and often attributed to other comorbidities that patients with cancer have. Now, we have evidence that CRCI is a measurable syndrome,” said Dr. Zhang.CRCI is still not being addressed on a day-to-day basis in the doctor's office, according to Dr. Zhang. “From our collective experience, unfortunately, many of our patients with cancer still feel that their concerns about cognitive impairment are brushed aside or minimalized by providers. Part of the problem is still a lack of awareness, which we hope to improve upon by bringing this syndrome to light,” said Dr. Zhang. Neurocognitive testing for CRCI?Another barrier to effective care is that patients who experience CRCI often test normal or with only mild impairment on formal neurocognitive testing. Yet, they are experiencing significant impairment. “Patients often will feel that their experience is invalidated by the normal neurocognitive testing. They also become upset and frustrated at providers when they hear reassurance that their testing was normal because that is not their experience, which becomes dangerous since it can lead to a breakdown between the trust and relationship between patient and provider,” said Dr. Zhang.The current neurocognitive testing wasn't developed for the assessment of CRCI, but rather for more significant cognitive disorders such as dementia and traumatic brain injury (TBI). CRCI is also challenging to diagnose as it may overlap with other comorbidities that contribute to cognitive problems.Dr. Ashley E. Aaroe, an assistant professor at MD Anderson Cancer Center, Houston said it's crucial to be aware of CRCI as a distinct entity that has tremendous impacts on a patient's Qol. “Naturally as oncologists, we tend to focus on treating the cancer itself, and there can be an impetus to dismiss CRCI as just a bit of ‘chemobrain’, but these symptoms can range from mild to debilitating, and may not always be reversible. It also impacts caregivers when their loved ones are cognitively impaired.” Dismissing cognitive symptoms in patients with cancer as simply having stress or anxiety is inappropriate, especially when there is no evaluation of or treatment plan for stress or anxiety provided. “CRCI is particularly challenging as there can be different mechanisms driving it, and a different pattern of cognitive symptoms, from one patient to the next,” said Dr Aaroe.Dr. Zhang noted that the strategies in his article are not evidence-based "but are what we found to be helpful in managing our patients. These are some helpful pragmatic ways of managing symptoms of CRCI while we are waiting for all the additional research as needed to provide evidence guided treatments, which may take many years.” Not knowing the exact pathophysiology underlying the brain injury that leads to CRCI has hampered treatment development. Mechanisms may be due to direct neurotoxicity, inflammation, oxidative stress, altered cerebral blood supply, DNA damage, mitochondrial dysfunction and hypothalamic-pituitary-adrenal axis dysregulation, noted the authors. Efforts are underway to test repurposed and novel drugs and nonpharmacologic therapies for treating and preventing CRCI. Some of the drugs investigated for use in CRCI include lithium and fluoxetine, which can potentially counteract the negative effects of chemotherapy on neurogenesis and gliogenesis seen in CRCI;Meanwhile, phosphodiesterase inhibitors, antidementia drugs, such as cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, and neurostimulant medications used for attention-deficit/hyperactivity disorder are under investigation, too. And anti-inflammatory drugs such as nonsteroidal anti-inflammatory drugs and tumour necrosis factor-alpha inhibitors to counteract inflammation and breakdown of blood-brain barrier are under consideration.The authors propose a practical approach for oncologists to screen and discuss CRCI with patients routinely. If CRCI is suspected, they suggest not waiting for the results of formal neurocognitive testing and instead implementing low-risk, simple interventions that may improve the patient's experience with CRCI. Depending on the severity of CRCI symptoms, they recommend shared decision-making to consider dose reduction, changing therapies, treatment breaks, and discontinuation of therapy. The interventions shown to have the most robust data for treating CRCI thus far is physical exercise. “Some of these simple changes can make a difference to the patient experience with CRCI.The most important take-home message is that while we don’t have any proven evidence-based treatments for CRCI, addressing CRCI is so important since some of these practical approaches can make a significant difference for patients,” said Dr. Zhang.

Not just a bit of ‘chemobrain’: Barriers persist to treating cancer-related cognitive impairment

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