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Nov 2, 2018

Mitigating Cognitive Effects of Chemotherapy and Radiation with Dr. Sara Hardy

Welcome to the ASCO Daily News Podcast. I'm Lauren Davis and joining me today is Dr. Sara Hardy, a resident in the Department of Radiation Oncology Medical Center and a neurologist in the University of Rochester. Dr. Hardy, welcome to the podcast.

 Thank you for inviting me. I'm happy to be here.

Today we're talking about cognitive dysfunction as it can happen in patients who receive both chemotherapy and radiation. How did you become interested in this side effect?

As treatments have gotten better over the years, patients with cancer are just living longer and longer. And so cancer survivors are living with a lot of the symptoms from treatments that we're giving them. As a neurologist, I think I am especially sensitive to changes in cognition and other side effects that relate to cognition and neurology.

I feel like cognition has a huge impact on quality of life. It impacts a survivor's ability to go back to work, survivor's ability to really go back to the life that they were living before. And I think it's an area where we can really have a huge impact.

What areas of thinking and cognition are affected, and why?
So it's a little different between chemotherapy-induced cognitive change and radiation-induced cognitive change. So for chemotherapy-induced cognitive change, there are deficits in memory, executive function, attention, and processing speed. These are higher level functions. They require a lot of different areas to work together. So it makes sense that these areas are affected. And then also, studies have shown that there is gray matter loss in the frontal and temporal lobes, which make sense-- this includes the hippocampus-- with chemotherapy.

And there are changes in white matter integrity, and changes in white matter can affect processing speed. So a lot of it really makes a lot of sense when you look at the areas that are affected. Additionally, they've shown that chemotherapy can inhibit neurogenesis within the hippocampus. And so that may also have something to do with why a memory is affected.

For radiation treatments, the most common thing that we see is probably verbal memory, so kind of that word-finding difficulty. And that's what was originally shown when they were looking at radiation for the whole brain. Additionally, they've shown that attention, executive function, and processing speed can also be affected.

The effect on verbal memory is currently the target of a clinical trial. So they did a phase two clinical trial looking at changes in the radiation plan to avoid radiation dose to the hippocampus on both sides. And because that was a positive study, they've moved on to a phase three trial that we are now waiting on.

How do other issues, including stress and sleeplessness from the worry of diagnosis and treatment, contribute to these issues?
Stress can definitely make you more vulnerable, I'd say, to cognitive change in the setting of cancer and cancer treatment and really impact acutely your ability to perform a task. What I would say is that especially I think right after diagnosis, it has a lot to do with some of the changes that people complain of with forgetfulness and inattention. And then later on, I suspect that it has less to do with what we're seeing, but it definitely has an impact.
That makes sense. Do you know any discrepancies between patient-reported outcomes of cognitive dysfunction and compared to objective results of testing?

Yeah. So patient-reported outcomes are not always associated with our objective findings on neurocognitive testing. And these outcomes, the patient-reported outcomes, are sometimes more correlated with distress. And it's possible that our neurocognitive test is not picking up some of these subtle changes that people are seeing in their daily lives. It's also possible that people are compensating. One of my theories is that the people that are prone to notice these things, kind of young, healthy people, are able to compensate. And so it's hard for us to pick it up on neurocognitive testing, even though they know that they are trying harder.
And as all people age, even those without cancer, we notice that we have that tip-of-the-tongue phenomenon, the characteristics of memory loss that happen more often than not. We know we want to say, but we can't quite convey the message. How do you differentiate between the natural progression of aging with other factors such as menopause or the onset of dementia with the cognitive effects of chemotherapy and/or radiation?

Well, the good thing about the cognitive effects from chemotherapy and radiation is that they're often subtle. So they're not as severe as a frank dementia. To be diagnosed with dementia, it has to impact your ability to care for yourself, your ability to have personal hygiene or cook food, the activities of daily living. So thankfully, these are usually more subtle changes.

But I think that there are a lot of things that contribute to these cognitive changes. Menopause is a time of life when people tend to complain more of forgetfulness, and there's some evidence that hormonal therapy in breast cancer patients can also cause some cognitive changes. Natural aging causes some subtle cognitive changes and some atrophy that we see on imaging.

So really, there are a lot of factors that contribute to this very complex process that we refer to as cognition and that we try to break into different domains. So I'd say that, in general, this is a very complex area with a lot of factors that are leading to changes in cognition. And thankfully, we're just seeing kind of these subtleties, rather than people who because of their care are not able to care for themselves.

How are people able to bounce back from cognitive effects of chemotherapy and radiation? Are there long-term effects and short-term effects that can be improved upon?

Yeah. So especially in the chemotherapy trials, we have more long-term data. And really, you're looking at about a third of patients who do not improve over time. They say about 75% of patients have acute cognitive changes when they're being treated, and then that goes down to about 30% or so as you get further and further out. So we're trying to identify those patients and trying to help them improve, much the way the others did.

And there are several different options in order to help patients to improve their cognitive training, and that's where you focus on a particular cognitive domain. And they work. They sometimes play games to try and target that area.

There's cognitive rehab, which allows you to find ways to work around the deficits so that you can do what you want to in your daily life. And also, exercise has been shown to really improve cognition. So especially executive function improves if you hit a certain target level of activity.

For radiation therapy, there's definitely some evidence that some patients are more affected than others. But we are still working to find ways to identify who is going to remain vulnerable, who is not going to improve, and who we really need to target.

OK. That's great to know. So I'm curious. How do you help educate others in the oncology field to look for and mitigate symptoms?
I think we're lucky here because we have a survivorship course at University of Rochester for both the medical oncology fellows and for the radiation oncology residents. And one of those classes is entirely devoted to cognitive changes in cancer survivors on both patients with brain tumors and those with tumors elsewhere in the body. And I think that does a lot to help people learn about this early on in their training.

Additionally, this year at ASCO, there was a panel where several of the leaders in the field, including my research mentor, Michelle Janelsins, discussed cognitive changes in cancer survivors, which was great. Additionally, I've been doing some lectures, so I do some lectures for the neurology residents on some of the neurologic complications we see in cancer survivors and then also for my co-residents in the radiation oncology department.

That's great. Again, today, my guest has been Dr. Sara Hardy. Thank you for joining us.
Thank you for having me.

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