Studying Accelerated Brain Age and Neurocognitive Impairments in Childhood Cancer Survivors With Nicholas Phillips, MD, PhD

In this interview from the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Nicholas Phillips, a Physician Scientist at St. Jude Children’s Research Hospital, discusses his research investigating accelerated brain age and associated neurocognitive impairments experienced by childhood cancer survivors.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we’re here at the ASCO Annual Meeting, and I’m joined by Dr. Nicholas Philips. Thanks so much for joining me today.

Nicholas Phillips, MD: Nice to meet you, and nice to be here. My name is Nick Philips. I’m a Physician Scientist at St. Jude Children’s Research Hospital in the Department of Epidemiology and Cancer Control, and I’m here at ASCO to present my poster.

Oncology Data Advisor: Yes, your poster here is on accelerated brain age and associated neurocognitive impairments in adult survivors of childhood cancer. For background, what is brain age acceleration, and how is it associated with neurocognitive impairment?

Dr. Phillips: Brain age is a metric that we use in neuroimaging to quantify changes in gray and white matter. We base this on nonclinical or clinically obtained 3D non-contrasted magnetic resonance imaging (MRI). What we do is we measure the volumes of the brains, and we compare that to a database of 30,000 patients and look at where their brains fit along that metric. In the non-cancer population, this is very helpful because it can predict morbidity and mortalities, like dementia.

Oncology Data Advisor: Why did you decide to investigate this in childhood cancer survivors?

Dr. Phillips: Recently, just last week, we published a paper from the Childhood Cancer Survivor Study (CCSS), which is a large cohort of 30,000 patients, and we asked them questions about their neurocognition. These are survivors who are about 20 to 30 years out from their diagnosis. What we found, surprisingly, was that a large proportion of them were reporting that they were having new onset memory impairment. Again, these are people who are 35 years out from diagnosis, and they’re reporting much more memory impairment than their siblings. It wasn’t just the patients who had received central nervous system (CNS) toxic therapy, but also patients who had not, like Hodgkin lymphoma survivors who don’t receive cranial radiation or chemotherapies to the brain. We began to ask that question, “What’s going on here? Are our patients experiencing a premature aging phenotype?”

Oncology Data Advisor: For this study, how did you go about designing and conducting it?

Dr. Phillips: We leveraged one of the largest pediatric cancer survivorship programs in the country, which is at St. Jude, called the St. Jude Lifetime Cohort. With this patient population, we recruit survivors who were treated at St. Jude between 1962 and 2012, and we bring them back every three to five years at no expense to themselves or their families. They undergo three-day evaluation that includes clinical testing, like an echocardiogram, a pulmonary function test, as well as an annual physical, to look at long-term effects of cancer therapy. A subset of these patients also agreed to participate in our program and underwent MRI imaging. We collected data from leukemia survivors, Hodgkin lymphoma survivors, and brain tumor survivors, and also a small cohort of community controls to look at the differences between these groups.

Oncology Data Advisor: What were the results that you found with the study?

Dr. Phillips: Surprisingly, we again found that all survivors across the board had older brains than their siblings, but the most at-risk group appears to be those who had received cranial radiation, whether they be acute lymphoblastic leukemia (ALL) survivors from the old treatment regimens or those who had been treated for brain tumors. They, on average, were about 10 years older than their chronologic age. Most surprisingly, though, was that young girls who were treated with cranial radiation below the age of 10 were the most adversely affected. They often had brain ages that were 30 years older than their siblings, which was really shocking. We know that cranial radiation can impact neurocognition, so we don’t routinely give it to children who are under three because of that. We know that it can severely impact their IQ. We didn’t realize that the risk extends up to almost 10 years of age.

Oncology Data Advisor: Now that you have these results, can brain age be used as a biomarker for predicting risk?

Dr. Phillips: That’s what our hope is. Now we’re going to try and validate this in a larger study. We also want to dig in a little bit deeper and see what exactly is going on, because when you look at the neurocognitive outcomes in relation to these brain changes, they’re telling us that this is not a normal phenotype for brain aging. Normally, as you grow older, your thinking is a little bit slower, your processing speech is a little slower, and your working memory’s not quite as good. These patients are seeing changes in word reading and vocabulary, which is normally preserved throughout your life. This gives us an indication that maybe something else is going on here. That’s the next step, to dig a little bit deeper into that and see if this is a different kind of brain aging.

Oncology Data Advisor: My last question for you is, since the theme of ASCO this year is “Partnering with Patients,” how do you strive to do this in both your practice and in your research?

Dr. Phillips: The first and most important thing is to get these results to our patients and to the community at large. One of the core missions of St. Jude’s, of course, is to disseminate all the information that we gather for free to everybody across the world. But more importantly, we want our patients to be able to act on the information. It may be 10 years before we develop a pharmaceutical intervention or some other kind of intervention for this brain aging phenotype, but there are things that our patients can do now, and we want them to realize that.

Being physically active—and this is also in the non-cancer population that you can see this—there’s a huge benefit for preserving brain age if you can maintain activity. I don’t mean going to the gym for 30 minutes a day and getting on a treadmill and lifting weights, but just staying physically active. Find a hobby that you’re engaged in that you can do three times a week—tennis, swimming, whatever—and do that, and that will help maintain your brain age. The other thing you can do is mental gymnastics or mental fitness and learning new things. Again, don’t have to go to college and learn calculus, but just pick up an activity that you’re interested in and read about that or engage and learn new things. That also will help preserve your brain age.

Oncology Data Advisor: That is great to know. Thank you so much for stopping by today to talk about this study.

Dr. Phillips: Thank you for inviting me.

About Dr. Phillips

Nicholas Phillips, MD, PhD is a Physician Scientist in the Department of Epidemiology and Cancer Control at St. Jude Children’s Research Hospital in Memphis, Tennessee. His research focuses on leveraging imaging, biologic, and behavioral data to develop interventions for neurologic and neurocognitive challenges experienced by survivors of childhood cancer.

For More Information

Phillips NS, Baedtke JL, Williams A, et al (2023). Accelerated brain age and associated neurocognitive impairments in adult survivors of childhood cancer. J Clin Oncol (ASCO Annual Meeting Abstracts), 41(suppl_6). Abstract 10028. DOI:10.1200/JCO.2023.41.16_suppl.10028

Phillips NS, Stratton KL, Williams AM, et al (2023). Late-onset cognitive impairments and modifiable risk factors in adult childhood cancer survivors. JAMA Netw Open, 6(5)e2316077. DOI:10.1001/jamanetworkopen.2023.16077

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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