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Biomarkers could help identify children with cancer at risk for cognitive impairments
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A child who has survived cancer has endured an extraordinary amount of adversity in an unusually short period of time.
Daily life in the shadow of this destructive disease often is fraught with pain, fear, inability to enjoy favorite activities and lapses in school attendance. Cancer treatments can cause fatigue, nausea and other short-term adverse events.
Children who have been cured of cancer have every reason to expect a full, healthy life ahead. However, even children with the best cancer outcomes may sustain long-term deterioration of brain function, resulting in serious struggles with attention, concentration, memory and learning.
“If you do research-based neuropsychological testing, you can detect, in approximately 40% to 50% of these children, deficits in specific components of cognitive function,” Peter D. Cole, MD, chief of pediatric hematology/oncology and the Embrace Kids Foundation endowed chair in pediatric hematology/oncology at Rutgers Cancer Institute of New Jersey, said in an interview with HemOnc Today. “These deficits among survivors lead to significant trouble in school. No matter how you define success in life, survivors of cancer are less likely to attain it. They are less likely to have graduated from high school, less likely to have graduated from college, and less likely to be gainfully employed than their age-matched peers who were never treated for cancer.”
To help this pediatric population, Cole and colleagues are studying biomarkers among children with acute lymphoblastic leukemia, the most common cancer among children. The goal is to identify children at risk for cognitive impairments early on in their cancer treatment. The research is funded by a $3.4 million, 5-year grant from the NIH.
Cole spoke with HemOnc Today about his inspiration for this project, the ability to detect chemical derangements that may be predictive of permanent damage, and how this could improve quality of life for these children.
Question: What prompted you to focus your research on cognitive impairment among pediatric cancer survivors?
Answer: This project was inspired by my patients. They are not shy about telling me all the problems I’ve caused for them in the process of curing their leukemia through chemotherapy. Many complained that they felt as though they were in a bit of a fog. They had trouble with attention span and spatial memory, and these problems affected their performance in school, which bothered them a lot. Some of these issues can be permanent.
This project was triggered by patients who were asking the “why me?” question. If they’re all getting the same type of therapy, why do some experience these effects and not others? We decided to try and understand what makes some of these children more susceptible to side effects.
Q: What factors did you evaluate?
A: We’ve looked at variations in environmental factors, such as diet, and in the past, we looked at genetic variation. The research has pointed us toward mechanisms, biochemical pathways, that might be impaired more in one patient than another. We’re measuring biomarkers; we’re measuring chemicals in cerebrospinal fluid that reflect derangements in the biochemical pathways that we suspect are related to causing toxicity. By doing that, we’re hoping to pick up toxicity earlier on, when intervention might prevent permanent damage.
Q: Have you identified anything in particular?
A: One of the leads we got is linked to derangements in our defenses against oxidative stress. Oxidative damage is induced by chemotherapy, and that can cause damage to normal structures. We’re getting baseline measures in these patients and looking at how these biomarkers change during treatment. Our hope is that early on in treatment, we can detect when these biomarkers start to change. That’s when we might be able to intervene. We want to protect against the side effects, not against the desired effects of the chemotherapy killing the cancer cells. If we can pick out patients who are at greatest risk for the side effects, those patients might be good subjects for a clinical trial testing whether antioxidants can reduce those effects.
Q: How might this research affect clinical practice in the long term?
A: We are hoping that when patients are first diagnosed with leukemia, we can give them more accurate, personalized advice about side effects for which they may be at risk. Right now, we tell everyone, “You may lose your hair. You may be nauseous. You may vomit.” With this research, we may be able to tell certain patients, “You are more at risk for toxicity to your bones,” or, “You may be more at risk for side effects to your brain or your heart.” This will influence how we monitor patients during treatment and how we think about modifying our therapies. We’ll be really giving personalized medicine. – by Jennifer Byrne
For more information:
Peter D. Cole, MD, can be reached at 195 Little Albany St., New Brunswick, NJ 08901.
Disclosure: Cole reports no relevant financial disclosures.