Children with low skeletal muscle density were more likely to have hematologic toxicities from chemotherapy, but more research is needed to determine whether this measure is an accurate predictor of chemotoxicities in lymphoma.
Measuring body composition including skeletal muscle density by computed tomography (CT) scans at cancer diagnosis may provide helpful information on the risk for chemotoxicity in children with lymphoma and rhabdomyosarcoma, according to recent study results.
In particular, low skeletal muscle density — when fat infiltrates muscle and increases the likelihood of inflammation, immune dysregulation and mortality risk — was associated with hematologic toxicities in children with lymphoma or rhabdomyosarcoma and may be linked to how chemotherapy was distributed throughout the body.
“What we have shown using our study is that low muscle density at the time of your cancer diagnosis could potentially increase your risk of toxicities from chemotherapy,” said Dr. Aman Wadhwa, an assistant professor in the Division of Pediatric Hematology and Oncology at the University of Alabama at Birmingham, in an interview with CURE®. “Ours was the first study to show that this methodology could be used in children with cancer. It's been explored further and further among older adults with cancer, but before our study, there were no data among the pediatric oncology population. What we've shown is an observation, and for us, the next steps are to try and understand the why behind this what.”
Assessing body composition to potentially predict chemotoxicity is becoming more common in adults, but data in this area are lacking in children. The current standard to determine dosing and potential risk for toxicity was body mass index (BMI), although this can indicate different body types especially in two patients with the same BMI.
“The way we estimate obesity is using a patient's height and weight to calculate BMI, but so many things can affect a patient's weight and it fluctuates so much during therapy, that it's really hard to use BMI as a measure of their adipose tissue and skeletal muscle mass within the body,” Wadhwa explained.
The potential association between body composition and chemotoxicity was assessed in 107 children with Hodgkin lymphoma (45 children), non-Hodgkin lymphoma (42 children) or rhabdomyosarcoma (20 children). All children underwent CT scans in a previous study to examine body composition, particularly skeletal muscle density (potentially indicating muscle quality), skeletal muscle index (the ratio of muscle at the third lumbar vertebral level to a patient’s height) and total adipose tissue (body fat) in relation to a child’s height.
“The thought process behind this study came from my time during fellowship,” Wadhwa said. “While we're making a lot of advances in terms of bringing new therapeutics to patients, the one thing that really struck me was how little we know about why certain patients develop side effects with the same treatment and why other patients do not. I felt there was a big difference in how kids tolerated the same chemotherapy regimen. And one of the thought processes behind that has been that obesity could potentially be contributing to differences in how patients tolerate chemotherapy.”
Researchers focused on a few main objectives including life-threatening or worse hematologic toxicities (such as decreased bone marrow activity and effects to blood cell counts) and severe or worse nonhematologic toxicities (such as infections, neutropenia with fever and toxicities to the kidneys, liver or heart) within six months of a child’s diagnosis.
In this study, children had a median skeletal muscle index of 41 cm2/m2, median skeletal muscle density of 54.1 HU and median total adipose tissue of 19.5 cm2/m2. Children also had a median BMI percentile of 62.5 (indicating a healthy weight).
Life-threatening or worse hematologic toxicities occurred in 74.7% of chemotherapy cycles, and severe or worse nonhematologic toxicities were observed in 66.3% of the cycles. Children who had a higher skeletal muscle density when diagnosed with lymphoma or rhabdomyosarcoma were less likely to have life-threatening or worse hematologic toxicities. Total adipose tissue was not linked with hematologic toxicities. Researchers did not observe an association between nonhematologic toxicities and body composition.
Even though findings from this study demonstrate that skeletal muscle density may be a better predictor of chemotoxicities than BMI, the fact that clinicians still use BMI as a dosing strategy for children may lie in the ease of its use.
“Our (electronic medical records) are designed in a way that when we enter a patient's height and weight, (and) we're automatically provided with the BMI of a patient and their body surface area,” Wadhwa said. “How we prescribe chemotherapy is based on a formula that was designed in the 1970s using the body surface area. That's really what we have stuck with 50 years later at this point. There's room to grow this field further and not completely shift from body surface area-based chemotherapy dosing, but at least incorporate these CT-based findings into that.”
Wadhwa explained that more research is needed to determine whether there is a way to reverse this increased risk for toxicities in children based on their body composition.
“If we can establish that repeatedly low muscle mass or density and/or increased adiposity truly impacts a select group of patients that experience a lot of toxicity from the same dose of chemotherapy, one intervention could be can we adjust their dose of chemotherapy so that they experience lower toxicities at the same cure rate,” he said. “The second way would be physical activity and diet interventions that are being tested and are being shown to be effective already, where we come up with individualized plans for patients where, in a way, in addition to your chemotherapy, you’re also prescribing these lifestyle modifications … that could potentially reverse, mitigate or prevent these body changes from getting worse during therapy.”
Although more work needs to be done before skeletal muscle density and other measures are used to determine chemotherapy dosing in children, Wadhwa added that researchers are aiming to improve outcomes and quality of life in these patients.
“We're constantly working towards improving the outcomes of our patients, not just from a survival standpoint, but also, we want to make sure that the treatments that we're giving them are as safe as possible,” Wadhwa said. “We're working towards ensuring that we're focusing on a patient's quality of life as well, not just survival.”
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