Cancer Treatment Timing and Long-Term Effects Under Study
New research examines both the long-term biological aging effects of childhood cancer treatments and proposes alternative treatment sequencing strategies to prevent tumor resistance and improve cure rates.
Cancer survivors who received childhood treatments showed accelerated biological aging, according to a study that analyzed blood samples from 1,400 long-term survivors treated at St. Jude Children's Research Hospital. Researchers at the University of Rochester Medical Center used epigenetic clocks — tools that estimate biological age by examining chemical tags on DNA — to determine whether life-saving treatments like chemotherapy and radiation could speed up biological aging.
Most of the group consisted of acute lymphoblastic leukemia survivors or Hodgkin lymphoma survivors. Participants were at least five years past their treatment, though some had survived for several decades. They underwent neurocognitive testing to measure their attention span, memory and information processing speed.
Chemotherapy was found to have the greatest impact on aging acceleration. The study suggests the treatment can alter DNA structure and cause cellular damage. Researchers also found that cellular aging was closely linked to cognitive performance, as survivors of a higher biological age had more difficulty with memory and attention.
"These well-established aging-related biomarkers have previously been associated with neurocognitive impairment and decline in older non-cancer populations, particularly in cognitive domains related to aging and dementia, such as memory, attention and executive function," the study stated.
The research team hopes to use these findings to focus on intervention efforts, specifically by determining when accelerated aging begins. "Young cancer survivors have many more decades of life to live," lead study author AnnaLynn Williams, PhD, said in a press release. "If these accelerated aging changes are occurring early on and setting them on a different trajectory, the goal is to intervene to not only increase their lifespan, but improve their quality of life."
There were some limitations to the study. The researchers could not adjust for chronic health conditions or education because they are directly impacted by treatment. Additionally, the study only looked at the survivors at a single point of time, so it could not directly prove causation. The study was published in the journal Nature Communications.
In separate research addressing treatment effectiveness, a new study provides hope that smarter timing of cancer treatments could improve cure rates. Although tumors may at first shrink under therapy, in many cases they eventually regrow. These relapses stem from a small number of cancer cells that have gained mutations making the cells resistant to the treatment.
The standard clinical approach is to wait and see if a tumor regrows before trying a different treatment. By this point, some tumor cells are likely to have gained mutations making them resistant to the second treatment, which then also fails.
Evolutionary theory suggests an alternative strategy. Instead of waiting, it might be better to switch to a second treatment while the tumor is still responding to the first one. This "kick it while it's down" approach is most appropriate when doctors know from experience that even the best option for a first treatment often fails due to resistance.
Researchers adapted mathematical methods more commonly used to understand how plants and animals evolve in response to environmental pressures, such as climate change. In their study, the team concludes that their findings justify further experimental and clinical testing of this innovative evolutionary treatment strategy. Three small clinical trials are already underway in soft-tissue cancer, prostate cancer, and breast cancer. Further trials are in development.
"Our models predict that this new approach will generally outperform the standard of care," explains the principal investigator. "A sequence of two treatments, even if optimally timed, is likely to succeed only in relatively small tumors. But we have reason to hope that switching between three or more treatments, following the same principle, could eliminate larger tumors." The study was published in the journal Genetics.