Although children are much more likely to survive cancer today than 50 years ago, as adults, unfortunately, many of them develop cardiovascular disease, secondary cancers, or both, believed to result from the toxic effects of chemotherapy and radiation.
But the full risk picture for survivors hasn’t been clear.
“Patients want to know how long they’ll live once they’ve been treated for cancer. They ask, ‘What’s going to happen to me?’” said American paediatric oncologist Lisa Diller, MD, who founded the cancer survivorship programme at Dana-Farber/Boston Children’s Cancer and Blood Disorders Centre.
“Our question was, can we look at more than one outcome at a time and have a comprehensive model of what life looks like for survivors as they age?”
Diller is co-author of a study in JAMA Oncology that used simulation modelling to answer this question. Led by Jennifer Yeh, PhD, a decision scientist in the Division of General Paediatrics at Boston Children’s Hospital, the study estimated the total lifetime risk for cardiovascular conditions and subsequent cancers, as well as their age of onset.
MedicalXPress reports that based on their findings, the researchers are calling for clinicians to offer cancer survivors preventative health screenings and interventions decades before people without a childhood cancer history typically receive them.
Early onset of secondary health conditions
The investigators obtained data on children diagnosed with cancer between 1970 and 1999 who were alive at least five years after treatment, drawn from the Childhood Cancer Survivor Study (CCSS) and other national data sources.
From these data, they created a model called COMPASS (Cancer Outcomes Microsimulation: Paediatric and Adolescent SurvivorShip) to estimate the lifetime risks of eight subsequent health conditions among survivors. These included six ageing-related conditions (breast cancer, colorectal cancer, heart failure, coronary artery disease or myocardial infarction, valvular disease, and stroke) and two common, life-threatening secondary cancers (glial tumours and sarcomas).
Their key findings:
• Five-year cancer survivors developed their first secondary health condition by an average age of 47 – nearly 18 years before the general population. By 65, 55% had at least one of the eight conditions, and 29% had two or more, versus 20% and 4% of the general population, respectively.
• Survivors who had received radiation therapy were at especially high risk, developing one of the eight conditions 22 years ahead of the general population. However, even survivors who did not receive radiation developed at least one condition 13.5 years before the general population.
• Survivors who reached 40 in good health were still 6.2 times more likely than the general population to develop one of the eight conditions within 10 years.
• Survivors had a reduced life expectancy: 46% died before 65 versus 15% of the general population.
• Risk varied by the type of original cancer. Survivors of central nervous system tumours had the earliest onset of at least one health condition, an average of 24 years earlier than the general population. For leukaemia survivors, this was just 11 years.
Can long-term health be improved in cancer survivors?
The analysis found that survivors of all diagnoses were at risk for accelerated onset of health conditions, regardless of prior radiation exposure.
Both Yeh and Diller note that many of the eight conditions they looked at have preventative measures that could make a difference in their outcome.
“Internal medicine has age-based care guidelines for breast and colon cancer screening, measuring blood lipid levels, treating mild hypertension, and other tests and interventions,” says Diller.
“All of those guidelines should probably be applied at a much younger age in cancer survivors. Assessing the harms and benefits of some of these interventions is the focus of ongoing work.”
Diller hopes the model’s estimates will be incorporated into the Children’s Oncology Group’s survivorship guidelines and lead to risk assessment tools that adult internal medicine providers can readily use.
What about cancer patients treated today?
The study and an accompanying editorial in JAMA Oncology describe survivors’ increased health risks as a form of accelerated ageing, which can also include frailty, fatigue, reduced strength, and cognitive impairment.
But cancer treatment has changed since 1999. Do people treated more recently have a better long-term outlook?
It’s hard to know, says Diller. Recent treatment trends have favoured trying to reduce the use of toxic therapies and using genetic profiling to identify patients who truly need aggressive treatment. These may lead to better outcomes in the future.
“For newer treatments, like CAR-T-cell therapies and antibody-based immunotherapies, we just don’t have any information yet on long-term survivorship,” Diller notes.
The CCSS is now assembling a cohort of more recently treated children, so there may be more answers soon. Future analyses will also examine whether preventative care and environmental and lifestyle factors modify survivors’ risk.
“We plan to use the COMPASS model to look at outcomes for specific treatment protocols or new therapeutic approaches to get an initial peek at what we might expect,” says Yeh. “Our current findings can provide a benchmark for assessing improvements over time.”
Study details
Accelerated Ageing in Survivors of Childhood Cancer – Early Onset and Excess Risk of Chronic Conditions
Jennifer Yeh, Zachary Ward, Kayla Stratton, et al.
Published in JAMA Oncology on 20 March 2025
Abstract
Importance
The lifetime risk of ageing-related diseases among survivors of childhood cancer, accelerated by cancer treatment exposures, is unknown. Understanding this risk can provide a more comprehensive assessment of long-term health across the lifespan of survivors and guide adult care.
Objective
To estimate the lifetime risks of eight treatment-related cancers and cardiovascular conditions among childhood cancer survivors and compare them with the general population.
Design, Setting, Participants
Using data from the Childhood Cancer Survivor Study and national databases, this simulation modelling study projected long-term outcomes for five-year survivors diagnosed between 1970 and 1999 based on treatment exposures and age-related risks. The general population comparator was simulated using age-, sex-, and calendar year–matched individuals who faced only age-related risks.
Exposures
Treatment era (1970s, 1980s, 1990s), original cancer diagnosis, radiation treatment for primary diagnosis (any, none).
Main Outcomes and Measures
Estimated lifetime risks of eight health conditions (breast cancer, colorectal cancer, glial tumours, sarcomas, heart failure, coronary heart disease/myocardial infarction, stroke, and valvular disease). Risks were projected and compared with the general population, stratified by radiation exposure.
Results
In the general population, 20% developed at least one health condition by age 65.0 years; in five-year survivors this threshold was reached at age 47.3 years, representing a 17.7-year (95% uncertainty interval [UI], 14.0-21.0) acceleration in disease onset. By age 65 years, 55% of survivors were projected to develop at least one condition, indicating a 2.7-fold (95% UI, 2.2-3.5) higher relative risk and 34.2% (95% UI, 28.3-42.5) absolute excess risk compared with the general population. Risks were higher among those treated with radiation therapy for childhood cancer (22.0 years earlier onset [95% UI, 18.0-25.0]; 37.3% excess risk [95% UI, 31.6%-44.7%]) but still elevated for those without radiation exposure (13.5 years earlier onset [95% UI, 10.0-16.0]; 31.0% excess risk [95% UI, 23.9%-40.3%]). Reaching middle age was still associated with increased health risks. Compared with the general population, survivors who reached 40 had a 6.2-fold higher risk (95% UI, 4.8-9.4) of developing a new condition within 10 years.
Conclusions and Relevance
This study found that survivors of childhood cancer experience accelerated onset of ageing-related diseases, regardless of prior radiation exposure. These findings underscore the importance of prioritising cancer and cardiovascular disease prevention among survivors decades earlier than for the general population.
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