Approximately 30-40% of long-term childhood cancer survivors (CCS) experience accelerated aging: the premature onset of cellular senescence and aging-related morbidities manifesting with physical and cognitive frailty and pre-frailty. Accelerated aging is associated with more frequent and severe chronic health complications that impact health care delivery needs. Critical research gaps in accelerating aging remain as past studies were done predominantly in non-Hispanic white survivors, a median of 2-3 decades post-therapy, with assessment of frailty in the research setting. The BRIDGES Study (R01CA261881) is our ongoing multi-site, NCI-funded randomized control trial that investigates a shared health care delivery model with community primary physicians, compared to cancer center survivorship clinic care, to provide recommended surveillance for chronic conditions among CCS. Our R01’s overarching goal is to better meet the health care delivery needs of CCS with an intervention that can potentially overcome disparities. Unique strengths of this trial include high proportions of typically understudied survivors (Latinx, Black, rural, socioeconomically disadvantaged), targeting of early survivors who are only 2-4 years off-therapy, and baseline assessment of individual and area-level social determinants of health. With administrative supplemental funding (PA-20-272) and within the scope of our R01, we seek to address many of the gaps in accelerated aging research. Within the structure of the ongoing BRIDGES study and building on previous work within the investigator team, we propose to measure physical frailty with the modified Fried Phenotype, cognitive impairment with the PROMIS Pediatric Cognitive Function– Short Form instrument, and cellular senescence with p16INK4a expression among the 66 CCS who will be randomized to cancer center survivorship clinic over the next 12 months. Feasibility is supported by the integration of measures into the overall survivorship clinic visit and previous research on accelerated aging by our research team. Race, ethnicity, and individual- and area-level social determinants of health are already available from the baseline, pre-randomization evaluation. Our Specific Aims are, in a racially and ethnically diverse sample of CCS, to 1) Determine the prevalence of accelerated aging early in the post-treatment period, as measured by physical frailty, cognitive frailty, and cellular senescence 2-4 years post-therapy, and 2) Measure associations between disparities in individual (e.g. insurance status, household income, food and housing insecurity) and area-level (e.g. neighborhood safety, access to health care, days access to exercise) disparities and accelerated aging. Transformative Impact: If a diverse sample of childhood cancer survivors affected by accelerating aging can be identified early in the post-therapy period and with routine assessments done by clinical staff, our data would support future interventions that could improve survivors’ aging trajectory.

Many young childhood cancer survivors experience accelerated aging manifesting as health problems, declines in physical and cognitive function, and damage to their cells typical of people many decades older. Among half of the patients participating in our ongoing BRIDGES clinical trial that is investigating how to best deliver health care to a diverse sample childhood cancer survivors who are just 2-4 years post-therapy, we propose to do clinical and blood measures indicative of accelerated aging to see if it is 1) detected early in the survivorship, and 2) whether it is associated with individual and neighborhood social vulnerabilities. Data from our study will inform future interventions to try to slow aging in childhood cancer survivors.