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Purpose: The primary goal of this scoping review was to summarize the literature published after the 2018 National Cancer Institute think tank, "Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors," on physical and cognitive functional outcomes among cancer survivors treated with chemotherapy. We focused on the influence of chemotherapy on aging-related outcomes (i.e., physical functional outcomes, cognitive functional outcomes, and frailty), given the known associations between chemotherapy and biologic mechanisms that affect aging-related physiologic processes., Methods: A search was conducted across electronic databases, including PubMed, Scopus, and Web of Science, for manuscripts published between August 2018 and July 2023. Eligible studies: 1) included physical function, cognitive function, and/or frailty as outcomes; 2) included cancer survivors (as either the whole sample or a subgroup); 3) reported on physical or cognitive functional outcomes and/or frailty related to chemotherapy treatment (as either the whole sample or a subgroup); and 4) were observational in study design., Results: The search yielded 989 potentially relevant articles, of which 65 met the eligibility criteria. Of the 65 studies, 49 were longitudinal, and 16 were cross-sectional; 30 studies (46%) focused on breast cancer, 20 studies (31%) focused on the age group 60 + years, and 17 (26%) focused on childhood cancer survivors. With regards to outcomes, 82% of 23 studies reporting on physical function showed reduced physical function, 74% of 39 studies reporting on cognitive functional outcomes found reduced cognitive function, and 80% of 15 studies reporting on frailty found increasing frailty among cancer survivors treated with chemotherapy over time and/or compared to individuals not treated with chemotherapy. Fourteen studies (22%) evaluated biologic mechanisms and their relationship to aging-related outcomes. Inflammation was consistently associated with worsening physical and cognitive functional outcomes and epigenetic age increases. Further, DNA damage was consistently associated with worse aging-related outcomes., Conclusion: Chemotherapy is associated with reduced physical function, reduced cognitive function, and an increase in frailty in cancer survivors; these associations were demonstrated in longitudinal and cross-sectional studies. Inflammation and epigenetic age acceleration are associated with worse physical and cognitive function; prospective observational studies with multiple time points are needed to confirm these findings., Implications for Cancer Survivors: This scoping review highlights the need for interventions to prevent declines in physical and cognitive function in cancer survivors who have received chemotherapy., (© 2024. The Author(s).)

Advances in cancer treatments have led to substantially improved survival for patients with cancer. However, many patients experience changes in cognition as a side effect of both cancer and cancer treatment. This occurs with both central nervous system (CNS) tumors and non-CNS tumors and in both children and adults. Studies of patients with non-CNS cancer have shown that cancer-related cognitive impairment (CRCI), which can include changes in memory, executive function, attention, and processing speed, occurs in up to 30% of patients prior to any treatment and in up to 75% of patients during treatment. A subset of patients with non-CNS and CNS cancer appear to be at higher risk for CRCI, so much research has gone into identifying who is vulnerable. Risk factors for CRCI in adults include cognitive reserve, age, genetic factors, and ethnicity; risk factors for children include genetic factors, female sex, younger age at diagnosis, chemotherapy dose, and both dose and field size for radiation. Although the field has made substantial strides in understanding and treating CRCI, more research is still needed to improve outcomes for both pediatric and adult cancer survivors.

Purpose: Cancer and its treatment may affect cognitive function through a number of direct and indirect pathways including inflammation, lipid metabolism, vascular damage, and changes in the blood-brain barrier. While short-term treatment-related cognitive changes are well recognized, only limited research is available in older, long-term survivors of cancer., Methods: Using NHANES data from 1999 to 2002, 408 cancer survivors and 2639 non-cancer participants aged 60 years old and above were identified. Cognitive function of these groups were compared using the Digit Symbol Substitution Test (DSST) and self-reported problems with memory or confusion., Results: After adjustment for covariates, cancer survivors scored, on average, 1.99 points lower on the DSST compared to non-cancer survivors (-1.99, 95 % CI -3.94, -0.05). Cancer survivors also had 17 % higher odds of self-reporting problems with memory or confusion (OR 1.17, 95 % CI 0.89, 1.53)., Conclusion: In this nationally representative sample of older US adults, cancer survivors had lower DSST scores than non-survivors and had more self-reported problems with memory or confusion.