Table 5.

Clinical studies demonstrating increased frailty in cancer survivors

Study	Study type	Frailty Measurement	Population of interest	Study groups	Methods	Findings
(K. K. Ness, et al., 2010)	Case control	Muscle strength Fitness Physical performance Participation	Survivors of childhood brain tumors treated at St. Jude or University of Minnesota	Cases: 78 survivors of childhood brain tumors Controls: 78 age, sex, and zip codematched population-based controls	In-home evaluations for muscle strength, fitness, physical performance, and an interview	Survivors with a median age of 22 demonstrated muscle strength and fitness similar to that expected of an individual in their 60’s.
(K. K. Ness, et al., 2012)	Cohort	Neuromuscular impairment	Survivors of childhood ALL enrolled in the St. Jude Lifetime Cohort Study	Participants : 415 survivors of childhood ALL Non-participants: 285 controls	Chart abstraction and tests for neuromuscular function	Survivors in their 30’s demonstrated neuromuscular impairments that limit physical performance similar to what is observed in individuals in their 60’s. This effect correlated with higher cumulative doses of vincristine and/or intrathecal methotrexate.
(Kirsten K. Ness, et al., 2013)	Cohort	Prefrailty Frailty Morbidity Mortality	Survivors of childhood cancer from the St. Jude Lifetime Cohort Study	Survivors: 1922 adult childhood cancer survivors Controls: 341 individuals without history of cancer	Chart extraction for medical records, questionnaires for frailty, and in-clinic assessments at follow up visits	Prevalence of prefrailty and frailty were higher in survivors compared to controls, particularly in women. Frailty was also associated with higher risk of chronic condition onset and with risk of death.
(Vatanen, et al., 2017)	Case control	Frailty Cardiovascular function Inflammatory markers Telomere length	Survivors of high-risk neuroblastoma who underwent high dose chemotherapy followed by autologous stem cell rescue	Cases: 19 survivors of high risk neuroblastoma Controls: 20 age and sex- matched volunteers	Assessed frailty using tests for muscle mass, energy expenditure, running, and weakness	Survivors were more likely to be “frail” and to report physical health limitations in vigorous activities compared to controls. Survivors also had higher CRP and shorter telomere length than controls.
(Smitherman, et al., 2018)	Cross sectional	Prefrailty Frailty Comorbid conditions	Adolescent- young adult cancer survivors treated at University of North Carolina	271 survivors who were diagnosed between ages 15–39	Frailty questionnaire to assess frailty status and comorbid conditions	Prevalence of prefrailty and frailty were high in AYA survivors. Frailty was associated with higher prevalence of comorbidities.
(Blair, et al., 2019)	Case control	Deficiencies in geriatric assessment domains All-cause mortality	Female survivors of any cancer in participants from the Iowa Women’s Health Study	Cases = 1723 female survivors of cancer Controls = 11,145 age matched cancer free women	Questionnaire to assess for Geriatric assessment domains and for all-cause mortality	Cancer survivors were more likely than controls to have deficits in multiple geriatric domains. Predicted 10- year mortality was higher in survivors than in controls.
(Hayek, et al., 2020)	Cohort	Prefrailty Frailty	Survivors of childhood cancer in the Childhood Cancer Survivor Study	Survivors: 10,899 survivors Controls: 2,097 Sibling controls	Baseline and follow up questionnaire	Demonstrated that prefrailty and frailty are higher in survivors compared to controls, and higher among females than in males. Exposure to cranial, abdominal/pelvic radiation, lung surgery, and comorbidities were also with risk of frailty. Findings suggest cancer therapies are a risk factor for the premature aging.

ALL, Acute lymphoblastic leukemia; AYA, Adolescent and young adult