REVIEW ARTICLE

Understanding Frailty in Cancer Patients Pooja Baijal, MD and Vyjeyanthi Periyakoil, MD Abstract: As population ages, the number of older adults with cancer is increasing rapidly. Chronological age per se is a poor guide for an oncologist to determine tolerance to cancer treatment. Older adults have been underrepresented in cancer clinical trials, leading to paucity of guidelines to meet the treatment challenges in this population. To evaluate an older adult with cancer, oncologists must understand age-related changes and identify the subset of population who is vulnerable and at risk of cancer treatment toxicity. Comprehensive geriatric assessments focusing on functional status, multimorbidity, nutritional status, cognitive impairment, and psychosocial support help recognize heterogeneity among older adults, leading to individualized approaches toward cancer treatment. The treatment decisions need to be made in collaboration with the patient’s values and preferences. Key Words: Frailty, older adults, cancer, geriatric assessment (Cancer J 2014;20: 358–366)

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he incidence of cancer increases with age. According to the Surveillance, Epidemiology, and End Results data, cancer is most frequently diagnosed among people aged 65 to 74 years, with 65 years being median age at diagnosis. In 2014, it is estimated that there will be 1,665,540 new cases of all cancer sites, and 25.4% of new cases will be between 65 and 74 years of age. Cancer is the second leading cause of death for age 65 years or older, lying next to heart disease according to the 2010 US Centers for Disease Control and Prevention data. Although the death rates of cancer and heart disease are both falling, those for heart disease are falling faster; it will not be long before cancer will be the leading cause of death. With this trend of more older adults being diagnosed with cancer and a rapid rise in the number of individuals 65 years or older, providing effective and tolerable cancer treatment becomes a daunting task to an oncologist. Identifying the robust from the frail based on assessment of biologic, psychological, and social aspects of the aging process becomes imperative. The concept of frailty has prevailed in the medical literature for a long time. It is known that certain subset of older adults can tolerate cancer treatment without compromise of their function or cognition. However, frail older adults may be less able to tolerate treatments and be more at risk of adverse health outcomes with long-lasting consequences. Identifying frail older adults allows the oncologist to identify these high-risk patients and tailor therapies to their specific needs.

UNDERSTANDING FRAILTY Frailty is a complex geriatric syndrome characterized by heightened vulnerability to minor stressors, leading to adverse health outcomes. Frailty lies in a midpoint between independence and predeath on spectrum of geriatric functional continuum.1 Individuals who are functionally dependent may be a step beyond From Stanford Hospital and Clinics, Palo Alto, CA. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Reprints: Pooja Baijal, MD, Stanford Hospital and Clinics, 1265 Welch Road, MSOB X216, MC: 5475, Palo Alto, CA 94305-5751. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 1528-9117

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frailty but can still express frailty as further functional decline or even death.2 Frail individuals are at high risk of worsening disability, falls, admission to hospital or care homes, and death,3–5 This expression of aging population needs to be identified especially in oncology as chronological age is a poor reflection of physiologic age.

FRAILTY DEFINITIONS Frailty can be roughly defined as a clinically recognizable state accounted by age-related decline in functional reserve, creating a state of vulnerability and inability to cope with acute stressors leading to adverse health outcomes. Recently, an international consensus group identified 4 major consensus point on physical frailty, although no single operational definition or simple assessment tool was agreed upon. (1) Physical frailty is defined as “ a medical syndrome with multiple causes and contributors that is characterized by decreased strength and endurance and reduced physiologic function that can lead to dependency and death; (2) it can be prevented or treated with exercise, reduction of polypharmacy, vitamin D supplementation, and protein calorie supplementation; (3) it can be recognized by validated screening scales; and (4) screening for physical frailty should be performed on all persons older than 70 years and people with weight loss of greater than 5%.6 Various models of frailty have been proposed.

Frailty Phenotype/Biological The Cardiovascular Health Study (CHS) defined frailty as a clinical syndrome in which 3 or more of the following criteria were present: unintentional weight loss (10 lb in past year), selfreported exhaustion, weakness (grip strength), slow walking speed, and low physical activity7 (Fig. 1). Individuals meeting 1 to 2 criteria were considered prefrail. This frailty phenotype was independently predictive of falls, disability, hospitalization, and death.7 It provided evidence that frailty is not synonymous with disability and comorbidity, whereas comorbidity is a cause for frailty, and disability is an outcome (Table 1). Prefrailty status showed intermediate risk of adverse outcomes and increased risk of becoming frail over 3- to 4-year follow-up.

Frailty Phenotype Women’s Health and Aging Studies (WHAS) I and II evaluated the validity of CHS frailty definition as a medical syndrome, applicable across populations, and identified a profile of high risk of adverse health outcomes.8 The prevalence of frailty on the basis of frailty phenotype in CHS and WHAS was 7% to 12% in community-dwelling adults 65 years or older. It increases with age, seen more in women than men and in African Americans than whites.

Combination of Functional and Biological Model The Study of Osteoporotic Fracture (SOF) Index uses a functional and biological model to make relevant clinical assessment. The SOF index uses 3 components; weight loss, inability to rise from chair 5 times without using arms, and reduced energy levels. The SOF index was compared with CHS index in a large cohort of The Cancer Journal • Volume 20, Number 5, September/October 2014

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The Cancer Journal • Volume 20, Number 5, September/October 2014

Frailty in Cancer Patients

FIGURE 1. Frailty as a functional continuum on the geriatric spectrum.

community-dwelling older women and effectively predicted falls, disability, fracture, and death, as well as the more complex CHS index. Because the participants were only community-dwelling older women, the finding may not be applicable in other populations.

severe frailty. The higher FI-CGA score was associated with higher risk of death or institutionalization.11

FRAIL Scale

Combination of Functional, Biological, and Accumulation of Deficits

International association of nutrition and aging proposed a FRAIL scale, which is 5-component scale with self-administered questions that are easy to complete. The scoring assesses fatigue, resistance, ambulation, illness, and weight loss.12 Score ranges from 0 to 5, 1 point for each component, 0 = best, 5 = worst; 3 to 5 represent frail, 1 to 2 are prefrail, and 0 has robust health status. Although it appears promising, this scale has not been validated in cancer patients. Balducci and Extermann13 developed a clinical tool for recognizing frailty. The tool combines several components of CGA including age older than 85 years, dependence on 1 or more ADLs, presence of 3 or more comorbid conditions, and the presence of 1 or more geriatric syndromes.

Jones et al11 developed an FI based on Comprehensive Geriatric Assessment (CGA) adapting a multidimensional approach to frailty. The FI was calculated by counting the number of deficits accumulated in 10 domains: cognition, mood and motivation, communication (vision, hearing, speech), mobility, balance, bowel function, bladder function, Instrumental Activities of Daily Living (IADLs), Activities of Daily Living (ADLs), nutrition, and social resources. The problems in each domain were scored from 0 (no problem), 1 (minor problem), to 2 (major problem). The sum would determine the index where a score greater than 13 was

A longitudinal cohort study of 998 African American health participants with 3- and 9-year follow-up determined the validity of FRAIL scale when compared with SOF, CHS, and FI. Overall FI and the FRAIL scale exhibited the strongest validity of disability and mortality.14 Another study compared the ability of FI, frailty phenotype, and FRAIL scale to predict mortality among community-dwelling individuals aged 40 to 79 years. All 3 frailty

Frailty Index/Accumulation of Deficits The Canadian Study of Health and Aging, which was a 5-year prospective cohort study, developed a frailty index (FI), which had 92 baseline variables based on symptoms, signs, disease states, and disability. Frailty index was a simple summation of all variables present divided by the total number of all potential deficits considered for a given person. In short, it showed a cumulative effect—the more the deficits, the more likelihood of frailty.9 Risk of death and institutionalization have been shown in relation to FI.10

COMPARISON OF FRAILTY MODELS

TABLE 1. FP Criteria

Measurement

Score

Weight loss Poor endurance

10-lb Unintentional in prior year Self-reported exhaustion CES-D depression scale (1) Everything I did was an effort. (2) I could not get going.

Physical activity

Minnesota Leisure time activity questionnaire; kcal/wk expended

Walk time

Stratified for sex and height

Grip strength

Stratified by sex and BMI

Yes-Frail 0—Rarely or none 1—Some or little of the time 2—Moderate amount of time 3—Most of the time Score 2 or 3 was frail Men- < 383 kcal/wk of physical activity—frail Women

Understanding frailty in cancer patients.

As population ages, the number of older adults with cancer is increasing rapidly. Chronological age per se is a poor guide for an oncologist to determ...
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