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Cited by 203Frailty in Older AdultsNutrition and Health in AgingPharmaceutical Practices and Patient Outcomes

Frailty as determined by a comprehensive geriatric assessment-derived deficit-accumulation index in older patients with cancer who receive chemotherapy

Open access
Cohen, Harvey Jay, Smith, David, Sun, Can‐Lan, Tew, William, Mohile, Supriya G., Owusu, Cynthia, Klepin, Heidi D., Gross, Cary P. +6 more·2016·Cancer
DOI 10.1002/cncr.30269PMC PMC5138076
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Abstract

BACKGROUND: Frailty has been suggested as a construct for oncologists to consider in treating older cancer patients. Therefore, the authors assessed the potential of creating a deficit-accumulation frailty index (DAFI) from a largely self-administered comprehensive geriatric assessment (CGA). METHODS: Five hundred patients aged ≥65 years underwent a CGA before receiving chemotherapy. A DAFI was constructed, resulting in a 51-item scale, and cutoff values were examined for patients in the robust/nonfrail (cutoff value, 0.0 < 0.2), prefrail (cutoff value, 0.2 < 0.35), and frail (cutoff value, ≥ 0.35) groups. RESULTS: Two hundred and fifty patients (50%) were nonfrail, 197 (39%) were prefrail, and 52 (11%) were frail. Older patients (aged ≥ 80 years) and those who had lower education, were living alone, and had higher stage disease were associated with prefrail/frail status. Prefrail/frail patients were more likely to have grade ≥3 toxicity but not to have a dose delay or reduction, and they were more likely to discontinue drug and be hospitalized. The association with grade ≥3 toxicity was attenuated by controlling for a toxicity risk calculator, but the other outcomes were not. CONCLUSIONS: A deficit-accumulation frailty index can be constructed from a CGA in older patients with cancer and can indicate the frailty status of the population. The frailty status so determined is associated both with outcomes likely because of chemotherapy toxicity and with those likely because of age-related physiologic and functional deficits and thus can be useful in the overall assessment of the patient. Cancer 2016;122:3865-3872. © 2016 American Cancer Society.

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Crossref · 10.1002/cncr.30269

Cites

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Claims the paper makes

0 of 35 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    A Deficit Accumulation Frailty Index can be constructed from a largely self-administered comprehensive geriatric assessment in older cancer patients.

    “A Deficit Accumulation Frailty Index can be constructed from a CGA in older cancer patients and can indicate the frailty status of the population.”
    • Also stated in: § Discussion · boosted
      “Here we have demonstrated the feasibility of calculating a Deficit Accumulation Frailty Index derived from a largely self-administered Comprehensive Geriatric Assessment to provide such a measure and related it to relevant outcomes in older patients undergoing chemotherapy.”
    Quote in the paperSubstantial claim
  • Findingown data

    Living alone was associated with pre-frail/frail status.

    “Older patients (80+), lower education, living alone, and higher stage were associated with pre-frail/frail.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Stepwise multivariate multinomial logistic regression retained age, education, living alone, and cancer stage as significant variables associated with pre-frail and frail status.

    “Stepwise multivariate multinomial logistic regression of the demographic characteristics retained age, education, living alone and cancer stage as significant variables associated with pre-frail and frail.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Older age (80+) was associated with pre-frail/frail status.

    “Older patients (80+), lower education, living alone, and higher stage were associated with pre-frail/frail.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Frail patients were more likely to be hospitalized due to toxicity than robust patients, with RR 1.98 (95% CI 1.26-3.11), after adjustment for toxicity risk group.

    “frail patients were more likely to discontinue their chemotherapy (RR=2.06, 95%CI, 1.26–3.38, p=0.004) and more likely to be hospitalized (RR=1.98, 95%CI 1.26–3.11, p=0.003) even after adjustment for toxicity risk group.”
    Quote in the paperSubstantial claim
  • May combine two claims. 13
  • Classified as probably not a substantial claim. 20

  • May combine two claims.

    Findingcitation

    The frailty distribution in this cohort had fewer robust patients and more pre-frail/frail patients than a previous study of older women with breast cancer.

    “The frailty distribution of the subjects reported here showed fewer patients in the robust category and more in the pre-frail and frail categories than in that study, perhaps reflecting the presence of more active disease or later stage in our cohort.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The DAFI constructed in this study comprises 51 items.

    “A 51-item scale was constructed by using individual items representing the various domains noted above.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the 500-patient cohort, 50% were non-frail, 39% pre-frail, and 11% frail.

    “Two Hundred and Fifty patients (50%) were non-frail, 197 (39%) pre-frail, 52 (11%) frail.”
    • Also stated in: § Results · plain
      “Two hundred and fifty (50%) of the patients were non-frail, 197 (39%) were pre-frail and 53 (11%) were frail.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Adjustment for the toxicity risk calculator attenuated the association between frailty and grade 3+ toxicity but did not attenuate the associations with discontinuation or hospitalization.

    “The association with grade 3+ toxicity was attenuated by controlling for a toxicity risk calculator but the other outcomes were not.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The distribution of robust, pre-frail, and frail status did not differ by gender, race, or employment.

    “The distribution of robust, pre-frail and frail did not differ by gender, race, and employment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The most common outcome was grade 3+ chemotherapy toxicity, while hospitalizations and drug discontinuation occurred in over 15% of patients.

    “The most common was grade 3+ chemotherapy toxicity but hospitalizations and drug discontinuation occurred in over 15% of the patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was approved by the Institutional Review Board of the City of Hope Comprehensive Cancer Center.

    “This study was approved by the Institutional Review Board of the City of Hope Comprehensive Cancer Center.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The analysis adjusted the association between frailty and outcomes for risk group determined by the previously reported toxicity risk calculator.

    “we also adjusted the association of frailty with outcomes, by risk group as determined by the calculator.(11)”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies have shown that regardless of which items are included, the points at which pre-frailty and frailty appear are remarkably similar.

    “Moreover a number of studies have shown that regardless of which items are included, there is a remarkable similarity of the points at which pre-frailty and frailty appear.(4,22,23)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The spectrum of DAFI scores reflects biological age, incorporating physiologic and disease-related changes.

    “Thus, the spectrum of the DAFI scores reflects the biological age of individuals taking into account physiologic as well as disease related changes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The DAFI-CGA as a single measure is associated with both direct chemotherapy and other important treatment outcomes.

    “Thus the DAFI-CGA as a single measure is associated with both direct chemotherapy and other important outcomes of treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The deficit accumulation approach can be applied to any dataset with enough varied items.

    “The deficit accumulation approach can be applied to any dataset as long as it contains enough varied items.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] source

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    Premisecitation

    A Frailty Index requires at least 30 items to be valid.

    “Song et. al have determined that if one has at least 30 items a Frailty Index can be calculated.(15)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] source

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    A Frailty Index can be calculated from a CGA in non-cancer patients and predicts length of stay, functional status, and mortality.

    “Rockwood and colleagues have shown that a Frailty Index based on a deficits accumulation principle (i.e. using information from a substantial number of indicators of a person’s health) can be calculated from information in a CGA in non-cancer patients, and used to predict subsequent events such as length of stay, functional status and mortality.(12,13)”
    Quote in the paperSubstantial claim0 of 2 sources checked
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    Premisecitation

    An index derived from data other than a CGA can predict initiation or non-initiation of adjuvant hormonal therapy in older women with breast cancer.

    “We previously reported that an index derived from data other than a CGA can predict initiation or non-initiation of adjuvant hormonal therapy in older women with breast cancer.(16)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study population included various tumor types and stages of disease.

    “our subjects included those with various tumor types and stages of disease”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Hospitalizations are often predictive of subsequent poor outcomes including mortality.

    “Since we know that hospitalizations are often predictive of subsequent poor outcomes including mortality”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Laboratory abnormalities were not included in the DAFI.

    “laboratory abnormalities were not included in the index and possibility might further enhance its utility.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study only reported grade 3+ toxicity, not lower levels of toxicity.

    “it reports only grade 3+ toxicity, while as indicated above lower levels of toxicity may be of importance to older patients”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The Frailty Index was initially operationalized from a CGA by Jones et al and a standard procedure by Searle et al, and predicts death, length of stay, and discharge to long-term care in hospitalized older patients.

    “The Frailty Index was initially operationalized from a CGA by Jones et al and a standard procedure for creating a Frailty Index as described by Searle et al in 2008 (12,14), and shown to predict the risk of death, length of stay, and discharge to long term care in hospitalized older patients.(13)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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    Premisecitation

    Clinicians and investigators find a summary measure useful for stratification and outcome prediction.

    “Though the individual components of the CGA are needed to direct specific interventions, clinicians and investigators find having a summary measure useful for stratification and outcome prediction (19).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] source

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    Premisecitation

    The CGA is now being used more widely in clinical trials and practice.

    “is now being used more widely in clinical trials and in practice (25,26)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Study design and conductnone given

    Bonferroni correction was used to correct for multiple testing for the five outcomes.

    “Bonferroni correction was used to correct for multiple testing for these five outcomes.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Frailty is a summary measure of the impacts of aging and disease on health status and represents vulnerability and risk for adverse outcomes.

    “Frailty in a sense is a summary measure of the impacts of aging and disease on a patient’s health status and has been shown to represent a state of vulnerability and risk for adverse outcomes.(4)”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    The frailty categories were defined as robust/non-frail 0.0<0.2, pre-frail 0.2<0.35, and frail ≥0.35.

    “Our cutpoints were as follows: Robust/Non-frail: 0.0 < 0.2; Pre-frail: 0.2 < 0.35; Frail: ≥ 0.35.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [15] source

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  • May combine two claims.

    Interpretationown data

    Frailty status determined by the DAFI is associated with outcomes likely due to chemotherapy toxicity and with outcomes likely due to age-related physiologic and functional deficits.

    “The frailty status so determined is associated both with outcomes likely due to chemotherapy toxicity as well as those likely due to age related physiologic and functional deficits and thus can be useful in the overall assessment of the patient.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Variables were selected because they are associated with health status, generally increase with age, are not universal in older age, and cover a range of systems.

    “Variables were selected because they are associated with health status, generally increase with age, are not universal in older age, and cover a range of systems (14).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] source

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  • May combine two claims.

    Study design and conductown data

    The Youden optimal cutpoint from logistic regression was comparable to the cutpoint between non-frail and pre-frail, supporting that cutpoint as reasonable for comparisons.

    “When we fit logistic regression to each outcome using the frailty index as the independent predictor, the Youden optimal cutpoint was comparable to the cutpoint between non-frail and prefrail, thus validating this as a reasonable cutpoint for comparisons.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The self-administered CGA has been shown to be feasible, taking less than 30 minutes with all but 5 minutes patient self-reported.

    “since the self-administered CGA has been shown to be feasible (less than 30 minutes, of which all but 5 minutes are patient self-reported) (9,10)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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29 of 29

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Frail count reported as 52 in Abstract but 53 in Results

    Minor

    The abstract and the later Results section give different counts for the frail group. This changes the category total and makes the paper internally inconsistent about the number of frail patients.

  • Laboratory measures are described as both included and excluded

    Minor

    The Methods section lists basic laboratory values among the index items, but the Discussion says laboratory abnormalities were not included in the index.

  • Frail-patient count differs between abstract and results

    Minor

    The abstract reports 52 frail patients, while the Results section reports 53. The abstract's three group counts also total 499, whereas the Results counts total the stated cohort of 500.

3 of 3

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Authors
Cohen, H. J., Smith, D., Sun, C., Tew, W., Mohile, S. G., Owusu, C., Klepin, H. D., Gross, C. P., Lichtman, S. M., Gajra, A., Filo, J., Katheria, V., Hurria, A., & for the Cancer and Aging Research Group
Affiliations
  • Duke Medical Center (US)
  • QIMR Berghofer Medical Research Institute (AU)
  • City Of Hope National Medical Center (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • University of Rochester Medicine (US)
  • University Hospitals Seidman Cancer Center (US)
  • Atrium Health Wake Forest Baptist (US)
  • Yale University (US)
  • SUNY Upstate Medical University (US)
Corresponding author
Cohen, Harvey Jay
ORCID
Venue
Cancer
Publisher
Wiley
Published
2016-08-16
Volume
122
Issue
24
Pages
3865-3872
ISSN
  • 0008-543X (ISSN-L)
  • 1097-0142
DOI
10.1002/cncr.30269
PMC
PMC5138076
OpenAlex
W2507232749
Cited by
203
References
27
Citations by year
2026: 14 · 2025: 12 · 2024: 26 · 2023: 29 · 2022: 33 · 2021: 28 · 2020: 13 · 2019: 13 · 2018: 19 · 2017: 14 · 2016: 2
FWCI
9.19
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health/National Cancer Institute Cancer Center (P30 CA008748 (S.M.L.))
  • Survey Research Core from the National Cancer Institute of the National Institutes of Health (P30CA033572)
  • National Institutes of Health to A.H (K23 AG026749-01), C.P.G. (1 K08 AG24842), H.D.K. (K23 AG038361))
  • American Society of Clinical Oncology to A.H
  • National Institute on Aging at the National Institutes of Health to H.J.C. (1P30 AG028716)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
Keywords
frailty, deficit accumulation frailty index, comprehensive geriatric assessment, elderly cancer patients, chemotherapy toxicity, hospitalization, treatment discontinuation
MeSH terms
Aged, Aged, 80 and over, Aging, Antineoplastic Agents, Female, Humans, Male, Neoplasms, Risk Factors, Geriatric Assessment

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