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Frailty Index, Not Age, Predicts Treatment Outcomes and Adverse Events for Older Adults with Cancer

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Abstract

Background

Frailty is an indicator of individual vulnerability and differentiates health status among people of the same chronological age.

Objectives

This study aimed to determine whether baseline frailty index (FI) was associated with systemic anticancer therapy treatment outcomes in older adults with solid cancers.

Design

Retrospective cohort study.

Setting

Major metropolitan outpatient oncology service.

Participants

Adults aged over 65 years with a solid malignancy who had been referred for consideration of systemic therapy, and had completed a baseline frailty assessment between January 2019 and July 2021.

Measurements

Frailty had been prospectively assessed with a 58-item FI derived from a geriatric oncology nurse assessment prior to initial oncologist appointments. Primary outcome was treatment completion, and secondary outcomes included incidence of high-grade treatment-related toxicity or unplanned hospital admissions, and survival outcomes. Univariate and multivariable regression analyses were conducted to test the association between treatment outcomes and baseline FI. Co-variates included age, sex, performance status, treatment intent, and stage. Kaplan-Meier and cox proportional hazard analysis were conducted for survival analysis.

Results

The median FI (IQR) was 0.24 (0.15–0.31) and 43% were frail (FI>0.25). FI was positively correlated with ECOG, however 28% of ECOG 0–1 were frail. In multivariable regression analyses, each 0.10 increase in FI was associated with an increased likelihood of not completing or not receiving treatment (OR 1.37, 95% CI 1.02–1.84; p=.04), treatment-related toxicity (OR 1.60, 95% CI 1.14–2.23; p<.01) and unplanned hospital admissions (OR 1.61; 95% CI 1.16–2.25; p<.01). Frail patients had increased mortality (adjusted HR 2.81, 95% CI 1.42–5.56; p<.01). Age did not predict treatment completion, toxicities, or survival.

Conclusion

Baseline FI is a granular measure that can help to identify frailer older patients who are more likely to require tailored therapy and support, and less frail older patients who are more likely to tolerate treatment.

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Availability of data: Data available from corresponding author on reasonable request with approval from data custodian at Princess Alexandra Hospital.

Abbreviations

FI:

Frailty index

ECOG:

Eastern Cooperative Oncology Group

PS:

Performance status.

References

  1. Australian Institute of Health and Welfare. Cancer data in Australia. Canberra: AIHW; 2021.

    Google Scholar 

  2. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62. https://doi.org/10.1016/s0140-6736(12)62167-9

    Article  PubMed  Google Scholar 

  3. Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. Cmaj. 2005;173(5):489–95. https://doi.org/10.1503/cmaj.050051

    Article  PubMed  PubMed Central  Google Scholar 

  4. Burn R, Hubbard RE, Scrase RJ, Abey-Nesbit RK, Peel NM, Schluter PJ, et al. A frailty index derived from a standardized comprehensive geriatric assessment predicts mortality and aged residential care admission. BMC Geriatr. 2018;18(1):319. https://doi.org/10.1186/s12877-018-1016-8

    Article  PubMed  PubMed Central  Google Scholar 

  5. Handforth C, Clegg A, Young C, Simpkins S, Seymour MT, Selby PJ, et al. The prevalence and outcomes of frailty in older cancer patients: a systematic review. Ann Oncol. 2015;26(6):1091–101. https://doi.org/10.1093/annonc/mdu540

    Article  CAS  PubMed  Google Scholar 

  6. Hernandez Torres C, Hsu T. Comprehensive Geriatric Assessment in the Older Adult with Cancer: A Review. Eur Urol Focus. 2017;3(4–5):330–9. https://doi.org/10.1016/j.euf.2017.10.010

    Article  PubMed  Google Scholar 

  7. Mohile SG, Dale W, Somerfield MR, Schonberg MA, Boyd CM, Burhenn PS, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. Journal of Clinical Oncology. 2018;36(22):2326–47. https://doi.org/10.1200/jco.2018.78.8687

    Article  PubMed  PubMed Central  Google Scholar 

  8. Puts MT, Tapscott B, Fitch M, Howell D, Monette J, Wan-Chow-Wah D, et al. A systematic review of factors influencing older adults’ decision to accept or decline cancer treatment. Cancer Treat Rev. 2015;41(2):197–215. https://doi.org/10.1016/j.ctrv.2014.12.010

    Article  PubMed  Google Scholar 

  9. Mohile SG, Epstein RM, Hurria A, Heckler CE, Canin B, Culakova E, et al. Communication With Older Patients With Cancer Using Geriatric Assessment: A Cluster-Randomized Clinical Trial From the National Cancer Institute Community Oncology Research Program. JAMA Oncol. 2020;6(2):196–204. https://doi.org/10.1001/jamaoncol.2019.4728

    Article  PubMed  Google Scholar 

  10. Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen ML, Extermann M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32(24):2595–603. https://doi.org/10.1200/jco.2013.54.8347

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dale W, Klepin HD, Williams GR, Alibhai SMH, Bergerot C, Brintzenhofeszoc K, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update. Journal of Clinical Oncology. 2023. https://doi.org/10.1200/jco.23.00933

  12. Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K. A standard procedure for creating a frailty index. BMC Geriatr. 2008;8:24. https://doi.org/10.1186/1471-2318-8-24

    Article  PubMed  PubMed Central  Google Scholar 

  13. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62(7):722–7. https://doi.org/10.1093/gerona/62.7.722

    Article  PubMed  Google Scholar 

  14. McCarthy AL, Peel NM, Gillespie KM, Berry R, Walpole E, Yates P, et al. Validation of a frailty index in older cancer patients with solid tumours. BMC Cancer. 2018;18(1):892. https://doi.org/10.1186/s12885-018-4807-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Reiser E, Pötsch N, Seebacher V, Reinthaller A, Wimazal F, Fleischmann E, et al. Impact of frailty on the management of patients with gynecological cancer aged 80 years and older. Arch Gynecol Obstet. 2021;303(2):557–63. https://doi.org/10.1007/s00404-020-05807-9

    Article  PubMed  Google Scholar 

  16. Cohen HJ, Smith D, Sun CL, Tew W, Mohile SG, Owusu C, et al. Frailty as determined by a comprehensive geriatric assessment-derived deficit-accumulation index in older patients with cancer who receive chemotherapy. Cancer. 2016;122(24):3865–72. https://doi.org/10.1002/cncr.30269

    Article  PubMed  Google Scholar 

  17. Guerard EJ, Deal AM, Chang Y, Williams GR, Nyrop KA, Pergolotti M, et al. Frailty Index Developed From a Cancer-Specific Geriatric Assessment and the Association With Mortality Among Older Adults With Cancer. J Natl Compr Canc Netw. 2017;15(7):894–902. https://doi.org/10.6004/jnccn.2017.0122

    Article  PubMed  Google Scholar 

  18. Hembree T, Theou O, Thirlwell S, Reich RR, Cao B, Sehovic M, et al. A simple test-based frailty index to predict survival among cancer patients with an unplanned hospitalization: An observational cohort study. Cancer Medicine. 2021;10(17):5765–74. https://doi.org/10.1002/cam4.4107

    Article  PubMed  PubMed Central  Google Scholar 

  19. Jin X, Ren Y, Shao L, Guo Z, Wang C, He Y, et al. Prevalence of frailty and prediction of mortality in Chinese cancer patients using a frailty index-based clinical algorithm—A multicentre study. Cancer Medicine. 2021;10(18):6207–17. https://doi.org/10.1002/cam4.4155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gomes F, Tay R, Chiramel J, Califano R. The Role of Targeted Agents and Immunotherapy in Older Patients with Non-small Cell Lung Cancer. Drugs & Aging. 2018;35(9):819–34. https://doi.org/10.1007/s40266-018-0573-z

    Article  CAS  Google Scholar 

  21. Fletcher JA, Logan B, Reid N, Gordon EH, Ladwa R, Hubbard RE. How frail is frail in oncology studies? A scoping review. BMC Cancer. 2023;23(1). https://doi.org/10.1186/s12885-023-10933-z

    Google Scholar 

  22. Rockwood K, Andrew M, Mitnitski A. A Comparison of Two Appoaches to Measuring Frailty in Elderly People. Journal of Gerontology. 2007;62A:738–43. https://doi.org/10.1093/gerona/62.7.738

    Google Scholar 

  23. Rockwood K, Mitnitski A. Limits to deficit accumulation in elderly people. Mech Ageing Dev. 2006;127(5):494–6. https://doi.org/10.1016/j.mad.2006.01.002

    Article  PubMed  Google Scholar 

  24. Bruijnen CP, Van Harten-Krouwel DG, Koldenhof JJ, Emmelot-Vonk MH, Witteveen PO. Predictive value of each geriatric assessment domain for older patients with cancer: A systematic review. Journal of Geriatric Oncology. 2019;10(6):859–73. https://doi.org/10.1016/j.jgo.2019.02.010

    Article  PubMed  Google Scholar 

  25. Schulkes KJ, Souwer ET, Hamaker ME, Codrington H, van der Sar-van der Brugge S, Lammers JJ, et al. The Effect of A Geriatric Assessment on Treatment Decisions for Patients with Lung Cancer. Lung. 2017;195(2):225–31. https://doi.org/10.1007/s00408-017-9983-7

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wang Y, Zhang R, Shen Y, Su L, Dong B, Hao Q. Prediction of chemotherapy adverse reactions and mortality in older patients with primary lung cancer through frailty index based on routine laboratory data. Clin Interv Aging. 2019;Volume 14:1187–97. https://doi.org/10.2147/cia.s201873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Narasimhulu DM, McGree ME, Weaver AL, Jatoi A, LeBrasseur NK, Glaser GE, et al. Frailty is a determinant of suboptimal chemotherapy in women with advanced ovarian cancer. Gynecologic Oncology. 2020;158(3):646–52. https://doi.org/10.1016/j.ygyno.2020.05.046

    Article  CAS  PubMed  Google Scholar 

  28. Ruiz J, Miller AA, Tooze JA, Crane S, Petty WJ, Gajra A, et al. Frailty assessment predicts toxicity during first cycle chemotherapy for advanced lung cancer regardless of chronologic age. J Geriatr Oncol. 2019;10(1):48–54. https://doi.org/10.1016/j.jgo.2018.06.007

    Article  PubMed  Google Scholar 

  29. van Walree IC, Scheepers E, van Huis-Tanja L, Emmelot-Vonk MH, Bellera C, Soubeyran P, et al. A systematic review on the association of the G8 with geriatric assessment, prognosis and course of treatment in older patients with cancer. J Geriatr Oncol. 2019;10(6):847–58. https://doi.org/10.1016/j.jgo.2019.04.016

    Article  PubMed  Google Scholar 

  30. Hamaker M, Lund C, Te Molder M, Soubeyran P, Wildiers H, Van Huis L, et al. Geriatric assessment in the management of older patients with cancer - A systematic review (update). Journal of Geriatric Oncology. 2022. https://doi.org/10.1016/j.jgo.2022.04.008

  31. Kalsi T, Babic-Illman G, Fields P, Hughes S, Maisey N, Ross P, et al. The impact of low-grade toxicity in older people with cancer undergoing chemotherapy. British Journal of Cancer. 2014;111(12):2224–8. https://doi.org/10.1038/bjc.2014.496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. To THM, Soo WK, Lane H, Khattak A, Steer C, Devitt B, et al. Utilisation of geriatric assessment in oncology - a survey of Australian medical oncologists. Journal of Geriatric Oncology. 2019;10(2):216–21. https://doi.org/10.1016/j.jgo.2018.07.004

    Article  PubMed  Google Scholar 

  33. Kirkhus L, Šaltytė Benth J, Rostoft S, Grønberg BH, Hjermstad MJ, Selbæk G, et al. Geriatric assessment is superior to oncologists’ clinical judgement in identifying frailty. British Journal of Cancer. 2017;117(4):470–7. https://doi.org/10.1038/bjc.2017.202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Antonio M, Saldaña J, Linares J, Ruffinelli JC, Palmero R, Navarro A, et al. Geriatric assessment may help decision-making in elderly patients with inoperable, locally advanced non-small-cell lung cancer. British Journal of Cancer. 2018;118(5):639–47. https://doi.org/10.1038/bjc.2017.455

    Article  PubMed  PubMed Central  Google Scholar 

  35. Rostoft S, O’Donovan A, Soubeyran P, Alibhai SMH, Hamaker ME. Geriatric Assessment and Management in Cancer. Journal of Clinical Oncology. 2021;39(19):2058–67. https://doi.org/10.1200/jco.21.00089

    Article  PubMed  Google Scholar 

  36. Li D, Sun C-L, Kim H, Soto-Perez-de-Celis E, Chung V, Koczywas M, et al. Geriatric Assessment-Driven Intervention (GAIN) on Chemotherapy-Related Toxic Effects in Older Adults With Cancer: A Randomized Clinical Trial. JAMA Oncology. 2021. https://doi.org/10.1001/jamaoncol.2021.4158

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Funding

Funding: The researchers also acknowledge the inkind funding and support provided by Division of Cancer Services, Princess Alexandra Hospital to conduct this research.

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Authors and Affiliations

  1. Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, Queensland, 4102, Australia

    J. Fletcher, R. E. Hubbard, R. Berry, M. Weston, E. Walpole, R. Kimberley & R. Ladwa

  2. Faculty of Medicine, The University of Queensland, 199 Ipswich Road, Woolloongabba, Queensland, 4102, Australia

    J. Fletcher, R. E. Hubbard, E. Walpole, D. A. Thaker & R. Ladwa

  3. Centre for Health Services Research, Faculty of Medicine, The University of Queensland, 199 Ipswich Road, Woolloongabba, QLD, 4102, Australia

    J. Fletcher, N. Reid & R. E. Hubbard

  4. Metro North Hospital and Health Service, Herston, Queensland, Australia

    D. A. Thaker

  5. Division of Cancer Services, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, QLD, 4102, Australia

    J. Fletcher

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  1. J. Fletcher
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Contributions

Author contributions: Study concepts: Fletcher J, Reid N, Hubbard RE, Berry R, Weston M, Walpole E, Ladwa R. Study design: Fletcher J, Reid N, Hubbard RE, Ladwa R. Data acquisition: Fletcher J, Berry R. Quality control of data and algorithms: Fletcher J. Data analysis and interpretation: Fletcher J, Reid N, Hubbard RE, Thaker DA, Ladwa R. Statistical analysis: Fletcher J, Reid N. Manuscript preparation: Fletcher J. Manuscript editing: Fletcher J, Reid N, Hubbard RE, Thaker DA, Ladwa R. Manuscript review: Fletcher J, Reid N, Hubbard RE, Berry R, Weston M, Walpole E, Kimberley R, Thaker DA, Ladwa R. All authors read and approved the final manuscript.

Corresponding author

Correspondence to J. Fletcher.

Ethics declarations

Conflicts of interest: The authors declare that they have no conflicts of interest.

Ethics approval: This study received ethics approval from local institution human research and ethics committee (HREC/2021/QMS/77072 (Sep ver 2)).

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Consent for publication: All authors have seen and approved the final manuscript, and agree to its submission to the Journal of Frailty & Aging.

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Fletcher, J., Reid, N., Hubbard, R.E. et al. Frailty Index, Not Age, Predicts Treatment Outcomes and Adverse Events for Older Adults with Cancer. J Frailty Aging (2024). https://doi.org/10.14283/jfa.2024.22

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  • DOI: https://doi.org/10.14283/jfa.2024.22

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