Characteristics Associated With Functional Changes During Systemic Cancer Treatments: A Systematic Review Focused on Older Adults

Authors:
Kah Poh Loh Division of Hematology/Oncology, Department of Medicine, James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York;

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Vivian Lam Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California;

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Katey Webber School of Public Health, University of California, Berkeley, Berkeley, California;

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Simran Padam Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California;

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Mina S. Sedrak Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California;

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Vivek Musinipally Department of Adult and Family Medicine, Kaiser Permanente, San Francisco, California;

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Madison Grogan Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio;

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Carolyn J. Presley Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio;

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Janice Grandi Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California;

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Chandrika Sanapala Division of Hematology/Oncology, Department of Medicine, James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York;

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Daniel A. Castillo Edward G. Miner Library, University of Rochester School of Medicine and Dentistry, Rochester, New York; and

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Grace DiGiovanni Division of Hematology/Oncology, Department of Medicine, James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York;

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Supriya G. Mohile Division of Hematology/Oncology, Department of Medicine, James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York;

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Louise C. Walter Division of Geriatrics, University of California, San Francisco, and
San Francisco Veterans Affairs Medical Center, San Francisco, California.

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Melisa L. Wong Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California;
Division of Geriatrics, University of California, San Francisco, and
San Francisco Veterans Affairs Medical Center, San Francisco, California.

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Background: Maintaining functional status is important to older adults with cancer, but data are limited on how systemic treatments affect functional status. We systematically reviewed changes in functional status during systemic cancer treatments and identified characteristics associated with functional decline and improvement. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Register of Controlled Trials for articles examining characteristics associated with functional changes in older adults during systemic cancer treatment published in English between database inception and January 11, 2019 (PROSPERO CRD42019123125). Findings were summarized with descriptive statistics. Study characteristics between older adult–specific and non–older adult–specific studies were compared using the Fisher exact test. Results: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 44 studies, which enrolled >8,400 patients; 39% of studies focused on older adults (1 study enrolled adults aged ≥60 years, 10 enrolled adults aged ≥65 years, and 6 enrolled adults aged ≥70 years). Almost all studies (98%) used patient-reported outcomes to measure functional status; only 20% used physical performance tests. Reporting of functional change was heterogeneous, with 48% reporting change scores. Older adult–specific studies were more likely to analyze functional change dichotomously (29% vs 4%; P=.008). Functional decline ranged widely, from 6% to 90%. The most common patient characteristics associated with functional decline were older age (n=7 studies), worse performance status (n=4), progressive disease status (n=4), pain (n=4), anemia (n=4), and worse nutritional status (n=4). Twelve studies examined functional improvement and identified 11 unique associated characteristics. Conclusions: Functional decline is increasingly recognized as an important outcome in older adults with cancer, but definitions and analyses are heterogeneous, leading to a wide range of prevalence. To identify patients at highest risk of functional decline during systemic cancer treatments, trials need to routinely analyze functional outcomes and measure characteristics associated with decline (eg, nutrition).

Submitted August 7, 2020; final revision received October 30, 2020; accepted for publication October 12, 2020.

Published online April 15, 2021.

Author contributions: Literature search: Loh, Lam, Castillo, Wong. Study design: Loh, Lam, Webber, Castillo, Walter, Wong. Data analysis and interpretation: Loh, Lam, Webber, Padam, Sedrak, Musinipally, Grogan, Presley, Grandi, Sanapala, DiGiovanni, Mohile, Walter, Wong. Manuscript preparation: Loh, Lam, Wong. Critical revision: All authors.

Disclosures: Dr. Loh has disclosed serving as a consultant for Pfizer and Seattle Genetics. Dr. Sedrak has disclosed receiving grant/research support from Seattle Genetics, Novartis, Eli Lilly, and Pfizer. Dr. Wong has disclosed having an immediate family member who is employed of Genentech with stock ownership. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was supported by the NCI of the NIH under award numbers K99CA237744 (K.P. Loh) and K12CA001727 (M.S. Sedrak); the National Institute on Aging of the NIH under grants R03AG064377 (M.S. Sedrak), K24AG056589 and R33AG059206 (S.G. Mohile), P30AG044281 (L.C. Walter and M.L. Wong), and K76AG064431 and R03AG056439 (M.L. Wong); a Wilmot Research Fellowship Award (K.P. Loh); and funding from the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center (M.L. Wong).

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Melisa L. Wong, MD, Divisions of Hematology/Oncology and Geriatrics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 550 16th Street, Box 1770, San Francisco, CA 94143. Email: melisa.wong@ucsf.edu

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