Making appropriate treatment decisions for older adults with cancer is one of the most important challenges that oncologists face in daily practice, as the therapy selected depends on an assessment of the patient’s “fitness.” The majority of cancer diagnoses and cancer mortalities occur in older adults, so oncologists make such assessments in this patient group at least several times a day. Often the assessment is based on a gestalt “She appears younger than her stated age”; or the patient’s fitness is indicated by Karnofsky or Eastern Cooperative Oncology Group performance status scores.
However, the aging process is more complex than a gestalt or a single-item assessment of function. In this article, we discuss specific considerations for evaluating patients who appear to be “fit” for chemotherapy treatment, and outline methods for integrating the principles of geriatric medicine to form a clear picture of an older adult’s level of fitness and thus his or her individual risk of significant toxicity from cancer therapy.
Although aging is universally associated with a decrease in physiologic reserve, this process is heterogeneous, often being unapparent during times of rest and only unmasked during times of physical or emotional stress. One can think of the aging process as similar to the gauge on a car’s gas tank. Life starts off on “full.”
At around 30 years of age, people begin to experience a progressive decline in physiologic reserve, which proceeds at a unique pace; hence, the “gas” begins to be used up. Thus, an individual may seem “fit” (ie, have enough “gas”) prior to the start of treatment; however, when placed under stress (ie, cancer therapy), the amount of reserve becomes apparent as the patient “runs out of gas” (manifested as a dose-limiting toxicity).
Calculating Risks of Chemotherapy Toxicity
A variety of tools are available to gauge an individual’s level of reserve, and these should be used even when a patient seems to be “fit” for cancer therapy. In a Cancer and Aging Research Group multicenter study, a total of 500 older adults with cancer were deemed by their treating oncologists to be “fit” for the treatment prescribed and received treatment at their oncologist’s discretion (including the drugs, dosing, and schedule). Fifty-three percent of the cohort experienced a grade 3–5 toxicity as determined by the National Cancer Institute Common Toxicity Criteria for Adverse Events, and among this group there was a 2% incidence of treatment-related mortality. The assessment of “fitness” based on Karnofsky performance status did not adequately identify those at risk—but a predictive model including tumor and treatment variables, laboratory values, and geriatric assessment questions could have better stratified that risk (see Table 1 and Figure). Another model, called CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients), which was developed by Extermann and colleagues, predicts the risk of hematologic and nonhematologic toxicity in older adults. These tools can pinpoint an older adult’s risk of significant toxicity with chemotherapy. They provide a specific platform from which to discuss risk with patients and families.
1. Smith BD, Smith GL, Hurria A, et al. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27:2758-65.
2. Karnofsky D, Burchenal J. The clinical evaluation of chemotherapeutic agents in cancer. In: Macleod CM. Evaluation of chemotherapeutic agents. New York: Columbia University Press; 1948. p. 191-205.
3. Zubrod C, Schneiderman M, Frei E. Appraisal of methods for the study of chemotherapy of cancer in man: comparative therapeutic trial of nitrogen mustard and triethylene thiophosphoramide. J Chronic Dis. 1960;11:7-33.
4. Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29:3457-65.
5. Extermann M, Boler I, Reich RR, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012;118:3377-86.
6. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25:1824-31.
7. Hurria A, Cirrincione C, Muss H, et al. Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. J Clin Oncol. 2011;29:1290-6.
8. Katz S, Ford AB, Moskowitz RW, et al. Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA. 1963;185:914-9.
9. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9:179-86.
10. Hurria A, Gupta S, Zauderer M, et al. Developing a cancer-specific geriatric assessment: a feasibility study. Cancer. 2005;104:1998-2005.
11. Hurria A, Cirrincione CT, Muss HB, et al. Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. J Clin Oncol. 2011;29:1290-6.
12. Hurria A, Wildes T, Blair SL, et al. Senior adult oncology, version 2.2014: clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2014;12:82-126.
13. Crawford J, Armitage J, Balducci L, et al. Myeloid growth factors. J Natl Compr Canc Netw. 2013;11:1266-90.
14. Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47:8-32.
15. Sessums LL, Zembrzuska H Jackson JL. Does this patient have medical decision-making capacity? JAMA. 2011;306:420-7.
16. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60:616-31.