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.”
Table 1: Predictors of Chemotherapy Toxicity, and Scoring Algorithm
Figure: Ability of (A) Risk Score vs (B) Physician-Rated Karnofsky Performance Status (KPS) to Predict Chemotherapy Toxicity
Table 2: Geriatric Assessment: Key Questions for the Oncologist to Consider in Treatment Planning, and Potential Interventions
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.[1] Often the assessment is based on a gestalt “She appears younger than her stated age”; or the patient’s fitness is indicated by Karnofsky[2] or Eastern Cooperative Oncology Group[3] 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).
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).[4] 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.[5] 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.
Chemotherapy prediction tools identify where a patient falls on the spectrum of toxicity risk from cancer therapy by pinpointing areas of vulnerability. A geriatric assessment should also be used, to provide a sense of the “functional age” of a given older adult patient. In addition to an evaluation of an individual’s functional status, comorbidity, psychological state, social support, cognition, and nutritional status, the geriatric assessment includes a medication review, to evaluate for polypharmacy and potentially inappropriate medications with a high risk of side effects in older adults.[6]
Although the term “geriatric assessment” may sound time-consuming and even daunting, this process can be tailored to an oncology practice in order to meet its specific needs and accommodate time constraints. Geriatric assessment is important because it can identify potential areas of vulnerability in an older adult and serve as a basis for targeted interventions. The components of a geriatric assessment are summarized in Table 2.[7] Functional status is measured by the ability to perform activities of daily living (those required to maintain independence in the home, such as an ability to bathe, dress, toilet, transfer, feed oneself, and maintain continence) and instrumental activities of daily living (those needed to maintain independence in the community, such as the ability to shop, take transportation, manage one’s finances, take medications, prepare meals).[8,9] An assessment of comorbidity evaluates other health problems and their potential impact on cancer therapy, as well the risk of overall mortality independent of cancer treatment. Nutritional status can be evaluated by simple metrics such as unintentional weight loss or low body mass index, which predict chemotherapy toxicity and increased risk of mortality. An evaluation of psychological state includes an assessment of anxiety and depression, which are often underdiagnosed in patients with cancer in general, but particularly in older adults who may present with more somatic symptoms compared to younger patients. Last, an assessment of social support determines whether support is present to assist the patient through treatment, especially if a decline in functional status occurs, as well as the patient’s ability to seek medical attention if he or she experiences chemotherapy toxicity. Part of this assessment should include an appraisal of whether the patient is a caregiver for another person, such as an aging spouse. Back-up provisions must be discussed in case the patient is unable to attend to caregiving duties during chemotherapy treatment.
There are many ways to perform a geriatric assessment, and one size does not fit all. Although time is often cited as a constraint, today more efficient screening tools are available. Furthermore, a primarily self-administered geriatric assessment, devised by the Cancer and Leukemia Group B, covers well-validated measures of geriatric assessment.[10] Feasibility data show that approximately 80% of patients can complete the patient self-report portion without assistance.[10,11] An internet-based version provides a summary of results for the healthcare team (www.mycarg.org).
Specific considerations regarding organ reserve should be evaluated in addition to performing a geriatric assessment.[12] Older adults are at risk for chemotherapy toxicity because of decreased bone marrow reserve, which occurs with aging. Receipt of polychemotherapy, in particular, can place an older adult at risk for toxicity; hence, single sequential-agent regimens should be considered, and further research regarding the efficacy of this approach is needed, particularly in the adjuvant setting. Primary prophylaxis with growth factors should be considered as per guidelines, with recognition that age ≥ 65 years is a risk factor for neutropenia-associated complications.[13,14]
Aging brings a decline in renal function, and because of the reduction in muscle mass that occurs with aging, serum creatinine levels can remain “normal” even in the setting of reduced renal function. A creatinine clearance test is needed in order to accurately characterize renal function and to dose renally metabolized drugs accordingly. As with patients of any age, cardiac function should be assessed prior to using drugs that pose a risk of cardiac toxicity. Hepatic function should be considered in patients of any age. Hypertension and heart-related conditions are the most common comorbidities facing older adults, and even if a cardiac ejection fraction test is normal, efforts should be made to decrease/optimize cardiac risk factors prior to and during cancer therapy. Patients should be encouraged to use their eyeglasses and/or hearing aides as necessary, especially when discussing risks/benefits of cancer therapy and specific side effects that will require immediate attention. Instructions should be written in large black letters on white paper, to maximize readability. If the patient is hearing-impaired and does not have a hearing aid, use a hand-held amplifier to improve communication.
Oncologists are called on daily to assess “fit” older persons for cancer therapy. An individual’s level of physiological reserve becomes unmasked during cancer therapy when the need arises to rely on this reserve. An in-depth assessment is essential in quantifying the level of an older adult’s fitness. Tools can assist with this evaluation, including chemotherapy toxicity calculators and web-based geriatric assessment scales. Integrating these tools into oncology practice will be well worth the time and effort for both the patient and the oncology care team.
Financial Disclosure:Dr. Hurria receives research support from Celgene and GlaxoSmithKline and is a consultant to GTx and Seattle Genetics. Dr. Siccion has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
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.
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