The Washington Manual of Oncology, 3 Ed.

Care of the Older Adult with Cancer

Tanya M. Wildes

  I. INTRODUCTION. Cancer is a disease of aging; the incidence of most malignancies increases with age. Over half of cancer diagnoses and nearly 70% of cancer deaths occur in patients over the age of 65. With the aging of the population, the number of older adults with cancer will increase by 67% by 2030. There are significant differences in cancer-specific death rates between older and younger individuals. These age-related disparities likely differ in cause among different malignancies, but contributory factors include differences in screening, more advanced stage at presentation, differences in biology of disease across the age spectrum, and less aggressive treatment in older adults.

  1.  Knowledge gaps in treatment of older adults with cancer. Contributing to differences in treatment between older and younger adults are the increased vulnerability of older adults to toxicity of therapy and the underrepresentation of older adults in clinical trials. Older adults are less likely to be enrolled in clinical trials owing to restrictive exclusion criteria based on organ function or comorbidities. In addition, clinicians are less likely to propose participation in a clinical trial, though, if asked, older adults are as likely as younger adults to agree to participate. This under-representation of older adults in clinical trials has resulted in substantial gaps in our knowledge about the safety and efficacy of cancer therapies when applied to older adults. With the growth in the number of older adults with cancer, thankfully, increasing attention is now being directed to the need to increase our knowledge base on treating older adults with cancer.
  2. BIOLOGY OF CANCER IN OLDER ADULTS. There is a commonly held perception that, overall, cancer in older adults is less aggressive than in younger adults. Breast cancer is one example of this, being more likely to be hormone-receptor positive. Overall, however, most cancers do not exhibit substantial age-related differences in biology. In some cases, older age is actually associated with more aggressive, treatment-resistant biology, as in acute myeloid leukemia and diffuse large B-cell lymphoma. Thus, in older adults, treatment decisions are largely not driven by biology of disease, but rather by the patient’s individual health status.

III. COMPREHENSIVE GERIATRIC ASSESSMENT. Increasing chronologic age is associated with an increasing prevalence of comorbidities and functional or cognitive impairment. A comprehensive geriatric assessment (CGA) is a multidimensional assessment of geriatric domains (Table 35-1). While the screening tools used are often referred to as “CGA,” in geriatrics, CGA refers to the multidisciplinary assessment, interpretation of screening tools, and recommended tailored interventions.

TABLE 35-1

Domains of a CGA

Domain

Commonly used scales/measures

Comorbidities

• Charlson comorbidity index

• Cumulative illness rating scale—geriatrics

• Adult comorbidity evaluation-27 (ACE-27)

• Hematopoietic cell transplantation comorbidity index (HCT-CI)

Physical performance

• Timed up and go

• Short physical performance battery

Functional status

• Activities of daily living

  • Bathing

  • Continence

  • Dressing

  • Toileting

  • Transferring

  • Feeding

• Instrumental activities of daily living

  • Using telephone

  • Getting to places out of walking distance

  • Shopping for groceries

  • Preparing meals

  • Doing housework

  • Doing laundry

  • Taking medications

  • Managing finances

• Performance status

Cognition

• Short Blessed test

• Montreal cognitive assessment (MOCA) (http://www.mocatest.org)

• Mini-mental status examination

Depression

• Geriatric depression scale (GDS)

• Patient-health questionnaire-9 (PHQ-9)

Polypharmacy and inappropriate medications

• Beers criteria for potentially inappropriate medications in the elderly

• STOPP/START criteria

       Geriatric syndromes are extremely common in older adults with cancer, and are inadequately described in a routine oncology assessment. Coexisting medical conditions are present in more than 80% of cancer patients over the age of 80. Functional decline or disability refers to the greater need for assistance with daily activities owing to physical or cognitive decline. Cognitive impairment is also common among older adults with cancer, with 15% to 25% in the outpatient setting, and 40% to 50% in the inpatient setting screening positive.

       Furthermore, evaluating only performance status significantly underestimates the level of impairment in an older individual. Comorbidities and functional status are entirely independent. Among older adults with cancer who had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1, 10% were dependent in one or more activities of daily living (ADLs), nearly 40% were dependent in one or more instrumental activities of daily living (IADLs), nearly 30% were cognitively impaired, and 30% were depressed. Thus, PS is an inadequate measure of the heterogeneous health statuses of older adults.

IV. TREATMENT OF CANCER IN OLDER ADULTS

  1.  Surgery. Surgical management of cancers does not differ between older and younger patients overall. Studies that appropriately control for confounders (such as comorbidities, advanced cancer stage, and functional impairment) demonstrate similar outcomes in older and younger patients undergoing cancer surgery. That said, some older adults are at greater risk for postoperative complications. In the Preoperative Assessment of Cancer in the Elderly (PACE) study, dependence in IADLs, self-reported fatigue, and an Eastern Cooperative Oncology Group performance status (PS) of two or more were associated with increased risk of complications of surgery (Crit Rev Onc Hem 2008;65:156). Similarly, dependence in ADLs, IADLs, and poor PS were associated with longer length of stay. Age was not associated with increased 30-day mortality, though male gender, advanced cancer stage, and extent of surgery were. Thus, age alone should not be a primary consideration in decisions regarding cancer surgery; decisions are better made in the context of evaluation of the patient’s individual functional status.
  2.  Radiation. Similarly, age alone is generally not a primary consideration in decision making regarding radiation therapy (RT) for cancer. Some studies have demonstrated greater acute functional decline during chemotherapy in older adults undergoing RT, but similar longer-term outcomes in patients undergoing curative-intent RT. Thus, among patients being treated with curative intent, the initial toxicity may be warranted given the longer-term outcomes. Conversely, among older adults treated with palliative intent, the risk of toxicity and functional decline must be balanced with the potential benefit of therapy. Among patients with glioblastoma, older age is associated with greater toxicity and cognitive impairment related to radiation with concurrent temozolomide. Little is known about predictors of toxicity of RT in older adults with cancer. In a small study of older adults with rectal cancer, comorbidities were associated with greater risk of acute toxicity. The role for evaluation with geriatric assessment in older adults undergoing RT remains to be examined.
  3.  Systemic therapy. Age-related physiologic changes may increase the risk of toxicity of chemotherapy among older adults; these include reduced gastrointestinal motility, decreased splanchnic blood flow, changes in body composition resulting in altered volume of distribution, decreased hepatic blood flow, polypharmacy and drug interactions, and declining renal function (J Clin Oncol 2007;25:1832).
  4.  Chemotherapy. A comprehensive discussion of age-related differences in toxicity of individual chemotherapeutic agents is beyond the scope of this chapter. However, some important themes merit discussion.
  5.  Hematologic toxicity. Older adults are at greater risk for myelosuppression than younger adults, particularly with the exposure to the alkylating agents, due to age-related decreases in hematopoietic stem cell reserve.
  6.  Mucositis. Older adults are at greater for mucositis with fluoropyrimidines, the liposomal anthracyclines, and high-dose melphalan, likely due to decreased ability to respond to mucosal damage.
  7.  Dose adjustments for renal insufficiency. Renal function declines with age. Serum creatinine levels alone are an inadequate reflection of renal function, which is better estimated with an equation, such as the Cockcroft–Gault or Modification of Diet in Renal Disease (MDRD) equation, or measured with a 24-hour urine collection. Many chemotherapeutic agents have not been thoroughly studied in patients with renal insufficiency.
  8.  Targeted agents. A large number of targeted agents have been brought from the bench to clinical trial and into the clinics in the past 15 years. The underenrollment of older adults in clinical trials has resulted in a paucity of data on most of these targeted agents in older adults, particularly older adults with comorbidities. A number of agents, including erlotinib, sorafenib, bevacizumab, imatinib, bortezomib, and lenalidomide, have been shown to have greater toxicity in older adults (Crit Rev Onc Hematol 2011;78:227). In other cases, subgroup analyses of patients fit enough to participate in clinical trials may demonstrate similar efficacy and toxicity, only to be found to have increased toxicity and decreased effectiveness when applied in “real-world” settings, among patients with comorbidities and functional impairment. Caution must be used in using targeted agents in older adults.
  9. PREDICTING TOXICITY OF CHEMOTHERAPY IN OLDER ADULTS. With the increased vulnerability to toxicity and lack of data on treating older adults with cancer, clinicians are left to make decisions by combining clinical trial data and clinical judgment. Several instruments are being evaluated to aid in risk stratification and decision making for older adults considering chemotherapy. In the Cancer and Aging Research Group study, over 500 patients underwent CGA prior to initiation of chemotherapy. Factors including age $73 years, anemia, renal insufficiency, recent falls, hearing impairment, limited ability to walk 1 block, decreased social activities, and requiring assistance with medications predicted greater risk of grade 3 to 5 toxicity of chemotherapy (J Clin Oncol 2011;29:3457). In the Chemotherapy Risk Assessment for High Age Patients (CRASH) trial, diastolic blood pressure, dependence in IADLs, elevated LDH, and the intensity of chemotherapy were associated with hematologic toxicity of chemotherapy, while ECOG PS, cognitive impairment, nutritional compromise, and intensity of chemotherapy were associated with nonhematologic toxicity (Cancer 2012;118:3377).

TABLE 35-2

Interventions for Geriatric Syndromes

Domain

Intervention

Comorbidities

Comanagement with primary care physician

Functional decline

Physical therapy consult

 

Occupational therapy consult

Falls

Physical therapy consult

 

Occupational therapy consult for home-safety evaluation

 

Screen for neuropathy

 

Medication review

Nutritional risk

Consultation with dietitian

 

Social work consult for resource assistance (meals-on-wheels, cancer foundation support for nutritional supplements)

Polypharmacy and inappropriate medications

Medication reconciliation and review

 

Home-health nursing for medication setup

 

Consultation with pharmacist

Lack of social support

Consultation with social worker

VI. PRACTICAL GUIDE TO ADDRESSING GERIATRIC SYNDROMES IN OLDER ADULTS WITH CANCER. Table 35-2 lists some potential interventions for geriatric syndromes identified in older adults.

VII.SURVIVORSHIP IN OLDER ADULTS. With the coming increase in the number of older adults with cancer, there will be a consequent increase in the number of older adult cancer survivors. Older adult cancer survivors are at greater risk for developing geriatric syndromes. In a study of over 12,000 older adults, cancer survivors were more likely to report hearing impairment, incontinence, depression, falls, and osteoporosis. Even after completion of cancer therapy, older adults will remain increasingly vulnerable and will require attention to long-term effects of their cancer therapy.

VIII.SUMMARY. The population is aging, and with the increased incidence of cancer with age, the number of older adults with cancer will increase significantly over the coming years. Older adults may be at increased risk for chemotherapy toxicity, but tools to better predict toxicity are being validated. CGA is a tool that holds promise to aid in individualizing cancer treatment for older adults.

SUGGESTED READINGS

Audisio RA, Pope D, Ramesh HS, et al. Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help: a SIOG surgical task force prospective study. Crit Rev Oncol Hematol 2008;65:156–163.

Exterman 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;118:3377–3786.

Gonsalves W, Ganti AK. Targeted anti-cancer therapy in the elderly. Crit Rev Oncol Hematol 2011;78:227–242.

Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 2011;29:3457–3465.

Lichtman SM, Wildiers H, Chatelut E, et al; International Society of Geriatric Oncology Chemotherapy Taskforce. International Society of Geriatric Oncology Chemotherapy Taskforce: evaluation of chemotherapy in older patients—an analysis of the medical literature. J Clin Oncol 2007;25:1832–1843.



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