Geriatric Perspectives on Cancer Care and Treatment
Harvey Jay Cohen, M.D., Duke University Medical Center, Durham, North Carolina
Cancer is the second leading cause of death for the growing number of individuals over the age of 65. Geriatrics and oncology share the approach of considering the whole patient. In that respect, many principles of care are similar. In the geriatric approach, however, particular attention is directed toward the situation in which aging-related changes affect the clinical expression, course, and treatment of disease. Applying geriatric principles to the care of elderly cancer patients may be one approach to enhancing care. These principles include recognizing that aging per se is not a disease but a process. It occurs at different rates in different organ systems and in different individuals. It reduces physiologic reserve and makes the elderly more susceptible to many diseases and also increases risks during diagnostic and therapeutic interventions. Improving and maintaining functional capacity is a major goal, as is recognizing the appropriateness of cure vs. care and the importance of comfort care when appropriate. In older individuals, cancer frequently occurs in persons who have other chronic comorbid conditions. They may be multiple in nature and present atypically and sometimes involve both physical and cognitive alterations. Diagnosis and planning for treatment should involve geriatric assessment to evaluate the biological, psychological, socioeconomic, and functional aspects of a patient's condition. Planning for care may incorporate all aspects of the evaluation including age-related alterations in physiologic status, altered functional status, altered pharmacokinetics, comorbidities, cognitive status, quality of life, and caregiver and family issues. All specific cancer-related therapeutic modalities (i.e., surgery, radiation therapy, and chemotherapy) may be affected by age-related changes. However, changes in drug metabolism and excretion demand particular attention. Hopefully, by incorporating these geriatric principles into the care of the elderly patient with malignancies, improved outcomes can be achieved.
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Late Effects of Cancer Treatment
Patricia A. Ganz, M.D., University of California at Los Angeles School of Medicine and Public Health, Jonsson Comprehensive Cancer Center, Los Angeles, California
With the growing number of cancer survivors, there is increased interest in the late effects of cancer treatment. As cancer is primarily a disease of older persons, there is an urgent need to address the interaction of the physiologic late effects of cancer treatment in the aging population as well as in association with various comorbid conditions. This presentation uses a quality-of-life perspective to review what is known about the late effects of various cancer treatments (e.g., surgery, radiation, chemotherapy) and their interaction in multimodal therapies. The tables below describe the content areas to be reviewed:
Table 1. Common Physical and Medical Late Effects of Cancer Treatment
Body changes: scars, disfigurement, amputation
Cardiorespiratory symptoms
Cognitive dysfunction
Fatigue or decreased energy
Immune dysfunction Infertility
Lymphedema Osteoporosis/fractures
Pain
Premature menopause
Second cancers
Sexual dysfunction
Skin sensitivity to UV radiation
Urinary incontinence
Table 2. Psychological Late Effects of Cancer
Concerns about the future, death
Depression, sadness
Feelings of gratitude and good fortune
Health worries, hypervigilance
Inability to make plans
Self-esteem, mastery
Uncertainty and vulnerability
Table 3. Social Late Effects of Cancer
Affinity and altruism
Alienation and isolation
Comparison with peers
Social relationship changes
Socioeconomic concerns: health insurance, job, return to school, financial impact
Table 4. Existential and Spiritual Late Effects of Cancer
Appreciation of life
Changed or new orientation to time and future
Changed values and goals
Concerns about death and dying
Sense of purpose
Example cases are discussed to illustrate the issues cancer survivors face and the strategies that might be used to increase systematic information gathering on this topic.
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Age Differences in Patterns of Cancer Treatment: A Summary and Review of Issues
Vincent Mor, Ph.D., Brown University, Providence, Rhode Island
Cancer is an age-related disease. Most cancers increase progressively with age and some do not peak until after age 85. Over the past 20 years there have been treatment advances in breast, colon, and even lung cancer along with other solid and hematological tumors, making it possible that overall cancer survival might increase. In spite of these advances, however, the proportion of the population with cancer who are receiving treatments that have been shown to be effective varies dramatically according to demographic characteristics of the patients as well as by region of the country. Thus, older persons, people of color, and the poor and uninsured, regardless of color, are less likely to receive "standard" and effective cancer treatment. Although treatment differences associated with race, poverty, and insurance status are attributable to the fact that these groups of individuals have less access to high-quality medical care, there is considerable argument about the legitimacy of the observed age-related differences. The purpose of this talk is to summarize the literature documenting age differences in cancer treatment and to highlight several factors that some suggest "explain" and justify these differences: comorbidity, patient and family preferences, and quality of life versus quantity of survival. Finally, I end by speculating that transmitting the message about the need to treat older cancer patients is difficult because it is conditional not on age but on preexisting health state and changing perspectives on the likelihood of survival.
Despite worldwide evidence about the effectiveness of treatments for early stage breast cancer, age differences persist in the receipt of appropriate therapy (Mor et al., 1985; Silliman et al., 1989; Bergman et al., 1991). Women older than 80 years of age (and younger than 40) have poorer survival rates than others (Chung et al., 1996). A recent analysis of the survival consequences of incomplete breast cancer treatment among older women revealed an adjusted relative risk of 5year mortality of 1.7 (Lash et al., 2001). In the case of lung cancer, advanced age is consistently associated with receiving less aggressive care. Surgery is potentially curative for patients with stages I, II, and IIIa/b non-small cell lung cancer, where preoperative assessment suggests that the patient would not be a respiratory cripple and would be able to undergo surgery. Although there is a slightly increased risk of mortality with age, more than 90% of people aged 80 and older who undergo surgery for lung cancer survive surgery. Yet, research clearly demonstrates that most elderly persons are not offered that treatment option (Greenberg et al., 1983; Mor et al., 1987). Indeed, a multivariate logistic regression model with SEER data found that age was inversely associated with receipt of chemotherapy (AOR 0.46 for each incremental decade of life). Similar findings obtain in the case of colon cancer (Chu, 1986; Mor et al., 1987; Samet et al., 1985). Interventions to reduce these differences in treatment have not been successful in changing physicians' referral patterns (Mor et al., 2001).
Critics of this research suggest that age-related comorbidity accounts for the differences, although many of the studies controlled for it. Others note that patients and their families are unwilling to undergo aggressive treatment, but there is little evidence to support this contention. However, because very old and sick patients are less likely to benefit from treatment in terms of survival, treatment recommendations for the aged are necessarily conditional, which complicates the message and, as we know, reduces its effectiveness. What is needed is research to understand how to best deliver such conditional messages in a manner that will overcome prejudice on the one hand without leading to excessive and unnecessary treatment on the other.
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Treatment Tolerance and Efficacy in the Elderly
Richard L. Schilsky, M.D., Cancer and Leukemia Group B, University of Chicago, Illinois
Cancer is largely a disease of the elderly and as the percentage of the U.S. population over the age of 65 continues to increase, a rapid expansion in the number of cancer cases among elderly individuals will occur. Special considerations in older cancer patients include the impact of comorbidity, organ dysfunction, drug interactions, cognitive dysfunction, and social support on treatment tolerance and outcomes. Because of these issues, elderly cancer patients display a great deal more interindividual variability than do younger patients and therefore represent a difficult challenge in treatment optimization. Although changes in body composition and organ function occur with age, there is little evidence that these changes result in significant differences in chemotherapy tolerance among older patients. For example, paclitaxel clearance declines with age and results in increased neutropenia but no clinically significant change in infectious complications or hospitalization rates.
The larger number of drugs used by older individuals has the potential to increase the frequency of drug interactions with chemotherapy agents, particularly those metabolized by CYP3A4. Although the elderly are underrepresented in cancer clinical trials, it is possible to examine the effect of age on treatment outcomes in many studies. In a study of non-small cell lung cancer patients up to age 80 years, the CALGB found no differences by age in treatment discontinuation for toxicity, response rate, or survival after treatment with cisplatin-based chemotherapy. In a meta-analysis of adjuvant chemotherapy trials for stage B2C colon cancer, the NCCTG found a similar benefit from treatment for all age groups examined with little difference in toxicity by age cohort.
Breast cancer in older women has been extensively studied and appears to have biological features associated with more indolent disease. The benefits of adjuvant hormone and chemotherapy are equivalent in older and younger women, and older women with metastatic disease achieve response rates, TTP, and survival similar to those of younger women following doxorubicin-based chemotherapy.
Women over age 70 years with early stage breast cancer are more likely to die from non-cancer-related causes than from complications of breast cancer and should be treated conservatively. Older patients with non-Hodgkin’s lymphoma appear to have worse survival than younger patients independent of stage and performance status, yet a priori attenuation of chemotherapy doses and death due to comorbid illness likely contribute to the apparently worse outcomes. Vigorous supportive care, including the use of hematopoietic growth factors, appears to permit maintenance of dose intensity with acceptable toxicity in patients up to age 70 years.
Important areas of future research include better defining and assessing functional status and "functional reserve," studying drug interactions between chemotherapy agents and other drugs commonly used by the elderly, and developing treatment regimens that are less toxic but retain the efficacy of established treatment programs.
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The Effect of Comorbidity on Cancer
William A. Satariano, Ph.D., M.P.H., Division of Epidemiology, School of Public Health, University of California, Berkeley, California
Comorbidity (i.e., the presence of two or more concurrent health conditions in the same person) has a significant effect on cancer incidence and survival. Specific health conditions, such as diabetes, have been shown to increase the risk of particular cancers. Other conditions (e.g., cardiovascular disease) have an adverse effect on the quality and duration of life among cancer patients.
Cancer patients aged 65 and older are more likely than younger cancer patients to have comorbid conditions. For that reason, comorbidity may significantly complicate the treatment protocols for older patients.
The purpose of this presentation is (a) to critically review the current methods and sources of data for studies of comorbidity, and (b) to identify and evaluate new directions for research on the effects of comorbidity on cancer treatment and prognosis. Criteria for the selection of comorbid conditions include the overall prevalence of the conditions and the effect of those conditions on health outcomes, such as cost of care, disability, and mortality. Severity of comorbidity is typically assessed in terms of the independent risk of death associated with that condition. Personal interviews, medical records, computerized hospital discharge summaries, and death certificates have all served as sources of data on comorbidity. Additive, summary comorbidity indexes, commonly used in studies of cancer treatment and prognosis, are reviewed, and the effects of those scales on the conduct of clinical and epidemiologic research are assessed.
New directions for clinical and epidemiologic research include the following: (a) identifying new sources of data on comorbidity, especially for longitudinal studies that involve repeated assessments of the number and types of health conditions; (b) establishing new criteria for assessing severity, including physiologic markers such as serum albumin; and (c) developing and evaluating multiplicative comorbidity indexes. Finally, it is recommended that studies also be developed to assess the effects of newly diagnosed cancer on the course of preexisting comorbid conditions in older patients. Together, these studies should contribute to effective treatments for cancer in older populations.
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Cancer Prevention in the Older Person: The Role of Comprehensive Cancer Centers (CCC)
Jeanne Mandelblatt, Ph.D., M.P.H., Lombardi Cancer Center, Georgetown University, Washington, D.C. and Lodovico Balducci M.D., H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida
The incidence and prevalence of malignant diseases continue to increase in the older population; the median age of cancer patients in the United States is 70 years. With the "graying of America," cancer prevention and early detection targeted to the growing older populations have the potential to lessen the morbidity and mortality related to cancer and cancer treatment. In this session, we examine (a) the biology of cancer and aging, which affect decisions about optimal prevention and early detection strategies; (b) current evidence about the effectiveness and cost-effectiveness of prevention and early detection; and (c) potential leadership roles of comprehensive cancer centers (CCC) in studying and promoting cancer prevention and early detection among the elderly.
Primary prevention of cancer through chemoprevention may have an appropriate role given the enhanced susceptibility of aging tissues to environmental carcinogens. However, these benefits need to be balanced by risks of susceptibility to therapeutic complications, such as deep vein thrombosis or cerebrovascular accidents caused by selective estrogen receptor modulators (SERMs) and reduced life expectancy due to comorbid conditions.
Secondary prevention of cancer through screening can be more effective in older than in younger populations because of the improved positive predictive value of screening tests as a result of the rising prevalence of cancer and the increased sensitivity of some screening techniques such as mammography. The value of early cancer detection may be lessened by reduced life expectancy from concomitant conditions. However, once prevalent disease is removed from the screening pool, true new disease rates may be lower. A number of sociocultural barriers may interfere with instituting effective cancer prevention in older individuals. Finally, the costs of continuing screening into the last decades of life may be high relative to the risks and benefits, although new screening technologies may hold greater promise as tools for older populations.
Given the concentration of resources devoted to cancer research, CCCs are in a privileged position to promote and study cancer prevention in this high-risk population. In addition to the development of new chemopreventive agents and new and more accurate screening techniques, CCCs could facilitate cancer prevention and early detection in the elderly through special initiatives that include the following: (a) research in molecular aging aimed at identifying the mechanisms of enhanced susceptibility to environmental carcinogens and at establishing which age-related changes favor the growth and the spread of cancer; (b) decision analysis aimed at selecting the older individuals who will most benefit from cancer primary and secondary prevention at the most reasonable costs; (c) research on patient preferences and shared decision making; and (d) establishing a network of institutions able to translate basic science insights, clinical trials, and observational research in cancer prevention/early detection into diverse communities. Such a network could share expertise, collaborate on research, build databases, and disseminate results.
CCCs are ideally positioned to take the lead in cancer control for older Americans. Such initiatives will readily translate into improvements in the quality of care delivered to older individuals at risk for and with cancer.
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Quality of Life of the Older Cancer Patient
Alice B. Kornblith, Ph.D., Dana-Farber Cancer Institute, Boston, Massachusetts
Two large separate bodies of literature describe the quality of life and psychosocial functioning of the geriatric population and the cancer patient population. Few studies are devoted to assessing the overlapping characteristics of these two groups: the older cancer patient population. Although the prevalence of psychiatric disorders is largely unknown in older cancer patients, studies have consistently found a modest, inverse relationship between age and adjustment, with better adjustment and less depression in older cancer patients than in their younger counterparts, a relationship that is independent of patients' physical status. Although possible reasons have been speculated to explain this phenomenon, none has been empirically determined. Greater psychological distress in older patients is significantly related to a worsening of their physical status, including issues such as metastatic disease, worsening physical functioning and symptom severity, and nonphysical factors such as inadequate social support. Those at greatest risk of poor social support were those aged 85 years and older, with lower income, and who had more recently moved to their current residence. Despite the shrinkage of older cancer patients' social support system with aging, due to deaths of family members and friends and to family and friends moving away, a number of studies document that most older cancer patients report high levels of social support. Goodwin et al. 's (1991) study documented that over 80% of newly diagnosed older cancer patients had weekly contact with friends and relatives in their area.
The impact of caring for older cancer patients on primary caregivers has also begun to be studied. As with older cancer patients, older caregivers report less depression, less disruption to their daily routines, and fewer financial problems than those who are younger. Yet, older caregivers report significant levels of depression, with 31.5% scoring at levels that suggest clinical depression and with 50% reporting disruption to their daily routines and socializing (Mor et al., 1994). Studies of mixed age groups of cancer patients indicate that caregivers' distress increases in relation to multiple factors, including patients' worsening physical condition, greater patient care needs, patients' increasing depression, increasing loss in caregivers' physical strength, a poor marital relationship, and a patient's nonempathic physician (Kurtz et al., 1995; Nijboer et al., 1999; Emanuel et al., 2000). The relative risk of mortality of older caregivers for cardiovascular patients was 1.63, representing a 63% increase in mortality over a 4year period compared with spouses of nondisabled patients (Schulz and Beach, 1999). If this finding applies to older spouses of cancer patients, it underscores the serious consequences of the stresses of caregiving on the older family member.
The primary future research needs in quality of life of the older cancer patient include the longitudinal evaluation of the impact of cancer treatment on the quality of life of older patients and their family members, primarily through the use of randomized Phase III trials, to compare the effect of different cancer treatments. Through this research paradigm, the prevalence of psychiatric disorders and psychological strengths of older cancer patients could be studied along with the neuropsychological effects of cancer treatments as well as the role of the relationship of the oncologist to patients' and family members' adjustment. The vulnerability model (Kornblith, 1998) is proposed as a theoretical framework by which to understand older cancer patients' adaptation, taking into account a range of factors (e.g., cancer and its treatment, physical functioning, economic, personality, social, and medical management) that may exacerbate or ameliorate the stress of having been treated for cancer. With a better understanding of the issues that affect older cancer patients' lives, interventions can be developed and targeted to improve the quality of life of the most vulnerable older cancer patients and their family members. The most promising areas include interventions designed to improve psychosocial functioning, informational devices such as decision aids to better meet patients' informational needs, and techniques to improve doctor-patient/family communication. This research agenda needs to go hand in hand with instrument development and refinement to improve assessment of geriatric specific quality-of-life issues along with a reexamination of the reliability and validity of existing measures to verify their adequacy for older cancer patients.
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Palliative Care in the Elderly
Kathleen M. Foley, M.D., Memorial Sloan-Kettering Cancer Center, New York, New York
As we focus on enhancing the quality of life for our aging population, special attention should be given to the quality of living for elderly cancer patients and their caregivers. Every day 1800 cancer patients die in the United States and most are over the age of 65. Numerous studies have identified deficiencies in end-of-life care for cancer patients. The Institute of Medicine 1997 report "Approaching Death" summarized the significant gaps in scientific knowledge needing serious attention from biomedical, social science, and health service researchers. The report recognized significant organizational, economic, legal, and educational impediments to good care and indicated health care professionals' lack of education and knowledge about end-of-life care as one of the major barriers to improving care.
The World Health Organization, the President's Cancer Panel, and the National Cancer Policy Board have strongly endorsed the importance of palliative care as an integral aspect of cancer care. "Palliative care is the active total care of patients whose disease is not responsive to cancer treatment. Control of pain, other symptoms, psychological and spiritual distress is paramount. Many aspects of palliative care are also applicable earlier in the course of the illness in conjunction with anti-cancer treatments." Elderly cancer patients with advanced disease experience eight major symptoms that interfere with their quality of life. Two recent nursing home studies reported that severe pain in elderly nursing home residents with cancer is prevalent, persistent, and poorly managed. Anxiety, depression, and suicide have an increased incidence in the elderly with cancer. Both underdiagnosis and undertreatment are well documented in national surveys.
Economic issues have focused attention on the fact that one of eight Medicare dollars is spent in the last 3 weeks of life and the cost of care for cancer patients is 20% higher than the cost of caring for other patients. An increasing shortage of nurses, a shortage of caregivers, and a high caregiver burden add complexity and urgency to the need to shape a better system of care appropriate for our aging population. Palliative care should be fully integrated into a geriatric cancer program to facilitate patients' ability to receive quality cancer care from diagnosis to death. Palliative care research must address the special needs of the aging population to facilitate the evidence-based guidelines for pain relief, symptom control, and service delivery models for the care of the frail elderly.
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Aging and Cancer: Biologic Interface
William B. Ershler, M.D., Institute for Advanced Studies in Aging and Geriatric Medicine, Washington, D.C.
Oncologists and gerontologists have long been examining common biological processes. Thus, the genetic, molecular, and biochemical regulators of cellular proliferation, transformation, and death are fertile investigational domains in both disciplines. Central to the aging/cancer nexus are two basic questions:
- How does aging predispose to cancer?
- Do tumors in older animals have different malignant properties?
Explanations for increased cancers in old animals include an increased susceptibility to carcinogenic exposure, impaired DNA repair, altered regulation of cellular proliferation, and impaired immune surveillance. Perhaps as significant as these factors, the most important explanation relates to the time required to progress from normal tissue to invasive cancer, which is estimated to be decades for most human epithelial cancers.
FIGURE 1
Clinicians are well aware that histologically identical tumors have different patterns of growth and spread in older patients. This may not be a consequence of aging as much as it is that older patients are more likely to have tumors that take a long time to develop and grow ("Seed Hypothesis"; Fig. 1). However, it is also clear that genetically identical cells growing in experimental animals of disparate ages have different rates of growth (Fig. 2) and different patterns of spread.
FIGURE 2
It is now clear that tumor cells are, indeed, different in young and old hosts. Thus, older women with breast cancer are more likely to have tumor cells that express estrogen and progesterone receptors, less accumulation of abnormal p53 and laminin, less lymphovascular invasion, less DNA ploidy, fewer cells in division, and more favorable histologies. Such is typically observed for all the common epithelial tumors, including colon, lung, and prostate—tumors for which the median age is older than 70 years. Yet, "soil" factors are also demonstrably influential. To the extent that aging influences those host-derived tissue factors that contribute to the tumor microenvironment, it might be less favorable for cell proliferation, tumor growth, and spread. Thus, host-derived angiogenesis and other growth factors, nutritional adequacy, and matrix protein alterations might, in composite, present a less favorable environment for tumor growth in senescent tissues ("Soil Hypothesis").
At the cellular and subcellular level, common processes of aging and cancer are becoming more clearly defined. It is no surprise that cancer is generally an old person's disease. Although this has been appreciated for a long time, clinical advances in oncology have been slow in developing.
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