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Radiation Therapy in the Elderly
Before discussing the implications of old age on cancer care, a definition of old age or geriatric seems needed. Unfortunately, a chronological definition of older age is difficult to provide. Old is a relative term. How societies define old age has several implications for their health, labor force, economy, laws, and family roles. In 1965, when the Social Security Act was passed, the average life expectancy for a US male was 66.8 years. Thus, defining older age as 65 years and older seemed legitimate. In 2014, US males had an average life expectancy of 76.5 years. With the US population now living longer, should we still consider a 65-year-old male to be geriatric? If the average retirement age in the United States is now 70 years, should that same chronological definition be used in an underdeveloped country where the average retirement age is 55 years? Thus, the chronological definition of old age is and will always be a moving target. Additionally, even if one were to attempt to define old age by a chronological cutoff, one would likely find a large amount of heterogeneity of biological and functional statuses among that older population. Humans, even within the same society, do not all age biologically at the same rate. Perhaps a definition of old age that includes the biological changes that lead to physical or functional decline is better suited for the needs of physicians attempting to care for this population.
As detailed later in this chapter, the aging process is associated with the decline of multiple organ systems over time. This decline also leads to a loss of functional reserve and ability to recover from harm that may occur to those organs. Patients with functional decline associated with aging may have less tolerance to and thus less benefit from standard cancer therapies, including chemotherapy, immunotherapy, surgery, and radiation. Therefore, “older” patients should not necessarily be approached or treated in the same manner as healthier, functionally intact, younger patients. At present, how these patients should be treated is still unclear. Older patients are poorly represented in standard setting trials, leaving physicians with little data to support their treatment decisions. Additionally, important functional assessment information is often not collected or not reported in large clinical trials or in most oncology clinics. Thus, the generalizability of the standard setting study results to our specific older patients in clinic is often murky.
With the increasing number of older adults in the United States, it is critical for oncologists to understand common issues faced by older adults. By 2030, it is projected that the United States will have more adults age 65 years and above than children age 18 years or younger. As cancer is often a disease of aging, oncologists can expect to see an increasing number of older patients, often with multiple comorbidities and/or geriatric syndromes that can impact treatment decisions and treatment tolerance. Radiation oncologists, in particular, may see a greater portion of older patients who are deemed ineligible for surgery or high-dose systemic chemotherapy due to the potentially lower rate of systemic toxicities from radiotherapy compared with cytotoxic drugs or general anesthesia. Thus, it is critical for radiation oncologists to understand how age and the aging process can impact our choices for best care. Owing to the local nature of radiotherapy, the impact that comorbidities have on tolerance to radiotherapy may be very different from how they impact surgery or systemic therapy. With local therapy, comorbidities may interact with treatment very differently depending on the area of the body being irradiated. Additionally, owing to the daily nature of many radiotherapy treatments, decline in physical function or social function, such as inability to drive or find transportation, could impact these treatments more so than with other modalities. However, the daily visits often required for radiotherapy also allow multiple opportunities for interventions to help improve possible syndromes associated with aging.
Despite the increasing number of older adults, many radiation oncologists feel undereducated on geriatric principles and the aging process. With this chapter, we hope to improve the readers’ understanding of geriatric principles and how the aging process may impact antineoplastic therapies and their outcomes. The chapter will detail the incidence of cancer in older adults and background of geriatric oncology in the United States, discuss the biology of the aging process, introduce the concept of the geriatric assessment and its clinical use, summarize key radiotherapy-related older adult studies, and offer future directions to improve evidence-based approaches and minimize key knowledge gaps for our increasing older adult cancer population. If the former president of the International Society of Geriatric Oncology (SIOG) is correct when he stated that “all oncologists are geriatric oncologists,” then it is our responsibility to improve our understanding of geriatric principles in order to better treat the increasing number of older adult patients in our clinics.
Incidence and Prevalence of Cancer in the Elderly
Based on data from the Surveillance Epidemiology End Results (SEER) database, through 2012 the median age at diagnosis of cancer in the United States is 65 years. Almost half (47%) of cancer survivors are 70 years or older. Additionally, the number of older patients with cancer is expected to continue to rise significantly over the next 20 to 30 years. Using incidence data from SEER and US census data from 2008, Smith et al. projected an increase in cancer incidences of 67% for adults over 65 years of age between 2010 to 2030, compared with only an 11% increase in those younger than 65 years. In a separate more recent study on increasing prevalence, Bluethmann et al. used a prevalence incidence approach statistical model with data from SEER, SEER-Medicare, and 2014 National Projections (estimated from the 2010 US census) to find that by 2040, roughly 73% of survivors of cancer will be 65 years or older. This rise in older adults in the United States is often referred to as the “silver tsunami,” owing to the number of older adult patients expected to inundate oncology clinics. In 2018, many radiation oncologists are already experiencing the beginnings of this wave. The “aging” of cancer patients not only affects clinicians’ initial treatment choices but can also impact supportive care throughout the treatment period and survival rates following therapy.
Despite the increase in older adults with cancer, the proportion of older patients enrolled in clinical studies remains low. A secondary analysis of greater than 160 consecutive non-age-restricted SWOG cooperative group studies from 1993 to 1996 demonstrated that although 63% of the estimated US cancer population in SEER was greater than or equal to 65 years of age, only 25% of the patients accrued to SWOG studies were 65 years and older. One of the potential reasons of low relative accrual of older patients is thought to be related to physician concern for higher toxicity rates among experimental systemic agents. However, an analysis of surgical oncology studies through the National Cancer Institute (NCI) showed significantly lower rates of older adult participation in surgical studies as well (odds ratio [OR], 0.2; 95% confidence interval [CI], 0.18–0.21, p < 0.001). Additionally, several recent site-specific (breast and lung) analyses of cooperative group studies have also demonstrated lower rates of accrual of older patients despite higher incidences of these cancers in older patients in the general population. Thus, for most cancer types (with the possible exception of genitourinary cancers ), clinicians are forced to extrapolate treatment outcomes data from younger, healthier patients in order to make treatment decisions for older and possibly less functional patients.
Extrapolating results from clinical trials on younger patients to older adults in clinic can often be inappropriate for a number of reasons. First, in certain disease types, the biological behavior of cancers in older individuals may be either more indolent (as in breast and prostate cancer) or significantly more aggressive (glioblastoma and endometrial cancer) than for younger individuals. Second, increasing rates of comorbidities and other competing risks of mortality can vastly alter the risk-benefit ratio of treatments for older adults compared with their younger peers ( Fig. 16.1 ). Third, common aging-related syndromes that lead to physical, social, and cognitive dysfunction may impact an older adult's ability to tolerate or comply with standard cancer therapies. For example, doses of radiotherapy to the pelvis that typically lead to grade 2 diarrhea are usually tolerated in younger adults but may lead some older adults with poor functional reserve to experience severe dehydration, hospitalizations, and treatment delays. Last, goals of antineoplastic treatments may be different with older adults favoring quality of life or quantity of life in certain situations. Of course, these four potential differences between older and younger adults with cancer are generalizations and may not apply to individual patients. Thus, a personalized approach to cancer care among older adults is critical.
A personalized approach to the treatment of older adults with cancer has been one of the major focuses of the geriatric oncology field since its inception in the early 1980s. In 1981, Dr. Rosemary Yancik organized a symposium entitled “Perspectives on Prevention and Treatment of Cancer in the Elderly,” co-sponsored by the NCI and the National Institute on Aging (NIA). This conference set the tone for the research agenda and education/training within the field of geriatric oncology and is considered to be one of the first steps in building and developing the field. Since then, several other organizations and individuals have continued to move the field forward through research and education. The American Society of Clinical Oncology (ASCO) continues to have separate geriatric oncology tracks at their annual meeting and occasionally publishes special issues of the Journal of Clinical Oncology focused on cancer in the elderly. SIOG ( www.siog.org ), has established annual meetings for education, research, and international collaboration, and sponsors the Journal of Geriatric Oncology . The Cancer in the Older Adult Committee of the Alliance for Clinical Trials Cooperative Group (formerly the Cancer in the Elderly Committee for the Cancer and Leukemia Group B [CALGB]) helps establish research protocols and secondary analyses focusing on older adult populations. The Cancer and Aging Research Group (CARG; www.mycarg.org ) has made great strides in coordinating studies to develop screening geriatric assessments and toxicity score calculators. These organizations and groups have helped established the importance of prioritizing the personalized care of older adults with cancer. The field of radiation oncology has been a little slower to recognize and prioritize older adults but has been catching up over the last few years. In October 2012, Seminars in Radiation Oncology published an issue focused on the impact of aging and comorbidities on cancer care. In 2014, the NRG clinical trials cooperative group established an elderly working group (incorporating the elderly working group from the Gynecologic Oncology Group). In 2016, the National Comprehensive Cancer Network (NCCN) updated the radiotherapy-related recommendations within the Older Adult Oncology Committee. In 2017, the International Journal of Radiation Oncology, Biology, Physics —the journal of the American Society for Radiation Oncology (ASTRO)–published a special issue on treatment of the elderly. All of these initiatives are rooted in the understanding that older adults cannot necessarily be assessed and treated in the same way as their younger peers and that a personalized approach will need to be established in order to improve the care of this growing population.
Biology of Aging
The treatment of older adults with cancer is not inherently different from that of younger patients such that treatment decisions are based on the anticipated benefits and risks from treatment in light of a patient's tumor characteristics, organ function, performance status, and comorbid conditions. However, the presence of clinically significant comorbid diseases and organ function is significantly higher in older adults compared with younger populations, both of which may alter the potential benefit from treatment due to competing risks of death and may adversely affect tolerability of cancer treatments. Although some age-related changes may be easily apparent from the “eyeball test” in clinic—such as the use of a walker or wheelchair—often, outward impressions can be deceiving. Many impairments and vulnerabilities in older adults, such as the presence of falls or impairments in instrumental activities of daily living (IADL; e.g., self-transportation, managing medication, telephone use, shopping, housework, paying bills, and preparing meals), are overlooked by traditional oncologic assessment but can have a tremendous impact on treatment tolerability and outcomes. In addition, the preferences in treatment outcomes may vary among older adults; many older patients differ in their willingness to trade increased survival for decreased quality of life compared with younger patients. The majority of older adults would decline treatments that may result in severe cognitive or functional declines.
A host of biological changes accompany the aging processes that have potential implications for cancer treatment planning and decision-making. Gradual losses in overall physiological and/or functional reserve are a hallmark of aging. Loses in renal function, hepatic function, muscle mass and strength, cardiac functional reserve, and pulmonary reserve all commonly accompany the aging process. These aging-related loses culminate in a reduced ability to adapt to stressful circumstances—such as surgery, chemotherapy, or radiation therapy—and increase the rate of potential complications. For example, age-dependent loses in skeletal muscle occur as early as the 4th decade of life and progress linearly with increasing age. With the increased use of routine computed tomography (CT) to assess body composition, numerous oncological studies have repeatedly demonstrated an association of low muscle mass with increased chemotherapy toxicities, surgical complications, hospitalizations, and reduced survival. Similarly, cardiorespiratory fitness declines with increasing age and can be measured by assessing peak oxygen consumption, known as VO 2 max. Low VO 2 max is an independent predictor of survival in patients with breast and lung cancer. Moreover, cancer and cancer treatments can also result in accelerated declines in both cardiorespiratory fitness and muscle mass that may have implications for cancer survival care in older adults. Becoming familiar with these age-related physiological changes and how they may impact cancer therapies is an important part of providing appropriately tailored treatments and survival care to the growing number of older adults with cancer.
As older adults age, they are increasingly likely to develop a physical or cognitive impairment that limits their ability to function and/or live independently. Many older adults with such limitations require assistance and support from family and/or friends to accomplish routine tasks, such as transportation to and from appointments or assistance with taking daily medications. Over half (58.5%) of older adults between the ages of 85 to 90 years receive caregiver assistance and, in adults over the age of 90, only a minority (24%) of individuals do not require assistance. Older adults are also at increased risk for disruptions to their social relationships, with 60% of women and 22% of men becoming widowed by their mid-70s and about half of older adults over the age of 85 years reporting the loss of a close friend in the past year. Assessing the social support system of older patients and identifying the role of caregivers is an important part of cancer treatment planning in older adults and may have significant implications for treatment (especially those who require frequent clinic visits). Patients without adequate social support may be at increased risk of health-related reduced quality of life and increased mortality. These individuals can often benefit from meeting with a social worker to identify available community resources.
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