Palliative radiotherapy in the older adult

Introduction

Many countries are in the early stages of a major demographic shift, stemming from the so-called “baby boomers” coming of age and thus an increasingly older population. This has clear implications for clinical practice, as age is the number one risk factor for the development of cancer, and therefore, we will see greater numbers of older adults with cancer in the coming years. In the United States alone, an estimated 74.1 million (21%) of Americans will be aged 65 or older in 2030, an increase from 46.2 million (15%) in 2014. The European Statistical Office (EUROSTAT) figures predict similar increases in those aged 65 and older in the coming years, and a marked increase in those aged 80 and older (i.e., the “oldest old”). It is very timely to consider the impact of these projected changes, not only on the oncology infrastructure required to effectively manage additional patients, but also the demands of an aging population and the health service planning changes that may be required to respond to their needs. A certain amount of “age attuning” of the oncology services is required to provide a more holistic approach to the care of older adults, in the palliative care setting, which will be discussed in this chapter.

First of all, what do we mean by “older”? There is no widely accepted definition of an older or elderly person. Most developed countries now accept 65+ years as a more suitable definition of “old.” This coincides with retirement age in many countries, although we know that this is a moving target, with some individuals opting to retire early even as some countries are raising the age of retirement. In health care, many organizations now consider 70 to be a truer reflection of old age in most developed countries, as people are aging better and continue to enjoy good health until much later than ever before. Most guidelines incorporate this age cut-off as an approximate indicator of the transition to old age.

Data from cancer registries have highlighted that older patients are less likely to undergo treatment for their cancer, ^, and often present at a later stage, commonly with a presentation at the emergency department. The reasons for this are unclear, as previous studies have highlighted that age should not be a barrier to referring an older patient for (palliative) radiotherapy. Still, studies demonstrate that age remains the main factor in determining receipt of active treatment in older adults, above comorbidities, tumor stage, and disease burden. The reasons for lack of adherence to standard treatment guidelines remain unknown. It should be noted that overtreatment also occurs, which can be just as detrimental as undertreatment.

Palliative radiation therapy is effective in the older patient, both in reducing symptom burden from advanced or metastatic cancer, and maintaining quality of life (QoL). A prospective Canadian study ( n = 558) showed no significant difference in response rates to radiation therapy for metastatic bone pain up to 3 months after radiotherapy for older patients, compared with younger patients. Despite this, research has shown that access to palliative radiation therapy progressively decreases with advanced age, and that older adults are less likely to access specialist palliative care services. ^, A SEER-Medicare study of patients with various metastatic cancers showed that rates of palliative radiation therapy for patients aged 70 and greater were substantially lower than for younger patients.

Compounding this issue regarding lack of standard treatment, underrepresentation of older adults in clinical trials is also a significant problem for evidence-based geriatric oncology, despite the incidence of cancer in this age group, which is estimated to be 60% of all cancer cases. Although approximately 60% of new cancer cases occur in older people, they comprise only a quarter of participants in cancer clinical trials. Clinically, patients will present with various comorbidities, differing performance status, frailty profiles, and physiological age. Characterizing the heterogeneity of older cancer patients and their ability to tolerate oncologic treatment is difficult without the aid of clinical trial information to guide clinicians. This information may be the decisive factor in determining which patient is suitable for radical treatment, or those patients for whom a palliative approach is a better option. In order to counteract the traditional lack of access for older adults with cancer to clinical trials, the European Organisation for Research and Treatment of Cancer (EORTC) established the Elderly Task Force. A joint position paper with the International Society of Geriatric Oncology (SIOG) has recommended standardized approaches to the assessment of functional reserve (frailty) and comorbidity in cancer clinical trials of older patients, with the removal of restrictive age criteria for enrolment.

Indications for palliative radiation therapy in older adults with cancer

Age alone should not preclude an older person from receiving palliative radiation therapy. As highlighted above, access to palliative radiation treatment has been suboptimal and this may be attributed to fears of reduced tolerance to acute toxicities in older adults. Nevertheless, treatment schedules and techniques used for younger patients have been shown to be just as well-tolerated in older patients. However, some age-related considerations include the risk of rapidly symptomatic dehydration caused, for example, by irradiation of the small bowel (diarrhea) and head/neck (mucositis), especially in more frail patients. Therefore, appreciation of underlying frailty is vital in order to preempt these issues in patients who might decline suddenly during treatment, as discussed below. Adequate supportive care is also necessary in order to prevent adverse effects, as well as treatment interruptions.

Nieder and Kampe found that older patients (>80 years) were less likely to complete a course of palliative radiation therapy, despite short fractionation schedules. Survival and toxicity were not associated with age; however, this was a small retrospective study including only 26 older versus 76 younger patients.

With regard to palliative radiotherapy, positioning and immobilization should ensure maximum comfort for the older patient, who may be more restricted as a result of age-related issues. Presence of certain geriatric syndromes might also affect a patient’s ability to complete parts of the radiation treatment process. For example, patients with hearing impairment, which is very common among older adults, may not be able to participate fully in discussions or adhere to directions for treatment. Similarly, patients with dementia may not be able to communicate their distress or pain during radiation therapy, orient themselves to time and place, or recall simple instructions. Another example is patients with movement disorders like Parkinson disease, or arthritis, who may have difficulty with maintaining their position each day for radiation therapy. Those with preexisting frailty might have difficulty fulfilling some of the technical requirements for radiation treatment.

Palliative radiotherapy treatment courses should thus be as short as possible. The patient’s unique circumstances and concerns should be taken into account when assessing an older adult for palliative radiation treatment. These include the additional burden of the treatment upon the patient, caregiver (if applicable), and family/support network. Offering single-fraction radiation treatments, where appropriate, and providing a rapid access solution whereby consultation, treatment planning, and treatment delivery are provided in a single visit are important considerations. ^, One such example is the treatment of uncomplicated bone metastases, where several studies support the use of single-fraction over multi-fraction radiation treatment, with equivalent efficacy in terms of palliation. ^,

While palliative treatments have traditionally been less complex, in terms of treatment planning, more advanced technologies can greatly aid the avoidance of excessive toxicity in older patients, and this is also relevant in the context of palliative care. Stereotactic radiosurgery (SRS) alone, compared to SRS and whole brain radiation therapy (RT), may provide better conservation of cognitive function and QoL, for example. ^, In addition, stereotactic body radiotherapy (SBRT) is increasingly used in the treatment of bone metastases and other extracranial sites of metastatic disease.

To date, one phase II randomized controlled trial (RCT), SABR-COMET, has investigated SBRT in the oligometastatic disease setting, in patients with five or fewer sites of oligometastatic disease. The primary outcome of overall survival favored SBRT over standard palliative radiotherapy (median: 41 vs. 28 months), with improved progression free survival and local control in the SBRT arm. However, there was a higher level of treatment-related grade ≥2 adverse events and three treatment-related grade 5 toxicities in the SBRT arm. QoL outcomes did not differ between the arms and the median age of patients in the SBRT arm was 67, with a maximum age of 74. Future phase III and phase IV trials are eagerly awaited in this setting in order to elucidate the role of SBRT in oligometastatic disease.

Other examples of the use of advanced technology include volumetric arc therapy (VMAT), which can reduce time on the treatment couch for those with mobility restrictions or movement disorders. In such cases, the use of more advanced technology may well be justified.

Characterizing heterogeneity in older adults with cancer

There are many important factors to consider when deciding on a course of cancer treatment for older adults. One notable way to categorize the heterogeneity of older patients with cancer is by actively looking at existing reserve capacity, or preexisting frailty. The gold standard in terms of clinical assessment of frailty remains the comprehensive geriatric assessment (CGA), often abbreviated to geriatric assessment (GA) in the oncology literature. The SIOG and National Comprehensive Cancer Network (NCCN) guidelines for older adults advocate the use of CGA as vital in “staging the aging,”—that is, assessing physiologic and functional capacity, which in turn has implications for predicting treatment tolerance and toxicity. Recently, four RCTs presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting have provided concrete evidence that the implementation of GA for older adults with cancer leads to improvements in QoL and decreased treatment toxicity, without compromising survival. These RCTs are considered practice changing for geriatric oncology; however, they do not include radiation oncology, and similar trials are long overdue in this setting.

The potential benefits in palliative radiation oncology are many, and include the identification of geriatric impairments, even in those with a good performance status. ^, When independence is not maintained and poor outcomes occur, patients require hospital care. Troubleshooting these issues before they arise, by using CGA as part of the diagnostic workup to determine the most appropriate treatment, can prevent reliance on hospital resources in the long-term. Frail patients are more likely to have poor outcomes following surgery, chemotherapy, and radiotherapy. In an outpatient setting, CGA-based care has resulted in fewer hospitalization days and enhanced survival in patients with no associated increase in cost. This not only benefits the patient, but also the health care system as a whole.

CGA also facilitates shared decision-making approaches, as it provides a multidimensional view of the patient’s overall health as a potential starting point for risk stratification. This is especially important in the palliative model of care. Knowledge of current functional and cognitive status, in particular, and the ability of treatment to cause declines in those domains, is especially important to patients, more so than survival. ^,

Fig. 24.1 depicts a conceptual model of how CGA can be incorporated into oncology assessment and treatment. Fit patients should be candidates for the same treatment as their younger counterparts, while frail patients would benefit from a more palliative approach. Vulnerable patients, on the other hand, may need to be offered a tailored treatment, in order to avoid decline during/after treatment, or may benefit from a dose-adapted approach, somewhere between radical and palliative treatment.

Frailty presentations

Frailty forms the basis for the practice of geriatric medicine, but remains poorly appreciated in other aspects of medicine, such as radiation oncology. It has been defined in the gerontology literature as a consequence of (usually) age-related decline in many physiological systems, resulting in a reduced reserve capacity and increased vulnerability to stressors. ^, This vulnerability is related to an inability to maintain homeostasis in the face of a physiological threat (e.g., infection, illness, and trauma).

In terms of etiology, frailty and cancer share common risk factors, such as smoking, sedentary lifestyle, malnutrition, and obesity. Recent research efforts have focused on quantifying the acceleration of frailty that is now known to occur due to cancer and its treatment. Accumulation of cellular damage and system dysregulation are common features of both aging and cancer. It is thought that aging and diseases such as cancer represent different courses with a common underlying cellular mechanism, which is also influenced by genetics and the environment. This partly explains the considerable differences observed in aging phenotypes; for example, one 70-year-old may already be quite frail on presentation and use a walking aid, while another may run marathons. Frailty has been associated with increased mortality in older adults with cancer, and therefore some baseline knowledge of its existence is essential in order to make informed treatment decisions for patients.

Tools for prognostication: Screening for frailty

CGA is known to be time-consuming and therefore frailty screening is considered a more feasible option, or a first step in identifying those who require CGA and associated interventions. Frailty screening should be routine for older adults with cancer. Those who screen positive may be candidates for a full CGA, and a more thorough investigation of needs and interventions should ensue. There has been a proliferation of frailty assessment tools in both geriatric medicine and in oncology over the past several years. Two schools of thought predominate in the gerontology literature: the phenotype of frailty defined by Fried et al., from the Cardiovascular Health Study (CHS), and Rockwood’s clinical frailty criteria, based on cumulative deficits on various CGA domains.

The frailty model established by Fried and colleagues, in the CHS study, which studied over 5000 men and women over the age of 65, is relatively short and easy to use. It focuses on physical frailty, and is assessed using five different components: unintended weight loss, weak grip strength, exhaustion, low-physical activity, and slow gait speed. People are categorized as robust if no deficits are identified, prefrail if only 1 to 2 deficits are present, and frail if there are 3 or more. This corresponds to the three-level categorization mentioned previously (i.e., fit, vulnerable, and frail).

Another frailty screening tool, Rockwood’s frailty index (FI), is often deemed more useful in a clinical setting, as it also encompasses cognitive, psychological, and social factors, which the Fried model does not ( Fig. 24.2 ). It is widely known that that these socio-environmental determinants of health are vital in overall health and well-being. This is especially important in palliative care. The FI was based on the results of a 5-year prospective cohort study of over 10,000 people over the age of 65. In the original FI, 92 individual deficits from a wide range of domains, were identified to collectively define frailty. Subsequent work has reduced the number of FI items required to predict frailty from 92 to 30 or so, with no subsequent loss of validity. ^, With a greater number of deficits required to define frailty, the FI is considered to have more built-in redundancy than the phenotypic model, and thus no individual deficit carries a great threat of adverse outcomes.

One way to conceptualize the difference between these two models is the famous Golden Gate Bridge in San Francisco. The phenotypic model has been described as being equivalent to the major structural components of the bridge (i.e., the towers or horizontal cables) as seen in Fig. 24.3 . Loss of even one of these towers would introduce greater instability, while three or more might be detrimental to its existence. Using the FI, or stochastic frailty model, on the other hand, is equivalent to looking at the multiple vertical cables in the bridge. Loss of one of these cables will not threaten the structural strength of the bridge, but the accumulation of numerous insults over time might cause a greater threat to the bridge’s integrity, and eventually lead to its collapse. Resilience on the other hand is a measure of the bridge’s ability to withstand expected stressors (e.g., wind, traffic, and water). The Golden Gate Bridge is well-designed to expect and deal with these stressors; however, unexpected adverse conditions, such as storms, combined with heavy traffic and accumulation of damage over time in the form of the loss of vertical cables, might represent a tipping point, beyond which collapse is inevitable.

Human frailty can be envisaged in much the same way. Under normal conditions, the human body is able to withstand a certain amount of physiological decline, without any great impact on its day-to-day function. However, when a major physiological stressor is introduced, such as a major illness like cancer, and ensuing treatment, this might destabilize an apparently well-functioning individual and lead to a loss of resilience in the face of this physiological threat. A high degree of instability may be the deciding factor between radical and palliative treatment, or previous oncologic treatment may result in lower physiologic reserve and less resilience in the face of recurrence and the prospect of further treatment.

Age-related loss of muscle mass and strength, known as sarcopenia, is often used as a surrogate measure of frailty. ^, It has been defined as “a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes, such as physical disability, poor QoL and death.” Skeletal muscle wasting is particularly noticeable in older adults who are treated with palliative intent.

Frailty screening in oncology

The prevalence of prefrailty and frailty among patients with cancer has been estimated to be approximately 42% (range 6% to 86%). The important thing to note in relation to the clinical presentation of frailty is that, compared to disability, frailty is potentially reversible when managed effectively with appropriate interventions are put in place to deal with deficits identified. ^, This has the potential to prevent falls, hospitalization, nursing home placement, and other important QoL indicators.

In oncology, rather than performing a CGA for all older patients, a two-step approach has been recommended by the NCCN, the SIOG ^, and EORTC. This involves the use of a short screening tool to identify those who would benefit from a full CGA, followed by administration of the CGA to this subgroup.

One of the most acceptable screening methods in the oncology literature is the Geriatric-8 or G8 ( Table 24.1 ) Use of a screening tool such as the G8 enables health care professionals to use (scarce) resources more efficiently while ensuring that patients still receive the optimum care. The G8 was the first screening tool devised specifically for oncology and has been validated in the ONCODAGE study of patients with cancer. It has been demonstrated to have high sensitivity (65% to 92%) and acceptable specificity, and only takes approximately 4 minutes to complete. Poor performance on the G8 is associated with poorer 1-year survival. A more recent systematic review incorporating 46 studies on the performance of the G8 have also confirmed an association with survival and treatment-related complications. Such tools are currently underutilized in the decision-making process for older adults with cancer, and may prove insightful in distinguishing those patients who will ultimately not benefit from a radical approach and for whom a palliative treatment is more advantageous.