Geriatric assessment
The aging process varies widely among individuals; elderly people of the same age do not necessarily have similar physical conditions, so treatment should be guided by individual health status. However, traditional oncology measures of PS, such as the Eastern Cooperative Oncology Group (ECOG) scale and Karnofsky Performance Scale, may not be reliable for assessing physical status in elderly patients because they do not take into account comorbidities or other aspects of frailty [
29,
30]. Consequently, performing a comprehensive geriatric assessment (CGA) is recommended for predicting chemotherapy toxicity and mortality in elderly patients with cancer (Fig.
1a) [
31]. A CGA is a series of standardized tests evaluating aspects of physical performance, comorbidity, cognition, medications, nutritional status, functional status, mental health, and social status in elderly patients [
23]. Conducting a CGA can help guide treatment decisions based on the overall health status of the elderly patient, preventing the undertreatment of medically fit elderly patients as well as limiting treatment intensity in medically unfit elderly patients [
23]. It should be noted that the CGA studies described below were conducted in patients with various tumor types; therefore, the results may not be directly applicable to patients with AGC.
A potential role for CGA may be to help predict which elderly patients are at risk of experiencing chemotherapy-related toxicities or not completing treatment (Fig.
1a). Three items on the Mini Nutrition Assessment (MNA; psychological distress or acute disease in past 3 months, neuropsychological problems, and using > 3 prescription drugs) independently predicted premature discontinuation of chemotherapy [
32]. In a comparative study of elderly patients with various cancers (approximately half with gastrointestinal cancer), those whose treatment was based on a CGA were more likely to complete cancer treatment as planned and had fewer treatment modifications than those who received routine care; however, grade ≥ 3 toxicity and 6-month mortality did not differ between groups [
33]. In the randomized phase III ESOGIA study, treatment allocation on the basis of CGA resulted in significantly less all-grade toxicity (but not grade 3/4 toxicity) and significantly fewer treatment failures due to toxicity compared with treatment allocation on the basis of PS and age in elderly patients with advanced NSCLC [
34]. The ability of CGA to predict chemotherapy-related toxicities has been used to guide the choice of treatment regimen, with a systematic review of 35 studies showing that, after CGA, treatment plans were modified in 28% of patients, usually to a less intensive regimen.
Other scoring systems have been designed to identify patients at risk of chemotherapy-related toxicities. The CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) score categorizes patients into different risk categories for toxicities according to diastolic blood pressure, IADL, lactate dehydrogenase levels, toxicity of individual chemotherapy drugs, ECOG PS, Mini-Mental Health Status, and MNA [
35]. The Cancer and Aging Research Group (CARG) tool model includes age, cancer type (with gastrointestinal or genitourinary cancer having a higher risk score), chemotherapy dosing, number of chemotherapy drugs, laboratory measures, hearing level, walking ability, number of recent falls, IADL score, and social activity level [
29,
36].
A related aspect to consider is the concept of frailty, defined as a complex, multidimensional, and cyclical state of diminished physiological reserve that results in decreased resiliency and adaptive capacity, and increased vulnerability to stressors [
30]. Frail patients are at increased risk of intolerance to chemotherapy, disease progression, and death; therefore, additional aspects of care are required (Fig.
1a) [
30]. Over 70 different measures of frailty have been proposed, including the CGA; however, the optimal measure for screening and assessment of frailty is unclear [
30].
Incorporation of CGA in prospective clinical trials of elderly patients with AGC, in particular, patients with poor PS, would help guide treatment choice in this population. Further research is required to determine which CGA items are most useful for predicting survival and toxicities in patients with AGC.
Symptom monitoring
Elderly patients with cancer may have symptoms such as fatigue, decreased appetite, pain, nausea, and depression arising from the cancer and/or treatment [
37,
38]. Elderly patients may underreport symptoms for several reasons, including viewing them as a normal part of aging, concern that the oncologist may discontinue treatment, and cognitive impairment and depression [
37‐
39]. Additionally, elderly patients may forget to report adverse effects occurring early in the chemotherapy cycle that have since resolved [
39]. Identifying toxicities early in the treatment cycle would allow the oncologist to intervene by adding/increasing supportive medications, modifying the chemotherapy dose, and/or referring the patient to a palliative care provider, which may reduce hospitalizations and emergency department visits (Fig.
1a) [
39].
Numerous scales and questionnaires are available to measure the various symptoms associated with cancer and its treatment [
37,
38]. More recently, a number of computer-/tablet-based patient-reported outcome (PRO) systems have been developed and shown to be feasible for use in the clinical care setting (e.g., Symptom Tracking and Reporting [STAR], Advanced Symptom Management System in Palliative Care [ASyMSp]) [
39,
40]. Basch et al. [
41] found that web-based symptom reporting resulted in a better quality of life (QoL), fewer emergency department visits, fewer hospitalizations, longer duration of palliative chemotherapy, and better quality-adjusted survival in patients with advanced solid tumors. Denis et al. [
42] found that web-mediated follow-up improved OS because of early relapse detection, with better PS at relapse, in patients with advanced-stage lung cancer. Although these two studies included elderly patients, studies to investigate if elderly patients derive the same benefits from electronic PRO systems as younger patients are needed [
39].
Polypharmacy and drug-drug interactions
Elderly patients with cancer are likely to experience polypharmacy (e.g., concurrent use of ≥ 5 prescription/over-the-counter medications and herbal supplements [
43]). In addition to receiving cancer therapy and supportive medications to prevent side effects, elderly patients are likely to have comorbidities requiring drug therapy. A complex medication regimen can be difficult to manage, potentially leading to inappropriate medication use and nonadherence, with a risk of increased and overlapping side effects [
44,
45].
Although polypharmacy does not necessarily result in inappropriate drug combinations, there is a risk of drug-drug interactions (DDIs), which is increased in elderly patients with cancer because of age- and comorbidity-related changes in drug absorption and excretion [
44,
46]. DDIs are an important concern (Fig.
1a) because of the potential to affect drug dosage, resulting in reduced efficacy or excessive toxicity [
46]. Of note, because the metabolism, distribution, and elimination of monoclonal antibodies are not mediated by cytochrome P450 or drug transporters, monoclonal antibody therapies are not expected to compete directly with chemically-derived drugs and, therefore, the risk of DDIs may be lower with such therapies [
47,
48]. In 13 studies of elderly patients with cancer, DDI prevalences ranging from 2 to 77% were reported [
43]. However, it should be noted that the studies differed in trial design, methodology, and, importantly, definitions of DDIs. To avoid harmful DDIs, the following are strongly recommended: a routine reassessment of all prescription and over-the-counter medications and herbal supplements; communication of a complete list of medications between healthcare providers on every referral, hospital admission, hospital transfer, and hospital discharge; and monitoring for signs of DDIs [
46,
49,
50]. However, the optimal approach for screening for DDIs (e.g., comprehensive medication review by a clinical pharmacist, consultation with a clinical pharmacologist, use of clinical decision support software) remains to be determined [
43].
Nutritional support
Nutritional status is of great importance during the treatment of all patients with cancer, and particularly in the elderly (Fig.
1a). Poor nutritional status/malnutrition is associated with increased risk of toxicity from chemotherapy and worse survival outcomes [
51,
52] and, in the elderly, inadequate protein intake can result in a reduction in lean muscle mass and increased risk of frailty [
53]. Malnourished patients commonly need dose reductions/delays, and possibly treatment discontinuation, and have a higher frequency of hospitalization, reduced QoL, and decreased survival [
10]. The International Society for Geriatric Oncology recommends including nutritional assessment before starting cancer treatment [
51]. Among the available nutritional assessment tools, the MNA Short Form was designed for elderly patients with cancer and includes questions on food intake, weight history, mobility, acute disease, neuropsychological problems, and body mass index [
51,
52]. However, nutritional assessment tools may not detect other symptoms that affect nutrition such as nausea and vomiting, which are common symptoms in patients with AGC receiving chemotherapy [
52].
Nutritional support may be of benefit in patients with AGC with respect to QoL and survival [
10] and, as recommended by the American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement, is an important contributor to recovery in elderly patients who have undergone major surgery, especially surgery for AGC [
53]. Following surgery, elderly patients can be at risk of malnutrition for a range of factors including decreased appetite, adverse effects of analgesics, and a lack of awareness of how diet can support recovery [
53]. Evidence from a clinical trial of elderly inpatients who were at risk of malnutrition demonstrated a 49% reduction in 90-day mortality and indicators of nutritional status in those receiving high-protein oral supplementation compared with placebo [
54]. Despite this, there are no specific guidelines for elderly patients with AGC or ascites, and studies of the value of nutritional counseling in patients undergoing active cancer treatment have only been conducted in younger populations [
51].
Prevention of falls
Falls are commonly reported in elderly patients with cancer, with several studies reporting a higher prevalence of falls in elderly patients with a cancer diagnosis compared with those without [
55,
56]. Side effects of cancer treatment can contribute to the increased fall risk. For example, neurotoxic agents (e.g., taxanes and platinum agents) have been associated with an increased risk of fall-related injuries, likely due to effects manifested as dizziness or orthostatic hypotension [
57]. Falls can result in serious injuries, such as fractures and head trauma, as well as a loss of confidence from fear of falling; this may ultimately lead to functional decline, affecting the patient’s ability to live independently [
56,
58]. In addition, previous falls are associated with an increased risk of chemotherapy toxicity and poorer survival [
29,
59]. Screening for falls in elderly patients is, therefore, strongly recommended, from simply asking the patient if they have had any falls since their last visit to administering gait and balance tests, such as Timed Up and Go or Gait Speed tests [
58,
60]. Patients at risk for falls should be offered a multifactorial assessment followed by referral to a primary care provider, geriatric team, or falls clinic (Fig.
1a) [
60]. Possible interventions to prevent falls include evaluation of additional risk factors for falls, home safety evaluation, physical therapy referral for strength and balance training, home exercise program, and fall counseling education [
60].
Caregivers of elderly patients
Another aspect to consider is the QoL of the caregiver of the elderly patient with cancer (Fig.
1a). Much of the day-to-day care of elderly patients is provided by informal caregivers, defined as a relative, partner, or friend who provides essential support, including assisting with ADL, performing medical- and nursing-related tasks, and providing physical and emotional assistance [
61,
62]. However, caregiving is associated with a physical, emotional, and financial toll [
61]. Kehoe et al. evaluated the relationship between impaired CGA domains of elderly patients with cancer and their caregivers’ QoL [
62]. Higher numbers of patient CGA domain impairments were associated with caregiver depression and lower caregiver QoL, with impaired patient nutrition associated with caregiver depression and impaired patient function associated with lower caregiver QoL. Thus, the CGA potentially provides valuable information on the well-being of the caregiver as well as that of the patient. Equally, patient needs identified by the CGA may ease the burden of the caregiver [
61]. For example, patients identified by the CGA as needing assistance with ADL could be referred for nurse/social work evaluations; patients identified as having depression or anxiety could be referred for a psychology/psychiatry evaluation; and patients identified as having unintentional weight loss could be referred for a nutritional consultation [
61]. Identifying the needs of the elderly patient early in the treatment course and providing the appropriate assistance would increase support for both patient and caregiver.