Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology Summary

The clinical practice guideline for older patients with cancer provides recommendations on the appropriate implementation of validated and standardized clinical assessment tools and decision-making models for this vulnerable and prevalent demographic group.^1a It provides information on how these tools can be integrated into clinical oncology care to efficaciously evaluate and manage age-related conditions associated with adverse outcomes in older patients with cancer.

ASCO believes that to improve the quality of care, oncologists and patients should carefully weigh the risks and benefits of cancer-directed therapy for patients with a low performance status, who are ineligible for a clinical trial, and for whom there is no strong evidence supporting the clinical value of standard cancer treatment.^1,2 These conditions apply most often to older patients.

Approximately 70% of patients with cancer are age 65 years and older.³ The number of patients with cancer over the age of 65 years is projected to significantly increase over the next 20 years.³ The lifetime probability of developing cancer in men and women aged 70 years and over is one in three and one in four, respectively.⁴ Although the majority of patients with cancer and who die of cancer are older, there is less evidence to guide chemotherapy treatment decisions for this population because older patients, especially those with age-associated conditions, are underrepresented in clinical trials. Less than 25% of patients enrolled in National Cancer Institute Cooperative Group Clinical Trials are age 65 to 74 years, and less than 10% are 75 years or older.⁵ Consequently, older patients are especially vulnerable to over-treatment (ie, less fit patients being provided with cancer treatment with low likelihood of benefit and high likelihood of complications/toxicity), or under-treatment (ie, fit older patients who are not provided with standard, evidence-based chemotherapy regimens).^6–8 Older patients from minority backgrounds are the most vulnerable to disparities in survival.⁸ Studies have shown that traditional oncology performance measures, such as the Karnofsky or Eastern Cooperative Oncology Group performance status scores, do not accurately predict which older adults are at highest risk of adverse outcomes from chemotherapy.^9,10 Implementing evidence-based approaches to the evaluation and management of aging-associated conditions in older patients could help inform decisions for chemotherapy and improve outcomes.² Given the rapidly aging population, it is important that all oncology clinical teams are equipped to prevent, assess, and manage issues for older adults that could affect outcomes, including complications and toxicities from chemotherapy. Older patients undergoing chemotherapy often visit more frequently with the oncology clinical team than other clinical teams, including primary care, giving oncologists the best opportunity to avoid, detect, and manage potential complications.¹¹

The cancer care delivery gaps for older patients with cancer were highlighted in a recent Institute of Medicine committee report, “Delivering High-Quality Cancer Care.”^12,13 This report stated that “The current care delivery system is poorly prepared to address the care needs of this population, which are complex due to altered physiology, functional and cognitive impairment, multiple coexisting diseases, increased side effects from treatment, and greater need for social support.”^{13a(pp 1-2)}

These knowledge gaps were also highlighted in a series of Cancer and Aging Research Group (CARG) U13 conferences held in collaboration with the National Cancer Institute and the National Institute on Aging.^5,7,14 The conferences highlighted that chemotherapy can worsen age-related conditions. Research has demonstrated that there can be considerable variation in how oncologists make decisions for chemotherapy for older patients with other comorbid health conditions.^15–17 In addition, there is considerable variation in how oncology teams intervene on underlying health problems that are negatively impacted by chemotherapy.^18–21

Geriatric assessment (GA) consists of a compilation of validated tools that assess specific domains (eg, function, cognition) that are known to be associated with adverse outcomes in older patients; evidence has been increasing for use of GA for evaluation and management of vulnerabilities in older patients with cancer to help guide shared decision-making for treatment as well as to guide interventions between patients, caregivers, and oncologists.^22,23 While caregiver input about a patient’s functioning is essential, and caregivers can provide critical support to older patients with cancer by facilitating GA-guided interventions, evidence-based interventions that also attend to caregiver burden are necessary.^14,24–26

The guideline was undertaken to facilitate the translation of available evidence into practical recommendations for oncology clinical practice and thereby improve the quality of care for older patients being treated for cancer with chemotherapy. While GA has been shown to potentially be beneficial for older patients undergoing different cancer treatments (eg, surgery, radiation), the guideline focuses on evidence for patients undergoing chemotherapy due to the robustness of data in this area.

Table 1.

Recommended Geriatric Oncology Tools

Assessment of the below GA domains recommended for all patients aged 65+	Recommended Tool and Score Signifying Impairment	Evidence to Support Recommendation	Administration Characteristics	Considerations and other evaluation options
Function	Instrumental Activities of Daily Living (IADLs): Dependence on any task signifies impairment	Large prospective studies of older patients with cancer show IADLs predict chemotherapy toxicity, mortality, hospitalizations, and functional decline. Advocated by experts in Delphi consensus panels.	PRO; <5 min	Consider Activities of Daily Living (ADLs); Any ADL deficit is utilized for characterization of frailty Consider objective measure of physical performance such as Short Physical Performance Battery; Timed Up and Go; or Gait Speed
Falls	Single item: “How many falls have you had over the last 6 months (or since the last visit)?”; one or more recent falls	Falls are common in older adults with cancer and can lead to serious injury. Falls have been associated with chemotherapy toxicity. Assessment for falls is recommended by geriatric oncology expert panels and the American Geriatrics Society for all older adults	PRO;<1 min
Comorbidity	Robust review of chronic medical conditions and medications through routine history: >3 chronic health problems or >1 serious health problem	Comorbidity is associated with poorer survival, chemotherapy toxicity, mortality, and hospitalizations.	Part of routine history	Consider validated tools such as Cumulative Illness Rating Score-Geriatrics (CIRS-G) or Charlson; history, CIRS-G, OARS comorbidity recommended by experts
Cognition	Mini-Cog; An abnormal test is defined by 0 words recalled OR 1-2 words recalled +abnormal clock drawing test. This a screening test for cognitive impairment and abnormal scores require further follow up and decision making capacity assessment.	Growing data shows cognitive impairment is associated with poorer survival in older patients with cancer and increased chemotherapy toxicity risk. Mini-Cog has been shown to have high sensitivity and specificity for identifying cognitive impairment when compared to longer tools.	Administered; <5 min	Multiple tools are available for cognitive assessment. Blessed Orientation Memory Scale is practical and is included in the Cancer-Specific GA developed by Hurria et al. The Mini Mental State Examination (MMSE) has more robust data for prediction of outcomes in older patients with cancer and has been shown to predict chemotherapy toxicity; it is included in the CRASH tool developed by Extermann et al. The Montreal Cognitive Assessment (MOCA) is also utilized by geriatricians. Both MMSE and MOCA are considerably longer than Mini-Cog and Blessed.
Depression	Geriatric Depression Scale (GDS)-15 item; A score of >5 suggests depression and requires follow-up.	Depression has been associated with unexpected hospitalizations, treatment tolerance, mortality, and functional decline in older adults with cancer receiving chemotherapy; these studies primarily assessed depression with the GDS.	PRO; <5 min	GDS recommended also by ASCO guidelines for depression. The Patient Health Questionnaire-9 is an alternative and is also recommended by ASCO guidelines for depression. The mental health inventory is an option and has been associated with outcomes in older patients with breast cancer.
Nutrition	Unintentional weight loss; >10% weight loss from baseline weight); body mass index < 21 kg/m2	Poor nutrition is associated with mortality in older patients with cancer.	PRO;<1 min	Consider G8 and Mini-Nutritional Assessment as alternatives; both are associated with mortality in older patients with cancer.
The following tools can provide estimates of risk for chemotherapy toxicity	Items	Study Population	Administration Characteristics	Considerations
Cancer and Aging Research Group toxicity tool: provides estimates for overall risk of grade 3-5 chemotherapy toxicity.	11 items; prior falls (1 or more vs none), hearing problems (deaf to excellent), limitations in walking one block (limited a lot, limited a little, not limited), difficulties with taking meds, interference of social activities by physical health and/or emotional problems (all of the time to none of the time) as well as age, height, weight, gender, cancer type (gastrointestinal vs genitourinary vs other), dosage (standard vs dose reduced), number of chemotherapy agents (mono vs poly), hemoglobin level, and creatinine clearance.	Patients aged 65+ with a solid tumor malignancy or lymphoma starting a new chemotherapy regimen (any-line)	PRO/Administered; 5 min Available on-line at: http://www.mycarg.org/(br/)Chemo_Toxicity_Calculator	Can ask geriatric assessment variables as part of history or include as part of PRO assessment
Chemotherapy Risk Assessment Scale for High-age patients (CRASH) tool ; provides estimates separately for risk of grade 3 hematologic and grade 3-4 non-hematologic toxicity	Assessment of risk of hematologic toxicity includes: diastolic blood pressure (>72), Instrumental Activities of Daily Living score (<26), and LDH (>459); Assessment of risk of non-hematologic toxicity includes: ECOG PS, Mini-Mental State Examination (<30), and Mini Nutritional Assessment (<28); Chemotherapy intensity is assessed with MAX2 index.	Patients aged 70+ years with histologically proven cancer who were starting chemotherapy	PRO/Administered; Estimated time to completion is on par with full GA (20-30 minutes) Available online: https://moffitt.org/for-healthcare-providers/clinical-programs-and-services/senior-adult-oncology-program/senior-adult-oncology-program-tools).	The CRASH Scale includes GA measures known also to predict other adverse outcomes such as mortality, functional decline, and hospitalizations: IADLs, MMSE, and MNA.
The following screening tools have been independently associated with adverse outcomes in older patients with cancer receiving chemotherapy.	Items	Study Population and Evidence	Administration characteristics	Considerations
G8	8 items covering appetite, weight loss, neuropsychological problems, BMI, number of medications, patient self rated health, and age; score of > 14 signifies impairment Derived from the Mini-Nutritional Assessment	Several large studies have been conducted that include patients aged 70+, which included patients with both solid and hematologic malignancies starting a new chemotherapy agent. G8 is independently associated with mortality (1 year and 3 years) even when controlling for ECOG PS and stage of cancer.	Administered; 5-10 min	G8 can also be used as a screening tool to identify older patients who need more comprehensive geriatric assessment.
Vulnerable Elders Survey-13	13 items including age, self-rated health, common functional tasks, and ability to complete physical activities Score of >3 is associated with mortality and chemotherapy toxicity in older patients with cancer. A score of >7 has been shown to be associated with functional decline	VES-13 score has been shown to be associated with mortality, chemotherapy toxicity, and functional decline.	Administered or PRO (but errors are common with PRO administration); 5-10 min	VES-13 can also be used as a screening tool to identify older patients who need more comprehensive geriatric assessment
Consider assessment of these domains if resources available	Items	Study Population	Administration characteristics	Considerations
Objective physical performance: Short Physical Performance Battery (SPPB), Timed Up and Go (TUG) or gait speed	SPPB includes 3 tests (balance, chair stands, and gait speed); a score of < 9 associated with increased functional decline, nursing home use, and mortality in community dwelling older adults. TUG measures ability for a patient to get out of chair and walk 3 meters or 10 feet and back; a score of > 12 seconds associated with increased risk of falling.	Low SPPB score associated with increased mortality in older women with gynecologic malignancies. TUG and gait speed have been shown to be associated with early mortality (6 months) in older patients with cancer receiving chemotherapy. SPPB and gait speed associated with functional decline in patients with non-metastatic breast cancer receiving chemotherapy.	All administered; 1-5 min depending on test

Table 2.

Geriatric Assessment-Guided Interventions

Geriatric Assessment (GA) Measure	GA-guided Interventions
FUNCTION and FALLS
Instrumental Activities of Daily Living deficit History of falls	-Physical therapy (PT) and/or occupational therapy referrals (OT) to prescribe strength and balance training, assist device evaluation, home exercise program, and safety evaluation -Fall prevention discussion -Home safety evaluation
COMORBIDITY DOMAIN
Comorbidity and polypharmacy considerations	-Involve caregiver in discussions to assess risks of therapy and management of comorbidities -Involve primary care physician and/or geriatrician in decision-making for treatment and management of comorbidities; consider referral to geriatrician -Review medication list and minimize medications as much as possible; consider involving a pharmacist -Assess adherence to medications; have patient bring in medications to review
COGNITION
Screen positive on validated cognitive screen	-Assess decision-making capacity and ability to consent for treatment -Identification of health care proxy and involve proxy in decision-making for treatment including signing consent forms with patient -Delirium risk counseling for patient and family -Medication review – minimize medications with higher risk of delirium -Consider further work up with geriatrician or cognitive specialist
DEPRESSION
Geriatric Depression Screen (GDS) >5	-Consider referral for psychotherapy/psychiatry -Consider cognitive-behavioral-therapy -Social work involvement -Consider pharmacologic therapy
NUTRITION
Weight loss >10%	-Nutrition counseling -Referral to nutritionist/dietician -Assess need for extra support for meal preparation and institute support interventions if necessary (e.g., caregiver, Meals-on-Wheels)

Table 3.

Randomized Controlled Trials of Geriatric Assessment Underway

Study	Design	Population	Intervention Delivery	Management Strategy	Outcomes
Hurria et al. -City of Hope	2:1 Patient randomization n=600	age 65+ with any stage solid tumor malignancies starting a new chemo regimen (any line)	Study NP in collaboration with the primary oncologist and clinic nurse	Established protocol for referral to the multidisciplinary team based on multidisciplinary team input and triggers based on GA results	4 Primary endpoints: Chemo toxicity (Gr3+); Rate of hospitalization; change in functional status; change in psychosocial status
Soubeyran et al.35 -28 Regional Coordination Units for Geriatric Oncology (mix of sites)	Patient randomization n=1200	age 70+ with most solid tumor malignancies candidate for first/second line medical treatment	Geriatrician with nurse follow up	Established protocol based on expert input	Co-primary endpoint of overall survival and dimensions of QoL; Response; PFS; other QoL; chemo tox, health care utilization
Puts et al. -multi-center study of centers in Canada	Patient randomization n=350	aged 70+ with most solid tumor malignancies starting first/second line chemotherapy	Geriatric oncology with nurse follow up	Established protocol based on Delphi consensus and guidelines	QoL; Cost-effectiveness; Function; Chemo tox; Satisfaction; Cancer tx changes; Survival
Mohile et al. -community oncology practices affiliated with University of Rochester NCORP Research Base	Cluster randomization by oncology practice GAP n=700 COACH n=528	aged 70+ with advanced solid tumor malignancies	GA summary results and recommendation given to oncology team	Established protocol based on Delphi consensus panel and guidelines	GAP: chemo toxicity (Gr3+), survival, function COACH: communication, satisfaction, patient and caregiver QoL; health care utilization

THE BOTTOM LINE.

Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology Summary

Overarching Guideline Purpose

To improve treatment outcomes for older patients with cancer through recommendations for appropriate application of validated decision-making models and standardized clinical assessment tools; and recommendations for management of common age-related conditions that may impact the care of older patients with cancer undergoing chemotherapy.

Target Population

Vulnerable older patients with cancer

Target Audience

Medical oncologists, pharmacists, oncology nurses, patients, caregivers, palliative care specialists, advanced practice providers, geriatricians, primary care physicians, social workers, physical therapists, occupational therapists, nutritionists/dieticians

Methods

An Expert Panel was convened to develop clinical practice guideline recommendations based on a systematic review of the medical literature.

Recommendations

1. In patients age 65 and older receiving chemotherapy, geriatric assessment (GA)—the evaluation of functional status, physical performance and falls, comorbid medical conditions, depression, social activity/support, nutritional status, and cognition—should be used to identify vulnerabilities or geriatric impairments that are not routinely captured in oncology assessments (Type: evidence-based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: strong).

2. While many tools are appropriate for assessment of each domain, the Expert Panel provided recommendations based on evidence supporting their utility for predicting adverse outcomes and for ease of administration. In patients aged 65 and older receiving chemotherapy, validated and practical geriatric assessment (GA)-based tools can be used to predict adverse outcomes.

   1. The evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition.
   2. The Expert Panel recommends IADLs to assess for function, a thorough history or validated tool to assess comorbidity, a single question for falls, the Geriatric Depression Scale (GDS) to screen for depression, the Mini- Cog or the Blessed Orientation-Memory-Concentration test (BOMC) to screen for cognitive issues, and assessment of unintentional weight loss to evaluate nutrition.
   3. Either the CARG or CRASH tools are best used to obtain specific estimates on risk of chemotherapy toxicity, while short tools such as G8 or VES-13 can help predict mortality. Table 1 in the full guideline^1a also provides alternatives to these options.

   (Type: evidence-based, benefits outweigh harms; Evidence quality: high that GA tools predict chemotherapy toxicity and mortality; Evidence quality: moderate to recommend specific tools to evaluate GA domains such as function, comorbidity, depression, cognition, and nutrition. Strength of recommendations: moderate.)

3. Based on the best clinical opinion of the Expert Panel, clinicians should use one of the validated tools listed at ePrognosis (https://eprognosis.ucsf.edu/) to estimate life expectancy (LE) greater than or equal to 4 years.

   1. The Expert Panel especially recommends either the Schonberg or Lee Index (https://eprognosis.ucsf.edu/ leeschonberg.php). The most common variables considered in these indices include age, sex, comorbidities (eg, diabetes, COPD), functional status (eg, ADLs, IADLs, mobility), health behaviors and lifestyle factors (eg, smoking status, body mass index), and self-reported health.^27–31
   2. Several indices have “presence of cancer” as a relevant variable; answering “no” to this question will allow for noncancer life expectancy, to consider competing risks of mortality.

   (Type informal consensus, benefits outweigh harms; Evidence quality: high that it predicts mortality, insufficient that it improves outcomes or improves decision making; Strength of recommendation: strong that it predicts mortality; weak that it improves outcomes or improves decision making).

4. Delphi consensus panels of experts have established approaches for implementing GA-guided care processes in older adults with cancer.^22,32

   1. The Expert Panel recommends that clinicians apply the results of GA with patients to develop an integrated and individualized plan that informs treatment selection helping to estimate risks for adverse outcomes (see Recommendation 2), and to identify nononcologic problems (see Recommendation 1) that may be amenable to intervention.
   2. Based on clinical experience and the results of formal expert consensus studies,^22,32 the Expert Panel suggests that clinicians take into account GA results when recommending treatment and that the information be provided to patients and caregivers to guide decision making for treatment.⁶ In addition, clinicians should implement targeted, GA-guided interventions to manage nononcologic problems.
   3. Consistent with the results of formal modified Delphi consensus studies, the ASCO Expert Panel supports the specific high-priority GA-guided interventions outlined in Table 2 in the full guideline.

   (Type of recommendation: informal consensus; Evidence quality: moderate; Strength of recommendation: moderate).

Additional Resources

More information, including a Data Supplement with additional evidence tables, a Methodology Supplement with information about evidence quality and strength of recommendations, slide sets, and clinical tools and resources, is available at www.asco.org/supportive-care-guidelines. Patient information is available at www.cancer.net

ASCO believes that cancer clinical trials are vital to inform medical decisions for older patients with cancer and improve cancer care, and that all older patients should have the opportunity to participate.