GERIATRIC ONCOLOGY

An Introduction

Dr Lissandra Dal Lago, MD, PhD1 and Dr Noam Pondé, MD2

1. Institut Jules Bordet, Brussels, Belgium
2. AC Camargo Cancer Center, São Paulo, Brazil
PLAN OF MODULE

Demographics of cancer and aging

Chronological age vs. functional age

The aging process – Impact on organs and systems

Comprehensive Geriatric Assessment

Chemotherapy toxicity in older patients – Prediction scores

Older patients in clinical research

Concluding remarks
LEARNING OBJECTIVES
At the end of this module you are expected to:

Understand the relationship between cancer and aging

Understand the particular issues, including frailty, that affect cancer management among older patients

Understand how comprehensive geriatric assessment works and what its uses are in oncology – including in
predicting chemotherapy toxicity

Understand the challenges for including older patients in clinical trials

GERIATRIC ONCOLOGY
Demographics of cancer and aging
Europe has a large older population…That will get even larger!
1
Europe2
Population (in millions) 2007 591
2050* 542
Population change 2007 to 2050, % –8.3
Average age 2005 38.9
2050* 47.3
Fertility rate 2006 1.50
Under 15 year olds, % 2007 16
2050* 15
Over 65 year olds, % 2007 16
2050* 28
Life expectancy 2006 76.0
2050* 82.0
*Projection
1. Delivorias A, Sabbati G. EU Demographic Indicators: Situation, Trends And Potential Challenges, March 2015;
https://epthinktank.eu/2015/03/20/eu-demographic-indicators-situation-trends-and-potential-challenges/; accessed Oct 2021. Copyright ©
European Union, 2014. All rights reserved; 2. Iris Hoßmann, Europe’s Demographic Future Berlin Institut, 2008.
GERIATRIC ONCOLOGY
Demographics of cancer and aging

All cancers excluding non-melanoma skin cancer (C00-C97 Excl. C44): UK, 2016–2018

Most adult cancer types increase in

incidence with age

In developed countries people with 75+ years

represent around 1/3 of cancer patients

Cancer Research UK. http://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/age#heading-Zero Accessed Oct 2021

GERIATRIC ONCOLOGY
Demographics of cancer and aging

Cancer is more common among older patients for multiple reasons:

◆ The accumulation of mutations along an extended lifespan
◆ Reduced fitness of intracellular mechanisms that protect from cancer
◆ A pro-tumourigenic tissue environment
◆ Immunosuppression
GERIATRIC ONCOLOGY
Demographics of cancer and aging

Why is cancer more common among older people?

Reprinted from The Cell, 153(6), Lopez-Otin C, et al. The Hallmarks of Aging, 1194-217, Copyright 2013, with permission from Elsevier.
GERIATRIC ONCOLOGY
Chronological age vs. functional age

What does being older mean?

◆ Older is a subjective cultural concept that varies from culture to culture depending on a mixture of
health-related, social and economic factors
◆ In industrialised societies, 70 years old is a standard cut-off point used to define a person as older;
however, in other, poorer or more traditional societies, a lower age may be more appropriate
(such as 65, 60, or even 55)
◆ Persons with the same chronological age can have widely different functional ages

In geriatric oncology, it is functional age that determines management – and, therefore, a great deal of effort
is dedicated to accurately evaluating functionality and maintaining it during treatment
GERIATRIC ONCOLOGY Age cut-off exists to promote awareness,
not to determine management!
Aging is a heterogeneous process

Not all “young Not all “older

persons” are healthy persons” are sick
and functional and dependent

ADLs, activities of daily living; IADLs, instrumental activities of daily living.

Lowsky J, et al. Gerontol A Biol Sci Med Sci 2014;69(6):640–9, by permission of Oxford University Press.
GERIATRIC ONCOLOGY
The aging process – Impact on organs and systems

Aging leads to decline in organ function – including kidney function, heart, respiratory and nervous system,
along others
This decline can be less than obvious based on tests alone, as under normal circumstances, function may be
adequate for necessity
During physiologically stressful moments (such as surgery, chemotherapy, radiotherapy), functional reserve is
necessary and thus limitation may be revealed
GERIATRIC ONCOLOGY
The aging process – Impact on organs and systems

Heart: Decreased heart rate, decreased responsiveness to adrenergic stimuli, increased afterload
Brain: Neuronal loss, changes in synaptic function, hyperactivation of microglial cells
Immune system: Reduced immune response to aggressors
Lungs: Decreasing lung volumes and maximal rates of airflow; decreasing forced vital capacity;
decreased diffusing capacity
Kidney: Including renal cortical loss; progressive decrease in glomerular filtration rate and renal blood flow

The end result = increased risk of acute illness and

of complications during cancer treatment
GERIATRIC ONCOLOGY
The aging process – Frailty

Frailty is a state of increased vulnerability to

stress, which increases the risk of adverse
outcomes – during cancer treatment

It is very important to note that risk factors for

frailty include psychological and social
issues, such as being in a minority ethnic
group, being unmarried or being depressed

Reprinted from The Lancet, 381(9868), Clegg A, et al. Frailty in elderly people, 752–62. Copyright 2013, with permission from Elsevier.
 GERIATRIC ONCOLOGY
The aging process – Frailty

Frailty impacts on surgical outcomes – 432,828 patients

30-d mortality 90-d mortality 180-d mortality

50 50 50
RAI category

180-d mortality rate (%)

30-d mortality rate (%)

90-d mortality rate (%)

40 ≤20 40 40
21-29
30 30-39 30 30
≥40
20 20 20

10 10 10

0 0 0
1 2 3 4 5 1 2 3 4 5 1 2 3 4 5
Operative stress score Operative stress score Operative stress score

Shinall M, et al. JAMA Surg 2020;155(1):e194620.

GERIATRIC ONCOLOGY
The aging process – Frailty

Can frailty be reversed or its onset delayed?

Some data suggests that group-based intervention with exercise can be useful1

Guidelines suggest2:
◆ Physical activity programmes or nutritional interventions or a combination of both
◆ Interventions based on tailored care and/or geriatric evaluation and management
◆ Interventions based on cognitive training (alone or in combination with exercise and
nutritional supplementation)

1. Apostolo J, et al. 2018;16(1):140–232;

2. Marcucci M, et al. BMC Med 2019;17(1):193.
GERIATRIC ONCOLOGY
The aging process – Frailty – Perioperative interventions

Patients aged ≥65 years CGA + Perioperative Geriatric Intervention

GI tumours
Programmed surgery R

N=160 Standard of Care

• Significantly shorter post-op LOS (5.9 vs. 8.2 days; P=0.02)

• Lower rates of post-op ICU use (13.3% vs. 32.4%; P<0.05)
• Readmission rates were not significantly different (16.7% vs. 25.0%; P=0.36)

CGA, Comprehensive Geriatric Assessment; LOS, length of stay.

Quian CL, et al. J Clin Oncol 2020;38(suppl): abstr 12012
GERIATRIC ONCOLOGY
The aging process – Functionality and stress

Minor illness (e.g., urinary tract infection)

Independent

Functional abilities

Dependent

Higher risk of disability, delayed convalescence and

permanent loss of functionality

Reprinted from The Lancet, 381(9868), Clegg A, et al. Frailty in elderly people, 752–62. Copyright 2013, with permission from Elsevier.
GERIATRIC ONCOLOGY IN PRACTICE
First visit to discuss treatment:
◆ Patient history
◆ Cancer
◆ G8 screening tool
◆ Life expectancy

G8 ≤14 Decision making G8 >14

◆ Evaluate patient autonomy or need for
Full CGA surrogate decision making
◆ Identification of domains ◆ Prognosis vs. life expectancy
◆ Benefit vs. toxicity of treatment
◆ Discuss patient’s priorities and goals
Proposed geriatric ◆ Possible social and economic issues
No need of full CGA
◆

interventions that may affect

No treatment Treatment

Follow-up during treatment

GERIATRIC ONCOLOGY
Screening tools – G8

CGA is time-consuming, and considering older heterogeneity, under situations of limited resources, it is possible to
spare some patients full evaluations

Multiple screening tools – shortened forms of CGA that select patients who need full CGA or not at any given
time point – are available

The G8 is a commonly used screening and validated tool that can be easily performed in approximately five minutes

G8 does not replace CGA but in clinical practice might already screen patients
at risk of frailty, and then rationalise the use of available resources –
ideally all patients, and certainly those 80 and above should undergo CGA
GERIATRIC ONCOLOGY
Screening tools – G8
A score of less than 14 is abnormal and correlates with OS

Kenis C, et al. Performance of Two Geriatric Screening Tools in Older Patients With Cancer. J Clin Oncol 2014;32 (1):19–26. Available at:
https://ascopubs.org/doi/full/10.1200/JCO.2013.51.1345; accessed Nov 2021. © 2014 American Society of Clinical Oncology.
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Principles

Comprehensive Geriatric Assessment (CGA) is the standard form of evaluation and follow-up for older patients
before and during cancer treatment
CGA can be defined as “multidimensional interdisciplinary diagnostic process focused on determining a frail older
person’s medical, psychological and functional capability, in order to develop a coordinated and integrated plan for
treatment and long-term follow-up”
It identifies problems that are not identified by routine patient history and physical examination
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Examples of scales/tools

Domains Scales
Functional status Eastern Co-operative Oncology Group performance status, Katz basic Activities of Daily Living
Scale, Simplified Lawton’s Instrumental Activities of Daily Living Scale
Comorbidities Charlson comorbidity index
Medications Number, type, indication
Cognitive function Folstein Mini-Mental State Examination, Schultz-Larsen Mini-Mental State Examination
Geriatric syndrome Repeated falls, faecal and/or urinary incontinence
Depression/mood Geriatric Depression Scale 5, Emotional questionnaire
Nutrition Body mass index
Mobility Timed Up and Go test
Situational assessment Accessibility of services, mobility, social environment, accessibility of home rooms

Corre R, et al. J Clin Oncol 2016;34(13):1476–83.

 GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Comparison of 4 tools of evaluation if frailty
All tools predict 1-year mortality All tools predict 6 month hospital admission
P-value, Admissions, n (%) P-value,
Classification Patients, n (%) Events, n (%) log-rank test; trend HR (95% CI)a log-rank test;
No (n=434) Yes (n=279)
Classification Patients, n (%) trend
Balducci <0.001; <0.001
Fit 97 (12.9) 11 (11.3) 1.00 (reference) Balducci <0.001; <0.001
Vulnerable 113 (14.9) 31 (27.4) 1.91 (0.95, 3.85) Fit 95 (13.8) 77 (18.4) 18 (6.6)
Frail 544 (72.2) 278 (51.1) 2.94 (1.59, 5.43) Vulnerable 106 (15.4) 70 (16.7) 36 (13.3)
Frail 489 (70.9) 272 (64.9) 217 (80.1)
SIOG1 <0.001; <0.001
Fit 147 (19.5) 19 (12.9) 1.00 (reference) SIOG1 <0.001; <0.001
Vulnerable 234 (31.1) 66 (28.2) 1.75 (1.03, 2.97) Fit 142 (20.6) 115 (27.5) 27 (10.0)
Frail 286 (37.9) 167 (58.4) 3.31 (2.00, 5.50) Vulnerable 213 (30.9) 132 (31.5) 81 (29.9)
Too sick 87 (11.5) 68 (78.2) 6.12 (3.45, 10.85) Frail 262 (38.0) 130 (31.0) 132 (48.7)
Too sick 73 (10.5) 42 (10.0) 31 (11.4)
SIOG2 <0.001; <0.001
Fit 134 (17.8) 11 (8.2) 1.00 (reference) SIOG2 <0.001; <0.001
Vulnerable 112 (14.8) 28 (25.0) 2.08 (1.02, 4.22) Fit 134 (19.4) 109 (26.0) 25 (9.2)
Frail 508 (67.4) 281 (55.3) 3.69 (1.97, 6.89) Vulnerable 107 (15.5) 75 (17.9) 32 (11.8)
Frail 449 (65.1) 235 (56.1) 214 (79.0)
LC typology <0.001; <0.001
Relatively healthy 227 (30.1) 27 (11.9) 1.00 (reference) LC typology <0.001; <0.001
Malnourished 252 (33.4) 110 (43.6) 2.15 (1.34, 3.47) Relatively healthy 216 (31.3) 172 (41.1) 47 (16.2)
Cognitively and/or 103 (13.7) 44 (42.7) 2.66 (1.54, 4.61) Malnourished 233 (33.8) 127 (30.3) 106 (39.1)
mood impaired 172 (22.8) 139 (80.8) 4.84 (2.82, 8.31) Cognitively and/or 87 (12.6) 50 (11.9) 37 (13.7)
Globally impaired mood impaired 154 (22.3) 70 (16.7) 84 (31.0)
Globally impaired

aAllCox models were stratified on in- or outpatient status and adjusted for composite variable, including tumour site and metastatic status,
age, year of inclusion, and treatment decision (palliative, curative, or not reported).
Ferrat E, et al. Performance of Four Frailty Classifications in Older Patients With Cancer: Prospective Elderly Cancer Patients Cohort Study.
J Clin Oncol 2017;35(7):766–77. Reprinted with permission. © 2017 American Society of Clinical Oncology.
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Functional status

Functional status is mainly determined by the capacity of performing:

◆ Activities of daily living (ADL): Concerns basic self care (e.g., bathing, dressing, eating), as well as
mobility, balance and continence
◆ Instrumental activities of daily living (IADL): Concerns the ability to perform daily activities, such as
shopping, banking, cooking, etc.

Performance status (ECOG or Karnofsky) lacks reliability as a form of functional evaluation in older patients
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Functional status

QoL
Quality of Life (QoL) questionnaires may also be a part of
functional assessment

IADL

Maione P, et al. Pretreatment Quality of Life and Functional Status Assessment Significantly Predict Survival of Elderly Patients With Advanced Non-Small-
Cell Lung Cancer Receiving Chemotherapy: A Prognostic Analysis of the Multicenter Italian Lung Cancer in the Elderly Study. J Clin Oncol 2005;23(28):6865–
72; Available at: https://ascopubs.org/doi/full/10.1200/JCO.2005.02.527; accessed Nov 2021. © 2005 American Society of Clinical Oncology.
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Comorbidities

Older patients have a higher incidence of other chronic diseases:

◆ Chronic diseases that are not immediately-life threatening, but can speed up loss of organ function and
limit survival
◆ More serious diseases, such as heart failure or emphysema, can be important competing causes of morbidity
and mortality in a older patient diagnosed with cancer
Therefore, before planning cancer treatment, it is important to estimate the patient’s life expectancy and what are the
limits that comorbidities will place on the treatment plan
Life expectancy is also deeply affected by other domains such as functionality, social status and cognition
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Comorbidities
Condition Assigned weight
Myocardial infarction 1
Congestive heart failure 1 Charlson Index measures risk of death in the next year
Peripheral vascular disease 1
Cerebrovascular disease 1 During CGA, comorbidities should be identified, and
Dementia 1 optimal management initiated
Chronic pulmonary disease 1
Connective tissue disease 1
Comorbid medical conditions might limit cancer
Ulcer disease 1
Liver disease, mild 1 treatment options in older patients.
Diabetes 1
Hemiplegia 2
Renal disease, moderate or severe 2
Diabetes with end organ damage 2
Any malignancy 2
Leukaemia 2
Malignant lymphoma 2
Liver disease, moderate or severe 3
Metastatic solid malignancy 6

Albertsen PC, et al. J Clin Oncol 2011;29(10):1335–41.

GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Comorbidities

• Charlson index increase correlates with risk

of dying from non-cancer causes

Albertsen PC, et al. Impact of Comorbidity on Survival Among Men With Localized Prostate Cancer. J Clin Oncol 2011;29(10):1335–41.
Available at: https://ascopubs.org/doi/full/10.1200/JCO.2010.31.2330; accessed Nov 2021. © 2011 American Society of Clinical Oncology.
 Four-Year Mortality Index for Older Adults
Parameter Result Points
GERIATRIC ONCOLOGY 1. Age (years) 60–64
65–69
1
2
Comprehensive Geriatric Assessment – 70–74 3
75–79 4
Estimating life expectancy 80–84 5
≥85 7
2. Sex (Male/Female) Male 2
Lee index predicts mortality in 4 and 10 years 3. BMI [703 × (weight in pounds/height in inches2)] BMI <25 1
4. Has a doctor ever told you that you have diabetes or high Diabetes 1
It integrates age, comorbidity and cognition and functionality blood sugar? (Y/N)
5. Has a doctor told you that you have cancer or a malignant Cancer 2
Age group (y)
tumour, excluding minor skin cancers? (Y/N)
≥80 (n=2579) AUC = 6. Do you have a chronic lung disease that limits your usual Lung 2
80 70–79 (n=4921) 0.7239 activities or makes you need oxygen at home? (Y/N) disease
50–69 (n=12,125) 7. Has a doctor told you that you have congestive heart failure? Heart 2
Four-year mortality (%)

60 0.7601 (Y/N) failure

8. Have you smoked cigarettes in the past week? (Y/N) Smoke 2
40 0.7708 9. Because of a health or memory problem do you have any Bathing 2
difficulty with bathing or showering? (Y/N)
20 10.Because of a health or memory problem, do you have any Finances 2
difficulty with managing your money—such as paying your bills
and keeping track of expenses? (Y/N)
0
11.Because of a health problem do you have any difficulty with Walking 2
0 2 4 6 8 ≥10 walking several blocks? (Y/N)
Risk score 12.Because of a health problem do you have any difficulty with Push or 1
(excluding age contribution) pulling or pushing large objects like a living room chair? (Y/N) pull

Lee S, et al. JAMA 2006;295(7):801–8.

GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Cognition

Cognition in cancer patients is crucial for treatment compliance

Patients need to be able to understand information given, prognosis and treatment options
When cognitive dysfunction is suspected, specific screening tools such as mini-Cog can be applied – caregivers can
also be a valuable source of additional information
Ideally, patients need to be able to make decisions independently
Older patients may have cognitive dysfunction that partly or completely precludes decision making – and in such
cases family members, caregivers and geriatricians who are familiar with the patient may give valuable information
Cognitive dysfunction should be carefully differentiated from depression and hearing problems

NCCN guidelines
GERIATRIC ONCOLOGY
Decision-making and priorities

Older persons may have different priorities when making decisions – such as maintaining functionality and
independence – that may be to them more important than living longer
Establishing these priorities clearly is a critical aspect of defining cancer care
Ideally, patients need to be able to make decisions independently
Older patients may have cognitive dysfunction that partly or completely precludes decision making – and in such
cases family members, caregivers and geriatricians who are familiar with the patient may give valuable information

Don’t forget that family members and caregiver (even geriatricians) can lose
objectivity and provide information based on their needs and not the patient’s
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Cognition
Multiple factors affect cognition of cancer patients

Reprinted from Cancer Treatment Reviews, 40(6), Lange M, et al. Cognitive dysfunctions in elderly cancer patients: A new challenge for
oncologists, 810–7. Copyright 2014, with permission from Elsevier.
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Nutritional status

Malnourishment can be defined as a state of nutrition in which a deficiency or imbalance of energy, protein,
and other nutrients causes measurable adverse effects on tissue and/or body form
In older patients, three different forms can be present separately or together:
◆ Wasting: loss of weight that is involuntary and due to low nutritional intake
◆ Cachexia: involuntary loss of body mass caused by catabolism
◆ Sarcopenia: involuntary loss of muscle mass and muscle function, which can be disease related or not
in older patients

Norman K, et al. Clin Nutr 2008.

GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Nutritional status
Malnutrition is a significant problem among older persons, specially those with cancer

General population data using MNA

Kaiser MJ, et al. J Am Geriatrics Soc 2010;58(9):1734–8. © 2010, Copyright the Authors. Journal compilation © 2010, The American
Geriatrics Society.
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Nutritional status

Causes for anorexia in older patients

 Energy expenditure Physiological changes with aging

Hormonal
Cytokines
Anorexia and aging  Taste and smell
 Changes in GI tract

 Exercise Pathological changes with aging

Medical
Drugs
Physiological
Social
Ahmed T, Haboubi N. Clin Interv Aging 2010;5:207–16. Reproduced under the terms of CC-BY-NC V3.0 licence (available at: .
https://creativecommons.org/licenses/by-nc/3.0/; accessed Nov 2021).
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Nutritional status

Malnutrition impacts chemotherapy toxicity:

◆ Weight loss
◆ Hypoalbuminemia
◆ Low body nitrogen
◆ Sarcopenia
◆ Low BMI

Malnutrition is also an independent negative prognostic factor

GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Psychological state

Link between old age and depression

Long-standing
Self-critical
vulnerabilities (e.g.
cognitions
cognitive style)

Low rate of
Stressful life events and Limitation of
positive Depression
loss of social roles activities
outcomes

Changes in health,
physical ability, or
cognitive ability

Fiske A, et al. Annu Rev Clin Psychol 2009;5:363–89.

GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Social support

Cancer patients of all ages profit from extensive social support

Older patients are likely to have less social support due to widowhood, death of friends and other family members
Social support is especially critical considering the complexity of undergoing cancer treatment – correctly taking
medications at home, keeping appointments, bringing exams and seeking assistance in case of complications
Abuse of older persons (physical, economic and emotional) also remains a problem, as well as the disempowerment
of independent patients by their family members after a diagnosis of cancer
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Medication use

Older patients often use multiple drugs besides those connected to cancer treatment, putting them at risk
of polypharmacy
Polypharmacy may be defined in different ways but is at its core the combination of number of medication and utility
of medications
Older persons tend to accumulate both physicians and treatments
E.g.: A 75-year-old man with metastatic lung cancer takes statins to control his cholesterol
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Medication use

What problems can polypharmacy cause?

Medication-related problems associated with polypharmacy
◆ Adverse drug reactions
◆ Duplication of therapy
◆ Adverse drug-drug interactions
◆ Adverse drug-disease interactions
◆ Adherence to treatment
◆ Cost

Balducci L, et al. Ann Oncol 2013;24(suppl_7):vii36-40.

GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Medication questions

Is there a proper indication for each drug?

Is the medication proving effective?
Is the medication causing side effects?
Is the dose appropriate?
Is there potential for significant interactions?
Is there potential of interaction with planned cancer treatment?
Can a drug affect the tumour?
Does the patient adhere to the treatment plan?
Are there other conditions that need treatment?

Adapted from Balducci L, et al. Ann Oncol 2013;24(suppl_7):vii36-40.

GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Geriatric syndromes

The concept of geriatric syndrome differ from those of disease and syndrome

Geriatric
syndrome

Multiple Interacting Unified

aetiological factors pathogenetic pathways manifestation

Inouye S, et al. J Am Geriatr Soc 2007;55(5):780–91

GERIATRIC ONCOLOGY
Chemotherapy side effects in older patients

Risk of chemotherapy side effects might be increased in older patients

Older patients can expect a higher rate of neutropenia, fatigue, cardiac toxicity and neuropathy than
younger patients
Older patients more often need dose reductions, delays and permanent interruptions than younger patients
However, older patients benefit from standard chemotherapy regimens, including doublets in breast cancer
and lung cancer, if carefully selected and followed
GERIATRIC ONCOLOGY
Chemotherapy toxicity in older patients – Prediction tools

Two scores developed in cancer population to predict treatment complications based on data generated by CGA

Chemotherapy Risk Assessment

Cancer and Age Research
Scale for High-Age Patients
Group (CARG) Score
(CRASH) Score

Extermann M, et al. Cancer 2012;118:3377–86.

GERIATRIC ONCOLOGY
Chemotherapy side effects in elderly patients – CRASH

Predicting the Risk of Chemotherapy Toxicity in Older Patients:

The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) Score1

Prospective study on patients seventy or older (N=331)

Estimates grade 3-4 CT toxicity
Score composed of a haematologic and non-haematologic variables
Divides patients into 4 groups: low, medium-low, medium-high and high
Internal validation (n=187)

1. Extermann M, et al. Cancer 2012;118(13):3377–86.

GERIATRIC ONCOLOGY
Chemotherapy side effects in older patients – CRASH score

Points
Predictors 0 1 2
Haematologic score
Diastolic BP ≤72 >72
IADL 26–29 10–25
LDH (if ULN 618 U/L;
0–459 >459
otherwise, 0.74/L*ULN)
Chemotox 0–0.44 0.45–0.57 >0.57
Nonhaematologic score
ECOG PS 0 1–2 3–4
MMS 30 <30
MNA 28–30 <28
Chemotox 0–0.44 0.45–0.57 >0.57

Extermann M, et al. Cancer 2012;118:3377–86

GERIATRIC ONCOLOGY
Chemotherapy side effects in older patients – CRASH score

Haematologic score Nonhaematologic score Combined score

*Only two patients

Reproduced from: Extermann M, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment
Scale for High-Age Patients (CRASH) score. Cancer 2012;118(13):3377–86. by permission of John Wiley and Sons Ltd. Copyright © 2011
American Cancer Society.
GERIATRIC ONCOLOGY
Chemotherapy side effects in elderly patients – CARG

Predicting chemotherapy toxicity in older adults with cancer:

A prospective multicentre study

◆ 65 or older
Diagnosis of cancer Chemotherapy with toxicity
CGA Post-chemo CGA
◆

◆ To start a new grading at each visit

chemotherapy regimen

Hurria A, et al. J Clin Oncol 2011;29(25):3457–65.

GERIATRIC ONCOLOGY
Predictors of CT toxicity – CARG score

◆ Age ≥72 years Age

◆ GI/GU cancer
◆ Standard dose Tumour/Treatment Variables
◆ Polychemotherapy
◆ Haemoglobin (male: <11, female: <10)
Labs
◆ Creatinine clearance (Jelliffe-ideal weight)
◆ Fall(s) in last 6 months
◆ Hearing impairment (fair or worse) Geriatric
◆ Limited in walking 1 block Assessment
◆ Assistance required in medication intake (IADL) Variables
◆ Decreased social activity

Hurria A, et al. J Clin Oncol 2016;34(20):2366–71.

GERIATRIC ONCOLOGY
CARG score

Estimates risk of grade 3-5 toxicity

Categorises patients into 3 risk groups

– low, intermediate and high
0–5 6–9 10–19

External validation

Hurria A, et al. Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer. J Clin Oncol 2016;34(20):2366–71.
Available at: https://ascopubs.org/doi/pdf/10.1200/JCO.2015.65.4327; accessed Nov 2021. Reprinted with permission. © 2016 American
Society of Clinical Oncology.
GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: GAIN Trial – Study design

Daneng Li, et al. J Clin Oncol 2020;38(15)_suppl):12010 (presented at ASCO 2020); ClinincalTrials.gov identifier: NCT02517034.
Reproduced with permission from Dr Daneng Li, et al.
GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: GAIN Trial (N=605)

n (%) [95% CI]

Toxic effects GAIN (n=402) SOC (n=203) Total (N=605) P-value
Patients with grade 3 or higher
203 (50.5) [45.6, 55.4] 123 (60.6) [53.9, 67.3) 326 (53.9) [49.9, 57.9] 0.02
chemotherapy-related toxic effects
Haematologic only 45 (11.2) [8.1, 14.3] 39 (19.2) [13.8, 24.6] 84 (13.9) [11.1, 16.6] 0.003
Non-haematologic only 74 (18.4) [14.6, 22.2] 54 (26.6) [20.5, 32.7] 128 (21.2) [17.9, 24.4] 0.007
Both haematologic and non-haematologic 84 (20.9) [16.9, 24.9] 30 (14.8) [9.9, 19.7] 114 (18.8) [15.7, 22.0] 0.64

Implementation of geriatric assessment and intervention reduced grade 3 or higher

adverse events related to chemotherapy

Daneng Li, et al. JAMA Oncol 2021;7(11):e214158.

 GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: GAIN Trial (N=605)

Secondary outcomes comparisons between GAIN and SOC arms

n (%) [95% CI]
Outcomex GAIN (n=402) SOC (n=203) Total (n=605) P-valuea
Absolute change in AD statusb 114 (28.4) [24.0, 32.8] 27 (13.3) [8.6, 18.0] 141 (23.3) [19.9, 26.7] <0.001
Emergency department visit 110 (27.4) [23.0, 31.7] 62 (30.5) [24.2, 36.9] 172 (28.4) [24.8, 32.0] 0.41
Unplanned hospitalisation 89 (22.1) [18.1, 26.2] 39 (19.2) [13.8, 24.6] 128 (21.2) [17.9, 24.4] 0.41
Average length of stay, days
Mean (SD) 5.9 (4.2) 6.8 (5.6) 6.2 (4.7) NA
Median (range) 5 (1–23) 5 (1–26) 5 (1, 26) 0.60c
Unplanned readmission 17 (19.1) [10.9, 27.3] 8 (20.5) [7.8, 33.2] 25 (19.5) [12.7, 26.4] 0.85
Early chemotherapy discontinuation 216 (53.7) [48.9, 58.6] 118 (58.1) [51.3, 64.9] 334 (55.2) [51.2, 59.2] 0.30
Chemotherapy dose modificationsd 218 (54.2) [49.4, 59.1] 95 (46.8) [39.9, 53.7] 313 (51.7) [47.8, 55.7] 0.08
A : P values were obtained from X2 test unless otherwise noted
b : Absolute change in AD status reflects the change from no AD at baseline to having an AD at the end of primary/secondary outcome follow-up
c: P value was obtained from Kruskal-Wallis test
d: dose modifications: reductions or delays

AD, Advance directive

Daneng Li, et al. JAMA Oncol 2021;7(11):e214158.
GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: GAP 70+

Study schema: Geriatric assessment for patients 70+

GA Intervention Arm
Oncology physician provided with GA
summary and GA-guided Endpoints
recommendations for each enrolled ◆ Clinician-rated grade 3-5 toxicity
participant prior to starting a new Survival at 6 months
R
◆

chemotherapy/agent(s) with similar ◆ Treatment decisions

prevalence of toxicity ◆ Functional and physical decline
◆ Patient-reported toxicities

Usual care

Presented at ASCO 2020; with permission from Dr Supriya Mohile.

Mohile SG, et al. The Lancet 2021, 398(10314); 1894-1904.
GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: GAP 70+

Any Grade 3-5 CTCAE toxicity in 3 months

◆ Any Grade 3-5 toxicity
◆ Adjusted Risk Ratio: 0.74
◆ 95% CI: 0.63, 0.87 (P<0.01)
◆ Clustering effect: P=0.15
◆ Any Grade 3-5 haematologic toxicity
◆ Adjusted Risk Ratio: 0.85
◆ 95% CI: 0.69, 1.05 (P=0.13)
◆ Clustering effect: P=0.30
◆ Any Grade 3-5 non-haematologic toxicity
◆ Adjusted Risk Ratio: 0.73
◆ 95% CI: 0.53, 0.996 (P=0.047)
◆ Clustering effect: P<0.01

Presented at ASCO 2020; with permission from Dr Supriya Mohile.

Reprinted from The Lancet, 398 (10314), Mohile SG, et al., Evaluation of geriatric assessment and management on the toxic effects of cancer
treatment (GAP70+): a cluster-randomised study, 1894-1904, Copyright (2021), with permission from Elsevier.
GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: GAP 70+

Treatment intensity
◆ Adjusted Risk Ratio = 1.37 ◆ Adjusted Risk Ratio = 0.85
95% CI: 1.06, 1.76 (P=0.016) 95% CI: 0.67, 1.08 (P=0.190)
Clustering effect: P=0.03 Clustering effect: P<0.01

Reduced dose intensity at Cycle 1 Dose modification at 3 months related to toxicity

Presented at ASCO 2020; with permission from Dr Supriya Mohile.

Reprinted from The Lancet, 398 (10314), Mohile SG, et al., Evaluation of geriatric assessment and management on the toxic effects of cancer
treatment (GAP70+): a cluster-randomised study, 1894-1904, Copyright (2021), with permission from Elsevier.
GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: INTEGERATE study

Integrated oncogeriatric care Primary: HRQOL

Age ≥70 years
n=76
Solid tumours Secondary:
For chemo-/ immuno-/ Healthcare utilisation
targeted therapy R Treatment delivery
Function
No treatment ≤3 months Institutionalisation
N=154
Usual care Mood
n=78 Nutrition
Health utility
Survival

Soo W-K, et al. J Clin Oncol 2020;38(15_suppl):12011. Presented at ASCO 2020.

GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: INTEGERATE study

Primary outcome: Health-related quality of life

Intervention group reported significantly better scores than usual care group in the following other HRQOL domains:
◆ Functioning (physical, role, social)
◆ Mobility
◆ Burden of illness
◆ Future worries
Functional benefits were maximal around Week 18, then reduced by Week 24
Benefits in the social functioning, burden of illness and future worries domains persisted (to end of study at Week 24)

Soo W-K, et al. J Clin Oncol 2020;38(15_suppl):12011. Presented at ASCO 2020.

GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: INTEGERATE study

Secondary outcomes: Hospitalisation Time to first planned hospital admission

39% fewer emergency presentations
◆ Incidence rate ratio (IRR)* 0.61 (95% CI: 0.46, 0.77; P=0.007)
◆ –1.3 emergency presentations per person-year
41% fewer unplanned hospital admissions
◆ IRR* 0.59 (95% CI: 0.41, 0.86; P<0.001)
◆ –1.2 admissions per person-year
24% fewer unplanned hospital overnight bed-days
◆ IRR* 0.76 (95% CI: 0.68, 0.85: P<0.001)
◆ –7.0 days per person-year

*Adjusted for age, gender, ECOG-PS, cancer type and treatment intent.
Soo W-K, et al. J Clin Oncol 2020;38(15_suppl):12011. Presented at ASCO 2020. With permission from Dr Wee-Kheng Soo
GERIATRIC ONCOLOGY
Evidence for the benefit of interventions: INTEGERATE study

Secondary outcomes: Treatment delivery

Lower early treatment discontinuation due to adverse events (32.9% vs. 53.2%; P=0.01)
◆ Driven by fewer discontinuations due to toxicity

No difference in treatment reduction, escalation or delay

Soo W-K, et al. J Clin Oncol 2020;38(15_suppl):12011. Presented at ASCO 2020.

GERIATRIC ONCOLOGY
Participation of older patients in clinical trials

Clinical trials are the main driver of improvement in cancer treatment outcomes
As the proportion of older patients increases for a large number of solid tumours, it becomes critical to ensure that
older patients participate in clinical trials
Historically, however, participation has been low in proportion to the actual number of older patients for
multiple reasons
Clinical trials targeting older and frail patients are necessary, and also for leveraging real-world data

Sedrak MS, et al. CA Cancer J Clin 2021:71(1):78–92; Wildiers H, A de Glas Nienke. Anticancer drugs are not well tolerated in all older
patients with cancer. The Lancet Healthy Longevity. Vol 1 Oct 2020: e43-e47.
GERIATRIC ONCOLOGY
Participation of older patients in clinical trials
A study of the participation of older patients in alliance trials

Freedman RA, et al. Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527. J Clin
Oncol 2016;35(4):421–31. Available at: https://ascopubs.org/doi/full/10.1200/JCO.2016.69.4182; accessed Nov 2021. © 2016 by American
Society of Clinical Oncology.
GERIATRIC ONCOLOGY
Participation of older patients in clinical trials

Present challenges in gaining informed consent

Multiple comorbid conditions may pose challenges in outcomes assessment
Polypharmacy may lead to drug-drug interactions
Challenges in compliance with clinical study procedures
May necessitate age-relevant formulations and packing
Fear of failure due to confounding behaviour of the drug in older patients
Sponsors may incur higher cost for medical management and compensation
Institutional and logistic problems
May need supportive care
Investigator's preferences and perceived difficulties in screening
Protocol restrictions with exclusion criteria on age or age-related comorbidities

Premath S, et al. Perspect Clin Res 2015;6(4):184–9.

 GERIATRIC ONCOLOGY
Participation of older patients in clinical trials
Beyond OS, iDFS and PFS for older patients: End-points that include tolerability
End Point Definition Current Situation Pro Con
TFFS and TTF: TFFS is time elapsing between Often used in addition to OS Integrates efficacy and toxicity Difficult to distinguish between
time or proportion random assignment and early efficacy and toxicity (e.g., toxic but
treatment discontinuation because of effective)
any reason (including disease
Treatment might be stopped for
progression, treatment toxicity, early
other reasons (e.g., chemotherapy
death), disease progression, death
holiday)
(resulting from any cause), or any
other event of interest; TTF is similar,
but death resulting from any other
cause is not considered an event

QoL-related endpoints: Evaluation of QoL through validated Often used as secondary endpoint QoL may be more important than Difficult to measure and identify
Level at specified timepoint or instruments at baseline and during in clinical trials but should be duration of life for many older clinically relevant cutoffs that
time until deterioration compared course of disease/treatment/study promoted as primary endpoint or individuals determine whether therapy is
with baseline part of composite endpoint worthwhile
Maintenance of functional Evaluation of evolution of functioning Rarely measured in oncology trials Main contributor to QoL in elderly No general consensus on optimal
capacity/dependence: level at and (in)dependence through but crucial to include patients with cancer measurement or clinically relevant
specified timepoint or time until validated instruments during course cutoffs determining whether therapy
deterioration compared with of disease/treatment/study is worthwhile
baseline

DSS, disease-specific survival; TFFS, treatment failure–free survival; TTF, time to treatment failure.
Wildiers, et al. J Clin Oncol 2013;31(29):3711–8.
GERIATRIC ONCOLOGY
Concluding remarks

Older patients will dominate future oncology practice

More initiatives are necessary to educate oncologists and integrate geriatrics into usual oncology practice
and services

Critically, more older-centred studies with appropriate endpoints are necessary to provide the basis for more specific
treatment standards

Together this will allow to close the gap that currently exists between younger and older patients, and will lead to
better outcomes
THANK YOU!