GERIATRIC ONCOLOGY

An Introduction

Dr Lissandra Dal Lago, MD, PhD

Dr Noam Pondé, MD
Institut Jules Bordet, Brussels, Belgium
PLAN OF MODULE

Demographics of cancer and aging

Chronological age vs. functional age

The aging process – Impact on organs and systems

Comprehensive Geriatric Assessment (CGA)

Chemotherapy toxicity in elderly patients – Prediction scores

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 that affect elderly cancer management

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

Demographics of cancer and aging

Europe has a large elderly population…That will get even larger!
EU28 population by age and sex (2013 and 2000)1
Europe2
Population (in 2007 591
millions) 2050* 542
Population change -8.3
2007 to 2050, %
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 May 2017. Copyright © European Union, 2014. All rights reserved;
2. Iris Hoßmann, Europe’s Demographic Future Berlin Institut. 2008
GERIATRIC ONCOLOGY

Demographics of cancer and aging

 Most adult cancer types increase in incidence with age

 In developed countries, people aged 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 February 2017

GERIATRIC ONCOLOGY

Demographics of cancer and aging

Cancer is more common in elderly patients for multiple reasons:

 The accumulation of mutations along an extended lifespan

 Reduced fitness of intracellular mechanisms that protect from cancer

 A pro-tumorigenic tissue environment

 Immunosuppression
 GERIATRIC ONCOLOGY

Demographics of cancer and aging

Why is cancer more common in

elderly people?

Reprinted from The Cell, Vol 153, issue 6, Lopez-Otin C, et al., The Hallmarks of Aging, 1194-1217, Copyright 2013, with permission from Elsevier.
GERIATRIC ONCOLOGY

Chronological age vs. functional age

What does being elderly mean?

 Elderly 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 elderly; however, in other, poorer or more traditional societies, a lower
age may be more appropriate (such as 65, 60 or even 55)
 Chronological age and functional age can differ greatly from person to person

In geriatric oncology, it is functional age that determines management –

and therefore a great deal of effort is dedicated to accurately evaluating
and maintaining functionality during treatment
GERIATRIC ONCOLOGY
Aging is a heterogeneous process

Not all “young

Not all ”elderly
persons” are
persons” are sick
healthy and
and dependent
functional

Age cut-off exists to promote awareness, not to determine management!

Lowsky J, et al., Gerontol A Biol Sci Med Sci (2014) 69 (6):640-649, 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 during chemotherapy, for example),

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: Increasing 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, Vol.381, Issue 9868, Clegg A, et al., Frailty in elderly people, 752-762,
Copyright 2013, with permission from Elsevier.
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, Vol.381, Issue 9868, Clegg A, et al., Frailty in elderly people, 752-762, Copyright 2013, with permission from Elsevier.
GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Principles

Comprehensive Geriatric Assessment (CGA) should be the standard form of evaluation

and follow-up for elderly 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 – Principles

CGA is classically divided into “domains”, with each domain corresponding to one
aspect of aging-related issues

Each domain is evaluated through one (or more) validated tools

Domains include: Comorbidity, functional status, cognition, psychological state,

nutrition, fatigue, medication and social status

During CGA, there is no definitive evidence to determine the specific use of a set of
tools over another
GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Examples of scales/tools

Domains Scales
Functional status Eastern Cooperative 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, fecal and/or urinary incontinence
Depression/mood Geriatric Depression Scale 5, Emotional questionnaire
Nutrition Body mass index
Mobility Timed Up and Go test
Situational Accessibility of services, mobility, social environment, accessibility of home rooms
assessment

Corre R, et al., J Clin Oncol 2016;34(13):1476–483.

GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment –
Comparison of 4 tools for evaluation of frailty
All tools predict 1-year mortality

Ferrat E, et al., Performance of Four Frailty Classifications in Older Patients With Cancer: Prospective Elderly Cancer Patients Cohort StudyJ Clin Oncol.
2017;35(7):766–777. Reprinted with permission. © 2017 American Society of Clinical Oncology
GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment –
Comparison of 4 tools for evaluation of frailty
All tools predict 6-month hospital admission

Ferrat E, et al., Performance of Four Frailty Classifications in Older Patients With Cancer: Prospective Elderly Cancer Patients Cohort StudyJ Clin Oncol.
2017;35(7):766–777. Reprinted with permission. © 2017 American Society of Clinical Oncology
GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Functional status

Functional status is determined principally by the capacity of performing essential acts

of self care:
 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 elderly patients
 GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Functional status

Quality of Life (QoL) questionnaires may

also be a part of functional assessment QoL

IADL

Maione P, et al., J Clin Oncol, 23(28) 2005: 6865-6872Reprinted with permission. © (2005) American Society of Clinical Oncology. All rights reserved.
GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Comorbidity

Elderly patients have a higher probability of having other diseases:

 Chronic diseases that are not immediately life-threatening 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 – and even more significant than
cancer, depending on the situation

Therefore, before planning cancer treatment, it is important to understand the patient’s

life expectancy and the limits 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 – Comorbidity
Condition Assigned weight
Myocardial infarction 1
Congestive heart failure 1
Peripheral vascular disease 1 The Charlson Index measures risk of death
Cerebrovascular disease 1 in the next year
Dementia 1
Chronic pulmonary disease 1 During CGA, these and other comorbidities
Connective tissue disease 1 should be identified and optimal
Ulcer disease 1 management initiated
Liver disease, mild 1
Diabetes 1 In certain situations, depending on the
Hemiplegia 2 seriousness of the comorbidities, treatment
Renal disease, moderate or severe 2
Diabetes with end organ damage 2
of cancer should be delayed, modulated or
Any malignancy 2 entirely foregone
Leukaemia 2
Malignant lymphoma 2
Liver disease, moderate or severe 3
Metastatic solid malignancy 6

Albertsen PC, et al., J Clin Oncol, 29(10), 2011: 1335–1341. Reprinted with permission. © (2011) American Society of Clinical Oncology. All rights reserved.
GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Comorbidity

A Charlson index increase

correlates with risk of dying
from non-cancer causes

Albertsen PC, et al., J Clin Oncol, 29(10), 2011: 1335–1341. Reprinted with permission. © (2011) American Society of Clinical Oncology. All rights reserved.
 GERIATRIC ONCOLOGY
Comprehensive Geriatric Assessment – Estimating life expectancy
Four-Year Mortality Index for Older Adults
Parameter Result Points
• Lee index predicts mortality in
1. Age (years) 60–64 1 4 and 10 years
65–69 2
70–74
75–79
3
4
• It integrates age, comorbidity,
80–84 5 cognition and functionality
≥85 7
2. Sex (Male/Female) Male 2
Age group (y)
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 ≥80 (n=2579) AUC =
blood sugar? (Y/N) 80 0.7239
70–79 (n=4921)
5. Has a doctor told you that you have cancer or a malignant Cancer 2 50–69 (n=12125)

Four-year mortality (%)

tumour, excluding minor skin cancers? (Y/N) 60 0.7601
6. Do you have a chronic lung disease that limits your usual Lung 2
activities or makes you need oxygen at home? (Y/N) disease
40 0.7708
7. Has a doctor told you that you have congestive heart failure? Heart 2
(Y/N) failure
8. Have you smoked cigarettes in the past week? (Y/N) Smoke 2 20
9. Because of a health or memory problem do you have any Bathing 2
difficulty with bathing or showering? (Y/N)
0
10.Because of a health or memory problem, do you have any Finances 2
difficulty with managing your money—such as paying your bills 0 2 4 6 8 ≥10
and keeping track of expenses? (Y/N) Risk score
11.Because of a health problem do you have any difficulty with Walking 2 (excluding age contribution)
walking several blocks? (Y/N)
12.Because of a health problem do you have any difficulty with Push or 1
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 – Estimating life expectancy

Kaplan-Meier survival by risk points

Points
100 =0
=3
75
Surviving (%)

=6
50
=9
25
= 12
≥14
0
0 1 2 3 4 5 6 7 8 9 10
Time since baseline interview (Years)

Lee S, et al., JAMA 2013;309:874-6

Kobayashi L, et al., Age Ageing 2017; 46: 427–432
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
Ultimately, patients need to be able to make decisions independently
Elderly patients may have cognitive dysfunction that partly or completely precludes
decision making – and cognitive evaluation is therefore crucial
Cognitive dysfunction should be carefully differentiated from depression and
hearing problems

Don’t forget that elderly persons may have different priorities when making
decisions – such as maintaining functionality and independence – that may,
to them, be more important than living longer
GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Cognition

Multiple factors affect cognition in cancer patients

Reprinted from Cancer Treatment Reviews, Vol. 40, Issue 6, Lange M, et al., Cognitive dysfunctions in elderly cancer patients:
A new challenge for oncologists ,810–817, 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 elderly 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, which can be disease related or
not in elderly patients

Norman C. Clinical Nutrition. 2008

GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Nutritional status

Malnutrition is a significant problem among elderly persons, especially those with cancer

General population data using Mini Nutritional Assessment (MNA)

Kaiser MJ, et al., J Am Geriatr 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 Elderly Anorexia

 Energy expenditure Physiological changes with aging

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

 Exercise Pathological changes with aging

Medical
Drugs
Physiological
Social

Ahmed T Clin Interv Aging. 2010; 5: 207–216. Licensed under CC-BY-NC V3.0. https://creativecommons.org/licenses/by-nc/3.0/
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 (eg,
cognitions
cognitive style)

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

Changes in health,
physical ability, or
cognitive ability

Fiske A, et al., Annu Rev Clin Psychol. 2009; 5: 363–389. Reproduced with permission from Annual review of Clinical Psychology, Volume 5, © by Annual reviews,
http://www.annualreviews.org
GERIATRIC ONCOLOGY

Comprehensive Geriatric Assessment – Social support

Cancer patients of all ages benefit from extensive social support

Elderly 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

Elderly abuse (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

Elderly patients often use multiple drugs besides those associated with cancer
treatment, putting them at risk of polypharmacy

Polypharmacy may be defined in different ways but is, at its core, the discord of
number of medication and utility of medications

Elderly 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. Ann Oncol (2013) 24 (suppl_7): vii36-vii40

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 for 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. Ann Oncol (2013) 24 (suppl_7): vii36-vii40

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

Screening Tools – G8

CGA is a long process, and considering elderly heterogeneity, it is possible to spare

some patients full evaluations under situations of limited resources

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

The G8 is a commonly used, validated tool that can be applied in approximately

10 minutes
GERIATRIC ONCOLOGY

Screening Tools – G8
A score of <14 is abnormal and
correlates with OS

Kenis C, et al., J Clin Oncol, 32 (1), 2014: 19-26. Reprinted with permission. © (2014) American Society of Clinical Oncology. All rights reserved.
GERIATRIC ONCOLOGY
First visit to discuss treatment:
• Patient history
• Cancer
• G8 screening tool
• Life expectancy

G8 ≤14 G8 >14
Decision making
• Evaluate patient autonomy or need
for surrogate decision making
Full CGA • Prognosis vs. life expectancy
• Identification of • Benefit vs. toxicity of treatment
domains • Discuss patient’s priorities and
goals
• Possible social and economic No need of full CGA
• Proposed geriatric
issues that may affect
interventions

No treatment Treatment

Follow-up during treatment

GERIATRIC ONCOLOGY

Chemotherapy side effects in elderly patients

Chemotherapy side effects are more intense

Elderly patients can expect a higher rate of neutropenia, fatigue, cardiac toxicity and
neuropathy than younger patients

Elderly patients more often need dose reductions, delays and permanent interruptions
than younger patients

However, elderly patients benefit from standard chemotherapy regimens, including

doublets in breast cancer and lung cancer, if carefully selected and monitored
GERIATRIC ONCOLOGY

Chemotherapy side effects in elderly patients – Prediction tools

Therefore, predicting chemotherapy toxicity is critical

Two scores have been developed in cancer populations 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

Validated
GERIATRIC ONCOLOGY

Chemotherapy side effects in elderly patients – CRASH

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 elderly patients – CARG

Score Risk of toxicity

0–5 6–9 10–19

Hurria A, et al., Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With CancerJ Clin Oncol. 2016;34(20):2366-71. Reprinted with
permission. © 2016 American Society of Clinical Oncology
GERIATRIC ONCOLOGY

Concluding Remarks

Elderly patients will dominate future oncology practice

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

Critically, more elderly-centred studies with appropriate endpoints are necessary to

provide the basis for more specific treatment standards

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