GERIATRIC ONCOLOGY. An Introduction. Dr Lissandra Dal Lago, MD, PhD Dr Noam Pondé, MD Institut Jules Bordet, Brussels, Belgium

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1 An Introduction Dr Lissandra Dal Lago, MD, PhD Dr Noam Pondé, MD Institut Jules Bordet, Brussels, Belgium

2 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

3 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

4 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 Population (in millions) Population change 2007 to 2050, % 1. Delivorias A, Sabbati G. EU Demographic Indicators: Situation, Trends And Potential Challenges, March 2015; Accessed May Copyright European Union, All rights reserved; 2. Iris Hoßmann, Europe s Demographic Future Berlin Institut Europe * Average age * 47.3 Fertility rate Under 15 year olds, % * 15 Over 65 year olds, % * 28 Life expectancy * 82.0 *Projection

5 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. Accessed February 2017

6 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, , Copyright 2013, with permission from Elsevier.

7 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

8 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

9 Aging is a heterogeneous process Not all young persons are healthy and functional Not all elderly persons are sick and dependent Age cut-off exists to promote awareness, not to determine management! Lowsky J, et al., Gerontol A Biol Sci Med Sci (2014) 69 (6): , by permission of Oxford University Press

10 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

11 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

12 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, , Copyright 2013, with permission from Elsevier.

13 Functional abilities GERIATRIC ONCOLOGY The aging process Functionality and stress Minor illness (e.g., urinary tract infection) Independent 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, , Copyright 2013, with permission from Elsevier.

14 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

15 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

16 Comprehensive Geriatric Assessment Examples of scales/tools Domains Functional status Comorbidities Medications Cognitive function Geriatric syndrome Depression/mood Nutrition Mobility Situational assessment Scales Eastern Cooperative Oncology Group performance status, Katz basic Activities of Daily Living Scale, Simplified Lawton s Instrumental Activities of Daily Living Scale Charlson comorbidity index Number, type, indication Folstein Mini-Mental State Examination, Schultz-Larsen Mini-Mental State Examination Repeated falls, fecal and/or urinary incontinence Geriatric Depression Scale 5, Emotional questionnaire Body mass index Timed Up and Go test Accessibility of services, mobility, social environment, accessibility of home rooms Corre R, et al., J Clin Oncol 2016;34(13):

17 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): Reprinted with permission American Society of Clinical Oncology

18 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): Reprinted with permission American Society of Clinical Oncology

19 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

20 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: Reprinted with permission. (2005) American Society of Clinical Oncology. All rights reserved.

21 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

22 Comprehensive Geriatric Assessment Comorbidity Condition Assigned weight Myocardial infarction 1 Congestive heart failure 1 Peripheral vascular disease 1 Cerebrovascular disease 1 Dementia 1 Chronic pulmonary disease 1 Connective tissue disease 1 Ulcer disease 1 Liver disease, mild 1 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 The Charlson Index measures risk of death in the next year During CGA, these and other comorbidities should be identified and optimal management initiated In certain situations, depending on the seriousness of the comorbidities, treatment of cancer should be delayed, modulated or entirely foregone Albertsen PC, et al., J Clin Oncol, 29(10), 2011: Reprinted with permission. (2011) American Society of Clinical Oncology. All rights reserved.

23 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: Reprinted with permission. (2011) American Society of Clinical Oncology. All rights reserved.

24 Four-year mortality (%) GERIATRIC ONCOLOGY Comprehensive Geriatric Assessment Estimating life expectancy Four-Year Mortality Index for Older Adults Parameter Result Points 1. Age (years) Sex (Male/Female) Male 2 3. BMI [703 (weight in pounds/height in inches 2 )] BMI < Has a doctor ever told you that you have diabetes or high Diabetes 1 blood sugar? (Y/N) 5. Has a doctor told you that you have cancer or a malignant Cancer 2 tumour, excluding minor skin cancers? (Y/N) 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 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 9. Because of a health or memory problem do you have any Bathing 2 difficulty with bathing or showering? (Y/N) 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) 11.Because of a health problem do you have any difficulty with Walking 2 walking several blocks? (Y/N) 12.Because of a health problem do you have any difficulty with pulling or pushing large objects like a living room chair? (Y/N) Push or pull 1 Lee index predicts mortality in 4 and 10 years It integrates age, comorbidity, cognition and functionality Age group (y) 80 (n=2579) (n=4921) (n=12125) Risk score (excluding age contribution) AUC = Lee S, et al. JAMA 2006;295(7):801 8

25 Surviving (%) GERIATRIC ONCOLOGY Comprehensive Geriatric Assessment Estimating life expectancy Kaplan-Meier survival by risk points 100 Points = 0 = 3 75 = 6 50 = 9 25 = Time since baseline interview (Years) Lee S, et al., JAMA 2013;309:874-6 Kobayashi L, et al., Age Ageing 2017; 46:

26 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

27 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, , copyright 2014, with permission from Elsevier.

28 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

29 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): , Copyright the Authors. Journal compilation. 2010, The American Geriatrics Society

30 Comprehensive Geriatric Assessment Nutritional status Causes for Elderly Anorexia Energy expenditure Anorexia of aging Physiological changes with aging Hormonal Cytokines Taste and smell Changes in GI tract Exercise Pathological changes with aging Medical Drugs Physiological Social Ahmed T Clin Interv Aging. 2010; 5: Licensed under CC-BY-NC V3.0.

31 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

32 Comprehensive Geriatric Assessment Psychological state Link between old age and depression Long-standing vulnerabilities (eg, cognitive style) Self-critical cognitions Stressful life events and loss of social roles Limitation of activities Low rate of positive outcomes Depression Changes in health, physical ability, or cognitive ability Fiske A, et al., Annu Rev Clin Psychol. 2009; 5: Reproduced with permission from Annual review of Clinical Psychology, Volume 5, by Annual reviews,

33 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

34 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

35 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

36 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

37 Comprehensive Geriatric Assessment Geriatric syndromes The concept of geriatric syndrome differ from those of disease and syndrome Geriatric syndrome Multiple aetiological factors Interacting pathogenetic pathways Unified manifestation Inouye S. et al. J Am Geriatr Soc 2007;55(5):780 91

38 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

39 Screening Tools G8 A score of <14 is abnormal and correlates with OS Kenis C, et al., J Clin Oncol, 32 (1), 2014: Reprinted with permission. (2014) American Society of Clinical Oncology. All rights reserved.

40 First visit to discuss treatment: Patient history Cancer G8 screening tool Life expectancy G8 14 Full CGA Identification of domains Proposed geriatric interventions Decision making Evaluate patient autonomy or need for surrogate decision making Prognosis vs. life expectancy Benefit vs. toxicity of treatment Discuss patient s priorities and goals Possible social and economic issues that may affect G8 >14 No need of full CGA No treatment Treatment Follow-up during treatment

41 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

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

43 Chemotherapy side effects in elderly patients CRASH Predictors Haematologic score Points Diastolic BP 72 >72 IADL LDH (if ULN 618 U/L; otherwise, 0.74/L*ULN) >459 Chemotox >0.57 Nonhaematologic score ECOG PS MMS 30 <30 MNA <28 Chemotox >0.57 Extermann M, et al., Cancer 2012;118:

44 Chemotherapy side effects in elderly patients CARG Score Risk of toxicity Hurria A, et al., Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With CancerJ Clin Oncol. 2016;34(20): Reprinted with permission American Society of Clinical Oncology

45 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

46 THANK YOU!