Geriatric Oncology
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Geriatric Oncology 1. Relationship between aging and cancer 2. Constructs of frailty and multimorbidity 3. Evidence for geriatric assessment in older adults living with cancer
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Geriatric Oncology
- 1. GERIATRIC ONCOLOGY: It’s not just about the cancer. Dr. Camilla Wong, MD FRCPC MHSc Annual Geriatric Oncology Conference 2019
- 2. I have no relationships with commercial interests. I have received research grant funding from the Ministry of Health and Long Term Care of Ontario (MOHLTC) for work related to geriatric oncology models of care. I have received a speaker honorarium from the Canadian Cardiac Oncology Network for a presentation related to geriatric oncology.
- 3. 1 Objectives To evaluate the evidence for geriatric assessment in older adults living with cancer. To discuss the relationship between aging and oncology. To review how the constructs of frailty and multimorbidity impact cancer management. 2 3
- 4. 1 Objectives To discuss the relationship between aging and oncology.
- 5. Can J Cardiol. 2016; 32(9): 1056–1064. The percentage of Canadians over age 75 is increasing.
- 6. Cancer incidence rises with age. Statistics Canada
- 8. J Clin Oncol. 2003;21(8):1618-23. Older adults are underrepresented in oncology trials. Older patients accounted for 22% of trial enrollees, compared with 58% of the Canadian population with cancer.
- 9. disease dominance psychosocial complexity pharmacokinetics geriatric syndromes and frailty common risk factors obesity, smoking, sedentary older age breast cancer cardiovascular disease trastuzumab anthracycline q3month cardiac monitoring type 1 cardiomyopathy type 2 cardiomyopathy cardiac toxicity LV dysfunction caregiver for spouse with dementia mild cognitive impairment delayed/missed monitoring heart failure functional decline falls delirium albumin eGFR symptomatic aortic stenosis beta-blocker ACE inhibitor statin The Big Picture polypharmacy polypharmacy multimorbidity
- 10. There are major changes with age, even without superimposed diseases. Lancet Oncol. 2018 Jun;19(6):e305-e316. Cancer J. 2005;11(6):449-73.
- 11. Concordant Conditions S i m i l a r p a t h o p h y s i o l o g i c p r o f i l e a n d d i s e a s e m a n a g e m e n t p l a n s .
- 12. Discordant Conditions N o t d i r e c t l y r e l a t e d i n e i t h e r p a t h o g e n e s i s o r m a n a g e m e n t .
- 13. Dominant Condition Identify and treat clinically dominant conditions that eclipse other less important conditions, which may be better left alone.
- 14. T I M E T O B E N E F I T ( T T B ) T h e t i m e u n t i l a s t a t i s t i c a l l y s i g n i f i c a n t b e n e f i t i s o b s e r v e d i n t r i a l s o f p e o p l e t a k i n g a t h e ra p y c o m p a re d t o a c o n t ro l g ro u p n o t t a k i n g t h e t h e ra p y.
- 15. WHAT MATTERS TO YOU? Moving from “What is the matter?”
- 16. Objectives To review how the constructs of frailty and multimorbidity impact cancer management. 2
- 17. Older Canadians are living with major chronic diseases. Canadian Community Health Survey, 2014 Chronic diseases: cancer, cardiovascular disease, chronic respiratory disease, diabetes.
- 18. Public Health Reviews. 2010;32:451-74. COMORBIDITY MULTIMORBIDITY Public Health Reviews 2011;32(2):451-474.
- 23. Objectives To evaluate the evidence for geriatric assessment in older adults living with cancer. 3
- 24. A comprehensive geriatric assessment (CGA) is a multidimensional, interdisciplinary diagnostic process to determine the medical, psychological, and functional capabilities of a frail elderly person in order to develop a coordinated and integrated plan for treatment and long-term follow-up.
- 25. BMJ 2019;364:l13
- 26. J Am Geriatr Soc. 2017;65(9):2115. The 5 M’s
- 28. Cochrane Database Syst Rev. 2017; CD006211.
- 29. “older people who received CGA probably have lower risk of dying, and that after discharge, were more likely to return to the same location they lived in before hospital admission” Cochrane Database of Systematic Reviews 2018, Issue 1. Art. No.: CD012485
- 30. GERIATRIC ASSESSMENT i s r e c o m m e n d e d b y s e v e r a l o r g a n i z a t i o n s J Clin Oncol 2014; 32: 2595-2603. J Natl Compr Canc Netw. 2012; 10(2): 162–209. Eur J Cancer. 2010;46(9):1502-13.
- 31. J Clin Oncol. 2018;36(22):2326-2347. “In patients age 65 and older receiving chemotherapy, geriatric assessment should be used to identify vulnerabilities or geriatric impairments that are not routinely captured in oncology assessments.” Evidence quality: high; Strength of recommendation: strong.
- 33. IMPACT IN ONCOLOGY EVIDENCE FOR GERIATRIC ASSESSMENT 01 02 03 04 05
- 34. Acta Oncologic 2014; 53:289-296. * *
- 35. IMPACT IN ONCOLOGY Identifies deficits not otherwise detected. EVIDENCE FOR GERIATRIC ASSESSMENT 01 02 03 04 05
- 36. Non-oncologic interventions were recommended in a median of 72% of patients (range 26–100%). J Geriatr Oncol. 2018;9(5):430-440. ** *
- 37. increase functional capacity in anticipation of an upcoming stress
- 38. IMPACT IN ONCOLOGY Identifies deficits not otherwise detected. Optimizes non-oncologic domains. EVIDENCE FOR GERIATRIC ASSESSMENT 01 02 03 04 05
- 39. PREDICTING TOXICITY Cancer and Aging Research Group (CARG) Chemo-Toxicity Calculator Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score
- 40. J Clin Oncol. 2011;29(25):3457–3465. Karnofsky performance status %chemotoxicity Classic oncology tools like the Karnofsky performance status poorly predict chemotoxicity in older adults.
- 41. CRASH Score Geriatric variables increase the predictive precision Cancer 2012;118:3377-86.
- 42. CARG Chemo-Tox Calculator mycarg.org J Clin Oncol. 2011; 29(25): 3457–3465. geriatric variables
- 43. J Clin Oncol. 2011; 29(25): 3457–3465. J Clin Oncol. 2016; 10;34(20):2366-71. CARG Chemo-Tox Calculator Geriatric variables increase the predictive precision (ROC 0.65-0.72)
- 44. IMPACT IN ONCOLOGY Identifies deficits not otherwise detected. Optimizes non-oncologic domains. Increases the precision of prognostication. EVIDENCE FOR GERIATRIC ASSESSMENT 01 02 03 04 05
- 45. 28% of initial oncologic treatment plans were modified based on the information from the geriatric assessment of which the majority resulted in less intensive options: different modality/regimen, dose reduction, best supportive care J Geriatr Oncol. 2018;9(5):430-440.
- 46. IMPACT IN ONCOLOGY Identifies deficits not otherwise detected. Optimizes non-oncologic domains. Increases the precision of prognostication. Influences oncologic treatment intensity. EVIDENCE FOR GERIATRIC ASSESSMENT 01 02 03 04 05
- 47. J Geriatr Oncol. 2018;9(5):430-440. TOX I C I T Y O R C O M P L I C AT I O N S 5 studies found a decrease 4 studies found no effect T R E AT M E N T C O M P L E T I O N 3 studies found higher rates 1 study found no effect
- 48. IMPACT IN ONCOLOGY Identifies deficits not otherwise detected. Optimizes non-oncologic domains. Increases the precision of prognostication. Influences chemotherapy intensity. May improve treatment completion and chemotherapy tolerance. EVIDENCE FOR GERIATRIC ASSESSMENT 01 02 03 04 05
- 49. “In ONCOLOGY, personalized treatment often begins with the tumour, its pathology, genetics and staging, which are incorporated in algorithms that yield treatment recommendations; the next step will then be to assess whether the patient is suitable for the treatment. A GERIATRIC approach to personalized treatment often starts at the other end, with an emphasis on the patient's health status, individual goals of care and physical strengths and limitations; subsequently, it is assessed whether the treatment is suitable for the patient.” J Geriatr Oncol. 2019. [Epub ahead of print]
- 51. “If you want to go fast, go alone; if you want to go far go TOGETHER” -- African Proverb
- 52. 1. The proportion of older adults in clinical trials should reflect the population. 2. Trials should include older adults with both cancer and frailty. 3. Trials of geriatric oncology collaborative care models should report frailty and patient-oriented outcomes. End ageism. Embrace complexity. Focus on what matters.
- 53. THANK YOU Dr. Camilla Wong, MD FRCPC MHSc camilla.wong@unityhealth.to @camilla_wong
Editor's Notes
- I have no relationships with commercial interests. However, I have received grant funding from the Ministry of Health and Long Term Care of Ontario for research related to geriatric oncology model of care and have received a speaker honorarium from the Canadian Cardiac Oncology Network for a presentation related to geriatric oncology.
- Older adults, in general, for this presentation will mean 65+
- Why is cancer more common in older adults? Cancer is more common in older adults 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
- And yet, in spite of this demographic and biologic imperative, older adults remain under-represented in oncology trials, accounting for only 22% of trial participants even though they represent 58% of the Canadian population living with cancer. The lack of inclusion in clinical trials and lack of outcome measures reflecting end points of importance to older people is a form of ageism that unfortunately leaves clinicians with little evidence on how to help treat older adults living with cancer.
- Let’s consider this example. [case flow diagram]
- Becoming familiar with age-related physiologic changes is the first step for tailoring treatments. Reduction in fat-free muscle mass alters drug distribution. Age-related changes in hepatic mass reduces drug metabolism. Renal mass and glomerular filtration rate decrease with age, affecting the clearance of many drugs. Bioavailability is dependent on gastrointestinal motility, splanchnic blood flow, digestive enzyme activity. With age, there is decreased drug absorption. Pacemaker and conduction pathway degeneration, valvular stiffening, myocyte hypertrophy primarily lead to reduction of the cardiac functional reserve, with a consequent increase in the risk of drug-related cardiomyoppathy. Age-related decrease in pulmonary reserve, such as reduced lung compliance, make result in ineligibility for curative surgical resection or at least have implications for thoracic radiation. Changes in memory increase the likelihood of developing delirium with treatment. Bone density declines with age and treatments such as gonadotropin-releasing hormone agonists and aromatase inhibitors can further increase fracture risk. Age-related changes in the immune system lead to an increased susceptibility to infection in the elderly. Bone marrow cellularity decreases with age, increasing the risk of developing anemia with consequent fatigue. All this to say that age-associated changes results in a diminished ability to tolerate the physiological stressors of chemotherapy.
- Most clinical practice guidelines address single diseases in accordance with modern medicine’s focus on disease and pathophysiology. When we practice in the silos of our subspecialty, the management of concordant conditions is not necessarily problematic.
- But more often than not, the patient has discordant or competing conditions whereby practicing in silos, may be problematic.
- The tricky part for frail individuals is that treatment of one condition can exacerbate other conditions that do not lead to net health improvements. The suggested management strategy is to identify and treat clinically dominant conditions that eclipse other less important conditions, which may be better left alone.
- Time to benefit: Many cancers in older adults are slower growing and may not contribute to morbidity and mortality. The timeline for developing late toxicities may not be within individual’s life expectancy. Thus, for many older adults with competing causes of death, the goal of treatment needs to extend beyond survival to include gains in quality of life (QoL), symptom control, and preservation of function.
- In embracing complexity, we need to see the forest for the trees. Moving from “What is the matter?” to “What Matters to You?”
- We’d be remiss to discuss geriatric oncology only in the context of simply aging. Chronological age alone is often a poor indicator of the physiological and functional status of older adults, and thus should not be the main factor guiding treatment decisions in oncology.
- Older Canadians are living with major chronic diseases – but not all of them are. Aging is heterogeneous.
- A co-morbidity framework looks at the index disease as centre of interest whereby only interaction with the index disease is assumed. A multimorbidity framework, on the other hand, looks at multiple interactions between chronic conditions.
- While “the more individuals have wrong with them, the more likely they are to be frail”, it is important to realize that frailty is not synonymous with getting older, nor is it the inevitable result of aging or multimorbidity.
- Frailty is broadly considered as decreased physiologic reserve across multiple organ systems leading to an impaired ability to withstand physiologic stress. On the x-axis you have time, and on the y-axis is level of function. In the green is the trajectory of someone who is fit, while in the red is the trajectory of an older adult who is frail. Frailty makes it difficult for individuals to respond to the acute stress of illness, such as cancer or cancer treatment.
- In a systematic review of 20 studies, more than half of older adults living with cancer have pre-frailty or frailty and these individuals are at increased risk of chemotherapy intolerance, postoperative complications, and mortality.
- In other words, ascertaining and addressing frailty matters. Although over treatment is a concern, older adults may also be undertreated because of potentially ‘ageist’ attitudes.
- The gold standard for ascertaining and managing frailty is the comprehensive geriatric assessment (CGA), the cornerstone of modern geriatric care. A CGA is a multidimensional interdisciplinary diagnostic process focused on determining a frail older person’s medical, psychological and functional capabilities in order to develop a coordinated and integrated plan for treatment and long-term follow-up.
- I will not go into details of what domains are part of a geriatric assessment nor will I discuss how to conduct a CGA as Dr. Alibhai will be addressing this in the following session.
- One of the reasons I love geriatrics because it allows me to practice medicine the way I want to practice medicine, holistically. Looking after the mind, mobility, medications, multicomplexity and what matters most.
- It is a process that results in therapeutic harmonization – the alignment of prognosis and goals with the care that we provide.
- The comprehensive geriatric assessment is evidence-based two. A Cochrane systematic review of 29 RCTs from 9 countries showed that when older adults receive a CGA compared to usual care, they are not only more likely to be alive at discharge but also be able to return home.
- And similarly, another Cochrane systematic review of 8 RCTs in surgical settings came to the same conclusion – more likely to be alive and at home at discharge.
- In fact, several oncology societies have recommended that all older patients receive some sort of geriatric assessment.
- Including ASCO, which in 2018 made a strong recommendation based on high quality of evidence that In patients age 65 and older receiving chemotherapy, geriatric assessment should be used to identify vulnerabilities or geriatric impairments that are not routinely captured in oncology assessments. And note that the terminology is geriatric assessment, not comprehensive geriatric assessment.
- Geriatric assessment alone is not an intervention in itself, but rater aims to identify opportunities for intervention. A CGA on the other hand, includes goal-directed intervention and follow-through. The latter has the potential to evaluate the balance of benefits and harms of performing or omitting specific interventions.
- In 2014 systematic review of 10 observational cohort studies the prevalence of geriatric conditions as identified by geriatric assessment is shown in this table. The most frequent issue detected was polypharmacy or inappropriate medication use, present in a median of 67%, followed by malnutrition with a median prevalence of 63%. The take home point is geriatric conditions are common, and unless you ask, you won’t know.
- In an updated systematic review in 2018 of 35 studies, geriatric assessment resulted in non-oncologic interventions in a median of 72% of patients (range 26–100%), most commonly involving social issues (39%), nutritional status (32%) and polypharmacy (31%).
- A super interesting area in geriatric oncology is unimodal or multimodal prehabilitation interventions improve health outcomes, but you will have to go to Drs. Santamina and Chesney session later to find out more.
- So we now understand that chronological age alone is often a poor indicator of the physiological and functional status of older adults, and thus should not be the main factor guiding treatment decisions in oncology.
- The argument then follows that classic oncology tools like the Karnofsky performance status poorly predict chemotoxicity in older adults because they fail to capture frailty. There are at least two chemotoxicity prediction tools used in older adults, the details of which will be covered in the afternoon session by Drs. Menjak and Haase.
- The first is the CRASH score and you can see it integrates results from geriatric assessment tools that capture function, nutrition, and cognition to better predict the risk of hematologic (p=.005) and nonhematologic (p>.05) toxicity in older adults 70+.
- The second is the CARG ChemoTox calculator which is a predictive model consisting of 11 items, of which five are geriatric variables. This tool takes 5 minutes to complete and is freely available online for use on the CARG website.
- It too discriminates chemotherapy toxicity risk in older adults with solid tumors better than the Karnofsky in those 65+. This is all to say that geriatric variables increase the predictive precision of which older adult will do well or be harmed by chemotherapy.
- 11 studies comparing oncologic treatment choice before and after the geriatric evaluation. The median proportion of patients in which the oncologic treatment was changed after the geriatric evaluation was 28% (range 8–54%). For the majority of patients, treatment was adjusted to a less intensive option: different type of treatment modality or regimen, dose reductions or best supportive care/no oncologic treatment. Only one study reported that the majority of changes resulted in a more intensive treatment option.
- In a systematic review on the effect of geriatric evaluation on treatment outcome, including 8 RCTs, and 5 studies using a historic or matched control cohort; 5 studies found a positive effect and 4 found no effect on treatment toxicity or complications; 3 out of 4 studies found that geriatric assessment resulted in higher treatment completion rates. The effect on survival, health care utilisation, physical functioning and quality of life appears limited.
- Future Directions in Geriatric Oncology should include: 1. The proportion of older patients in clinical trials to reflect the population (end AGEISM!) 2. Trials should include older adults with both cancer and frailty (embrace complexity) 3. Trials of geriatric oncology collaborative care models should report frailty and patient-oriented outcomes (what matters).