Transcript Cancer treatment modification

An Overview of Geriatric
Oncology:
From Research to Clinical Practice
Melissa Loh, MBBCh BAO
Wilmot Cancer Center
University of Rochester Medical Center
Outline
• Epidemiology of aging
• Geriatric domains: comorbidities, geriatric
syndromes, polypharmacy, cognition, social support
• Utility of geriatric assessment
- Prediction of chemotherapy toxicity
- Decision-making
- Interventions
Epidemiology of Aging
Population 65+ by Age: 1900-2050
Source: U.S. Bureau of the Census
100,000,000
90,000,000
Number of Persons 65+
80,000,000
70,000,000
60,000,000
50,000,000
40,000,000
30,000,000
20,000,000
10,000,000
0
1900
1910
1920
1930
1940
1950
1960
Age
65-74
1970
Age
75-84
1980
Age
85+
1990
2000
2010
2020
2030
2040
2050
Epidemiology of Aging
Older Population by Age: 1900-2050 - Percent 60+, Percent 65+, and 85+
30%
25%
20%
15%
10%
% 60+
% 65+
% 85+
5%
0%
1900
1910
1920
1930
1940
1950
1960
1970
1980
1990
2000
2010
2020
2030
2040
2050
Age Distribution in Specific Cancer
Breast cancer
Age Distribution
<65 years
≥ 65 to <75
≥ 75 years
Age at diagnosis
59%
20%
21%
Age Distribution
<65 years
≥ 65 to <75
≥ 75 years
Age at diagnosis
39%
24%
37%
Age Distribution
<65 years
≥ 65 to <75
≥ 75 years
Age at diagnosis
42%
36%
23%
Age Distribution
<65 years
≥ 65 to <75
≥ 75 years
Age at diagnosis
32%
31%
37%
Colorectal cancer
Prostate cancer
Lung cancer
Lack of Enrollment of Older Adults in
Treatment Trials
*From NCI Surveillance, Epidemiology, and End Results (SEER) Program for 2005 to 2009
**For Phase 2 & 3 Tx Trials 2001 to 2011 - NCI/DCTD Clinical Data Update System May 2012
Important Variables for Prognostication in
Older Adults with Cancer
Impact of Comorbidities on Life Expectancy
Increasing Severity of Comorbidities
with Aging
Piccirillo et al. Crit Rev Oncol Hematol. 2008
Impact of Multimorbidity on Outcomes
Increased risk of:
• Death
• Institutionalization
• Increased utilization of healthcare resources
• Decreased quality of life
• Higher rates of adverse effects of treatment or interventions
Brendan Smialowski (NY Times)
AGS Expert Panel on the Care of Older Adults with Multimorbidity. J Am Geriatr Soc 2012;60:1957-68
Ferrat et al. J Gerontol A Biol Sci Med Sci. 2015
A High Prevalence Geriatric Syndrome and Functional
Impairment in Older Adults with Cancer
Mohile et al. JNCI. 2009
Impact of Geriatric Syndromes on Survival
in Patients with Colon Cancer
Geriatric syndromes and mortality
• One syndrome HR=1.18 (0.99-1.41)
• Two syndromes HR=2.34 (1.74-3.15)
Koroukian et al. J Gerontology Med Science, 2009
Polypharmacy
People 65+
People <65
65+ share of prescriptions
<65 share of presciptions
100
90
80
70
60
50
40
30
20
10
0
Present
•
•
•
2040
Now, people age 65+ are 13% of US population,
buy 33% of prescription drugs.
By 2040, will be 25% of population, will buy 50% of prescription
drugs
Risk Factors for Adverse Drug Events
•
•
•
•
•
•
•
6 or more concurrent chronic conditions
12 or more doses of drugs/day
9 or more medications
Prior adverse drug reaction
Low body weight or low BMI
Age 85 or older
Estimated CrCl < 50 mL/min
Common Drug-Drug Interactions
Combination
ACE inhibitor + diuretic
ACE inhibitor + potassium
Antiarrhythmic + diuretic
Benzodiazepine +
antidepressant, antipsychotic,
or benzodiazepine
Calcium channel blocker +
diuretic or nitrate
Digitalis + antiarrhythmic
Risk
Hypotension, hyperkalemia
Hyperkalemia
Electrolyte imbalance,
arrhythmias
Confusion, sedation, falls
Hypotension
Bradycardia, arrhythmia
Cognitive Disorders
• Cognitive disorders are frequently under-
diagnosed
• 24% of geriatric cancer patients are screened
positive for cognitive disorders
• Risks of treatment in patients with dementia
Mohile SG, et al. Cancer 109: 802-10, 2007.
Decreased Survival in Patients with
Cognitive Impairment
Robb C, Boulware D, Overcash J, Extermann M. Patterns of care and survival in cancer patients with cognitive impairment.
Critical Reviews in Oncology/Hematology 4: 218-24, 2010.
Psychological Status
• Prevalence up to 50% in patients with cancer
• Clinical depression predicts severe treatment
related-toxicity and overall survival
• Depression diagnosed prior to and after diagnosis
of cancer were associated with mortality
Freyer G, et al. Ann Oncol. 2005
Pinquart M, et al. Psychol Med. 2010
Massie MJ. JNCI. 2004
Social Support
Influence of marital status on breast cancer
•Unmarried women were more likely to be diagnosed
with breast cancer stage II-IV versus stage I or in situ
•Unmarried women diagnosed with Stage I or II breast
cancer were less likely to receive definitive treatment
•Unmarried women were at increased risk of death
from breast cancer
Osborne C, et al. Breast Cancer Res Treat. 2005
All Older Patients with Cancer are
Not the Same
Oncology versus Geriatrics
• Oncology  stage the cancer
– Make predictions of life expectancy
– Expected side effects of cancer therapy
• Geriatrics  stage the “aging”
– Make predictions of life expectancy
– Anticipate potential complications
– Better evaluate whether the benefits of therapy
outweigh the risks in the context of physiologic age
Chronologic versus Physiologic Age
When considering prognosis and treatment options in
this population, decisions should be based more on
“physiologic” age versus chronologic age.
It is necessary for oncologists to be adept at efficiently
and accurately estimating physiologic and functional
capacity in older patients.
Conceptual Model of GA
Comprehensive Geriatric Assessment
• Functional status
• Psychological status
• Activities of daily Living
• Depression/Anxiety
• Instrumental activities of daily • Cognitive impairment
living
• Dementia
• Physical function
• Delirium
• Falls
• Nutrition
• Comorbidities
• Social support
• Vision/hearing
• Medications
• Goals of Care
• Polypharmacy
• Frailty
• Inappropriate medications
Developing a Cancer-Specific Geriatric
Assessment (CSGA): A Feasibility Study
FEASIBILITY
Time to complete
ABILITY TO COMPLETE
UNASSISTED
Mean 27 min (SD 10)
Range 8-45 min
No: 22%
No association of age with time to
complete assessment
(p = 0.13)
Yes: 78%
No association of age with ability to
complete without assistance (p=0.16)
Hurria A et al. Cancer. 2005.
Utility of Comprehensive Geriatric
Assessment in Older Adults with Cancer
Risk
Prediction
Cancer
treatment
modification
Intervention
Surgical
Complications
and
Chemotherapy
Toxicity
Modification of
treatment/
chemotherapy
General
Geriatrics vs.
Cancer-focused
Survival
Modification of
supportive
care
Goals
Chemotherapy Toxicity Prediction
• Identify risk factors for chemotherapy toxicity in
the geriatric oncology population incorporating
CGA
• Develop a risk stratification schema for
chemotherapy toxicity
Hurria A, et al. J Clin Oncol. 2011.
Adverse Events
Incidence of Toxicity
CARG Toxicity Profile
Risk factor for Grade III-V Toxicity
OR (95% CI)
Score
Age ≥73 years
1.8 (1.2-2.8)
2
GI/GU Cancers
2.1 (1.4-3.2)
3
Standard dose chemotherapy
2.1 (1.3-3.5)
3
Polychemotherapy
1.7 (1.1-2.6)
2
Anemia (Male < 11, female <10)
2.3 (1.1-4.6)
3
Cr Cl <34 ml/min (using Jeliffe equation/IBW)
2.5 (1.1-5.4)
3
Falls in last 6 months
2.5 (1.4-4.3)
3
Hearing impairment
1.7 (1.0-2.7)
2
Limited ability to walk 1 block
1.7 (1.0-2.8)
2
Requires assistance with medications
1.5 (0.7-3.2)
1
Decreased social activities
1.4 (0.9-2.0)
1
Possible score 0-25
http://www.mycarg.org/Chemo_Toxicity_Calculator
Utility of Comprehensive Geriatric
Assessment in Older Adults with Cancer
Risk
Prediction
Surgical
Complications
and
Chemotherapy
Toxicity
Survival
Cancer
treatment
modification
Modification of
treatment/
chemotherapy
Modification of
supportive
care
Intervention
General
Geriatrics vs.
Cancerfocused
Goals
CGA Influences Clinical Care
Caillet P et al. J Clin Oncol 2011.
CGA Influences Clinical Care
Treatment modification occurred in 78 patients
• Intensification -> 10.2%
• Delay -> 9%
• Decrease -> 80.8%
Factors independently associated with changing the
treatment plan
• Functional impairment (ADL score)
• Malnutrition
• Trend towards association with depression and higher number of
comorbidities
Cancer Treatment Modifications
Based on CGA
Oncologist
assessment: Initial
treatment plan
•
•
•
•
CGA
Oncologist and
geriatrician: Final
treatment plan
French ASRO study
N=217, mean age 83 years
40% treatment recommendation modifications
On multivariate analysis: ADL dependence and Fried’s
frailty markers associated with treatment modifications
Farcet et al. PLOS One. 2016
Utility of Comprehensive Geriatric
Assessment in Older Adults with Cancer
Risk
Prediction
Surgical
Complications
and
Chemotherapy
Toxicity
Survival
Cancer
treatment
modification
Modification of
treatment/
chemotherapy
Modification of
supportive care
Intervention
General
Geriatrics vs.
Cancer-focused
Goals
Geriatric-Assessment Guided Interventions
Mohile et al, JNCCN, 2015
Delphi Participants
Interventions
• Evaluates the impact of geriatrician-delivered CGA interventions
on chemotherapy toxicity and tolerance for older people with
cancer
• Observational study
Results
• More participants in the intervention group completed
treatment as planned (33.8% vs 11.4%, OR 4.14, P=0.006)
• Fewer required treatment modifications (43.1% vs 68.6%, OR
0.34, P=0.006)
• Non-significant trend towards fewer discontinuing treatment
early (40.0% vs 51.4%, OR 0.63, P=0.183)
• No difference in all-cause death rates at 6 months (20.0%
control, 15.4% intervention, P.0.483).
*Adjusted for age, comorbidity, metastatic disease and initial
dose reductions
Toxicity
• Non-significant trend for a lower grade 3+ toxicity
rate in the intervention cohort (43.8% vs 52.9%,
P=0.292)
A Pilot Study of Geriatric Assessment
Intervention for Older Cancer Patients
Receiving Systemic Cancer Treatment
• Prospective, randomized pilot study evaluating the effect
GA-driven interventions
• Primary Aim:
– To determine if providing information regarding GA and
GA-guided interventions to oncologists reduces grade 3-5
toxicity in patients aged 70 and over receiving first or
second-line treatment with chemotherapy
A Pilot Study of Geriatric Assessment
Intervention for Older Cancer Patients
Receiving Systemic Cancer Treatment
• Secondary Aims:
– To determine the effects of GA-guided interventions on
functional measures, hospitalizations, and dose delays/early
termination of treatment
– To determine if providing oncologists with the results of GA
and GA-guided interventions influences overall survival
– To determine whether providing oncologists with the results of
GA influences decision making
Eligibility Criteria
•Patients age 70 and older
•Solid tumor malignancies
•Recommended by primary oncologist to receive treatment
with chemotherapy/chemoRT
– First or second line treatment
•Have decision-making capacity or an assigned HCP
Pilot Study Results
Baseline Characteristics balanced between the two
groups with the exception of
• IADL impairment: higher in the intervention group (p = 0.046)
• CARG-toxicity score: higher in intervention group (8% vs 27%, p=0.10)
Pilot Study Results
3 month follow-up:
Overall 58% of patients experienced grade 3-5 toxicity within 3 months
There was no significant difference between the control and intervention
group (48.3 % vs 51.7%, p = 0.96)
There were no significant differences in rates of:
Hospitalization (38% vs 23%, p= 0.26)
Dose reduction (42% vs 39%; p= 0.82)
Dose delays (42% vs 35%; p= 0.61)
Pilot Study Results

Consider meals-on-wheels – 33%

Nutrition referral – 67%

Consider PT/OT Referral – 33%

Consider more aggressive antiemetic regimen – 50%

Fall counseling handout – 44%

Ride assistance programs – 50%

Home safety evaluation – 39%

Social work involvement – 80%

Check vitamin D and repletion as indicated – 17%

Identification of HCP– 30%

Consider initial dose reduction – 72%

Co-sign for consents – 10%

Medication review – minimize psychoactive meds – 
Delirium risk handout – 30%
57%

Pillbox – 19%

PERS if alone – 0%

Medication review – minimize high risk medications –

Energy conservation handout – 36%

Exercise handout – 36%

Consider depression pharmacological therapy – 17%

VNS/home health aide referral – 42%

Consider referral for psychotherapy/psychiatry – 17%

Nutrition counseling (handout) – 50%

Support Group Information – 71%
36%
Pilot Study Results
3-month follow up
Depression
•GA at 3 months demonstrated increased interval
development of depression in the control group
•(36% vs 5%; p = 0.02)
Pilot Study Results
3-month follow up
Function
• Resolution of baseline differences in IADL
dependence
•(44% vs 42%; p=0.90)
Pilot Study Discussion
Conclusions:
• Able to enroll older, advanced cancer patients to a clinical trial in a
reasonable timeframe
• Patients not being referred to the geri-onc clinic have a good deal
of geriatric-related issues
• Unfortunately, we weren’t able to see that the intervention
algorithm improved the primary outcome – chemotherapy toxicity
for patients
• Did see improvements with regards to function and depression
A Geriatric Assessment Intervention for Patients
Aged 70 and Over Receiving Chemotherapy for
Advanced Cancer: Reducing Chemotherapy Toxicity
in Older Adults
-GAP-70+: Funded by NCI R01
Study Chair
Supriya Mohile, MD, MS, University of Rochester
Study Co-Investigators
Garry Morrow PhD, MS University of Rochester
Karen Mustian PhD, MPH, University of Rochester
Ron Epstein, MD, University of Rochester
Arti Hurria, MD, City of Hope
William Dale, MD, PhD, University of Chicago
Primary Aim
To determine if providing information
regarding GA and GA-driven
recommendations to oncologists reduces
grade 3-5 chemotherapy toxicity in
patients aged 70 and over with advanced
solid tumor malignancy
Conceptual Model
Schema
Summary
• The population is aging
• Older adults often have other comorbidities, geriatric
syndromes, functional and cognitive impairment,
polypharmacy and reduced social support
• GA can help predict outcomes and decision-making
• More data is needed on impact of GA-driven interventions
on outcomes
Acknowledgement
New York Cancer Registrar’s Association
Dr. Supriya Mohile
Dr. Allison Magnuson
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