1. An Overview of Geriatric Oncology: From Research to Clinical Practice
Melissa Loh, MBBCh BAO
Wilmot Cancer Center
University of Rochester Medical Center

2. Outline Epidemiology of aging
Geriatric domains: comorbidities, geriatric syndromes, polypharmacy, cognition, social support
Utility of geriatric assessment
Prediction of chemotherapy toxicity
Decision-making
Interventions

3. Epidemiology of Aging

4. Epidemiology of Aging

5. Age Distribution in Specific Cancer
Breast cancer
Age Distribution
<65 years
≥ 65 to <75
≥ 75 years
Age at diagnosis
59%
20%
21%
Colorectal cancer
Age Distribution
<65 years
≥ 65 to <75
≥ 75 years
Age at diagnosis
39%
24%
37%
Prostate cancer
Age Distribution
<65 years
≥ 65 to <75
≥ 75 years
Age at diagnosis
42%
36%
23%
Lung cancer
Age Distribution
<65 years
≥ 65 to <75
≥ 75 years
Age at diagnosis
32%
31%
37%

6. 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 NCI/DCTD Clinical Data Update System May 2012

7. Important Variables for Prognostication in Older Adults with Cancer

8. Impact of Comorbidities on Life Expectancy

9. Increasing Severity of Comorbidities
with Aging
Piccirillo et al. Crit Rev Oncol Hematol. 2008

10. 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:
Ferrat et al. J Gerontol A Biol Sci Med Sci. 2015

11. A High Prevalence Geriatric Syndrome and Functional Impairment in Older Adults with Cancer
Mohile et al. JNCI. 2009

12. Impact of Geriatric Syndromes on Survival in Patients with Colon Cancer
Geriatric syndromes and mortality
One syndrome HR=1.18 ( )
Two syndromes HR=2.34 ( )
Koroukian et al. J Gerontology Med Science, 2009

13. Polypharmacy 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

14. 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

15. Common Drug-Drug Interactions
Combination
Risk
ACE inhibitor + diuretic
Hypotension, hyperkalemia
ACE inhibitor + potassium
Hyperkalemia
Antiarrhythmic + diuretic
Electrolyte imbalance, arrhythmias
Benzodiazepine + antidepressant, antipsychotic, or benzodiazepine
Confusion, sedation, falls
Calcium channel blocker + diuretic or nitrate
Hypotension
Digitalis + antiarrhythmic
Bradycardia, arrhythmia

16. 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: , 2007.

17. 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: , 2010.

18. 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

19. 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

20. All Older Patients with Cancer are Not the Same

21. Oncology versus Geriatrics
Oncology  stage the cancer
Make predictions of life expectancy
Expected side effects of cancer therapy
Geriatrics  stage the “aging”
Anticipate potential complications
Better evaluate whether the benefits of therapy outweigh the risks in the context of physiologic age

22. 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.

23. Conceptual Model of GA

24. Comprehensive Geriatric Assessment
Functional status
Activities of daily Living
Instrumental activities of daily living
Physical function
Falls
Comorbidities
Medications
Polypharmacy
Inappropriate medications
Psychological status
Depression/Anxiety
Cognitive impairment
Dementia
Delirium
Nutrition
Social support
Vision/hearing
Goals of Care
Frailty

25. Developing a Cancer-Specific Geriatric Assessment (CSGA): A Feasibility Study
Time to complete
Mean 27 min (SD 10)
Range min
No association of age with time to complete assessment
(p = 0.13)
No association of age with ability to complete without assistance (p=0.16)
ABILITY TO COMPLETE
UNASSISTED
No: 22%
Yes: 78%
Hurria A et al. Cancer

26. 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
Geriatrics vs. Cancer-focused
General
Goals

27. 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

28. Adverse Events

29. Incidence of Toxicity

30. CARG Toxicity Profile Risk factor for Grade III-V Toxicity OR (95% CI)
Score
Age ≥73 years
1.8 ( ) 2
GI/GU Cancers
2.1 ( ) 3
Standard dose chemotherapy
2.1 ( )
Polychemotherapy
1.7 ( )
Anemia (Male < 11, female <10)
2.3 ( )
Cr Cl <34 ml/min (using Jeliffe equation/IBW)
2.5 ( )
Falls in last 6 months
2.5 ( )
Hearing impairment
1.7 ( )
Limited ability to walk 1 block
1.7 ( )
Requires assistance with medications
1.5 ( ) 1
Decreased social activities
1.4 ( )
Possible score 0-25

32. 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
Geriatrics vs. Cancer-focused
General
Goals

33. CGA Influences Clinical Care
Caillet P et al. J Clin Oncol 2011.

34. 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

35. 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

36. 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
Geriatrics vs. Cancer-focused
General
Goals

37. Geriatric-Assessment Guided Interventions
Mohile et al, JNCCN, 2015

38. Delphi Participants

39. Interventions

41. Evaluates the impact of geriatrician-delivered CGA interventions on chemotherapy toxicity and tolerance for older people with cancer
Observational study

42. 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

43. Toxicity
Non-significant trend for a lower grade 3+ toxicity rate in the intervention cohort (43.8% vs 52.9%, P=0.292)

44. 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

45. 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

46. 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

47. 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)

48. 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)

49. 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 – 57%
Delirium risk handout – 30%
Pillbox – 19%
PERS if alone – 0%
Medication review – minimize high risk medications – 36%
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%

50. 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)

51. Pilot Study Results 3-month follow up Function
Resolution of baseline differences in IADL dependence
(44% vs 42%; p=0.90)

52. 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

53. Study Co-Investigators
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

54. 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

55. Conceptual Model

56. Schema

57. 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

58. Acknowledgement New York Cancer Registrar’s Association
Dr. Supriya Mohile
Dr. Allison Magnuson