Comorbidities and Geriatric Assessments in Older Adults with Cancer

1
Comorbidities and Geriatric Assessments in Older
Adults with Cancer

• Tanya Wildes, M.D.
• February 15, 2008

2
Incident Cancers by Age2000-2004
SEER Cancer Statistics http//seer.cancer.gov
3
Cancer Mortality by Age 2000-2004
SEER Cancer Statistics http//seer.cancer.gov
4
Leading Causes of Death by Age
Jemal, et al. CA Cancer J Clin, 2007
5
Comorbidity Indices

• Charlson Comorbidity Index
• Cumulative Illness Rating Scale (CIRS)
• Adult Comorbidity Evaluation (ACE-27)
• Sorror Hematopoietic Cell Transplantion
  Comorbidity Index (HCT-CI)
• Many more

6
Cancer and ComorbiditiesEindhoven Cancer
Registry
Coebergh et al. Journal of Clinical Epidemiology
1999
7
Prognostic Comorbidities and Survival
Piccirillo et al. Cancer 1996
8
Comorbidities and Survival Adult Comorbidity
Evaluation 27
Piccirillo, JAMA, 2004
9
Performance StatusIs it a surrogate for
comorbidities?
Piccirillo et al. Cancer 1996
10
Cancer and Performance Status

• Overall, older patients with cancer have
  relatively preserved performance statuses.
• In one cohort of newly diagnosed cancer patients
  over the age of 65, 74 had an ECOG PS of 0-1.
• In a cohort of patients with cancer who were
  undergoing chemotherapy, 92 had an ECOG PS of
  0-1.

Repetto, J Clin Onc, 2002 Extermann, Eur J Cancer
2002
11
Performance status and comorbidity

• Extermann, et al, performed a cross-sectional
  review of 203 patients seen in the Moffitt Senior
  Adult Oncology Program to evaluate the
  relationship between functional status and
  comorbidities

• Extracted data on
• Cancer staging
• Age
• Sex
• ECOG PS
• ADL
• IADL
• Lab data
• Charlson comorbidity index
• CIRS-G comorbidity score

Extermann et al. J Clin Oncol, 1998
12
Performance status and comorbidity
Extermann et al. J Clin Oncol, 1998
13
Performanc status and comorbidity
Extermann et al. J Clin Oncol, 1998
14
Performance status and comorbidity
Extermann et al. J Clin Oncol, 1998
15
Performance status and comorbidity
Perforamance Status and comorbidity are
independent
Extermann et al. J Clin Oncol, 1998
16
Comprehensive Geriatric Assessment (CGA)

• Function
• Performance Status
• Activities of Daily Living
• Instrumental Activities of Daily Living
• Comorbidity number and severity
• Socioeconomic conditions
• Living conditions
• Presence and adequacy of caregiver
• Cognition
• Folstein Mini Mental Status Exam

Balducci. Comprehensive Geriatric Oncology, 2004.
17
Comprehensive Geriatric Assessment (CGA)

• Emotional Condition
• Geriatric Depression Scale
• Pharmacy
• Number of medications
• Appropriate medications (Beers criteria)
• Risk of drug interactions
• Nutrition
• Mini-nutritional assessment
• Geriatric Syndromes
• Dementia
• Delirium
• Depression
• Falls
• Neglect/Abuse
• Spontaneous bone fractures

• Function
• Performance Status
• Activities of Daily Living
• Instrumental Activities of Daily Living
• Comorbidity
• Number and severity
• Socioeconomic conditions
• Living conditions
• Presence and adequacy of caregiver
• Cognition
• Folstein Mini Mental Status Exam

Balducci. Comprehensive Geriatric Oncology, 2004.
18
CGA in cancer patients

• Italian Group for Geriatric Oncology
• Multi-institutional investigation of
  Comprehensive Geriatric Assessment
• N363 hospitalized patients

• Tumor/stage
• Socioeconomic factors
• Comorbidities
• ECOG PS
• IADLs
• ADLs
• Geriatric Depression Scale
• Mini Mental Status Exam (excluded MMS lt10)

Repetto L et al. J Clin Oncol 2002.
19
CGA in cancer patients
Repetto L et al. J Clin Oncol 2002.
20
CGA in cancer patients
Repetto L et al. J Clin Oncol 2002.
21
Repetto L et al. J Clin Oncol 2002.
22
Repetto L et al. J Clin Oncol 2002.
23
Repetto L et al. J Clin Oncol 2002.
24
Repetto L et al. J Clin Oncol 2002.
25
Repetto L et al. J Clin Oncol 2002.
26
Repetto L et al. J Clin Oncol 2002.
27
MSKCC Cancer-Specific Geriatric Assessment

• Assessment created using previously validated,
  brief, reliable metrics
• Administered to patients over the age of 65 with
  breast, lung, colorectal cancer or lymphoma.

Hurria. Cancer, 2005
28
Hurria. Cancer, 2005
29
Hurria. Cancer, 2005
30
MSKCC Cancer-Specific Geriatric Assessment

• Mean age 74 (65-87 years)
• Cancer types
• Breast 25
• Colorectal 18
• Lung 38
• Lymphoma 20
• Married 55
• Lives alone 33
• Retired 83
• White 90, Black 10

Hurria. Cancer, 2005
31
MSKCC Cancer-Specific Geriatric Assessment

• Comorbidities95 reported at least 1
• 43 HTN
• 38 arthritis
• 28 heart disease
• 25 other cancer
• Completion of CSGA 2710 minutes
• 78 of patients successfully completed the
  self-administered portion of assessments unaided.
• Age and education level were not associated with
  ability to complete assessments.

Hurria. Cancer, 2005
32
MSKCC Cancer-Specific Geriatric Assessment

• Functional status
• 38 dependent on IADLs
• KPS
• 58 discordance between physician and patient
  rated KPS
• Patient reported higher KPS
• Falls
• 28 of patients had at least 1 fall in past 6
  months
• Poor correlation between measures of physical
  functioning, Up and Go Test and falls.

Hurria. Cancer, 2005
33
MSKCC Cancer-Specific Geriatric Assessment

• Psychosocial status
• 8 of patients with significant depression or
  anxiety
• 45 had limitations in social activities
• Nutritional status
• Mean BMI 28
• 5 had BMI lt22
• 38 reported weight loss gt5 of body weight

Hurria. Cancer, 2005
34
Summary

• Comorbidities are prevalent and prognostic in
  patients with cancer
• Performance status and comorbidities are
  independent
• ECOG PS underestimates level of functional
  limitations, which are better described by
  comprehensive geriatric assessment
• So how does this impact treatment?

35
Predicting outcomes of chemotherapy
Frasci G, et al. J Clin Oncol. 2000.
36
Elderly Patients with NSCLC Trial
Frasci G, et al. J Clin Oncol. 2000.
37
Elderly Patients with NSCLC Trial

• Early discontinuation of therapy
• 82 of patients with Charlson comorbidity score
  gt2 discontinued therapy early, compared to 30 of
  those with Charlson lt2.
• 59 of patients with ECOG 2 discontinued therapy
  early, compared to 31 of those with ECOG 0-1

Frasci G, et al. J Clin Oncol. 2000.
38
Predicting tolerance of chemotherapy

• Freyer G, et al. Ann Oncol. 2005.

39
GINECO study

• Prospective study of 83 patients gt age 70 with
  Stage III/IV ovarian cancer
• Objectives
• To evaluate tolerance of a combined carboplatin
  and cyclophosphamide regimen
• To calculate the percentage completing six 28-day
  cycles
• To assess the relevance of CGA parameters to
  predict the probability of severe toxicity

Freyer G, et al. Ann Oncol. 2005.
40
GINECO study

• CGA parameters
• Autonomy or dependence
• Comorbidities
• Polypharmacy
• Nutritional status BMI, albumin, cholesterol
• Mini-Mental Status
• Depression (as diagnosed by clinician)
• Severe Toxicity
• Febrile neutropenia
• Grade IV neutropenia
• Early treatment withdrawal because of grade
  III/IV toxicity
• Re-hospitalization gt7 days for grade III/IV
  toxicity

Freyer G, et al. Ann Oncol. 2005.
41
GINECO study
Freyer G, et al. Ann Oncol. 2005.
42
GINECO study
Freyer G, et al. Ann Oncol. 2005.
43
GINECO
Freyer G, et al. Ann Oncol. 2005.
44
GINECO
Freyer G, et al. Ann Oncol. 2005.
45

• N59
• Enrolled patients who were to receive a
  well-defined chemotherapy regimen for solid
  tumors or non-leukemic hematologic malignancies.
• Excluded concomitant radiation

• Predictor variables
• Age, sex, marital status
• Presence of a caregiver
• Bone marrow invasion
• Previous treatment
• Polypharmacy (gt3)
• ECOG PS
• Lawtons IADLs
• Geriatric Depression Scale
• Mini-mental status
• Mini-nutritional assessment
• FACT-G (QOL measure)
• CIRS-G
• Charlson comorbidity index
• Labs
• Creatinine clearance
• MAX2 (index adjusting for different chemotherapy
  regimens)

Extermann M, et al. Eur J Cancer, 2002
46
Extermann pilot study
Extermann M, et al. Eur J Cancer, 2002
47
Extermann pilot study
Mean dose intensity 90.316.3, median 100
Extermann M, et al. Eur J Cancer, 2002
48
Extermann pilot study
Extermann M, et al. Eur J Cancer, 2002
49
Extermann pilot study
Note absence of PS, comorbidities, IADLs, ADLs
as predictors of toxicity not explained by less
toxic chemotherapy
Extermann M, et al. Eur J Cancer, 2002
50
Extermann pilot study
Extermann M, et al. Eur J Cancer, 2002
51
Protocol Tolerance of chemotherapy in Senior
Adults with Cancer
52
Tolerance of Chemotherapy in Senior Adults with
Cancer

• Primary Aim
• To determine whether the comprehensive geriatric
  assessment (CGA) predicts for the completion of
  course of chemotherapy
• Secondary Aims
• To determine whether CGA predicts
• Dose reductions and dose delays
• Grade III/IV toxicities
• Hospitalizations

53
Inclusion criteria

• Age gt 65 years
• Biopsy-proven malignancy of the breast,
  colon/rectum, lung or lymphoma
• Enrolled prior to a planned course of
  chemotherapy of pre-specified duration.

54
Exclusion criteria

• Concurrent radiation
• Inability to sign informed consent

55
Baseline assessment

• Demographic information
• Medication form
• Center for Epidemiologic Studies Depression Scale
• Short Blessed Test
• Katz Index of Activities of Daily Living
• Lawton Index of Instrumental Activities of Daily
  Living
• Mini Nutritional Assessment short form

56
Baseline assessment

• Adult Comorbidity Evaluation 27
• ECOG Performance Status
• Baseline Laboratories CBC, CMP
• Glomerular Filtration Rate (MDRD)
• Planned chemotherapy regimen
• Exact chemotherapeutic/ immunotherapeutic agents,
  dosing, duration of cycles, number of cycles
  planned.

57
Baseline assessmentCenter for Epidemiologic
Studies Depression Scale
I felt depressed.. YES NO I felt
that everything I did was an effort... YES
NO My sleep was restless. .. YES NO I
was happy... YES NO I felt
lonely..... YES NO People were
unfriendly.. YES NO I enjoyed
life.. YES NO I felt
sad.... YES NO I felt that
people disliked me.. YES NO I could not
get going YES NO
Burnam, Med Care, 1988
58
Baseline assessment Short Blessed Test
Katzman et al. Am J Psychiatry 1983
59
Baseline assessmentKatz ADLs
1. Bathing (either sponge bath, tub bath, or
shower) Receive no assistance (gets in and out
of tub by self if tub is usual means of
bathing).. 3 Receives assistance in bathing
only one part of body, such as the back or a leg.
. . .. 2 Receives assistance in bathing more
than one part of body or is not bathed. . . . . .
.. 1 2. Continence Controls urination and
bowel movement completely by self. . . . . . . .
. . . . . . . . . . . . . . 3 Has occasional
accidents . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . 2 Needs supervision to keep urine or
bowel control, uses catheter, or is incontinent .
. . . . .. 1 3. Dressing (getting clothes from
closets and drawers, including underclothes,
outer garments uses fasteners, including
braces, if worn) Gets clothes and gets
completely dressed without assistance . . . . . .
. . . . . . . . . . . . . . . . . 3 Gets clothes
and gets dressed without assistance except in
tying shoes . . . . . . . . . . . . . .
2 Receives assistance in getting clothes or
getting dressed or stays partly or completely
undressed . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . 1 4. Feeding Feeds self
without assistance. . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . .. 3 Feeds self except for assistance in
cutting meat or buttering bread . . . . . . . . .
. . . . . 2 Receives assistance in feeding
or is fed partly or completely by nasogastric or
gastric tubes or intravenous fluids . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . .. 1 5. Toileting (going to
the toilet room for bowel and urine
elimination cleansing self after elimination
and arranging clothes) Goes to toilet room,
cleans self, and arranges clothes without
assistance (may use objects for support, such as
cane, walker, or wheelchair, and may manage night
bedpan commode and empty same in morning) . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . 3 Receives assistance in going to
toilet room, cleaning self, or arranging
clothes after elimination or receives
assistance in using night bedpan or commode . . .
. . . . . . 2 Does not go to room termed
toilet for the elimination process . . . . . .
. . . . . . . . . . . . .. 1 6. Transferring M
oves in and out of bed or chair without
assistance (may use object for support such as
cane or walker) . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . 3 Moves in and out of
bed or chair with assistance . . . . . . . . . .
. . . . . . . . . . . . . . . . . . .
.. 2 Does not get out of bed . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . 1
Katz, JAMA, 1963
60
Baseline assessmentLawton IADLs
1. Can you use the telephone Score Without
help . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . 3 With some help . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . 2 Completely
unable . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . 1 2. Can you get to places out of walking
distance Without help . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . 3 With some help
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. 2 Completely unable to travel unless special
arrangements are made? . . . . . . . . 1 3. Can
you go shopping for groceries (once at the
store) Without help . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . 3 With some help .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . .
. 2 Are you completely unable to do any
shopping? . . . . . . . . . . . . . . . . . . . .
. . . . 1 4. Can you prepare your own
meals Without help . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . 3 With some help .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . .
. 2 Are you completely unable to prepare any
meals? . . . . . . . . . . . . . . . . . . . . .
. 1 5. Can you do your own housework Without
help . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . 3 With some help . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . 2 Are you
completely unable to do any housework? . . . . .
. . . . . . . . . . . . . . . . . . 1 6. Can you
do your own laundry Without help . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . 3 With
some help . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . 2 Are you completely unable to do any
laundry at all? . . . . . . . . . . . . . . . . .
. . . . 1 7a. Do you take medicines or use any
medications (if yes, answer Question 7b) Yes .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . 1 (if no, answer Question
7c) No . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . 2 7b. Do you
take your own medicine Without help (in the
right doses at the right time) . . . . . . . . .
. . . . . . . . . . . . . . . 3 With some help
(take medicine if someone prepares it for you)
and/or reminds you to take it, or . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . 2 (are
you/would you be) completely unable to take your
own medicine? . . . . . . 1 7c. If you had to
take medicine, can you do it Without help (in
the right doses at the right time) . . . . . . .
. . . . . . . . . . . . . . . . . 3 With some
help (take medicine if someone prepares it for
you) and/or reminds you to take it, or . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . .
2 (are you/would you be) completely unable to
take your own medicine? . . . . . . 1 8. Can you
manage your own money Without help . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . .
3 With some help . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . 2 Are you completely
unable to handle money? . . . . . . . . . . . . .
. . . . . . . . . . . . . . 1
Lawton, Gerontologist, 1969
61
Baseline assessmentMini-Nutritional Assessment

• 1. Has food intake declined over the past 3
  months due to loss of appetite, digestive
  problems, chewing or swallowing difficulties?
• 0 severe loss of appetite
• 1 moderate loss of appetite
• 2 no loss of appetite
• 2. Weight loss during last months
• 0 weight loss greater than 3 kg (6.6 lbs)
• 1 does not know
• 2 weight loss between 1 and 3 kg (2.2 and 6.6
  lbs)
• 3 no weight loss
• 3. Mobility
• 0 bed or chair bound
• 1 able to get out of bed/chair but does not go
  out
• 2 goes out

• 4. Has suffered psychological stress or acute
  disease in past 3 months
• 0 yes
• 2 no
• 5. Neuropsychological problems
• 0 severe dementia or depression (SBT score ? 20
  and/or CES-D score ? 4)
• 1 mild dementia (SBT score 9-19)
• 2 no psychological problems
• 6. Body Mass Index (BMI)
• Weight (kg)_______
• Height (inches)_________
• 0 BMI less than 19
• 1 BMI 19 to less than 21
• 2 BMI 21 to less than 23
• 3 BMI 23 or greater

Rubenstein J Gerontology 2001
62
Baseline assessmentAdult Comorbidity Evaluation
27
Piccirillo, JAMA, 2004
63
Baseline assessment Glomerular Filtration Rate
(MDRD)

• Glomerular Filtration Rate
• 175 X standardized Scr-1.154 X age-0.203 X
  1.212if black X 0.742if female

Levey, Ann Int Med 2006
64
Outcomes

• Primary
• Completion of planned chemotherapy
• Secondary
• Received dose intensity
• Reason for cessation of therapy
• Completion, toxicity, disease progression
• Grade III/IV toxicities
• Hospitalizations

65
Received Dose Intensity

• Total mg/m2/days of treatment/7
• Relative received dose intensity
• RDIreference regimen

Hryniuk, J Clin Oncol 1990 Longo, J Clin Oncol,
1991
66
Statistical considerations

• The main focus is the feasibility of
  comprehensive assessment in the outpatient
  setting, prior to initiation of chemotherapy,
  responsiveness of assessments, and whether the
  outcomes of completion of therapy, received dose
  intensity and toxicities adequately describe the
  outcome of treatment tolerance.
• Baseline characteristics will be summarized and
  compared between those who complete the full
  course of chemotherapy as planned versus those
  who do not, using student t-test or Chi-square
  test.
• Multivariate logistic regression will also be
  fitted to identify potential independent risk
  factors for the inability to complete a planned
  course chemotherapy.
• Statistical significance will be determined at
  plt0.05.

67
Statistical considerations sample size

• As a pilot study, the intention of this study is
  to obtain preliminary information with a
  reasonable precision rather than formal
  hypothesis testing.
• Based on clinical considerations, the study will
  consider all eligible patients within 1-year
  period. We anticipate that 70 patients will be
  enrolled.
• Freyer et al found that 70 of elderly patients
  (n83) with advanced ovarian cancer completed
  chemotherapy as scheduled.
• If we assume similar proportion in our patient
  population, the designed sample size will allow
  us less than 6 measurement error for estimating
  the true proportion.

68
Future directions

• Developing a prognostic model for tolerance of
  chemotherapy
• Intervention based on results of CGA versus
  customary care
• Tailored chemotherapeutic decision-making based
  on CGA
• Bernardi et al treatment for lymphoma based on
  CGA