Evaluation of the Frail Old Cancer Patient

1
Evaluation of the Frail Old Cancer Patient

• Silvio Monfardini
• Division of Medical Oncology
• Istituto Oncologico Veneto
• Italy

2
THE FRAIL PATIENTNo broadly accepted definition

• Combination of aging, disease and other factors
  that make some people vulnerable to stress
• Poor tolerance to stress and at high risk of
  loss of independence

3
Causes of frailty
4
Fried et al. Frailty in older adults. Evidence
for a phenotype. J Gerontol. Med. Sci.
2001

• Loss of 10 or more of body weight in over 1 year
• low energy level
• difficulty in initiating movements
• slow movements
• decreased grip strenght
• Frailty is defined by three or more of these
  criteria

5
Is frailty a disease?

• By the Fried definition,
• frailty is not a disease
• but rather a sort of being in the middle state
• between being functional and nonfunctional,
• and between being healthy and being sick.

6
Who are Elderly Frail Cancer Patients?( The
operational concept of aging in Medical Oncology)

• They are those with age-associated conditions
  interfering with treatment and possibly leading
  to no treatment and barriers to trials entry
  such as
• associated diseases
• functional status impairement
• mental deterioration and depression
• lack of family and social support
• How to measure these age-associated conditions?

7
Activity of daily living(ADL)

• Based on 6 criteria
• Dressing
• Toilet Use
• Bathing with sponge, bath, or shower
• Transferring (in and out of bed or chair)
• Urine and Bowel Continence
• Eating

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Cumulative illness rating scale for geriatrics
(CIRS-G)
Rating 0- No problem 1- Current mild problem or
past significant problem 2- Moderate disability
or morbidity/requires first line therapy 3-
Severe/constant significant disability/
uncontrollable chronic problems 4- Extremely
severe / immediate treatment required/end organ
failure/severe impairment in function Organ
system Heart, Vascular, Haematopoietic,
Respiratory, Eyes/ENT, Larynx, Upper GI, Lower
GI, Liver, Renal, Genitourinary,
Musculoskeletal/Integument, Neurological,
Endocrine/Metabolic, Psychiatric Illness Miller
MD, Paradis CF. HoucK PR, Mazumdar S, Stack JA,
Rifai AH et al., Rating chronic mediacal illness
burden in geropsychiatric practice and research
an application of the Cumulative Illness rating
scale, Psychiatry Res. 1992 41 237-348
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The basic components of the Comprehensive
Geriatric Assessment(CGA)

• Functional status ADL (Activity of Daily Living),
  IADL (Instrumental Activity of Daily Living)
• Comorbidity (number, type and rating of comorbid
  conditions)
• Cognition (Mini-Mental Status Examination)
• Depression (Geriatric Depression Scale)
• Polypharmacy
• Nutrition (Mini-Nutritional Assessment)
• Presence of Geriatric Syndromes (dementia,
  delirium, depression, failure to thrive, neglect
  or abuse, osteoporosis, falls, incontinence)
• Socio-economic factors

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An operational definition of frailty for the
Elderly Cancer Patient

• What defines a frail patient?
• Dependence in one or more ADL
• 3 or more severe comorbidities (CIRS)
• Presence of one or more geriatric syndromes
• Agegt 85 years ?

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Clinical Definition and Therapeutic Implications
of Aging (from L. Balducci et al. Cancer Control
8 1-25, 2001 and Crit. Rew. Oncol.Haematol. 46
211-220, 2003) A possible model for future
controlled studies
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CLINICAL VALUE OF SUBDIVIDING ELDERLY CANCER
PATIENTS AS FIT, VULNERABLE AND FRAIL IN A
GERIATRIC ONCOLOGY CLINIC.
Vamvakas L,Monfardini S.et.al.
SIOG 2005

• INTRODUCTION AND AIMS
• The aim of this work was to determine the
  relative amount of Fit, Frail and Vulnerable
  patients and to verify the therapeutic approach
  for each subgroup in a Geriatric Oncology Clinic.

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RESULTS Frail Patients according to MGE
14
RESULTS Subdivision of Causes of Frailty
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MANAGEMENT AND SURVIVAL OF FRAIL
ELDERLY CANCER PATIENTS WITHIN A GERIATRIC
ONCOLOGY PROGRAM U. Basso1, L. Vamvakas2, C.
Falci1, A. Jirillo1, E. Lamberti1, L. M.
Pasetto1, A. Brunello1, S. Tonti1, S. Lonardi1,
S. Vigorelli1, S. Monfardini1 From the
Department of Medical Oncology, Istituto
Oncologico Veneto1, Padova, Italy University
General Hospital 2 , Heraklion, Greece.
16

• METHODS
• To evaluate management and survival of all
  consecutive frail patients ? 70 years, seen from
  October 2004 to December 2005 within our
  Geriatric Oncology Program.
• Frailty was defined by one or more of the
  following
• ? age ? 85 years
• ? dependence in one or more ADL
• ? at least three grade 3 comorbidities, or one of
  grade 4 (CIRS-G scale)
• ? one or more geriatric syndromes
• Balducci L, Cancer Control 2001.

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RATIONALE RATIONALE
Management of frail elderly patients
adapted treatment or only supportive care?
Few data on outcome and survival.
Management of frail elderly
patients adapted treatment or only supportive
care? Few data on outcome and survival.
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RESULTS PATIENTS

• A total of 364 elderly patients underwent
  Multidimensional Geriatric Assessment fit
  (26.4), vulnerable (49.5) and frail patients
  (24.2)
• 88 eligible frail patients had a median age of
  79 years (range, 70-93), 43.2 males.

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RESULTS PATIENTS
Treatment of 88 frail patients
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• RESULTS CHEMOTHERAPY
• 8 patients gastro-intestinal tumors, 7 lung, 7
  hematological and 8 other sites.
• These 30 Patients received
• standard regimens at standard doses (26.6)
• or with ? 25 dose reduction (23.3),
• age-adapted regimens at standard doses (43.3)
• or with reduced doses (6.6).

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RESULTSChemotherapy

• Six patients (20) derived some clinical benefit
  but only two (6.7) showed a radiological
  response.
• Twenty patients interrupted chemotherapy
  prematurely due to either toxicity/death (23.3)
  or refusal/drop out (43.3).

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OVERALL SURVIVAL
So far, 30 patients have died (34), with a
projected 1 and 2-year overall survival of 61 and
35, respectively.
23
DISCUSSION

• Frailty was observed in 1/4 of all patients our
  elderly but it did not prevent treatment of tumor
  with either chemo- or endocrine therapy in 66 of
  cases.

• Dose reductions or adapted regimens were
  frequently applied,
• but almost 30 were still treated with regimens
  studied only in younger patients.

24

• DISCUSSION
• Chemotherapy very few radiological responses,
  some form of clinical benefit reported by 20 of
  patients, high rate of early interruption due to
  toxicity or refusal.
• New treatment algorythms are urgently needed in
  order to help the oncologist in the pivotal
  decision of whether to treat or not these
  patients.

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Definition of frailty from oncological causes

• Neoplastic comorbidity grade 4
• ADL lt 6 due to neoplastic disease
• Grade 3 neoplastic comorbidity plus two or
  more grade 3 comorbidities

• Defined as any advanced tumor amenable with
  chemotherapy or hormonotherapy, but not curable
• If ADLand /or tumor related comorbidity grade
  4 may improve after therapy, frailty may be
  reversible
• 
  S.Monfardini and U.Basso

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ONCOLOGICAL CAUSES OF FRAILTY (COMORBIDITY GRADE
4)

• Liver failure from primary or metastatic disease
• Pulmonary insufficiency from primary or
  metastatic disease
• Brain or meningeal extensive primary or
  metastatic disease

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ONCOLOGICAL CAUSES OF FRAILTY EXAMPLES OF
INFLUENCE ON ADLS

• Cachexia
• Uncontrolled pain
• Loss of mobility from refractory pathological
  fractures
• Esofageal stenosis
• Intestinal obstruction
• Recurrent peritoneal effusion

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ONCOLOGICAL CAUSES OF FRAILTY TO BE CONSIDERED IN
GERIATRIC SYNDROMES

• Neoplastic urinary incontinence (due to neoplasia
  or surgical or RT sequelae)
• Neoplastic rectal incontinence (due to neoplasia
  or surgical or RT sequelae)

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Treatment of elderly cancer patientswe probably
only know the tip of the iceberg,frail are in the
base
Elderly selected for clinical studies
?
Elderly selected for empirical treatment
Elderly not receiving any treatment because of
frailty, lack of family support, other
age-associated conditions
?
30
Clinical trials in the elderly frail patients are
lacking

• Elderly frail patients excluded from clinical
  trials
• Results from trials conducted with younger adults
  may not2 be applicable to the majority of
  elderly cancer patients
• Different chemotherapy regimens should also be
  tested in elderly frail patients3

2Brunello A et al. Ann Oncol 20051612761282 3
Monfardini S et al. Ann Oncol 20051613521358
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Example A trial designed for frail elderly
patients
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Barriers to the informed consent to be overcome
in elderly (frail) cancer patients before trials
entry

• Hearing defects
• Not easily readable document (small print)
• Lack of understanding of the real meaning of the
  information (cognition deficit and/or very low
  scientific knowledge)
• Family interference
• (Monfardini S., Prescribing anticancer drugs in
  elderly cancer patients, Eur. J. Cancer 2002,
  2341-2346)
• Physician reluctance to provide full information