Transcript 4-LEIBOVICI-Prague lecture V3

THE FRAILTY SYNDROME AND
CANCER TREATMENT IN THE ELDERLY
Judith Leibovici, Orit Itzhaki, Tatiana Kaptzan, Raida
Asfour, Monica Huszar, Judith Sinai, Ehud Skutelsky
and Moshe Michowitz
Department of Pathology, Sackler Faculty of Medicine,
Tel-Aviv University, 69978 Tel-Aviv, Israel
International Federation on Ageing (IFA) 11th Global
Conference on Ageing, Prague 2012
About 60% of cancers appear in
people aged over 65 years.
Nevertheless, elderly cancer patients
are not receiving the same standard
of oncological care as younger
patients.
Treatment of aged cancer patients
constitutes a yet unsolved problem,
particularly for those who are frail.
Cancer treatments now in use most often
include aggressive procedures which are
particularly harmful to elderly frail
individuals.
Treatment of cancer in elderly patients is
extremely problematic due to their increased
tendency to:
Frailty
Comorbidities
Polypharmacy
Increased sensitivity to drug toxicity
In view of the aggressiveness of anti-cancer
therapies in use, not all aged patients are fit for
these treatments.
Frailty confers high risk of falls,
fractures, disability, hospitalization
and mortality.
Mortality is a function of frailty
Degree of frailty
Non-frail
Pre-frail
Frail
Prevalence
7.4%
15%
53.3%
5 year mortality
13.6%
20.4%
44.5%
Until recently, a clear definition of frailty
remained elusive.
The
American
Medical
Association
characterized the term “frailty” as:
"The most complex and challenging
problem to the physician and all health
care professionals".
A large variety of properties have been
attributed to the frailty syndrome, up to
75, by the group of Rockwood.
The definition of FRAILTY now mostly adopted,
that of Fried et al. (2001), includes 5 items:
1) Unintentional weight loss or sarcopenia
2) Weakness as measured by grip strength
3) Poor endurance resulting in self-reported exhaustion
4) Slowness as measured by walking speed
5) Self-reported low physical activity
Patients with 3 or more of these criteria are
considered FRAIL. Patients with 1 or 2 of these
signs are considered PRE-FRAIL.
Frailty depends on:
1)Age
2)Gender
3)Socio-economic conditions
4)Level of education
Very recently Shamliyan et al. calculated
the pooled prevalence of frailty in function
of age of the two types of groups: those
who define frailty according to phenotype
(Fried-like) and those who define it by
accumulation of deficits (Rockwood- like).
Shamliyan et al. Ageing Res Rev, 2012
Pooled prevalence of frailty in function of age
Age
65-70
70-80
80-84
>85
Fried-like
3-6%
5-12%
>16%
26%
Shamiylian et al. 2012
Rockwood-like
5-15%
8-17%
>16%
50-56%
Elderly
cancer
patients
were
traditionally under-treated or not treated
at all.
Moreover, the under-treatment was not
evidence- based, since aged cancer
patients were most often not included in
clinical trials.
Cancer treatment in the aged was viewed
differently by different groups.
Balducci stressed the idea that age per se
should not preclude "classical" cancer
treatment and this should include the "fit"
elderly patients who, he considered,
constitute the majority of the elderly
population.
Balducci L. Aging, frailty and chemotherapy. Cancer
Control 14: 7-12, 2007
According to Balducci, "Most older
patients appear to benefit from cancer
treatment to an extent comparable to
that of younger individuals and only a
minority should be excluded from
treatment due to reduced tolerance"
Balducci, 2007
Santos-Eggimann et al. reported
the prevalence of frailty and prefrailty in 10 European countries.
The
frailty
phenotype
was
assessed in this study for more
than 16,000 participants.
Santos- Eggiman 2009
One notable result of this study was that the
proportion of frailty was higher in Southern than
in Northern European countries.
Frailty was more frequent in Spain, Italy and
Greece than in Sweeden and Switzerland.
The data suggested that socio-economic
factors and education level contribute to this
difference.
Comparison of frail and pre-frail prevalence
in different countries
Country
Non frail
(%)
Pre-frail
(%)
Frail
(%)
Frail + Pre
frail
Reference
Belgium
Brazil
Canada
Finland
Germany
Israel
Japan
Russia
Spain
Switzerland
Taiwan
USA
60.0
22.8
42.9
40.0
33.6
24.5
44.0
15.9
34.6
50.0
45.7
45.6
30.7
60.1
49.7
50.4
52.1
56.0
44.0
63.0
48.5
40.6
44.5
47.6
9.3
17.1
7.4
9.6
14.3
19.5
12.0
21.1
16.9
9.4
9.9
6.8
40.0
77.2
57.1
60.0
66.4
75.5
56.0
84.1
65.4
50.0
54.4
54.4
Hoeck S. et al.
De Albuqerqrque-Sousa A.C.P. et al.
Wong C.H. et al.
Sirola C. et al.
Drey M. et al.
Jacobs J.M. et al.
Nemoto M. et al.
Gurina N.A. et al.
Abizanda-Soler P. et al.
Rochat S. et al.
Lin C.C. et al.
Frisoli A. et al.
Average
38.3
48.9
12.9
67.7
The range of frailty prevalence is situated
between 4.3-21.1 % (mean 11.9) However, the
prevalence of pre-frailty is very high, ranging
between 40.0-84.1 (mean 49.0 ), most values
being situated around 50%. The dimension of
the prevalence of non-fit individuals in the
aged population is definitely very high. The
prevalence of pre-frail plus frail reaches in
certain populations 75-80 percent!
Indeed, the percentage of those considered
to be frail among the elderly is low in many
Western countries (4-8%). However, they may
constitute more than 20-30% in countries
such as those in Southern Europe.
(Data concerning developing countries are
very few and they risk to be much higher).
In addition, the percentage of pre-frail
individuals is very high (close to 50%), in all
European countries.
.
Importantly,
pre-frail
individuals
expected to become in 3-4 years frail
are
It follows that up to 70%-80% of
elderly patients (frail+ pre-frail) are
non-fit and thus have to undergo
milder treatments.
The fraction of non-fit elderly people
constitutes thus a majority in the aged
population,
indicating
that
cancer
treatment in the old is even more
complicated than previously thought.
Thus, only a minority of elderly people
are "fit" (about 30%) and can be treated
"traditionally".
For the majority of aged cancer patients
(about 70%), milder treatments have
thus to be adopted.
We suggest, moreover, that the
usually aggressive anti-cancer
procedures may even precipitate
the transit from pre-frail to frail
status.
The social aspects of the frailty problem
(the need of elevating the socioeconomic status and education level),
may finally be more efficient, less
expensive and - most important - entail
less suffering to aged cancer patients
than the treatment of frailty.
Treatment of frail cancer patients: New suggestions
Only recently, treatment of the main types of
cancer, adapted for the different stages of frailty
(and beyond -disability- ) have been suggested
(Monfardini S, Int Emerg Med 6: S115 –S118,
2011).
The new suggestions include:
1) Reduced doses of chemotherapy
2) Use of less toxic drugs
3) Administration of cytotoxics at hospital
4) Supervised conditions of post-treatment
With reference to Balducci’ s statement:
Numerous studies were published in recent
years showing that selected fit elderly
individuals are able to undergo the same
aggressive therapies as successfully as
young cancer patients.
It is therefore true that chronological age
alone should not prevent elderly cancer
patients from receiving usual anti-cancer
treatment.
In addition, whenever a less aggressive
therapy is discovered (minimally invasive
surgery, for instance), it might also be
appropriate for less fit senior patients.
The question is, what is the percentage
of those elderly fit patients in the aging
population. According to Balducci,
they constitute the majority. We
contend that, on the contrary, they
constitute a minority in the elderly
population.
Based on the published prevalence of
frailty and pre-frailty in the elderly
population, we suggest that most elderly
patients are not fit for the now existing
anti-neoplastic treatment modalities.
Therefore, novel approaches, adapted to
the aging host and to the specific biology
of tumors in the old, should be
investigated.
Balducci states that the very concept of
frailty
has
prevented
life-saving
interventions in anti-neoplastic treatment in
older patients.
However, frailty – though complex – does
exist and may, moreover, be fatal.