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INTRODUCTION
More than half of
all new cancers occur in patients 65 years of
age or older [40]. The incidence of cancer in
this age group is 11 times that in the population
under 65 (2261 per 100,000 population, as compared
with 207 per 100,000 population), and more than
half of all deaths due to cancer occur in patients
65 or older. The increasing longevity of our population
makes these statistics especially sobering. Moreover,
life expectancy continues to rise. The median
survival for healthy women and men who are 70
years old is 15.7 and 12.4 years, respectively,
and for those 80 years old it is 8.6 and 6.7 years,
respectively [39]. Many older people are healthy,
but others, particularly people of advanced age
have several chronic diseases and present with
an important co-morbidity. Older people have an
increased risk for cancer-specific mortality and
are at higher risk for treatment-associated morbidity
than younger persons. Older cancer patients admitted
to a geriatric or an internal medicine unit present
with multiple active geriatric problems and have
characteristics distinct from traditional geriatric
patients [29]. However, older patients who are
in good health tolerate commonly used chemotherapy
regimens as well as younger patients [5]. Chronologic
age alone is an inadequate predictor of treatment
tolerance and benefit in this heterogeneous population.
A diagnosis of cancer in an older person is likely
to be made in the context of that individual's
pre-existing health problems, which introduces
very important issues in clinical decision making
and treatment. Multiple issues associated with
aging impact cancer care, including functional
impairment, co-morbidity, social support, cognitive
function, psychological state, and financial stress.
Evaluation of the co-morbidity in an older person
newly diagnosed with cancer and assessment of
the severity of the various pre-existing conditions
and their overall and individual impact on the
cancer course are crucial to providing quality
cancer care to older individuals [13]. In this
respect a multidisciplinary approach might be
useful in the management of the geriatric oncology
patient. Although Comprehensive Geriatric Assessment
(CGA) should evaluate different domains in this
co-morbidity, malnutrition has a particular place
in it, because it still is a potentially treatable
condition. This review aims to discuss the available
nutritional screening tools and their limitations
in clinical oncogeriatric practice.
Key words:
geriatrics, cancer, nutritional assessment, screening
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GERIATRIC PROFILE
Geriatric patients are
not defined by their age but by their general profile.
Aging is characterized by loss of organ function such
as loss of muscle mass or bone mineral density together
with a reduced capability for adapting to changes in
the environment (loss of homeostatic mechanisms). These
changes in physical function are paralleled by changes
in cognitive function, mental health and socio-economic
status. This can lead progressively to a state of increased
vulnerability or frailty [4]. This evolution shows a
distinct correlation with age. Data from the Belgian
Health Surveys 1997-2004 have shown that the percentage
of people with frailty as assessed with the VIP-tool
(Variable Indicator for Placement [37]) was 5.1 % for
the people aged 65 -70 years, but had already risen
to 48.9 % in the cohort older than 85 [17]. Further
progression of decline in organ function will induce
functional impairment and finally disability. When a
geriatric patient develops a tumor, the systemic effects
induced by the tumor (local effect, host response to
the tumor…) will superimpose on the geriatric profile
of the patient, thereby further compromising prognosis.
It has been shown that CGA adds useful information to
the evaluation of WHO-ECOG performance status in older
patients with cancer and is able to predict efficacy
and tolerance of chemotherapy [14, 19]. Geriatric instruments
appear more sensitive than classic oncological instruments
in measuring functional status [9].
MALNUTRITION
COMPONENTS
Involuntary weight loss is common in older people and
is an unfavorable prognostic sign. Data from the Belgian
Health Interview Surveys show a progressive loss of
weight with aging. Moreover, this weight loss is significantly
correlated with frailty and loss of mobility in community
dwelling elderly [36]. A large component of involuntary
weight loss in older persons is a loss in fat-free mass.
This loss of muscle mass with aging is clinically important
because it leads to diminished strength and exercise
capacity. [33]
In general, three primary categories of skeletal muscle
loss can be distinguished: starvation, sarcopenia, and
cachexia.
Starvation is a pure protein-energy deficiency, forcing
a reduction in both fat and fat-free mass. The key physiological
sign of starvation is that it is reversed solely by
the replenishment of nutrients [1].
Age-related decline in muscle mass has been termed sarcopenia,
a term first introduced by Rosenberg in 1989 [32]. The
definition of sarcopenia continues to evolve. The reduction
of muscle mass and strength that occurs with aging may
be independent of body mass as measured by body weight
[24]. The recognition of impairment in muscle strength
and functional status with sarcopenia has added the
inclusion of function in the definition. Sarcopenia
is therefore defined as the loss of muscle protein mass,
function and muscle quality that accompanies advancing
age [20].
Severe wasting of both fat and fat-free mass is termed
cachexia. Cachexia accompanies diseases such as cancer
or immunodeficiency states. Cachexia is best viewed
as the cytokine-associated wasting of protein and energy
stores due to the effects of disease [34]. Systemic
inflammation mediated through cell injury or activation
of the immune system triggers an acute inflammatory
response [7]. Persons with cachexia lose fat as well
as fat-free mass, while maintaining extracellular water
and intracellular potassium. The loss of fat-free mass
is mainly from the skeletal muscle and is an essential
component in the definition. A panel of experts has
recently tried to improve the operational definition
of cachexia [8]. The definition that emerged is: ''cachexia
is a complex metabolic syndrome associated with underlying
illness and characterized by loss of muscle with or
without loss of fat mass. The prominent clinical feature
of cachexia is weight loss in adults (corrected for
fluid retention)." Other diagnostic criteria for
cachexia besides loss of muscle mass and evidence of
accelerated protein degradation in muscle are decreased
muscle strength, fatigue, anorexia, and biochemical
abnormalities characteristic of inflammation, anemia
or hypoalbuminemia. Persons with cachexia due to cancer
may deplete up to 80% of their muscle mass [2]. More
than 80% of persons with upper gastrointestinal cancer
have cachexia at diagnosis and more than 60% of lung
cancer patients develop cachexia. The key clinical question
is whether starvation, sarcopenia and cachexia are distinct
entities or represent an interdependent continuum. In
the older patient with cancer there can be problems
of dietary intake next to the effects of aging per se.
On top of this situation the deleterious effects of
the inflammatory processes induced by the tumor are
superimposed. When these changes are translated into
nutritional concepts it is clear that in the older cancer
patient there is a strong overlap of starvation, sarcopenia
and cachexia. The final result is a complex metabolic
state resulting in a therapy resistant malnutrition
syndrome.
SCREENING
TOOLS
Implementing routine screening to detect malnutrition
has been hindered by the lack of universally agreed
criteria to identify it. Consequently, there are a variety
of nutritional tools in use that incorporate different
anthropometric, biochemical and clinical criteria which
have often been developed for use in a particular setting
or for a specific patient group. Most instruments screen
for nutritional risk and not for existing malnutrition.
Actually, this indicates that the first screening level
is based on simple measurements that identify people
who may be at risk for malnutrition. Only after that
a complete nutritional assessment should describe their
actual nutritional status with biochemical, anthropometric,
functional parameters of muscle strength (handgrip),
bio-impedance and dexa-measurements. Although slight
declines in weight have been observed with aging alone,
clinically important weight loss (>5% of usual body
weight) is almost always the result of disease. In older
people weight loss and low Body Mass index (BMI, defined
as weight in kilograms, divided by height squared) have
been associated with adverse outcomes such as decreased
functional abilities and increased morbidity and mortality.
BMI demonstrates a U-shaped relationship with functional
impairment, with greater risk in those with the lowest
and highest BMI [36]. The annual incidence of involuntary
weight loss (defined as loss of greater than 4% of body
weight) was reported to be 13.1% in community-dwelling
veterans. Over a 2-year follow-up period, involuntary
weight loss was associated with a greater relative risk
of mortality (RR=2.4, 95% confidence interval 1.3-4.4)
[38]. Because routine weighing is an inexpensive method
to screen for energy undernutrition, patients should
be weighed at their primary visit and the weight should
be documented in their medical record [30].
The 'malnutrition universal
screening tool' (MUST) for adults has been developed
for multi-disciplinary use by the Malnutrition Advisory
Group of the British Association for Parenteral and
Enteral Nutrition (www.bapen.org.uk) for use in all
health care settings. It also has good reproducibility
between users, and is acceptable to patients and health
care workers. The MUST score is able to predict increased
mortality in older hospitalized patients [16]. MUST
is a five-step screening tool to identify adults, who
are malnourished, at risk of undernutrition or obese.
It also includes management guidelines which can be
used to develop a care plan. The MUST tool scores for
Body Mass Index, loss of weight in the past 3-6 months
and the presence of an acute illness or no nutritional
intake for 5 days or more.
The NRS (Nutritional Risk Score)
[22] is based on the concept that nutritional support
is indicated in patients who are severely ill with increased
nutritional requirements, or who are severely undernourished,
or who have certain degrees of severity of disease in
combination with certain degrees of undernutrition.
Patients are characterized by scoring the components
'undernutrition' and 'severity of disease' in four categories
(absent, mild, moderate and severe). The patient can
have a score of 0-3 for each component which results
in a total score of 0-6. Any patient with a total score?
3 is considered at nutritional risk. Undernutrition
is evaluated using three variables (BMI, percent recent
weight loss and recent change in food intake). The most
compromised of the three variables is used to categorize
the patient. With age >70 years, a value of 1 is
added to the total score.
The SNAQ (Short Nutritional
Assessment Questionnaire) was validated in a population
of mixed internal, surgical and oncological patients
[23]. It consists of three questions regarding involuntary
weight loss, loss of appetite and recent use of supplemental
drinks or tube feeding. Those questions appeared to
be the best indicators for malnutrition. The SNAQ has
also been validated for an outpatient population [25].
However, it was not specifically validated in an older
population.
The Mini Nutritional Assessment
(MNA) is both a screening and assessment tool for the
identification of malnutrition in older people [15].
The MNA is composed of 18 items, including anthropometric
measurements [weight, height, mid-arm circumference,
calf circumference, and weight loss during the past
3 months], a global assessment (six questions related
to lifestyle, medication, and mobility), a dietary assessment
(eight questions related to number of meals, food and
fluid intake, and autonomy of feeding), and a subjective
assessment (self-perception of health and nutrition).
The maximum score is 30 points, with the risk of malnutrition
increasing with lower scores. The MNA score was used
to classify subjects as well-nourished (a score of 24-30),
at-risk for malnutrition (a score of 17-23.5), or malnourished
(a score of <17) according to the original cut-off
point of the MNA full test. The screening section of
the questionnaire uses 6 items from the global test,
namely reduction in food intake, weight loss, mobility,
acute stress, neuropsychological problems and BMI. If
the score is 12 points or greater, the patient is not
at risk and there is no need to complete the rest of
the questionnaire. If the score is 11 points or less,
the patient may be at risk from malnutrition and the
full MNA-assessment should be completed.
The assessment of nutritional
status could be questioned in view of the many non-nutritional
factors affecting the results. Subjective assessment
of nutritional status has been proposed to overcome
these difficulties [21]. Subjective global assessment
(SGA) is a validated method of nutritional assessment
based on the features of a medical history (weight change,
dietary intake change, gastrointestinal symptoms that
have persisted for more than 2 weeks, changes in functional
capacity) and physical examination (loss of subcutaneous
fat, muscle wasting, ankle or sacral edema and ascites)
[6]. The patient-generated-subjective global assessment
(PG-SGA) was adapted from the SGA and developed specifically
for patients with cancer [27]. It includes additional
questions regarding the presence of nutritional symptoms
and short-term weight loss. It was designed so that
the components of the medical history can be completed
by the patient using a check box format. The physical
examination is then performed by a health professional,
e.g. physician, nurse or dietitian. The scored PG-SGA
is a further development of the PG-SGA concept that
incorporates a numerical score as well as providing
a global rating of well-nourished, moderately or suspected
of being malnourished or severely malnourished. For
each component of the scored PG-SGA, points (0 - 4)
are awarded depending on the impact of the symptom on
nutritional status. A total score is then summed and
this provides a guideline as to the level of nutrition
intervention required [26]. The scored PG-SGA, unlike
SGA, which is categorical, is a continuous measure.
Higher scores indicate a greater risk for malnutrition.
DISCUSSION
In older patients presenting with an oncological pathology
several problems are interacting. The cancer will add
its effects on the frailty which itself is an expression
and consequence of the aging process. When people grow
older they lose the capacity of adapting well to changes
in their environment. This loss of homeostasis in the
broad sense leads to an increased vulnerability, called
frailty. Although no universal definition has been defined,
frailty could be described as an unstable equilibrium
carrying a high risk for functional loss. Losing weight
with the emergence of malnutrition is part of it. The
decline in nutritional status in the geriatric oncology
patient is the result of the effects of lower dietary
intake (starvation), the effects of aging (sarcopenia)
and the effects of the tumor (cachexia). The resulting
condition can lead to a complex malnutrition syndrome
with a major impact on prognosis and the beneficial
effects of the intended treatment. The screening for
co-morbidity in older people is therefore essential
and nutritional assessment is a major issue in this
regard. During the period of treatment an objective
measure to demonstrate patient outcomes is essential
for proving the value of nutrition intervention. Baseline
screening for malnutrition is therefore mandatory in
the pre-treatment strategy for older oncology patients.
Several screening instruments have been developed. Most
of them have not been validated in an older population.
This is the case for the SNAQ, the MUST and the NRS,
although recently the MUST has shown to be able to predict
increased mortality in older hospitalized patients [16].
NRS has proven not sensitive enough to predict weight
loss in diseased older subjects [31]. NRS adds one point
when age is above 70. In a geriatric population this
item scores 100% positive and therefore has no additional
discriminative value.
There is a significant overlap in the methodology of
the different screening tools. For example, the assessment
of weight loss is a major issue in most of them. Second
the use of BMI is enforced. However, in older people
the body length is not a constant factor [35]. It tends
to decrease with age. This leads to a systematic error
in the calculation and an overestimation of the BMI.
Furthermore, in older disabled people body weight and
body length are often the result of estimation. The
official guidelines for the MUST, for example, give
alternative ways for dealing with this problem with
the following advice, "If unable to obtain height
and weight, see for alternative measurements and use
of subjective criteria". When two variables are
not measured but estimated, when subsequently one is
squared and the quotient is taken, one can doubt the
exactness of the final result. On the other hand, when
BMI is systematically overrated, a low BMI, indeed,
may be a significant sign for the risk of malnutrition.
Taking into account the systematic overestimation of
BMI, the classical cut-off value of <18.5 [12] may
be increased to the cut-off value used in the MUST guideline
(<20.0). However, a normal or even high BMI does
not exclude nutritional problems. Increase in body fat
may, indeed, mimic the loss of muscle mass. It has been
recently corroborated that sarcopenic obesity, or low
muscle mass in relation to fat mass, predicted onset
of IADL disability in community-dwelling elders who
had no disability [3]. In cancer patients it was shown
that sarcopenic obesity was associated with poorer functional
status compared with obese patients who did not have
sarcopenia and that sarcopenia was an independent predictor
of survival [28]. This may be particularly important
because fat free mass represents the volume of distribution
of many cytotoxic chemotherapy drugs. Estimation of
relative sarcopenia (muscle mass adjusted for body fat
mass) may, therefore, be a better predictor than absolute
sarcopenia.
In summary we can conclude that
nutritional assessment should be part of the routine
preliminary evaluation of the older oncology patient.
Difference should be made between assessment of risk
and actual nutritional status, which should be assessed
with specific malnutrition indices. Body weight assessment
with specific attention to unintended weight loss is
essential in this evaluation. We should recognize the
fact that BMI should be interpreted with caution, but
that a low value for BMI still heralds an increased
malnutrition risk. Weight loss alone, however, does
not identify the full effect of cachexia on physical
function. It can be helpful to add to the item of weight
loss an estimate of reduction in food intake and systemic
inflammation. This would help to identify patients with
both adverse function and prognosis [11]. This increased
alertness based on a relative subjective global assessment
has a lot to offer in the willingness for early intervention.
The nutritional assessment must be framed in a larger
CGA (comprehensive geriatric assessment) addressing
several functional domains [10]. This may lead to an
optimalization of the strategy for the management of
oncological problems in older people. Some evidence
is beginning to appear as to the impact a comprehensive
geriatric assessment could have on the oncologic management
of older patients with cancer [18].
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