Critical Reviews in Oncology/Hematology 67 (2008) 243–254

Undernutrition in elderly patients with cancer: Target

for diagnosis and intervention
Christèle Blanc-Bisson a , Marianne Fonck b , Muriel Rainfray a,d ,
Pierre Soubeyran b,c,d , Isabelle Bourdel-Marchasson a,e,∗
a Pôle de gérontologie, CHU de Bordeaux, Hôpital Xavier Arnozan, 33400 Pessac, France
b Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux, France
c Unité INSERM/CRLC Bordeaux, Institut Claudius Regaud E0347, France
d Université V Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux France
e UMR 5536, CNRS/Université V Segalen Bordeaux 2, Bordeaux, France

Accepted 24 April 2008

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
2. Tumoral cachexia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
2.1. Anorexia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
2.2. Intake inability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
2.3. Changes in carbohydrates, lipid and protein metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
2.4. Nutritional alterations linked to anticancer treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
2.5. Metabolic activity of tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
2.6. Hypothesis of intratumoral hypoxia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
3. Impact of undernutrition on neoplastic pathology prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
4. Undernutrition and elderly patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
5. Cancer treatment effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
6. Nutritional intervention in cancerology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

Abstract
In recent years, geriatricians and oncologists have worked together to evaluate elderly patients with cancer before and during treatment, to
estimate the balance between the efficacy and safety of chemotherapy and to upgrade treatment in this population according to their comorbidity
and physiological status. The clinical and biological factors of this population need to be assessed in multidisciplinary comprehensive geriatric
assessment (CGA) in order to optimize treatment without inducing major adverse effects. We reviewed the nutritional aspects of this evaluation
that highlight the impact of undernutrition on poor survival. In this paper we briefly describe tumoral cachexia (molecular and physiological),
the impact of undernutrition on cancer prognosis (predictive factors), therapeutic effects of cancer on nutritional status, nutritional indicators
(biological, anthropometric) and undernutrition in the elderly (specific needs of this population). The potential for nutritional intervention in
geriatric oncology with regard to CGA is explored.
© 2008 Elsevier Ireland Ltd. All rights reserved.

Keywords: Undernutrition; Elderly; Cancer; Survival; Dietary intervention; Comprehensive geriatric assessment

∗ Corresponding author at: Pôle de gérontologie, CHU de Bordeaux, Hôpital Xavier Arnozan, 33400 Pessac, France. Tel.: +33 5 57 65 66 72;

fax: +33 5 57 65 65 60.

E-mail address: isabelle.bourdel-marchasson@chu-bordeaux.fr (I. Bourdel-Marchasson).

1040-8428/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.critrevonc.2008.04.005
244 C. Blanc-Bisson et al. / Critical Reviews in Oncology/Hematology 67 (2008) 243–254
1. Introduction
The number of elderly patients older than 70 years in
France and in the industrialized world is steadily increas-
ing. In 2002, the average life expectancy at 75 years was 12
years for both males and females. At that time in Aquitaine,
France, 273,741 individuals were over 75 years and repre-
sented 9.2% of the population. The incidence of cancer at this
age was 72,000 new cases per year in France in 2000. Older
subjects (>70 years) represent more than 40% of patients with
cancer [1]. Diagnosis and treatment of older patients is one
of the priorities of the cancer campaign set up by the French
government. Despite the difficulties of physicians to evaluate
the ratio between risk and benefits, the fears of patients and
their families, studies focusing on elderly patients have been
conducted in recent years [2,3]. The few oncologic thera-
peutic studies conducted in this older population have shown
excellent results with tolerable toxicities [4–6] despite the
presence of comorbidity (cardio-vascular diseases, diabetes,
hypertension, etc.).
Undernutrition is frequent after 70 years of age due to
inadequate dietary intake and particularly protein intake [7].
It is now considered as one of the criteria of frailty in older
patients due to the major association of undernutrition with
altered cognition, mobility, mood, physiological status and
quality of life in environmental, social and familial contexts
[8]. Nutritional prognostic factors during medical treatments
are poorly understood. No simple specific undernutrition
marker is available in daily practice. Furthermore, indepen-
dently of tumor specificity, central anorexia was noted to
differing degrees associated with hypothalamic dysfunction
interfering via an inflammatory process with serotoninergic
systems or neuropeptides that control dietary intake. Inter-
actions between inflammatory mediators, nutritional status,
tumor course, chemotherapy-related events and survival are
likely.
We aimed to describe the influence of undernutrition in
elderly patients with cancer on cancer course and prognosis
and to explore any positive effects of nutritional interventions
in geriatrics.
2. Tumoral cachexia
Cancer is generally associated with undernutrition, partic-
ularly in advanced stages. Cancer cachexia is characterized
by a slow weight loss consequence of abnormal metabolic
activity and anorexia, altered immune function, modified
prognosis, and decreased efficacy of chemotherapy regimens
(Table 1) [9,10].
The cancer process involves extensive tissue remodeling
including modulation of numerous cellular activities and tis-
sue functions [11]. Cytokine expression (Il-1␤, Il-2, Il-6,
TNF␣, IFN␥, IGF-1) and C-reactive protein (CRP) synthe-
sis by cell-mediated immunity cells (macrophages) and by
cancer cells have been reported [12–15]. Aging is related
Table 1
Main phenomena implicated in development of cancer cachexia
Weight loss/cachexia Mechanisms
Anorexia Proinflammatory cytokines
Anatomic incapacity Loss of swallowing ability, digestive
hindrance,
Metabolism changes Neoglucogenesis inducing fat mass
(hypercatabolism) and lean mass atrophy, insulin
resistance, increasing free fatty acid
level
Hypercatabolism Neoglucogenesis inducing fat mass
cancer dependent and lean mass atrophy
Treatment of cancer Nausea, vomiting, mucositis,
diarrhea, constipation
Hypoxia Decrease in O2 pressure, increase in
HIF-1␣ expression (stimulating
GLUT-1 expression (glucose
transporter)), increase in GLUT-1
expression suggestive of glucose
accumulation in cells
to important changes in lymphocyte subsets and innate and
non-specific immune response. Moreover, protein-energy
malnutrition and micronutrient deficiencies are common in
the elderly and undernutrition is a major factor leading to
immunodeficiency [16–19].
Undernutrition in patients with cancer, termed tumoral
cachexia, concern about 50% of subjects during the course of
the pathology [20,12]. Potential causes in the elderly include
hypercatabolic activity [21,22], the impact of cancer and
cancer treatment on dietary intake and the digestive appa-
ratus [23], depression, comorbidity, swallowing disorders,
radiotherapy, xerostomia, functional and anatomic hindrance,
presbyphagia decompensation due to asthenia, pulmonary
infections and hypoxia. The highest prevalence was observed
in patients with aerodigestive tract cancers [24]. Cancers thus
play a role in pathologies that can induce cachexia such as
anorexia, asthenia and progressive decrease in body mass
index due to chronic inflammation [25,26]. Furthermore, the
origins of undernutrition in elderly cancer patients are numer-
ous [20] and involve the cancer per se and the conditions of
the patient in different proportions.
2.1. Anorexia
This symptom is present in as many as 50% of patients
during cancer and is only partly due to hypercatabolism
[27]. Proinflammatory cytokines play their part as follows:
Il-1 could inhibit Y neuropeptide that stimulates hunger
hypothalamic neurons. TNF alpha may stimulate the genetic
expression of mitochondrial decoupling proteins (UCP 1-2-
3) and muscular thaw (induction of degradation of muscular
proteins). Interferon gamma and Il-6 production promote
cachexia. Inflammatory cytokines produced by the host in
response to the tumor are thought to play a role in cancer-
associated malnutrition [27]. TNF alpha, Il-6 and leptin act
on the central nervous system and alter the release and func-
tion of several key neurotransmitters, thereby altering both
 C. Blanc-Bisson et al. / Critical Reviews in Oncology/Hematology 67 (2008) 243–254
appetite and metabolic rate. Proinflammatory cytokines also
activate the transcription nuclear factor kappa-B, resulting
in decreased protein synthesis. This stimulates the ubiquitin-
mediated proteasome, which is the major system involved in
increased protein degradation. The pattern of cytokine secre-
tion in cancer is not similar to that observed during infections.
Tryptophane and serotonin could participate in anorexia via
leptin secretion, inducing anorexia. Tryptophan inhibits lep-
tin secretion and stimulates ghrelin expression and secretion.
The implication of leptin hormone and possible ghrelin resis-
tance has been suggested in the onset of anorexia [22,28].
Leptin is secreted by adipocytes (OB gene) and is mainly
regulated by fat mass, so plasma leptin concentrations cor-
relate with fat mass. Energy intake, cortisol and insulin also
stimulate leptin secretion. This secretion is nycthemeral with
maximal levels observed between midnight and 8 a.m. [29].
However, in cancer, it has been shown that leptin concentra-
tions are correlated with fat body mass [29] with no evidence
of abnormal regulation, in contrast to severe infectious dis-
ease where leptin secretion is increased despite loss of fat
mass and decreased dietary intake [30].
2.2. Intake inability
Reduced intake could result from loss of swallowing abil-
ity, anatomical or functional hindrance in the digestive tract,
or from pain induced by food in relationship with a tumor,
radiotherapy [31] or post-surgical status [32]. It can also result
from aging due to neurological and muscular age-related
alterations (presbyphagia) [33,34], local reasons, iatrogeny
and other reasons (diabetes, undernutrition, dehydration, ter-
minal status).
Fig. 1. Switch between aerobic dissimulation to anaerobic dissimulation during tumor growth that contributes to tumor cachexia.
245
2.3. Changes in carbohydrates, lipid and protein
metabolism
Metabolic changes such as increased neoglucogenesis,
insulin resistance and elevated free fatty acids as seen in a
hypercatabolic state are observed in cancers. The increasing
energy and oxygen demand that can result from hyper-
catabolism is not specific to cancer [35,36].
2.4. Nutritional alterations linked to anticancer
treatment
The adverse effects of anticancer treatments can decrease
dietary intake, such as mucositis, nausea, vomiting, diar-
rhea, constipation, oral health status, and hyposialia after
chemotherapy or radiotherapy.
2.5. Metabolic activity of tumor
Tumor metabolism induces changes that promote
neoglucogenesis (Fig. 1) [36]. More lactate may be gener-
ated, resulting in increased anaerobic activity involving the
hepatic metabolism for lactate recycling (Cori cycle), which
stimulates neoglucogenesis via the mobilization of fatty acids
and amino acids. This process could account for the wast-
ing of both these compartments. Proteoglycan secretion by
tumors leading to muscular hypercatabolism was demon-
strated in an animal model but was not confirmed in human
[37]. The lipolytic activity of a factor extracted from urine
of patients with cachexia was shown on a murine model
[38].
246 C. Blanc-Bisson et al. / Critical Reviews in Oncology/Hematology 67 (2008) 243–254

Fig. 2. Hypoxia stimulates HIF-1 and GLUT-1 expression that contributes to anaerobic glycolysis.

2.6. Hypothesis of intratumoral hypoxia
Hypoxia could participate in different ways in tumor
cachexia. Cells residing at the limits of oxygen diffusion from
functional blood vessels could undergo chronic hypoxia.
Blood flow fluctuations can expose tumor cells to short-term
hypoxia that is characterized by acute or fluctuating hypoxia
[39]. Nutrients and growth factors under adequate oxygen
pressure induce mTOR expression, which in turn stimulates
protein synthesis, cell growth and survival (Fig. 2). Hypoxia
can stimulate HIF-1␣ expression, a pivotal multipotent fac-
tor stimulating gene expression in response to stress and
intervening in the early phase of development of invasive
lesions.
HIF-1␣ stimulates GLUT-1 gene expression which
encodes transmembrane glucose transporter protein (GLUT-
1). Elevated intracellular glucose concentrations promote
accelerated anaerobic glycolysis and lactate production,
thereby enhancing the Cori cycle. A major decrease in
intracellular pH participates in acidosis and contributes to
apoptosis/autophagia [40]. When the activities of HIF-1␣
and GLUT-1 were evaluated in human colorectal cancer, they

Table 2
Nutritional parameters
Categories Factors Threshold value for undernutrition diagnosis
when consensual
Anthropometry Weight
Height or estimation with knee height
Body mass index (current weight (kg)/height (m)2 [98] <21 kg/m2
Weight loss ((usual weight − current weight)/usual weight) × 100 Moderate: 5 to <10% , severe: >10%
Triceps and subscapular skin folds
Mid-arm and calf circumferences
Biochemistry Serum albumin (g/l) [99] <35 g/l
Prealbumin
CRP
Leptin
Ghrelin
Hematology Hemoglobin
Blood cell count
Differential blood cell count
Cytokines Il-1
Il-6
IFN gamma
TNF alpha
 C. Blanc-Bisson et al. / Critical Reviews in Oncology/Hematology 67 (2008) 243–254
were more expressed in non-mucinous than in mucinous ade-
nocarcinoma: GLUT-1 expression was significantly related to
nodular invasion status (N+) and moderately differentiated
tumors (G2) expressed a higher rate of HIF-1␣ than poorly
differentiated tumors (G3). Histological type, depth of inva-
sion and cell differentiation were correlated with HIF-1␣ and
GLUT-1 gene expression, thus reflecting the poor prognosis
and aggressive course of the disease [41]. The consequences
of these phenomena are decreased fat and lean mass via
inhibition of protein synthesis and lactate hyperproduction.
3. Impact of undernutrition on neoplastic pathology
prognosis
The notion of nutritional status involves the association
of several markers (Table 2). Anthropometric parameters
include weight, weight changes expressed as percent of initial
body mass, BMI (body mass index weight (kg/m2 )), skin fold
and calculation of muscle area. The most widely used anthro-
pometric measures are BMI and percent of recent weight loss.
When baseline weight or healthy weight is not known, it is
possible to refer to ideal body weight determined with the
Lorentz formulae. Dietary intake determinations are particu-
larly valuable for preventive and caring purposes. The plasma
protein profile includes serum albumin, the main visceral
protein with a long half-life (21 days), prealbumin, another
visceral protein with a short half-life (<48 h) and inflamma-
tory acute phase proteins such as CRP. Serum albumin level
is a very important prognostic factor. Serum protein profile
determination is valuable in inflammatory diseases. Buzby et
al. determined an index of undernutrition using serum albu-
min concentration, current weight and usual weight [42,43].
In geriatric patients, usual weight is not easy to obtain, so
the GNRI (geriatric nutritional risk index) was adapted from
the BUZBY index. It expresses weight loss versus ideal
weight instead of usual weight [44]. In geriatric patients,
other multidimensional tools are necessary such as the MNA
[7], which combines anthropometric measures with risk fac-
tors for undernutrition (disease, mental health and functional
dependency, ingestive behavior, subjective health). While the
maximal score is 30, a score < 17 indicates undernutrition and
a score between 17 and 23.5 patients at risk of undernutrition.
The relationship between undernutrition and prognosis
has been established in numerous studies. In a cohort study
including 38–90-year-old patients with pulmonary cancer,
patients with the best survival had larger triceps skin fold
values, reflecting a higher fat mass. However, this anthropo-
metric prognostic value disappeared after adjustment with
other characteristics such as pathology stage, ECOG Per-
formance Status, serum albumin dosage and hemoglobin
level, suggesting that nutritional status may reflect poor
patient health status [45]. In another study in 51 patients
with advanced colorectal cancer, median survival was 9.9
months, 56% patients were at risk for undernutrition and
38% required nutritional support. A positive correlation
247
was established between nutritional status and CRP level
(>10 mg/l) by using the patient’s subjective global assess-
ment (p = 0.003; r = 0.430). In univariate analysis, survival
duration decreased with high ECOG score (p = 0.001), low
serum albumin level (p = 0.017) and poor nutritional sta-
tus (p = 0.02). In a multivariate model, type of treatment
(HR = 1.48; IC95% = 1.11–1.79); p = 0.005) and ECOG score
(HR = 2.37; IC95% = 1.11–5.09; p = 0.026) were predictive
factors of survival [46]. In a study including 120 patients
with esophageal cancer (median age 68.8 ± 9.9 years), the
introduction of a therapeutic prosthesis induced a decrease
in BMI, serum albumin level and ECOG, though dyspha-
gia was improved in 89.1% of patients. Serum albumin
level, BMI < 18 kg/m2 and ECOG > 2 at prosthesis insertion
were independent predictive factors of mortality at 30 days
[47]. In 100 colorectal cancer patients, preoperative circulat-
ing Il-1 receptor antagonist level remained an independent
predictor of postoperative infection. Postoperatively, elderly
patients with low BMI showed a major Il-6 response followed
by an exaggerated postoperative inflammatory response and
increased postoperative loss of body weight. In contrast,
normal immunoreactivity was preserved in well-nourished
elderly patients [48]. Multivariate analysis in a group of 66
patients with pulmonary cancer (age not specified) showed
that prognosis was linked to high Il-6 level, low IFN␥ level,
older age and metastatic tumor index. Weight loss, low BMI,
hypoalbuminemia and relevant factors in univariate analy-
sis were not significant in the multivariate model [49]. A
low leptin level was equally a poor prognostic factor in pul-
monary cancer with a threshold set at 2.4 ␮g/l [29]. For these
26 patients, leptin level was inversely correlated with inten-
sity of inflammatory reaction and was correlated with fat
mass. In a population of 192 patients (median age 85 ± 7
years), leptin was the only independent biological prognos-
tic parameter correlated with nutritional status as defined by
BMI and skin fold. The threshold value for leptin concen-
tration was estimated at 4 mg/l for men and 6.48 mg/l for
women. Other parameters like serum albumin and prealbu-
min reflected nutritional status but were equally dependent
on morbidity and inflammatory status [50].
It is well established that loss of weight is a poor prognostic
factor in patients receiving chemotherapy for digestive cancer
(colorectal and gastric) [51]. Moreover, median survival was
significantly decreased in patients with loss of weight within
6 months before chemotherapy (median age 61 years, range
16–84 years). In pulmonary cancer, loss of weight defined
as percentage of loss of healthy body weight at the diagno-
sis of cancer was a highly significant factor of poor survival
when ≥11% [45]. In another study on prostate pathology
(80 patients), 50% of patients with cancer were identified
as being at risk of undernutrition according to the MNA
score compared to only 7.5% of patients with benign pathol-
ogy. Among the patients with cancer, 39.5% had weight loss
(>3 kg within 3 months) and experienced more depressive
symptoms [52]. As may be seen, a limited number of studies
have focused on the role of biological markers of undernu-
248 C. Blanc-Bisson et al. / Critical Reviews in Oncology/Hematology 67 (2008) 243–254
trition as prognostic factor during neoplastic pathology and
on the role of correcting undernutrition to improve the vital
prognosis. Most of these studies concerned patients requiring
surgery. Among the numerous biological and clinical param-
eters studied, serum albumin was the main prognostic factor
of infectious and non-infectious adverse events and mortality
within 30 days after intervention [53]. The benefit of peri-
operative artificial nutrition was established only in patients
presenting acute hypoalbuminemia (Alb < 35 g/l): infectious
adverse events were decreased by 33% and deaths during
hospitalization were encountered only in the control group in
this study of 90 patients [54].
Loss of weight could be associated with a shorter treat-
ment because of chemotherapy termination due to toxicity or
administration of lower dose medications. This could par-
tially explain a lower response to treatment [51]. Severe
undernutrition significantly decreased median survival in a
group of 44 children treated for acute lymphoid leukemia
independently of their initial response to chemotherapy [55].
Severe undernutrition was defined as weight loss <10% to
15% during the last 6 months under the standard deviation
of minimal normal weight corresponding to age and sex. The
proportion of relapses at 5 years was greater in the under-
nourished group due to borderline toxicity with reduced dose
intensity [55].
4. Undernutrition and elderly patients
Undernutrition in the elderly may result from various
causes including inactivity, cachexia from other patholo-
gies, physical inabilities, cancer and cancer treatments. Frail
elderly patients are characterized by decreasing functional,
psychological and social capacities as attested by progres-
sive decline in functional, cognitive and social activities.
Decreased dietary intake that is not identified by relatives
is common in such subjects. All these modifications lead
to a lower nutritional status that impairs immune functions.
Undernutrition and partial loss of muscular function are con-
sidered as major factors of frailty [8].
Protein-energy malnutrition appears frequently in the
elderly for multiple reasons and is particularly due to chronic
pathologies inducing cachexia. Poor quantitative or quali-
tative dietary intake can promote frailty. In a study of 802
patients older than 65 years and selected for frailty (meeting
at least two of the following criteria: low muscular function,
tiredness, low walking speed, reduced physical activity) and
low dietary intake (<22 kcal/kg) were associated to frail sta-
tus (OR: 1.24 IC 95%: 1.02–1.5). After adjustment for energy
intake, low intake of protein, vitamins D, E, C, folate and low
intake of three or more nutrients were associated with frailty
[56] (Table 3).
Nutritional status could be impaired in 66% of elderly
patients with cancer in France according to MNA ques-
tionnaire scores (score < 24) and low serum albumin levels
(<35g/l) (unpublished personal data). These impairments
induce immune system defects and decreased resistance to
opportunistic infections [57]. Moreover, fatty acid membrane
composition (n-3 and n-6 lipid) influenced by dietary intake
seems to play a role in cellular function, especially in lym-
phocytes. With the association of cancer, undernutrition and
old age, survival prognosis is likely to be poor.
The efficacy of artificial nutritional support (enteral and
parenteral) on survival and quality of life has not been con-
firmed by randomized studies, although such treatments are
widely used in patients with cerebral infarction, dementia and
neurodegenerative disease [58,59]. In dementia, long-lasting
enteral nutrition proved deleterious and increased mortality
[60]. In another study if 150 elderly patients of whom 13%
had cancer, no survival benefit was associated with enteral
nutrition [61].
These disappointing results concerning enteral nutrition
led physicians to prefer oral nutritional support in geri-
atric populations. A little more than 50% of elderly patients
agreed to take oral nutritional support with commercially
available products during hospitalization [62–64]. Such sup-
port increased dietary intake and particularly protein intake
[62,65]. Oral nutrition support (540 kcal, 22.5 g protide/day)
prescribed to half of 381 patients hospitalized for acute
pathology resulted in weight gain and improved func-
tional capacity in undernourished patients [65]. However,
the efficacy of this support on the incidence of infec-
tion was less clear. In subjects 70 years old and over
hospitalized for an immobilizing pathology, supplementa-
tion was associated with decreased bedsore stage I risk
(672 patients) [62] but other studies with less power
(approximately 100 subjects in each study) showed no
difference [64,66,67].
Adhesion to nutritional support seems to be better at
home than during hospitalization. Oral supplementation
(industrial type: 300–500 kcal, 10–20 g protein) given for
3 months at home in elderly patients presenting dementia
and nutritional risk improved dietary intake by 5 kcal/kg and
0.12 g protein/kg body weight [68]. This phenomenon was
accompanied by weight and muscle mass gain but there was
no effect on functional capacities. The MNA questionnaire
was used to identify undernourished patients and those at risk
of undernutrition [7]. In the latter study [68], subjects had
a score lower than 23.5 and MNA gain was 3.4 ± 3.1 in the
intervention group compared to the control group (1.9 ± 3.5),
However, the number of subjects was limited (37 in interven-
tion group and 43 in control group) and patients receiving
chemotherapy were excluded.
None of the abovementioned studies specifically dif-
ferentiated undernourished patients and those at risk of
undernutrition. In a small institution-dwelling group (66
patients), homemade oral supplementation administered to
subjects at risk of undernutrition (MNA 17–23.5) decreased
usual dietary intake, resulting in a daily total intake similar
to that ingested before intervention. In contrast, undernour-
ished patients (MNA < 17) significantly increased their total
intakes [69].
 C. Blanc-Bisson et al. / Critical Reviews in Oncology/Hematology 67 (2008) 243–254 249

Table 3
Comprehensive geriatric assessment (CGA): numerous factors are evaluated using dedicated tools to take action, if necessary
Subject Scale and evaluation Action if worsening
Mental status
Cognition MMS [100] Memory consultation
Mood GDS-15 [101] or CES-D Depression treatment
Delirium CAM (confusion assessment method) [102] Etiological research
Fall risk Clinical examination Etiological research
Timed up and go test Rehabilitation, physical activity
One leg stance Nutritional support
Functional status ADL (activity of daily living-elementary needs) [103] Individual help
Technical help
IADL (instrumental activity of daily living, —house House-keeper, personal assistance
keeping, financial management and medications, use of
transport and phone) [104]
If inability to financial management, help from close relations
or asking for legal protection
Sensorial deficiency Technical help, medico-surgical intervention, environmental
adaptation
Etiological research
Nutrition BMI [98] Dietetic advice to patient or helpers,
MNA [7]
Weight course Domestic helper, personal assistance to do
Dietary intake shopping and help with meals,
Swallowing test Meals-on-wheels, food texture adaptation,
Mouth and dental check-up mouth and dental care
Etiological inquiry
Polypathology Clinical examination Cancer screening
Pathology priority determination
Pressure sore risk Braden scale [105] Positional changes
Equipment
Nutrition and hygiene
Early rise from immobilization
Pain Analogical Visual Scale Etiologic pathology
Heteroevaluation scale Adapted analgesia dose regimen
Physical measures and follow-up
Medication Creatinine clearance Treatment revision
Adverse effect research Help to take medications
Interactions ratio benefit/risk
Renal function Creatinine clearance [106] Dose regimen adaptations
Stop some treatments
Etiologic research
Biology Blood cell count, serum albumin, CRP Etiologic inquiry
Social Environment Help to get private or public financial assistance (social help,
Financial and social resources autonomy personalized help, retirement fund, care insurance or
Needs and ability of helpers private insurance)
Initiation, follow-up of planned help

Prescription of commercially available or homemade sup- 5. Cancer treatment effects

plements is not the only measure to improve dietary intake.
The impact of human assistance on the choice of food,
cooking and feeding and how they impact on the quality
and quantity of dietary intake should also be tested. How-
ever, a study testing the efficacy of human help in 600
hospitalized patients (65 years and older) who were not
selected and whose nutritional status was not tested did not
show any qualitative or quantitative improvement in dietary
intake [70].
Standard therapeutic measures may contribute to undernu-
trition and must be considered in any decision about nutrition.
Surgery, chemotherapy [71] and radiotherapy [72] alone or
associated can induce different acute or delayed toxicities at
different levels of the digestive tract. Nausea and vomiting
are more frequent events during chemotherapy cycles and
anti-emetics are prescribed preventively [73]. Several drugs
can induce mucositis, a frequently reported event. Although
250 C. Blanc-Bisson et al. / Critical Reviews in Oncology/Hematology 67 (2008) 243–254
this disorder can appear minor and reversible, its conse-
quences are important and anorexia can persist for several
days and recur at each cycle. Oral and dental care is an
effective preventive measure. Irradiation may induce acute
events such as erythema, hyposialia, laryngitis, esophagitis,
dysphagia, anorexia, heartburn, nausea, vomiting, dysgeusia
and diarrhea. These toxic events may be delayed without any
predictive factors [74]. New radiotherapy techniques such
as intensity modulated radiotherapy (IMRT) can limit these
adverse outcomes [75]. Radiation-induced hyposialia in cer-
vical locations or in the Waldeyer ring in head and neck cancer
and lymphoma may occur transiently during treatment, for
few months or definitively. Hyposialia is very crippling and
induces a notable decrease in dietary intake [76]. Heartburn
and esophageal stenosis resulting from chemotherapy, endo-
prothesis, gastrectomy and an early feeling of satiety are
frequent events in gastric and pulmonary tract cancers. In
colon cancer, one of the most frequently diagnosed cancers
in men and women, surgery is the gold standard. However, the
patient may need a temporary or definitive colostomy, which
requires an adapted diet particularly in the early phase. This
diet may be poorly tolerated by the patient. Symptoms of
constipation and/or diarrhea resulting from chemotherapy,
abdominal radiotherapy (rectal or gynecologic site) alone
or after surgery need to be managed temporarily or defini-
tively. Fistula and ulcerative lesions must be managed in
diabetic patients due to difficulty in wound healing. Chronic
gastro-intestinal ischemia and abnormal intestinal absorp-
tion may require specific nutritional supplementation (routine
multivitamins, mineral and trace elements) [77]. Repetitive
hematuria or rectal hemorrhage may be responsible for iron
depletion.
6. Nutritional intervention in cancerology
Oral, enteral and parenteral nutritional interventions have
been studied in trials with small numbers of patients. The
impact of renutrition in patients with severe loss of weight
(>10%) was demonstrated pre- and postoperatively [54], but
few studies have examined non-surgical treatment in cancer
pathology.
Nutritional intervention in undernourished patients with
cancer seems to improve their nutritional status, quality of
life and prognosis. Enteral or parenteral intervention modali-
ties have been prescribed to patients with loss of weight. For
example, enteral nutrition reduced the number of hospitaliza-
tions in undernourished patients with digestive tract cancer
[78]. However, the series was small (60 patients) and patients
in the control arm received oral nutrition without dietary
advice. Another study failed to find any benefit with enteral
nutrition prior to surgery in patients presenting head and neck
cancer (45 pts, randomized study) [79]. In palliative care,
parenteral nutrition did not improve the prognosis and qual-
ity of life in an intent-to-treat analysis [80]. Oral nutritional
support prior to surgery seemed to be equivalent to perioper-
ative artificial support (enteral and parenteral) in decreasing
the infection rate in hospital and the mean hospital stay [81].
Such a preventive approach has not only been used in surgery.
Among 50 undernourished patients with esophageal can-
cer treated by radiochemotherapy, undernourished dysphagic
patients randomly received enteral nutrition and the others
were given control oral nutrition for 1 year [82]. The exper-
imental group maintained stable weight while the control
group lost weight. In another study, 600 patients on ambu-
latory radiotherapy treatment for head and neck cancer were
randomized into two groups. One group received individual
nutritional advice to improve the choice and quantity of food
at the beginning of treatment while the control group received
usual care from the center (general advice and information
booklet). Patients in the intervention group maintained their
weight and had better quality of life than controls [83]. More-
over, they were more satisfied with the treatment proposed
(therapeutic and no therapeutic) [83]. In a randomized study,
nutritional intervention in 67 patients with colon or gastric
cancer resulted in a weight increase after 12–24 months com-
pared with usual guidelines; however, quality of life, survival
and nutritional status at inclusion were not reported [84]. A
recent meta-analysis showed no benefit of nutritional inter-
vention in patients treated by radiochemotherapy for pelvic
cancer [85] but the objective was to treat digestive symptoms
induced by radiochemotherapy and not overall nutritional
status. Only four randomized studies (204 patients) concern-
ing enteral nutrition showed no benefit for safety or survival
[85]. A recent study on patients with prostate cancer who
received oral nutritional support showed an increase in dietary
intake of 500 kcal/D and in weight compared with patients
non-compliant for oral supplementation [86].
In another study, response to chemotherapy was studied
in patients with pulmonary or colorectal cancer. The exper-
imental group received nutritional information to increase
dietary intake to 25% from baseline. There was no difference
in response to chemotherapy between the two groups but their
nutritional parameters were not reported [87].
Guidelines from the European Society for Parenteral
and Enteral Nutrition published in 2006 proposed nutri-
tional intervention with oral or artificial nutrition (preferably
enteral) prior to chemotherapy (Table 4). They recom-
mend a 30–35 kcal/day dietary intake for valid patients and
20–25 kcal/day for those unable to walk [21]. Protein intake
guidelines are 1 g/(kg day) to 1.2 g/(kg day). The general
guidelines for vitamins and minerals can be met but caution is
required with antioxidant intakes because serum antioxidant
levels are decreased in cancer patients. Age is not mentioned
in these guidelines, but the proposed intakes do not differ from
recommended dietary allowances in elderly subjects [88].
Ghrelin, a gastric peptide hormone, stimulates dietary
intake and lipid accumulation in adipocytes by activa-
tion of neuropeptide Y, the main stimulating appetite
hormone. Ghrelin has positive consequences on energy
balance decreasing mobilization of lipids independently
of the action of growth hormone. Ghrelin levels were
 C. Blanc-Bisson et al. / Critical Reviews in Oncology/Hematology 67 (2008) 243–254
Table 4
Basic principles of nutritional care in geriatric patients
Situation Nutritional intervention mode
Undernutrition prevention Dietary intake targets
Dietary records
Mouth and dental examination
Swallowing disorder examination
Undernutrition treatment Same procedure as for prevention
And enteral nutrition if <60% from dietary intake targets
significantly increased in 21 patients with pulmonary can-
cer associated with cachexia compared with non-cachectic
patients, suggesting the onset of “ghrelinoresistance” [28].
This hypothesis was supported by elevated ghrelin levels in
patients presenting anorexia during chemotherapy. Ghrelin
administration to patients with cancer (7 patients in a ran-
domized study) or to patients with heart failure (10 patients)
induced an increased dietary intake (30% of dietary intake)
and was related to ECOG, vital functions and decreased sym-
pathetic activity [89].
In clinical practice and irrespective of their age, nutritional
intervention is not routine in cancer patients even when their
nutritional status is known. A study of more than 900 patients
consulting for digestive cancer in ambulatory treatment ward
with a dedicated dietician showed that only 36% patients
received a nutritional intervention [90]. The probability of
receiving such an intervention increased with time. It was
greater for patients presenting a weight loss >10% (56% at
12 months) and was similar for patients without loss of weight
or with a loss from 5 to 10% (40% at 12 months). The inter-
vention was delayed (up to 3 months) and a large proportion
of the undernourished patients were not referred.
7. Conclusion
To date, no biological marker or single clinical diagnostic
marker of nutritional status in oncology or CGA has been
identified. A combination of markers easily used in, rou-
tine screening such as MNA, NRI or GNRI could allow
better access to care. Moreover, undernourished patients
with cancer could suffer from increased mortality compared
with well-nourished patients, even if they are progression-
free. The qualitative and quantitative benefits of nutrition
in elderly patients with or without cancer are now known
[22,91–93]: better response to treatment, fewer side effects
due to chemotherapy [94,95], and better immune function
[96]. On the other hand, no benefit in terms of survival
was shown in a recent meta-analysis by Koretz [97]. No
251
Effects
20–25 kcal/(kg D)—1 g protein for
bedridden patients
30–35 kcal/(kg D)—1.2 g protein for patients
more than 50% of confinement a day
Dietician advice (face-to-face)
Oral supplementation
Regular food or manufactured products
Dental care
Adapted texture of food
Mouth care
Etiological treatment
Adapted texture of food
At least 15 days
effect on mortality was observed in studies conducted in
different situations (perisurgery, chronic pathology, geriatric
population) where different nutritional interventions were
compared: enteral, parenteral, oral supplementation or no
intervention. However, there was a trend in favor of nutri-
tional intervention.
Evaluation of nutritional status in oncogeriatric popu-
lations tends to receive little attention. The present study
suggests that nutritional status should be assessed as part of
CGA, so that efficient action may be implemented to main-
tain it. Moreover, transfer from hospital to home or to another
institution requires special attention so that efficient nutrition
is maintained, thereby impacting quality of life. While one of
the aims in cancer research is to identify elderly patients able
to undergo chemotherapy safely, nutritional changes should
also be particularly investigated as part of CGA and correc-
tive action should be implemented. This may help to prevent
further deterioration in such patients and to maintain quality
of life.
Conflict of interest
There is no conflict of interest.
Reviewers
Dr. Nathalie Jacquelin-Ravel, Clinique de Genolier, 1
route du Muids Genolier 1272, Switzerland.
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Biographies
Christele Blanc-Bisson graduated on 16th September
2002 in biology at University Victor Segalen Bordeaux 2
(France) and University of Liege (Belgium). She studied
metalloproteinase activity produced by myofibroblasts from
stroma in breast and liver cancer. Since May 2002, she
has participated in geriatric oncology research in Aquitaine,
south-west France and onco-hematology research at the
Institut Bergonie cancer center in Bordeaux (Director Pr P
Soubeyran). In January 2007, she joined the geriatric depart-
ment of the University Hospital of Bordeaux to take part in the
INOGAD clinical trial, which investigates the effect on sur-
vival of nutritional support in elderly cancer patients at risk of
undernutrition (main investigator Pr Bourdel-Marchasson).
Marianne Fonck (physician in oncology), Muriel Rainfray
(Professor in geriatrics) and Pierre Soubeyran (Professor in
onco-hematology) are founders of the oncogeriatric group
in Aquitaine and Isabelle Bourdel-Marchasson (Professor in
geriatrics), who is involved in nutritional research in geron-
tology, is the main INOGAD investigator.