Malnutrition in patients treated for oral or oropharyngeal cancer--prevalence and relationship with oral symptoms: an explorative study.

Abstract

This study aimed to assess prevalence of malnutrition after treatment for oral/oropharyngeal cancer and to explore how oral symptoms relate to malnutrition after treatment.
In this cross-sectional study, malnutrition (weight loss ≥ 10% in 6 months or ≥ 5% in 1 month), oral symptoms (EORTC QLQ-H&N35 questionnaire and additional questions to assess chewing problems), dental status, trismus and dietary intake were assessed in 116 adult patients treated for oral/oropharyngeal cancer.
Prevalence of malnutrition was 16% (95%CI: 10% to 23%). Prevalence of malnutrition in the period 0-3 months after treatment was significantly higher (25%) than in the periods >3-12 months (13%) and >12-36 months after treatment (3%, p = 0.008). Logistic multivariate regression analysis revealed that swallowing problems (p = 0.021) and insufficient protein intake were significantly related to malnutrition (p = 0.016).
In conclusion, malnutrition is a considerable problem in patients treated for oral/oropharyngeal cancer, shortly after treatment. Of all oral symptoms, only swallowing problems were significantly related to malnutrition in the period after treatment for oral/oropharyngeal cancer.

Full text

Page 1

ORIGINAL ARTICLE
Malnutrition in patients treated for oral or oropharyngeal
cancer—prevalence and relationship with oral symptoms:
an explorative study
Harriët Jager-Wittenaar & Pieter U. Dijkstra &
Arjan Vissink & Rob P. van Oort &
Bernard F. A. M. van der Laan & Jan L. N. Roodenburg
Received: 29 November 2009 /Accepted: 31 August 2010 /Published online: 16 September 2010
# The Author(s) 2010. This article is published with open access at Springerlink.com
Abstract
Purpose This study aimed to assess prevalence of malnutri-
tion after treatment for oral/oropharyngeal cancer and to
explore how oral symptoms relate to malnutrition after
treatment.
Methods In this cross-sectional study, malnutrition (weight
loss ≥10% in 6 months or ≥5% in 1 month), oral symptoms
(EORTC QLQ-H&N35 questionnaire and additional ques-
tions to assess chewing problems), dental status, trismus
and dietary intake were assessed in 116 adult patients
treated for oral/oropharyngeal cancer.
Results Prevalence of malnutrition was 16% (95%CI: 10% to
23%). Prevalence of malnutrition in the period 0–3 months
after treatment was significantly higher (25%) than in the
periods >3–12 months (13%) and >12–36 months after
treatment (3%, p=0.008). Logistic multivariate regression
analysis revealed that swallowing problems (p=0.021) and
insufficient protein intake were significantly related to
malnutrition (p=0.016).
Conclusions In conclusion, malnutrition is a considerable
problem in patients treated for oral/oropharyngeal cancer,
shortly after treatment. Of all oral symptoms, only
swallowing problems were significantly related to malnu-
trition in the period after treatment for oral/oropharyngeal
cancer.
Keywords Malnutrition.Weight loss.Mouth neoplasms.
Oropharyngeal neoplasms.Oral symptoms
Introduction
Malnutrition has been defined as a subacute or chronic state
of nutrition, in which a combination of undernutrition
(insufficient food intake) and inflammation has led to a
decrease in muscle mass, fat mass, and diminished function,
i.e., immune function, cognitive function and muscle
strength [33]. In the period before head and neck cancer
(HNC) treatment, prevalence of severe weight loss, an
indicator of subacute malnutrition, varies from 19% to 45%
[17, 23, 39, 40].
Malnutrition in HNC patients may have multiple causes.
In the period before treatment, a major cause of malnutri-
tion is insufficient food intake, related to mechanical
obstruction of food or pain caused by the tumor. In this
period, cachexia, a complex metabolic syndrome associated
with underlying illness and characterized by loss of muscle
with or without loss of fat mass may contribute to
malnutrition as well [13]. During and after treatment,
H. Jager-Wittenaar (*):P. U. Dijkstra:A. Vissink:
R. P. van Oort:J. L. N. Roodenburg
Department of Oral and Maxillofacial Surgery, University
Medical Center Groningen, University of Groningen,
Internal zip code BB70, PO Box 30001, 9700 RB Groningen,
The Netherlands
e-mail: h.jager@onco.umcg.nl
P. U. Dijkstra
Department of Rehabilitation, University Medical
Center Groningen, University of Groningen,
PO Box 30001, 9700 RB Groningen, The Netherlands
P. U. Dijkstra
Graduate School for Health Research, University Medical
Center Groningen, University of Groningen,
Groningen, The Netherlands
B. F. A. M. van der Laan
Department of Otorhinolaryngology/Head & Neck Surgery,
University Medical Center Groningen, University of Groningen,
PO Box 30001, 9700 RB Groningen, The Netherlands
Support Care Cancer (2011) 19:1675–1683
DOI 10.1007/s00520-010-1001-z

Page 2

malnutrition may develop or aggravate as a result of oral
symptoms related to treatment, such as chewing and
swallowing problems, pain, dry mouth, sticky saliva, and
taste disturbances [42]. In this period, increased inflamma-
tory activity may also contribute to malnutrition, for
example due to radiation-induced mucositis [19].
Although malnutrition in the period before HNC
treatment is often reported [17, 21, 39], few data are
available on prevalence of malnutrition after treatment for
oral/oropharyngeal cancer. Previous studies in HNC
patients treated with radiotherapy reported that prevalence
of malnutrition is highest during radiotherapy and declines
during the first 3 months after radiotherapy [16, 26]. These
studies were heterogeneous regarding tumor localization
and follow-up was limited to the first 6 months after
treatment. Consequently, prevalence of malnutrition in the
long-term period after treatment for oral/oropharyngeal
cancer is unclear.
It is well known that oral symptoms are risk factors for
malnutrition [42]. In the period before treatment, swallow-
ing problems and pain in the mouth are identified as main
risk factors for malnutrition in HNC patients [17, 20].
Besides swallowing problems, patients treated for oral/
oropharyngeal cancer may also suffer from chewing
problems, either due to poor dental status or trismus.
Edentulous patients often cannot wear their prosthesis for
about 3 months after surgery and not uncommonly even up
to 6 months after radiotherapy or chemoradiation, due to
either radiation-induced mucositis, oral edema, tender oral
mucosal surfaces, surgically induced changes in anatomy,
or time needed to manufacture a new prosthesis. Addition-
ally, trismus may result from scar tissue formation, as a
result of surgery and from radiotherapy [15, 43]. The
relationship between poor dental status and trismus and
malnutrition in patients treated for oral/oropharyngeal
cancer has not been studied before. Thus, it is unclear
which oral symptom(s) are risk factors for malnutrition in
the period after treatment for oral/oropharyngeal cancer.
The primary aim of this cross-sectional study was to test
the hypothesis that prevalence of subacute malnutrition, as
indicated by severe involuntary weight loss, in patients
treated for oral/oropharyngeal cancer declines in the period
after treatment. The secondary aim of the study was to test
the hypothesis that swallowing problems, poor dental status
and trismus are risk factors for malnutrition in the period
after treatment for oral/oropharyngeal cancer.
Patients and methods
A convenience sample of 185 consecutive adult patients
was asked to participate in this cross-sectional study
between October 2004 and February 2006. These patients
had been treated for oral or oropharyngeal cancer at
the University Medical Center Groningen (UMCG), the
Netherlands. Patients willing to participate underwent
assessment after their visit to the physician. Diagnosis and
treatment information were retrieved from medical records
(Table 1). The study was approved by the Ethics Committee
of the UMCG. Informed consent was obtained from all
participants.
Inclusion criteria were: age ≥18 years and completed
treatment for oral/oropharyngeal cancer ≤3 years before
study measurement. Treatment modalities were: surgery
(local tumor excision and/or neck dissection); surgery and
radiotherapy; radiotherapy (conventional or accelerated
scheme); or radiotherapy with concomitant chemotherapy
(carboplatin and 5-FU). Exclusion criteria were: a recurrent,
residual or newly diagnosed tumor within 3 months after
study measurement; edema due to liver, kidney or cardiac
disease, to eliminate confounding by edema on body
weight; uncontrolled diabetes mellitus to eliminate possible
confounding in risk factors for weight loss.
Patients received dietary counseling from a dietitian
working at the UMCG at time of diagnosis, during
admission for surgery and weekly during radiotherapy.
Duration of dietary counseling was generally limited to the
first half year after treatment.
Assessment of malnutrition
Actual body weight (kilogram) was measured on a
calibrated Seca 701 scale (Medical scales & Measuring
Systems Seca Ltd., UK). Patients were measured in indoor
clothing without shoes, after voiding the bladder. Weight
for clothing (1.0–1.5 kg) was deducted from measured
weight and this corrected weight was used for further
analysis. Patients were asked for their body weight 1 and
6 months before study measurement. Pre-treatment body
weight was retrieved from the medical records. Height was
measured by a stadiometer (Seca 222, Medical scales and
Measuring Systems Seca ltd., UK).
Percentage weight loss was calculated as:
body weight ? actual body weightÞ=normal body weight??
100. Normal body weight was defined as body weight
1 month, or 6 months ago, or prior to treatment.
Malnutrition was defined as involuntary weight loss
≥10% in 6 months or ≥5% in 1 month [1, 3, 25, 30,
34, 39]. BMI (kg/m2) was calculated as [actual body
weight/(body height2)].
normal
ð ½
Assessment of oral symptoms
The EORTC QLQ-H&N35 questionnaire was used to
assess pain in mouth or throat, swallowing problems,
senses problems, dry mouth, and sticky saliva [2]. Scale
1676Support Care Cancer (2011) 19:1675–1683

Page 3

scores were calculated according to the manual and range
from 0 to 100 [12]. In addition, three questions regarding
chewing problems were asked: (1) How much difficulty did
you experience while chewing solid food (like meat/solid
bread)?; (2) How much difficulty did you experience while
chewing dry food (like cookies)?; (3) How much difficulty
did you experience while chewing soft food (like soft
bread)? Possible answers to the additional questions were:
(1) no difficulty; (2) little difficulty; (3) much difficulty;
and (4) so much difficulty that eating was impossible.
Answers (3) and (4) were dichotomized to ‘chewing
problems’ and answers (1) and (2) to ‘no chewing
problems’. Time frame for all questions was the week prior
to assessment.
Dental status was assessed by number of natural teeth and/
or presence or absence of a dental prosthesis. Dental status
was considered poor if: edentate without prosthesis, edentate
plus prosthesis in upper/lower jaw, or one edentulous jaw
without prosthesis and 1–16 elements in the other jaw,
otherwise dental status was considered acceptable.
Maximal mouth opening was measured three times using
two calibrated calipers, one for edentates or partially
dentate patients wearing their prosthesis and one for
edentates not wearing their prosthesis. Trismus was defined
as mean mouth opening ≤35 mm [10, 18].
Dietary intake and requirements
Dietary intake of the last week before measurement was
assessed by means of dietary history, by a registered
dietitian (HJ) [4]. Energy and protein intake were calculated
using food calculation software (JOULE v.02r80 by iSOFT,
The Netherlands). Nutritional requirements were estimated
conform practical guidelines used in the UMCG: 30 or
35 kcal and 1.0 or 1.5 g protein per kg actual body weight
for well-nourished and malnourished patients respectively
[29]. For patients with a BMI>27, body weight equivalent
to BMI=27 was calculated and used in the calculations, to
correct for the relatively lower metabolic active muscle
mass [9]. Energy or protein intake <90% of requirements
was considered insufficient.
Patients were asked if they (partly) mashed or grinded
their food. Patients not using oral food were able to answer
with ‘not applicable’.
Age (years), mean (SD)
Gender
Male
Female
Number of treated head and neck tumors
1
2
3
Last treated tumor
Squamous cell carcinoma
Salivary gland tumor
Other
Size of last treated tumor
T1
T2
T3
T4
Unknown
Site of last treated tumor
Oral cavity
Oropharynx
Otherb
Treatment of last tumor
Surgery
Surgery+radiotherapy
Radiotherapy
Chemoradiation
Interval between end of treatment and assessment (months), median (IQRc)
59.7 (11.7)%a
62
38
77
21
2
89
9
3
46
29
3
11
11
71
26
3
53
30
10
6
4.3 (1.4, 12.6)
Table 1 Patient characteristics
(n=116)
aSum of percentages may be
dissimilar to 100%, due to
rounding
bNeck metastasis, maxillary
sinus, unknown primary
cIQR Interquartile range
Support Care Cancer (2011) 19:1675–1683 1677

Page 4

Statistical analysis
Statistical analyses were performed using SPSS 16.0 for
Windows software (SPSS Inc., Chicago, IL, USA). Interval
after treatment (months) was categorized into 0–3 months
after treatment, >3–12 months after treatment and >12–
36 months after treatment. An independent samples
Student’s t test was used to test differences in continuous
variables between two groups. A paired sample Student’s t
test was used to test differences in the mean of a continuous
variable between two related groups. The Mann–Whitney U
test was used to test differences in continuous variables
between two groups if not distributed normally and in
ordinal variables. The chi-square test was used to test
differences between categorical variables. The Fisher’s
exact test was used for categorical variables if ≥20% of
the cells had an expected count less than 5, in 2×2 tables.
The relationship between oral symptoms and malnutri-
tion was analyzed in a multivariate logistic regression
analysis. Malnutrition (yes/no) was entered as outcome
variable. Age (years), gender (male versus female), tumor
size (T1/T2 versus T3/T4), treatment with or without
radiotherapy (surgery alone versus radiotherapy, surgery
and radiotherapy or chemoradiation), single or combined
treatment modality (surgery alone or radiotherapy alone
versus surgery and radiotherapy or chemoradiation), interval
after treatment (continuous variable (months)), dental status
(poor versus acceptable), chewing problems (yes versus no),
trismus (yes versus no), energy intake (sufficient versus
insufficient), protein intake (sufficient versus insufficient),
EORTC QLQ-H&N35 scale scores (continuous variables) on
swallowing problems, sticky saliva, senses problems, dry
mouth,andpaininmouthorthroatwereenteredinthe logistic
regression analysis (method stepwise backward), entry
criterion p≤0.05, removal criterion p>0.10.
The relationship between percentual decline in pre-
treatmentbodyweightandintervalaftertreatment(categorical
variable) was analyzed by one-way analysis of variance.
In all analyses, statistical significance was set at p<0.05.
Results
Patients
Of the 185 eligible patients, 63 patients declined participa-
tion. Reasons to decline participation were: not interested in
the study (36%, 23/63), fatigue (14%, 9/63), time invest-
ment too long (17%, 11/63) and unknown reasons (32%,
20/63). One-hundred and 21 patients were included in the
study. Six patients had to be excluded because of either still
being under treatment (n=1), tumor recurrence shortly after
inclusion (n=1), or not being able to undergo nutritional
assessment (n=4). Data of the remaining 116 patients
(Table 1) were used in the various analyses on malnutrition,
unless stated otherwise. Data on pre-treatment body weight
were complete in 112 patients. Data on energy and protein
intake were complete in 109 patients.
Nutritional assessment
Overall prevalence of malnutrition was 16% (18/116, 95%
CI: 10% to 23%). Prevalence of malnutrition in the period
0–3 months after treatment was significantly higher (25%,
13/53) than in the periods >3–12 months after treatment
(13%, 4/32) and >12–36 months after treatment (3%, 1/31;
p=0.008). Mean pre-treatment body weight significantly
declined from 78.7±13.4 kg to 75.9±14.0 kg post-
treatment (p<0.001; mean decline 2.8±5.9 kg). Mean
percentual decline in pre-treatment body weight was 3.4±
7.3% and no significant differences in percentual decline in
pre-treatment body weight between the three intervals after
treatment were found (p=0.220). Mean pre-treatment BMI
declined from 26.3±4.0 to 25.4±4.0 kg/m2post-treatment
(p<0.001; mean decline 1.0±2.0 kg). Five percent (6/114)
of all patients had a BMI<18.5 kg/m2.
Prevalence of malnutrition per treatment modality is
presented in Table 2. Analyzed univariately, no differences
in age (years), gender, tumor size (T1/T2 versus T3/T4),
number of treated head and neck tumors and localization of
last tumor (oral cavity versus oropharynx) were found
between malnourished and well-nourished patients.
Oral symptoms
Analyzed univariately, malnourished patients scored worse
on swallowing problems (p=0.005), dry mouth (p=0.032)
and sticky saliva (p=0.011) compared to well-nourished
patients (Table 3).
Table 2 Prevalence of malnutrition related to last type of HNC
treatment
Type of treatment (n)Malnutrition
n%a
Surgery (62)
Treatment including radiotherapy (54)
Radiotherapy (12)
Surgery and radiotherapy
(before or after surgery) (35)
Chemoradiation (7)
58
1324b
25
26
3
9
114
aPercentages are row percentages
bPrevalence of malnutrition in patients treated with radiotherapy, surgery
and radiotherapy, or chemoradiation is significantly higher than in patients
treated with surgery alone (p=0.034), analyzed by chi-square test
1678Support Care Cancer (2011) 19:1675–1683

Page 5

Dietary intake
Ninety-six percent of all patients (111/115) used an oral
diet, either with (3%, 3/115) or without tube feeding (94%,
108/115; Table 1). Four patients used tube feeding only
(3%, 4/115). Of the patients using oral food (with or
without tube feeding), 87% (97/111) used a solid diet and
13% (14/111) a liquid/mashed diet. Patients using a liquid/
mashed diet were significantly more often malnourished
(36%, 5/14) than patients able to use a solid diet (11%,
11/97, p=0.003).
Mean actual intake was 2185±699 kcal and 83±24 g
protein. No significant differences were found in intake
between malnourished and well-nourished patients.
Frequency of insufficient protein intake, related to
requirements, was significantly higher in malnourished
patients (65%, 11/17) than in well-nourished patients
(29%, 27/92 p=0.011).
Multivariate logistic regression analysis
Swallowing problems and insufficient protein intake
were significantly related to malnutrition in the logistic
multivariate regression analysis (Table 4).
Discussion
The results of our study demonstrate that one out of six
patients is malnourished after treatment for oral/oropharyn-
geal cancer, with the highest prevalence of malnutrition
shortly after treatment (one out of four patients). The
decline in prevalence of malnutrition within the first year
after treatment in our study is in accordance with results of
other studies [16, 26, 36].
Very limited data are available on prevalence of
malnutrition after treatment for oral/oropharyngeal cancer.
In a randomized controlled trial 48% of the patients was
malnourished 3 months after start of radiotherapy. If
patients received dietary counseling during and shortly
after radiotherapy this percentage was 24% [16]. In HNC
patients, in which malnourished patients received tube
feeding during and after radiotherapy, prevalence of
malnutrition was 27% and 6% in the third and sixth month
after start of radiotherapy, respectively [36]. Other studies
on malnutrition in HNC patients focused on changes in
nutritional status during and after treatment. In a random-
ized controlled trial, performed in HNC patients treated
with radiotherapy, nutritional status was deteriorated
3 months after treatment in all patients not receiving dietary
counseling nor dietary supplements, but if patients received
dietary counseling during radiotherapy this frequency was
limited to 12% [26]. In HNC patients not receiving dietary
counseling during and after treatment, mean body weight
significantly declined with 2.3±4.0 kg during treatment and
2.2±5.5 kg in the period after treatment [40]. In all of these
studies prevalence of malnutrition declined in the first
6 months after treatment in patients receiving dietary
intervention [16, 26, 36].
Of all oral symptoms, swallowing problems was the only
one related to malnutrition in the logistic multivariate
regression analysis. Although swallowing problems may
be present in the long-term period after treatment for oral or
oropharyngeal cancer [28], swallowing problems are most
Table 3 Univariate analysis on malnutrition and oral symptoms
Oral symptoms (n)a
MalnutritionNo malnutritionp MalnutritionNo malnutrition
n%c
n%c
Median IQRb
MedianIQR
Chewing problems (31/116)
Trismus (30/116)
Poor dental status (37/116)
Pain in mouth/throat (113)
Swallowing problems (113)
Senses problems (113)
Dry mouth (113)
Sticky saliva (113)
7
7
9
23
23
24
24
23
28
77
77
76
0.248d
0.239d
0.129e
0.092f
0.005f
0.211f
0.032f
0.011f
25.0
29.2
16.7
66.7
66.7
14.6, 37.5
0.0, 52.1
0.0, 37.5
33.3, 100.0
0.0, 100.0
16.7
0.0
0.0
33.3
0.0
0.0, 25.0
0.0, 25.0
0.0, 16.7
0.0, 66.7
0.0, 66.7
aNumber of valid observations (patients with this symptom/total number of patients)
bInterquartile range
cPercentages are row percentages
dAnalyzed by Fisher’s exact test
eAnalyzed by chi-square analysis, with continuity correction
fAnalyzed by Mann–Whitney U test
Support Care Cancer (2011) 19:1675–1683 1679

Page 6

severe during and shortly after treatment, due to radiation-
induced mucositis and reduced mobility of the tongue due
to surgery [35, 42]. Probably swallowing problems will
cause malnutrition predominantly during treatment, and to a
lesser extent in the period after treatment. To reduce post-
treatment malnutrition risk due to swallowing problems, we
recommendroutinescreeningforbothpresenceofswallowing
problems and malnutrition in patients after treatment for oral
or oropharyngeal cancer. Future research should investigate
whether the prevalence of post-treatment malnutrition can be
reduced or even prevented by strategies to overcome the
swallowing problems. For example, the assumed efficacy of
multidisciplinary treatment of treatment-related swallowing
problemsbyboththedietitianandspeechtherapistneedstobe
investigated. Furthermore, the role of early tube feeding, e.g.,
by prophylactic gastrostomy placement, should be more
thoroughly investigated, because large randomized controlled
trials on this topic are still lacking.
The multiple regression analysis corrected for confound-
ers like energy and protein intake and other oral symptoms.
Poor dental status, trismus, and chewing problems were no
risk factors for malnutrition in the multivariate regression
analysis. Patients having chewing problems often change
their diet into a soft, mashed or liquid diet. As nutritional
density of a mashed or liquid diet is lower than that of a
solid diet, these patients also are advised to use energy- and
protein-enriched liquid dietary supplements. Use of these
supplements increases energy and protein intake and in turn
decreases the risk for malnutrition. Only one other study
assessed the relationship between dental status and malnu-
trition, but this study was performed in the period before
treatment [20]. In the latter study also, no significant
relationship between these variables was found [20].
No significant relationship was found between percen-
tual decline in body weight and interval after treatment.
Mean decline in pre-treatment body weight was limited to
3%. However, this 3% weight loss may be additional to
weight loss that already may have developed before start of
treatment. At time of diagnosis, 34% of patients with oral/
oropharyngeal cancer have already lost ≥10% of body
weight in 6 months or ≥5% in 1 month [17]. Additionally,
in the current study difference between pre-treatment and
actual body weight ranged widely, indicating that a subgroup
of patients fails to regain body weight to pre-illness or even
pre-treatment level.
Although patients treated with radiotherapy were signif-
icantly more frequently malnourished than patients treated
with surgery alone in the univariate analysis, treatment with
any type of radiotherapy was not significantly related to
malnutrition in the multivariate logistic regression analysis.
In a prospective study on weight loss in HNC patients not
receiving dietary counseling, patients treated with any type
of radiotherapy lost significantly more body weight than
patients treated with surgery alone [40]. In the current
study, swallowing problems and insufficient intake were
more strongly related to malnutrition than type of treatment,
in the period after treatment.
Averagely, both malnourished and well-nourished
patients seemed to have a rather adequate intake of energy
and protein. However, insufficient protein intake related to
requirements was significantly related to malnutrition.
Energy and protein intake of our patients were similar to
intake reported in other studies in HNC patients [16, 26,
40]. On the other hand, mean body weight of our patients
was higher than reported in two of these studies [26, 40],
suggesting that dietary requirements of our patients were
higher as well. As the 95% confidence interval of the odds
ratio of insufficient protein intake was wide, the significant
relationship found between insufficient protein intake and
malnutrition should be interpreted with caution. This wide
confidence interval may be the result of insufficient power
due to the relatively low prevalence of malnutrition. On the
other hand, the effect of protein intake on malnutrition may
vary per patient. As malnutrition is the result of a
combination of insufficient intake and inflammation activ-
ity [33], inflammation activity may have continued in the
period after treatment.
Unfortunately, currently a gold standard for the assess-
ment of malnutrition unfortunately does not exist [33].
Weight loss is one of the criteria commonly used for
Table 4 Results of multivariate logistic regression analysis on malnutrition and oral symptoms (n=109)
Variableß SE ßOR95% CI of ORp
Swallowing problemsa
Insufficient protein intakeb
Interval after treatment (months)
Constant
0.03
1.60
−0.13
−2.37
0.01
0.66
0.06
0.64
1.03
4.93
0.89
0.09
1.01 to 1.06
1.35 to 18.06
0.79 to 1.00
0.021
0.016
0.057
<0.001
Β regression coefficient, SE β standard error of β, OR odds ratio=eβ, 95% CI of OR 95% confidence interval of odds ratio
aScale score, as assessed by EORTC QLQ-H&N35. A difference of, for instance, 20 points in swallowing problems between two patients results in an OR
for malnutrition of 1.82 20 ? b ¼ 20 ? 0:03 ¼ 0:06 ! e0:06¼ 1:82
b0 absent, 1 present
ðÞ
1680 Support Care Cancer (2011) 19:1675–1683

Page 7

assessment of malnutrition [34]. Weight loss of ≥10% in
6 months/≥5% in 1 month is a generally accepted cutoff for
clinically relevant weight loss. Such a weight loss is
associated with increased morbidity, such as impaired
wound healing and reduced immune function [6, 37].
Besides that, weight loss of ≥10% in 6 months/≥5% in
1 month has shown to be of great prognostic value in the
occurrence of major postoperative complications and has
been associated with higher mortality and reduced quality
of life [1, 6, 25, 30, 37–39, 41].
Whereas involuntary weight loss reflects (sub)acute
malnutrition, underweight reflects chronic malnutrition [14,
31]. Cutoff values for BMI varying from 18.5 to 20.0 kg/m2
have been used as an indicator of chronic malnutrition
[34, 45]. If a BMI<18.5 kg/m2was added to our criteria for
malnutrition, total prevalence of malnutrition would have
risen to 19% (22/116). Prevalence of malnutrition in the
period 0–3 months after treatment (28%, 15/53) also would
have been significantly higher than in the periods >3–
12 months and >12–36 months after treatment (16%, 5/32
and 7%, 2/31, p=0.012). If this cutoff for BMI is increased to
BMI<20 kg/m2, total prevalence of malnutrition would have
increased further to 22% (25/116). Prevalence of malnutrition
per interval after treatment would have been 32% (17/53),
16% (5/32) and 10% (3/32) respectively (p=0.012). These
findings indicate that the choice of the cutoff values is of the
utmost importance for assessment of malnutrition. Obviously,
a gold standard for the assessment of malnutrition is required.
To test the hypothesis that prevalence of malnutrition
declines after treatment, we classified patients into three
groups: 0–3 months after treatment, >3–12 months after
treatment and >12–36 months after treatment. We chose
these cutoff values, to distinguish between acute and late
side effects of HNC treatment. Radiation-induced acute side
effects, such as mucositis, will diminish in the first 3 months
after treatment [5, 42]. In the period between 3 months and
1 year after treatment, existing oral symptoms may recover
or may become chronic, as oral symptoms present 1 year
after treatment usually do not recover in the period after
that [22, 35]. Furthermore, in the short-term period after
treatment, inflammation activity related to treatment may
still be present [11, 19, 32]. One year after treatment, it is
expected that patients reach a ‘steady state’ with regard to
their nutritional problems.
The current study has some limitations. The first one is
the modest participation rate of 66%. In 14% of the patients
not willing to participate fatigue has played a major role in
the decision to refuse participation in the study. As it cannot
be excluded that fatigue was the result of malnutrition, the
modest participation rate may have resulted in underesti-
mation of malnutrition.
The second study limitation is the use of a self
reported body weight. Generally, men slightly overesti-
mate body weight (0.3 kg), whereas women tend to
underestimate their body weight (−1.4 kg) [24]. In our
study population, the majority (62%) of patients was male.
As a result, prevalence of malnutrition may have been
slightly overestimated.
The third study limitation was the use of prediction
equations to estimate nutritional requirements [8, 27, 44].
Indirect calorimetry is the gold standard to assess energy
requirements [7]. However, for practical reasons it was not
possible to perform indirect calorimetry in the current
study. Therefore, energy requirements had to be estimated.
We have chosen to compare energy intake to energy
recommendations conform clinical practice in the UMCG.
Use of equations to predict energy expenditure may lead to
errors [8, 44] Such prediction errors may vary from 235 to
425 kcal, which is about 15–30% of resting energy
expenditure as measured by indirect calorimetry [44].
Therefore, evaluation of dietary intake in relation to
requirements requires further research.
In conclusion, malnutrition is a considerable problem in
patients treated for oral/oropharyngeal cancer, shortly after
treatment. Of all oral symptoms, only swallowing problems
were significantly related to malnutrition in the period after
treatment for oral/oropharyngeal cancer.
Acknowledgments
grant from the Stimulation Fund of the University Medical Center
Groningen, Groningen, the Netherlands. The study sponsor did not
have any involvement in the study design, data collection, analysis
and interpretation of data, the writing of the manuscript, and in the
decision to submit the manuscript for publication. The authors
thank Greet van Rijn and Sietske Huitema for reviewing the
manuscript.
This study was financially supported by a
Conflict of interest
None declared.
Open Access
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
This article is distributed under the terms of the
References
1. Barbosa-Silva MC, Barros AJ (2005) Bioelectric impedance and
individual characteristics as prognostic factors for post-operative
complications. Clin Nutr 24(5):830–838
2. Bjordal K, Hammerlid E, Ahlner-Elmqvist M, de Graeff A,
Boysen M, Evensen JF, Biorklund A, de Leeuw JR, Fayers PM,
Jannert M, Westin T, Kaasa S (1999) Quality of life in head and
neck cancer patients: validation of the European organization for
research and treatment of cancer quality of life questionnaire-
H&N35. J Clin Oncol 17(3):1008–1019
3. Blackburn GL, Bistrian BR, Maini BS, Schlamm HT, Smith MF
(1977) Nutritional and metabolic assessment of the hospitalized
patient. JPEN J Parenter Enteral Nutr 1(1):11–22
Support Care Cancer (2011) 19:1675–16831681

Page 8

4. Burke BS (1947) The dietary history as a tool in research. J Am
Diet Assoc 23:1041–1046
5. Cheng KK, Leung SF, Liang RH, Tai JW, Yeung RM, Thompson
DR (15-11-2009) Severe oral mucositis associated with cancer
therapy: impact on oral functional status and quality of life.
Support Care Cancer Epub ahead of print
6. Correia MI, Waitzberg DL (2003) The impact of malnutrition
on morbidity, mortality, length of hospital stay and costs
evaluated through a multivariate model analysis. Clin Nutr 22
(3):235–239
7. da Rocha EE, Alves VG, da Fonseca RB (2006) Indirect
calorimetry: methodology, instruments and clinical application.
Curr Opin Clin Nutr Metab Care 9(3):247–256
8. da Rocha EE, Alves VG, Silva MH, Chiesa CA, da Fonseca RB
(2005) Can measured resting energy expenditure be estimated by
formulae in daily clinical nutrition practice? Curr Opin Clin Nutr
Metab Care 8(3):319–328
9. Dickerson RN, Boschert KJ, Kudsk KA, Brown RO (2002)
Hypocaloric enteral tube feeding in critically ill obese patients.
Nutrition 18(3):241–246
10. Dijkstra PU, Huisman PM, Roodenburg JLN (2006) Criteria for
trismus in head and neck oncology. Int J Oral Maxillofac Surg 35
(4):337–342
11. Ehrsson YT, Hellstrom PM, Brismar K, Sharp L, Langius-Eklof
A, Laurell G (15-10-2009) Explorative study on the predictive
value of systematic inflammatory and metabolic markers on
weight loss in head and neck cancer patients undergoing
radiotherapy. Support Care Cancer Epub ahead of print
12. EORTC Quality of Life Study Group (2001) EORTC QLQ-C30
Scoring Manual (Third edition)
13. Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D,
Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, Marks D,
Mitch WE, Muscaritoli M, Najand A, Ponikowski P, Rossi Fanelli
F, Schambelan M, Schols A, Schuster M, Thomas D, Wolfe R,
Anker SD (2008) Cachexia: a new definition. Clin Nutr 27
(6):793–799
14. Ferro-Luzzi A, Sette S, Franklin M, James WP (1992) A
simplified approach of assessing adult chronic energy deficiency.
Eur J Clin Nutr 46(3):173–186
15. Goldstein M, Maxymiw WG, Cummings BJ, Wood RE (1999)
The effects of antitumor irradiation on mandibular opening and
mobility: a prospective study of 58 patients. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 88(3):365–373
16. Isenring EA, Bauer JD, Capra S (2007) Nutrition support using
the American Dietetic Association medical nutrition therapy
protocol for radiation oncology patients improves dietary intake
compared with standard practice. J Am Diet Assoc 107(3):404–
412
17. Jager-Wittenaar H, Dijkstra PU, van der Laan BFAM, Vissink A,
van Oort RP, Roodenburg JLN (2007) Critical weight loss in head
and neck cancer patients—prevalence and risk factors at diagno-
sis: an explorative study. Supp Care Cancer 15:1045–1050
18. Jager-Wittenaar H, Dijkstra PU, Vissink A, van Oort RP,
Roodenburg JL (2009) Variation in repeated mouth-opening
measurements in head and neck cancer patients with and without
trismus. Int J Oral Maxillofac Surg 38(1):26–30
19. Ki Y, Kim W, Nam J, Kim D, Park D, Kim D (2009) C-reactive
protein levels and radiation-induced mucositis in patients with
head-and-neck cancer. Int J Radiat Oncol Biol Phys 75(2):393–
398
20. Kubrak C, Olson K, Jha N, Jensen L, McCargar L, Seikaly H,
Harris J, Scrimger R, Parliament M, Baracos VE (2010)
Nutrition impact symptoms: key determinants of reduced
dietary intake, weight loss, and reduced functional capacity of
patients with head and neck cancer before treatment. Head
Neck 32(3):290–300
21. Lees J (1999) Incidence of weight loss in head and neck cancer
patients on commencing radiotherapy treatment at a regional
oncology centre. Eur J Cancer Care (Engl) 8(3):133–136
22. Logemann JA, Pauloski BR, Rademaker AW, Lazarus CL,
Gaziano J, Stachowiak L, Newman L, MacCracken E, Santa D,
Mittal B (2008) Swallowing disorders in the first year after
radiation and chemoradiation. Head Neck 30(2):148–158
23. Matthews TW, Lampe HB, Dragosz K (1995) Nutritional
status in head and neck cancer patients. J Otolaryngol 24
(2):87–91
24. Merrill RM, Richardson JS (2009) Validity of self-reported height,
weight, and body mass index: findings from the National Health
and Nutrition Examination Survey, 2001–2006. Prev Chron Dis 6
(4):A121
25. Nguyen TV, Yueh B (2002) Weight loss predicts mortality after
recurrent oral cavity and oropharyngeal carcinomas. Cancer 95
(3):553–562
26. Ravasco P, Monteiro-Grillo I, Marques VP, Camilo ME (2005)
Impact of nutrition on outcome: a prospective randomized
controlled trial in patients with head and neck cancer undergoing
radiotherapy. Head Neck 27(8):659–668
27. Reeves MM, Battistutta D, Capra S, Bauer J, Davies PS (2006)
Resting energy expenditure in patients with solid tumors under-
going anticancer therapy. Nutrition 22(6):609–615
28. Rieger JM, Zalmanowitz JG, Wolfaardt JF (2006) Functional
outcomes after organ preservation treatment in head and neck
cancer: a critical review of the literature. Int J Oral Maxillofac
Surg 35(7):581–587
29. Sauerwein HP, Strack van Schijndel RJ (2007) Perspective: how
to evaluate studies on peri-operative nutrition? Considerations
about the definition of optimal nutrition for patients and its key
role in the comparison of the results of studies on nutritional
intervention. Clin Nutr 26(1):154–158
30. Seltzer MH, Slocum BA, Cataldi-Betcher EL, Fileti C, Gerson
N (1982) Instant nutritional assessment: absolute weight loss
and surgical mortality. JPEN J Parenter Enteral Nutr 6(3):218–
221
31. Shetty PS, James WP (1994) Body mass index. A measure of
chronic energy deficiency in adults. FAO Food Nutr Pap 56:1–57
32. Silver HJ, Dietrich MS, Murphy BA (2007) Changes in body
mass, energy balance, physical function, and inflammatory state in
patients with locally advanced head and neck cancer treated with
concurrent chemoradiation after low-dose induction chemothera-
py. Head Neck 29(10):893–900
33. Soeters PB, Reijven PL, van Bokhorst-de van der Schueren MA,
Schols JM, Halfens RJ, Meijers JM, van Gemert WG (2008) A
rational approach to nutritional assessment. Clin Nutr 27(5):706–
716
34. Stratton RJ, Green CJ, Elia M (2003) Disease-related malnu-
trition: an evidence based approach to treatment. CABI,
Wallingford
35. Tei K, Maekawa K, Kitada H, Ohiro Y, Yamazaki Y, Totsuka Y
(2007) Recovery from postsurgical swallowing dysfunction in
patients with oral cancer. J Oral Maxillofac Surg 65(6):1077–1083
36. Unsal D, Mentes B, Akmansu M, Uner A, Oguz M, Pak Y (2006)
Evaluation of nutritional status in cancer patients receiving
radiotherapy: a prospective study. Am J Clin Oncol 29(2):183–
188
37. van Bokhorst-de van der Schueren MA, von Blomberg-van der
Flier BM, Riezebos RK, Scholten PE, Quak JJ, Snow GB, van
Leeuwen PA (1998) Differences in immune status between well-
nourished and malnourished head and neck cancer patients. Clin
Nutr 17(3):107–111
38. van Bokhorst-de van der Schueren MA, van Leeuwen PA, Kuik
DJ, Klop WM, Sauerwein HP, Snow GB, Quak JJ, Andrews E
(1999) The impact of nutritional status on the prognoses of
1682 Support Care Cancer (2011) 19:1675–1683

Page 9

patients with advanced head and neck cancer. Cancer 86(3):519–
527
39. van Bokhorst-de van der Schueren MA, van Leeuwen PA,
Sauerwein HP, Kuik DJ, Snow GB, Quak JJ (1997) Assessment
of malnutrition parameters in head and neck cancer and their
relation to postoperative complications. Head Neck 19(5):419–
425
40. van den Berg MG, Rasmussen-Conrad EL, Gwasara GM, Krabbe
PF, Naber AH, Merkx MA (2006) A prospective study on weight
loss and energy intake in patients with head and neck cancer, during
diagnosis, treatment and revalidation. Clin Nutr 25(5):765–772
41. van den Berg MG, Rasmussen-Conrad EL, van Nispen L, van
Binsbergen JJ, Merkx MA (2008) A prospective study on
malnutrition and quality of life in patients with head and neck
cancer. Oral Oncol 44(9):830–837
42. Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP
(2003) Oral sequelae of head and neck radiotherapy. Crit Rev Oral
Biol Med 14(3):199–212
43. Wang CJ, Huang EY, Hsu HC, Chen HC, Fang FM, Hsiung CY
(2005) The degree and time-course assessment of radiation-
induced trismus occurring after radiotherapy for nasopharyngeal
cancer. Laryngoscope 115(8):1458–1460
44. Weijs PJ, Kruizenga HM, van Dijk AE, van der Meij BS, Langius
JA, Knol DL, Strack van Schijndel RJ, van Bokhorst-de van der
Schueren MA (2008) Validation of predictive equations for resting
energy expenditure in adult outpatients and inpatients. Clin Nutr
27(1):150–157
45. World Health Organization (1995) Physical status: the use and
interpretation of anthropometry. Report of a WHO expert
committee. Technical Report Series, No 854. WHO: Geneva
Support Care Cancer (2011) 19:1675–16831683