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Original article

Impact of mood disturbance, sleep disturbance, fatigue and

pain among patients receiving cancer therapy
ecc_1372

70..78

K.K.F. CHENG, rn, pgdip epidemiol & biostat, phd, associate professor, Alice Lee Centre for Nursing Studies,
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, & R.M.W. YEUNG, md, consultant, Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hospital Authority, Hong Kong
CHENG K.K.F. & YEUNG R.M.W. (2013) European Journal of Cancer Care 22, 7078
Impact of mood disturbance, sleep disturbance, fatigue and pain among patients receiving cancer therapy
This paper describes the prevalence of mood disturbance, sleep disturbance, fatigue and pain (MSFP), either
alone or in combination in patients receiving cancer therapy, and determines its impact and whether it is a
predictor for functional status and the impairment of quality of life (QoL). This is a cross-sectional study using
secondary data from a sample of 214 patients being treated by chemotherapy or radiotherapy. In all, 87%, 68%,
66% and 38% of the patients reported MSFP respectively. Co-occurrence of any three and all of the four
symptoms, were reported separately at rates of 29% and 31%. Patients with all four symptoms recorded
significantly lower Karnofsky Performance Scale (KPS) scores (mean 77.7 12.9) and QoL scores (mean
subscales scores 9.017.6) than those with none or up to any three of the symptoms (P < 0.001). Regression of
the KPS and QoL scores against the MSFP revealed an increase in the explained variance of 25%, 43%, 27%,
37% and 41% respectively for KPS, physical, emotional, functional and total QoL. The results suggest that
MSFP are highly prevalent, whether alone or in combination, in patients receiving cancer therapy, and may
negatively influence the patients functional status and QoL during cancer therapy.

Keywords: symptoms, mood disturbance, sleep disturbance, fatigue, pain, chemotherapy, radiotherapy,
quality of life.

INTRODUCTION
Many cancer patients continue to struggle with myriad
symptoms and morbidities. Mood disturbance, sleep disturbance, fatigue and pain (MSFP), are four of the most
common self-reported symptoms. Each of these has been
shown to affect patients throughout the process of diagnosis and treatment for cancer and can persist into the
survivorship period (Stone et al. 2000; Wells 2000; Savard

Correspondence address: Karis Kin-Fong Cheng, Alice Lee Centre for

Nursing Studies, Yong Loo Lin School of Medicine, National University of
Singapore, Level 2, Clinical Research Centre, Block MD11, 10 Medical
Drive, Singapore 117597 (e-mail: nurckfk@nus.edu.sg or karis_cheng@
nuhs.edu.sg).

Accepted 6 April 2012

DOI: 10.1111/j.1365-2354.2012.01372.x
European Journal of Cancer Care, 2013, 22, 7078

2012 Blackwell Publishing Ltd

& Morin 2001; Shi et al. 2011). However, the underlying

mechanisms and the patho-biological basis are unclear. It
is of note that self-reporting of the four symptoms of
MSFP in cancer patients varies widely and has been
reported as 58% (Massie 2004), 24% to 95% (DelgadoGuay et al. 2011), 75% to 100% (Stone et al. 1998; Hickok
et al. 2005; Kim et al. 2006), 14% to 100% (Meuser et al.
2001; Patrick et al. 2004) respectively, at the stage of diagnosis, and during or after treatment for cancer (Meuser
et al. 2001; Savard & Morin 2001; Koopman et al. 2002;
Servaes et al. 2002). The prevalence rates of clinically relevant levels of anxiety and depression in cancer patients
have been estimated to be up to 45% (McDaniel et al.
1995; Grassi et al. 1996). Previous studies suggest that
nearly 20% of cancer sufferers meet the sleep disturbance
diagnostic criteria (Davidson et al. 2002).
The literature has indicated that the morbidities and
distress resulting from cancer and treatment-related

Cancer therapy-related affective and somatic symptoms

symptoms can lead to a profound impairment of the

patients quality of life (QoL) and functional status (Grassi
et al. 1996; Cleeland 2007; Delgado-Guay et al. 2011). In
addition, cancer and treatment-related symptoms can
directly affect survival rates if they become so severe that
patients abandon their cancer treatments, or if they give
rise to delays in the cancer treatment. Residual treatmentrelated symptoms can also complicate post-cancer treatment rehabilitation (Cleeland 2007). Snyderman and
Wynn (2009) revealed that depression adversely affects the
cancer patients QoL, their compliance with the cancer
treatment and their relationship with their carers and may
ultimately have an effect on mortality (Snyderman &
Wynn 2009). The effects of sleep disturbance are physical
as well as psychological, with some research suggesting
that sleep disturbance may be associated with an
increased risk of immuno-suppression, as it carries with it
the potential to affect the course of the cancer (Davidson
et al. 2002; Bardwell et al. 2008). Fatigue in cancer
patients can interfere with their self-care activities, and be
extreme enough at times to cause a postponement or
reduction of the treatment (Delgado-Guay et al. 2011).
Pain is considered to be one of the most feared symptoms
of cancer and the one that most disrupts all aspects of life
(Cleeland et al. 2000; Tavoli et al. 2008).
Recent identification of correlated and co-varied symptoms has revealed novel insights into the co-occurrence of
the symptoms as a cluster. More pre-clinical and observational clinical studies on the etiological processes and
related physical and psychosocial implications of such a
symptom cluster should become available in the next few
years. To date, several studies documenting the multiplicity of the symptoms experienced by cancer patients have
shown that pain, fatigue, sleep disturbance, emotional
distress and poor appetite are almost universally found to
be co-occurring. More than 20 studies into symptom clusters for any of the MSFP symptoms in combination have
been undertaken (Spiegel et al. 1994; Glover et al. 1995;
Gaston-Johansson et al. 1999; Miaskowski & Lee 1999;
Redeker et al. 2000; Theobald 2004; Beck et al. 2005; Mystakidou et al. 2007; Kozachik & Bandeen-Roche 2008;
Tavoli et al. 2008; So et al. 2009; Stepanski et al. 2009;
Laird et al. 2011; Manitta et al. 2011). Pain sleep disturbance fatigue (Miaskowski & Lee 1999; Beck et al. 2005;
Mystakidou et al. 2007; Kozachik & Bandeen-Roche
2008) and pain depression fatigue (Spiegel et al. 1994;
Gaston-Johansson et al. 1999; So et al. 2009; Laird et al.
2011) are commonly recognised as clinical symptom clusters. These studies have shed much light on the possible
existence of symptom clusters of MSFP and the possibility
of streamlining treatments. Nonetheless, most of the prior
2012 Blackwell Publishing Ltd

research into MSFP has focused on any two or three symptoms in combination, rather than on exploring the potential interactions and interrelationships between all of the
MSFP symptoms together. In addition, only a limited
number of studies have dealt with clusters of MSFP symptoms in patients receiving cancer treatment as compared
with those who are receiving palliative care and are at an
advanced stage of the disease. Thus, it is becoming
increasingly critical to address the effect of MSFP on
patients lives in order to reduce the burden of cancer
treatment. The purpose of the present study is to determine the impact of MSFP on patients functional status
and QoL, and evaluate whether MSFP can be a predictor of
functional status and the impairment of QoL during
cancer therapy, after adjusting for demographic and clinical factors.

METHODS
This cross-sectional study used secondary data from a
convenience sample of 214 patients, 18 years of age and
older, with head/neck, colorectal, breast, lung, gynaecological or other cancers receiving chemotherapy or radiotherapy at an oncology unit of a regional hospital in Hong
Kong. The study sample was drawn from a previously
conducted observational validation study (Cheng et al.
2009). The original database consisted of 370 patients who
were undergoing cancer therapy or at the early posttreatment stage for any diagnosed cancer. The study was
conducted in accordance with the Declaration of Helsinki;
all of the subjects provided written informed consent
before being enrolled in the study.
Mood disturbance, sleep disturbance, fatigue and pain
were measured using the respective items from the
Chinese version of the Symptom Distress Scale (SDS). The
possible score ranges from 1 to 5, with 5 indicating a high
level of symptom distress (McCorkle & Young 1978). For
this study, a symptom was considered to be present if the
SDS score was 2. The patients QoL was assessed using
the Chinese version of the Functional Assessment of
Cancer Therapy-General (FACT-G). The physical, social,
emotional, and functional subscales and total scores were
computed as previously described. A lower score indicates
a poorer QoL (Cella et al. 1993). The Chinese versions of
both the SDS and FACT-G are accepted as being valid and
reliable psychometric tools, and to have an acceptable
cultural equivalence with the original version (Chan 2000;
Yu et al. 2000).
The observer rated Karnofsky Performance Scale (KPS)
was used to measure functional status. This is an 11-point
rating scale ranging from 0 to 100 (0 = dead, 100 = normal
71

CHENG & YEUNG

function) widely used to assess patients physical functional level related to cancer and its treatment (Yates et al.
1980). A validation study strongly suggests that the score
reflects the physical functioning of the patient (Mor et al.
1984).

Statistical analysis
Pearsons simple correlation test was performed for the
correlations between the MSFP symptoms, and thus to
determine the relationships between those symptoms, the
KPS, and the FACT-G subscale/total scores. Univariable
and multivariable conditional logistic regression analyses
were performed in order to estimate the odds ratios (OR) for
the patients who reported co-occurrence of any three symptoms of MSFP or all of the four symptoms. Any variables
with P-values <0.50 in the univariate model were tried in
the multivariate model in order to avoid excluding independent variables that might be non-significant in the
univariable analysis due to confounding. One-way analyses
of variance were used to determine if there were significant
differences among the patients who reported different
numbers of combinations of symptoms on KPS, and on the
FACT-G (C) subscale and total scores. The influence of the
MSFP symptoms on the patients functional status and
QoL was determined by a two-stage hierarchical multiple
regression. As the first step, gender, age, cancer diagnosis
and treatment modality were entered into the regression
model as covariates. To analyse whether the MSFP symptoms influenced the patients QoL over and above the
influences of the covariates, the four symptoms were
entered into the hierarchical analysis as a second step. This
resulted in a statistical significance of P < 0.05.
RESULTS
As shown in Table 1, the mean age of the patients was
54.24 11.56 years (range 2078 years); 51.4% (n = 110)
were men. About 22% were diagnosed with head/neck
cancer (n = 48), and 21% with colorectal cancer (n = 45).
More than half of the patients were at the early stage of
the disease (66.1%). More than half of the patients were
receiving chemotherapy (61.2%, n = 128), and 27% undergoing chemoradiotherapy.
The patients reported MSFP, at rates of 87%, 68%, 66%
and 38% respectively. Pain was the most distressing
symptom, with a mean score of 3.17 1.0. The mean
distress scores for sleep disturbance, fatigue and mood
disturbance were 2.94 0.9, 2.92 0.9 and 2.81 0.7
respectively. Among patients reported pain, 65.4% of
them were taking analgesics. Co-occurrence of any three
72

Table 1. Subject characteristics (n = 214)

Characteristics

Frequency (%)

Age (mean SD)

Gender
Male
Female
Educational level
No formal education
Primary
Secondary
Tertiary
Cancer diagnosis
Head and neck
Colorectal
Breast
Lung
Gynaecological
Others
Cancer therapy
Chemotherapy
Chemoradiotherapy
Radiotherapy

54.24 11.56
110 (51.4)
104 (48.6)
16
78
101
19

(7.5)
(36.4)
(47.2)
(8.9)

48
45
41
34
15
31

(22.4)
(21.0)
(19.2)
(15.9)
(7.0)
(14.5)

128 (61.2)
57 (27.3)
24 (11.5)

symptoms of MSFP and all of the four symptoms, were

reported separately at rates of 29% and 31%. The intercorrelations between the MSFP symptoms were mild to
moderate (r = 0.25 to 0.42, P < 0.001). Mood disturbance
showed moderate positive correlations with fatigue (r =
0.33, P < 0.001) and sleep disturbance (r = 0.32, P < 0.001).
Fatigue was moderately correlated with sleep disturbance
(r = 0.42, P < 0.001) and pain (r = 0.39, P < 0.001) (Table 2).
As shown in Table 3, gender, cancer diagnosis and the
type of cancer therapy all had P < 0.50 in the univariable
models and were thus included as candidate variables for
the multivariable model. In the multivariable model, only
lung cancer (OR = 2.81; 95% CI = 1.166.85; P = 0.023) was
significantly associated with a higher risk of developing
any three or all of the MSFP symptoms.
The mean KPS score was 87.7 12.1. A KPS score >80
was found for 84% of these patients. Table 4 reveals the
KPS and FACT-G (C) subscale/total scores for patients
with a different number of combinations of the MSFP
symptoms. Significant differences were found in all KPS
and FACT-G (C) subscale/total scores among the five subgroups of patients (P < 0.001). Post hoc comparisons with
Bonferroni corrections show that the KPS and FACT-G
subscale/total scores of patients with co-occurrence of all
four of the symptoms (KPS: 77.7; FACT-G subscales: 9.0
to 17.6, FACT-G total: 63.0) were significantly lower than
those without any of the symptoms (KPS: 92.8; FACT-G
subscales: 21.1 to 26.6, FACT-G total: 99.7), and those
with any one symptom (KPS: 94.1; FACT-G subscales:
16.6 to 23.2, FACT-G total: 85.0) and any two of the four
symptoms (KPS: 94.4; FACT-G subscales: 16.0 to 22.6,
2012 Blackwell Publishing Ltd

Cancer therapy-related affective and somatic symptoms

Table 2. Correlation coefficients among mood disturbance, sleep disturbance, fatigue and pain, and among KPS and FACT-G subscale and
total scores (n = 214)
Sleep disturbance
Fatigue
Pain
KPS
QoL scores
Physical
Social
Emotion
Functional
Total

Mood

Sleep disturbance

Fatigue

Pain

0.32*
0.33*
0.25*
-0.29*

0.42*
0.26*
-0.28*

0.39*
-0.48*

-0.57*

-0.49*
-0.27*
-0.53*
-0.48*
-0.57*

-0.39*
-0.20*
-0.29*
-0.44*
-0.44*

-0.50*
-0.32*
-0.39*
-0.52*
-0.55*

-0.55*
-0.26*
-0.24*
-0.43*
-0.47*

Coefficients greater than 0.30 are in bold type.

*P < 0.001.
FACT-G, Functional Assessment of Cancer Therapy-General; KPS, Karnofsky Performance Scale; QoL, quality of life.

Table 3. Associations between patients characteristics and the no. of combined mood disturbance, sleep disturbance, fatigue and pain
(n = 214)

Age
Gender
Male
Female
Cancer diagnosis
Head and neck
Colorectal
Breast
Lung
Gynaecological
Others
Cancer therapy
Chemotherapy
Radiotherapy
Chemoradiotherapy

02 symptoms
(n = 85)

3 symptoms
(n = 127)

Bivariate analysis
Odds ratio (95% CI)

P-value

Odds ratio (95% CI)

P-value

53.81 11.4

54.52 11.7

1.01 (0.981.03)

0.659

42 (48.8%)
44 (51.2%)

68 (53.1%)
60 (46.9%)

1.0 (referent)
1.19 (0.692.05)

0.539

1.46 (0.663.20)

0.350

19
20
21
7
8
11

29
25
20
27
7
20

1.0
0.82
0.62
2.58
0.57
1.19

(referent)
(0.361.87)
(0.271.45)
(0.926.96)
(0.181.84)
(0.473.04)

0.635
0.272
0.073
0.350
0.714

0.64
0.46
2.81
0.40
1.14

0.328
0.163
0.023*
0.179
0.791

1.0 (referent)
2.12 (0.795.70)
0.84 (0.451.58)

0.136
0.593

1.68 (0.574.98)
0.84 (0.431.63)

(22.1%)
(23.3%)
(24.4%)
(8.1%)
(9.3%)
(12.8%)

53 (62.4%)
6 (7.1%)
26 (30.6%)

(22.7%)
(19.5%)
(15.6%)
(21.1%)
(5.5%)
(15.6%)

75 (60.5%)
18 (14.5%)
31 (25.0%)

Multivariate analysis

(0.271.56)
(0.161.37)
(1.166.85)
(0.101.53)
(0.423.10)

0.351
0.598

Values are mean SD or frequency (%).

*P < 0.05.
Any variables with P-values 0.50 in the univariate model were tried in the multivariate model.

FACT-G total: 84.3) (P < 0.001). As for patients with any

three of the four symptoms, post hoc comparisons with
Bonferroni corrections show that the FACT-G social,
emotional and functional subscale and total scores were
significantly lower than those without any symptoms and
for those with any one or two of the four symptoms
(P < 0.001).
The correlations between the KPS scores, the FACT-G
subscale/total scores and the MSFP showed moderate
negative correlations (r = -0.20 to -0.57, P < 0.001)
(Table 2). Only those with r > 0.3 are reported here. In
terms of functional status, the KPS scores showed a mild
to moderate negative correlation with the four symptoms
(r = -0.28 to -0.57, P < 0.001). Correlations between the
FACT-G subscale/total scores and the symptoms of MSFP
2012 Blackwell Publishing Ltd

showed moderate negative correlations of the physical

(r = -0.39 to -0.55, P < 0.001), emotional (r = -0.24 to
-0.53, P < 0.001) and functional (r = -0.43 to -0.52, P <
0.001) subscales and total (r = -0.44 to -0.57, P < 0.001)
scores for the four symptoms.
As shown in Table 5, regression of the KPS scores
against the symptoms of MSFP revealed that the increase
in explained variance of 25% was significant (F change =
25.3, P < 0.0001). Pain (b = -0.34, P < 0.001) and fatigue
(b = -0.26, P < 0.001) showed significant independent
effects on the KPS scores, whereas mood disturbance and
sleep disturbance were not seen as influencing the KPS
scores independently (P > 0.05).
As for the QoL, regression of the FACT-G physical subscale score against the symptoms of MSFP revealed that
73

Post hoc comparisons:

KPS and FACT-G physical subscale scores: no, any one, any two, any three MSFP > all MSFP.
FACT-G social subscale score: no, any one MSFP > any three/all MSFP.
FACT-G emotional subscale score: no, any one, any two MSFP > all MSFP; no MSFP > any three MSFP.
FACT-G functional subscale score: no, any one, any two, any three MSFP > all MSFP; no, any one, any two > any three MSFP.
FACT-G total score: no, any one, any two, any three MSFP > all MSFP; no, any one, any two > any three MSFP.
*The mean KPS score ranges 0 to 100; higher score represents a better functional status.
The mean FACT-G physical, social, and functional subscale scores range 0 to 28; higher score represents a better QoL.
The mean FACT-G emotion subscale score range 0 to 24; higher score represents a better QoL.
The mean FACT-G total score range 0 to 116; higher score represents a better QoL.
FACT-G, Functional Assessment of Cancer Therapy-General; KPS, Karnofsky Performance Scale; MSFP, mood disturbance, sleep disturbance, fatigue and pain; QoL, quality of
life.

P-value

<0.001
<0.001
<0.001
<0.001
<0.001
30.7
8.7
9.5
25.4
32.9
15.6 5.6 (14.216.9)
17.6 4.2 (16.518.6)
15.5 4.6 (14.416.7)
9.0 5.7 (7.510.4)
63.0 16.3 (58.967.1)
4.3 (20.122.2)
3.8 (17.419.4)
4.0 (15.717.7)
5.3 (11.714.4)
12.7 (70.977.6)

21.1
18.4
16.7
13.0
74.3
4.6 (20.924.2)
3.4 (19.521.8)
3.9 (17.720.4)
5.8 (14.117.9)
12.3 (80.088.6)

22.6
20.6
19.1
16.0
84.3
4.1 (21.624.6)
3.8 (19.722.5)
3.4 (17.119.5)
4.9 (14.818.4)
11.4 (80.889.3)

23.2
21.1
18.3
16.6
85.0
(25.527.7)
(20.324.1)
(19.522.7)
(18.923.7)
(95.2104.1)
2.2
3.5
3.1
4.8
8.1

26.6
22.2
21.1
21.3
99.7

25.3

F
All MSFP (n = 64)

77.7 12.9 (74.580.9)

89.5 9.4 (87.291.9)

Any three of MSFP (n = 63)

Any two of MSFP (n = 35)

94.4 6.1 (92.496.5)

Any one of MSFP (n = 32)

94.1 6.7 (91.796.5)

92.8 10.7 (87.498.1)

KPS*
FACT-G scores
Physical
Social
Emotion
Functional
Total

Mean SD (95% CI)

No MSFP (n = 18)

Table 4. The mean KPS and FACT-G (C) subscale scores by the no. of combined MSFP (n = 214)

74

<0.001

CHENG & YEUNG

the increase in explained variance of 43% was significant

(F change = 42.1, P < 0.001). Pain (b = -0.33, P < 0.001),
mood disturbance (b = -0.29, P < 0.001), fatigue (b = -0.23,
P < 0.001) and sleep disturbance (b = -0.12, P < 0.05)
showed significant independent effects for the FACT-G
physical subscale score. As the b coefficients of pain and
mood disturbance are similar in value, their effects on the
patients physical well-being are roughly equal. Regression of the FACT-G social subscale score against the
symptoms of MSFP revealed that the increase in explained
variance of 9% was significant (F change = 4.98, P = 0.001).
Only fatigue (b = -0.20, P = 0.013) showed significant
independent effects for the FACT-G social subscale score.
Regression of the FACT-G emotional subscale score
against the symptoms of MSFP revealed that the increase
in the explained variance of 27% was significant (F change
= 22.5, P < 0.001). Mood disturbance (b = -0.40, P < 0.001)
and fatigue (b = -0.22, P < 0.01) showed significant independent effects for the FACT-G emotional subscale score,
whereas sleep disturbance and pain were not found to
influence the FACT-G emotional subscale score independently (P > 0.05). Regression of the FACT-G functional
subscale score against the symptoms of MSFP revealed
that the increase in explained variance of 37% was significant (F change = 34.1, P < 0.001). All of the four symptoms
of mood disturbance (b = -0.26, P < 0.001), sleep disturbance (b = -0.29, P < 0.001), pain (b = -0.29, P < 0.001) and
fatigue (b = -0.27, P < 0.001) showed significant independent effects for the FACT-G functional subscale score. As
the b coefficients of all of these four symptoms are similar
in value, their effects on the patients functional wellbeing are roughly equal. Regression of the FACT-G total
score against the symptoms of MSFP revealed that the
increase in explained variance of 41% was significant
(F change = 44.5, P < 0.001). All four of the symptoms of
mood disturbance (b = -0.35, P < 0.001), fatigue (b = -0.27,
P < 0.001), pain (b = -0.19, P < 0.01) and sleep disturbance
(b = -0.14, P < 0.05) showed significant independent effects
for the FACT-G total score. As demonstrated by the relative sizes of the beta weights, the symptoms explaining
the greatest proportion of the variances in overall wellbeing were mood disturbance and fatigue.

DISCUSSION
The above data have shown that MSFP are highly prevalent, whether alone or in combination, in patients who
have undergone cancer therapy. It is to be noted that the
reported mood disturbance (87%) and sleep disturbance
(68%) was higher than in the previous study of patients
prior to the initiation of radiotherapy (mood disturbance
2012 Blackwell Publishing Ltd

Cancer therapy-related affective and somatic symptoms

Table 5. Regression coefficients of the KPS and FACT-G subscale and total scores against mood disturbance, sleep disturbance, fatigue
and pain (n = 214)
Standardised coefficients b
FACT-G (C)
KPS
Age
Gender
Male
Female
Cancer diagnosis
Head and neck
Colorectal
Breast
Lung
Gynaecological
Others
Cancer therapy
Chemotherapy
Radiotherapy
Chemoradiotherapy
Mood disturbance
Sleep disturbance
Fatigue
Pain
DR2
DF-value
P-value

-0.11

Physical
0.05

Social
-0.03

Emotional
0.22**

Functional
0.03

Total
0.10

1 (Referent)
0.05

1 (Referent)
-0.03

1 (Referent)
0.19*

1 (Referent)
0.02

1 (Referent)
0.15

1 (Referent)
0.10

1 (Referent)
-0.28
-0.34*
0.13*
-0.20
0.01

1 (Referent)
-0.26
-0.23
0.29
-0.38
-0.13

1 (Referent)
0.14
0.01
0.16
0.06
0.19

1 (Referent)
-0.29
-0.33
0.11
-0.22
-0.01

1 (Referent)
-0.28
-0.34
0.13
-0.20
0.01

1 (Referent)
-0.27
-0.39
0.20
-0.42
-0.50

1 (Referent)
-0.25
0.02
-0.05
-0.04
-0.26
-0.34
0.25
25.3
<0.0001

1 (Referent)
-0.10
-0.02
-0.29
-0.12*
-0.23
-0.33
0.43
42.1
<0.0001

1 (Referent)
-0.13
-0.01
-0.11
0.01
-0.20*
-0.12
0.09
4.98
0.001

1 (Referent)
-0.22**
-0.05
-0.40
-0.06
-0.22**
0.03
0.27
22.5
<0.0001

1 (Referent)
-0.05
0.10
-0.26
-0.29
-0.27
-0.29
0.37
34.1
<0.0001

1 (Referent)
-0.15*
-0.03
-0.35
-0.14*
-0.27
-0.19**
0.41
44.5
<0.0001

*P < 0.05; **P < 0.01; P < 0.001; P < 0.0001.

FACT-G, Functional Assessment of Cancer Therapy-General; KPS, Karnofsky Performance Scale.

38%, sleep disturbance 57%). One probable explanation

for the high prevalence of mood disturbance in our study
was the escalating distress associated with the debilitating
side effects or medical complications of cancer therapy.
Palesh et al. (2010) also indicated that mood disturbance
and sleep disturbance often increase during the treatment
period. The incidence of fatigue (66%) and pain (38%)
reported by patients in this study is consistent with earlier
reports of haemato-oncological patients receiving inpatient and outpatient services (fatigue 69%, pain 39%)
(Manitta et al. 2011). Hickok et al. (2005) studied 372
patients undergoing radiotherapy and found that 57% of
the patients reported some degree of fatigue at the initiation stage of radiotherapy, and the proportion increased to
76% by week 3 and then to 78% at week 5. The current
study also showed that MSFP were moderately distressing
for patients during cancer therapy. A cross-sectional study
of 263 cancer patients who were undergoing chemotherapy also found a moderate distress level for fatigue
(mean = 2.64) and sleep disturbance (mean = 2.08) as measured by a 5-point SDS (Redeker et al. 2000).
The present study reveals that 60% of patients receiving
cancer therapy suffered from a co-occurrence of any three
or all of the four symptoms. The high prevalence of the
co-occurrence of multiple symptoms in cancer settings
2012 Blackwell Publishing Ltd

indicates areas for continued research into symptom clusters and innovative treatment to target multiple symptoms. The results also show that patients with lung cancer
are associated with a greater risk of co-occurrence of any
three or all four of the MSFP symptoms. In a populationbased study to examine cancer symptoms and performance outcomes, Barbera et al. (2010) also found that lung
cancer patients had the worst burden of symptoms. Nevertheless, differences in the symptoms reported for cancer
subgroups require further investigation. Congruent with
other studies, the inter-correlation found in this study
between MSFP was mild to moderate (Gaston-Johansson
et al. 1999; Theobald 2004; Stepanski et al. 2009). There is
a growing volume of literature that supports its observations that MSFP occur concurrently and are interrelated.
Several other recent studies have shown that depression is
also often part of a cluster of interrelated symptoms,
including pain, fatigue and sleep disturbance (Redeker
et al. 2000; Theobald 2004). It has been suggested that the
link between pain and depression are reciprocally related.
Fatigue is another symptom related to both pain and
depression in cancer patients (Spiegel et al. 1994; Glover
et al. 1995; So et al. 2009). It is notable that sleep disturbance in the context of cancer seldom occurs by itself
and is more commonly clustered with pain, fatigue and
75

CHENG & YEUNG

depression (Redeker et al. 2000; Theobald 2004). Stepanski et al. (2009) studied the relationship between trouble
in sleeping, depressed moods, pain and fatigue in 11 445
cancer patients undergoing treatment in a large community oncology practice, and revealed that trouble in sleeping occurred in 55% of patients and was associated with
significantly increased fatigue, pain and depressed moods.
The same study indicated that the effect of depressed
moods on fatigue and pain was mediated by trouble in
sleeping, and the effect of trouble in sleeping on fatigue
was mediated by pain as shown by structural equation
modelling. The relationship between pain and sleep has
often been assumed to be reciprocal pain can lead to
disturbed sleep, and vice versa (Smith & Haythornthwaite
2004). A small body of research has accumulated which
suggests that there is a bi-directional link between depression and sleep disturbance (Ford & Kamerow 1989; Savard
& Morin 2001). In a study of patients with advanced
cancer receiving palliative care, Delgado-Guay et al.
(2011) revealed that patients with sleep disturbance were
more likely to report pain (P = 0.0132), depression (P =
0.019), anxiety (P = 0.01) and a poorer sense of well-being
(P = 0.035) compared with patients who did not experience
sleep disturbance. A sample of adult patients with lung
and colon cancer revealed that 56% attributed their sleep
disturbance to experiencing pain (Savard & Morin 2001).
Several studies have established relationships between
fatigue and sleep disturbance both during cancer treatment as well as after (Servaes et al. 2002; Hickok et al.
2005). Beck et al. (2005) examined the interrelationships
between symptoms of pain, fatigue and sleep disturbance,
and found that pain and sleep disturbance predicted
fatigue. In future, more empirical data are needed to determine the interrelationships and the complex patterns of
co-variation among MSFP symptoms, as well as the trajectories and response shift of the symptoms over the
course of cancer therapy in order to develop a robust
causal model of the symptoms in order to improve MSFP
management strategies.
The results in this study suggest an association
between the symptoms of MSFP, functional status and
QoL. Patients who had a co-occurrence of any three or all
four of the symptoms of MSFP reported the worst functional status and poorest QoL. Miaskowski et al. (2006)
and Pud et al. (2008) analysed 191 and 228 adults undergoing active cancer treatment respectively, and also
found that the subgroup of patients who had high levels
of MSFP reported poor functional status and QoL. In the
current study, one-fifth to half of the variance (2543%)
in functional status as well as physical, emotional and
functional well-being and total QoL was explained by the
76

symptoms of MSFP in patients receiving cancer therapy

after adjustment for gender, age, cancer diagnosis and
treatment modality. These findings are consistent with
those of Redeker et al. (2000) in whose study fatigue,
sleep disturbance, anxiety and depression together
explained 47% of the variance in QoL in patients undergoing initial chemotherapy for cancer. On the other hand,
our data revealed that all four of these symptoms have
less effect on the social well-being (9% of the variance) of
patients during cancer therapy. It is notable that the variables explaining the greatest proportion of the variance
in functional status were pain and fatigue. Dodd et al.
(2001) also revealed that the symptoms of pain and
fatigue contributed most to explaining the change in
functional status for patients receiving chemotherapy.
The findings in the present study also suggest that MSFP
appear to be equally important in explaining changes in
the functional sphere of QoL for patients receiving cancer
therapy. It was notable that pain and mood disturbance
had the greatest influence on physical QoL, while mood
disturbance and fatigue had the greatest influence on
emotional and total QoL. Redeker et al. (2000) studied
263 patients undergoing chemotherapy using the Profile
of Mood States. They found that depression, fatigue and
anxiety affected the patients QoL, and that depression
was the largest contributor. Undoubtedly, the experience
of the diagnosis and treatment of cancer for an individual
is a life episode that represents an emotional challenge.
The literature indicates that mood disturbance often
increase during the treatment period (Glajchen 1999;
Palesh et al. 2010) and should not be neglected. A previous review also indicated that the psychological burden
of the diagnosis and treatment of cancer can reach clinically significant levels (Martin & Cheng 2006). Nevertheless, it seems possible that mood disturbance was not
merely additive in its influence on the patients functional status and QoL. Rather, it would occur in association with sleep disturbance, fatigue and pain as a cluster
of symptoms that reinforce each other in an interactive
manner. Lenz et al. asserted that concurrent symptoms
are likely to result in an experience that is multiplicative
rather than additive (Lenz et al. 1997). More work is
needed to determine the causal nature of the relationships between these symptoms in patients and to support
this theoretical proposition.
The present study provides some insights contributing
to a better understanding of the prevalence, co-occurrence
and morbidities of MSFP symptoms in patients during
cancer therapy. These symptoms are critical and should be
monitored beyond the routine assessments of nausea
and vomiting, myelo-suppression and other biomedical
2012 Blackwell Publishing Ltd

Cancer therapy-related affective and somatic symptoms

toxicities during cancer therapy. Nevertheless, there were

limitations that might affect the interpretation of the
study findings. This study only described MSFP symptoms at a single point in time, and was subject to potential
confounders because of possible variation in the preexisting coping ability of the patients and the availability
of support mechanisms, as well as the presence of other
symptoms and the supportive care given to the patients. In
addition, the SDS adopted in this study to assess MSFP
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