Physiotherapy programme reduces fatigue in patients with advanced cancer receiving palliative care: randomized controlled trial

Abstract

Purpose:
Cancer-related fatigue (CRF) is a common and relevant symptom in patients with advanced cancer that significantly decreases their quality of life. The aim of this study was to evaluate the effect of a physiotherapy programme on CRF and other symptoms in patients diagnosed with advanced cancer.

Methods:
The study was designed as a randomized controlled trial. Sixty patients diagnosed with advanced cancer receiving palliative care were randomized into two groups: the treatment group (n = 30) and the control group (n = 30). The therapy took place three times a week for 2 weeks. The 30-min physiotherapy session included active exercises, myofascial release and proprioceptive neuromuscular facilitation (PNF) techniques. The control group did not exercise. The outcomes included Brief Fatigue Inventory (BFI), Edmonton Symptom Assessment Scale (ESAS) and satisfaction scores.

Results:
The exercise programme caused a significant reduction in fatigue scores (BFI) in terms of severity of fatigue and its impact on daily functioning. In the control group, no significant changes in the BFI were observed. Moreover, the physiotherapy programme improved patients' general well-being and reduced the intensity of coexisting symptoms such as pain, drowsiness, lack of appetite and depression. The analysis of satisfaction scores showed that it was also positively evaluated by patients.

Conclusion:
The physiotherapy programme, which included active exercises, myofascial release and PNF techniques, had beneficial effects on CRF and other symptoms in patients with advanced cancer who received palliative care. The results of the study suggest that physiotherapy is a safe and effective method of CRF management.

Full text

ORIGINAL ARTICLE
Physiotherapy programme reduces fatigue in patients
with advanced cancer receiving palliative care: randomized
controlled trial
Anna Pyszora
1
&Jacek Budzyński
2
&Agnieszka Wójcik
3
&Anna Prokop
4
&
Małgorzata Krajnik
1
Received: 18 October 2016 /Accepted: 4 May 2017 /Published online: 16 May 2017
#The Author(s) 2017. This article is an open access publication
Abstract
Purpose Cancer-related fatigue (CRF) is a common and rele-
vant symptom in patients with advanced cancer that signifi-
cantly decreases their quality of life. The aim of this study was
to evaluate the effect of a physiotherapy programme on CRF
and other symptoms in patients diagnosed with advanced
cancer.
Methods The study was designed as a randomized controlled
trial. Sixty patients diagnosed with advanced cancer receiving
palliative care were randomized into two groups: the treatment
group (n= 30) and the control group (n= 30). The therapy
took place three times a week for 2 weeks. The 30-min
physiotherapy session included active exercises, myofascial
release and proprioceptive neuromuscular facilitation (PNF)
techniques. The control group did not exercise. The outcomes
included Brief Fatigue Inventory (BFI), Edmonton Symptom
Assessment Scale (ESAS) and satisfaction scores.
Results The exercise programme caused a significant reduc-
tion in fatigue scores (BFI) in terms of severity of fatigue and
its impact on daily functioning. In the control group, no sig-
nificant changes in the BFI were observed. Moreover, the
physiotherapy programme improved patients’general well-
being and reduced the intensity of coexisting symptoms such
as pain, drowsiness, lack of appetite and depression. The anal-
ysis of satisfaction scores showed that it was also positively
evaluated by patients.
Conclusion The physiotherapy programme, which included
active exercises, myofascial release and PNF techniques, had
beneficial effects on CRF and other symptoms in patients with
advanced cancer who received palliative care. The results of
the study suggest that physiotherapy is a safe and effective
method of CRF management.
Keywords Physiotherapy .Cancer-related fatigue .
Exercises .Palliative care
Background
Cancer-related fatigue (CRF) is one of the most common and
complex symptoms experienced by patients diagnosed with
cancer. The National Comprehensive Cancer Network
(NCCN) defines CRF as Ba distressing, persistent, subjective
sense of physical, emotional, and/or cognitive tiredness or
exhaustion related to cancer or cancer treatment that is not
proportional to recent activity and interferes with usual
functioning^[1]. Fatigue associated with cancer has a
*Anna Pyszora
aniap30@wp.pl
Jacek Budzyński
budz@cps.pl
Agnieszka Wójcik
maw5@tlen.pl
Anna Prokop
agajewska@vp.pl
Małgorzata Krajnik
malgorzata.krajnik@wp.pl
1
Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus
Copernicus University in Toruń,Skłodowskiej –Curie 9,
85-094 Bydgoszcz, Poland
2
Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus
Copernicus University in Toruń, Ujejskiego 75,
85-168 Bydgoszcz, Poland
3
Faculty of Rehabilitation, Józef Piłsudski University of Physical
Education in Warsaw, Marymoncka 34, 00-968 Warszawa, Poland
4
The Blessed Father Jerzy Popiełuszko Hospice in Bydgoszcz, Ks.
Prałata Biniaka 3, 85-862 Bydgoszcz, Poland
Support Care Cancer (2017) 25:2899–2908
DOI 10.1007/s00520-017-3742-4
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

complex aetiology. It results from the interaction of two fac-
tors: those related to the disease itself or its treatment, and
reduced physical activity [2,3]. For this reason, the treatment
of CRF should be multi-faceted and include, among others,
physiotherapy [1]. The maintenance of physical activity plays
an important role in the treatment of fatigue. The application
of selected physiotherapy methods enables patients to increase
their physical activity, reduce fatigue and improve their func-
tional status, which has a direct positive impact on their qual-
ity of life [4–27]. The issues of evaluating the effectiveness of
physiotherapy programmes in the treatment of CRF have been
the subject of interest for numerous researchers. Most studies
were conducted in patient populations undergoing an inten-
sive anticancer regime (i.e. chemotherapy or radiation thera-
py) or those successfully treated [4–22]. Much less interest
was devoted to the merits of inclusion of physiotherapy in
the treatment of CRF in patients with advanced cancer who
are not given causal treatment anymore and receive palliative
care [23–27]. The following study constitutes an attempt to
assess the advisability of including physiotherapy as a treat-
ment for CRF in patients with advanced cancer who were
receiving palliative care. The aims of the study were to assess
the effect of authorial physiotherapy programme on the inten-
sity of CRF and comorbid symptoms and to evaluate whether
the patients were satisfied with such kind of treatment.
Methods
Participants
The study was designed as a randomized, controlled trial. The
study protocol was approved by the Bioethics Committee of
the L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus
Copernicus University in Torun (KB 156/2009). Participants
were recruited from the Palliative Care Department,
Bydgoszcz University Hospital No. 1 and from the in-
patient and home care provided by the Blessed Father
Popieluszko Hospice in Bydgoszcz between January 2010
and May 2011. Eligible patients admitted to the palliative care
service were identified by their physicians and informed about
the study. After giving their preliminary consent to participat-
ing in the study, patientswere offered detailed information and
had the opportunity to ask questions. Patients had 2 days to
decide whether to participate, which was confirmed by their
submission of written consent. The inclusion criteria were
diagnosis of advanced cancer, intensity of fatigue ≥4 in a 10-
point NRS (Numerical Rating Scale) obtained during the first
visit, survival expectancy of a month at the very least, func-
tional status allowing the patient to participate in the proposed
therapy, ≥18 years old and written consent to participate in the
study. The exclusion criteria were anaemia (haemoglobin
≤8 g/dl), the existence of comorbidities causing fatigue (e.g.
multiple sclerosis, Parkinson’s disease, heart failure), infection
requiring antibiotics, age <18 and inability to understand writ-
ten and spoken Polish.
Randomization
Patients were randomized into the therapy group and the con-
trol group at the ratio of 1:1. Patients were assigned to respec-
tive groups using a list of numbers ranked in no particular
order, with each new patient assigned a subsequent available
number from the list. Even numbers designated the therapy
group, while odd ones the control group.
Sample size calculation
At the planning stage of the research protocol, the number of
patients required to meet the objectives of the study was spec-
ified. The following assumptions were adopted for the calcu-
lation of the number of sub-groups: normal distribution of
obtained values in the sample, target test power >90% and
the value of statistical significance for the difference—alpha
<0.05 (type I error), beta (type II error) <10%, combined stan-
dard deviation (sigma) of 10% of the average and a two-way
test of the null hypothesis assuming no differences in mean
values of the studied parametres between the two groups.
Moreover, the following effectiveness criteria of the therapeu-
tic methods (differences in mean values of the evaluated
parametres) were applied:
&Comparison of two dependent means—effective final
treatment effect was defined as a 25% reduction in fatigue
after 2 weeks of physiotherapy [28–30]
&Comparison of two independent means (therapeutic and
control groups)—the final difference in fatigue severity
between the therapy group and the control group was set
at 25%
The required numbers were similar and totalled respective-
ly 21 and 23. Due to the specifics of the population studied—
the severity of the disease and the high risk of discontinuation
of the study due to deterioration in the general condition of the
patient or death, the target number of patients in each group
(therapy and control) was set at 30.
Main outcome measures
The primary outcomes were use to measure the severity of
fatigue and its impact on daily functioning and well-being
(Brief Fatigue Inventory—BFI) and intensity of other symp-
toms associated with the disease (Edmonton Symptom
Assessment Scale—ESAS).
The BFI has nine items, with the items measured on 0–10
numeric rating scales. Three items ask patients to rate the
2900 Support Care Cancer (2017) 25:2899–2908
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

severity of their fatigue at its Bworst^,Busual^and Bnow^
during normal waking hours, with 0 being Bno fatigue^and
10 being Bfatigue asbad as you can imagine^. Six items assess
the extent to which fatigue interfered with different aspects of
the patient’s life during the past 24 h. The interference items
include general activity, mood, walking ability, normal work
(includes both work outside the home and housework), rela-
tions with other people and enjoyment of life. The interference
items are measured on a 0–10 scale, with 0 being Bdoes not
interfere^and 10 being Bcompletely interferes^[31]. The se-
lection of this particular tool was dictated by its concise and
simple form as well as the capacity to assess both the fatigue
severity and its impact on patient’s daily activities.
ESAS assists in the assessment of nine symptoms common
in patients diagnosed with cancer: pain, fatigue, nausea, de-
pression, anxiety, drowsiness, appetite, well-being and breath-
lessness. The severity at the time of assessment of each symp-
tom is rated from 0 to 10 on a numerical scale, 0 meaning that
the symptom is absent and 10 that it is of the worst possible
severity [32].
Additionally, patient satisfaction was also evaluated in the
treatment group (satisfaction scores, SS). To that end, points
of satisfaction were used ranging from −3to+3(where−3
means complete dissatisfaction, 0 no change and +3 complete
satisfaction).
Additionally, data were collected on the following
variables:
&Demographic details such as gender, age and primary
diagnosis
&Karnofsky Performance Scale Index
Interventions
Patients in the therapy group were included into the physio-
therapy program. During the 2-week study period, there were
six therapy sessions in total (three per week). Each individual
session lasted 30 min. The physiotherapy programme includ-
ed active exercises of the upper and lower limbs, selected
techniques of myofascial release (MFR) and selected tech-
niques of proprioceptive neuromuscular facilitation (PNF).
Physiotherapy sessions were always conducted by the same
therapist, licensed in PNF method and trained in the applica-
tion of myofascial release techniques.
For the study design, see Fig. 1.
Parallel treatment
In line with the research protocol, no restrictions were im-
posed on parallel pharmacological treatment. Patients re-
ceived their previous medications, which were entered in the
clinical outcomes record. In the event that during the study a
patient was started on a new regimen that might affect fatigue
severity, it was decided that the patient should be excluded
from the statistical analysis evaluating the effect of physiother-
apy on CRF.
Additionally, throughout the study, the intensity of symp-
toms was monitored using ESAS.
The study protocol assumed that any increase in the sever-
ity of symptoms such as pain, nausea, depression, anxiety and
breathlessness by at least two points on a 0–10 scale (observed
during two consecutive visits) excluded a patient from the
statistical analysis that assessed the effect of physiotherapy
on CRF. Such an assumption was based on observations from
the study by Yennu et al. and Yennurajalingam et al. [33,34]
in an advanced cancer population, which showed that the in-
tensity of these symptoms strongly correlated with fatigue
severity.
Statistical analysis
The statistical analysis of the study results was performed
using Statistica 9.1 for Windows.
DAY 0, VISIT 1
- qualification for the study (inclusion/exclusion criteria)
- Karnofsky Performance Scale Index
- obtaining patient consent
- randomization
Randomized patients
(n=60)
THERAPY GROUP
(n=30)
DAY 1
BFI, ESAS, THERAPY
DAY 3
BFI, ESAS, THERAPY
DAY 5
BFI, ESAS, THERAPY
DAY 8
BFI, ESAS, THERAPY
DAY 10
BFI, ESAS, THERAPY
DAY 12
BFI, ESAS, THERAPY
CONTROL GROUP
(n=30)
DAY 1
BFI, ESAS
DAY 3
BFI, ESAS
DAY 5
BFI, ESAS
DAY 8
BFI, ESAS
DAY 10
BFI, ESAS
DAY 12
BFI, ESAS
Withdrawn (n=1).
Death
Withdrawn (n=1).
Death
Completed trial (n=29)
Excluded from analysis
(n=1)
Completed trial (n=29)
Excluded from analys is
(n=1)
Fig. 1 Study design
Support Care Cancer (2017) 25:2899–2908 2901
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

The obtained data are presented as mean or median
values ± SD (standard deviation) or 95% CI (confidence in-
terval). The distribution of variables was verified using the
Shapiro-Wilk test. Comparisons of statistical significance of
differences between the median values of parametres on suc-
cessive observation days and between groups were performed
using one- and two-way ANOVA (analysis of variance) with
an appropriate number of repeats. In order to assess the sig-
nificance of differences in the tested parametres at individual
measurement points, a post hoc LSD (least significant differ-
ence) test was used. The significance of differences between
mean values in the treatment and control groups was assessed
using Student’sttest for independent samples (normal vari-
able distribution) or the Mann-Whitney Utest. The power of
the statistical analysis was 90%; the differences between
groups or the analysed time points were considered statistical-
ly significant at P<0.05.
Results
Characteristics of study participants
The study included 60 patients (n= 60). Participants were
randomized into the therapy group and the control group at
the ratio of 1:1. Study groups (therapy and control) did not
differ significantly with respect to age, tumour location and
the study site. However, a significant gender difference was
observed with respect to the assignment to the control or ther-
apy groups, respectively (P= 0.03). Demographic and clinical
characteristics of the patients qualified for the study are shown
in Table 1.
Parallel treatment
In the course of the study, drug regimen was modified in two
patients (one in each group) whose general condition had de-
teriorated, which excluded them from the study. These pa-
tients were also excluded from the statistical analysis of the
impact of physiotherapy on the fatigue level. None out of the
60 patients in the study sample was on the anticancer therapy.
Discontinuation of the study
The study was discontinued for two patients (n=1,therapy
group and n= 1, control group). The cause of their death was
advanced cancer. Those patients were excluded from the sta-
tistical analysis of the impact of physiotherapy on the severity
of fatigue. They were the same patients who needed modified
pharmacological treatment.
Effect of physiotherapy program on fatigue (BFI)
The analysis of the impact of physiotherapy program on the
severity of fatigue included 29 patients from the treatment
group and 29 patients from the control group. It was found
that physiotherapy program significantly reduced fatigue se-
verity in patients evaluated using the BFI. After 12 days, the
results demonstrated a significant decrease in fatigue scores
(BFI) compared with baseline (Wilcoxon test):
&In the treatment group on all the questions, mean score
6.4 ± 1.0 vs. 4.4 ± 1.4, P<0.01
&In the control group on questions 1 and 3, mean score
6.13 ± 1.4 vs. 5.9 ± 1.44, P<0.01
As compared with the control group, the treated individuals
had significantly lower scores on the BFI on questions 1, 2, 3,
4a, 4b, 4e and 4f. Significant differences were observed on
average as of day 8 of physiotherapy (Figs. 2and 3).
Impact of physiotherapy program on the severity
of fatigue and other symptoms (ESAS)
Throughout the study, the severity of symptoms was evaluated
using ESAS both in the treatment and in the control groups. At
baseline, no significant differences were observed regarding
ESAS parametre values between the groups (Table 2).
However, the comparison of scores for individual symptoms
between baseline and the evaluation at the end of the study
revealed a statistically significant beneficial effect of therapy
in terms of reduced severity of the following: pain, fatigue,
depression, anxiety, drowsiness, well-being and improved ap-
petite (P< 0.01) (Table 3). Similar effects were not observed
in the control group (Table 4). After 14 days of physiotherapy,
the therapy group compared with the control group reported a
statistically significant reduced severity of fatigue and drows-
iness; moreover, patients in the therapy group rated their well-
being higher (Table 2, Fig. 4).
Satisfaction with physiotherapy program
At the end of physiotherapy program, the mean level of patient
satisfaction was 1.6 ± 0.8 (min. = 0, max. = 3). Of the 29
patients under observation, 26 rated the therapy as positive
(+3, n=3;+2,n= 14; +1, n= 9), whereas three patients rated
it as neither positive nor negative.
Discussion
One of the elements of multifaceted symptom management in
palliative care is physiotherapy. The main aim of physiother-
apy in this patient population is to improve quality of life by
2902 Support Care Cancer (2017) 25:2899–2908
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

way of alleviating troublesome symptoms and allowing the
patients to function at an optimal level [35]. The effectiveness
of physiotherapy in the treatment of selected symptoms in
patients with advanced cancer has been confirmed on numer-
ous occasions. These symptoms include, among others,
myofascial pain, lymphoedema, breathlessness, constipation
or motor deficits secondary to neurological disorders [36–41].
CRF is rarely recognized as an indication for physiothera-
py. The effect of physiotherapy programs on CRF in patients
with advanced cancer had not been extensively studied. So far,
the issue of physical exercises used for relieving fatigue in
patients with advanced cancer was analysed only by Porock
et al., Buss et al., Oldervoll et al., Van den Dungen et al. and
Cheville et al. [24–28]. In their study, Porock et al. [24]
Fig. 2 Mean change in BFI score
from baseline (questions 1–3).
Legend: rate your (1) level of fa-
tigue right now, (2) level of fa-
tigue during the past 24 h, and (3)
the worst level of fatigue during
the past 24 h
Tabl e 1 Demographic and
clinical characteristics of patients
qualified for the study
Data Therapy group Control group P
Age (mean ± SD) 72.4 ± 9.5 69.3 ± 13.7 0.32
Gender F = 15 (50%) F = 24 (80%) 0.03
M = 15 (50%) M = 6 (20%)
Tumour location Alimentary system, n= 7 Alimentary system, n= 8 0.33
Urogenital system, n= 8 Urogenital system, n=5
Lung, n=2 Lung,n=3
CNS, n= 4 CNS, n=1
Mammary gland, n= 2 Mammary gland, n=6
Haematological, n= 2 Haematological, n=4
Indefinite origin, n= 4 Indefinite origin, n=2
Mouth, n= 1 Skin, n=1
Study site Home care, n=24 Homecare,n=21 0.54
Hospice, n= 3 Hospice, n=6
PCD, n= 3 PCD, n=3
KPSI 46.0 ± 7.2 48.0 ± 11.0 0.41
Fatigue
NRS, 0–10
6.8 ± 1.1 6.5 ± 1.4 0.41
Pborderline level of statistical significance, SD standard deviation, Mmale, Ffemale, CNS central nervous
system, PCD palliative care department, KPSI Karnofsky Performance Scale Index, NRS numeric rating scale
Support Care Cancer (2017) 25:2899–2908 2903
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

included only 11 patients with advanced cancer, suffering
from fatigue. The study lasted 28 days and patients did not
follow a single exercise therapy. The therapy involved exer-
cises in bed, exercises in a sitting position, treadmill walking,
cycle-ergometer exercises and dancing to the rhythm of
favourite music. The exercise programs were tailored to the
needs and physical capacity of individual patients. Therefore,
individual interventions differed significantly in duration
(ranging from 22 to 180 min per week). Although the authors
did not observe any significant reduction in fatigue levels
within the studied group, they pointed to the fact that the
therapy regimens patients received did not increase their
Fig. 3 Mean change inBFI score from baseline(questions 4a–4f). Legend: rate how fatiguehas interfered with the following: 4a—general activity, 4b—
mood, 4c—walking ability, 4d—normal work, 4e—relations with other people and 4f—enjoyment of life).
Tabl e 2 Scores representing the
severity of symptoms evaluated
using ESAS in both subsets at
baseline and after 12 days of
physiotherapy
Symptoms (ESAS) Treatment group (n= 29) Control group (n=29) P
pain_1 1.5 ± 1.9 1.7 ± 2.1 0.6
fatigue_1 6.8 ± 1.1 6.5 ± 1.4 0.4
nausea_1 0.4 ± 1.0 1.1 ± 2.2 0.1
depression_1 2.9 ± 2.3 2.9 ± 2.5 0.9
anxiety_1 2.7 ± 2.3 2.7 ± 2.5 1.0
drowsiness_1 3.6 ± 2.9 4.0 ± 2.7 0.6
appetite_1 4.3 ± 2.9 4.0 ± 3.0 0.7
well-being_1 4.8 ± 0.9 5.3 ± 1.3 0.1
breathlessness_1 1.0 ± 1.8 0.9 ± 1.6 0.9
pain_12 1.2 ± 1.5 1.7 ± 2.0 0.2
fatigue_12 4.6 ± 1.6 6.3 ± 1.2 <0.01
nausea_12 0.3 ± 0.8 0.9 ± 2.0 0.1
depression_12 2.7 ± 2.1 2.8 ± 2.6 0.8
anxiety_12 2.5 ± 2.1 2.5 ± 2.5 0.9
drowsiness_12 2.3 ± 2.1 3.8 ± 2.7 <0.05
appetite_12 3.1 ± 2.5 3.8 ± 2.8 0.4
well-being_12 3.0 ± 1.2 5.0 ± 1.3 <0.01
breathlessness_12 0.8 ± 1.5 0.9 ± 1.6 0.7
ESAS Edmonton Symptom Assessment Scale, Pborderline level of significance
2904 Support Care Cancer (2017) 25:2899–2908
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

fatigue levels. Furthermore, the applied therapy regimens
were positively evaluated by the patients, as they tangibly
increased patients’daily physical activity. Buss et al. also
attempted to assess the effectiveness of exercise interventions
in reducing fatigue in the terminal hospice cancer patients
[25]. They assessed the effect of a single, well-defined, repro-
ducible across the entire group of patients’exercise program
on quality of life and fatigue in the hospice terminal cancer
patients. The study group comprised 38 patients. Their analy-
sis showed that, on average, after 3 weeks of a physical ther-
apy exercise program, a significant decrease in fatigue levels
was observed, while in the control group, it increased after
2 weeks of observation. It should be noted, however, that
patients with short life expectancy (approx. 1–2 months) were
among those admitted into the study by Buss et al. A similar
criterion was used in the present study, i.e. approx. 1–
3 months. For that reason, a timeline for the study was set at
2 weeks. Extending time frames of interventions in the case of
short life expectancy patients increases a risk of their non-
completion of a study. This is usually associated with deteri-
oration of general condition, disease progression or death.
Oldevoll et al. [26] pursued their study for 8 weeks. Patients
with advanced cancer with a life expectancy <2 years were
included in the study. Out of 231 patients, 68 (29%) were lost
as a result of disease progression. The study evaluated the
effects of a group exercise intervention, supervised by a phys-
iotherapist. The exercise group had two exercise sessions per
week over an 8-week period. Each session lasted 50–60 min
and included a warm-up (10–15 min), circuit training with six
stations (30 min) and stretching/relaxation (10–15 min). The
analysis showed no significant reduction in fatigue levels in
the study group. The applied intervention enhanced physical
performance. The gait and muscle strength test results were
significantly improved after 8 weeks of physical exercise.
Improvement in physical fitness was also noted by van den
Dungen et al. [27]. Their non-randomized pilot study com-
prised 26 palliative care patients with advanced cancer.
Participants followed an individually graded group exercise
program, consisting of resistance training and aerobic exer-
cise, twice a week during 6 weeks. Apart from improved
physical fitness, the authors observed improved quality of life
and reduced fatigue in patients. Cheville et al. [28] assessed
the effectiveness of a home-based physiotherapy. Sixty-six
adults with stage IV lung or colorectal cancer were admitted
into the study. They were randomized, in an 8-week trial, to
usual care or incremental walking and home-based strength
training. The exercising participants were instructed during a
single physiotherapy visit and subsequently exercised 4 days
or more per week; training and step-count goals were ad-
vanced during bimonthly telephone calls. A home-based ex-
ercise program seems capable of improving the mobility, fa-
tigue and sleep quality of patients with stage IV lung and
colorectal cancer.
Much more research on the evaluation of physiotherapy
treatment in terms of CRF reduction was conducted in popu-
lations of patients undergoing an intensive oncological regi-
men and those who have been successfully treated. Results of
research in this area show that the treatment groups achieve a
statistically more effective fatigue reduction compared with
controls. The authors have identified exercise as a beneficial
and valuable form of treatment for fatigue among patients
undergoing intensive anticancer therapy and patients with
chronic fatigue that persists despite completed oncological
treatment. At the same time, they signalled the need for re-
search aimed at optimizing the type, intensity and duration of
specific therapeutic interventions. The need to develop clear
guidelines on the use of physiotherapy in the treatment of
fatigue was also confirmed by a survey conducted among
British physiotherapists working with cancer patients and
Tabl e 3 Scores representing the severity of symptoms evaluated using
ESAS in the treatment group at baseline and after 12 days of
physiotherapy
Symptoms (ESAS) symptom_1 symptom_12 P
Pain 1.5 ± 1.9 1.2 ± 1.5 <0.01
Fatigue 6.8 ± 1.1 4.6 ± 1.6 <0.01
Nausea 0.4 ± 1.0 0.3 ± 0.8 0.08
Depression 2.9 ± 2.3 2.7 ± 2.1 <0.01
Anxiety 2.7 ± 2.3 2.5 ± 2.1 <0.01
Drowsiness 3.6 ± 2.9 2.3 ± 2.1 <0.01
Appetite 4.3 ± 2.9 3.1 ± 2.5 <0.01
Well-being 4.8 ± 0.9 3.0 ± 1.2 <0.01
Breathlessness 1.0 ± 1.8 0.8 ± 1.5 0.18
symptom_1 intensity of a particular symptom on day 1 of observation,
symptom_12 intensity of a particular symptom on day 12 of observation,
ESAS Edmonton Symptom Assessment Scale, Pborderline level of
significance
Tabl e 4 Scores representing the severity of symptoms evaluated using
ESAS in the control group at baseline and after 12 days of physiotherapy
Symptoms (ESAS) symptom_1 symptom_12 P
Pain 1.7 ± 2.1 1.7 ± 2.0 0.16
Fatigue 6.5 ± 1.4 6.3 ± 1.2 0.031
Nausea 1.1 ± 2.2 0.9 ± 2.0 0.33
Depression 2.9 ± 2.5 2.8 ± 2.6 0.33
Anxiety 2.7 ± 2.5 2.5 ± 2.5 0.16
Drowsiness 4.0 ± 2.7 3.8 ± 2.7 0.08
Appetite 4.0 ± 3.0 3.8 ± 2.8 0.057
Well-being 5.3 ± 1.3 5.0 ± 1.3 0.022
Breathlessness 0.9 ± 1.6 0.9 ± 1.6 1.0
symptom_1 intensity of a particular symptom on day 1 of observation,
symptom_12 intensity of a particular symptom on day 12 of observation,
ESAS Edmonton Symptom Assessment Scale, Pborderline level of
significance
Support Care Cancer (2017) 25:2899–2908 2905
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

members of the Association of Chartered Physiotherapists in
Oncology and Palliative Care (ACPOPC) [42].
Studies evaluating the effectiveness of selected physiother-
apy methods in the treatment of fatigue support the use of this
form of therapy among patients diagnosed with cancer.
However, there are substantial differences among individual
researchers concerning the duration of the therapy and its fre-
quency. The authors of the publications studied, among
others, the effectiveness of an exercise regimen carried out
individually or in groups 2–7timesaweekfor2–8weeks.
The duration of a single therapy session ranged from 20 to
90 min. The protocol adopted for the present study included
30-min physiotherapy sessions three times a week for 2 weeks.
The planned follow-up period proved to be long enough to
observe changes in fatigue severity due to physiotherapy,
since statistically significant differences were already ob-
served on average as of day 8 of the intervention.
Simultaneously, in the vast majority of patients (n=58),there
was no disease progression or increased severity of symp-
toms; hence, they did not require additional pharmacological
treatment. The comparison of ESAS scores between baseline
and the day the observation ended showed statistically signif-
icant beneficial effects of the physiotherapy. It may have had a
significant impact on the high level of treatment satisfaction.
The proposed physiotherapy program, including active ex-
ercises of upper and lower extremities, selected techniques of
myofascial relaxation and PNF, was devised by the author of
the study. The selection of individual components of the treat-
ment program reflected the desire to devise a treatment plan
specially tailored to the condition of the patients participating
in the study. However, the formulation of specific guidelines
on physical therapy programs used as part of fatigue treatment
requires more research. In most published studies, the selec-
tion of specific physiotherapy techniques is quite varied.
Therapies include, among others, active exercises (resisted
and unresisted), balance exercises, breathing and relaxation
and ergometer training [4–27]. The selection of specific ther-
apies should be based on a careful individual analysis of the
potential and limitations of particular patients. This is espe-
cially important in a population of patients diagnosed with
advanced cancer receiving palliative care. They tend to be
reluctant to undertake physical activity giving reasons such
as limited fitness and functional capacity [43]. Moreover, in
this population, fatigue is often accompanied by the anorexia-
cachexia syndrome. The patient who notes a progressive loss
of body mass and suffers from anorexia, whose fatigue in-
creases with each movement, may at first refuse to participate
in any treatment proposed by a physiotherapist for fear that
his/her exhaustion may increase. Hence, the physiotherapy
program should include both the treatment elements that do
not require large expenditures of energy on the part of the
patients and methods that actively engage them. For this rea-
son, the proposed program included relaxation techniques
(myofascial relaxation, breathing stimulation) and more active
methods (active exercises, selected PNF techniques).
The rationale for the use of this kind of fatigue treatment
programs was evaluated in studies conducted by Fernández-
Lao et al. [44,45] among patients with breast cancer once they
completed their anticancer treatment. The proposed physio-
therapy regime included core stability exercises and elements
Fig. 4 Self-rated severity of
symptoms on consecutive
observation days (ESAS)
2906 Support Care Cancer (2017) 25:2899–2908
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

of myofascial release. Results of the study indicate a high
effectiveness of the proposed physiotherapy program in re-
lieving fatigue and other symptoms associated with anxiety
and depression. Moreover, the treatments improved the pa-
tients’muscle strength and their overall fitness. Similar posi-
tive therapeutic effects were not observed in the control group.
In devising physiotherapy programs for the treatment of
fatigue, it is very important to include simple exercises easy
to remember by the patient. The inclusion of such therapy
forms is of great importance since they can be used as part
of movement activation exercises to be performed by each
patient individually.
The results of the present study clearly demonstrate that
cancer-related fatigue in patients with advanced cancer consti-
tutes an indication for the inclusion of physiotherapy in their
non-pharmacological treatment. However, the issue requires
more detailed research involving large groups of advanced
cancer patients receiving palliative, hospice and home care,
respectively.
The main limitation of the study was the fact that despite
the randomization, the process of group assignment itself
showed a significant association with gender (P=0.03).Itis
worth noting, however, that there was no significant correla-
tion between gender and the effect of physiotherapy on the
severity of fatigue.
Conclusions
The proposed physiotherapy program significantly reduces
the severity of fatigue in patients diagnosed with advanced
cancer receiving palliative care. Additionally, this program
improves the general well-being of patients and reduces the
severity of their comorbid symptoms, especially pain, drows-
iness, loss of appetite and depression. The proposed physio-
therapy program was positively rated by patients who com-
pleted treatment satisfaction questionnaire. Non-
pharmacological treatment of fatigue in advanced cancer pa-
tients receiving palliative care should include an appropriate
selection of physiotherapy methods.
ANOVA, analysis of variance; BFI, Brief Fatigue
Inventory; CI, confidence interval; CRF, cancer-related fa-
tigue; ESAS, Edmonton Symptom Assessment Scale; LSD,
least significant difference; MFR, myofascial release; NCCN,
National Comprehensive Cancer Network; NRS, Numerical
Rating Scale; P, borderline level of statistical significance;
PNF, proprioceptive neuromuscular facilitation; SD, standard
deviation; SS, satisfaction scores
Acknowledgments The authors thank all medical and nursing staff of
the Blessed Father Jerzy Popieluszko Hospice in Bydgoszcz and of the
Palliative Care Department, University Hospital No. 1 in Bydgoszcz,
where patients were recruited. Finally, the authors wish to thank all the
participating patients.
Authors’contributions AP conceived the idea for the study. AP, MK,
JB and AW contributed to the design of the research. AP and APr were
involved in data collection. AP, MK and JB analysed the data. MK coor-
dinated funding for the project (institutional funding). All authors edited
and approved the final version of manuscript.
Compliance with ethical standards
Competing interests The authors declare that they have no competing
interests.
Funding Funding for this study was provided by the Nicolaus
Copernicus University Collegium Medicum, Bydgoszcz, Poland (institu-
tional funding).
Consent for publication Not applicable.
Ethical approval and consent to participate Written informed con-
sent was obtained from all participants. Confidentiality and anonymity
were guaranteed. The study protocol was approved by the Bioethics
Committee of the L. Rydygier Collegium Medicum in Bydgoszcz,
Nicolaus Copernicus University in Torun (KB 156/2009).
Open Access This article is distributed under the terms of the Creative
Commons Attribution-NonCommercial 4.0 International License (http://
creativecommons.org/licenses/by-nc/4.0/), which permits any noncom-
mercial use, distribution, and reproduction in any medium, provided
you give appropriate credit to the original author(s) and the source, pro-
vide a link to the Creative Commons license, and indicate if changes were
made.
References
1. NCCN Clinical practice guidelines in oncology: cancer-related fa-
tigue, version I.2017 - December 19, 2016 https://www.nccn.org/
professionals/physician_gls/pdf/fatigue.pdf. Accessed 22 Jan 2017
2. Winningham ML, Nail LM, Burke MB et al (1994) Fatigue and
cancer experience. Oncol Nurs Forum 2:23–36
3. Peters ME, Goedendorp MM, Verhagen CA et al (2016) Fatigue
and its associated psychosocial factors in cancer patients on active
palliative treatment measured over time. Support Care Cancer 24:
1349–1355. doi:10.1007/s00520-015-2909-0
4. Windsor PM, Nicol KF, Potter J (2004) A randomized controlled
trial of aerobic exercise for treatment-related fatigue in men receiv-
ing radical external beam radiotherapy for localized prostate carci-
noma. Cancer 3:550–557
5. Mock V, Dow KH, Meares C et al (1997) Effects of exercise on
fatigue, physical functioning and emotional distress during radia-
tion therapy for breast cancer. Oncol Nurs Forum 24:991–1000
6. Schwartz A, Mor M, Gao R et al (2001) Exercise reduces daily
fatigue in women with breast cancer receiving chemotherapy.
Med Sci Sports Exerc 33:717–723
7. Segal R, Reid R, Courneya KS et al (2003) Resistance exercise in
men receiving androgen deprivation therapy for prostate cancer. J
Clin Oncol 21:1653–1659
8. Duijts SF, Faber MM, Oldenburg HS et al (2011) Effectiveness of
behavioral techniques and physical exercise on psychosocial func-
tioning and health-related quality of life in breast cancer patients
and survivors—a meta-analysis. Psychooncology 2:115–126
Support Care Cancer (2017) 25:2899–2908 2907
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

9. Losito JM, Murphy SO, Thomas ML (2006) The effects of group
exercise on fatigue and quality of life during cancer treatment.
Oncol Nurs Forum 4:821–825
10. Campbell A, Mutrie N, White F et al (2005) A pilot study of a
supervised group exercise program as a rehabilitant treatment for
women with breast cancer receiving adjuvant treatment. Eur J of
Oncol Nurs 9:56–63
11. Courneya KS, Mackey JR, Jones LW (2000) Coping with cancer.
Can exercise help? Phys Sportsmed 28:49–73
12. Courneya KS, Segal R, Mackey J et al (2007) Effect of aerobic and
resistance exercise in breast cancer patients receiving adjuvant che-
motherapy: a multicenter randomized controlled trial. J Clin Oncol
25:4396–4404
13. Adamsen L, Midtgaard J, Rorth M et al (2003) Feasibility, physical
capacity, and health benefits of a multidimensional exercise pro-
gram for cancer patients undergoing chemotherapy. Support Care
Cancer 11:707–716
14. Conn V, Hafdahl A, Porock D et al (2006) A meta-analysis of
exercise interventions among people treated for cancer. Support
Care Cancer 14:699–712
15. Cramp F, Daniel J (2008) Exercise for the management of cancer-
related fatigue in adults (review). Cochrane Database Sys Rev. doi:
10.1002/14651858.CD006145
16. Knobel H, Loge JH, Nordøy T et al (2000) High level of fatigue in
lymphoma patients treated with high dose therapy. J Pain Symptom
Manag 6:446–456
17. Bower JE, Ganz PA, Aziz N et al (2003) T-cell homeostasis in
breast cancer survivors with persistent fatigue. J Natl Cancer Inst
15:1165–1168
18. Fosså SD, Dahl AA, Loge JH (2003) Fatigue, anxiety, and depres-
sion in long-term survivors of testicular cancer. J Clin Oncol 7:
1249–1254
19. Rüffer JU, Flechtner H, Tralls P et al (2003) Fatigue in long-term
survivors of Hodgkin’s lymphoma; a report from the German
Hodgkin Lymphoma Study Group (GHSG). Eur J Cancer 15:
2179–2186
20. Weert E, Hoekstra-Weebers J, Otter R et al (2006) Cancer-related
fatigue: predictors and effects of rehabilitation. Oncologist 11:184–
196
21. Courneya KS, Mackey JR, Bell GJ et al (2003) Randomized con-
trolled trial of exercise training in postmenopausal breast cancer
survivors: cardiopulmonary and quality of life outcomes. J Clin
Oncol 9:1660–1668
22. Dimeo CF, Thomas F, Raabe-Manssen C et al (2004) Effect of
aerobic exercise and relaxation training on fatigue and physical
performance of cancer patients after surgery. A randomized con-
trolled trial. Support Care Cancer 12:774–779
23. Porock D, Kristjanson LJ, Tinnelly K et al (2000) An exercise
intervention for advanced cancer patients experiencing fatigue: a
pilot study. J Palliat Care 3:30–36
24. Buss T, de Walden-Gałuszko K, Modlińska A (2010) Kinesitherapy
alleviates fatigue in terminal hospice cancer patients—an experi-
mental, controlled study. Support Care Cancer 6:743–749
25. Oldervoll LM,Loge J, Lydersen S et al (2011) Physical exercise for
cancer patients with advanced disease: a randomized controlled
trial. Oncologist 16:1649–1657
26. van den Dungen IA, Verhagen CA, Van den Graaf WT et al (2014)
Feasibility and impact of a physical exercise program in patients
with advanced cancer: a pilot study. J Palliat Med. doi:10.1089/jpm.
2013.0638
27. Cheville AL., Kollasch J, Vandenberg J et al. (2012) A home-based
exercise program to improve function, fatigue, and sleep quality in
patients with IV stage lung cancer and colorectal cancer: a random-
ized controlled trial. doi: 10.1016/j.jpainsymman.2012.05.006
28. Reddy S, Bruera E, Pace A et al (2007) Clinically important im-
provement in the intensity of fatigue in patients with advanced
cancer. J Palliat Med 5:1068–1075
29. Cella D, Eton DT, Lai JS et al (2002) Combining anchor and
distribution-based methods to derive minimal clinically important
differences on the Functional Assessment of Cancer Therapy
(FACT) anemia and fatigue scales. J Pain Symptom Manag 24:
547–561
30. Patrick DL, Gagnon DD, Zagari MJ (2003) Assessing the clinical
significance of health-related quality of life (HRQoL) improve-
ments in anaemic cancer patients receiving epoetin alfa. Eur J
Cancer 39:335–345
31. Mendoza TR, Wang XS, Cleeland CS et al (1999) The rapid assess-
ment of fatigue severity in cancer patients. Use of the Brief Fatigue
Inventory. Cancer 85:1186–1196
32. Bruera E, Kuehn N, Miller MJ et al (1991) The Edmonton
Symptom Assessment System (ESAS): a simple method for the
assessment of palliative care patients. J Palliat Care 7:6–9
33. Yennu S, Urbauer DL, Bruera E (2012) Factors associated with the
severity and improvement of fatigue in patients with advanced can-
cer presenting to an outpatient palliative care clinic. BMC Palliative
Care 11:16. doi:10.1186/1472-684X-11-16
34. Yennurajalingam S, Palmer JL, Zhang T et al (2008) Association
between fatigue and other cancer-related symptoms in patients with
advanced cancer. Support Care Cancer 16:1125–1130
35. Tookman AJ, Hopkins K, Scharpen-von-Heussen K (2004)
Rehabilitation in palliative medicine. In: Doyle D, Hanks G,
Cherny N, Calman K (eds) Textbook of palliative medicine, 3rd
edn. Oxford University Press, Oxford, pp 1021–1032
36. Hately J, Laurence V, Scott A et al (2003) Breathlessness clinics
within palliative care settings can improve the quality of life and
functional capacity of patients with lung cancer. Palliat Med 17:
410–417
37. Belletti M, Mallia L, Lucidi F et al (2010) Complementary therapy
and support services for formal and informal caregivers in Italian
palliative care hospices: an exploratory and descriptive study. doi:
10.1007/s00520-010-1034-3
38. Cassileth BR, Vickers AJ (2004) Massage therapy for symptom
control: outcome study at a major cancer centre. J Pain Symptom
Manag 3:244–249
39. Polubiński JP, West L (2005) Implementation of a massage therapy
program in the home hospice setting. J Pain Symptom Manag 1:
104–106
40. Preece J (2002) Introducing abdominal massage in palliative care
for the relief of constipation. Compl Ther Nurs Midwifery 8:101–
105
41. Pyszora A, Wójcik A, Krajnik M (2010) Are soft tissue therapies
and Kinesio Taping useful for symptom management in palliative
care? Three case reports. Adv Pall Med 3:89–94
42. Donnelly CM, Lowe-Strong A, Rankin JP et al (2010)
Physiotherapy management of cancer-related fatigue: a survey of
UK current practice. Support Care Cancer 7:817–825
43. Blaney J, Lowe-Strong A, Rankin J et al (2010) The cancer reha-
bilitation journey: barriers to and facilitators of exercise among
patients with cancer-related fatigue. Phys Ther 8:1135–1147
44. Fernández-Lao C, Cantarero-Villanueva I, Díaz-Rodríguez L et al
(2012) Attitudes towards massage modify effects of manual therapy
in breast cancer survivors: a randomizedclinical trial with crossover
design. Eur J Cancer Care 2:233–241
45. Cantarero-Villanueva I, Fernández-Lao C, Del Moral-Avila R
(2012) Effectiveness of core stability exercises and recovery
myofascial release massage on fatigue in breast cancer survivors:
a randomized controlled clinical trial. Evid Based Complement
Alternat Med. doi:10.1155/2012/620619
2908 Support Care Cancer (2017) 25:2899–2908
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

1.
2.
3.
4.
5.
6.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com