Cancer Treatment Reviews 40 (2014) 327–340

Contents lists available at SciVerse ScienceDirect

Cancer Treatment Reviews

journal homepage: www.elsevierhealth.com/journals/ctrv

General and Supportive Care

Evidence-based physical activity guidelines for cancer survivors: Current

guidelines, knowledge gaps and future research directions
L.M. Buffart a,⇑, D.A. Galvão b,1, J. Brug a,2, M.J.M. Chinapaw c,3, R.U. Newton b,4
a
EMGO Institute for Health and Care Research and the VU University Medical Center, Department of Epidemiology and Biostatistics, Van der Boechorststraat 7,
1081 BT Amsterdam, The Netherlands
b
Edith Cowan University Health and Wellness Institute, Edith Cowan University, Joondalup, WA 6027, Australia
c
EMGO Institute for Health and Care Research and the VU University Medical Center, Department of Public and Occupational Health, Van der Boechorststraat 7,
1081 BT Amsterdam, The Netherlands

a r t i c l e i n f o a b s t r a c t

Article history: Physical activity during and after cancer treatment has beneficial effects on a number of physical and psy-
Received 7 February 2013 chosocial outcomes. This paper aims to discuss the existing physical activity guidelines for cancer survi-
Received in revised form 20 June 2013 vors and to describe future research directions to optimize prescriptions. Studies on physical activity
Accepted 25 June 2013
during and after cancer treatment were searched in PubMed, Clinicaltrials.gov, Australian New Zealand
Clinical Trials Registry, and Dutch Trial registry. Physical activity guidelines for cancer survivors suggest
that physical activity should be an integral and continuous part of care for all cancer survivors. However,
Keywords:
the development of these guidelines has been limited by the research conducted. To be able to develop
Exercise
Health
more specific guidelines, future studies should focus on identifying clinical, personal, physical, psychoso-
Neoplasms cial, and intervention moderators explaining ‘for whom’ or ‘under what circumstances’ interventions
Physical activity work. Further, more insight into the working mechanisms of exercise interventions on health outcomes
Quality of life in cancer survivors is needed to improve the efficacy and efficiency of interventions. Finally, existing pro-
Review grams should embrace interests and preferences of patients to facilitate optimal uptake of interventions.
In conclusion, current physical activity guidelines for cancer survivors are generic, and research is needed
to develop more personalized physical activity guidelines.
Ó 2013 Elsevier Ltd. All rights reserved.

Introduction [6]. Several reviews and meta-analyses demonstrate beneficial ef-

In developed countries, approximately one in three persons will
be directly affected by cancer before the age of 75 years, with breast
cancer, prostate cancer, lung cancer and colorectal cancer the most
common diagnoses [1]. It has been estimated that 12.7 million can-
cer cases and 7.6 million cancer deaths occurred worldwide in 2008
[1]. Advances in early detection and treatment have improved sur-
vival rates over the past decades, with approximately 60% of pa-
tients living over 5 years after diagnosis [2,3]. However, cancer
and its treatment are often associated with physical and psychoso-
cial problems, negatively affecting quality of life (QoL) [4,5].
Anyone who has been diagnosed with cancer, from the time of
diagnosis through the rest of life, is considered a cancer survivor
⇑ Corresponding author. Tel.: +31 20 444 9931; fax: +31 20 444 8387.
E-mail addresses: l.buffart@vumc.nl (L.M. Buffart), d.galvao@ecu.edu.au
(D.A. Galvão), j.brug@vumc.nl (J. Brug), m.chinapaw@vumc.nl (M.J.M. Chinapaw),
r.newton@ecu.edu.au (R.U. Newton).
1
Tel.: +61 8 6304 3420; fax: +61 8 6304 2499.
2
Tel.: +31 20 444 8192; fax: +31 20 444 8171.
3 vivors. Evidence-based PA guidelines have been published, but the
Tel.: +31 20 444 8203; fax: +31 20 444 8387.
4
Tel.: +61 8 6304 3443; fax: +61 8 6304 5106.
fects of physical activity (PA) and exercise (i.e. form of PA that is
planned, structured and repetitive and aims to improve fitness,
performance or health [7]) in cancer survivors during and after
treatment on physical and psychosocial outcomes, [8,9] including
increased aerobic fitness, [10] reduced fatigue [11,12] and depres-
sion, [13] and improved QoL [14,15]. Sufficient levels of PA may
also be important to improve disease free and overall survival.
Observational studies showed higher levels of moderate-to-
vigorous PA to be associated with lower mortality risk in survivors
[16] of breast, [17–19] colon, [20,21] and prostate cancer, [22,23]
with physically active survivors having approximately 50% lower
mortality. However, to establish a causal relationship between PA
and survival, randomized controlled trials (RCTs) are needed. The
first RCT evaluating the effects of PA on survival is currently being
conducted among survivors with colon cancer who have com-
pleted adjuvant chemotherapy in the Colon Health and Life-Long
Exercise Change (CHALLENGE) trial [24].
Given the increasing number of studies showing the safety and
benefits of PA, it should be part of standard care for all cancer sur-
development of these guidelines is limited by the research

0305-7372/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ctrv.2013.06.007
328 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340
conducted in this area. This paper reviews the current evidence-
based PA guidelines for cancer survivors, identifies current knowl-
edge gaps and describes the research needed to fill these gaps. This
synopsis may inform future studies evaluating exercise as medi-
cine for cancer, as well as the development of more personalized
PA guidelines for cancer survivors.
Current guidelines and their empirical basis
In 2003, the American Cancer Society (ACS) published a report in-
tended to present health care providers with the best possible infor-
mation on which to assist cancer survivors and their families to
make informed choices related to nutrition and PA [25]. This was
ACS’s second report on nutrition, but the first to also include infor-
mation on PA. Although evidence was generally insufficient to draw
conclusions about the benefits and risks of PA, a probable beneficial
effect of PA on QoL was found for survivors of breast and colorectal
cancer during and after cancer treatment, and for survivors of pros-
tate cancer after cancer treatment, as well as for overall survival after
treatment for colorectal, lung, and prostate cancer. Importantly, no
evidence of harm was reported. The ACS report was updated in
2006 [26]. Despite methodological limitations and small sample
sizes, evidence strongly suggested that exercise is safe and feasible
during cancer treatment and can improve physical functioning and
some aspects of QoL [26]. It was also suggested that regular PA after
cancer treatment is essential for recovery and to improve fitness.
Also, after recovery it was concluded that PA is important to promote
overall health, QoL and longevity. For the prevention of cancer, the
ACS recommends at least 30 min, and preferably 45–60 min, of
moderate-to-vigorous PA above usual activities, on 5 or more days
of the week (Table 1). Although these PA levels have not been studied
systematically in cancer survivors, these recommendations may
also benefit cancer survivors, as it may reduce the risk of recurrence
or developing secondary cancers and extend survival. Therefore, ACS
recommended that daily and regular PA is preferred, but any steps
that are taken to move from a sedentary to a more active lifestyle
should be encouraged, with higher levels of PA leading to more
health benefits [25,26] (Table 1). However, specific precautions
should be heeded for survivors with severe anemia, compromised
immune function, severe fatigue, indwelling catheters and periphe-
ral neuropathies or ataxia [25,26] (Table 2).
In 2009, Exercise and Sport Science Australia (ESSA) published
exercise guidelines for cancer survivors with the intention of guid-
ing exercise practitioners in their work with cancer survivors [27].
The document provided specific recommendations for aerobic
exercise and for the first time, also for resistance exercise (Table 1),
particularly important for cancer survivors experiencing loss of
lean mass during and following treatment. The ESSA position state-
ment indicated that the optimal exercise prescription remains un-
known, and may depend on the type of cancer, treatment and
characteristics of the patient. It was recognized that participation
in some PA is better than none, and that more is generally better
than less, at least up to levels meeting national PA guidelines
[27]. It was also recommended to avoid certain types of aerobic
or resistance exercises (e.g. high impact activities) during periods
of increased risk of infection, ataxia, dizziness, peripheral sensory
neuropathy, low platelet counts, bone pain, or in patients with pri-
mary or metastatic bone cancer (Table 2).
In 2010, the American College of Sports Medicine (ACSM) orga-
nized a roundtable on exercise guidelines for cancer survivors given
the proliferation of exercise programs, and the lack of structured
exercise guidelines for health and fitness professionals to draw
upon in working with cancer survivors [28]. Evidence was reviewed
for adult survivors of breast, prostate, colon, hematologic, and gyne-
cologic cancers. This was the first time that evaluation of the evi-
dence in exercise oncology for development of guidelines was
conducted more systematically and based on categories A–D, out-
lined by the National Heart, Lung and Blood Institute. Overall, the
ACSM guidelines fall into evidence category level B, indicating that
few RCTs exist or they are small and results are inconsistent. The
expert panel reported consistent evidence regarding the safety of
exercise during and after cancer treatment (including intensive
treatments such as bone marrow transplant) and reported that
improvements can be expected in aerobic fitness, muscle strength,
QoL and fatigue in survivors of breast, prostate, and hematologic
cancer. The expert panel acknowledged that the extent to which
these findings may generalize to other cancer survivor groups re-
mains unknown, and that exercise prescriptions should be individ-
ualized according to cancer survivors’ pre-treatment aerobic
fitness, medical co-morbidities, response to treatment, and the
immediate or persistent negative effects of treatment.
The ACSM generally recommends avoiding inactivity, returning to
normal daily activities as quickly as possible after surgery, and to con-
tinue normal daily activities and exercise as much as possible during
and after nonsurgical treatments. Recommendations for aerobic,
resistance, and flexibility exercises are the same as the age-appropri-
ate PA guidelines for the general population [28,29] (Table 1), with
several alterations for patients with and at risk for lymphedema, skel-
etal fractures or infections. In addition, several contraindications for
exercise were identified, including arm and shoulder problems sec-
ondary to breast cancer treatment, having an ostomy after colon can-
cer, or swelling or inflammation in the abdomen, groin, or lower
extremity following gynecologic cancer (Table 2).
In 2011, PA guidelines for cancer survivors were developed in
the Netherlands recommending at least moderate intensity exer-
cise to all cancer survivors and to tailor exercise programs to indi-
vidual fitness levels to obtain optimal training effects [30,31].
Individual cardiopulmonary fitness levels can be assessed by mea-
suring peak oxygen uptake (peakVO2) which is feasible and safe for
cancer survivors prior to an exercise program [32]. In case of logis-
tical problems related to cost, lack of appropriate equipment or
experienced health care professionals to use this test in clinical
practice, [32] a 6 min walk-test, shuttle walk test, or steep ramp
test [33] is recommended [32]. To adequately tailor resistance
exercises to individual patients, the Dutch guidelines recommend
using indirect 1-repetition maximum (1-RM) assessments to as-
sess muscle strength (Table 1) [33,31].
In 2012, the ACS updated their report from 2006 and 2003 [34].
Generally, they recommended cancer survivors to engage in regu-
lar PA, to avoid inactivity and return to normal daily activities as
soon as possible following diagnosis. The ACS recommends cancer
survivors to aim for exercising at least 150 min per week and to in-
clude strength exercises following the comprehensive guidelines
suggested by the ACSM expert panel, after consideration of specific
precautions (Table 2). In the same year, the British Association of
Sport and Exercise Science (BASES) published an expert statement
on exercise and cancer survivorship [35]. They reported that there
is consistent evidence confirming that exercise is safe during and
after cancer treatment, provided that individual limitations and
specific side effects associated with cancer therapies are consid-
ered and monitored, and that improvements in aerobic and muscu-
lar fitness, QoL and fatigue can be expected. They recommended all
cancer survivors be encouraged to avoid being sedentary, and un-
less advised otherwise, follow the PA guidelines of the general UK
population [36] (Table 1), as no formal guidelines for cancer survi-
vors have been published in the UK.
Knowledge gaps to be addressed
Although the significant work conducted to formulate the above
mentioned guidelines is important and has changed clinical
practice for management of cancer, current recommendations are
 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340 329

Table 1
Overview of PA guidelines for cancer survivors.

Year Institute PA recommendations

2003/ ACS  Follow guidelines for the general population for cancer prevention, i.e. at least 30 min of moderate-to-vigorous PA, above
2006 [25,26] the usual activities, on 5 or more days of the week. Forty-five to 60 min of intentional PA are preferable
 Daily and regular activity may be preferred and may be the goal. Any steps that are taken to move from a sedentary to an
active lifestyle should be encouraged

2009 ESSA Aerobic exercise:  Type: exercises involving large muscle groups
[27]  Frequency: at least 3–5 times per week, but daily exercise may be preferable for deconditioned patients who do lower
intensity and shorter duration exercise sessions
 Intensity: moderate, depending on current fitness level. Guidelines recommend 50–75% VO2max, or HRreserve, 60–80%
HRmax, or a RPE of 11–14 (original Borg scale)
 Duration: at least 20–30 min continuous exercise; however, deconditioned patients or those experiencing severe side
effects of treatment may need to combine short bouts (e.g. 3–5 min) with rest intervals
 Progression: would be slower and more gradual for deconditioned patients or those who are experiencing severe side-
effects of treatment

Resistance exercise:  Type: exercises using machine-weights, free weights, body weight and/or elastic bands that involve major functional
lower- and upper-body muscle groups. Targeting large muscle groups. Exercises should be dynamic in nature using both
concentric and eccentric muscle contractions
 Frequency: 1–3 times per week, with minimum one rest day between sessions
 Intensity: 50–80% of 1-RM or 6–12 RM
 Duration: 6–10 exercises, 1–4 sets per muscle group
 Progression: as described for aerobic exercise

2010 ACSM Aerobic exercise:  Avoid inactivity and be as physically active as abilities and conditions allow
[28]  For patients with breast, prostate, colon, hematologic (no HSCT) and gynaecologic cancer, recommendations are the same
as age-appropriate guidelines for the general American population, i.e. to engage in at least 150 min per week of moderate
intensity or 75 min per week of vigorous intensity aerobic PA or an equivalent combination of moderate and vigorous
intensity aerobic PA, for adults aged 18–64 years. Activity should be done in episodes of at least 10 min per session
and preferably spread throughout the week; some activity is better than nothing and exceeding the guideline is likely
to provide additional health benefits
 For patients with HSCT, it is ok to exercise everyday, however lighter intensity and lower progression of intensity is
recommended
 Women with gynaecologic cancer who are morbidity obese may require additional supervision and altered programming

Resistance exercise:  For patients with prostate, colon, and hematologic cancer, recommendations for resistance training are the same as age-
appropriate guidelines for the general American population, i.e. Muscle-strengthening activities involving all major mus-
cle groups at least 2 days per week for adults aged 18–64 years
 For patients with breast cancer, start with a supervised program of at least 16 sessions and very low resistance; progress
resistance at small increments
 For patients with prostate cancer: add pelvic floor exercises for those who undergo radical prostatectomy
 For patients with colon cancer with a stoma, start with low resistance and progress resistance slowly to avoid herniation
at the stoma
 For bone marrow transplant patients, resistance exercises might be more important than aerobic exercise

2011 CCCN  Systematically identify physical and psychosocial problems using for example the distress thermometer
[30,31]  At least moderate intensity physical exercise should be recommended to all patients with cancer, using the Dutch phys-
ical activity norms as a guideline: at least 30 min moderate intensity (4 MET, and 3 MET for people aged P55 years) on at
least 5 but preferable all days per week
 Physical exercise programs should be tailored to patients’ individual cardiopulmonary fitness levels to obtain optimal
training effects
 Assessments of CPET, 6-min walk test, shuttle walk test or steep ramp test should be performed to tailor aerobic exercises
to individual disease characteristics, preferences and goals
 Assessments of 1-RM should be performed to tailor resistance exercises to individual disease characteristics, preferences
and goals

2012 ACS [34]  Engage in regular PA

 Avoid inactivity and return to normal daily activities as soon as possible following diagnosis
 Aim to exercise at least 150 min per week
 Include strength training exercises at least 2 days per week
 Follow the survivor-specific guidelines written by the ACSM expert panel

2012 BASES  All cancer survivors should be encouraged, as a minimum, to avoid being sedentary
[35]  Unless advised otherwise, cancer survivors should follow the health-related PA guidelines provided for the general UK
population i.e. 150 min each week of moderate to vigorous intensity PA for adults (and adults should aim to do some
PA every day) and include muscle strengthening activities twice a week

ACS = American Cancer Society; ACSM = American College of Sports Medicine; BASES = British Association of Sport and Exercise Science; CCCN = Comprehensive Cancer
Center the Netherlands; CPET = cardiopulmonary exercise testing; ESSA = Exercise and Sport Science Australia; HR = heart rate; HSCT = hematopoietic stem cell transplan-
tation; MET = metabolic equivalent; RM = repetition maximum; RPE = rating of perceived exertion; UK = United Kingdom; VO2 = oxygen uptake.

rather general due to gaps in specific areas of exercise oncology.
The ultimate aim is to have specific guidelines to inform a given
exercise intervention (e.g. mode, frequency, intensity, duration),
for a given cancer site at a particular phase of the cancer trajectory
(e.g. during treatment, survivorship, end of life), for specific end
points (e.g. fatigue, physical function, QoL, survival) and to address
specific treatment side-effects and co-morbidities (e.g. osteoporo-
sis, metabolic syndrome, sarcopenia, functional decline) [28]. A
meta-analysis by Speck et al. [9] concluded that the current vol-
ume of literature was not large enough to summarize findings
per time point within PA across the Cancer Continuum (PACC)
framework, [37] which proposes four post-diagnosis (pre-treat-
ment, treatment, survivorship, and end of life) cancer-related time
periods [37]. Nevertheless, results of exercise during and post
cancer treatment were separately presented in this meta-analysis.
During treatment, small-to-moderate effects of PA were reported
330 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340

Table 2
Precautions for exercise.

Year Institute Precautions

2003/ ACS  Survivors with severe anemia should delay exercise, other than activities of daily living, until the anemia is improved
2006 [25,26]  Survivors with compromised immune function should avoid public gyms and public pools until their white blood cell counts return to safe
levels. Survivors who have completed a bone marrow transplant are usually advised to avoid such exposures for one year after
transplantation
 Survivors suffering from severe fatigue from their therapy may not feel up to an exercise program, so they may be encouraged to do 10 min
of stretching exercises daily
 Survivors undergoing radiation should avoid chlorine exposure to irradiated skin (e.g. from swimming pools)
 Survivors with indwelling catheters or feeding tubes should be cautious or avoid pool, lake, or ocean water or other microbial exposures that
may result in infections, as well as resistance training of muscles in the area of the catheter to avoid dislodgment
 Survivors with significant peripheral neuropathies or ataxia may have a reduced ability to use the affected limbs because of weakness or loss
of balance. They may do better with a stationary reclining bicycle, for example, than walking on a treadmill

2009 ESSA  Patients are recommended to avoid swimming or the use of public facilities such as machine-weights in gymnasiums during periods of
[27] increased infections (e.g. low absolute neutrophil counts, when catheters are being used, during wound recovery from surgery)
 Patients with primary or metastatic bone cancer, patients with low platelet counts, or patients experiencing bone pain should avoid high-
impact activities or contact sports
 Patients with ataxia, dizziness, or peripheral sensory neuropathy are recommended to avoid activities requiring balance and coordination
(e.g. treadmill exercise, cycling) and specific resistance exercises such as those using free weights
 Patients should avoid the use of public facilities (e.g. local gymnasium) during periods of increased infection risk
 When nausea, dyspnoea, fatigue and/or muscle weakness exist, exercise intensity and duration should be prescribed to tolerance

2010 ACSM  Beware of fracture risk in patients with breast and prostate cancer who are treated with hormone of androgen deprivation therapy, respec-
[28] tively, or diagnosed with osteoporosis or bone metastases
 Women with immediate arm or shoulder problems secondary to breast cancer treatment should seek medical care to resolve those issues
before exercise training with the upper body
 If an ostomy is present in patients with colon cancer, physician permission is recommended before participation in contact sport and weight
training, excessive intra-abdominal pressure should be avoided, and modifications will be needed for swimming and contact sports
 In adults with HSCT, care should be taken to avoiding overtraining given immune effects of vigorous exercise
 If peripheral neuropathy is present in patients with gynaecologic cancer, a stationary bike might be preferable over weight bearing exercise
 Women with gynaecologic cancer with swelling or inflammation of the abdomen, groin or lower extremities should seek medical care to
resolve these issues before exercise training with the lower body
 Patients with bone metastases may need to alter their exercise program given the increased risk for skeletal fractures
 Care should be taken to reduce infection risk in fitness centers for patients who are currently undergoing chemotherapy or radiation treat-
ment or have compromised immune function
 Patients with cardiac conditions will require modifications and may require increased supervision for safety

2012 ACS [34]  See also precautions from ACS published in 2003 and 2006
 Survivors with multiple or uncontrolled comorbidities need to consider modifications to their exercise program in consultation with their
physicians

ACS = American Cancer Society; ACSM = American College of Sports Medicine; ESSA = Exercise and Sport Science Australia.

for aerobic fitness, upper and lower body muscle strength, body
weight, functional QoL, anxiety, and self-esteem. Post treatment,
large effects were found for upper and lower body muscle strength
and breast cancer-specific concerns, and small to moderate effects
for PA level, aerobic fitness, overall QoL, insulin-like growth factor
(IGF)-1, and symptoms and side effects [9]. For many outcomes,
there have been too few studies to draw conclusions. Similar
small-to-moderate effect sizes were reported in other meta-
analyses on this topic [12–15,38,39].
Explanations for small-to-moderate effects of exercise in cancer
survivors include problems with program participation and adher-
ence, and the use of one-size-fits-all approaches in a heterogeneous
group of cancer survivors. Thus, similar to developments in personal-
ized primary cancer treatment, exercise prescription for cancer survi-
vors should be optimally tailored to the individual characteristics,
states, needs, capabilities and preferences of a patient. To be able to
shift towards personalized PA and exercise programs, it is essential
to know which mode of exercise, at which frequency, intensity and
duration is best for whom, and under what circumstances, for exam-
ple the timing with respect to the treatment phase (i.e. treatment
moderators). To further optimize exercise interventions, it is essential
to gain insight into the working mechanisms and to identify effective
intervention components (i.e. treatment mediators).
Moderators of exercise intervention effects
Specific treatment moderators can help determine which pa-
tients should receive a particular treatment [40]. Few previous
studies have examined moderators of exercise intervention effects
on QoL in cancer survivors. Greater QoL benefits were found in
lymphoma patients who had no preference for exercise, were
unmarried, had normal weight or were obese, or had poor/fair
health [41]. During chemotherapy for breast cancer, aerobic train-
ing was most beneficial for patients who had no exercise prefer-
ence, were unmarried, aged <50 years and had more advanced
disease stage [42]. Resistance exercise was most beneficial for pa-
tients who preferred it, were unmarried, received nontaxane-based
chemotherapy and had more advanced disease stage [42]. Prostate
cancer patients with lower psychosocial function at baseline
showed higher improvements in QoL after completing a lifestyle
PA program [43]. These studies indicate that demographic, clinical
and personal factors may help us to understand differences in exer-
cise responses. Insight into moderators of interventions is needed
to maximize benefits of interventions for individual patients.
Future studies should focus on identifying relevant moderators of
exercise intervention effects.
Exercise mode, frequency, intensity and duration
RCTs directly comparing different exercise modes, frequencies,
intensities and durations in cancer survivors are necessary to iden-
tify optimal exercise prescriptions. Unfortunately, few RCTs have
been published (Table 3). Regarding exercise mode, Courneya
et al. [44] found peak oxygen uptake (peakVO2) to be superior after
aerobic exercise training (AET) compared with usual care (UC) and
resistance exercise training (RET), and lower and upper body
strength to be superior after RET compared with AET and UC in wo-
men with breast cancer during chemotherapy. Neither exercise
interventions prevented weight gain, but they both altered body
 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340 331

Table 3
Overview of studies directly comparing different exercise modes, frequencies, intensities, durations, and timing.

Author Population Study design Main findings

Trial identification
Exercise mode
Courneya et al. [44]Supervised
Trial of Aerobic versus
Resistance Training (START)
trial
Segal et al. [45]
Newton et al.
[48](ACTRN12609000200280)
Jones et al. [46]The Lung Cancer
Exercise Training (LUNGEVITY)
study (NCT00018255)
Winters-Stone
[50](NCT00662103)
Diagnosis, n
Breast cancer during
chemotherapy; n = 242
Men with prostate cancer
during radiation therapy;
n = 121
Men with prostate cancer
during ADT; n = 195
Histologically confirmed
stage I-IIIA post-operative
NSCLC; n = 160
Older (>65 years) female
breast cancer after
treatment. n = 141
3-armed RCT:  PeakVO2 (ml/kg/min):
AET > RET (4 1.4, 95% CI = 0.1; 2.7, p = 0.031)
 AET
RET = UC (4 0.5, 95% CI = -0.8; 1.8, N.S.)
 RET
AET > UC (4 2.0, 95% CI = 0.6; 3.3, p = 0.004)
 UC
 Lower body strength (1 RM in kg):
RET > AET (4 5.2, 95% CI = 2.5; 7.9, p = 0.001)
RET > UC (4 6.8, 95% CI = 4.2; 9.5, p = 0.001)
AET = UC (4 1.6, 95% CI = 1.1; 0.12, N.S.)
 Upper body strength (1 RM in kg):
RET > AET (4 6.8, 95% CI = 4.5; 9.0, p = 0.001)
RET > UC (4 7.7, 95% CI = 5.5; 9.9, p = 0.001)
AET = UC (4 1.0, 95% CI = 1.3; 3.2, N.S.)
 Body weight (kg):
AET = RET (4 -0.7, 95% CI = 0.4; 0.9, N.S.)
RET = UC (4 0.5, 95% CI = 1.6; 0.6, N.S.)
AET = UC (4 0.2, 95% CI = 0.9; 1.4, N.S.)
 Body fat (%):
AET = RET (4 0.0, 95% CI = 1.0; 1.0, N.S.)
RET = UC (4 0.9, 95% CI = 0.1; 1.9, N.S.)
AET > UC (4 0.9, 95% CI = 0.1; 1.9, p = 0.076)
 Lean mass (kg):
RET = AET (4 0.6, 95% CI = 0.1; 1.3, N.S.)
RET > UC (4 1.0, 95% CI = 0.3; 1.6, p = 0.004)
AET = UC (4 0.3, 95% CI = 0.3; 1.0, N.S.)
 Chemotherapy completion rate:
RET = AET (4 3.3, 95% CI = 2.5; 9.2, p = 0.266)
RET > UC (4 5.7, 95% CI = 0.4; 11.0, p = 0.033)
AET = UC (4 not reported, N.S.)
Self esteem:
RET = AET (4 0.0, 95% CI = 1.1; 1.1, N.S.)
RET > UC (4 1.2, 95% CI = 0.2; 2.3, p = 0.025)
AET > UC (4 1.2, 95% CI = 0.1; 2.3, p = 0.026)
3-armed RCT:  QoL*:
RET > UC (4 4.3, 95% CI = 0.9; 7.8, p = 0.015)
 AET
AET > UC (4 2.5, 95% CI = -0.9; 5.9, p = 0.141)
 RET
Fatigue*:
 UC
RET > UC (4 4.8, 95% CI = 1.8; 7.8, p = 0.002)
AET > UC (4 2.7, 95% CI = 0.3; 5.6, p = 0.08)
 PeakVO2 (ml/kg/min)
RET > UC (4 1.6, 95% CI = 1.0; 3.1, p = 0.037)
AET > UC (4 1.4, 95% CI = 0.1; 2.8, p = 0.063)
Lower body strength (8 RM in kg):
RET > UC (4 25.1, 95% CI = 15.3; 34.9, p < 0.001)
AET = UC (4 3.7, 95% CI = 6.0; 13.4 p = 0.45)
 Upper body strength (8 RM in kg):
RET > UC (4 13.7, 95% CI = 10.7; 16.6, p < 0.001)
AET > UC (4 4.0, 95% CI = 1.2; 6.9, p = 0.006)
 Body fat (%):
RET > UC (4 1.5, 95% CI = 3.1; 0.03, p = 0.055)
AET = UC (4 0.2, 95% CI = 1.7; 1.4, p = 0.847)
 Triglyceride (mmol/L):
RET > UC (0.1 (SD = 0.6) decrease in RET vs 0.3 (SD = 0.7)
increase in
UC, p = 0.036)
AET = UC (0.3 (SD = 0.7) increase in AET and UC, N.S.)
3-armed RCT: Study is ongoing
 RET + impact loading
 RET + AET
 UC
4-armed RCT: Study is ongoing
 RET
 AET
 RET + AET
 Attention-control
(progressive stretching)
3-armed RCT: Study is ongoing
 AET
 RET
 Flexibility and relaxation (control)

(continued on next page)

332
Table 3 (continued)
Author
Trial identification
Young-McCaughan
[51](NCT00237926)
National Institutes of Health
Clinical Center
[47](NCT00246818)
Siew Yim
[49](ACTRN12611000093987)
Exercise frequency
–
Exercise intensity
Burnham and Wilcox [54]
Gibbs et al.
[55](ACTRN12612000256875)
Cormie et al.
[56](ACTRN12610000788077)
Kampshoff et al. [57]Resistance
and Endurance exercise After
ChemoTherapy (REACT)
study.(NTR2153)
L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340
Population Study design Main findings
Diagnosis, n
Sedentary adults after 2-armed RCT: Study is ongoing
treatment with
 AET
chemotherapy or radiation
 RET
therapy n = 58
Adult survivors of solid 3-armed RCT: Study is ongoing
tumours. n = 76
 Tai Chi
 AET
 UC
Breast cancer after 3-armed RCT: Study is ongoing
treatment n = 114
 QuiGong
 AET (line dancing)
 UC
Survivors of breast and 3-armed RCT: Differences at post-test between moderate (n = 6) and low
colon cancer n = 18 AET (n = 6):
 Moderate AET
 Low AET  PeakVO2 (ml/kg/min): p = 0.824
 UC  Body fat (%): p = 0.512
 Sit and reach (cm): p = 0.722
Exercise (n = 12) vs UC (n = 6)
 " PeakVO2 (ml/kg/min): p < 0.001
 ; Body fat (%): p < 0.001
 " Sit and reach (cm): p = 0.027
 " QoL: p < 0.001
 " Energy: p = 0.038
Breast cancer patients 3-armed RCT:  Lymphatic relative volume (%):
with lymphedema after High vs Low: N.S.
 High intensity RET
cancer treatment; n = 73 High vs UC: 4 8.6; p = 0.001
 Low intensity RET
Low vs UC: 4 7.8; p = 0.001
 UC
 Chest press (kg):
High vs Low: N.S.
High vs UC: 4 4.7; p = 0.001
Low vs UC: 4 3.8; p = 0.001
 Seated row (kg):
High vs Low: N.S.
High vs UC: 4 9.7; p = 0.001
Low vs UC: 4 4.9; p = 0.001
 Leg extension (kg):
High vs Low: N.S.
High vs UC: 4 5.6; p = 0.001
Low vs UC: 4 3.9; p = 0.001
 400 m walk (sec):
High vs Low: 4 16.3; p = 0.020
High vs UC: 4 36.2; p = 0.025
Low vs UC: 4 18.9; p = 0.004
 General fatigue (%)
High vs Low: N.S.
High vs UC: 4 28.2; p = 0.001
Low vs UC: 4 25.3; p = 0.001
 Body image (%)
High vs Low: N.S.
High vs UC: 4 20.8; p < 0.05
Low vs UC: 4 23.4; p < 0.05
 Breast symptoms (%)
High vs Low: N.S.
High vs UC: 4 9.5; p < 0.05
Low vs UC: 4 10.8; p < 0.05
 Arm symptoms (%)
High vs Low: N.S.
High vs UC: 4 15.2; p < 0.05
Low vs UC: 4 13.6; p < 0.05
Women with breast cancer 3-armed RCT: Study is ongoing
related lymphedema.
 High intensity RET
n = 60
 Low intensity RET
 UC
Mixed group after 3-armed RCT: Study is ongoing
chemotherapy; n = 400
 High intensity RET + AET
 Low-moderate intensity RET + AET
 Wait-list
 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340 333

Table 3 (continued)

Author Population Study design Main findings

Trial identification Diagnosis, n
Jones et al. [58]Exercise Intensity Postmenopausal, operable 3-armed RCT: Study is ongoing
trial (EXCITE)(NCT01186367) breast cancer after
 High intensity aerobic
treatment; n = 174
 Moderate-high intensity aerobic
 Attention control
Exercise duration
Sprod et al. [59] Breast cancer survivors; 3-armed RCT:  Cardiovascular endurance (treadmill time):
n = 114 6M=3M
 3 months exercise
6 M > UC (p < 0.05)
 6 months exercise
3 M > UC (p < 0.05)
 UC
 Forced Vital Capacity:
6 M > 3 M (p < 0.05)
6 M > UC (p < 0.05)
3 M = UC
 Upper body muscle endurance (bench press) :
6 M > 3 M (p < 0.05)
6 M = UC
3 M = UC
 Crunches:
6M=3M
6 M > UC (p < 0.05)
3 M > UC (p < 0.05)
 Affective fatigue:
6 M > 3 M (p < 0.05)
6 M = UC
3 M = UC
Timing of exercise
Gibbs et al. Breast cancer survivors 3-armed RCT: 12 weeks/3 months follow-up
[60](ACTRN1212000646842) scheduled for
 RET + AET during treatment  MFI, general fatigue (%)
radiotherapy; n = 63.
 RET + AET post treatment During vs Post: N.S./N.S.
 UC During vs UC: 4 17.2; p = 0.042/4 10.8; p = 0.012
Post vs UC: 4 14.4; p = 0.031/4 9.2; p = 0.031
 MFI, physical fatigue (%)
During vs Post: 4 5.5; p = 0.045/N.S.
During vs UC: 4 18.7; p = 0.034/4 11.1; p = 0.034
Post vs UC: 4 13.0; p = 0.038/4 10.3; p = 0.035
 Chest press (1-RM in kg)
During vs Post: N.S./4 3.2; p = 0.026
During vs UC: 4 6.5; p = 0.001/4 2.3; p = 0.002
Post vs UC: 4 5.3; p = 0.002/N.S.
 Seated row (1-RM in kg)
During vs Post: N.S./4 3.5; p = 0.002
During vs UC: 4 7.3; p = 0.002/4 1.5; p = 0.045
Post vs UC: 4 4.4; p = 0.001/N.S.
 Leg extension (1-RM in kg)
During vs Post: N.S./N.S.
During vs UC: 4 5.8; p = 0.006/4 1.4; p = 0.042
Post vs UC: N.S./N.S.
 Upper body endurance (rep)
During vs Post: N.S./N.S.
During vs UC: 4 6.3; p = 0.011/4 2.9; p = 0.038
Post vs UC: 4 4.5; p = 0.025/N.S.
 Lower body endurance (rep)
During vs Post: N.S./N.S.
During vs UC: 4 7.1; p = 0.022/4 3.9; p = 0.032
Post vs UC: 4 6.9; p = 0.021/N.S.
 Global health (%):
During vs Post: N.S./N.S.
During vs UC: 4 23.5; p = 0.006/N.S.
Post vs UC: N.S./N.S.
 Physical functioning (%)
During vs Post: N.S./N.S.
During vs UC: 4 12.0; p = 0.010/N.S.
Post vs UC: N.S./N.S.
 Role functioning (%)
During vs Post: N.S./N.S.
During vs UC: 4 13.3; p = 0.010/N.S.
Post vs UC: N.S./N.S.
 Emotional functioning (%)
During vs Post: N.S./N.S.
During vs UC: 4 20.1; p = 0.002/N.S.
Post vs UC: N.S./N.S.

(continued on next page)

334 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340

Table 3 (continued)

Author Population Study design Main findings

Trial identification
Newton et al.
[61](ACTRN12612000097842)
Walenkamp & Gietema [62]
Optimal timing of PA in Cancer breast cancer n = 206
Treatment (ACT)
study(NCT01642680)
Diagnosis, n
Prostate cancer during 2-armed RCT Study is ongoing
ADT; n = 124
 Commence exercise simultaneously
with ADT
 start after 6 months
Testicular, colon and 2-armed RCT Study is ongoing
 PA program during (3 months) and
after chemotherapy (3 months)
 PA after chemotherapy (6 months)

ACTRN = Australian New Zealand Clinical Trials Registry Number; ADT = androgen deprivation therapy; AET = aerobic exercise training; NCT = ClinicalTrials.gov Identifier;
N.S. = not significant; NSCLC = non-small cell lung cancer; RCT = randomized controlled trial; RET = resistance exercise training; RM = repetition maximum; UC = usual care;
VO2 = oxygen uptake.
*
Unadjusted for covariates. > = more benefits.

composition compared to UC: AET prevented fat gain, and RET
added lean body mass. Further, compared to AET (87.4%) and UC
(84.1%), chemotherapy completion rate was higher during RET
(89.8%) [44]. Both RET and AET improved self-esteem compared
to UC, but no differences were found between AET and RET. Also
cancer-specific QoL, fatigue, anxiety, depression and arm volumes
did not differ between groups. QoL and lower body strength were
higher, and body fat and triglycerides lower after 24 weeks of RET
compared to UC in men receiving radiotherapy for prostate cancer
[45]. No significant differences were found between AET and UC
(Table 3) [45]. Compared with UC, both RET and AET improved
upper body strength and peakVO2, and reduced fatigue. No signif-
icant differences between groups were found for prostate-specific
symptoms, body weight, body fat, hemoglobin, testosterone, and
prostate-specific antigen. Although both RET and AET were com-
pared with UC, with RET showing longer-term improvements and
additional benefits for QoL, strength, triglycerides and body fat, di-
rect comparisons between RET and AET were not reported. To be
able to tailor exercise interventions to individual cancer-related se-
quelae, more studies evaluating the effects of different exercise
modes on specific outcomes are needed. Few studies are currently
underway [46–51] (Table 3). In addition to RET and AET, specific
clinical exercises may be recommended for specific cancer diagno-
ses. For example, for survivors of prostate cancer, pelvic floor train-
ing before surgery and during radiation and ADT may be important
to reduce incontinence and to improve QoL [52,53].
RCTs directly comparing different exercise frequencies among
cancer survivors have not been published. The majority (59%) of
studies evaluating effects of PA in cancer survivors focused on a
frequency of 3–5 times per week, [9] corresponding with general
PA guidelines. Interventions focusing on structured supervised
exercise generally offered two sessions per week with or without
additional PA counseling.
Two studies compared responses to different exercise intensi-
ties [54,55] (Table 3). Comparisons of 10 weeks of moderate and
low intensity AET with UC in a small group (n = 18) of breast and
colon cancer survivors after completion of treatment showed no
differences in peakVO2, lower-body flexibility and body fat be-
tween the two exercise groups [54]. Both exercise groups com-
bined showed increased peakVO2, lower-body flexibility, QoL,
and energy, and decreased body fat compared to UC [54]. A
three-armed RCT among 73 women with breast cancer-related
lymphedema showed that 12 weeks of both high and low intensity
RET are safe and effective in reducing lymphatic relative volume,
improving upper and lower body muscle strength, 400 m walk test,
general fatigue, body image, and breast and arm symptoms [55].
High intensity RET was superior to low intensity RET on the 400-
m walk [55]. Three [56–58] RCTs comparing effects of different
exercise intensities are currently being conducted (Table 3).
Regarding exercise duration, physiological and psychological
outcomes following 3 or 6 months of prescriptive, individualized
exercise were compared with UC in a non-randomized controlled
trial among 114 breast cancer survivors [59] (Table 3). Exercising
for 6 months showed additional improvements in pulmonary func-
tion (forced vital capacity) and upper body muscle endurance
(bench press) compared with 3 months. No significant differences
between the exercise groups were found in cardiovascular endur-
ance (treadmill time) and abdominal muscle endurance (crunches),
but both showed improvements compared to UC. No differences
between groups were found for forced expiratory volume in one
second, leg press, lateral pull-down, shoulder press, fatigue and
depression, except for affective fatigue, which improved more after
6 months than after 3 months, but showed no differences com-
pared to UC [59].
Optimal timing of interventions
Although studies have shown beneficial effects of exercise both
during and after cancer treatment, little is known about the opti-
mal timing of starting exercise interventions. A three-armed RCT
in 63 survivors of breast cancer scheduled for radiotherapy com-
paring RET + AET during treatment with RET + AET post treatment
and UC showed that both exercise groups reduced general and
physical fatigue, and improved muscle strength and endurance
compared to UC at 12 weeks and 3 months follow-up [60] (Table 3).
In patients who exercised during treatment, improvements in glo-
bal health, physical functioning, role functioning and emotional
functioning compared to UC were found at 12 weeks, but not at
3 months follow-up. Improvements in physical fatigue at
12 weeks, and improvements in upper body muscle strength at
3 months follow-up were superior after exercising during treat-
ment compared to exercising post treatment, [60] indicating that
it may be more beneficial to start exercising during treatment.
Two RCTs comparing early versus delayed onset of exercise are
currently being conducted [61,62] (Table 3). Although it may be
expected that early initiation of exercise is better, patients may
experience specific barriers to exercise at different time points in
the cancer trajectory, limiting them to comply with specific exer-
cise programs early in the trajectory. Starting later would then
be more effective and efficient. Therefore, more insight into the
optimal timing of interventions is warranted.
Mediators of exercise effects
Insight into mediators of exercise programs is important for
identifying and subsequently targeting critical intervention com-
ponents to improve effectiveness and efficiency and to reduce
the costs [40,63,64]. Few studies examined mediators of exercise
interventions in cancer survivors. In uncontrolled trials and a
 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340 335

Table 4
Cancer survivors’ interests and counseling and program preferences regarding PA and exercise.

Reference number [134] [135] [136] [137] [138] [139] [140] [141] [142] [143] [144] [145] [146] [147] Total
Characteristics
n 588 1284 307 106 386 397 90 50 192 90 483 345 703 431 5452
Country Can Nor Can USA Can Can USA Can USA USA USA Can Can Can
Diagnosis Mixed Mixed Mixed Brain Endometrial Bladder Breast Palliative Breast Head Breast Ovarian Kidney NHL Mean 
Neck (rural)
Months since diagnosis, mean (SD) 73.6 42.9 28; 6– 28; 6– 52 (32) 74 14.9 62.5 39.0 73.6 69.0 62 50
(52.1) (15.5) 18 178 (14.7) (25.9) (21.5) (52.6) (55.5) (25)
Age in years, mean (SD) 38.2 56.6 60.8 44.8 64.5 (10.6) 30% < 65 57.1 61.5 64 65% < 65 63 (12) 60.2 65.0 61 57
(5.6) (13.8) (11.5) (12.0) (12.0) (13.1) (11.5) (12.6) (11.1) (13)
Gender, % male 30 44 41.1 49.1 0 74.3 0 40 100 78 0 0 63 52 39

COUNSELLING
b c
Interest
Yes 51.7 55 60.3 29.2 55.7 47.5 44 51.7 51
No 19.5 24 15.9 37.7 22.6 29.6 24.8 22.9 23
Maybe 28.8 21 23.7 16 14.2 22.9 31.2 25.4 25
Source
Physician 17.2 12 9.8 18.7 20.5 4 5 11 9 21.9 16
Nurse 2.2 7 4.6 12.7 12.7 3 2 6 0.6 12.2 7
Exercise specialist from cancer 49.6 53 76.8 40.9 40.1 71 25 11 18 55.7 47
center
Exercise specialist from health 13.8 27 4.9 17.3 15.9 12 26 6 22 19.1 19
club or community center
Cancer patient/survivor 6.5 2 3.6 10.4 11 9 2 0 2 19.6 7
Delivery
Face-to-face 47.2 95 85.3 82.8 77.7 55 61 40 47 34 68
Telephone 11.2 0 1.7 3.4 3.5 3 0 0 0.8 6.1 3
(self-help) video 15.1 2 6.5 7 9 6 13.5 6
Print material 63.5 2 6.5 11.8 17.7 7 5 3 11 50 21
Internet 38.5 1 0 6 0 1 3 13.9 8
By e-mail 45.9 19.5 9
Other 1 2 30 3 3 2

PROGRAM
Interested
Yes 48 67 29 56 41.5 44.5 78 38 33 33 53.8 34.2 55.4 49
No 21.7 9 38 23 18.3 18.8 8 26 25 26 13.3 28.5 18.9 19
Maybe 30.3 24 16 14 35.3 36.6 14 36 42 41 32.9 37.3 25.7 31
Able to
Yes 62.2 74 30.2 65.1 46.4 47 58 64 51 55 64.6 48 52.9 59
No 12.5 6 32.1 8.5 18.3 15.7 8 14 17 15 6.6 18.9 15.5 13
Maybe 25.3 20 17 18.9 35.3 37.3 34 22 32 30 28.9 33.1 31.6 28
Preferred timing
At the time of diagnosis, before 25.8 10 32 18.1 21.4 17.9 17 27.7 19
treatment
During treatment 10.1 14 17 6 10.6 12.6 4.7 16.6 11
Immediately after treatment 16.6 46 24 26.8 39.1 25.5 22.4 29
At 3–6 months after treatment 33.5 26 23 39.3 21.4 25.8 36.5 38.2 30
At least 1 year after treatment 14.1 5 5 9.7 7.5 18.2 20.9 18.1 12
Company
Alone 16.7 17 44 23.8 35.8 21 54 41 50 41 29 39.1 30.8 29
With other cancer patients/ 16.9 26 34 4.7 4.7 11.7 6 25 0 15.9 20.6 12.7 16
survivors
Family/ friends/ spouse/ coworker 31.6 26 4 26.4 51.9 31.8 22 30 16 35 30 38 30.5 22.5 24
Location
Outside around my neighborhood 46.3 16 29 47 25 46.8 16
At home 43.5 20 40 25.5 43.4 32.7 53.7 37 84 36 33 38 48.9 52 42.6 38
At a community/local fitness 53.5 35 13 9.4 22.6 24.3 11.4 16 0 15 8 19 20.9 32.5 17.3 27
center
At a cancer center 11.2 23 19 10.2 7.8 33 0 6 0 3 6.9 7.3 12.6 12
Time of the day
Morning 34 48 51.3 36.6 40 52 47 53 48.9 58.3 41.3 45
Afternoon 32 23 12.3 15.6 32 13 17 11 15 25.9 17.4 22
Evening 16 5 12.9 11.4 4 20 15 20 17.4 30.3 18.7 18
* * * *
Mode
Walking 45.7 33 81 51 53 68.6 81.1 61 72 55.5 45.5 48.5 62.7 69.4 55
Cycling 16.6 14 4 19 16.1 24 7.5 4.5 8.5 3.3 23.8 12
Swimming 20.8 14 4 15 7.5 8.5 4.4 16.9 10
Resistance training 23 4 44 36 26.9 20.5 24 12 3 9.5 5 12
Intensity

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336 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340

Table 4 (continued)

Reference number [134] [135] [136] [137] [138] [139] [140] [141] [142] [143] [144] [145] [146] [147] Total
Light 11 35 26.3 26.1 45 22 26 26 35.3 23.1 23
Moderate 77 56 61.1 61.7 47 64 50 65 58.4 62 64
Vigorous 9 4 7.7 6.7 3 7 6 4 6.3 9.7 7
Variability
Same each time 34 51 40.9 49.1 22 27 35 28
Different each time 66 49 59.1 50.9 78 21 23 64.7 38.9 54
Supervision
Supervised 64 43 53.1 29.4 66 25 12 22 40.8 41.5 45
Unsupervised 36 57 46.9 70.6 34 49 55 47 59.2 58.5 49
Structure
Spontaneous/Flexible 21 47 35.5 56.9 46 66 62 49.2 45 41
Structured/scheduled 79 53 64.5 43.1 54 10 24 50.8 55 57

NHL = Non-Hodgkin lymphoma. aBefore diagnosis.

b
During treatment.
c
After treatment.
*
Summer and winter averaged.
 
weighted according to sample size. Proportions do not add up to 100 due to missing categories (e.g. no preference, other).

cross-sectional study, exercise effects on QoL were found to be Endocrine function

mediated by fatigue [65–67]. As another example, the effects of
an 8-week mixed modality community-based group exercise and
information support intervention on QoL of patients with breast
cancer was mediated by exercise familiarity and self-efficacy but
not by social support [68].
In addition to personal and psychosocial working mechanisms,
biological factors (e.g. function of immune and endocrine systems)
and physiological factors (e.g. neuromuscular function) may medi-
ate the effect of PA and exercise on relevant health outcomes,
including fatigue, QoL and survival.
Immune system function
Cancer and its treatments may alter immune system function
[69]. C-reactive protein (CRP) is a sensitive marker of low-grade
systemic inflammation [70]. In cancer survivors, elevated concen-
trations of CRP have been found to be associated with fatigue
[71] and reduced overall and disease-free survival [72]. Exercise
can have a beneficial effect on the immune system, [73–76] includ-
ing cancer survivors [16,69]. Reductions in CRP after exercise [16]
were found in an observational study among breast cancer survi-
vors [77] and RCTs among survivors of breast, [78] lung, [79] and
prostate cancer [80].
Pro-inflammatory cytokines (e.g. tumor necrosis factor-alpha
(TNF-a) and Interleukin (IL)-6) may be released in response to
the tumor or cancer treatment, and may promote tumor growth
and angiogenesis [81–83]. TNF-a and IL-6 have been associated
with cancer-related anemia, [83] cachexia, [84] loss of muscle
mass, [84,85] and cancer-related fatigue [86,87]. PA and exercise
may have an anti-inflammatory effect in cancer survivors, [88] as
cytokines may be expressed and released by muscle fibers [89–
92]. However, no change in IL-6 levels after exercise was found
in 20 patients with breast cancer [93]. Comparably, a study in 10
patients with prostate cancer did not find changes in resting serum
concentrations of IL-6 and TNF-a after a 20-week resistance exer-
cise program, but increased IL-6 levels were found after acute
resistance exercise [94]. Exercise improved Natural Killer cell cyto-
toxity among cancer survivors, [16,69] indicating improved im-
mune function. Other beneficial effects included increased
lymphocyte proliferation and granulocyte cell counts. Although
evidence is still preliminary, PA and exercise may be associated
with beneficial changes in inflammation and immunity [16]. Fu-
ture studies among cancer survivors should examine immune sys-
tem responses to exercise and their mediating role on reducing
fatigue, and improving QoL and survival.
Insulin, IGF, and IGF binding proteins (IGFBP) are important reg-
ulators of energy metabolism and growth, and may also be in-
volved in tumor development and progression. High insulin
levels have been associated with increased risk of tumor recur-
rence or death in survivors of breast [95,96] and colon cancer
[97,98]. In addition, increasing evidence suggests that insulin, IGF
and IGFBP may have an important mediating role in the effect of
exercise on cancer risk and prognosis.
Recently, Ballard-Barbash et al. [16] systematically reviewed
studies among cancer survivors examining associations between
PA and biomarkers. One observational study [77] and four RCTs
[99–102] evaluated effects of PA on insulin, IGF and IGFBP among
breast cancer survivors [16]. Higher levels of PA were found to be
associated with lower levels of C-peptide (marker of insulin secre-
tion) and leptin, and higher levels of IGF-1, but no association was
found for IGFBP-III [77]. Results from RCTs provide preliminary evi-
dence that PA may result in beneficial changes in the circulating
levels of insulin and insulin-related pathways, which may be more
pronounced for obese or sedentary women who generally have
higher serum insulin levels at baseline, and for women who are
not taking Tamoxifen [16]. Weighted-mean effect size of the effect
of post-treatment PA on IGF-1 was found to be significant but
small-to-moderate [9]. No changes were reported for insulin and
IGFBP-III, and evidence was insufficient for IGF-II and IGFBP-I [9].
The number of studies on the effects of PA on insulin, IGF and
IGFBPs during treatment was too small to draw conclusions [9].
Three RCTs in prostate cancer survivors on androgen depriva-
tion therapy (ADT) [45,80,103] showed consistent evidence that
exercise does not alter prostate-specific antigen (PSA) or testoster-
one levels, [16] however, the effect on survivors not on ADT is un-
clear. Studies on the effect of PA on biomarkers, such as serotonin,
cortisol, bilirubin [93] or others are limited or nonexistent [16].
Future studies among cancer survivors should further explore
the effects of PA on biomarkers of endocrine function and their
mediating role in the association between PA and health outcomes.
Neuromuscular function
Cancer and its treatment may affect neuromuscular function.
Peripheral neuropathy has emerged as a side effect of several che-
motherapeutic agents including thalidomide, [104,105] paclitaxel
[106,107], and oxaliplatin [108–110]. Cancer treatment may also
damage the muscle itself. Several case reports describe
chemotherapy-induced myopathy or myopathy-related disorders
among cancer survivors [111–113]. Deconditioning, neuropathy
and myopathy may lead to PA avoidance and consequently to
 L.M. Buffart et al. / Cancer Treatment Reviews 40 (2014) 327–340
muscle atrophy. Sarcopenia (age-related loss of skeletal muscle
mass and strength) is present in many cancer survivors, and may
be associated with poor outcomes including increased fatigue, re-
duced QoL, and higher mortality risk. Sarcopenia has been associ-
ated with time to tumor progression and overall survival after
breast cancer [114–115]. Also, androgen deprivation therapy
(ADT), which is used as adjuvant therapy for patients with prostate
cancer, may result in toxicity-related musculoskeletal deficits,
including loss of skeletal muscle and strength, reducing physical
function and QoL[116–119].
Exercise may improve muscle strength [9] and reverse muscle
loss, [116] thereby reducing the acceleration of sarcopenia. Com-
bined resistance and aerobic exercise has been demonstrated to
improve muscle mass and strength in patients undergoing ADT
for prostate cancer [80,120]. Further knowledge on the detrimental
effects of various types of cancer treatment on muscle mass and
neuromuscular function, and potential counteractive effects of PA
and exercise is necessary. The use of voluntary and electrically
stimulated contractions may be helpful in identifying these
changes in contractile muscle properties (e.g., force production
and rate of force development and relaxation) [121].
How to motivate cancer survivors to exercise?
Traditionally, exercise trials were designed as efficacy trials to
examine whether the intervention produced the intended effect
on health outcomes under ideal circumstances [122]. The
effectiveness, which refers to whether an intervention works in
‘‘real-world’’ conditions, largely depends on the motivation and
adherence of patients [122]. To improve the effectiveness of exer-
cise, it is essential to improve the uptake, dissemination and main-
tenance of PA and exercise interventions. Common barriers to PA
among cancer survivors include physical discomfort, feeling sick,
having low mood, feelings of self-consciousness relating to physi-
cal appearance, fatigue, fear of overdoing it, and being too busy
[123–128]. Also, socio-demographic and clinical variables, smok-
ing, alcohol consumption, obesity as well as attitude, self-efficacy,
and intention may play a role [129–131]. Specific PA barriers may
vary between patient groups [128] and exercise modes. To be able
to increase adoption and maintenance of a physically active life-
style, we need to obtain insight into barriers to specific modes of
exercise, to develop strategies that help patients overcome these
barriers, and to identify the most effective formats of delivering
PA and exercise interventions (e.g. home-based, supervised, hospi-
tal-based, internet-based) and whether or not this should be com-
bined with nutrition and/or psychosocial support interventions.
Incorporation of behavior change techniques may further assist
with PA adoption and maintenance [122]. Development of inter-
ventions to improve PA behavior – i.e. behavior change trials-,
should be theory-based incorporating a clearly defined set of
behavioral change techniques [132,133].
PA participation and adherence can also be influenced by pa-
tients’ preferences. Previous studies have investigated patients’
interests in PA and exercise and their preferences regarding exer-
cise programs in various groups of cancer survivors [134,147] (Ta-
ble 4). A summary of these studies showed that most patients were
interested in receiving PA information, preferably by an exercise
specialist from a cancer center, and face-to-face (Table 4). Most pa-
tients were interested in an exercise program, feel able to partici-
pate, prefer to start exercising after completion of therapy, at
moderate intensity, alone, at home, and in the morning. Walking
is the preferred type of exercise for most patients, both in summer
and in winter. Some patients prefer a different activity each ses-
sion, whereas others prefer the same activity each time. Most pa-
tients prefer unsupervised exercise with a flexible structure
(Table 4). However, patients’ interests, counseling and program
337
preferences depend on age, current PA level, employment status,
education, income, the presence of overweight or obesity, and
medical variables including the type and stage of cancer, time since
diagnosis, type of treatment, and the presence of comorbidities
[134–139,141–147]. Also self-efficacy, enjoyment, social support,
perceived barriers, and the presence of depressive symptoms and
fatigue determine exercise preferences [142,144]. For optimal par-
ticipation in and adherence to PA and exercise programs, it is nec-
essary that they fit with patients’ interests, abilities, opportunities,
and preferences while being aware of the therapy intent of the
exercise prescription.
Conclusions
Current PA guidelines for cancer survivors are generic. It is nec-
essary to move from a one-size fits all approach to specific PA
guidelines tailored to the characteristics, needs, capabilities and
preferences of individual patients. More research is needed to be
able to develop specific guidelines for a given exercise prescription
(e.g. mode, frequency, intensity, duration), for a given cancer site at
a particular phase of the cancer trajectory, disease impact and
treatment side-effects, and for specific outcomes. These studies
should focus on identifying clinical, personal, physical, psychoso-
cial, and intervention moderators explaining ‘which’ interventions
work ‘for whom’ and ‘under what circumstances.’ It is time to
move towards second generation studies that compare different
exercise modes, frequencies, intensities, duration and timing.
Further, more insight into the working mechanisms of exercise
interventions on health outcomes in cancer survivors is needed to
improve the efficacy and efficiency of interventions. Future studies
should identify the mediating role of personal, psychosocial,
immunological, endocrine, and physiological factors in the exercise
intervention effects on health outcomes among cancer survivors.
For optimal uptake of PA and exercise interventions, it is necessary
that existing programs embrace interests and preferences of indi-
vidual patients or patient groups.
Conflict of interest statement
All authors have declared no conflicts of interest.
Authorship
All authors have made a substantial contribution to the concep-
tion and design of the study, drafting or critically revising the man-
uscript, and approved the version to be submitted.
Acknowledgements
The contribution of LMB was funded by a ‘Bas Mulder’ grant of
the Alpe d’HuZes foundation, which is part of the Dutch Cancer
Society, a fellowship granted by the EMGO Institute for Health
and Care Research, and a travel grant funded by the Edith Cowan
University.
The contribution of DAG was funded by a Movember New
Directions Development Award obtained through Prostate Cancer
Foundation of Australia’s Research Program. All sponsors had no
involvement in the content of the manuscript and in the decision
to submit the manuscript for publication.
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