The effect of exercise on cancer-related fatigue. A meta-analysis

(1)

Appendix 1. Search strategies

MEDLINE

Set History Results Comments

1 exp asthenia/ or exp fatigue/ or exp sleep deprivation/

or exp muscle weakness/ or (asthenia or fatigue or sleep deprivation or muscle weakness).mp.

71106 Fatigue terms

2 exp neoplasms/ or stem cell transplantation/ or hematopoietic stem cell transplantation/ or peripheral blood stem cell transplantation/ or cancer$.mp. or neoplasm$.mp.

2512947 Neoplasm terms

3 (randomized controlled trial or controlled clinical trial or clinical trial).pt. or (randomized controlled trial or controlled clinical trial or clinical trial).mp. or randomized controlled trials/ or random allocation/ or double-blind method/ or single-blind method/ or exp clinical trial/ or randomized controlled trials as topic/

or comparative study/ or cross-over studies/

2214724 Study design/

methodology terms

4 exp exercise therapy/ or exp exercise/ or exp physical fitness/ or exp physical exertion/ or exp physical fitness/ or exp sports/ or exp exercise movement techniques/ or exercise$.mp. or sport$.mp. or

$fitness.mp.

347927 Exercise terms

5 1 and 2 and 3 and 4 205 Base clinical set

EMBASE

1 exp fatigue/ or exp cancer fatigue/ or exp exhaustion/

or exp lassitude/ or exp asthenia/ or exp sleep deprivation/ or (fatigue$ or exhaust$ or sleep deprivation).mp.

183692 Fatigue terms

2 exp neoplasm/ or exp bone marrow transplantation/ or exp stem cell transplantation/ or exp hematopoietic stem cell transplantation/ or exp cancer therapy/ or exp cancer chemotherapy/ or exp cancer

immunotherapy/ or (cancer$ or neoplasm$).mp.

3 exp exercise/ or exp kinesiotherapy/ or exp sport/ or (exercise$ or sport$ or $fitness).mp.

428142 Exercise terms 4 randomized controlled trial/ or (random* or (doubl*

adj2 dummy) or ((singl* or doubl* or tripl* or trebl*) adj25 (mask* or blind*)) or rct or rcts or (control adj25 trial*) or multicent* or placebo* or metaanalys*

or (meta adj5 analys*) or sham or effectiveness or efficacy or compar*).ti,ab. or ct.fs. or random allocation/ or double-blind method/ or single-blind method/

4803342 Study design/

methodology terms

PsycINFO

1

(2)

Set History Results Comments 1 exp fatigue/ or exp sleepiness/ or exp hypersomnia/ or

exp sleep deprivation/ or (fatigue.mp. or exhaust$ or sleep deprivation).mp.

27992 Fatigue Terms

2 exp neoplasms/ or exp antineoplastic drugs/ or exp chemotherapy/ or (cancer$ or neoplas$).mp.

38934 Neoplasm terms 3 exp Exercise/ or exp Aerobic Exercise/ or exp

physical activity/ or exp movement therapy/ or exp physical fitness/ or exp sports/ or (exercise$ or sport$

or $fitness).mp.

5 exp clinical trials/ or exp evidence based practice/ or exp treatment effectiveness evaluation/ or

(randomized controlled trial or controlled clinical trial or clinical trial).mp.

36300 Study

design/methodology terms

EBM Reviews - Cochrane Central Register of Controlled Trials

1 exp fatigue/ or exp asthenia/ or exp sleep deprivation/

or (fatigue$ or exhaust$ or sleep deprivation).mp.

8133 Fatigue Terms 2 exp neoplasms/ or exp antineoplastic agents/ or exp

stem cell transplantation/ or exp hematopoietic stem cell transplantation/ or exp bone marrow

transplantation/ or (cancer$ or neoplas$).mp.

3 exp Exercise/ or exp Exercise Therapy/ or exp Exercise Movement Techniques/ or exp physical exertion/ or exp physical fitness/ or exp sports/ or (exercise$ or sport$ or $fitness).mp.

CINAHL

1 (MH "Fatigue+") OR "fatigue" OR (MH "Cancer Fatigue") OR (MH "Asthenia") OR (MH "Sleep Deprivation") OR "sleep deprivation" OR

"exhaustion"

17813 Fatigue Terms

2 ((MH "Neoplasms, Germ Cell and Embryonal+") OR (MH "Neoplasms+") OR (MH "Antineoplastic Agents+") OR (MH "Cell Transplantation+") OR cancer OR neoplasms)

3 ((MH "Exercise+") OR (MH "Physical Fitness+") OR (MH "Sports+") OR (MH "Exertion+") OR exercise OR sport OR fitness)

5 (MH "Clinical Trials+") OR (MH "Double-Blind Studies") OR (MH "Randomized Controlled Trials") OR (MH "Single-Blind Studies") OR (MH "Triple- Blind Studies") OR "randomized controlled trial" OR

"randomized clinical trial" OR "clinical trial"

110299 Study

design/methodology terms

2

(3)

3

(4)

Appendix 2. Characteristics of 72 randomized controlled trials included in the systematic review

Study, Year

Intervention No.

Randomized /Analyzed

Control No.

Randomized /Analyzed

Female, n (%)

Diagnosis Treatment Type and

Status

Exercise Type

Duration (weeks)

Delivery Control Group

Jadad Score

Mock, 1994¹

9/9 5/5 14 (100) Breast Chemotherapy,

radiation

Walking 20 Group

supervision

Usual care 1 Mock,

1997²

22/22 24/24 46(100) Breast Radiation Walking 6 Exercise

prescription

Usual care 1 Dimeo,

1999³

29/27 33/32 37 (67.7) Mixed SCT Aerobic

(biking)

- Individual supervision

Usual care 2 Burnham,

2002⁴

7/6 7/6 10 (83.3) Mixed Off treatment Aerobic

(treadmill)

10 Individual supervision

Usual care 1 Pinto,

2003⁵

12/12 12/6 91 (84.3) Breast Off treatment Aerobic 12 Individual

supervision

Wait list 1 Courneya^c,

2003⁶

25/24 28/28 48 (47.1) Breast Off treatment Aerobic (cycling)

Wait list 3 Coleman,

2003⁷

14/14 10/10 10 (41.7) Multiple myeloma

SCT Aerobic,

resistance, stretching

22 Exercise prescription

Contact 1

Courneya^b, 2003⁸

60/60 48/48 91 (84.3) Mixed Chemotherapy,

radiation

Walking 10 Home

exercise

Other (psychothera

py)

2

Courneya, 2003⁹

69/62 33/31 48 (47.1) Colon Off treatment Walking 16 Home

exercise

Usual care 3 Segal,

2003¹⁰

82/82 73/73 0 (0) Prostate Chemotherapy Resistance 12 Individual

supervision

Wait list 3 Headley,

2004¹¹

16/- 16/- 32 (100) Breast Chemotherapy Gentle

exercise, stretching

12 Home

exercise

Usual care 0

Cohen, 2004¹²

20/- 19/- 24 (61.5) Lymphoma Chemotherapy, radiation, off

treatment

Yoga 7 Group

supervision

Wait list 2

Dimeo, 2004¹³

34/34 35/35 19 (27.1) Mixed Surgery Aerobic

(biking)

Relaxation 3

4

(5)

Windsor, 2004¹⁴

33/33 33/32 0 (0) Prostate Radiation Walking 8 Home

exercise

Usual care 2 Campbell,

2005¹⁵

radiation

Aerobic, Walking

12 Group

supervision

Usual care 1 Pinto,

2005¹⁶

43/43 43/43 86 (100) Breast Off treatment Walking 12 Home

exercise

Contact 2

Mock, 2005¹⁷

60/54 59/54 119 (100) Breast Chemotherapy, radiation

Walking 6 Home

exercise

Usual care 3 Thorsen,

2005¹⁸

69/59 70/52 75 (67.6) Mixed Off treatment Aerobic, walking

14 Home

exercise

Usual care 2 Culos-Reed,

2006¹⁹

20/18 18/18 36 (94.7) Breast, Colon

Off treatment Yoga 7 Home

exercise

Wait list control

0 Hartvig,

2006²⁰

- - 49 (66.2) Mixed Chemotherapy Not specified - Exercise

prescription

Wait list control

1 Houbourg,

2006²¹

60/60 59/59 59 (49.6) Colon Surgery Aerobic,

resistance

12.9 Individual supervision

Relaxation 3 Brown,

2006²²

radiation

Resistance, stretching

4 Group

supervision

Usual care 1 Yuen,

2007²³

10/8 9/7 15 (100) Breast Off treatment Aerobic,

walking

Usual care 0 Daley,

2007²⁴

34/33 38/33 108 (100) Breast Off treatment Aerobic, resistance

Usual care 2 Moadel ,

2007²⁵

108/84 56/44 128 (100) Breast Chemotherapy, radiation,

surgery

Yoga 12 Group

supervision

Wait list control

2

Courneya, 2007²⁶

78/74 82/73 160 (100) Breast Chemotherapy Aerobic 18 Group

supervision

Usual care 3 Mutrie,

2007²⁷

Aerobic, resistance

12 Group

supervision

Usual care 3 Bennett,

2007²⁸

28/20 28/26 50 (89.3) Mixed Off treatment Aerobic, Walking

Contact 3

Hinds, 2007²⁹

14/14 15/15 17 (58.6) Mixed Chemotherapy Aerobic

(cycling)

Usual care 3 Monga,

2007³⁰

11/11 10/10 0 Prostate Radiation Aerobic,

walking

Usual care 0

Battaglini, 10/10 10/10 20 (100) Breast Chemotherapy, Aerobic, 15 Individual Wait list 0

5

(6)

2008³¹ radiation stretching supervision control Payne,

2008³²

10/- 10/- 20 (100) Breast Off treatment Walking 14 Exercise

prescription

Usual care 1 Hwang,

2008³³

17/17 23/20 40 (100) Breast Radiation Aerobic,

stretching

5 Group

supervision

Usual care 1 Milne,

2008³⁴

29/29 29/29 58 (100) Breast Off treatment Aerobic, resistance

Wait list control

3 Fillion,

2008³⁵

48/46 44/43 87 (100) Breast Off treatment Walking 4 Exercise

prescription

Usual care 1 Courneya,

2008³⁶

radiation

Aerobic 12 Individual

supervision

Other 3

Chang, 2008³⁷

12/11 12/11 10 (45.4) Leukemia Chemotherapy, radiation

Walking 3 Individual

supervision

Contact 1

Carson, 2009³⁸

17/17 20/17 37 (100) Breast Off treatment Yoga 8 Group

supervision

Wait list control

3 Rogers,

2009³⁹

21/20 24/21 41 (100) Breast Off treatment Not specified 12 Home

exercise

Usual care 3 Danhauer,

2009⁴⁰

radiation

Yoga 10 Group

supervision

Wait list control

2 Mustian,

2009⁴¹

20/19 20/19 27 (71.0) Mixed Radiation Aerobic,

resistance

4 Home

exercise

Usual care 3 Jarden,

2009⁴²

21/17 21/17 16 (38.1) Leukemia SCT Aerobic,

resistance, stretching

Usual care 3

Courneya, 2009⁴³

60/60 62/62 50 (41.0) Lymphoma Radiation, off treatment

supervision

Usual care 3 Adamsen,

2009⁴⁴

135/118 134/117 196 (72.9) Mixed Chemotherapy, radiation

Aerobic, resistance,

stretching

6 Group

supervision

Usual care 3

Segal, 2009⁴⁵

40/40 41/41 0 Prostate Chemotherapy,

radiation

supervision

Usual care 2 Vadiraja,

2009⁴⁶

40/40 34/34 74 (100) Breast Radiation Yoga 6 Group

supervision

Counselling 3 Yang,

2010⁴⁷

22/19 22/21 40 (100) Breast Chemotherapy Walking 12 Exercise

prescription

Wait list 1

Poorkiani, 33/27 33/30 57 (100) Breast Off treatment Not specified 8 Individual Usual care 1

6

(7)

2010⁴⁸ supervision Banasik,

2011⁴⁹

9/7 9/7 18 (100) Breast Off Treatment Yoga 8 Group

supervision

Wait list 0 Chandwani,

2010⁵⁰

30/27 31/31 61 (100) Breast Radiation Yoga 6 Individual

supervision

Wait list 2 Dodd,

2010⁵¹

44/37 39/37 83 (100) Mixed Chemotherapy,

radiation

Aerobic (treadmill),

resistance

Contact 1

Goedendorp, 2010⁵²

radiation

Walking 24 Exercise

prescription

Usual care 3 Galvao,

2010⁵³

29/29 28/28 0 (0) Prostate Chemotherapy Aerobic,

resistance

12 Group

supervision

Usual care 3 Cheville,

2010⁵⁴

49/- 54/- 37 (35.9) Mixed Chemotherapy,

radiation

Resistance 3 Group

supervision

Usual care 2 Oh,

2010⁵⁵

radiation

Stretching 10 Group

supervision

Usual care 2 Culos-Reed,

2010⁵⁶

53/37 47/24 0 Prostate Chemotherapy Aerobic,

resistance, walking

16 Home

exercise

Wait list 2

Kim, 2011⁵⁷

23/23 22/22 55 (100) Breast Off treatment Aerobic 12 Home

exercise

Usual care 2 Wang,

2011⁵⁸

35/35 37/37 72 (100) Breast Surgery Walking 6 Home

exercise

Contact 2

Vigario, 2011⁵⁹

19/19 17/17 34 (94.4) Thyroid Chemotherapy Not specified 12 Individual supervision

Usual care 0 Bourke^a,

2011⁶⁰

9/9 9/8 6 (33.3) Colon Off treatment Aerobic,

resistance

12 Group

supervision

Usual care 3 Hacker,

2011⁶¹

8/8 9/9 5 (26.3) Mixed SCT Resistance 10 Individual

supervision

Usual care 1 Baumann,

2011⁶²

24/17 23/16 17 (51.5) Leukemia/

Lymphoma

SCT Aerobic

(mobilization)

Usual care 1 Bourke,

2011⁶³

25/25 25/25 0 Prostate Chemotherapy Aerobic,

resistance

12 Group

supervision

Usual care 3 Wiskemann,

2011⁶⁴

52/40 53/40 34 (32.4) Leukemia/

Lymphoma

SCT Aerobic,

resistance

Other (pedometer)

2

Knols, 64/64 67/67 54 (41.2) Leukemia/ Off Aerobic, 12 Individual Usual care 3

7

(8)

2011⁶⁵ Lymphoma treatment/postS CT

resistance supervision

Oldervoll, 2011⁶⁶

121/121 110/110 144 (62.3) Mixed Palliative Aerobic, resistance

8 Group

supervision

Usual care 2 Donnelly,

2011⁶⁷

16/16 17/17 33 (100) Gynecologi c

Off treatment Walking, resistance

10 Home

exercise

Contact 3

Littman, 2012⁶⁸

32/30 31/27 63 (100) Breast Off treatment Yoga 24 Group

supervision

Wait list control

2 Cantanero-

Villanueva, 2012⁶⁹

38/32 40/35 78 (100) Breast Off treatment Aerobic 8 Individual

supervision

Usual care 3

Eakin, 2012⁷⁰

Aerobic, resistance

32 Home

exercise

Usual care 2 Ligibel,

2012⁷¹

61/48 60/51 112 (92.6) Mixed Chemotherapy, radiation

Aerobic 16 Home

exercise

Usual care 1 Yeo,

2012⁷²

54/54 48/48 45 (44.1) Pancreatic Surgery Walking 18 Exercise

prescription

Usual care 2 Abbreviations used: SCT – stem cell transplantation

8

(9)

Appendix 3a: Forest plot of depression reduction following an exercise versus control intervention for patients with cancer

Appendix 3b: Forest plot of sleep disruption reduction following an exercise versus control intervention for patients with cancer

9

(10)

Appendix 4a. Stratified analysis of the effect of exercise on depression

Outcome/

Subgroup

Number Studies

Number Participants

Effect (95% CI)* I²(%) P Value for Interaction Gender

Female Male

10 8 2

684 602 82

-0.72 (-1.19, -0.25) -0.02 (-0.46, 0.42)

85 0

0.03

Exercise Type**

Aerobic Walking Yoga Mixed

19 7 4 3 5

1622 470 244 123 785

-0.73 (-1.34, -0.11) -0.03 (-0.29, 0.23) -0.29 (-0.64, 0.07) -0.41 (-0.64, -0.18)

88 0 0 31

0.07

Delivery Method Home-Based Supervised

20 4 16

1658 307 1351

-0.19 (-0.44, 0.05) -0.33 (-0.46, -0.21)

94 0

0.31

Treatment Status On treatment Off treatment Mixed

20 11 7 2

1658 1161 337 160

-0.22 (-0.39, -0.06) -0.95 (-1.62, -0.28) -0.15 (-0.46, 0.16)

25 86 0

0.10

Malignancy Type Hematologic Solid

Mixed

19 5 11

3

1592 666 747 179

-0.34 (-0.55, -0.12) -0.54 (-0.91, -0.17) -0.00 (-0.39, 0.38)

3 81 29

0.14

* All analyses used a random effects model

** Resistance not included as only one study in this stratum

10

(11)

Appendix 4b. Stratified analysis of the effect of exercise on sleep disturbance**

Outcome/

Subgroup

Number Studies

Number Participants

Effect (95% CI)* I²(%) P Value for Interaction Exercise Type***

Aerobic Yoga Mixed

13 3 4 6

938 129 198 611

-0.12 (-0.46, 0.23) -0.40 (-0.74, -0.06) -0.27 (-0.43, -0.11)

0 28

0

0.53

Delivery Method Home-Based Supervised

17 3 14

1125 187 938

-0.21 (-1.00, 0.59) -0.29 (-0.41, -0.16)

86 0

0.85

Treatment Status On treatment Off treatment

16 13 3

1087 858 229

-0.28 (-0.45, -0.11) -0.14 (-0.44, 0.16)

26 19

0.42

Malignancy Type Hematologic Solid

Mixed

17 5 7 5

1125 316 387 422

-0.37 (-0.63, -0.11) -0.32 (-0.62, -0.03) -0.16 (-0.35, -0.03)

19 52 0

0.38

* All analyses used a random effects model

** Gender not included because only one study in male stratum

***Walking and resistance not included since only one study in each stratum

11

(12)

Appendix 5a. Funnel plot of fatigue

Appendix 5b. Funnel plot of depression

12

(13)

Appendix 5c. Funnel plot of sleep disturbance

13

(14)

Appendix 6. Forest plot of fatigue reduction following an exercise versus control intervention for patients with cancer stratified by year

14