Evidencetabel Tabel 1. Uitgangsvraag 1 - Welke klachten komen voor na in opzet curatieve behandeling?

Study

(trial) ID

Study type

Source of

funding/

conflicts

of interest

Setting

Hypo-

theses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Rando-

mization

method

Patient characteristics

and group

comparability

Inter-

ventions

and

compli-

ance

Control/ Compa-rator (including duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary outcome(s)

Effect size –

Secondary

outcome(s)

All other

outcom

es, end-

points

Critical

apprais

al of

study

quality

Level of

evi-

dence

Parker 2003

Cross-sectional study

Patients in oncologic follow-up in a tertiary center on average 3 years after diagnosis.

351 Not applicable

Outpatients in tertiary cancer center; response rate 92%

32% suffered from depression QoL reasonably well; average score (SF-12) 43; general population 50; SD 10). Prognostic

factors: age (↑+), gender (M +), marital status (married: +),

social support (↑+)

B

Hewitt 2003

Controlled cross-sectional study

Cancer survivors compared to the general population

4878 Not applicable

Representative sample

Cancer survivors have worse general health (odds ratio 2.97; CI 2.6, 3.4) and have more psychological problems (OR 2.2; CI 1.7, 2.8)

A2

Burgess 2005

Controlled prospec-tive cohort study

Women with breast cancer

222 5 years Follow-up every 18 months

50% had depression and/or anxiety in the 1st year, 25% in the het 2nd, decreasing to 15% after 5 years.

B

Stommel 2004

Prospec-tive cohort study

Older cancer patients (breast, lung, colon, prostate)

860 1 year Follow-up after 2-3, 5-7 months and 1 year; 93% participated in ≥2 follow-up waves

Depressive symptoms decreased after 1 year, but perceived general health did not improve in this period

B

Study

(trial) ID

Study type

Source of

funding/

conflicts

of interest

Setting

Hypo-

theses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Rando-

mization

method

Patient characteristics

and group

comparability

Inter-

ventions

and

compli-

ance

Control/ Compa-rator (including duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary outcome(s)

Effect size –

Secondary

outcome(s)

All other

outcom

es, end-

points

Critical

apprais

al of

study

quality

Level of

evi-

dence

Kim 2008

Prospec-tive cohort study with 1 assess-ment

Breast cancer survivors (mean age 47; mean 4.6 years after treatment)

1933 Not applicable

Cohort selected by cancer registry; respon-se question-naire? Multivariate analysis of determinants of fatigue and depression

22% were both fatigued and depressed; 43% were only fatigued and 3% were only depressed; More fatigue if women were younger (<50 years) (OR 1.3; CI 1.0-1.7) employed (OR 1.6; CI 1.2-2.0), GI disease (OR 2.1; CI .3-3.2).

B

Loge 1999

Controlled cross-sectional study

Hodgkin’s disease survivors (19-74 years old) compared with 2214 population controls

557 Not applicable

Questionnaires completed by 96% of cases and 99% of controls; No matching procedures;

HD survivors had higher levels of total fatigue (14.3 vs. 12.2% on a scale of 0-?; p<0.001). More HD survivors (61% vs 31%) than controls reported fatigue symptoms ≥6 months

B

Mao 2007

Controlled cross-sectional study

1904 cancer survivors and 29092 controls

30996 Not applicable

National health interview survey; response rate 74%

More cancer survivors reported recurrent pain (34 vs 17% and depressed or anxious mood (26 vs. 15%) Presence of co-morbidity increased symptom burden.

B

Study

(trial) ID

Study type

Source of

funding/

conflicts

of interest

Setting

Hypo-

theses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Rando-

mization

method

Patient characteristics

and group

comparability

Inter-

ventions

and

compli-

ance

Control/ Compa-rator (including duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary outcome(s)

Effect size –

Secondary

outcome(s)

All other

outcom

es, end-

points

Critical

apprais

al of

study

quality

Level of

evi-

dence

Peuck-mann 2007

Controlled cross-sectional study

2000 long term breast cancer survivors and 3104 controls

5104 Not applicable

Nationwide postal survey; response rate 79%

Breast cancer survivors reported slightly better general health (SF-36 subscale 72 vs 69), less bodily pain, but worse mental health (SF-36 subscale 79 vs 81).

B

Paskett 2008

Controlled cross-sectional study

5021 breast cancer survivors and 88532 controls

93553 Not applicable

Identification through Women’s Health Initiative; response?

White survivors reported lower physical functioning (-1; CI –1.5,-0.46) and general health (-3.4; CI –3.9,-2.9) and greater role limitations (-2.5; CI –3.4, -1.5) than controls.

B

Bower 2000

Controlled cross-sectional study

Breast cancer survivors in compare-son with published population surveys

1957 Not applicable

Patients recruited from 2 surveys

On average similar levels of fatigue in survivors compared to population. However, ⅓ of survivors had more severe fatigue associated with higher levels of depression, pain and sleep disturbances. More fatigue if treated with chemotherapy.

B

Study

(trial) ID

Study type

Source of

funding/

conflicts

of interest

Setting

Hypo-

theses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Rando-

mization

method

Patient characteristics

and group

comparability

Inter-

ventions

and

compli-

ance

Control/ Compa-rator (including duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary outcome(s)

Effect size –

Secondary

outcome(s)

All other

outcom

es, end-

points

Critical

apprais

al of

study

quality

Level of

evi-

dence

Ganz 2002

Prospec-tive uncontrol-led cohort study

Breast cancer survivors≥5 years after diagnosis (=baseline assess-ment)

817 Mean 6.3 years

Response rate 89%; data only for diseasefree survivors

Slight deterioration (<0.1 SD) since baseline in physical functioning, role functioning, and general health. Past use of chemotherapy predictive of poor current health.

B

Hjermstad 2005

Folow-up study with a second assessment of chronic fatigue (CF)

Patients with Hodgkin ‘s Disease aged 15-39 in Norway

476/280 with 2 CF assessments

8 years Total Fatigue score (TF) was higher for HD survivors than for the general population (14.6; CI 14.1-158.7 vs 12.1; CI 11.9-12.3; p<0.001). Of 70 patients with CF at 1st assessment 35 recovered at follow-up and 35 still had CF. Presence of B symptoms associated with continued CF (OR 1.6; CI 1.0-2.4) as was a diagnosis before 1980.

B

Tabel 2. Uitgangsvraag 2 - Welke klachten komen voor tijdens de (ziekte- en symptoomgerichte) palliatieve fase?

Author

year

Design Selection criteria Quality Results Level of

Evidence

Solano

2006

Systematic

review

Studies reporting symptom prevalence in patients with

advanced illness suffering from AIDS, heart disease, COPD,

renal disease or cancer

Search +, Selection +,

Quality ass ±

64 articles included. Depression common in all chronic diseases

(60-82% maximum prevalences). Constipation and anorexia most

common in cancer patients

A2

Teunissen

2007b

Systematic

review

Studies reporting symptom prevalence in patients with

incurable cancer

Search ± , Selection + ,

Quality ass ?, Pooling +

46 studies on 26223 patients included. Pain, lack of energy,

weakness and appetite loss occurred in >50%. Among patients in

last 1-2 weeks of life occurred fatigue, weight loss, weakness and

appetite loss in >50%

A2

Van den

Beuken

2007

Systematic

review

Studies reporting prevalence of pain in patients with cancer Search + ,Selection +,

Quality ass +, Pooling +

52 studies included. Prevalence of pain 64% (CI 58-69%) in

patients with advanced disease; 59% (CI 44-73%) in patients on

anti-cancer treatment; 33% (CI 21-46%) after curative treatment.

A2

Tabel 3. Uitgangsvraag 4 - Welke vorm van revalidatie kan klachten voorkomen/verminderen tijdens de in opzet curatieve behandeling?, Overzicht van systematische reviews. Author year

Design Selection criteria Quality Results Level of Evidence

Stevinson 2004

Systematic review

RCTs till 2003 testing excercise interventions in cancer patients

Search, selection, quality assessm +; Quality included trials poor

Effect excercise on physical functioning

Breastcancer: SMD 0.96; CI 0.49,1.43 (n=10) Any form of cancer: SMD 0.55; CI 0.12,0.97 (n= 9)

Effect excercise on fatigue

All trials: SMD -0.15; CI –0.38,0.09 (n=12) Breast cancer: SMD –0.52; CI –0.95,-0.09 (n=5) Effect on quality of life or depression infrequently reported

A2

Cramp 2008

Systematic review

RCTs till 2007 testing the effect of excercise on cancer-related fatigue in adults

Search, selection, quality assessm +; small trials (20-60 patients)

Effect excercise on fatigue

SMD (post test) -0.23; CI –0.33,-0.13 (n=22; all cancer) SMD (post test) –0.36; CI –0.49,-0.23 (n=13; breast cancer) Only during cancer therapy: SMD -0.18; CI –0.32,-0.05 (all cancer) Only post anti-cancer therapy: SMD –0.37; CI –0.55,-0.18 (all cancer)

A2

Goedendorp 2009

Systematic review

RCTs till 2008 evaluating the effect of psychosocial interventions during active cancer treatment on fatique

Search, selection, quality assessm +

There is limited evidence that psychosocial interventions are effective in reducing fatigue. Short interventions specific for fatigue seemed more effective than other interventions; these consisted of education about fatigue (1), teaching in self-care and coping (2) and teaching activity management (3)

A2

Liu 2009

Systematic review

RCTs till 2007testing the effect of excercise in patients with hematologic cancer

Search, selection, quality assessm +; Quality included trials poor

10 trials, of which only 3 were RCTs testing a variety of excercise protocols, which revealed encouraging results

Lofti-Jam 2008

Systematic review

RCTs relating to self-care strategies for chemotherapy-induced adverse effects

Search, selection, quality assessm +; Quality RCTs generally low

Nausea & vomiting: 2 of 2 studies show significant effect for cognitive distraction and for excercise, 10 of 13 for relaxation and 2 of 2 for systematic desensitization. No firm conclusions possible

A2

Conn 2006

Systematic review

Any intervention study to increase resistance, flexibility or endurance excercise

Poor quality. No selection for study design, quality assessment unclear; pooling studies of variuous study designs without sensitivity analyses on higher quality studies

It is unclear what can be concluded from this review

Markes 2006

Systematic review

Studies till 2004 testing the effect of excercise in women undergoing adjuvant treatment for breast cancer

Search, selection, quality assessm +;

Cardioresp. fitness (4 trials; 217 pat.): SMD –0.12; CI –0.37,0.13 Fatigue (5 trials; 317 pats): SMD –0.12; CI -0.37,0.13

Author year

Design Selection criteria Quality Results Level of Evidence

Included studies generally of moderate quality

Quality of life cancer specific (1 trial; 19 pats): SMD 0.95; CI –0.01,1.91 Breast cancer specific (1 trial; 19 pats): SMD 0.78; CI –0.16,1.72 Anxiety (1 trial, 44 pats) WMD –0.66; CI –1.25,-0.06.

Lee 2007

Systematic review

Trials about effect tai chi in cancer patients Search, selection, quality assessm +; Only 3 RCTs of limited quality included

Inconclusive results from 3 trials

Knols 2005

Systematic review

Trials till 2004 reporting the effect of physical excercise during or after cancer therapy

Search, selection, quality assessm +; most included trials were of limited quality

Cancer patients may benefit from physical excercise during or after treatment.

Jacobsen 2007

Systematic review

RCTs till 2005 including a psychological or activity-based intervention on fatigue in cancer patients

Search, selection, quality assessm +; No description of individual studies

Overall a significant effect was seen for psychological interventions (SMD 0.10; CI 0.02,0.18), but not for activity based interventions (SMD 0.05; CI –0.08,0.19). Only significant effects for other cancers on fatigue (SMD 0.13; CI 0.01,0.25), not for breast cancer (SMD 0.07; CI –0.03,0.17) and no effects seen on vigor. Group interventions (SMD 0.15; CI 0.1,0.28, but not individual interventions (SMD 0.07; CI –0.02, 0.17) were effective.

Tompkins-Stricker 2004

Systematic review

Intervention studies till 2003 reporting the effect of excercise on fatigue in cancer patients

Search, selection +, quality

assessm -;

No summary estimates presented

Kirshbaum 2006

Systematic review

Studies till 2004 reporting the effect of excercise in breast cancer patients

Search, selection, quality assessm +; Results RCTs not differentiated from results other designs

Most investigated interventions seem effective, but no summary estimates presented

De Nijs 2008

Systematic review

Studies till 2005 reporting effect of nursing interventions during cancer treatment

Search +, selection+; no quality assessment

No summary estimates presented

McNeely 2006

Systematic review

RCTs till 2005 reporting effect of excercise interventions on stage 0-III breast cancer patients

Search, selection, quality assessm +; Only 4 of 14 studies of high quality

Fatigue: WMD (FACT-B; 3 studies) 6.6; CI 1.21,33.6. after treatment; no significant effect during treatment. Cardioresp fitness (3 studies): WMD (VO2peak) 3.4;CI 1.7,5.1ml/kg/min Physical functioning (4 studies): SMD 0.84; CI 0.36, 1.32.

Kangas 2008

Systematic review

Studies till 2006 reporting the effect of non-pharmacological interventions on patients treated for cancer

Search +, selection+; quality assessm +; Meta-analysis produces WMDs?? Unclear!

Meta-analyses conducted on 57 RCTs indicated that exercise and psychological interventions provided reductions in CRF, with no significant differences between these 2 major types of interventions considered as a whole Results of comparison of excercise with psychological treatment in a wide range of subgroups presented.

Strong 2006

Systematic review

Studies till 2005 on the effect of excercise on cancer patients with osteolytic lesions

Search +, selection+; Physiological and psychological effects of excercise. A specific protocol is reccommended

Tabel 4. Uitgangsvraag 4 - Welke vorm van revalidatie kan klachten voorkomen/verminderen tijdens de in opzet curatieve behandeling?, Overzicht vanRCT’s

Study

(trial) ID

Study type

Source of

funding/

conflicts of

interest

Setting

Hypot-

heses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Randomi-

zation

method

Patient

Characte-

istics and

group

compara-

bility

Interventions

and

compliance

Control/ Comparator (including duration, dose)

Primary Outcome Measure (s)

Secondary

Outcome

Measure (s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level

of evi-

dence

Cour-neya 2007a

RCT

Public research funds

Multi-center study Canada

Breast cancer survivors receiving chemo-therapy

242/19 Median 17 weeks (CI 9-24)

Computer generated + concealed allocation

Mean age 49; groups comparable

78 Aerobic excercise training; 82 resistance exercise Compliance 70%

82 usual care

P: Cancer-specific QOL S: self-esteem, physical fitness

P: no improve-ment

Both aerobic and resistance excercise improved self-esteem, physical fitness and chemotherapy comple- tion rate. Sustained effects at 6 months.

Blinded outcome assessment?

B

Study

(trial) ID

Study type

Source of

funding/

conflicts of

interest

Setting

Hypot-

heses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Randomi-

zation

method

Patient

Characte-

istics and

group

compara-

bility

Interventions

and

compliance

Control/ Comparator (including duration, dose)

Primary Outcome Measure (s)

Secondary

Outcome

Measure (s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level

of evi-

dence

Segal 2009

RCT Public research funds

Radiothe-rapy-treated prostate cancer patients

121/11 24 weeks Computer-generated numbers; central concealed allocation

Mean age 66; comparable groups

40 Resistance excercise; 40 aerobic exercise; Compliance 86%

41 usual care

P: fatigue Fatigue improved at 12 weeks after resistance (MD –1.5; CI –3.8, 0.9 and aerobic exercise (MD –0.9; CI –3.2,1.3) compared to usual care. (MD –5.6; CI –7.8,-3.3) Only resistance excercise induced improvements at 24 weeks (MD 2.3; CI 0.1,4.5)

Improvements in aerobic fitness, body strength after aerobic and resistance excercise

Blinded outcome assessment?

B

Mutrie 2007

RCT Public research funds

Chemo- or radiotherapy-treated stage 0-III breast cancer patients

203/11 6 months With randomised permuted blocks by telephone to an interac-tive voice response system

Mean age 52; comparable groups

101 excercise program: 20 minutes excercise (low level aerobics + muscle strength-ening; com-pliance?

102 Usual care + leaflet with instuctions for safe excercise after cancer

Quality of life (FACT-G)

No improve-ment of FACT-G (p=0.053) MD 3.6; CI 0.0,7.3 MD FACT-B: 1.5; CI 0.1,2.9 (p=0.039)

Significant effects for reported activity and positive mood (MD 3.9; CI 1.6-6.1)

Outcome assessment blinded? Compliance?

B

Study

(trial) ID

Study type

Source of

funding/

conflicts of

interest

Setting

Hypot-

heses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Randomi-

zation

method

Patient

Characte-

istics and

group

compara-

bility

Interventions

and

compliance

Control/ Comparator (including duration, dose)

Primary Outcome Measure (s)

Secondary

Outcome

Measure (s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level

of evi-

dence

Daley 2007a

RCT Public research funds

Inactive women treated for localized breast cancer

108/12 8 weeks Telephone randomi-zation using stratified random permuted blocks

Mean age 51; no smokers in interventiongroup compared to 14 and 11% in control groups

50 m. 1 to 1 ecercise session (34) 77% compliance

36 excercise placebo (compliance 89%); 36 usual care

1: Quality of life (FACT-G) 2nd: fatigue, depression

MD 9.8 (CI?) Also significant effects for well-being, physical well-being. Modest improvements for psychological outcomes

Outcome assessors not blinded

B

Courn-eya 2008

Anemic solid cancer patients receiving darbepoetin α

12 weeks Computer-generated randomization; concea-led alloca-tion

Areobic excercise 3 times/week

Quality of life FACT-anemia scale. 2nd: fatigue

FACT-an: MD –6.9; CI –22, 8.3. fatigue: MD –1.3; CI –8.0, 5.4

greater VO2peak in intervention group

Outcome assessors blinded?

B

Tabel 5. Uitgangsvraag 5 – Welke vorm van revalidatie kan klachten voorkomen/verminderen na afloop van de in opzet curatieve behandeling?, Overzicht systematische reviews. Author year

Desing Selection criteria Quality Results Level of evidence

De Backer 2009

Systematic review

Studies till dec 2008 reporting the effect of resistance training ikn adult cancer patients treated with curative intent

Search, selection, quality assessm +; Resistace training generally composed of 1-3 sets of 8-12 repititions of large muscle groups. Positive training effects observed for cardiopulmonary and muscle function.

B

Knols 2005

Systematic review

Trials till 2004 reporting the effect of physical excercise after cancer therapy.

Search, selection, quality assessm +; most included trials were of limited quality and most were very small (12-60 pats)

Among larger trials in breast cancer patients improvement in various physiologic measurements. No improvements in clinically important outcomes reported. Larger trials in a mixed solid tumor population were generally larger and reported improvements in fatigue, anxiety, physical strength, and functional well-being.

B

Cramp 2008

Systematic review

RCTs till 2007 testing the effect of excercise on cancer-related fatigue in adults.

Search, selection, quality assessm +; small trials (most 2-60 patients 1 of 86, 1 of 101 patients) of poor quality. Mode, intensity and timing of excercise varied greatly.

Effect excercise on fatigue. Only post anti-cancer therapy: SMD –0.37; CI –0.55,-0.18 (all cancer)

B

Van Weert 2008

Systematic review

Systematic reviews and RCTs on the effect of excercise interventions (combined interventions excluded) in cancer survivors.

Search + selection + results quality assessment not reported.

Evidence supports the effectiveness of aerobic exercise on exercise performance (meta-analyses, moderate effect size). There is meta-analysis evidence on the effectiveness of exercise on fatigue and role functioning, but effect sizes are contradictory and small, respectively. Evidence on the effectiveness of progressive resistance exercise (PRE) in cancer patients is promising (on the RCT level). Concerning the content, two modalities of exercise are commonly described: aerobic exercise training and PRE. Aerobic training seems to have beneficial effects on aerobic capacity, fatigue and physical role functioning. PRE alone or combined with aerobic training may have a beneficial effect on muscle strength, fatigue and physical role functioning. Regarding the intensity, training programmes with a moderate to high intensity seem to be effective in improving aerobic capacity and muscle strength. Concerning reduction of fatigue and the improvement of physical role functioning, findings are not consistent and some argue against a high training intensity. Furthermore, aerobic training (cycling or walking) alone or combined with PRE seems to be effective and applicable to all defined problems.

B

Cheema 2008

Systematic review

RCTs and nonrandomized studies till May 2007 reporting the effect of progressive resistance traing in adult breast cancer patients.

Search +, selection +, quality assessment + Only 1 large RCT (n=242); other RCTs with 16-86 participants. Only outcomes

The 2 largest RCTs included in this review reported significant results on a variet of outcomes. However, because selective reporting is likely, no conclusion possible.

C

Author year

Desing Selection criteria Quality Results Level of evidence

with significant results presented

McNeely 2006

Systematic review

RCTs till 2005 reporting effect of excercise interventions on quality of life, cardiorespiratory fitness or physical functioning in stage 0-III breast cancer patients

Search, selection, quality assessm +; Only 4 of 14 studies of high quality and most were very small (19-52 pats; one had 119 and one had 123 patients)

Fatigue: WMD (FACT-B; 3 studies) 6.6; CI 1.21, 33.6 after treatment; no effect during treatment? Cardioresp fitness (3 studies): WMD (VO2peak) 3.4; CI 1.7, 5.1ml/kg/min. Physical functioning (4 studies): SMD 0.84; CI 0.36, 1.32.

B

Schmitz 2007

Systematic review

Studies till 2005 reporting the effect of physical activity interventions on fatigue quality of life and cardio-respiratory fitness in cancer survivors

Search +, selection unclear , quality assessment unclear

No conclusions possible, because no distinction made between RCTs and other studies.

C

Kangas 2008

Systematic review

Studies till 2006 reporting the effect of non-pharmacological interventions on cancer-related fatigue in patients treated for cancer

Search +, selection+; quality assessm +; Meta-analysis produces WMDs? Unclear!

Meta-analyses conducted on 57 RCTs indicated that exercise and psychological interventions provided reductions in CRF, with no significant differences between these 2 major types of interventions considered as a whole. Results of comparison of excercise with psychological treatment in a wide range of subgroups presented

C

Osborn 2006

Systematic review

Studies reporting naar het effect van cognitieve gedragstherapie en ‘patient education’op KvL bij volwassen kankerpatiënten

Search +, selection + , quality assessment – , unclear analysis included trials are small and unblinded

Effect on depression: SMD 1.2;CI 0.2-2.2; anxiety: SMD 2.0; CI 0.7-3.3; no effect on pain or physical functioning Quality of life: WMD 0.91; CI 0.38—1.44.

C

Newell 2002

Systematic review

RCTs reporting the effect of psychological interventions on outcome of cancer patients and other study designs

Search +, selection vague, quality assessment + Methodological quality RCTs poor

Only tentative conclusions possible B

Rehse 2003

Systematic review

Controlled studies reporting the effect of psychosocial interventions on quaality of life of cancer patients.

Search +, selection vague, quality assessment unclear; unconventional analysis

No conclusions possible C

Tatrow 2006

Systematic review

RCTs till 2004 reporting the effect of CBT* on distress and pain in breast cancer patients.

Search + , selection +, quality trials not reported, but small size (most 16-92 pats) unclear wether effects size represents relative risk or risk difference

Effect CBT on distress 0.31; CI 0.07-0.55 Egffect CBT on pain: 0.49; CI 0.09-0.90 Individual treatment approaches had significantly larger effects compared to studies employing group approaches (but individual approach studies were lsmaller)

C

Graves 2003

Systematic review

RCTs reporting the effect of interventions based on social cognitive theory on quality of life of cancer patients

Search +, selection +, no quality assessment; characteristics individual studies not presented

Interventions with more SCT-based components had greater effect sizes (p≤0.01)

C

*CBT: Cognitive behavioral treatment

Tabel 6. Uitgangsvraag 5 - Welke vorm van revalidatie kan klachten voorkomen/verminderen na afloop van de in opzet curatieve behandeling?, Overzicht RCT’s

Study

(trial) ID

Study type

Source of

funding/

conflicts of

interest

Setting

Hypothe-

ses

Eligibility criteria

Sample size/

Lost to

follow up

Duration

of the

Study

Randomi-

zation

method

Patient Character-ristics and group compare-ability

Interven-

tions and

compli-

ance

Control/ Compa-rator (including duration, dose)

Primary Outcome Measure(s),

Secondary

Outcome

Measure(s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

outcomes,

endpoints

Critical

appraisal

of study

quality

Level of

eviden-

ce

Gielis-sen 2006

RCT Public research funds

Out-patient clinics

Disease-free cancer patients with severe fatigue

98/7 6 months By sequen-ce of labe-led cards in sealed numbered envelopes.

Mean age 45; no baseline differences reported

5-26 ses-sions of Cogni-tive beha-viorral therapy; compli-ance?

Waiting list

Fatigue severity by the Checklist Individual Strenth (CIS) subscale and functi-onal impair-ment by the Sickness Impact Profile (SIP)

CIS: MD 13.3; CI 8.6,18.1 SIP: MD 383; CI 197,569 More clinically significant improvement in fatigue severity for CBT (54% vs. 4%) and functional impairment (50% vs. 18%) compared to controls

MD Psychological distress 21.6; CI 12.7, 30.4

Open label RCT: envelopes opened by researcher in presen-ce of patients

B

Study

(trial) ID

Study type

Source of

funding/

conflicts of

interest

Setting

Hypothe-

ses

Eligibility criteria

Sample size/

Lost to

follow up

Duration

of the

Study

Randomi-

zation

method

Patient Character-ristics and group compare-ability

Interven-

tions and

compli-

ance

Control/ Compa-rator (including duration, dose)

Primary Outcome Measure(s),

Secondary

Outcome

Measure(s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

outcomes,

endpoints

Critical

appraisal

of study

quality

Level of

eviden-

ce

Milne 2008a

RCT Public research funds

Hospital-based

Excercise training improves QOL, fatigue, anxiety and fitness

Women with stage I-II breast cancer≥18 years, <2 years after diagnosis with no evidence of disease recurrence

58/2 24 weeks Computer-generated program; concealed allocation

Mean Age 55; 70% received chemotherapy

Imme-diate excer-cise (IE) (week 1-12): 3 sessions/ week of aerobic (20 min.) + resis-tance training (10-15 repititions of 12 dif-ferent excerci-ses); 60% compli-ance

Delayed excercise (DE) (week 13-24): only telephone calls from week 1-12) therafter intervention described; IE: reverse order; 62% compliance

QOL (FACT-B); fatigue (Schwartz cancer fatigue scale); anxiety (social physique anxiety scale-7); aerobic fitness

QOL: ↑ in IE (21 p) in 1-12 week period compared to ↑ 5.3 p in DE; in week 13-24 ↑6.5 in IE and ↑ 30 in DE. (ANOVA: p<0.001) Similar results for other outcomes

Blinding unclear

B

De Backer 2007b

Uncontrolled observatio-nal study

Public research funds

Hospital-based

Strength training is more effective than aerobic training

Patients treated with chemotherapy with a curative intention.

57/9 18 weeks Not stated High intensity strength training; 6 dropped out due to cancer recur-rence, 5 for others reasons.

No controls

Muscular strength, VO2max, QOL

VO2max increased by 10%; muscular strenth increased. HRQOL improved

Lack of control group precludes conclusion about effects.

C

Study

(trial) ID

Study type

Source of

funding/

conflicts of

interest

Setting

Hypothe-

ses

Eligibility criteria

Sample size/

Lost to

follow up

Duration

of the

Study

Randomi-

zation

method

Patient Character-ristics and group compare-ability

Interven-

tions and

compli-

ance

Control/ Compa-rator (including duration, dose)

Primary Outcome Measure(s),

Secondary

Outcome

Measure(s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

outcomes,

endpoints

Critical

appraisal

of study

quality

Level of

eviden-

ce

De Backer 2008

Quasi-experimental study

Private funds

Hospital-based

High intensity resistance training improves quality of life

Cancer patients curatively treated with chemotherapy

49/4 and 22/5 controls

1 year Not applicable

No significant differences in age, gender, cance diagnosis or drop-outs

18 wks 2/wk training program conprising high intensity (6 excer-cises tar-geting large muscle groups at 65-80% of one-repition maximum ) and interval training

No excercise under supervision

Muscle strength, cardiopulmonary function, fatigue, HRQOL

Muscle strength and cardio-pulmonary strength improved more in intervention group. No differences between groups in HRQOL or fatigue

Compara-ble groups; confounding by indica-tion not likely

B

Study

(trial) ID

Study type

Source of

funding/

conflicts of

interest

Setting

Hypothe-

ses

Eligibility criteria

Sample size/

Lost to

follow up

Duration

of the

Study

Randomi-

zation

method

Patient Character-ristics and group compare-ability

Interven-

tions and

compli-

ance

Control/ Compa-rator (including duration, dose)

Primary Outcome Measure(s),

Secondary

Outcome

Measure(s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

outcomes,

endpoints

Critical

appraisal

of study

quality

Level of

eviden-

ce

May 2008

RCT Public research funds

Referrals to rehabi-litation

Patients ≥18 years; last cancer treatment>3 months; ≥3 positive findings on physical complaints, reduced physical capacity, psychological pro-blems, fatigue or sleep pro-blems

147/144? 1 year Randomisation list used by indepen-dent re-searcher at each center

Rehabilitation in groups of 8-12 cancer survivors; PT super-vised by physical therapists; 84% adheren-ce

CBT supervi-sed by psycholo-gist and social worker; 82% adheren-ce

Physical activity (Physical Activity Scale for the elderly (PASE); VO2 peak; muscle strength Quality of life (EORTC QLQ-C30)

Changes in excercise capacity, muscle strength and physical activity not different between groups. No dif-ference between groups

Good quality; lack of blinding participants or staff not likely to effect the results

A2

Daley 2007a

RCT Public research funds

Excercise therapy improves quality of life

Inactive women treated for localized breast cancer

108/12 8 weeks; follow-up 24 weeks

Telephone randomization using stratified random permuted blocks

Mean age 51; no smokers in interventiongroup compared to 14 and 11% in control groups

34 excer-cise ther-apy: 50 m. 1 to 1 aerobic ecercise 77% complian-ce

36 excer-cise pla-cebo: 24 1 to 1 50 m sessions with condi-tioning/ stretching excerci-ses. 89% compliance. 38 usual care

1: Quality of life (FACT-G) 2nd: fatigue, depression

Excerrcise vs usual care: MD FACT-G 9.8; CI 2.2,17. after 8 weeks. Excercise placebo vs usual care: MD 6.6; CI –0.9, 14. No differences after 24 weeks

After 24 weeks modest improve-ments in depression

Outcome assessors not blinded

B

Study

(trial) ID

Study type

Source of

funding/

conflicts of

interest

Setting

Hypothe-

ses

Eligibility criteria

Sample size/

Lost to

follow up

Duration

of the

Study

Randomi-

zation

method

Patient Character-ristics and group compare-ability

Interven-

tions and

compli-

ance

Control/ Compa-rator (including duration, dose)

Primary Outcome Measure(s),

Secondary

Outcome

Measure(s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

outcomes,

endpoints

Critical

appraisal

of study

quality

Level of

eviden-

ce

Cadmus2009

RCT (YES study)

Public research funds

Home-based

Excercise improves QOL ans psychoso-cial and physical functioning

Inactive post-menopausal breast cancer survivors 34-79 tears who com-pleted adjuvant therapy ≥1 yr

75/1 6 months Computer generated; concealed allocation

Mean age 55; groups comparable

Supervi-sed trai-ning pro-gram at local health club/67%

Usual care + excercise program materials

Happiness, depression (CES-D), anxiety

Overall no significant changes in QOL

In subset of patients with low QOL at baseline intervene-tion better on FACT-B social/ family well being (p<0.001) and SF-36 social funct. (p<0.05)

B

Tabel 7. Uitgangsvraag 6 – Welke vorm van revalidatie kan klachten voorkomen/verminderen tijdens de ziekte- en symptoomgerichte palliatieve fase?

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

Brown

2006

Stratified

RCT

Linse Bock

Foundation

and Saint

Mary’s Hosp-

ital Spon-

sorship

Board. No

indication of

conflicts of

interest

Division of

Radiation

Oncology

Mayo Clinic

Rochester

To examine

the effect of

participation

in a structu-

red, multidis-

ciplinary in-

tervention on

fatigue for

advanced

cancer

patients

Inclusion

criteria: adult

advanced

cancer

patients

planned to

undergo

radiation

therapy –

cancer diag-

nosis within

the last 12

months,

expected

survival of at

least 6

months, but

5-year

survival

probability <

50%,

treatment

recommenda

tion of

radiation

therapy for at

Randomi-

zed: Inter-

vention: 57;

control: 58

Completed

week 4 as-

sessment:

Intervention:

46; control:

54

4 weeks

intervention.

Completion

of question-

naires at

week 4, 8,

and 27

Stratification

for tumor

type, age,

gender, and

ECOG

score, using

a minimize-

tion pro-

cedure that

balances the

marginal dis-

tributions

Comparable

groups. 35%

women, 80%

over 50

years, 60%

on current

chemo-

therapy,

mean radio-

therapy dose

5322 cGy in

29 fractions,

80%

married,

55% em-

ployed,

median

hemoglobin

12,3, mean

MMSE 28,7,

mean POMS

68, mean

SDS 66,

mean LASA

54, mean

STAI 55

Participants

attended 8

90-minutes

sessions

over 4

weeks.

Manual

about the

sessions.

Each

sessions had

a theme

focusing on

quality of life.

Begin: 20

minutes

exercise,

followed by

educati-onal

information,

cognitive-

behavioral

strategies,

discussi-on,

and support.

Motion,

No inter-

vention,

standard

care

Primary:

single-item

Linear Ana-

logue Self

Assessment

(LASA) fati-

gue ques-

tion. Secon-

dary: Profile

of Mood

States

(POMS),

Fatigue-

Inertia

Subscale

and Vigor-

Activity Sub-

scale, Spiel-

berger’s

State-Trait

Anxiety

Inventory

(STAI),

Symptom

Distress

Scale (SDS)

No signi-

ficant differ-

rences in

mean fatigue

scores be-

tween arms

at any week.

There were

trends noti-

ced favoring

the standard

treatment

(less fatigue

when no

intervention)

Overall qua-

lity of life

improved in

the interven-

tion arm (i.e.

primary end-

point of the

initial study,

but not re-

ported in

detail in this

article)

Randomized

study, but

not blinded

(full blinding

is not possi-

ble because

of the inter-

vention, but

the investi-

gators could

have been

blinded). To-

tal number of

participants

is not that

high

B

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

least 2

weeks. Ex-

clusion crite-

ria: MMSE <

20, ECOG >

3, active al-

cohol or sub-

stance de-

pendence

(except nico-

tine), active

thought dis-

order, sui-

cidal plans,

participation

in psycho-

social re-

search trial

stretching,

functional

exercises.

Individualize

d home

program.

End of ses-

sion:

relaxation

exercise

Cristo-

pher

2004

Pilot pre-

post

study in

one

group

No

information

Oncology

Community

Outreach

Program,

University of

Masachu-

setts

To evaluate

the impact of

a commu-

nity-based

12-week

exercise

program on

physical and

psychosocial

well-being in

Participants

of fall and

winter

exercise pro-

grams.

Women that

survived

cancer. No

criteria about

life expect-

21 patients

(12 fall

exercise, 9

winter

exercise)

12 week

exercise

program,

pre- en post-

test

question-

naires

No randomi-

zation

All women,

al-most all

breast can-

cer patients,

mean age 60

years, al-

most all

white

patients,

80%

12 week

exercise

program,

twice a

week, low-

impact

aerobics,

toning,

flexibility

exercises,

No control

group

Pscychosoci

al Adjust-

ment to Ill-

ness Scale

(PAIS-SR),

Profile of

Mood

States-short

form (POMS-

SF), Symp-

Almost no

statisti-cally

significant

differrences

were found.

In the group

that attended

the fall

exercise

statisti-cally

No other

outcomes

No compara-

tive design,

weak de-

scription of

important

parameters,

e.g. exercise

program,

patient re-

cruitment,

C

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

women

cancer

survivors

ancy married,

mean time

since

diagnosis 44

months,

mean time

since treat-

ment ended

22 months

relaxation

techniques

tom Distress

Scale (SDS),

Piper Fati-

gue Scale

(PFS), Qua-

lity of Life-

Cancer Sur-

vivors Scale

(QOL-CS)

significant

improvement

was mea-

sured on

subscales

(domestic

environment,

psychosocial

distress, and

social well-

being)

poor article,

very few pa-

tients, no

distinction in

cancer stage

and life

expectancy

Cramp

2008

Coch-

rane

syste-

matic

review

No external

sources of

support,

internal

source:

faculty health

social care,

University

West Eng-

land, no indi-

cations of

conflict of

interest

- To evaluate

the effect of

exercise on

cancer-rela-

ted fatigue

during and

after cancer

treatment

Only RCT’s

were inclu-

ded. Adults

of any age,

regardless of

gender, tu-

mour type,

tumour sta-

ge, type of

cancer treat-

ment. Pa-

tients could

be in active

treatment, in

long-term

follow-up or

receiving

28 RCT’s

included,

total 2083

patients

- - Most

patients had

breast can-

cer, stages

of cancer

varied, sta-

ges of treat-

ment varied,

most pa-

tients were

women,

mean age

39-69 years

Any exercise

intervention

aimed to

reduce fa-

tigue asso-

ciated with

cancer

No exercise,

usual care,

alternateve

treatment

Patient-

reported

fatigue (mul-

tiple scales),

exercise

maintenance

on follow-up,

attrition, time

spent exer-

cising, aero-

bic capacity,

quailty of life

measures,

anxiety, de-

pression,

self-efficacy

Less fatigue

in pa-tients

that were in

the inter-

vention

group (SMD

-0,23; 95%

BI -0,33- -

0,13). Pre-

post test

changes:

intervention

more effect-

tive (SMD -

0,23; 95% BI

-0,36- -0,09)

In breast

Only meta-

analyses

reported in

this evidence

table. To re-

port valid re-

sults of sing-

le studies

(that are

mentioned in

the review),

one should

have more

information

of those

single trials

Good Coch-

rane syste-

matic re-

view. Value

for this

guideline

however

limited,

because of

no distincti-

on in the

analyses in

subgroups of

cancer stage

(although

these data

are collected

A1

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

palliative

care

cancer pa-

tients this

effect was

even bigger

as stated in

the paper)

London

2005

Prospec-

tive ob-

servatio-

nal study

Robert Wood

Johnson

Foundation

Promoting

Excellence

National Pro-

gram Office,

Supportive

Care of the

Dying

CALL Care

sites, facile-

ties of sup-

portive care

for the dying:

a coalition

for compas-

sionate care

To evalu-ate

the CALL-in-

terventi-on in

pa-tient with

life-threa-

tening can-

cer, cardiac

illness, res-

piratory

conditions or

dementia

Cancer

stage IV,

Car-diac

illness stage

III or IV or

ejection

fraction <

25%, De-

mentia stage

6 or 7 of

FAST, Res-

piratory

Illness Kar-

novsky score

< 50 or re-

quired oxy-

en for acti-

vities of daily

living

295 pa-tients

at enrol-

ment, no

completed

question-

naires at 18

months (94

patients died

during the

study)

18 months No randomi-

zation

Mean age 72

years, 62%

female, 88%

whites, 41%

lived at

home with

family, 21%

alone at

home, and

26% in a

nursing

home

CALL Care

Approach: a

variety of

services

(e.g. coordi-

nate physic-

cian visits,

connect with

spiritual care

provider,

educate

patient and

family, plan

for universal

activities,

pro-active

bereavement

follow-up),

coordinated

by a specific

multidisciplin

ary CALL

Care team

No control

group

Scores on

Modified City

of Hope

Patient

Question-

naire (55

items on

physical,

emotionnal/

relationship,

spiritual,

health-care

experience,

and health

care provi-

ders commu-

nication) at

enrollment,

1, 3, 6, 9, 12,

15, and 18

months

Comparing

the enroll-

ment score

and the last

data alive

there were

better, but

insignificant

scores on

fatigue and

nau-sea, and

better sig-

nifycant

scores on

sleep,

mouth/ food

symptoms

(e.g. dry

mouth,

appetite

changes),

intestinal

problems,

breathing

No other

outcomes

No compara-

tive design,

no informa-

tion on pa-

tient recruit-

ment, large

amount of

patients lost-

to-follow-up,

probably

selective

C

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

problems,

and pain

Lowe

2009

Syste-

matic

review

National

Cancer

Institute of

Canada

Canadian

Cancer So-

ciety, Socio-

behavioral

Cancer Re-

search Net-

work

- To review

the evid-

ence of

physical

activity as

supportive

care inter-

vention in

palliative

cancer

patients

A study had

to examine a

physical act-

vity inter-

vention in

palliative

cancer pa-

tients, aged

18 years or

older, re-

gardless of

gender, tu-

mor type, or

type of can-

cer treat-

ment.

Palliative

cancer was

defined as

progressive,

incurable lo-

cally recur-

rent or me-

tastatic can-

cer, with a

life expec-

6 studies,

total 84

patients. All

pilot studies,

some case-

reports

- - Mean age 58

years, 64/84

women,

most pa-

tients having

breast can-

cer, followed

by gastroin-

testinal can-

cer

Supervised

group exer-

cise pro-

grams and

unsupervi-

sed home-

based phy-

sical activity

program

(Duke Ener-

gizing Exer-

cise Plan for

9 patients,

Arm-chair

Fitness and

gentle exer-

cise video for

38 breast

cancer

patients,

group

exercise

program

focused on

muscle

strength,

Most studies

had no com-

parison

Primary

outcomes:

Patient-re-

ported

quality of life,

patient-

reported

physical

functioning,

patient-

reported

fatigue.

Secondary

outcomes:

objective

measures of

physical

fitness and

physical

functioning,

patient-re-

ported

palliative

symptoms

In one of the

studies sig-

nificant lower

decline in

total well-

being scores

in intervene-

tion group.

The only

RCT showed

no significant

differences

No other

outcomes

Systematic

review of

poor studies,

only one

RCT, rest of

the studies

non-compa-

rative and

even case

reports. No

meta-analy-

sis. Classifi-

cation on the

validity is not

possible due

to the poor

quality of the

underlying

studies

No level

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

tancy of less

than 12

months

standing

balance and

aerobic en-

durance for

34 patients)

Mustian

2006

Newly diag-

nosed can-

cer patients

undergoing

curative

treatment �

therefore this

study is

excluded for

further

analysis

Oldervoll

2006

Pilot

study,

Phase II

Norwegian

Foundation

for Health

and Reha-

bilitation and

the

Norwegian

Cancer So-

ciety. No in-

dication of

conflict of

interest

Oncological

outpa-tient

clinic at St.

Olav Hospi-

tal in Trond-

heim and

Hos-pice

Lovenberg

To evaluate

the effect of

a 6-week

structured

exercise pro-

gram on

HRQOL,

fatigue, and

physical per-

formance in

cancer pa-

tient with

Cancer pa-

tients with a

life expec-

tancy be-

tween 3 and

12 months,

Karnofsky

performance

score > 60,

adequate

pain relief,

and lived

63 patients

at enroll-

ment, 29

patients

dropped out

due to

sudden

death, or

medical or

social rea-

sons. There

seems to be

6 weeks No randomi-

zation

15 males, 19

females,

mean age 65

years, 88%

not employ-

yed, median

KPS 80,

differ-rent

types of

cancer (16

gastro-intes-

tinal cancer),

Exercises in

groups (3-8

patients per

group), twice

a week, 50

minutes per

session, 6

weeks long.

Warm-up

session,

circuit trai-

ning with 6

No control

group

EORTC-

Quality of

Life Ques-

tionnaire-C

30 (EORTC

QLQ-C30),

Fatigue

Question-

naire (FQ), 6

minute walk,

timed sit-to-

stand, functi-

Significant

improvement

in emotional

functioning

(69�78, p=

0,002).

Fatigue

score de-

creased:

51�43

(p=0,06; less

fatigue).

Increase in

walking

distance by

29 meter (p=

0,007), de-

crease in

time sit-to-

stand of 1

second

(p=0,001)

Well-docu-

mented

study, but

non-compa-

rative de-

sign. Only a

few patients

in the study

C

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

short life

expectancy

less than 30

minutes from

the hospital.

Consecutive

patients

selective

follow-up �

34 pa-tients

in analysis

80% meta-

stases

stations,

relaxation/

stretching

session.

Focus on

muscle

strength,

standing ba-

lance, and

aerobic en-

durance

onal reach Same trends

on other sca-

les. Physical

functioning

and global

quality of life

remained

stable. Dys-

pnea redu-

ced (42

�60, p=

0,006), role

+ social

functioning

improved

(50� 63,

p=0,02 and

55�65,

p=0,008).

Porock

2000

Pre-test

post-test

design,

pilot

study

Silver Chain

Nursing

Foundation

and Edith

Cowan Uni-

versity

Home Hos-

pice Care

Service in

Perth, Wes-

tern Austra-

lia

To deter-

mine the

effects of an

individuali-

zed exercise

program

(Duke Ener-

gizing Exer-

cise Pro-

Patients with

advanced

cancer,

ECOG clas-

sification of 1

and more,

estimated life

expectancy

of at least 1

11, 2 drop-

ped out for

selective

reasons

(feeling

unwell, fin-

ding it all too

much), 6

comple-ed

4 weeks No randomi-

zation

9 patients,

mean age 60

years, 6

female, 4

bowel can-

cer, 2

pancreas

cancer, 7 pa-

tients with

Physiotherap

ist spe-

cialized in

oncology

and palliative

care conduc-

ted home vi-

sit and edu-

cated the

No control

group

Multidimen-

sional

Fatigue

Inventory

(MFI), Symp-

tom Distress

Scale (SDS),

Hospital

Anxiety and

Minimal

fluctuation in

the mean

MFI sub-

scale sco-

res, quality

of life scores

improved

from day 0 to

No other

outcomes

Very few

patients in

the study,

lack of com-

plete data,

non-compa-

rative study

C

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

gram) on

levels of

fatigue in

patient with

advanced

cancer

month. Ex-

clusion cri-

teria: eviden-

ce of confu-

sion or de-

mentia,

uncontrolled

symptoms

over the past

24 hours,

inability to

walk 50 me-

ers or more

pain free,

any preex-

sting condi-

ions or other

medical rea-

son for which

exercise

would be

contraindi-

cated

all 5 MFI

scale mea-

surements

metastases,

3 patients on

current treat-

ment, 7 pa-

tients on

opioids, 7 on

antiemetics,

4 on anal-

gesics, 4 on

bowel treat-

ment, 4 pa-

tients had

additional

care

patient and

prescri-bed

an indivi-uali-

zed plan.

Patients

were given a

range of

activities

through the

day. Home

visit in the

week follo-

wing the

start, and

telephone

call in the

second week

Depression

Scale

(HADS),

Quality of

Life Scale

(QOL Scale)

day 14

Rad-

bruch

2008

Narrative

review �

therefore

no further

analysis

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

Strasser

2004

Retro-

spective

descrip-

tive com-

parative

study

Swiss

Cancer Re-

search

Multidisci-

plinary Clinic

and traditi-

onal pain

and symp-

tom mana-

gement clinic

at the U-

niversity of

Texas MD

Anderson

Cancer

Center

To cha-

racterize

symp-toms,

recommen-

dations, and

effect of

multidisc-

ciplinary

team on

symptom

expression

and overall

satisfaction

of patient

and fami-

lies. Com-

parison with

traditional

pain and

symptom

manage-

ment

First 138

consecutive

patients at

the MD clinic

and a cones-

cutive sam-

ple of 77 pa-

tients seen

at the PSM

clinic

138 patients

in MD clinic,

77 patients

in PSM cli-

nic. No lost-

to-follow-up

due to retro-

specttive

design

Retrospec-

tive chart

analysis, +

follow-up

(mean 9

days) at MD

Center

No randomi-

zation

Adults with

primary

tumors of

various

types. Refer-

ral to the

clinics for

pain control,

end-of-life

issues (only

MD), and

management

of multiple

symptoms

(only MD),

54% female,

mean age 54

years, me-

dian survival

10 weeks in

MD, and 51

weeks in

PSM clinic

MD Clinic

has no wait--

ing area, pa-

tients have

private room

with bed and

bathroom. In

5 hours the

patient is

assessed by

a physician,

nurse, social

worker,

physical, oc-

cupational,

speech the-

rapist, phar-

macist, nu-

tritionist,

psychiatric

nurse practi-

tioner, and

pastoral care

worker. On-

site counse-

ling, specific

education,

and simple

interventions

Traditio-nal

pain and

symptom

management

given by a

physician

and a nurse

In MD Clinic:

ad-hoc

question-

naire with 7

items, to be

answered on

a 5-point

scale, focus-

sed on satis-

action. Re-

trospective

chart review

on symp-

toms, results

of stand-

ardized as-

sessments,

and recom-

mendations

In the MD

group pa-

tients

received

median 4

non-phy-

sician

recommend-

dations, in

the PSM

group none.

In MD group

significant

improvement

in pain,

nausea, de-

pression,

anxiety,

sleep,

shortness of

breath, and

well-being,

but not in

fatigue, a-

norexia, or

drowsiness.

No compa-

rative data,

patients in

No other

outcomes

Both groups

are not com-

parable at

baseline due

to differen-

ces in the

severity of

the disease.

Almost no

comparisons

have been

made be-

tween the

groups, so

this study is

best worth

given a non-

comparative

retrospective

study, how-

ever with

useful infor-

mation

C

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

are provided.

Multidiscipli-

nary team

discussion

on assess-

ment and

recommenda

tion, given to

the patient.

Follow-up in

1-2 weeks is

provided

the MD clinic

were overall

as on sub-

scores very

satisfied

Solà

2004

Coch-

rane

syste-

matic

review

To deter-

mine the

effective-

ness of non-

invasive

inter-entions

delivered by

health-care

professio-

nals in im-

proving

symptoms,

psychosocial

functionning

and quality

of life

Only RCT’s

and CCT’s

were inclu-

ded. Studies

on patients

of either sex

and any age

diagnosed

with lung

cancer (also

with some

patients with

other thora-

cic cancer)

at any stage

of their ill-

9 studies - - No aggre-

gate data on

patient cha-

racteristics,

no speci-fic

data for

those pa-

tients that

are in the

palliative

phase of

their disea-

se, all pa-

tients had

lung cancer

Various

interventi-

ons have

been stu-

died in the

RCT’s and

CCT’s,

divided in 6

groups:

Nursing

interven-ions

to manage

breathless-

ness, nur-

sing pro-

grams, nutrit-

- Well-being

(sub-jective

or objective

perception of

improvement

in physical

health, or of

symptoms

related to

cancer, me-

tastases or

side effects

of treat-

ment; or

improvement

of psycho-

Nurse led

breathing

programs

may produce

beneficial

effects.

Nurse follow-

up can be as

effect-tive

and leads to

greater

patients

satisfaction

than phy-

sician follow-

up, coun-

No other

outcomes

Well design-

ned Coch-

rane syste-

matic review

with exten-

sive descrip-

tion of the

methods, no

metaanalysis

A1

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

ness. Non-

invasive

interventions

ional inter-

ventions,

psychothe-

apeutic in-

terventions,

exercise,

and refle-

xology

social funct-

oning), qua-

lity of life (by

validated

scales, clas-

sification and

measure-

ment)

seling may

be effective

in helping

patient to

cope, no evi-

dence of any

beneficial

effect of in-

creasing oral

nutritional

intake

Temel

2009

Uncon-

trolled

feasibility

study

Public funds Hospital-

based

To assess

feasibility of

exercise pro-

gram for

patients with

advanced

NSCLC

Patients<12

weeks of

diagnosis of

non-small

cell lung

cancer

(NSCLC)

25/14 12 weeks None Patients

aged 48-81

with advan-

ed NSCLC,

mostly (70%)

treated with

chemothera-

py

A Structured

exercise pro-

gram consis-

ting of 16

twice weekly

sessions

over 12

weeks. The

program took

place in

groups (8-10

patients)

lasting 90-

120 minutes.

After warm-

ing up a 30

minutes ae-

No control Feasibility

(adherence

to the inter-

vention);

secondary:

functional

capacity (6

m walking

test), quality

of life (QOL),

symptoms

and fatigue

(FACT-L)

Of 25 ac-

crued pa-

tients, 20

completed

baseline

assessment

and 11 atten-

ded all ses-

sions (44%

adherence) ;

No changes

in QOL, fati-

gue or mood.

Lung cancer

symptoms

improved.

- It is unclear

what selec-

tion of eligi-

ble patients

participated.

It is unclear

whether

observed

effect is re-

lated to the

intervention

C

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

robic exer-

cise. A

strength

component

consisted of

3 sets of 10

repititions of

6 different

excercises

over 30-40

minutes

Yoshioka

1994

Uncon-

trolled

study

Hospice-

based

Terminal

cancer pa-

tients (<6

months to

death)

admitted to a

hospice and

provided with

a rehabil-

itation pro-

gram.

355/? 6 months Patients

aged 17-88

with terminal

cancer

Comfortable

or relaxed

positioning

with pillow

for relief of

cancer pain,

therapeutic

exercise

saimed at

improvement

in muscular

strength,

range of

motion and

balance,

ADL excer-

cises compri-

No control ADL (Barthel

index).

Question-

naires

mailed to

relatives 3

months after

death.

No adheren-

ce data.

Most pa-

tients

experienced

some relief

- 26% of

eligible pa-

tients accru-

ed in the

study

C

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

sed bed

excercises,

endurance

training,

chesty

physiothera-

py, + some

specific

treatments

Marciniak

1996

Retro-

spective

case

series

Hospital-

based

Adult cancer

patients

admitted for

comprehensi

ve inpatient

rehabilitation

159 Patients

aged 17-88,

38% of

which had

metastatic

disease

No specific

intervention

mentioned

No control Functional

status

Functional

gains be-

tween ad-

mission and

discharge

(mean 42.9-

>56.0) (p<

0.001) Pre-

sence of

metastatic

disease did

not influence

funct. out-

come.

C

Headley

2004

Quasi-

experime

ntal study

Women ≥17

years with

stage IV

breast can-

cer

38/32 No rando-

mization

30min. sea-

ted exercise

program

(armchair

fitness) 3

No exercise

program

Fatigue and

QOL

(FACIT-F);

pain

Less in-

crease in

fatigue and

less decine

in QOL for

Unclear how

patients

were assign-

ned to treat-

ment group.

B

Study

(trial) ID

Study

type

Source of

fun-ding/

conflicts of

interest

Setting Hypotheses Eligibility

criteria

Sample size/

Lost to follow

up

Duration of

the Study

Randomi-

zation

method

Patient cha-

racteristics

and group

comparability

Interventions

and compli-

ance

Control/

Comparator

(including

duration,

dose)

Primary

Outcome

Measure (s)

Secondary

Outcome

Measure (s)

Effect size –

Primary

outcome(s)

Effect size –

Secondary

outcome (s)

All other

outcomes,

endpoints

Critical

appraisal of

study quality

Level of

eviden-

ce

schedule-ed

to receive

chemothera-

py and able

to sit.

times a

week.

84% adhe-

rence

expirimental

group

Subjects in

the control

group more

educated

and more

frequently

unmarried.

Tabel 8. Uitgangsvraag 7 – Welk instrument is valide en bruikbaar in Nederland voor screening van kanker gerelateerde vermoeidheid tijdens en na afronding van de in opzet curatieve behandeling en in de (ziekte- en symptoomgerichte) palliateve fase?

Author year

Level of evidence

Study type Number of pts Inclusion Criteria

Index test (diagnostic test) Control (gold standard, reference test)

Result Other remarks

Kirsh

2001

B Comparative study

52 - Cancer treatment

- Able to read and write English

- Over 18 years of age

- No cognitive impairment

Zung Self-rating Depression Scale (ZSDS) single fatigue item

FACT-An cutoff >115

cutoff >2: sensitiviteit 79% specificiteit 88%

Pre-determined cut-off score referentietest Small study

Van Belle 2005

B Comparative

study

834 (470 patients filled in the FACT-F and VAS scales

No clear eligibility criteria are mentioned. It is described that the study involves cancer patients suspected to be fatigued.

1. Diagnostic Question. ICD

10 (3 items)

2. Diagnostic Question. ICD

10 (3 items)

3. FACT F

4. VAS 1 energy level VAS

2 QoL

VAS 3 daily activities

Diagnostic Question. ICD 10 (alle items) VAS (energy level) cutoff 50-75 mm Diagnostic Question. ICD 10 (alle items) Diagnostic Question. ICD 10 (alle items)

sensitiviteit 100% specificiteit 86% sensitiviteit 76-83% specificiteit 55-77% cutoff <34: sensitiviteit 91% specificiteit 75% VAS 1 cutoff <61mm/ VAS 2 cutoff <68mm/ VAS 3 cutoff < 65mm: sensitiviteit ±90% specificiteit <50%

No pre-determined cut-off scores. No information on patient recruitment, poor study a lot of analyses

Temel 2006

B Comparative study

100 Patients presenting to thoracic oncology clinic, regardless of type of malignancy, stage of disease, duration of illness

One-item fatigue scale (OIFS) ‘How would you rate your fatigue on a scale of 0 to 10 with 0 being ‘no fatigue’ and 10 being ‘the worst possible fatigue?‘

FACIT-F cutoff <30

Cut-off >3: sensitiviteit 89% specificiteit 77%

Pre-determined cut-off referentietest

Alexander 2009

B Comparative study

200 - Histologically proven breast

cancer (stage I/IIb) at time of

diagnosis

- Disease-free at time of study

entry

1. BFS

2. FACT-F

Diagnostic Interview ICD- 10 & structured psychiatric interview

cutoff >10: sensitiviteit 92% specificiteit 53% cutoff<36: Sensitiviteit 80% Specificiteit 71%

No pre-determined cut-off scores

Tabel 9. Uitgangsvraag 9 – Welke meetinstrumenten zijn valide en bruikbaar in Nederland voor de effectevaluatie van oncologische revalidatie tijdens en na afronding van de in opzet curatieve behandeling en in de (ziekte- en symptoomgerichte) palliatieve fase?, Overzicht van RCT’s en gebruikte meetinstrumenten

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Battaglini 2008

Breast cancer + chemo- or radio-thereapy,Italy

RCT N=20 F Cardiovascular activity (6-12 min), followed by stretching (5-10 min), resistance training (15-30 min), and a cool-down (approximately 8 min) x 6 months

Usual care Total caloric intake (3-day food diary), %BF (skinfolds), fatigue (revised Piper Fatigue Scale

Battaglini 2007

Inactive breast cancer patients, Italy

RCT N=20 F 21-week exercise low to moderate intensity for 60 minutes on two days/week

Body composition (skinfold method); muscle strength (one repetition maximum).

Burnham 2002

Eighteen survivors of breast or colon cancer, USA

RCT, matched for VO2peak, QoL (15 female and 3 male, 40–65 yr of age)

moderate- (40–50% HRR) intensity exercise group; low-body aerobic exercise three times a week for 10 wk

Low- (25–35% heart rate reserve (HRR) exercise low-body aerobic exercise three times a week for 10 wk

Aerobic capacity (treadmill) comfortable walking pace (1.5–4 mph) on the treadmill, then the grade of the treadmill increased 1° every minute. Quality of Life Index for Cancer Patients Linear Analog Self-Assessment (LASA) (100-mm analog, mea-suring fatigue, anxiety, confusion, depression, energy, and anger)

Cadmus 2009

Newly diagnosed breast cancer survivors, USA

RCT N=45 F 6-month, home-based exercise program. 30 min of moderateto- vigorous physical activity 5 days per week.At the beginning of the program, each participant received an educational book, a binder containing specialized weekly informational handout and a Polar heart rate monitor (used to maintain activity at 60–80% of predicted maximal heart rate in accordance with American College of Sports Medicine guidelines

Usual care Physical activity: recorded the type, duration, and perceived intensity of any recreational/fitness activity performed on each of seven consecutive days on the 7-Day Physical Activity Log (PAL) + daily steps on a 7-day pedometer log. Exercise group participants also completed the PAL (including average heart rate from each workout) for each of the 26 weeks of the intervention. Height, Weight, % body fat: whole-body dual energy X-ray, absorptiometry scans, QOL: happiness: Fordyce Happiness Measure, Self-esteem: Rosenberg Self-Esteem Scale, Depression CES-D, Anxiety : State-Trait Anxiety Index (STAI), Stress: Cohen’s 10- item Perceived Stress Scale, physical, emotional, social, and functional well-being: FACT-B, SF-36

Cadmus 2009

Post-treatment survivors breast cancer, USA

RCT N=67 F Idem Idem Idem

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Campbell 2005

Women under-going chemohe-apy and/or radio-therapy+ early

RCT N=22 F Supervised exercise programme twice weekly for 12 weeks. Warm-up, 10–20 minutes exercise (which varied from week to week

Usual care FACT-G, FACT-B, Satisfaction with Life Scale (SWLS), Revised Piper Fatigue Scale (PFS), The Scottish Physical Activity Questionnaire (SPAQ), The 12-minute walking test

stage breast cancer, UK

and included walking, cycling, low-level aerobics, muscle-streng-thening exercises, circuits etc.), a cool down and relaxation period

Cho 2006

Women with early breast cancer post treatment, post mastectomy, Korea

RCT N=55 F Mean age 49.1 yr

Intervention was provided three times per week for 10 weeks consisted of psychology based education, exercise (group and home-based), and peer support group activity. Ninety minutes of education was provide once per week for 10 weeks in a group

ROM of the affected shoulder joint: goniometer Psychosocial adjustment, 18-item, 4-point scale revised by Lee (1999) Quality of life: the instrument developed by Chae & Choe (2001a) on the subject of South Korean breast cancer patients domestically

Cinar 2008

Women with mo-dified radical mas-tectomy, Turkey

RCT N=57 Individual 15 sessions of physio-therapy program in physical medicine and rehabilitation department, including pendulum, wall climbing, overhead pulley, horizontal abduction, posture, wand, dorsal strengthening, and stretching exercises for levator scapula. The patients performed the exercises at home in the following 8 weeks.

The HG received a form to perform the exercises by themselves after removal of the drains

Rom shoulder: goniometer

Lymphedema: circumferential measurements of operated and

unoperated extremities were taken preoperatively and then

postoperatively Function: Wingate upper extremity function questionnaire

Coleman 2008

135 patients with multiple myeloma, USA

RCT N=135 Exercise group received an individualized exercise prescript-tion, a set of color-coded exercise stretch bands with varying resis-tance, and a notebook and video-tape illustrating the exercises. Strength resistance training was included to strengthen muscles so patients could improve the aerobic component of the exercise program

Usual care group were advised to follow the written exercise recom-mendations provided by their physician. The pa-ients were generally ad-vised to remain as active as possible and to try to walk 20 minutes per day.

Number of red blood cell and platelet transfusions during transplantation Number of attempts at and total number of days of stem cell collection, time to recovery after transplantation, Response to intensive therapy for multiple myeloma.

Weekly activity logs, aerobic capacity: 6 minute walk, Borg scale

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Coleman 2003 (feasibility)

Patients receiving high-dose chemo-therapy and tan-dem peripheral blood stem cell transplantations for the treatment of

RCT N=24 10 F 14 M

Home based exercise, see above 6 months

Usual care, see above Exercise log, Aerobic capacity: Modified Balke protocol (min walked), Strength: 1RM, lean body weight: air displacement plethysmography, fatigue: POMS, mood: POMS, sleep measurements: Actigraph, Epworth Sleepiness Scale

multiple myeloma, USA

Coleman 2003 (ad-herence)

Idem Idem Idem Idem Idem

Courneya 2008

Mild-to-moderately anemic patients with solid tumors, Canada

RCT N=55 Darbepoetin alfa + exercise aerobic exercise training three times per week at 60%-100% of baseline exercise capacity for 12 weeks

Darbepoetin alfa QoL: Functional Assessment of Cancer Therapy-Anemia scale (FACT-A)

Fatigue, Cardio-respiratory fitness (VO(2peak)), Hemo-globin (Hb) response, darbe-poetin alfa dosing (full text N/A)

Courneya 2007b (f/u)

Breast cancer patients initiating adjuvant chemo-therapy

RCT N=242 Resistance exercise training: thrice per week performing two sets of 8 to 12 repetitions of nine different exercises at 60% to 70% of their estimated one repetition maximum and to progress the weight by 10% when they could complete >12

repetitions OR Aerobic exercise training: thrice per week on a cycle ergometer,

treadmill, or elliptical trainer beginning at 60% of VO2peak for 15 min and progressing to 80% of VO2peak for 45 min. Duration chemotherapy

Usual care QoL: FACT-AN Self-esteem,

Rosenberg Self-Esteem Scale

fatigue: FACT-AN anxiety: Spiel-berger State Anxiety Inventory depression: Center for Epidemiological Studies-Depres-sion Scale Godin Leisure Time Exercise Questionnaire @ 6 months f/u

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Courneya 2007b (multi-center)

Idem Idem Idem Idem Idem Idem + VO2peak treadmill max test + O2 uptake Strength: esti-mated 1 RM Body weight: balance beam scale, Whole body fat and lean tissue: dual x-ray absorp-tiometry scan, Lymphedema :

standard volume-tric arm measure-ments based on water displace-ment. Chemothe-rapy completion rate was assessed

as the average relative dose-intensity (RDI) for the originally plan-ned regimen based on standard formulas

Culos-Reed 2010

Prostate cancer patients receiving androgen deprivation therapy > 6 months Canada

RCt N=100 M

16 weeks home-based portion three to five times per week at moderate intensity and weekly group sessions

Wait list QoL : EORTC QLQ C30 Expanded prostate cancer index composite (EPIC) Fatigue: Fatigue severity scale (FSS) Depression: center for epidemiological studies depression scale (CES-D) Godin’s leisure score index

aerobic capacity (6-min walk test), Grip strength (grip dynamometer), flexibility (modified sit and reach). Height Weight Waist and hip circumference Blood pressure Heart rate

Culos-Reed 2007

N/A RCT

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Daley 2007a

Lokalised breast cancer, post treat-ment, UK

RCT N=108 F Supervised aerobic exercise therapy or Exercise-placebo three times per week for 8 weeks

Usual care QoL: FACT-G and FACT-B

Heart rate, RPE Fatigue: revised Piper, satisfaction with life scale, De-pression: Beck Depression, In-ventory Physical Self-Perception

Profile exercise behavior: stage of

change for exer-cise ladder ques-tionnaire (SOC). aerobic fitness: 8-minute, single-sta-

ge walking test

performed on a treadmill, height weight, % body fat: bioelectrical impe-dance analysis muscle function: Biodex adherence: session attendan-ce and the amount

(duration, RPE, HR) of exercise

Dimeo 2004

Patients who un-derwent surgery for lung or gastro-intestinal tumours 120 days post treatment, Germany

RCT N=72 51 M, 19 F mean age 55 (exerc), 60 (relax)

Aerobic exercise group (stationary biking 30 min five times weekly)

Progressive relaxation training group (45 min three times per week). Both interventions were carried out for 3 weeks

Physical, cognitive and emotional status and somatic complaints with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC-QLQ-30) questionnaire

Physical capacity: bike ergometry start 25 watts and increased

by 25 watts every 3 minutes until exhaustion (wattsmax)

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Dimeo 1999

Cancer patients with solid tumours receiving high dose chemothe-rapy followed by autologous peri-pheral blood stem cell transplantation Germany

RCT N=59 Hospital setting

Biking on an ergometer in the supine position following an interval training pattern for 30 minutes daily 50% of the cardiac reserve (duration?)

Usual care Psychologic distress: POMS, SCL-90

Drouin 2006

Twenty sedentary females with breast carcinoma during 7 wks radia-tion therapy, USA

RCT N=20 F Aerobic exercise (AE) of walking for 20 to 45 minutes, 3 to 5 times per week, at 50% to 70% of mea-sured maximum heart rates

Placebo stretching (PS) activities 3 to 5 days per week

Erythrocyte measures, Physical capacity: VO2peak + modified Bruce treadmill protocol + O2 uptake

Hayes 2009

Women younger than 76 yr, who completed breast cancer treatment at least 6 months prior and had sub-sequently devel-oped unilateral, upper-limb lymph-

RCT N=32 F 20 supervised, group, aerobic and resistance exercise sessions over 12 wk

Instructed to continue habitual activities.

Lymphedema status: bioimpedance spectroscopy (impedance ratio between limbs) and perometry (volume difference between limbs)

edema, Australia

Headley 2004

Women with meta-static breast can-cer beginning outpatient chemo-therapy, USA

RCT N=38 F Performance of a seated exercise program using home videotape three times per week for four cycles of chemotherapy

Continue any usual physical activity

Fatigue: FACIT-F Intensity of exer-cise : RPE monthly calender log

Hwang 2008

Postoperative radiotherapy for breast cancer, Korea

RCT N=40 F Supervised moderate-intensity exercise therapy for 50 min 3 times per week for 5 weeks.

Self-shoulder stretching exercise

QoL: WHOQOL-BREF), Fatigue: brief fatigue inventory (BFI), range of motion (ROM) of the shoulder:goniometer pain score: VAS 0-100 worst pain past week

Irwin 2009a

Breast cancer sur-vivors, USA

RCT N=75 F physically inactive

150 min/week of supervised gym- and home-based moderate-intensity aerobic exercise 6 months

Usual physical activity Body composition: dual-energy X-ray absorptiometry (DXA) % body fat,lean mass, Bone mineral density

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Irwin 2009b

Postmenopausal breast cancer survivors, USA

RCT N=75 F 150 minutes per week of moderate-intensity aerobic exercise 6 months

Usual physical activity Blood levels of insulin and IGF: ELISA

Jarden 2009

Allogeneic hema-opoietic cell tran-splantation, Denmark

RCT, N=42 Hospital based

Supervised multimodal intervention exercise, psychoeducation, progressive exercise 4-6 weeks

Usual care Aerobic capacity measured in VO(2) max: Astrand test muscle strength: 1 RM, functional performance 2 min stairclimb, physical activity level: QOL, EORTC QLQ-C30 fatigue, FACT-AN psychological well-being HADS clini-al outcomes

Kim 2006

Newly diagnosed with breast cancer undergoing adju-vant therapy, South Korea

RCT N=41 F Mean age 50 yrs

8-week moderate intensity (60-70% VO2 peak) supervised aerobic exercise program 3 times a week

Usual care Physical capacity: Bruce treadmill protocol + O2 uptake Resting HR, HRmax, BP, Post intervention: 7-day Physical Activity Questionnaire

Korstjens 2008

Mixed cancer, post treatment, Netherlands

RCT N=209 12-week group-based multi-disciplinary self-management reha-bilitation program, combining phy-sical training (twice weekly) and cognitive-behavioral therapy (once weekly)

12-week group-based physical training (twice weekly) aerobic bicycle training (30 min) and muscle strength training (30 min)] followed by group sports (60 min).

QOL: SF-36

Ligibel 2008

Sedentary, ove-weight breast can-cer survivors, USA

RCT N=101 F 16-week cardiovascular and strength training exercise inter-vention

Usual care Fasting insulin and glucose levels, weight, body composition, bioelectric impedance analyzer height, weight: calibrated Scale-Tronix scale circumference at the waist and hip

Daily minutes of aerobic activity in exercise logs for

the duration of the study strength: 1 RM

Matthews 2007

Early-stage breast cancer post treat-ment, USA

RCT N=36 F 12-week home-based walking intervention single in-person counseling visit (30 min) followed by up to five short telephone-counseling calls in weeks 1, 2, 4, 7, and 10 after randomization

Usual care Physical activity: Community Health Activities Model Program for Seniors Physical Activity Questionnaire (CHAMPS), Actigraph, Diet intake : 21-item diet habits questionnaire (DHQ) 19-item National Cancer Institute (NCI) all day fruit and vegetable screener, Body composition: dual X-ray absorptiometry (DEXA)

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

May 2009

Mixed cancer, post treatment, Nether-ands

RCT N=147 Mean age 48.8 yrs

12-week group-based multidisc-ciplinary self-management reha-bilitation program, combining phy-sical training (twice weekly) and cognitive-behavioral therapy (once weekly)

12-week group-based physical training (twice weekly) aerobic bicycle training (30 min) and muscle strength training (30 min)] followed by group sports (60 min).

QOL: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 questionnaire Physical activity: Physical Activity Scale for the Elderly (PASE)

Muscle strength 1 RM, HR peak (see Korstjens)

McNeely 2008

Post-surgical head and neck cancer survivors, Canada

RCT N=52 15 F, 37 M

Progressive resistance exercise training 12 wk supervised active and passive ROM/stretching exer-cises, postural exercises + 2 sets of 10 to 15 repetitions of 5 to 8 exercises, starting at 25% to 30% of their 1-repetition maximum (1-RM) strength and slowly progress-sing to 60% to 70% of their 1-RM strength by the end of the inter-vention period

Standardized therapeutic exercise protocol 12 wk supervised active and passive ROM/stretching exercises, postural exer-cises, and basic streng-thening exercises with light weights (1-5 kg) and elastic resistance bands

Patient-rated shoulder pain: 0-100 (VAS?), shoulder disability: SPADI

Muscle strength: 1 RM, Shoulder ROM: goniometer, Generic QOL and fatigue: Functional Assessment of Cancer Therapy-Anemia (FACT-An), Specific QOL: Neck Dissection Impairment Index (NDII)

McNeely 2004

Idem RCT N=20 Idem Idem Idem Idem

Mello 2003

Patients post allogeneic bone marrow transplant-tation, Brazil

RCT N=18 6-week exercise program with acti-ve exercise, muscle stretching and treadmill walking in- and outpatient

Usual care Muscle strength test: Chatillon Inc. strain-gauge dynamometer

Milne 2008b

Breast cancer sur-vivors post treat-ment, Australia

RCT N=58 F Immediate exercise group 12 weeks of supervised aerobic and resistance exercise, three times per week

Delayed exercise group (same therapy 12 weeks later)

QoL: Functional Assessment of Cancer Therapy-Breast (FACT-B)

Fatigue: Schwartz Cancer Fatigue Scale (SCFS) social physique and anxiety: Social Physique Anxiety Scale-7 items (SPAS-7), Aerobic fitness using the Aerobic Power

Index (API) cycle test. Submaximal test, starting at 25 W increased by 25 W every minute

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Mock 2005

Sedentary women with Stage 0-III breast cancer re-ceiving out-patient adjuvant chemo-herapy or radiation therapy, USA

RCT N=119 F Home-based moderate-intensity walking exercise program duration treatment written prescription to walk five to six times per week at a moderate pace in the target heart rate range (approximately 50–70% of maximum heart rate)

Usual care Fatigue: Total Score of the Piper Fatigue Scale (PFS) Physical func-tioning and activity levels: 12-min Walk Test, SF-36 Physical Activity Questionnaire (PAQ), Adherence: weekly dairies + measures above.

Mock 2001

Idem RCT N=52 Full text n/a

Monga 2007

Localized prostate cancer patients undergoing radio-therapy, USA

RCT N=21 10-minute warm-up, a 30-minute aerobic segment consisting of walking on a treadmill, and a 5-10-minute cool down period 3x week for 8 weeks Target HR 65%

Usual care fFtness, modified Bruce treadmill test protocol (METS) fatigue: Piper Fatigue Scale (PFSRevised), depression: Beck Depression, QOL: FACT-P, leg strength: time it takes to stand up and sit down 5 times from an armless chair, flexibility: modified sit-and-reach test

Mutri 2007

Early stage breast cancer during treatment chemo-

or radiotherapy, UK

RCT N=203 F 12 week supervised group exercise programme: exercise intervention

was based on guidelines for prescription of exercise for cancer

patients and survivors. The classes consisted of a warm-up of 5-10 minutes, 20 minutes of exercise (for example walking, cycling, low level aerobics, muscle streng-thening exercises, or circuits of specifically tailored exercises), and a cool-down and relaxation period. The exercise class lasted 45 minutes in total. Exercise at a moderate level (50-75% of age

adjusted maximum heart rate).

Usual care Functional assessment of cancer therapy (FACT-G) questionnaire, incl. FACT-B, FACT-F, and FACT-ES.

Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity (Scottish physical activity questionnaire) 12 minute walk test, assessment of shoulder mobility.

Payne 2008

Older women re-ceiing hormonal treatment for breast cancer, USA

RCT N=20 F Prescribed home-based walking exercise intervention x 12 wks

Usual care Sleep: Pittsburgh Sleep Quality Index (PSQI), Fatigue: Piper Revised Fatigue Scale, Depression : CES-D

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Pinto 2005

Sedentary women with breast cancer post treatment

RCT N=86 F 12 weeks of PA counseling deli-vered via telephone, as well as weekly exercise tip sheets + pedo-meter moderate- intensity activities

at 55% to 65% of maxi-mum heart rate

Usual care, Usual activity Seven-Day Physical Activity Recall. The Seven-Day Physical Activity Recall (7-Day PAR), Physical fitness: Rockport 1-mile walk test. Objective activity monitoring: Caltrac accelerometer Stage of Motivational Readiness for PA, Mood: POMS Fatigue: 0-10 VAS, Body esteem : Body Esteem Scale

Pinto 2003 Sedentary women Breast cancer post treatment

RCT N=24 F 12-week supervised aerobic exer-cise program in a hospital setting

Wait list control Physical capacity: 50 rpm on a calibrated cycle ergometer with an increase in workload of 25W every 2 min (in watts and time) Mood: POMS, Positive and Negative Affect Scale (PANAS), Body Esteem Scale

Schmitz 2009

Female breast cancer survivors 1 to 15 years post-diagnosis among those with stable lymphedema and 1–5 years post-diagnosis for those without lymphe-dema at study entry. Eligible wo-men were free of cancer at study en-try and had had at least 1 lymph node removed, USA

RCT N=295 F Participants attended twice-weekly strength training sessions for 12 months, supervised in small groups of 2–6 for the first 3 months YMCA, and then unsupervised for the remaining 9 months.

12 months later Limb volume: water displacement, circumferential measurement, Bioelectrical spectroscopy, Pain: VAS 0-10 (recall?), Pain questions from revised Brief Pain Inventory (validity?), Coordination: Nine Hole Peg Test of Finger Dexterity ROM: goniometer, Body fat (percent and total), fat free mass, and bone density: dual energy X-ray absorptiometry (DeXA) Muscle strength: 1 RM, QoL: Health and Attitudes Survey (home made) incl: Pittsburgh sleep quality index ,Relationship and body image, Fatigue symptom Inventory, SF-36, Coopersmith self-esteem inventory Life orientation test Visual analog scale (QOL), Medical outcome study social support, Temporal satisfaction with Life scale Depression survey, International physical activity questionnaire Diet history questionnaire, Demographics Menstrual tracking Medical history

Segal 2001

Women with sta-

ges I and II breast

cancer within 2

weeks of the initia-

tion of their pre-

scribed adjuvant

therapy (radio-

therapy, hormonal

therapy, or chemo-

therapy, Canada

RCT N=123 Self-directed exercise, home exercise prescription and were asked to exercise five times per week for a 26-week or Supervised exercise supervised

exercise program three times per week for 26 weeks in the rehabilitation

Usual care QOL: SF-36, FACT-G, FACT-B Weight aerobic capacity: modified

Canadian Aerobic Fitness Test (mCAFT).

Author year

Population Design, N Intervention Control Primairy outcome(s) Secondairy outcome(s)

Segal 2009

Men with prostate cancer receiving radiotherapy with or without andro-en deprivation the-rapy, Canada

N=121 M 24 weeks of resistance three times per week performing two sets of eight to12 repetitions of 10 different exercises at 60% to 70% of their estimated one-repetition maximum

(1 RM) or Aaerobic training: three times per week on a cycle ergo-meter, treadmill, or elliptical trainer beginning at 50% to 60% of their predetermined peak oxygen consumption (VO2peak) for weeks 1 to 4 and progressing to 70% to 75% for weeks 5 to 24.

Usual care Fatigue: FACT-F, QOL: Prostate (FACT-P), and General (FACT-G) scales

Physical fitness: maximal incre-mental exercise protocol on a tread-mill with O2 uptake (?protocol) body composition, DEXA scan, strength: 1 RM (estimated from 8 RM), prostate-specific antigen, testosterone, hemoglobin, and lipid levels

Segal 2003

Men with prostate cancer who were scheduled to recei-ve androgen depri-vation therapy for at least 3 months after recruitment, Canada

RCT N=155 M Resistance exercise program three times per week for 12 weeks: nine strength-training exercises carried out under supervision three times per week, at 60% to 70% of one-repetition maximum

Wait list Fatigue: FACT-F, and disease-specific quality of life: FACT-P Body weight, body mass index, waist circumference, subcutaneous

skinfolds

Van Weert 2006

Cancer survivors with different diag-noses, and cancer-related physical and psychosocial problems, Nether-lands

RCT N=72 M/F 15-week rehabilitation program including individual exercise, sports, psycho-education, and information full program

Choose components considered relevant

Health-Related Quality of Life [RAND-36 and Rotterdam Symptom Check List (RSCL)], exercise capacity (symptom limited bicycle ergometry), muscle force (hand-held dyna-mometry), patient preferences

Windsor 2004

Radiotherapy for localized prostate carcinoma, UK

N=66 M Hme-based, moderate-intensity, continuous walking for 30 minutes on at least 3 days of each week of radiotherapy at a target heart rate of 60-70% calculated maximum heart rate x 4 weeks

Usual care Fatigue: Brief Fatigue Index, distance walked in a modified shuttle test 10 meter course, Physical activity: Scottish Physical Activity Questionnaire (SPAQ), Adherence: patient-activity diary during radiotherapy detailing the frequency and duration of the walking intervention together with the heart rate achieved / frequency and duration of everyday aerobic activity

Tabel 10. Uitgangsvraag 10 – Hoe is empowerment van de (ex)patient te vergroten zodat oncologische revalidatie mogelijk is?, Overzicht van studie karakteristieken naar determinanten van revalidatie participatie en intentie tot participatie.

Study (trial)

ID

Study type

Source of

funding/

conflicts

of interest

Setting

Hypotheses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Primary Outcome Measure (s) Secondary Outcome Measure (s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

Level of evidence

Thorson

2008

Systematic

review inclu-

ding 3 deter-

minants of

exercise

studies

Identify

determinants of

physical activity

Patients with

prostate cancer

Self-reported leisure

time exercise,

interest in exercise

Perceived Behavioral control

predicted 36% variance in exercise

behavior (1 study). Perceived

behavioral control and subjective

norm predicted exercise intention (1

study). Younger patients more

interested in exercise (1 study).

B

Karvinen

2009

Uncontrolled

prospective

study

To identify

determinants of

exercise behavior

Bladder cancer

survivors >18 year

525 Exercise behavior

(Leisure

Adjuvant therapy (p=0.04), invasi-

veness (p=0.05) and age (p=0.04)

were significantly associated with

exercise. Constructs of the theory of

planned behavior mediated these

associations; Exercise correlated

strongly with excercise intention and

this correlated with perceived

behavioral control, instrumental and

affective attitude.

B

Jones

2007

To assess

demographic,

medical and

social determ-

inants of excer-

cise intentions

Brain cancer

patients >18 yrs

106 Theory of planned

behavior correlates.

Predictors of exercise intentions were

affective attitude (p=0.02) and

perceived behavioral control

(p<0.001). Higher pre-diagnosis

excercise levels correlated with

higher intention (p=0.04) and

affective attitude (p=0.002).

B

Study (trial)

ID

Study type

Source of

funding/

conflicts

of interest

Setting

Hypotheses

Eligibility criteria

Sample size/

Lost to

follow up

Duration of

the Study

Primary Outcome Measure (s) Secondary Outcome Measure (s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

Level of evidence

White

2009

Systematic

review

To provide a

quantitative

estimate of the

reporting of

internal and

external validity

RCTs adressing

effect physical

activity

In contrast to internal validity,

external validity was poorly reported.

C

Pinto

2009

Study along-

side a RCT

To obtain des-

criptive data on

adherence and to

identify predictors

of adherence

Breast cancer

patients

43 Predictors of

adherence

Baseline self efficacy (OR 1.61;

p=0.03) was a significant predictor of

achieving weekly goals, but not

demograhic and medical variables

B

Courneya

2002

Study along-

side a RCT

To examine

correlates of

adherence

96 cancer

survivors

Independent predictors of overall

RCT excercise were past excercise,

assignment to experimental condition

and intention. For excercise adhe-

rence in the excercise condition,

predictors were sex, extrversion,

normative beliefs and perceived

behavioral control

B

Courneya

2004

RCT Public funding

To examine the

Exercise Stage

of Change, PBC,

employment

status, and treat-

ment protocol as

predictors of ex-

ercise adherence

Prostate cancer

survivors sched-

uled for ADT,

approval oncolo-

gist, no cardiac

disease, less than

1 hours from

exercise center

155/4 12 weeks TPB constructs,

QoL-FACT-P scale

Exercise adherence better for higher

exercise stage of change, younger

age, and higher exercise intention

B

Tabel 11.Uitgangsvraag 10 – Hoe is empowerment van de (ex)patient te vergroten zodat oncologische revalidatie mogelijk is?, Overzicht van studie karakteristieken naar interventie studies om adherence aan revalidatieprogramma’s te vergroten.

Study

(trial)

ID

Study type

Source

of

funding/

conflicts

of

interest

Setting

Hypotheses

Eligibility criteria

Sample size/

Lost to

follow

up

Duration

of the

Study

Randomization

method

Patient characteristics and group comparability

Interventions

and compliance

Control/ Comparator (including duration, dose)

Primary Outcome Measure (s) Secondary Outcome Measure (s)

Effect size - Primary outcome(s) Effect size – Secondary outcome (s)

All other

out-

comes,

end-

points

Critical

appraisal of

study quality

Level

of evi-

dence

Jones, 2005

3-armed RCT

Does theory of planned beha-vior mediate effects of an oncologists re-commendation to ecercise?

Newly diagnosed breast cancer survivors

450 5 weeks Computer-generated random num-bers in per-muted blocks; sealed enve-loppes.

Balanced groups except more postme-nopausal wo-men in RR group

Recommenda-tion+ referall (RR: 150). Recommenda-tion only (RO; 150)

Usual care (UC: 150)

Theory of planned behavior (TPB) constructs

RO vs. UC: RO better for normative belief (p= 0.001), attitude (p= 0.045) and intention (p= 0.001). RR vs. UC: RR better for normative belief, sub-jective norm, and intention.

Randomization & allocation concealment adequate; blin-ding unclear

B

Benett 2007

RCT Fatigued cancer survivors >18 years

56/1 6 months

Computer generated randomization scheme.

Comparable groups

Motivitaional interviewing counseling sessions

No difference in aerobic fitness, men-tal health or fatigue

Low risk of bias, but blinding unclear

B