Background
Fatigue in patients with incurable cancer
Exercise interventions for CRF in cancer patients
Cognitive behaviour therapy for CRF in cancer patients
The role of physical activity and fitness versus fatigue-related cognitions as mediators of the reduction in CRF
Aims of the TIRED study
Methods
Design
Participants
Inclusion criteria | |
---|---|
(1) | Age ≥ 18 years. |
(2) | Able to read, speak and write the Dutch language. |
(3) | Diagnosis of incurable cancer (i.e. breast, colorectal, prostate, renal cell, bladder, endometrial, ovarian, cervical, bone and soft tissue cancer, or melanoma). |
(4) | Scheduled for or receiving systemic cancer treatment with palliative intent (i.e., chemotherapy, and/or hormone therapy, and/or targeted therapy, and/or immunotherapy, possibly combined with surgery and/or radiotherapy). |
(5) | Cancer treatment plan based on an expected survival of ≥ 6 months as judged by their oncologist. |
(6) | Severely fatigued (CIS-fatigue score ≥ 35). |
Exclusion criteria | |
(1) | Treatable somatic cause that could explain the presence of severe fatigue (other than the underlying disease and the cancer treatment itself). |
(2) | Karnofsky Performance Status < 70. |
(3) | Symptomatic brain metastases. |
(4) | Severe cognitive problems. |
(5) | Not able to walk at least 6 min successively. |
(6) | Contra-indication for physical exercise. |
(7) | Current treatment by a psychiatrist or psychologist for a psychiatric disorder. |
Recruitment
Procedure
Randomisation
Interventions
Graded exercise therapy
Cognitive behaviour therapy
CBT Module | Instrument | Rating (RANGE) | Cut-off value |
---|---|---|---|
Sleep problems and deregulated sleep-wake cycle | Sleep-wake diary | Bedtimes and wake up times of 12 consecutive days and nights | Visual inspection of bedtimes and wake up times |
Sickness Impact Profile [41]: subscale Sleep and Rest | Number and type of items endorsed, weighted according to a standardised weighting scheme | Score ≥ 60 | |
Symptom Checklist-90 [52]: subscale Sleeping Problems | 5-point Likert scale (3–15) | Score ≥ 6 | |
Dysfunctional cognitions regarding cancer (prognosis) and cancer treatment | Impact of Event Scale [53]: subscale Intrusion subscale Avoidance | 4-point Likert scale (7–28) 4-point Likert scale (8–32) | Score ≥ 10 Score ≥ 10 |
Pictorial Representation of Illness and Self Measure [54] | Self-illness separation (SIS) in cm Self-fatigue separation (SFS) in cm | Fatigue-related suffering: SIS > SFS Illness-related suffering: SFS > SIS | |
subscale Acceptance subscale Helplessness | 4-point Likert scale (6–24) 4-point Likert scale (6–24) | Score ≤ 12 Score > 14 | |
Beck Depression Inventory-II Primary Care [57] | 4-point Likert scale (0–21) | Score ≥ 4 | |
Hospital Anxiety and Depression Scale [58]: subscale Anxiety subscale Depression | 4-point Likert scale (0–21) 4-point Likert scale (0–21) | Score ≥ 9 Score ≥ 9 | |
Dysfunctional fatigue-related cognitions | Fatigue Catastrophising Scale [45] | 5-point Likert scale (10–50) | Score ≥ 16 |
4-point Likert scale (7–28) | Score ≤ 19 | ||
Illness Management Questionnaire-factor III [60] | 6-point Likert scale (9–54) | Score ≥ 30 | |
Anxiety for Fatigue | 4-point Likert scale (8–32) | Score ≥ 14 | |
Deregulated activity pattern | Actigraphy during 12 consecutive days | Number of days with a mean physical activity level > 66 | Low-active: 0-1 Relatively-active: ≥ 2 |
Sickness Impact Profile [41]: subscale Social Interactions | Number and type of items endorsed, weighted according to a standardised weighting scheme | Score ≥ 100 | |
Checklist Individual Strength [33]: subscale Concentration | 7-point Likert scale (5–35) | Score ≥ 18 | |
Negative social interactions and low perceived social support | Van Sonderen Social Support Inventory [61] (shortened version): subscale Negative Interactions subscale Discrepancies | 4-point Likert scale (7–28) 4-point Likert scale (8–32) | Score ≥ 10 Score ≥ 14 |
Usual care and use of co-intervention
Adverse events
Adherence and treatment integrity
Refusal of study participation and study dropout
Outcomes
Concept | Questionnaire | Measurement time points | |||
---|---|---|---|---|---|
T0 | T1 | T2 | T3 | ||
Socio-demographics | Self-report questionnaire | X | |||
Medical characteristics | Medical chart review | X | X | ||
Primary outcome: | |||||
Fatigue severity | CIS fatigue severity
| X | X | X | X |
Secondary outcomes: | |||||
Fatigue | EORTC QLQ-C30 fatigue
| X | X | X | X |
Quality of life | EORTC QLQ-C30 global health status
| X | X | X | X |
Functional impairments | SIP | X | X | X | X |
EORTC QLQ-C30 emotional functioning
| X | X | X | X | |
EORTC QLQ-C30 physical functioning
| X | X | X | X | |
Proposed mediators: | |||||
Physical activity | Actigraphy during 12 consecutive days | X | X | ||
Physical fitness | 6MWT | X | X | ||
Self-efficacy | SES | X | X | ||
Fatigue catastrophising | FCS | X | X |