Breast Neoplasm, Pain
Conditions
Brief summary
In addition to fatigue, pain is the most frequent and persistent symptom following breast cancer and breast cancer treatment. Despite the effectiveness of different physical therapy modalities, such as manual techniques, passive mobilizations and exercises, many patients still experience pain and subsequent difficulties in daily functioning at short and long term. Past decades, the awareness on the important role of educational interventions in the management of pain in general has increased. Educational interventions aim at explaining and improving the knowledge, control and attitude of the patient regarding his/her pain complaint. However, these educational interventions are often restricted to more biomedical pain management instructions and general advice on physical activity and analgesics (= traditional biomedical education). Only recently, increased knowledge on pain mechanisms led to a more modern educational approach. This modern approach is suited to explain more complex issues associated with pain and takes into account many more factors related to pain. To our knowledge, only one controlled trial investigated the effectiveness of a modern educational intervention in the early stage of breast cancer treatment. The results were very promising for shoulder function. However, only short-term effects were examined, no randomization was performed and no pain-related and socio-economic outcomes were evaluated. Therefore, the aim of the proposed project is to investigate the effectiveness of a similar modern educational program, in addition to standard physical therapy care, in the early treatment phase of breast cancer in comparison with traditional biomedical education. A randomized controlled trial will be performed with a long-term follow up period. The primary outcome parameter is pain-related disability. Secondary outcomes are different dimensions of pain, physical and mental functioning, return to work and health-care related costs.
Interventions
Mobilisations, stretching, scar tissue treatment and exercises * Start immediately after surgery, sessions are individual and take 30 minutes * Intensive phase (4 months): 1-2x/week * Maintenance phase (8 months, 3 sessions): 6, 8 and 12 months post-surgery
OTHERModern educational program
This modern neuroscience educational approach is suited to explain more complex issues associated with pain such as the involvement of peripheral and central mechanisms, neuroplasticity and pain behaviour. * Sessions are individual and take 30 minutes, in addition to the standard physical therapy sessions * 3 sessions during week 1-2, 3 booster sessions at 6, 8 and 12 months post-surgery
OTHERTraditional biomedical educational program
Traditional educational interventions are applied according to the biomedical model. This means that the patient's pain experience is explained from a tissue (injured versus healthy tissue) and biomechanics perspective * Sessions are individual and take 30 minutes, in addition to the standard physical therapy sessions * 3 sessions during week 1-2, 3 booster sessions at 6, 8 and 12 months post-surgery
Sponsors
Fund for Scientific Research, Flanders, Belgium
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Patients with primary breast cancer * Unilateral surgery including, either: Axillary lymph node dissection and mastectomy/breast -conserving/reconstructive surgery OR Sentinel Node Biopsy and mastectomy/reconstructive surgery
Exclusion criteria
* Active metastasis * Cannot participate during the entire study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Self-reported Change in Pain-related Disability | Change between baseline and one year follow-up assessment | Measured with Pain Disability Index, an instrument for measuring the impact that pain has on the ability of a person to participate in essential life activities. Scores between 0 and 70. The higher the score the greater the person's disability due to pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Self-reported Pain-intensity | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with Visual Analogue Scale (0-100), lower scores indicate a better outcome. |
| Self-reported Central Sensitization Symptoms | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with the Central Sensitization Inventory (0-100). The Central Sensitization Inventory (CSI) includes 25 items about symptoms related to altered central somatosensory functioning, scored on a five-point Likert scale from 0 (never) to 4 (always). Scores range from 0-100 and a higher score represents greater symptomatology associated with altered central somatosensory processing. |
| Altered Somatosensory Functions (Touch) | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Mechanical detection sensitivity (mN) measured with Von Frey monofilaments at the arm at the affected side. A series of stimulus intensities are given and the stimulus intensity (mN) that is first identified is recorded (min-max 8 mN-512 mN). A lower value indicates a higher sensitivity to mechanical sensitivity. |
| Altered Somatosensory Functions (Temperature-warmth) | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Thermal detection sensitivity (degrees Celsius) for warmth at the arm at the affected side measured with computerized thermotests. Temperature when a change from a thermoneutral state to a distinct warm is recorded. A lower value indicates a higher sentivity to temperature. |
| Endogenous Pain Facilitation Assessed by a Temporal Summation Paradigm (0-10) | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with repetitive pinprick stimuli (using Von Frey Monofilament of 256 mN) at the pectoral region of the affected side. Pain rating after a single stimulation and after 30s of stimulation is recorded. The outcome of interest is the pain rating after 30s stimulation - pain rating single stimulation on a Numeric Rating Scale (0-10) with lower scores meaning less endogenous pain facilitation. |
| Endogenous Pain Inhibition Assessed by a Conditioned Pain Modulation Paradigm (0-10) | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Conditioned Pain Modulation Measured with TSA-II NeuroSensory Analyzer from Medoc. Parallel heat design is used with 1. Test stimulus (45s): Individually determined test stimulus (temperature with a Numeric Rating Scale score of at least 4 out of 10) applied alone. Pain rating (Numeric Rating Scale 0-10) at 10s, 20s, 30s and 40s of stimulation. 2. Break (120s) 3. Conditioning stimulus (temperature of test stimulus + 0.5°C) (65s) + test stimulus in parallel (45s). Pain rating (Numeric Rating Scale 0-10) at 10s, 20s, 30s and 40s of stimulation. The outcome of interest is the a rithmetic mean differences between the Numeric Rating Scale score of the conditioning + test stimulus and test stimulus alone for 4 10s-long epochs (Numeric Rating Scale 0-10) Lower scores indicate better endogenous pain inhibition. |
| Self-reported Upper Limb Function | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with Disability of Arm, Shoulder and Hand Questionnaire (0-100) with lower scores indicating less disability. |
| General Physical Activity Level | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) | Step count average (steps/day) measured with an accelerometer |
| Self-reported Pain-related Disability | Postoperatively after 4 months of intensive treatment and at 1,5 years (after follow-up) | Measured with Pain Disability Index, an instrument for measuring the impact that pain has on the ability of a person to participate in essential life activities. Scores between 0 and 70. The higher the score the greater the person's disability due to pain. |
| Self-reported Emotional Functioning: Depression | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with Depression Anxiety Stress scales 21(0-42) with lower scores indicating less depression. |
| Self-reported Health-related Quality of Life | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with the existential well-being sub scale of the McGill Quality of Life questionnaire (0-10) with higher scores reflecting a better health-related quality of life. |
| Socio-economic Outcomes: Return to Work Rate | Postoperatively after 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Work status at 12 and 18 months postoperatively, i.e. the proportion of women working at 12 and 18 months after surgery, respectively |
| Altered Somatosensory Functions (Temperature-cold) | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Thermal detection sensitivity (degrees Celsius) for cold at the arm at the affected side measured with computerized thermotests. Temperature when a change from a thermoneutral state to a distinct cold is recorded. |
| Altered Somatosensory Functions (Nociception: Pinprick Sensation) | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Mechanical pain sensitivity (mN) measured at the arm at the affected side with Von Frey Monofilaments. A series of stimulus intensities are given and the stimulus intensity that is first identified as painful (not unbearable) is recorded (mN). Min-max 8mN-512mN. |
| Altered Somatosensory Functions (Nociception: Deep Pain Sensitivity) | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Pressure pain sensitivity (kgf) at the pectoralis region at the affected side measured with an algometer. The amount of pressure (kgs) by which the perception of pressure turns for the first time into a painful (not unbearable) sensation. Lower values indicate higher pain sensitivity. |
| Self-reported Emotional Functioning: Anxiety | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with Depression Anxiety Stress scales 21 (0-42). Lower scores indicate less anxiety. |
| Self-reported Emotional Functioning: Stress | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with Depression Anxiety Stress scales 21 (0-42). Lower scores indicate less stress. |
| Self-reported Emotional Functioning: Pain Catastrophizing | Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up) | Measured with the Pain Catastrophizing scale (0-52), with higher scores corresponding to more pain-related catastrophizing. |
Countries
Belgium
Participant flow
Recruitment details
Recruitment took place at the Multidisciplinary Breast Center of the University Hospitals Leuven campus Gasthuisberg (Belgium) between November 2017 and March 2020.
Pre-assignment details
In total, 493 women were eligible, of which 184 were included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group Standard physical therapy program + Modern educational program
Standard physical therapy program: Mobilisations, stretching, scar tissue treatment and exercises
* Start immediately after surgery, sessions are individual and take 30 minutes
* Intensive phase (4 months): 1-2x/week
* Maintenance phase (8 months, 3 sessions): 6, 8 and 12 months post-surgery
Modern educational program: This modern neuroscience educational approach is suited to explain more complex issues associated with pain such as the involvement of peripheral and central mechanisms, neuroplasticity and pain behaviour.
* Sessions are individual and take 30 minutes, in addition to the standard physical therapy sessions
* 3 sessions during week 1-2, 3 booster sessions at 6, 8 and 12 months post-surgery | 92 |
| Control Group Standard physical therapy program + Traditional biomedical educational program
Standard physical therapy program: Mobilisations, stretching, scar tissue treatment and exercises
* Start immediately after surgery, sessions are individual and take 30 minutes
* Intensive phase (4 months): 1-2x/week
* Maintenance phase (8 months, 3 sessions): 6, 8 and 12 months post-surgery
Traditional biomedical educational program: Traditional educational interventions are applied according to the biomedical model. This means that the patient's pain experience is explained from a tissue (injured versus healthy tissue) and biomechanics perspective
* Sessions are individual and take 30 minutes, in addition to the standard physical therapy sessions
* 3 sessions during week 1-2, 3 booster sessions at 6, 8 and 12 months post-surgery | 92 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| End of Trial (18 mo FU) | Withdrawal by Subject | 1 | 1 |
| Intensive Treatment Phase (4 mo FU) | Death | 0 | 1 |
| Intensive Treatment Phase (4 mo FU) | Withdrawal by Subject | 6 | 4 |
| Maintenance Treatment Phase (12 mo FU) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Intervention Group | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 16 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 74 Participants | 76 Participants | 150 Participants |
| Age, Continuous | 55.4 years STANDARD_DEVIATION 11.5 | 55.2 years STANDARD_DEVIATION 11.4 | 55.3 years STANDARD_DEVIATION 11.4 |
| BMI | 25.4 kg/m^2 STANDARD_DEVIATION 4.3 | 25.9 kg/m^2 STANDARD_DEVIATION 5.9 | 25.6 kg/m^2 STANDARD_DEVIATION 5.2 |
| Chemotherapy | 63 participants | 55 participants | 118 participants |
| Educational Level Higher education: academic bachelor or master | 25 participants | 19 participants | 44 participants |
| Educational Level Higher education: professional bachelor | 30 participants | 32 participants | 62 participants |
| Educational Level Lower secondary education | 5 participants | 5 participants | 10 participants |
| Educational Level Primary education or no diploma | 3 participants | 3 participants | 6 participants |
| Educational Level Upper secondary education | 23 participants | 28 participants | 51 participants |
| Hormone therapy | 69 participants | 68 participants | 137 participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Radiotherapy | 74 participants | 66 participants | 140 participants |
| Region of Enrollment Belgium | 92 participants | 92 participants | 184 participants |
| Sex: Female, Male Female | 92 Participants | 92 Participants | 184 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Surgery at dominant side Surgery at dominant side (no) | 48 participants | 51 participants | 99 participants |
| Surgery at dominant side Surgery at dominant side (yes) | 44 participants | 41 participants | 85 participants |
| Type of surgery 1ME+SLNB | 41 participants | 43 participants | 84 participants |
| Type of surgery BCS+ALND | 4 participants | 9 participants | 13 participants |
| Type of surgery ME+ALND | 47 participants | 40 participants | 87 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 1 / 92 |
| other Total, other adverse events | 0 / 92 | 0 / 92 |
| serious Total, serious adverse events | 0 / 92 | 0 / 92 |
Outcome results
Primary
Self-reported Change in Pain-related Disability
Measured with Pain Disability Index, an instrument for measuring the impact that pain has on the ability of a person to participate in essential life activities. Scores between 0 and 70. The higher the score the greater the person's disability due to pain.
Time frame: Change between baseline and one year follow-up assessment
Population: Using likelihood-based estimation, subjects with a missing at one or more timepoints were still included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention Group | Self-reported Change in Pain-related Disability | 4.22 score on a scale |
| Control Group | Self-reported Change in Pain-related Disability | 5.53 score on a scale |
Comparison: The sample size was based on comparing the changes for the primary outcome measure (PDI-DLV) at 12 months after surgery. The calculation was based on comparing the values at 12 months. Assuming a coefficient of variation (CV) equal to 0.5, 87 participants per group were needed based on a two-sample pooled t-test of a mean ratio with lognormal data and α=0.05 to detect with 80% power a difference of 20% in PDI. To anticipate a drop-out ratio of 5%, a total of 184 subjects were needed.p-value: 0.516395% CI: [-5.28, 2.65]Multivariate linear model
Secondary
Altered Somatosensory Functions (Nociception: Deep Pain Sensitivity)
Pressure pain sensitivity (kgf) at the pectoralis region at the affected side measured with an algometer. The amount of pressure (kgs) by which the perception of pressure turns for the first time into a painful (not unbearable) sensation. Lower values indicate higher pain sensitivity.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Altered Somatosensory Functions (Nociception: Deep Pain Sensitivity) | Mean change from baseline to 4 months | 1.05 kgf |
| Intervention Group | Altered Somatosensory Functions (Nociception: Deep Pain Sensitivity) | Mean change from baseline to 1 year | 0.84 kgf |
| Intervention Group | Altered Somatosensory Functions (Nociception: Deep Pain Sensitivity) | Mean change from baseline to 1.5 years | 0.81 kgf |
| Control Group | Altered Somatosensory Functions (Nociception: Deep Pain Sensitivity) | Mean change from baseline to 4 months | 0.94 kgf |
| Control Group | Altered Somatosensory Functions (Nociception: Deep Pain Sensitivity) | Mean change from baseline to 1 year | 0.75 kgf |
| Control Group | Altered Somatosensory Functions (Nociception: Deep Pain Sensitivity) | Mean change from baseline to 1.5 years | 0.78 kgf |
Comparison: Difference in change in pressure pain sensitivity at the pectoral region from baseline to 4 monthsp-value: 0.127895% CI: [0.97, 1.27]Multivariate linear model
Comparison: Difference in change in pressure pain sensitivity at the pectoral region from baseline to 1 yearp-value: 0.187595% CI: [0.95, 1.3]Multivariate linear model
Comparison: Difference in change in pressure pain sensitivity at the pectoral region from baseline to 1.5 yearsp-value: 0.561295% CI: [0.89, 1.23]Multivariate linear model
Secondary
Altered Somatosensory Functions (Nociception: Pinprick Sensation)
Mechanical pain sensitivity (mN) measured at the arm at the affected side with Von Frey Monofilaments. A series of stimulus intensities are given and the stimulus intensity that is first identified as painful (not unbearable) is recorded (mN). Min-max 8mN-512mN.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Altered Somatosensory Functions (Nociception: Pinprick Sensation) | Mean change from baseline to 4 months | 19.77 mN |
| Intervention Group | Altered Somatosensory Functions (Nociception: Pinprick Sensation) | Mean change from baseline to 1 year | -22.24 mN |
| Intervention Group | Altered Somatosensory Functions (Nociception: Pinprick Sensation) | Mean change from baseline to 1.5 years | -17.91 mN |
| Control Group | Altered Somatosensory Functions (Nociception: Pinprick Sensation) | Mean change from baseline to 4 months | 14.99 mN |
| Control Group | Altered Somatosensory Functions (Nociception: Pinprick Sensation) | Mean change from baseline to 1 year | 35.02 mN |
| Control Group | Altered Somatosensory Functions (Nociception: Pinprick Sensation) | Mean change from baseline to 1.5 years | 2.19 mN |
Comparison: Difference in change in mechanical pain sensitivity at the arm from baseline to 4 monthsp-value: 0.858495% CI: [-47.72, 57.28]Multivariate linear model
Comparison: Difference in change in mechanical pain sensitivity at the arm from baseline to 1 yearp-value: 0.035395% CI: [-110.57, -3.93]Multivariate linear model
Comparison: Difference in change in mechanical pain sensitivity at the arm from baseline to 1.5 yearsp-value: 0.486595% CI: [-76.72, 36.52]Multivariate linear model
Secondary
Altered Somatosensory Functions (Temperature-cold)
Thermal detection sensitivity (degrees Celsius) for cold at the arm at the affected side measured with computerized thermotests. Temperature when a change from a thermoneutral state to a distinct cold is recorded.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Altered Somatosensory Functions (Temperature-cold) | Mean change from baseline to 4 months | -4.77 degrees Celsius |
| Intervention Group | Altered Somatosensory Functions (Temperature-cold) | Mean change from baseline to 1 year | -3.36 degrees Celsius |
| Intervention Group | Altered Somatosensory Functions (Temperature-cold) | Mean change from baseline to 1.5 years | -3.90 degrees Celsius |
| Control Group | Altered Somatosensory Functions (Temperature-cold) | Mean change from baseline to 4 months | -5.00 degrees Celsius |
| Control Group | Altered Somatosensory Functions (Temperature-cold) | Mean change from baseline to 1 year | -4.16 degrees Celsius |
| Control Group | Altered Somatosensory Functions (Temperature-cold) | Mean change from baseline to 1.5 years | -4.35 degrees Celsius |
Comparison: Difference in change in cold detection sensitivity from baseline to 4 monthsp-value: 0.849795% CI: [-2.17, 2.64]Multivariate linear model
Comparison: Difference in change in cold detection sensitivity from baseline to 1 yearp-value: 0.497195% CI: [-1.52, 3.14]Multivariate linear model
Comparison: Difference in change in cold detection sensitivity from baseline to 1.5 yearsp-value: 0.683195% CI: [-1.72, 2.62]Multivariate linear model
Secondary
Altered Somatosensory Functions (Temperature-warmth)
Thermal detection sensitivity (degrees Celsius) for warmth at the arm at the affected side measured with computerized thermotests. Temperature when a change from a thermoneutral state to a distinct warm is recorded. A lower value indicates a higher sentivity to temperature.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Altered Somatosensory Functions (Temperature-warmth) | Mean change from baseline to 4 months | 3.54 degrees celcius |
| Intervention Group | Altered Somatosensory Functions (Temperature-warmth) | Mean change from baseline to 1 year | 2.67 degrees celcius |
| Intervention Group | Altered Somatosensory Functions (Temperature-warmth) | Mean change from baseline to 1.5 years | 2.74 degrees celcius |
| Control Group | Altered Somatosensory Functions (Temperature-warmth) | Mean change from baseline to 1.5 years | 2.72 degrees celcius |
| Control Group | Altered Somatosensory Functions (Temperature-warmth) | Mean change from baseline to 4 months | 3.32 degrees celcius |
| Control Group | Altered Somatosensory Functions (Temperature-warmth) | Mean change from baseline to 1 year | 2.38 degrees celcius |
Comparison: Difference in change in warmth detection sensitivity from baseline to 4 monthsp-value: 0.770895% CI: [-1.25, 1.69]Multivariate linear model
Comparison: Difference in change in warmth detection sensitivity from baseline to 1 yearp-value: 0.70695% CI: [-1.23, 1.81]Multivariate linear model
Comparison: Difference in change in warmth detection sensitivity from baseline to 1.5 yearsp-value: 0.980695% CI: [-1.38, 1.42]Multivariate linear model
Secondary
Altered Somatosensory Functions (Touch)
Mechanical detection sensitivity (mN) measured with Von Frey monofilaments at the arm at the affected side. A series of stimulus intensities are given and the stimulus intensity (mN) that is first identified is recorded (min-max 8 mN-512 mN). A lower value indicates a higher sensitivity to mechanical sensitivity.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Altered Somatosensory Functions (Touch) | Mean change from baseline to 4 months | 2.37 mN |
| Intervention Group | Altered Somatosensory Functions (Touch) | Mean change from baseline to 1 year | 1.68 mN |
| Intervention Group | Altered Somatosensory Functions (Touch) | Mean change from baseline to 1.5 years | 2.35 mN |
| Control Group | Altered Somatosensory Functions (Touch) | Mean change from baseline to 1.5 years | 1.87 mN |
| Control Group | Altered Somatosensory Functions (Touch) | Mean change from baseline to 4 months | 1.76 mN |
| Control Group | Altered Somatosensory Functions (Touch) | Mean change from baseline to 1 year | 1.95 mN |
Comparison: Difference in change in mechanical detection sensitivity at the arm from baseline to 4 monthsp-value: 0.346395% CI: [0.72, 2.51]multivariate linear model
Comparison: Difference in change in mechanical detection sensitivity at the arm from baseline to 1 yearp-value: 0.661395% CI: [0.451, 1.66]Multivariate linear model
Comparison: Difference in change in mechanical detection sensitivity at the arm from baseline to 1.5 yearsp-value: 0.490895% CI: [0.65, 2.42]Multivariate linear model
Secondary
Endogenous Pain Facilitation Assessed by a Temporal Summation Paradigm (0-10)
Measured with repetitive pinprick stimuli (using Von Frey Monofilament of 256 mN) at the pectoral region of the affected side. Pain rating after a single stimulation and after 30s of stimulation is recorded. The outcome of interest is the pain rating after 30s stimulation - pain rating single stimulation on a Numeric Rating Scale (0-10) with lower scores meaning less endogenous pain facilitation.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differs per timepoints
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Endogenous Pain Facilitation Assessed by a Temporal Summation Paradigm (0-10) | Mean change from baseline to 1.5 years | 0.48 score on a scale |
| Intervention Group | Endogenous Pain Facilitation Assessed by a Temporal Summation Paradigm (0-10) | Mean change from baseline to 4 months | 0.95 score on a scale |
| Intervention Group | Endogenous Pain Facilitation Assessed by a Temporal Summation Paradigm (0-10) | Mean change from baseline to 1 year | 0.24 score on a scale |
| Control Group | Endogenous Pain Facilitation Assessed by a Temporal Summation Paradigm (0-10) | Mean change from baseline to 4 months | 0.21 score on a scale |
| Control Group | Endogenous Pain Facilitation Assessed by a Temporal Summation Paradigm (0-10) | Mean change from baseline to 1 year | 0.15 score on a scale |
| Control Group | Endogenous Pain Facilitation Assessed by a Temporal Summation Paradigm (0-10) | Mean change from baseline to 1.5 years | 0.17 score on a scale |
Comparison: Difference in change in wind-up from baseline to 4 monthsp-value: 0.028495% CI: [0.08, 1.4]Multivariate linear model
Comparison: Difference in change in wind-up from baseline to 1 yearp-value: 0.777695% CI: [-0.55, 0.73]Multivariate linear model
Comparison: Difference in change in wind-up from baseline to 1.5 yearsp-value: 0.382995% CI: [-0.39, 1.01]Multivariate linear model
Secondary
Endogenous Pain Inhibition Assessed by a Conditioned Pain Modulation Paradigm (0-10)
Conditioned Pain Modulation Measured with TSA-II NeuroSensory Analyzer from Medoc. Parallel heat design is used with 1. Test stimulus (45s): Individually determined test stimulus (temperature with a Numeric Rating Scale score of at least 4 out of 10) applied alone. Pain rating (Numeric Rating Scale 0-10) at 10s, 20s, 30s and 40s of stimulation. 2. Break (120s) 3. Conditioning stimulus (temperature of test stimulus + 0.5°C) (65s) + test stimulus in parallel (45s). Pain rating (Numeric Rating Scale 0-10) at 10s, 20s, 30s and 40s of stimulation. The outcome of interest is the a rithmetic mean differences between the Numeric Rating Scale score of the conditioning + test stimulus and test stimulus alone for 4 10s-long epochs (Numeric Rating Scale 0-10) Lower scores indicate better endogenous pain inhibition.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Endogenous Pain Inhibition Assessed by a Conditioned Pain Modulation Paradigm (0-10) | Mean change from baseline to 4 months | 0.30 score on a scale |
| Intervention Group | Endogenous Pain Inhibition Assessed by a Conditioned Pain Modulation Paradigm (0-10) | Mean change from baseline to 1 year | 0.13 score on a scale |
| Intervention Group | Endogenous Pain Inhibition Assessed by a Conditioned Pain Modulation Paradigm (0-10) | Mean change from baseline to 1.5 years | -0.13 score on a scale |
| Control Group | Endogenous Pain Inhibition Assessed by a Conditioned Pain Modulation Paradigm (0-10) | Mean change from baseline to 4 months | -0.01 score on a scale |
| Control Group | Endogenous Pain Inhibition Assessed by a Conditioned Pain Modulation Paradigm (0-10) | Mean change from baseline to 1 year | -0.04 score on a scale |
| Control Group | Endogenous Pain Inhibition Assessed by a Conditioned Pain Modulation Paradigm (0-10) | Mean change from baseline to 1.5 years | -0.36 score on a scale |
Comparison: Difference in change in conditioned pain modulation from baseline to 4 monthsp-value: 0.194895% CI: [-0.16, 0.77]Multivariate linear model
Comparison: Difference in change in conditioned pain modulation from baseline to 1 yearp-value: 0.493795% CI: [-0.31, 0.65]Multivariate linear model
Comparison: Difference in change in conditioned pain modulation from baseline to 1.5 yearsp-value: 0.36995% CI: [-0.27, 0.73]Multivariate linear model
Secondary
General Physical Activity Level
Step count average (steps/day) measured with an accelerometer
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment)
Population: Available data differed per time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | General Physical Activity Level | Mean change from baseline to 1 year | 1100 steps/day |
| Intervention Group | General Physical Activity Level | Mean change from baseline to 4 months | 50 steps/day |
| Control Group | General Physical Activity Level | Mean change from baseline to 4 months | 342 steps/day |
| Control Group | General Physical Activity Level | Mean change from baseline to 1 year | 261 steps/day |
Comparison: Difference in change in step count from baseline to 4 monthsp-value: 0.533295% CI: [-1218, 632]Multivariate linear model
Comparison: Difference in change in step count from baseline to 1 yearp-value: 0.120195% CI: [-221, 1900]Multivariate linear model
Secondary
Self-reported Central Sensitization Symptoms
Measured with the Central Sensitization Inventory (0-100). The Central Sensitization Inventory (CSI) includes 25 items about symptoms related to altered central somatosensory functioning, scored on a five-point Likert scale from 0 (never) to 4 (always). Scores range from 0-100 and a higher score represents greater symptomatology associated with altered central somatosensory processing.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed on timepoints
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Central Sensitization Symptoms | Mean change from baseline to 4 months | 3.61 score on a scale |
| Intervention Group | Self-reported Central Sensitization Symptoms | Mean change from baseline to 1 year | 2.14 score on a scale |
| Intervention Group | Self-reported Central Sensitization Symptoms | Mean change from baseline to 1.5 years | 3.15 score on a scale |
| Control Group | Self-reported Central Sensitization Symptoms | Mean change from baseline to 4 months | 3.43 score on a scale |
| Control Group | Self-reported Central Sensitization Symptoms | Mean change from baseline to 1 year | 2.39 score on a scale |
| Control Group | Self-reported Central Sensitization Symptoms | Mean change from baseline to 1.5 years | 3.43 score on a scale |
Comparison: Difference in change in self-reported central sensitisation symptoms from baseline to 1.5 yearsp-value: 0.845495% CI: [-3.16, 2.59]Multivariate linear model
Comparison: Difference in change in self-reported central sensitisation symptoms from baseline to 4 months.p-value: 0.749495% CI: [-2.39, 3.32]Multivariate linear model
Comparison: The difference in change in self-reported central sensitisation symptoms from baseline to 12 months.p-value: 0.861795% CI: [-3.09, 2.58]Multivariate linear model
Secondary
Self-reported Emotional Functioning: Anxiety
Measured with Depression Anxiety Stress scales 21 (0-42). Lower scores indicate less anxiety.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Emotional Functioning: Anxiety | Mean change from baseline to 4 months | 1.045 score on a scale |
| Intervention Group | Self-reported Emotional Functioning: Anxiety | Mean change from baseline to 1 year | 0.783 score on a scale |
| Intervention Group | Self-reported Emotional Functioning: Anxiety | Mean change from baseline to 1.5 years | 0.829 score on a scale |
| Control Group | Self-reported Emotional Functioning: Anxiety | Mean change from baseline to 4 months | 0.987 score on a scale |
| Control Group | Self-reported Emotional Functioning: Anxiety | Mean change from baseline to 1 year | 0.839 score on a scale |
| Control Group | Self-reported Emotional Functioning: Anxiety | Mean change from baseline to 1.5 years | 0.821 score on a scale |
Comparison: Difference in change in self-reported anxiety from baseline to 4 monthsp-value: 0.790295% CI: [0.693, 1.62]Multivariate linear model
Comparison: Difference in change in self-reported anxiety from baseline to 1 yearp-value: 0.757895% CI: [0.604, 1.443]Multivariate linear model
Comparison: Difference in change in self-reported anxiety from baseline to 1.5 yearsp-value: 0.9695% CI: [0.679, 1.504]Multivariate linear model
Secondary
Self-reported Emotional Functioning: Depression
Measured with Depression Anxiety Stress scales 21(0-42) with lower scores indicating less depression.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Emotional Functioning: Depression | Mean change from baseline to 4 months | 0.802 score on a scale |
| Intervention Group | Self-reported Emotional Functioning: Depression | Mean change from baseline to 1 year | 0.625 score on a scale |
| Intervention Group | Self-reported Emotional Functioning: Depression | Mean change from baseline to 1.5 years | 0.718 score on a scale |
| Control Group | Self-reported Emotional Functioning: Depression | Mean change from baseline to 4 months | 0.930 score on a scale |
| Control Group | Self-reported Emotional Functioning: Depression | Mean change from baseline to 1 year | 0.774 score on a scale |
| Control Group | Self-reported Emotional Functioning: Depression | Mean change from baseline to 1.5 years | 0.749 score on a scale |
Comparison: Difference in change in self-reported depression from baseline to 4 monthsp-value: 0.501895% CI: [0.558, 1.33]MUltivariate linear model
Comparison: Difference in change in self-reported depression from baseline to 1 yearp-value: 0.336295% CI: [0.522, 1.248]Multivariate linear model
Comparison: Difference in change in self-reported depression from baseline to 1.5 yearsp-value: 0.837595% CI: [0.633, 1.449]Multivariate linear model
Secondary
Self-reported Emotional Functioning: Pain Catastrophizing
Measured with the Pain Catastrophizing scale (0-52), with higher scores corresponding to more pain-related catastrophizing.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Emotional Functioning: Pain Catastrophizing | Mean change from baseline to 4 months | 0.896 score on a scale |
| Intervention Group | Self-reported Emotional Functioning: Pain Catastrophizing | Mean change from baseline to 1 year | 0.894 score on a scale |
| Intervention Group | Self-reported Emotional Functioning: Pain Catastrophizing | Mean change from baseline to 1.5 years | 0.762 score on a scale |
| Control Group | Self-reported Emotional Functioning: Pain Catastrophizing | Mean change from baseline to 4 months | 1.077 score on a scale |
| Control Group | Self-reported Emotional Functioning: Pain Catastrophizing | Mean change from baseline to 1 year | 1.065 score on a scale |
| Control Group | Self-reported Emotional Functioning: Pain Catastrophizing | Mean change from baseline to 1.5 years | 0.898 score on a scale |
Comparison: Difference in change in self-reported pain catastrophizing from baseline to 4 monthsp-value: 0.35995% CI: [0.561, 1.233]Multivariate linear model
Comparison: Difference in change in self-reported pain catastrophizing from baseline to 1 yearp-value: 0.374495% CI: [0.57, 1.236]Multivariate linear model
Comparison: Difference in change in self-reported pain catastrophizing from baseline to 1.5 yearsp-value: 0.453395% CI: [0.522, 1.304]Multivariate linear model
Secondary
Self-reported Emotional Functioning: Stress
Measured with Depression Anxiety Stress scales 21 (0-42). Lower scores indicate less stress.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Emotional Functioning: Stress | Mean change from baseline to 4 months | 0.812 score on a scale |
| Intervention Group | Self-reported Emotional Functioning: Stress | Mean change from baseline to 1 year | 0.782 score on a scale |
| Intervention Group | Self-reported Emotional Functioning: Stress | Mean change from baseline to 1.5 years | 0.857 score on a scale |
| Control Group | Self-reported Emotional Functioning: Stress | Mean change from baseline to 4 months | 0.760 score on a scale |
| Control Group | Self-reported Emotional Functioning: Stress | Mean change from baseline to 1 year | 0.721 score on a scale |
| Control Group | Self-reported Emotional Functioning: Stress | Mean change from baseline to 1.5 years | 0.868 score on a scale |
Comparison: Difference in change in self-reported stress from baseline to 4 monthsp-value: 0.761995% CI: [0.696, 1.639]Multivariate linear model
Comparison: Difference in change in self-reported stress from baseline to 1 yearp-value: 0.716995% CI: [0.702, 1.673]Multivariate linear model
Comparison: Difference in change in self-reported stress from baseline to 1.5 yearsp-value: 0.953595% CI: [0.639, 1.525]Multivariate linear model
Secondary
Self-reported Health-related Quality of Life
Measured with the existential well-being sub scale of the McGill Quality of Life questionnaire (0-10) with higher scores reflecting a better health-related quality of life.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Health-related Quality of Life | Mean change from baseline to 4 months | 0.19 score on a scale |
| Intervention Group | Self-reported Health-related Quality of Life | Mean change from baseline to 1 year | 0.90 score on a scale |
| Intervention Group | Self-reported Health-related Quality of Life | Mean change from baseline to 1.5 years | 1.07 score on a scale |
| Control Group | Self-reported Health-related Quality of Life | Mean change from baseline to 4 months | 0.51 score on a scale |
| Control Group | Self-reported Health-related Quality of Life | Mean change from baseline to 1 year | 0.71 score on a scale |
| Control Group | Self-reported Health-related Quality of Life | Mean change from baseline to 1.5 years | 0.61 score on a scale |
Comparison: Difference in change in self-reported health-related quality of life from baseline to 4 monthsp-value: 0.174595% CI: [-0.78, 0.14]Multivariate linear model
Comparison: Difference in change in self-reported health-related quality of life from baseline to 1 yearp-value: 0.502595% CI: [-0.35, 0.71]Multivariate linear model
Comparison: Difference in change in self-reported health-related quality of life from baseline to 1,5 yearsp-value: 0.136395% CI: [-0.14, 1.05]Multivariate linear model
Secondary
Self-reported Pain-intensity
Measured with Visual Analogue Scale (0-100), lower scores indicate a better outcome.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed between timepoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Pain-intensity | Mean change from baseline to 4 months | 7.26 score on a scale |
| Intervention Group | Self-reported Pain-intensity | Mean change from baseline to 12 months | 6.31 score on a scale |
| Intervention Group | Self-reported Pain-intensity | Mean change from baseline to 1.5 years | 3.91 score on a scale |
| Control Group | Self-reported Pain-intensity | Mean change from baseline to 4 months | 9.49 score on a scale |
| Control Group | Self-reported Pain-intensity | Mean change from baseline to 12 months | 10.61 score on a scale |
| Control Group | Self-reported Pain-intensity | Mean change from baseline to 1.5 years | 8.71 score on a scale |
Comparison: Difference in change in self-reported pain intensity from baseline to 4 monthsp-value: 0.56395% CI: [-9.84, 5.37]Multivariate linear model
Comparison: Difference in change in self-reported pain intensity from baseline to 12 monthsp-value: 0.252495% CI: [-11.68, 3.09]Multivariate linear model
Comparison: Difference in change in self-reported pain intensity from baseline to 1.5 yearsp-value: 0.231595% CI: [-12.69, 3.09]Multivariate linear model
Secondary
Self-reported Pain-related Disability
Measured with Pain Disability Index, an instrument for measuring the impact that pain has on the ability of a person to participate in essential life activities. Scores between 0 and 70. The higher the score the greater the person's disability due to pain.
Time frame: Postoperatively after 4 months of intensive treatment and at 1,5 years (after follow-up)
Population: Available data differed between timepoints
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Pain-related Disability | Change from baseline to 4 months | 3.70 score on a scale |
| Intervention Group | Self-reported Pain-related Disability | Change from baseline to 1.5 years | 3.13 score on a scale |
| Control Group | Self-reported Pain-related Disability | Change from baseline to 4 months | 4.67 score on a scale |
| Control Group | Self-reported Pain-related Disability | Change from baseline to 1.5 years | 4.19 score on a scale |
Comparison: Difference in change in self-reported pain-related disability from baseline to 4 monthsp-value: 0.565595% CI: [-4.26, 2.33]multivariate linear model
Comparison: Difference in change in self-reported pain-related disability from baseline to 1.5 yearsp-value: 0.559295% CI: [-4.64, 2.51]multivariate linear model
Secondary
Self-reported Upper Limb Function
Measured with Disability of Arm, Shoulder and Hand Questionnaire (0-100) with lower scores indicating less disability.
Time frame: Postoperatively after 4 months of intensive treatment, at 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: Available data differed per timepoints
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Self-reported Upper Limb Function | Mean change from baseline to 1 year | 8.51 score on a scale |
| Intervention Group | Self-reported Upper Limb Function | Mean change from baseline to 1.5 years | 6.56 score on a scale |
| Intervention Group | Self-reported Upper Limb Function | Mean change from baseline to 4 months | 10.05 score on a scale |
| Control Group | Self-reported Upper Limb Function | Mean change from baseline to 1.5 years | 9.72 score on a scale |
| Control Group | Self-reported Upper Limb Function | Mean change from baseline to 4 months | 7.81 score on a scale |
| Control Group | Self-reported Upper Limb Function | Mean change from baseline to 1 year | 10.15 score on a scale |
Comparison: Difference in change in self-reported upper limb function from baseline to 4 monthsp-value: 0.291595% CI: [-1.94, 6.43]Multivariate linear model
Comparison: Difference in change in self-reported upper limb function from baseline to 1 yearp-value: 0.463295% CI: [-6.02, 2.75]Multivariate linear model
Comparison: Difference in change in self-reported upper limb function from baseline to 1,5 yearsp-value: 0.194495% CI: [-7.94, 1.63]Multivariate linear model
Secondary
Socio-economic Outcomes: Return to Work Rate
Work status at 12 and 18 months postoperatively, i.e. the proportion of women working at 12 and 18 months after surgery, respectively
Time frame: Postoperatively after 1 year (after maintenance treatment) and at 1,5 years (after follow-up)
Population: One hundred fifteen participants (62.5%) were working at time of diagnosis (IG=58; CG=57); available data differed per time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intervention Group | Socio-economic Outcomes: Return to Work Rate | At 1 year | 41 Participants |
| Intervention Group | Socio-economic Outcomes: Return to Work Rate | At 1.5 years | 47 Participants |
| Control Group | Socio-economic Outcomes: Return to Work Rate | At 1 year | 30 Participants |
| Control Group | Socio-economic Outcomes: Return to Work Rate | At 1.5 years | 41 Participants |
Comparison: Difference in proportion of working participants at 1 yearp-value: 0.07495% CI: [-0.358, 0.008]Fisher Exact
Comparison: Difference in proportion of working participants at 1,5 yearsp-value: 0.35295% CI: [-0.26, 0.078]Fisher Exact