Photobiomodulation Therapy for the Management of Breast Cancer-related Lymphedema

Study Overview
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Brief Summary
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Up to one out of five patients with breast cancer will develop lymphedema in the upper extremity after cancer treatment. Patients with breast cancer-related lymphedema (BCRL) suffer from pain, heaviness, tightness, and a decreased range of motion. Photobiomodulation therapy (PBMT) is a non-invasive therapy based on the application of visible and/or near-infrared light produced by a laser diode or a light-emitting diode. The scientifically proven biologic effects of PBM are improved wound healing, and a reduction in pain, inflammation, and oedema. Therefore, the aim of this study is to evaluate the effectiveness of PBMT on the management of BCRL.

Detailed Description
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This aim of this study is to determine the efficacy of PBMT in combination with the institutional therapy on the management of BCRL. Therefore, we hypothesize that PBMT in combination with manual lymphatic drainage is able to reduce the limb circumference and the associated pain and improve the QoL of patients with BCRL during treatment and up to 12 months post-treatment. Primary Objective 1: Arm circumference The study seeks primarily to determine the effectiveness PBMT and manual lymphatic drainage in reducing the arm circumference in patients with established BCRL during PBM treatment and up to 12 months post-PBMT. Primary Objective 2: Activity and participation Another primary aim of this study is to evaluate the effectiveness of PBMT and manual lymphatic drainage in the enhancement of the patients' activity and participation status. Secondary Objective 1: Pain A secondary aim of this study is to evaluate if PBMT and manual lymphatic drainage can reduce the BCRL-related pain during PBM treatment and up to 12 months post-PBMT. Secondary Objective 2: Quality of life A secondary aim of this study is to evaluate if PBMT and manual lymphatic drainage can improve the patients' QoL during PBM treatment and up to 12 months post-PBMT. Secondary Objective 3: Depression A secondary aim of this study is to evaluate if PBMT and manual lymphatic drainage can improve the patients' mental status during PBM treatment and up to 12 months post-PBMT. Secondary Objective 4: Patient satisfaction A secondary aim of this study is to evaluate if patients are satisfied with PBMT and manual lymphatic drainage as a treatment for BCRL during the treatment sessions and up to 12 months post-therapy. Secondary Objective 5: PBM safety A secondary aim of this study is to evaluate the safety of PBM in oncologic patients up to 5 years post-PBMT.

Official Title
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Evaluating the Effectiveness of Photobiomodulation Therapy in the Management of Breast Cancer-Related Lymphedema: a Randomized Controlled Trial

Conditions
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Breast Cancer, Breast Cancer Related Lymphedema, Lymphedema of Upper Arm

Intervention / Treatment
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* Device: Photobiomodulation therapy (PBMT)
* Procedure: Manual Lymphatic drainage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with breast cancer Underwent ipsilateral lumpectomy or mastectomy + sentinel lymph node biopsy +/- lymph node dissection Underwent radiotherapy with or without chemotherapy Diagnosed with BCRL (i.e. International Society of Lymphology (ISL) lymphedema stage I or higher) Age ≥ 18 years Able to comply to the study protocol Able to sign written informed consent Exclusion Criteria: Metastatic disease Pregnancy History of surgery or trauma to the arm History of arm infection in the past 3 months Use of medications that affect body fluid (e.g., diuretics) in the last 3 months Severe psychological disorder or dementia Any condition that is unstable or could affect the safety of the patient and their compliance in the study as judged by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: prospective randomized, controlled cross-over trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Group A will receive first PBM + manual lymphatic drainage for 9 weeks (2 sessions/week), followed by 9 weeks only manual lymphatic drainage. | Device: Photobiomodulation therapy (PBMT)<br>* The MLS M6 laser from ASA will be used to apply the laser therapy.<br>* Other names: LLLT;Procedure: Manual Lymphatic drainage<br>* Patients will receive twice weekly MLT executed by trained physiotherapist<br>* Other names: MLT;|
| Active Comparator: Group B<br>Group B will first receive only manual lymphatic drainage for 9 weeks, followed by the combination of PBM and manual lymphatic drainage for 9 weeks (2x/week). | Device: Photobiomodulation therapy (PBMT)<br>* The MLS M6 laser from ASA will be used to apply the laser therapy.<br>* Other names: LLLT;Procedure: Manual Lymphatic drainage<br>* Patients will receive twice weekly MLT executed by trained physiotherapist<br>* Other names: MLT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | Baseline | 
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | week 5 | 
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | week 9 | 
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | Week 14 | 
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | Week 18 | 
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | 3 month follow-up | 
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | 6 month follow-up | 
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | 9 month follow-up | 
| Arm circumference and volume | The arm circumferences will be measured at olecranon and at 4, 8, 12, 16 and 20 cm proximal and distal of olecranon. The circumference at each point will be recorded in cm. The calculated arm volume will be estimated by the formula of the truncated cone of each 4 cm segment proximal (towards the wrist) and distal (towards the acromion) from the olecranon. The following truncated cone formula was used: 4 * (C1* C1 +C1*C2+C2*C2)/12π C1 is the upper circumference and C2 is the lower circumference of each segment. The calculated volume of whole arm is the sum of the volume of all segments of the arm expressed in kubic centimeter | 12 month follow-up | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | Baseline | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | week 5 | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | week 9 | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | week 14 | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | week 18 | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | 3 month follow-up | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | 6 month follow-up | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | 9 month follow-up | 
| Arm mobility measurement | A standard plastic goniometer will be used to measure active range of mobility (ROM) for shoulder flexion, abduction, and external rotation. | 12 month follow-up | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. | Baseline | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. The score can range from 0 (no disability) to 100 (most severe disability). | week 5 | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. The score can range from 0 (no disability) to 100 (most severe disability). | week 9 | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. The score can range from 0 (no disability) to 100 (most severe disability). | week 14 | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. The score can range from 0 (no disability) to 100 (most severe disability). | week 18 | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. The score can range from 0 (no disability) to 100 (most severe disability). | 3 month follow-up | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. The score can range from 0 (no disability) to 100 (most severe disability). | 6 month follow-up | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. The score can range from 0 (no disability) to 100 (most severe disability). | 9 month follow-up | 
| Activity and participation | The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is a 30-item questionnaire that looks at the ability of a patient to perform certain upper extremity activities. The score can range from 0 (no disability) to 100 (most severe disability). | 12 month follow-up | 
| ISL classification | The severity of BCRL will be evaluated using the ISL criteria. This will be performed by the treating physician. | Baseline | 
| ISL classification | The severity of BCRL will be evaluated using the ISL criteria. This will be performed by the treating physician. | Week 9 | 
| ISL classification | The severity of BCRL will be evaluated using the ISL criteria. This will be performed by the treating physician. | Week 18 | 
| ISL classification | The severity of BCRL will be evaluated using the ISL criteria. This will be performed by the treating physician. | 3 month follow-up | 
| ISL classification | The severity of BCRL will be evaluated using the ISL criteria. This will be performed by the treating physician. | 6 month follow-up | 
| ISL classification | The severity of BCRL will be evaluated using the ISL criteria. This will be performed by the treating physician. | 9 month follow-up | 
| ISL classification | The severity of BCRL will be evaluated using the ISL criteria. This will be performed by the treating physician. | 12 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | Baseline | 
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | week 5 | 
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | week 9 | 
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | week 14 | 
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | week 18 | 
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | 3 month follow-up | 
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | 6 month follow-up | 
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | 9 month follow-up | 
| Pain assessment | The patients will be asked to evaluate their pain related to BCRL by using the Visual Analogue Scale (VAS). This scale ranges from 0 (no pain at all) to 10 (extreme agony). | 12 month follow-up | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | Baseline | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | week 5 | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | week 9 | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | week 14 | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | week 18 | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | 3 month follow-up | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | 6 month follow-up | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | 9 month follow-up | 
| Quality of life assessment | The validated Lymphedema Functioning, Disability, and Health questionnaire for the upper limb (Lymph-ICF-UL) will be used to evaluate the patients' QoL. This scale ranges from 0 (no problem at all) to 100 (very severe problem). | 12 month follow-up | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). Three different scores will be calculated: depression (0-21), anxiety (0-21) and stress (0-18). A lower score indicates a normal mental health, while a higher score indicates extremely severe depression, anxiety and/or stress. | Baseline | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). Three different scores will be calculated: depression (0-21), anxiety (0-21) and stress (0-18). A lower score indicates a normal mental health, while a higher score indicates extremely severe depression, anxiety and/or stress. | week 5 | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). Three different scores will be calculated: depression (0-21), anxiety (0-21) and stress (0-18). A lower score indicates a normal mental health, while a higher score indicates extremely severe depression, anxiety and/or stress. | week 9 | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). Three different scores will be calculated: depression (0-21), anxiety (0-21) and stress (0-18). A lower score indicates a normal mental health, while a higher score indicates extremely severe depression, anxiety and/or stress. | week 14 | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). Three different scores will be calculated: depression (0-21), anxiety (0-21) and stress (0-18). A lower score indicates a normal mental health, while a higher score indicates extremely severe depression, anxiety and/or stress. | week 18 | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). | 3 month follow-up | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). Three different scores will be calculated: depression (0-21), anxiety (0-21) and stress (0-18). A lower score indicates a normal mental health, while a higher score indicates extremely severe depression, anxiety and/or stress. | 6 month follow-up | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). Three different scores will be calculated: depression (0-21), anxiety (0-21) and stress (0-18). A lower score indicates a normal mental health, while a higher score indicates extremely severe depression, anxiety and/or stress. | 9 month follow-up | 
| Depression, anxiety and stress | The mental health of the patients will be determined using the Depression Anxiety Stress-Scale (DASS-21). Three different scores will be calculated: depression (0-21), anxiety (0-21) and stress (0-18). A lower score indicates a normal mental health, while a higher score indicates extremely severe depression, anxiety and/or stress. | 12 month follow-up | 
| Patients' satisfaction with the therapeutic intervention | The patients will be asked to evaluate the general pleasantness and soothing effect of the therapeutic intervention and their global satisfaction with the therapeutic intervention, using the Numerical Rating Scale (NRS). This is scored on a scale from 0 (extremely dissatisfied) to 10 (extremely satisfied). | At week 9 | 
| Patients' satisfaction with the therapeutic intervention | The patients will be asked to evaluate the general pleasantness and soothing effect of the therapeutic intervention and their global satisfaction with the therapeutic intervention, using the Numerical Rating Scale (NRS). This is scored on a scale from 0 (extremely dissatisfied) to 10 (extremely satisfied). | At week 18 | 
| Patients' satisfaction with the therapeutic intervention | The patients will be asked to evaluate the general pleasantness and soothing effect of the therapeutic intervention and their global satisfaction with the therapeutic intervention, using the Numerical Rating Scale (NRS). This is scored on a scale from 0 (extremely dissatisfied) to 10 (extremely satisfied). | 3 month follow-up | 
| Patients' satisfaction with the therapeutic intervention | The patients will be asked to evaluate the general pleasantness and soothing effect of the therapeutic intervention and their global satisfaction with the therapeutic intervention, using the Numerical Rating Scale (NRS). This is scored on a scale from 0 (extremely dissatisfied) to 10 (extremely satisfied). | 6 month follow-up | 
| Patients' satisfaction with the therapeutic intervention | The patients will be asked to evaluate the general pleasantness and soothing effect of the therapeutic intervention and their global satisfaction with the therapeutic intervention, using the Numerical Rating Scale (NRS). This is scored on a scale from 0 (extremely dissatisfied) to 10 (extremely satisfied). | 9 month follow-up | 
| Patients' satisfaction with the therapeutic intervention | The patients will be asked to evaluate the general pleasantness and soothing effect of the therapeutic intervention and their global satisfaction with the therapeutic intervention, using the Numerical Rating Scale (NRS). This is scored on a scale from 0 (extremely dissatisfied) to 10 (extremely satisfied). | 12 month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphedema, Breast cancer, Photobiomodulation