LLLT for BCRL: a Randomized, Placebo-controlled Study

Study Overview
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Brief Summary
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This study is conducted to compare between efficacy of large and small area of low-level laser therapy (LLLT) in treatment of post mastectomy lymphedema. The change of severity of BCRL will be measured by the difference of circumference and skin thickness, detected by ultrasound. The influence on clinical symptoms, such as pain, shoulder mobility and hand function, are also investigated in the study.

Detailed Description
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Breast cancer-related lymphedema (BCRL) is common complication after cancer treatment. The incidence of BCRL around is 16.6% (95% CI 13·6-20·2) after the diagnosis and higher among the group receiving the sentinel biopsy or axillary lymph dissection. The lymphedema arises from the accumulation of protein-rich lymph fluid in the interstitial spaces then results in chronic inflammation with symptoms of fibrosis, pain, limited range of motion or paresthesia. The BRCL is chronic and progressive condition, and the severity also changes over time. The definition and cut points of BCRL using inter-limb volume or arm circumference varied across the studies by different measure method. Currently, the International Society of Lymphology suggests calculating arm volume from circumferences through the truncated cone formula to qualify the severity. On the other hand, previous research found the skin and subcutis were thickened in the ipsilateral arm of patients with BCRL. Thus, the measurement of skin thickness using ultrasound may also practical to detect the progression of lymphedema. Except for physical change of upper limb, the symptoms of BCRL are also concerned. One of the most common morbidity is pain, mostly presenting 1 month after surgery (56.6%). Furthermore, BCRL might decrease shoulder range of motion. Previous study demonstrated that shoulder mobility was usually restricted at 1 month postoperatively and abduction and forward flexion were limited at first. Thus, functional disability may occurred and life of quality may be influenced. To evaluate the ability to perform functional activities, the Disability of Arm, Shoulder, and Hand Questionnaire (DASH) is an useful tool to assess the patients with BCRL. Currently, although complete decongestive therapy (CDT) has been the standard therapy, there is still various type of noninvasive treatment on BCRL, for example, low-level laser therapy (LLLT). Low-level laser therapy (LLLT), also named photobiomodulation therapy (PBMT), is a conservative therapy through utilizing wave lengths of red or near infrared light between 650 and 1000 nm to stimulate wound healing and reduce inflammation, edema, and pain. Moreover, the Food and Drug Administration (FDA) approved the use of the LLLT for treatment of postmastectomy lymphedema in November 2006. Previous studies have demonstrated the effect of LLLT on BCRL with comparison to physical therapy or placebo. However, there is still limited data about the LLLT with different light area on improvement of severity and symptoms of BCRL. Therefore, this study is conducted to compare between efficacy of large and small area of low-level laser therapy (LLLT) in treatment of post mastectomy lymphedema.

Official Title
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Large-area Low-level Laser Therapy for Breast Cancer-related Lymphedema: a Randomized, Placebo-controlled Study

Conditions
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Breast Cancer Lymphedema

Intervention / Treatment
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* Device: Large-area low-level laser therapy(Venusure)
* Device: Conventional low-level laser therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects, 20 years age or older, suffered from unilateral breast cancer with ipsilateral lumpectomy or mastectomy and lymph node dissection (sentinel biopsy or axillary dissection) Stage I or II unilateral secondary upper extremity lymphedema(as defined by the International Society of Lymphology) Girth≥ 2 cm circumferential difference compared with the uninvolved upper extremity at any 4 cm segment Able to commit to a long-term follow-up schedule Exclusion Criteria: Metastatic cancer(stage IV) Pregnancy Presence of other extremity lymphedema (primary or secondary) History of deep vein thrombosis Pacemaker Artificial joints, implant or tattoo(area≥4 cm2) at the involved upper extremity Previous treatment with low-level laser therapy (within 3 months) Body mass index (BMI) > 35 (morbid obesity) High bleeding tendency(hemophilia) Receiving long-term steroid treatment (oral or systemic)

Ages Eligible for Study
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Minimum Age: 20 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Large-area low-level laser therapy<br>Large-area low-level laser therapy(Venusure) was administered at proximal forearm, upper arm and axillary region of affected side. The wavelength was 980±15nm, average dose was 10-40nm/cm2 and maximal output was 1000mW. Total treatment duration was 30 min and frequency was 3 sessions/week for 4 weeks. | Device: Large-area low-level laser therapy(Venusure)<br>* The wavelength was 980±15nm, average dose was 10-40nm/cm2 and maximal output was 1000mW. Total treatment duration was 30 min and frequency was 3 sessions/week for 4 weeks; for a total of 12 sessions<br>|
| Placebo Comparator: Conventional low-level laser therapy<br>Conventional low-level laser therapy was administrated on antecubital fossa and the axilla of affected side. The wavelength was 808nm and maximal output was 60 mW. Total treatment duration was 30 min and frequency was 3 sessions/week for 4 weeks. | Device: Conventional low-level laser therapy<br>* The wavelength was 808 nm and maximal output was 60 mW. Total treatment duration was 30 min and frequency was 3 sessions/week for 4 weeks; for a total of 12 sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circumference discrepancy of bilateral upper arm | Record the circumference of arm and forearm of involved and uninvolved upper extremity at 4 cm segment from cubital fossa and calculate the circumference discrepancy. | Day 30 (change of circumference discrepancy of bilateral upper limbs, comparing with the data in baseline) of each section | 
| Circumference discrepancy of bilateral upper arm | Record the circumference of arm and forearm of involved and uninvolved upper extremity at 4 cm segment from cubital fossa and calculate the circumference discrepancy. | Day 60 (change of circumference discrepancy of bilateral upper limbs, comparing with the data in baseline) of each section | 
| Circumference discrepancy of bilateral upper arm | Record the circumference of arm and forearm of involved and uninvolved upper extremity at 4 cm segment from cubital fossa and calculate the circumference discrepancy. | Day 120 (change of circumference discrepancy of bilateral upper limbs, comparing with the data in baseline) of each section | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual analogue scale (VAS) | Record visual analogue scale (VAS) to rate the severity of pain. The total score ranges from 0 to 10. Higher score indicates greater pain intensity. | Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section | 
| Range of motion of involved shoulder | involved upper extremity. | Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section | 
| Skin thickness | Use ultrasound to measure the skin thickness of arm and forearm of involved upper extremity. | Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section | 
| QuickDASH | QuickDASH(Quick Disabilities of Arm, Shoulder & Hand) is a questionnaire for patients presenting with self-reported disabilities of the arm, shoulder and hand. The QuickDASH contains 11-items; the score of each item ranges from 1 to 5 and total score ranges from 0 to 100. Higher score indicates greater level of disability and severity. | Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer Lymphedema, Lymphedema, Breast cancer, Low level laser therapy