LLLT for BCRL: a Randomized, Placebo-controlled Study

Official title

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

Overview

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

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.

Interventions

• Device Large-area low-level laser therapy(Venusure)
  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
• Device Conventional low-level laser therapy
  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.

Primary outcome measures

• Circumference discrepancy of bilateral upper arm [Time frame: 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 [Time frame: 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 [Time frame: Day 120 (change of circumference discrepancy of bilateral upper limbs, comparing with the data in baseline) of each section]

Secondary outcome measures (4)

• visual analogue scale (VAS) [Time frame: Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section]
• Range of motion of involved shoulder [Time frame: Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section]
• Skin thickness [Time frame: Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section]
• QuickDASH [Time frame: Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• National Taiwan University Hospital — Taipei

Publications

• DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013 May;14(6):500-15. doi: 10.1016/S1470-2045(13)70076-7. Epub 2013 Mar 27. PMID 23540561
• Grada AA, Phillips TJ. Lymphedema: Pathophysiology and clinical manifestations. J Am Acad Dermatol. 2017 Dec;77(6):1009-1020. doi: 10.1016/j.jaad.2017.03.022. PMID 29132848
• Eyigor S, Cinar E, Caramat I, Unlu BK. Factors influencing response to lymphedema treatment in patients with breast cancer-related lymphedema. Support Care Cancer. 2015 Sep;23(9):2705-10. doi: 10.1007/s00520-015-2633-9. Epub 2015 Feb 8. PMID 25663541
• Mellor RH, Bush NL, Stanton AW, Bamber JC, Levick JR, Mortimer PS. Dual-frequency ultrasound examination of skin and subcutis thickness in breast cancer-related lymphedema. Breast J. 2004 Nov-Dec;10(6):496-503. doi: 10.1111/j.1075-122X.2004.21458.x. PMID 15569205
• Swenson KK, Nissen MJ, Ceronsky C, Swenson L, Lee MW, Tuttle TM. Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer. Ann Surg Oncol. 2002 Oct;9(8):745-53. doi: 10.1007/BF02574496. PMID 12374657
• Verbelen H, Gebruers N, Eeckhout FM, Verlinden K, Tjalma W. Shoulder and arm morbidity in sentinel node-negative breast cancer patients: a systematic review. Breast Cancer Res Treat. 2014 Feb;144(1):21-31. doi: 10.1007/s10549-014-2846-5. Epub 2014 Feb 5. PMID 24496928
• Lee D, Hwang JH, Chu I, Chang HJ, Shim YH, Kim JH. Analysis of factors related to arm weakness in patients with breast cancer-related lymphedema. Support Care Cancer. 2015 Aug;23(8):2297-304. doi: 10.1007/s00520-014-2584-6. Epub 2015 Jan 10. PMID 25576430
• Smile TD, Tendulkar R, Schwarz G, Arthur D, Grobmyer S, Valente S, Vicini F, Shah C. A Review of Treatment for Breast Cancer-Related Lymphedema: Paradigms for Clinical Practice. Am J Clin Oncol. 2018 Feb;41(2):178-190. doi: 10.1097/COC.0000000000000355. PMID 28009597

Identifiers

NCT: NCT05725265 · 202210064DIPD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗