Clinical trial NCT05725265: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer Lymphedema
Keywords: Breast Cancer Lymphedema
Lymphedema
Breast cancer
Low level laser therapy
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2023-02-13
Enrollment: 54
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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)

Primary outcomes:
measure: Circumference discrepancy of bilateral upper arm
timeFrame: Day 30 (change of circumference discrepancy of bilateral upper limbs, comparing with the data in baseline) of each section
measure: Circumference discrepancy of bilateral upper arm
timeFrame: Day 60 (change of circumference discrepancy of bilateral upper limbs, comparing with the data in baseline) of each section
measure: Circumference discrepancy of bilateral upper arm
timeFrame: Day 120 (change of circumference discrepancy of bilateral upper limbs, comparing with the data in baseline) of each section
Secondary outcomes:
measure: visual analogue scale (VAS)
timeFrame: Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section
measure: Range of motion of involved shoulder
timeFrame: Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section
measure: Skin thickness
timeFrame: Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section
measure: QuickDASH
timeFrame: Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan
name: Chueh-Hung Wu, PHD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Robijns J, Censabella S, Bulens P, Maes A, Mebis J. The use of low-level light therapy in supportive care for patients with breast cancer: review of the literature. Lasers Med Sci. 2017 Jan;32(1):229-242. doi: 10.1007/s10103-016-2056-y. Epub 2016 Aug 19.
citation: Wang Y, Ge Y, Xing W, Liu J, Wu J, Lin H, Lu Y. The effectiveness and safety of low-level laser therapy on breast cancer-related lymphedema: An overview and update of systematic reviews. Lasers Med Sci. 2022 Apr;37(3):1389-1413. doi: 10.1007/s10103-021-03446-3. Epub 2021 Nov 15.
citation: Levenhagen K, Davies C, Perdomo M, Ryans K, Gilchrist L. Diagnosis of Upper Quadrant Lymphedema Secondary to Cancer: Clinical Practice Guideline From the Oncology Section of the American Physical Therapy Association. Phys Ther. 2017 Jul 1;97(7):729-745. doi: 10.1093/ptj/pzx050.