LLLT for BCRL: a Randomized, Placebo-controlled Study

Breast Cancer Lymphedema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05725265
• Other study ID #: 202210064DIPD
• Status: Recruiting
• Phase: N/A
• Start date: October 24, 2023
• Est. completion date: October 31, 2024

Study information

• Verified date: December 2022
• Source: National Taiwan University Hospital
• Contact: Ying-Chun Chen, MD
• Phone: 23123456
• Email: yasandy2000[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: October 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Breast Cancer Lymphedema
• Breast Neoplasms
• Lymphedema

Intervention

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
• 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.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (11)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	Range of motion of involved shoulder	involved upper extremity.	Day 30, Day 60, Day 120 (comparing with the data in baseline) of each section
Secondary	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
Secondary	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