Microsurgical Treatment of Breast Cancer-related Lymphedema by Lymphaticovenous Anastomosis

NCT02790021 | Completed DMC

• 1 other identifier: NL67059.068.18
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

Research question: Is lymphaticovenous anastomosis (LVA) for the treatment of breast cancer-related lymphedema of the arm (BCRL) more effective and cost-effective compared to standard conservative treatment? Hypothesis: LVA improves the health-related quality of life of patients who developed BCRL after breast cancer treatment and is cost-effective compared to conservative treatment. Study design: A multicenter randomised controlled trial (RCT) consisting of two treatment groups: conservative treatment (group A) and LVA (group B). The study is conducted in Maastricht University Medical Center, Radboud University Medical Center, Zuyderland Medical Center and Canisius-Wilhelmina Hospital. Study population: Women over 18 years old who underwent (axillary) treatment for breast cancer presenting with early stage lymphedema of the arm for which they received at least three months conservative treatment Intervention: LVA involves anastomosing lymphatic vessels to small veins to bypass obstructions in the lymphatic system. Usual care: Complex decongestive therapy (CDT) which includes skin care, manual lymphatic drainage, and compression therapy. Outcome measures: The primary outcome is health-related quality of life after 12 months follow-up measured with the Lymph-ICF questionnaire. Secondary outcomes are (in)direct costs, QALYs, cost-effectiveness ratio, the discontinuation rate of conservative treatment, and excess limb volume. Sample size: A total of 120 patients will be included and randomised in two groups of 60 patients each. Cost-effectiveness analysis: A trial-based economic evaluation is performed from the societal perspective to determine the cost-effectiveness, expressed in an incremental cost-effectiveness ratio (ICER) (i.e. cost per QALY gained), of LVA compared to CDT. Direct and indirect cost data is collected on the patient-level. The difference in QALYs is assessed with the EQ-5D-5L questionnaire. A Budget Impact Analysis (BIA) will be performed to analyse the financial consequences related to implementing LVA. Time schedule: Patient inclusion will take maximally 21 months. With a follow-up of 24 months, the total study period will be 48 months. The last three months are used for data analysis. Outcome assessment is at inclusion (before randomisation) and 3, 6, 12, 18, and 24 months later.

Conditions

Lymphedema

Outcome Measures

Primary Outcomes (1)

• Health-related quality of life: Lymph-ICF questionnaire

  To assess the efficacy of the treatment on disease-related symptoms we will use the "Lymphedema Functioning, Disability and Health" (Lymph-ICF)" questionnaire. This disease-specific questionnaire assesses the impairments in function, activity limitations, and participation restrictions of patients with arm lymphedema. This is a validated questionnaire, based on 5 domains with 29 questions. Each of the 29 questions corresponds to a score between 0-100. The total score on the Lymph-ICF is equal to the sum of the scores on the questions divided by the total number of answered questions. A higher score on the Lymph-ICF indicates more problems with functioning related to arm lymphedema.

  12 months

Secondary Outcomes (3)

• Cost-effectiveness of LVA compared to complex decongestive therapy

  24 months

• Excess limb volume

  24 months

• Discontinuation rate conservative therapy

  24 months

Study Arms (2)

Complex decongestive therapy

NO INTERVENTION

Group A will continue complex decongestive therapy consisting of skin care, manual lymphatic drainage, and compression therapy using compression stockings.

Lymphaticovenous anastomosis (LVA)

EXPERIMENTAL

Group B will undergo an LVA procedure under local anesthesia in surgical daycare setting. Patients are not allowed to wear compression stockings or have decongestive therapy for four weeks after the surgery.

Procedure: Lymphaticovenous anastomosis (LVA)

Interventions

Lymphaticovenous anastomosis (LVA) PROCEDURE

LVA is a minimally invasive procedure that can be performed under local anesthesia. Indocyanine green (ICG) lymphography is used to visualize the (obstructed) lymphatic vessels. When using the images as a guide, the lymphatic pathways and the sites for incisions for lymphaticovenous anastomoses are marked with a pen. The patient's limb is then prepared for surgery. Under a surgical microscope the lymphatic vessels are identified and viable lymphatic vessels are anastomosed to similarly sized adjacent recipient venules in the subdermal plane.

Also known as: LVA

Lymphaticovenous anastomosis (LVA)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women over 18 years old
• Treated for early stage breast cancer and who underwent an sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND) or axillary radiotherapy
• Early stage lymphedema of the arm (ISL classification stage I/IIa; pitting edema without fibrosis) with viable lymphatic vessels as determined by indocyanin green (ICG) lymphography
• Primary breast cancer
• Unilateral lymphedema
• Informed consent

You may not qualify if:

• Male sex
• Late stage lymphedema of the arm (ISL classification IIb/III lymphedema) with evident fat deposition and/or fibrosis
• History of earlier lymph reconstruction efforts
• Recurrent breast cancer
• Distant breast cancer metastases
• Bilateral lymphedema
• Primary congenital lymphedema
• Non-viable lymphatic system as determined by ICG lymphography

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (2)

Radboud University Medical Center

Nijmegen, Gelderland, 6526 GA, Netherlands

Location

Yasmine Jonis

Maastricht, Limburg, 6229 HX, Netherlands

Location

Related Publications (2)

• Jonis YMJ, Wolfs JAGN, Hummelink S, Tielemans HJP, Keuter XHA, van Kuijk S, Ulrich DJO, van der Hulst RRWJ, Qiu SS. The 6 month interim analysis of a randomized controlled trial assessing the quality of life in patients with breast cancer related lymphedema undergoing lymphaticovenous anastomosis vs. conservative therapy. Sci Rep. 2024 Jan 26;14(1):2238. doi: 10.1038/s41598-024-52489-3.

  PMID: 38278856 DERIVED

• Wolfs J, Beugels J, Kimman M, Piatkowski de Grzymala AA, Heuts E, Keuter X, Tielemans H, Ulrich D, van der Hulst R, Qiu SS. Improving the quality of life of patients with breast cancer-related lymphoedema by lymphaticovenous anastomosis (LVA): study protocol of a multicentre randomised controlled trial. BMJ Open. 2020 Jan 15;10(1):e035337. doi: 10.1136/bmjopen-2019-035337.

  PMID: 31948992 DERIVED

MeSH Terms

Conditions

Lymphedema

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• René Van der Hulst, MD, PhD

  Maastricht University Medical Center

  STUDY DIRECTOR

• Shan Shan Qiu Shao, MD, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: June 3, 2016
• Study Start: January 1, 2019
• Primary Completion: January 7, 2025
• Study Completion: January 7, 2025
• Last Updated: May 19, 2025

Record last verified: 2025-05

Locations

NL (2)