Reduction of Arm Volume and Improvement in Lymphedema Via Surgery (REFRESH)

Influence of the Microsugical Treatment (by Free Node Transfer And/or Lympho-venous Anastomosis (LVA)) of Secondary Lymphedema Following Axillary Lymph Node Dissection or Sentinel Node Biopsy, on the Health Related Quality of Life, Limb Volume Change, Subcutal and Dermal Thickness

This clinical trial aims to evaluate the effectiveness of lymphatic microsurgical treatments in reducing limb volume in female patients with breast cancer-related lymphedema (BCRL).

The study focuses on three treatments: Lymphovenous Anastomosis (LVA), Vascularized Lymph Node Transfer (VLNT), and Complex Decongestive Therapy (CDT).

The main questions it aims to answer are:

• Can LVA, VLNT, or their combination significantly reduce limb volume in patients with BCRL?
• How does the effectiveness of these surgical interventions compare to CDT alone?

Researchers will compare patients who undergo LVA, VLNT, or a combination of both to those receiving only CDT to determine the effectiveness of surgical interventions in reducing lymphedema symptoms.

Participants will:

• Undergo pre- and post-operative limb volume measurements.
• Receive either LVA, VLNT, or combined LVA and VLNT surgery, or continue CDT alone.
• Be monitored for one year to assess changes in limb volume and quality of life.

Study Overview

• Status: Completed
• Conditions: Lymphedema; Lymphedema of Upper Limb; Lymphedema, Secondary; Lymphedema Arm; Lymphedema of Arm
• Intervention / Treatment: Procedure: Lymphovenous Anastomosis; Procedure: Vascularized Lymph Node Transfer; Procedure: Combined Lymphovenous Anastomosis and Vascularized Lymph Node Transfer; Procedure: Complex Decongestive Therapy

Detailed Description

This clinical trial aims to explore the effectiveness of surgical interventions for breast cancer-related lymphedema (BCRL), a chronic and often debilitating condition caused by lymphatic system damage following breast cancer treatments, such as lymph node dissection or radiation therapy. BCRL affects a significant proportion of breast cancer survivors, leading to arm swelling, discomfort, restricted mobility, and recurrent infections.

Standard management of BCRL includes conservative measures known as Complex Decongestive Therapy (CDT), which involves manual lymphatic drainage, compression therapy, exercise, and skincare. While CDT offers symptomatic relief, it does not address the underlying lymphatic dysfunction. In contrast, microsurgical procedures like Lymphovenous Anastomosis (LVA) and Vascularized Lymph Node Transfer (VLNT) are emerging as more definitive treatments for BCRL, targeting the lymphatic system itself.

LVA involves connecting small functional lymphatic vessels to nearby veins, allowing lymphatic fluid to bypass damaged lymph nodes and enter the venous system, improving drainage. It is particularly suited for patients with early-stage lymphedema (ISL stage I) where functional lymphatic vessels are still present.

VLNT involves transferring healthy lymph nodes along with their blood supply from a donor site (such as the groin or lateral thorax) to the affected area, promoting lymphangiogenesis and improving lymphatic transport. VLNT is more suitable for advanced stages of lymphedema (ISL stage II), where lymphatic vessels are more severely damaged.

The study will evaluate the outcomes of patients who undergo LVA, VLNT, or a combination of both, in comparison to a control group receiving only CDT. The surgical selection is based on preoperative imaging with indocyanine green (ICG) lymphography to assess the status of the lymphatic system. Each patient's lymphedema stage, severity, and individual characteristics are taken into consideration when choosing the most appropriate treatment.

Patients will be followed for one year postoperatively to measure the effectiveness of each treatment, with the primary outcome being limb volume reduction. Limb volume will be assessed using a perometer, an objective and reliable tool for measuring arm volume. Secondary outcomes include improvement in quality of life, frequency of infections, and the need for ongoing CDT post-surgery.

This study seeks to provide valuable insights into the comparative effectiveness of LVA, VLNT, and CDT in managing BCRL. While the benefits of microsurgical interventions are promising, particularly in reducing limb volume and infections, this trial aims to provide robust evidence to guide clinical decision-making and improve patient outcomes. By comparing different approaches, the study will help to clarify which surgical interventions are most beneficial for different stages of BCRL and establish clearer selection criteria for these treatments.

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussel Capital
    • Jette, Brussel Capital, Belgium, 1090
      • Universitair Ziekenhuis Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• at least one of the following persistent complaints of one of the upper extremities: heaviness, pain, recurrent infections

Exclusion Criteria:

• negative volume difference between affected and normal limb, bilateral mastectomy, bilateral axillary lymph node dissection (ALND), ongoing radio- and chemotherapy, ISL stage III, and receiving other simultaneous debulking procedures during lymphedema surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lymphovenous Anastomoses (LVA); Patients with BCRL recieve one ore more Lymphovenous Anastomoses (LVA) on the affected limb. This involves connecting functional lymphatic vessels to nearby veins, allowing for the rerouting of lymphatic fluid into the venous system, thus improving lymphatic drainage. All patients had CDT pre- and post-op.	Procedure: Lymphovenous Anastomosis; LVA involves connecting functional lymphatic vessels to nearby veins, allowing for the rerouting of lymphatic fluid into the venous system, thus improving lymphatic drainage.; Other Names: LVA; LVB; Lymphovenous Bypass; Lymphaticovenous Anastomosis; Lymphatico-venous Anastomosis
Experimental: Vascularized Lymph Node Transfer (VLNT); Patients with BCRL recieve a Vascularized Lymph Node Transfer (VLNT) on the affected limb. This involves transferring healthy lymph nodes along with their blood supply to the affected lymphoedematous area, aiding in lymphatic fluid transport and potentially promoting lymphangiogenesis. All patients had CDT pre- and post-op.	Procedure: Vascularized Lymph Node Transfer; VLNT involves transferring healthy lymph nodes along with their blood supply to the affected lymphoedematous area, aiding in lymphatic fluid transport and potentially promoting lymphangiogenesis.; Other Names: VLNT; Lymph Node Transfer; Lymph Node Transplant; Vascularized Lymph Node Transplant
Experimental: LVA + VLNT; Patients with BCRL recieve a combined simultaneous surgical intervention during which both VLNT and one or more LVA are performed on the affected limb. All patients had CDT pre- and post-op.	Procedure: Combined Lymphovenous Anastomosis and Vascularized Lymph Node Transfer; Combined simultaneous surgical intervention during which both VLNT and LVA are performed on the operated limb.; Other Names: LVA + VLNT; LVA & VLNT
Active Comparator: Complex Decongestive Therapy (CDT); Patients with BCRL who refuse to undergo further surgical treatment after breast cancer surgery are offered conservative therapy. The current standard of care for most BRCL patients includes conservative measures known as Complex Decongestive Therapy (CDT) consisting of compression therapy with low-stretch bandages, manual lymphatic drainage, exercise, and skincare.	Procedure: Complex Decongestive Therapy; The current standard of care for most BRCL patients includes conservative measures known as Complex Decongestive Therapy (CDT), consisting of compression therapy with low-stretch bandages, manual lymphatic drainage, exercise, and skincare.; Other Names: CDT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative interlimb difference	Change in relative interlimb difference (RID) between the affected and contralateral limb	Before intervention and one year post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of infection episodes after surgery	The number of post-interventional erysipelas episodes is recorded for 12 months after the intervention.	One year post-intervention

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: September 18, 2024
• First Submitted That Met QC Criteria: September 18, 2024
• First Posted (Actual): September 20, 2024

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: lymphedema; LVA; VLNT; lymphovenous anastomosis; vascularized lymph node transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Lymphatic Diseases; Neoplastic Processes; Lymphedema; Neoplasm Metastasis
• Other Study ID Numbers: BUN 143201316894

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymized individual participant data can be provided upon request by ICMJE journal editors.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No