The Effectiveness of Lymphatic Bypass Supermicrosurgery

Study Overview
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Brief Summary
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This study evaluate the effectiveness of lymphatic bypass supermicrosurgery (LBS) and axillary lymph node dissection (ALND) compare to ALND alone to prevent breast cancer treatment-related lymphedema (BCRL).

Detailed Description
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In the intervention group, LBS was performed after ALND with the intima-to-intima coaptation using the supermicrosurgery technique. The anastomosis is done between the afferent lymphatic vessel to the recipient's vein, or if possible, from the afferent to the efferent lymphatic vessel. The upper extremity lymphedema (UEL) index and indocyanine green (ICG) lymphography are utilized to evaluate the development of lymphedema.

Official Title
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The Effectiveness of Lymphatic Bypass Supermicrosurgery for Primary Lymphedema Prevention After Breast Cancer Axillary Lymph Node Dissection: a Randomized Controlled Study

Conditions
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Lymphedema Arm, Breast Cancer Related Lymphedema

Intervention / Treatment
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* Procedure: Lymphatic Bypass Supermicrosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer patient aged >18 years old Breast cancer patient with clinically ALNs metastases (cN1 or cN2). Breast cancer patient with no clinical metastasis and tumor size ≥5cm or no sentinel lymph node biopsy facility in the hospital. Any breast cancer patients that receive neoadjuvant systemic therapy. Exclusion Criteria: Stage IV breast cancer patients who do not show clinical and radiological improvement after primary systemic therapy. Breast cancer patients with previous surgeries such as mastectomy, axillary lymph node biopsy, sentinel lymph node biopsy (SLNB), and ALND. Breast cancer patients with prior breast, chest wall, axillary, or neck radiotherapy. Breast cancer patients with preoperative lymphatic system abnormality detected by ICG lymphography. Breast cancer patients with iodine allergy, asthma, decreased kidney function, pregnancy, and lactation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is a single-blind pragmatic parallel arm randomized clinical trial to analyze the effectiveness of lymphatic bypass supermicrosurgery (LBS).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axillary lymph node dissection with LBS<br>70 subjects will be needed for each group. A standard mastectomy or lumpectomy incision is made and ALND will be done in the same incision. The lymphatic vessels and lymph nodes will be resected using a near-infrared (NIR) camera. To locate lymphatic vessels, a microscope with ICG lymphography navigation is employed. LBS was performed by making intima-to-intima anastomosis between the afferent lymphatic vessels and the recipient's veins, or to the efferent lymphatic vessels. The anastomosis patency will be assessed by observing the ICG fluorescent flow. After surgery, follow-up will be done every 2 months and every 3 months in the second year. UEL index, ICG lymphography, and quality of life evaluation will be done. The cumulative incidence of BCRL, the free survival time of BCRL, and subclinical lymphedema (SCL) progression will be reported descriptively. BCRL risk factors and collateral lymphatic pathway will be observed as well. | Procedure: Lymphatic Bypass Supermicrosurgery<br>* Axillary Lymph Node Dissection with Lymphatic Bypass Supermicrosurgery<br>|
| No Intervention: Axillary lymph node dissection without LBS<br>70 subjects will be needed for each group. A standard mastectomy or lumpectomy incision is made and ALND will be done in the same incision. After primary breast cancer removal, a standard ALND level I, II, and if necessary, level III is performed. After surgery, follow-up will be done every 2 months and every 3 months in the second year. History taking, physical examination, radiology and histopathology examination, UEL index, and ICG lymphography evaluation will be done during follow-up. Each subject will complete the lymphedema quality of life questionnaire. The cumulative incidence of BCRL, the free survival time of BCRL, and SCL progression will be reported descriptively. BCRL risk factors and collateral lymphatic pathway will be observed as well. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of BCRL | BCRL definition: Post operation subject condition with presence of minimum DB 2 with one or both symptoms (swelling, heaviness), and increment of UEL index >10% compared to pre operation OR Post operation subject condition with presence of ≥ DB 2 with minimum area 30% in one arm region in one of the arm lymphatic pathway (anterior or posterior), without presence of symptoms (swelling or heaviness), and increment of UEL index >10% compared to pre operation | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BCRL and SCL progression-free survival rate | Percentage of subjects who do not progress to subclinical lymphedema or lymphedema during the research. | 1 year | 
| Collateral lymphatic pathway | The number of lymphatic pathways flow into the region: supraclavicular, internal mammary, and contralateral axillary and supraclavicular nodes based on the ICG lymphography. | 1 year | 
| Quality of life lymphedema | Assessment of lymphedema quality of life score after the surgery using the lymphedema quality of life score questionnaire that is self-reported by the subjects every 2 months and every 3 months in the second year. Calculation of the lymphedema quality of life score is the summation of the score from each question. The minimum score is 0 and the maximum score is 100. A higher score indicates lower lymphedema quality of life. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphatic Bypass Supermicrosurgery, Primary Lymphedema Prevention, Axillary Lymph Node Dissection