Back to resultsThe Effectiveness of Lymphatic Bypass Supermicrosurgery (ELYBS)
Primary Purpose
Breast Cancer Related Lymphedema, Lymphedema Arm
Status
Recruiting
Phase
Not Applicable
Locations
Indonesia
Study Type
Interventional
Intervention
Lymphatic Bypass Supermicrosurgery
Sponsored by
About this trial
This is an interventional prevention trial for Breast Cancer Related Lymphedema focused on measuring Lymphatic Bypass Supermicrosurgery, Primary Lymphedema Prevention, Axillary Lymph Node Dissection
Eligibility Criteria
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.
Sites / Locations
- Dharmais National Cancer Center HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Axillary lymph node dissection with LBS
Axillary lymph node dissection without LBS
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Cumulative incidence of BCRL
The number of patients that had a condition with an increment of UEL index > 10% and minimum arm dermal backflow (ADB) 2 as measured by ICG lymphography.
Secondary Outcome Measures
BCRL and SCL progression-free survival rate
Percentage of subjects who do not progress to subclinical lymphedema or lymphedema during the research.
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.
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.
Full Information
NCT ID
NCT05682885
First Posted
November 22, 2022
Last Updated
February 3, 2023
Sponsor
Dharmais National Cancer Center Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05682885
Brief Title
The Effectiveness of Lymphatic Bypass Supermicrosurgery
Acronym
ELYBS
Official Title
The Effectiveness of Lymphatic Bypass Supermicrosurgery for Primary Lymphedema Prevention After Breast Cancer Axillary Lymph Node Dissection: a Randomized Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 6, 2022 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dharmais National Cancer Center Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer Related Lymphedema, Lymphedema Arm
Keywords
Lymphatic Bypass Supermicrosurgery, Primary Lymphedema Prevention, Axillary Lymph Node Dissection
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This study is a single-blind pragmatic parallel arm randomized clinical trial to analyze the effectiveness of lymphatic bypass supermicrosurgery (LBS).
Masking
Participant
Masking Description
Blinding is implemented in two conditions: the main researcher (Bayu Brahma) will not know the identity and medical history of the patient when assessing the indocyanine green (ICG) lymphography results and the patients will not know the received type of surgical procedure.
Allocation
Randomized
Enrollment
140 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Axillary lymph node dissection with LBS
Arm Type
Experimental
Arm Description
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.
Arm Title
Axillary lymph node dissection without LBS
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Lymphatic Bypass Supermicrosurgery
Intervention Description
Axillary Lymph Node Dissection with Lymphatic Bypass Supermicrosurgery
Primary Outcome Measure Information:
Title
Cumulative incidence of BCRL
Description
The number of patients that had a condition with an increment of UEL index > 10% and minimum arm dermal backflow (ADB) 2 as measured by ICG lymphography.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
BCRL and SCL progression-free survival rate
Description
Percentage of subjects who do not progress to subclinical lymphedema or lymphedema during the research.
Time Frame
1 year
Title
Collateral lymphatic pathway
Description
The number of lymphatic pathways flow into the region: supraclavicular, internal mammary, and contralateral axillary and supraclavicular nodes based on the ICG lymphography.
Time Frame
1 year
Title
Quality of life lymphedema
Description
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.
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Association of body mass index (BMI) with BCRL
Description
BMI was calculated by weight (kilograms) and height (centimeters). Categorized based on Asia Pacific classification are overweight (BMI ≥ 23 kg/m^2) and no overweight (BMI < 23 kg/m^2). Measured at one time point.
Time Frame
1 year
Title
Association of number of axillary lymph nodes metastases with BCRL
Description
The number of metastases lymph nodes and classified into >3 lymph nodes and ≤3 lymph nodes. Measured at one time point.
Time Frame
1 year
Title
Association of number of taxane chemotherapy with BCRL
Description
Taxane chemotherapy data from the subject's medical record and categorized into yes or no. Measured at one time point.
Time Frame
1 year
Title
Association of regional lymph node radiation with BCRL
Description
Regional lymph node radiation data from the subject's medical record and categorized into yes or no. Measured at one time point
Time Frame
1 year
Title
Association of axillary fat weight with BCRL
Description
Axillary fat weight in grams is taken at the time of surgery. Measured at one time point.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bayu Brahma, MD
Phone
+62215681570
Ext
2372
Email
bbrahma@dharmais.co.id
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayu Brahma, MD
Organizational Affiliation
Dharmais Hospital National Cancer Center, Indonesia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dharmais National Cancer Center Hospital
City
Jakarta
ZIP/Postal Code
11420
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ramadhan Karsono, PhD
Phone
+62-812-1045-970
Email
ramadhan@dharmais-surgonc.com
First Name & Middle Initial & Last Name & Degree
Bayu Brahma, MD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All of the individual participant data collected during the trial will be shared. The researcher provides a methodologically sound proposal. The proposal should be directed to bbrahma@dharmais.co.id. To gain access, data requestors will need to sign a data access agreement.
IPD Sharing Time Frame
Beginning 6 months and ending 3 years following article publication.
IPD Sharing Access Criteria
Qualified researchers who have received principal investigator's approval.
Citations:
PubMed Identifier
30638810
Citation
Brahma B, Yamamoto T. Breast cancer treatment-related lymphedema (BCRL): An overview of the literature and updates in microsurgery reconstructions. Eur J Surg Oncol. 2019 Jul;45(7):1138-1145. doi: 10.1016/j.ejso.2019.01.004. Epub 2019 Jan 4.
Results Reference
background
PubMed Identifier
33648010
Citation
Brahma B, Putri RI, Reuwpassa JO, Tuti Y, Alifian MF, Sofyan RF, Iskandar I, Yamamoto T. Lymphaticovenular Anastomosis in Breast Cancer Treatment-Related Lymphedema: A Short-Term Clinicopathological Analysis from Indonesia. J Reconstr Microsurg. 2021 Oct;37(8):643-654. doi: 10.1055/s-0041-1723940. Epub 2021 Mar 1.
Results Reference
background
PubMed Identifier
21681123
Citation
Yamamoto T, Yamamoto N, Doi K, Oshima A, Yoshimatsu H, Todokoro T, Ogata F, Mihara M, Narushima M, Iida T, Koshima I. Indocyanine green-enhanced lymphography for upper extremity lymphedema: a novel severity staging system using dermal backflow patterns. Plast Reconstr Surg. 2011 Oct;128(4):941-947. doi: 10.1097/PRS.0b013e3182268cd9.
Results Reference
background
PubMed Identifier
24322632
Citation
Yamamoto T, Narushima M, Yoshimatsu H, Yamamoto N, Kikuchi K, Todokoro T, Iida T, Koshima I. Dynamic Indocyanine Green (ICG) lymphography for breast cancer-related arm lymphedema. Ann Plast Surg. 2014 Dec;73(6):706-9. doi: 10.1097/SAP.0b013e318285875f.
Results Reference
background
PubMed Identifier
28173818
Citation
Brahma B, Putri RI, Karsono R, Andinata B, Gautama W, Sari L, Haryono SJ. The predictive value of methylene blue dye as a single technique in breast cancer sentinel node biopsy: a study from Dharmais Cancer Hospital. World J Surg Oncol. 2017 Feb 7;15(1):41. doi: 10.1186/s12957-017-1113-8.
Results Reference
background
PubMed Identifier
27465179
Citation
Akita S, Nakamura R, Yamamoto N, Tokumoto H, Ishigaki T, Yamaji Y, Sasahara Y, Kubota Y, Mitsukawa N, Satoh K. Early Detection of Lymphatic Disorder and Treatment for Lymphedema following Breast Cancer. Plast Reconstr Surg. 2016 Aug;138(2):192e-202e. doi: 10.1097/PRS.0000000000002337.
Results Reference
background
PubMed Identifier
28538568
Citation
Ishiura R, Yamamoto T, Saito T, Mito D, Iida T. Comparison of Lymphovenous Shunt Methods in a Rat Model: Supermicrosurgical Lymphaticovenular Anastomosis versus Microsurgical Lymphaticovenous Implantation. Plast Reconstr Surg. 2017 Jun;139(6):1407-1413. doi: 10.1097/PRS.0000000000003354.
Results Reference
background
PubMed Identifier
21734534
Citation
Yamamoto T, Yamamoto N, Hara H, Mihara M, Narushima M, Koshima I. Upper extremity lymphedema index: a simple method for severity evaluation of upper extremity lymphedema. Ann Plast Surg. 2013 Jan;70(1):47-9. doi: 10.1097/SAP.0b013e3182275d23.
Results Reference
background
PubMed Identifier
32456209
Citation
Suami H. Anatomical Theories of the Pathophysiology of Cancer-Related Lymphoedema. Cancers (Basel). 2020 May 23;12(5):1338. doi: 10.3390/cancers12051338.
Results Reference
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The Effectiveness of Lymphatic Bypass Supermicrosurgery
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