The Effectiveness of Lymphatic Bypass Supermicrosurgery

NCT05682885 | Active Not Recruiting DMC

• 1 other identifier: 227/KEPK/IX/2022
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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).

Conditions

Breast Cancer Related Lymphedema; Lymphedema Arm

Keywords

Lymphatic Bypass Supermicrosurgery; Primary Lymphedema Prevention; Axillary Lymph Node Dissection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• BCRL and SCL progression-free survival rate

  1 year

• Collateral lymphatic pathway

  1 year

• Quality of life lymphedema

  1 year

Other Outcomes (5)

• Association of body mass index (BMI) with BCRL

  1 year

• Association of number of axillary lymph nodes metastases with BCRL

  1 year

• Association of number of taxane chemotherapy with BCRL

  1 year

Study Arms (2)

Axillary lymph node dissection with LBS

EXPERIMENTAL

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

Axillary lymph node dissection without LBS

NO INTERVENTION

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.

Interventions

Lymphatic Bypass Supermicrosurgery PROCEDURE

Axillary Lymph Node Dissection with Lymphatic Bypass Supermicrosurgery

Axillary lymph node dissection with LBS

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dharmais National Cancer Center Hospital: lead

Study Sites (1)

Dharmais National Cancer Center Hospital

Jakarta, Jakarta Special Capital Region, 11420, Indonesia

Location

Related Publications (9)

• 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.

  PMID: 30638810 BACKGROUND

• 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.

  PMID: 33648010 BACKGROUND

• 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.

  PMID: 21681123 BACKGROUND

• 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.

  PMID: 24322632 BACKGROUND

• 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.

  PMID: 28173818 BACKGROUND

• 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.

  PMID: 27465179 BACKGROUND

• 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.

  PMID: 28538568 BACKGROUND

• 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.

  PMID: 21734534 BACKGROUND

• Suami H. Anatomical Theories of the Pathophysiology of Cancer-Related Lymphoedema. Cancers (Basel). 2020 May 23;12(5):1338. doi: 10.3390/cancers12051338.

  PMID: 32456209 BACKGROUND

MeSH Terms

Conditions

Breast Cancer Lymphedema

Condition Hierarchy (Ancestors)

Lymphedema; Lymphatic Diseases; Hemic and Lymphatic Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bayu Brahma, MD

  Dharmais Hospital National Cancer Center, Indonesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study is a single-blind pragmatic parallel arm randomized clinical trial to analyze the effectiveness of lymphatic bypass supermicrosurgery (LBS).

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: January 12, 2023
• Study Start: October 6, 2022
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): November 18, 2027
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months and ending 3 years following article publication.
• Access Criteria: Qualified researchers who have received principal investigator's approval.

Locations

ID (1)