Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Blood and Lymph Conditions

Breast Neoplasms

Lymphedema

Lymphatic Diseases

Post-operative (lumpectomy or mastectomy) female breast cancer patients who will receive radiation to the whole breast or chest wall and the regional nodes.

Dana Casey

The goal of this prospective study is to investigate the role of axillary reverse mapping (ARM) in radiation therapy planning of patients with breast cancer. Lymphedema is a common side effect after surgery and radiation therapy for breast cancer. The use of ARM is becoming more routine in surgery to differentiate the upper extremity lymphatics (UELs) from the breast axillary drainage to preferentially spare the UELs and reduce the rates of lymphedema.

Reverse Axillary Mapping in Breast Radiation Treatment Planning

Reverse Axillary Mapping as a Lymphedema Prevention Strategy in Breast Radiation Treatment Planning

ARM uses dye to track lymphatic flow of the upper extremities.We hypothesize that iodinated contrast injected into the upper inner arm (same site that surgeons inject during ARM) 15 minutes before the time of CT simulation will similarly be able to track the UELs. We will contour the visible iodinated dye and will measure if that anatomically correlates with the general known location of the UELs. Two radiation oncologists will independently determine if they can delineate the UELs. If both radiation oncologists can identify and contour the UELs in a reproducible fashion, we will code the patient as "UEL identified." If one or both physicians are either not able to identify the UEL on CT images or the contoured UEL structures are significantly different from each other, we will code the patient as "UEL not identified."

We will measure the Dmax, Dmin, Dmean, D25%, and D75%. Dmax is the maximum dose (in units of Gray) delivered to the UEL, while Dmin is the minimum dose and Dmean is the mean dose. D25% and D75% are the minimum dose delivered to 25% and 75% of the UEL, respectively. We will also look at the percent of theoretical radiation plans that could be safely modified. This will be a binary outcome: either the plan can be modified safely, or it cannot.

We will measure the lymphedema rates before the start of radiation and at 6 months, 12 months, 24 months, 36 months, and 60 months after the end of radiation therapy. Arm circumference will be measured 15 cm above the medial epicondyle (upper arms) and 15 cm below the medial epicondyle (lower arms. An increase in arm circumference of at least 10% in the lower arm or the upper arm, or both, compared with the contralateral arm at the same time-point will be considered clinically significant lymphedema.

UNC Lineberger Comprehensive Cancer Center

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Methylene Blue

ARM +ve LN PRESERVED , ALND COMPLETED LATER ON

subcutaneous injection of 1to 2 ml methylene blue 15 minutes before the procedure, identification of blue LN and lymphatic vessels

AXILLARY REVERSE MAPPING

hazem nour, MD

study patients; axillary node negative breast cancer female, 74 patients randomly allocated in two groups each 37 patients , group I , where axillary reverse mapping(ARM) +ve nodes were preserved and axillary lymph node dissection completed.and group II where axillary reverse mapping +ve nodes were taken with axillary lymph node dissection(ALND) primary outcome is histopathological examination of a ARM +ve lymph nodes and volume measurements of the ipsilateral arm for development of lymphedema at 6 ,12 , and 24 months

This study is comparative clinical trial carried out in the period between February 2015 and August 2019 on 74 female patients with early breast cancer. All patients were informed and signed a written consent. The study was approved from institutional review board (IRB) and ethical committee of our university.

Patient selection Patients included in the study are female patients above 18 years old, known breast cancer with clinically negative nodal metastasis who were admitted for completion ALND, after positive sentinel lymph node biopsy (SLNB).

Patients excluded from the study are those who had received chemotherapy for breast cancer, recurrent cases after conservative breast surgery, bilateral disease and pregnant cases.

Patients were randomly divided into two equal groups each 37 patients, group A; (ARM preserving ALND), where arm lymphatics and lymph nodes were identified and preserved, subsequently ALND was completed, group B; where arm lymphatics and lymph nodes were identified, marked and removed with ALND.

Technical procedures:

Axillary reverse mapping (ARM) procedure; one to two ml of methylene blue dye was subcutaneously injected in the upper medial arm in the groove between biceps muscle and triceps muscle then subsequently the area of injection was massaged for 5 minutes. During axillary dissection the (ARM) positive lymphatics and lymph nodes were identified and carefully dissected as the lymphatic vessels are very delicate, in group A the (ARM) positive lymphatics and lymph nodes were preserved and axillary clearance was completed, in group B (ARM) positive lymphatics and lymph nodes were identified, dissected, marked and taken out with ALND. The procedures were carried out with oncological surgeons familial with ALND. The limits of axillary dissection was axillary vein from above, lateral border subscapularis muscle laterally and medial border of pectoralis minor medially, long thoracic and lateral thoracic nerves were preserved intercostobrachial nerve wasn't preserved in all cases.

Data collection

* Preoperative data including demographic criteria, histopathological findings of breast biopsy and SLNB, preoperative measurement of arm volume by water displacement, circumferential measurement of the arm at the metacarpopharyngeal level, wrist level, 10 cm and 15 cm distal and proximal to the lateral epicondyle respectively.
* State of ARM positive or negative
* Follow up was carried out on outpatient clinic basis, monthly in the first 6 months then every 3 months for 2 years for data collection and later dates for regular follow up. Data was recorded including ARM histopathology (considered as the primary outcome), development of lymphedema defined as increase in arm volume by 10 % of the original size, tingling, numbness, paraesthesia and restricted shoulder movement were considered secondary outcome. Shoulder movement restriction was calculated by decrease of abduction by 10 degrees in comparison to the contralateral arm, development of local axillary recurrences, arm volume was measured at 6,12 and 24 months by water displacement method.

The collected data was properly analyzed using the proper statistical methods in SPSS 21 package.

2 groups of patients each 37 patient with early breast cancer one underwent ARM +ve LN biopsy with ALND, the other underwent ARM+ve LN preservation with completion of ALND

Axillary Reverse Mapping Using Methylene Blue Subcutaneous Injection Can Identify Arm Lymph Nodes and Vessels, Measuring Arm Size for Lymphedema, Histopathological Examination of Arm Lymph Nodes Included With Axillary Lymph Node Dissection

Evaluation of Axillary Reverse Mapping (ARM) in Clinically Axillary Node Negative Breast Cancer Patients

Zagazig University

Assistant professor

The prophylactic LVB cohort will undergo ALND plus ARM and immediate lymphatic reconstruction with lymphaticovenous bypass (LVB). During the ALND, axillary reverse mapping will be used to visualize the lymphatics draining into the axilla, to aid in preserving the draining lymphatic vessels for anastomosis in LVB.

Radiation therapy will be administered as determined by the treating radiation oncologist.

Patients in the ALND alone cohort will undergo ALND plus ARM

Radiation therapy will be administered as determined by the treating radiation oncologist.

ALND happens after cancer cells are found during a sentinel lymph node biopsy.

ALND can remove lymph nodes located above, below or directly underneath a muscle that runs along the side of the upper chest.

Axillary Lymph Node Dissection

Axillary reverse mapping (ARM) is a technique where blue dye is injected into the upper arm at surgery, allowing direct visualization of arm lymphatics and nodes during ALND

Axillary Reverse Mapping

Lymphaticovenous bypass/anastomosis (LVB/LVA) involves supramicrosurgery in which the blocked lymphatic vessel of an affected limb is connected to a nearby vein with the aid of ultra-fine instruments and a powerful operating microscope.

Lymphaticovenous Bypass

Julie E Lang, MD, FACS

Lymphedema is a devastating complication of breast cancer surgery that decreases the quality of life of up to 40% of breast cancer survivors. Most lymphedema in breast cancer patients is because lymphatics shared between the axilla and the arm are sacrificed during axillary lymph node dissection (ALND) surgery, which removes an average of 15 lymph nodes in node positive patients. CCF's breast cancer plastic microvascular surgeons and breast surgical oncologists have collaborated to refine a surgical technique known as LVB that may be used either as a preventive measure (prophylactic LVB) or as a therapeutic intervention (therapeutic LVB). Lymphatic reconstruction with LVB may be an improvement to the current standard of care for node positive breast cancer patients undergoing ALND.

Axillary Node Dissection w or w/o LVB in Node Positive Breast Cancer Patients

A Prospective Randomized Trial of Axillary Node Dissection With or Without Lymphaticovenous Bypass (LVB) in Node Positive Breast Cancer Patients

This is defined as a diagnosis of lymphedema by at least three of the four objective measurements performed serially every four months after baseline.

The four diagnostic measurements to be performed at baseline and then every four months during the study timeframe are: a) Limb measurements; b) 3D Infrared optoelectronic volumetry (Perometer); c) Bioimpedence Spectroscopy (LDEX); d) LymphaTech handheld 3D scan.

The patient-reported outcomes survey Lymph-ICF-UL will be used to compare subjective symptoms of lymphedema to the four diagnostic measurements to determine which is the most sensitive and evaluate the concordance of these tests.

Case Comprehensive Cancer Center

Symptoms and General Pathology

Breast Cancer Lymphedema

Postoperative Complications

Antineoplastic Agents

Taxane

Based on the intraoperative lymphedema prediction nomogram, individualized treatment was recommended to breast cancer patients with different level of risk. For patients with low possibility of developing breast cancer related lymphedema, it was not necessary to preserve arm lymphatics. While the breast cancer patients who were performed mastectomy and ALND with 28 kg/m2 prepared to receive taxane-based chemotherapy, supraclavicular and infraclavicular radiotherapy, according to the established intraoperative nomogram, the proportion of the arm lymph flow above the axillary vein needed to exceed 52%. Otherwise, the arm lymphatics should be identified and preserved.

Standard axillary lymph node dissection was performed with complete resection of Berg's levels I and II.

Axillary surgery based on lymphedema prediction nomogram

Qianqian Yuan, M.D.

Qianqian Yuan, MD.

Gaosong Wu, Ph.D.

It has been hypothesized that damaged arm lymphatic drainage is associated with the arm lymphedema after axillary lymph node dissection (ALND). However, the majority of breast cancer patients with complete ALND has not suffered from arm lymphedema, which appears to be due to the residual arm lymph nodes that has not been removed in the axillary dissection. With the compensation of the residual arm lymph flow above the level of axillary vein, the arm lymphatic drainage could keep balance and remain normal function.

This arm lymphedema prediction model that included the protective factor, the proportion of arm lymph flow above the level of axillary vein, allows intraoperative intervention to be performed for the high-risk group. The arm lymphatics of these distinguished patients would be preserved to eliminate the occurrence of arm lymphedema in this study.

Nomogram to Predict Breast Cancer Related Lymphedema

Intraoperative Nomogram to Predict Breast Cancer- Related Lymphedema Based in Artificial Intelligence Image Recognition: a Randomized Controlled Trial

A difference in volume between the arms \< 10% was defined as lymphedema

Locoregional recurrence included local recurrence and regional recurrence. Local recurrence was defined as chest wall recurrence of breast cancer, and regional recurrence was defined as the axilla recurrence of breast cancer

Cancer cells from breast metastasized to other organs.

Wuhan University

Director

Seroma

Neuroma

Technetium Tc 99m Sulfur Colloid

During surgery, the technetium-99m sulfur colloid will be injected into the breast and the blue dye injected (if the patient is not allergic and it is not required to locate the SLN) in the patient's ipsilateral upper arm. The lymph node biopsy and/or dissection will be performed by the surgeon, according to standard practice.

Daniela Ochoa, MD

We hypothesize that variations in anatomic location of the arm lymphatic drainage system put the arm lymphatics at risk for disruption during a SLNB and / or ALND. Therefore, mapping the drainage of the arm during the procedure would decrease the likelihood of inadvertent disruption of the lymphatics and the subsequent development of lymphedema. A combination of radioactivity and blue dye will be used.

Mapping Procedure:

Each patient will receive an injection of 1.0 mCi of technetium-99m sulfur colloid into the normal breast tissue surrounding the primary cancer or biopsy cavity directed subareolar or around the tumor.

If the radioactive SLN cannot be located prior to incision via gamma probe then the blue dye will be used in the breast either in the subareolar plexus or peritumorally at the discretion of the surgeon. For this contingency (expected to occur \<3% of the time), the blue dye will be used in the breast (and NOT the arm), as the prime concern is locating the SLN for staging.

If the blue dye is unnecessary to find the sentinel node draining from the breast, then it will be injected dermally in the upper inner arm along the Biceps groove of the ipsilateral arm in order to locate the draining lymphatics from the arm. No more than 5cc of blue dye will be injected in either the subareolar plexus, peritumorally (intraparenchymal or dermally), or dermally in the patient's ipsilateral arm dependent upon the contingencies stated above. Site of all injections (radioactivity and/or blue dye) will be recorded.

ARM: Axillary Reverse Mapping, A Prospective Study

An occurrence will consist of an increase of 20% or more in ipsilateral arm volume over the pre-surgery volume, and be accompanied by a confirmatory diagnosis of lymphedema from the UAMS lymphedema clinic.

successful localization of one or more lymph nodes to which the peritumoral breast region drains

brief location details will also be collected.

successful avoidance of resection and/or successful preservation of structural integrity of arm lymphatics during the surgical procedure.

A crossover event will consist of identification of one or more lymph nodes that are both focally radioactive following peritumoral Tc99m injection and noticeably stained blue following ipsilateral arm injection with Lymphazurin.

University of Arkansas

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Lymphazurin, isosulfan blue dye, injected into arm then a standard axillary lymph node surgery to remove any blue dyed lymph nodes found (lymph nodes that have traveled down the drainage pathways).

Funda Meric-Bernstam, MD

Primary Objectives:

* To determine the feasibility of axillary reverse mapping (ARM) in patients undergoing axillary lymph node dissection for breast cancer therapy.
* To determine the incidence of breast cancer metastasis in lymph nodes draining in the arm as identified by axillary reverse mapping.
* To determine the safety of axillary reverse mapping.

Lymphazurin is a blue dye used usually in breast cancer surgery to trace the drainage pathway that flows to lymph nodes. The dye will travel to the lymph system and will end up in the lymph nodes that are draining the arm.

In this study, lymphazurin will be used to find the drainage routes from your arm, rather than your breast.

AXILLARY REVERSE MAPPING:

Before axillary lymph node surgery, your surgeon will inject lymphazurin into your arm. Your surgeon will watch how the dye flows and find the channels and nodes draining the arm. You will then have standard axillary lymph node (lymph nodes found under the arm) surgery. Any lymph nodes found that are dyed blue (lymph nodes that have traveled down the drainage pathways) that would normally be removed will be removed and sent to the pathology department. Pathologists will check the nodes to see if they have breast cancer cells in them. Also as part of routine care, all other axillary lymph nodes draining the breast will be removed and checked for breast cancer cells.

This is an investigational study. Lymphazurin is FDA approved and commercially available. The use of lymphazurin with axillary reverse mapping is investigational.

Up to 30 patients will take part in this study. All will be enrolled at M. D. Anderson.

Axillary Reverse Mapping for Invasive Carcinoma of the Breast

Axillary reverse mapping (ARM) performed using 2 - 5cc of isosulfan blue, injected into the inner arm prior to skin incision for the axillary lymph node dissection. Blue channels identified during surgery and locations compared to axillary vein. Any blue nodes within the standard axillary lymph node dissection field removed then sent to pathology as a separate specimen labeled "axillary reverse mapping nodes" and evaluated with serial sectioning, and hematoxylin-eosin stain (H\&E) as well as immunohistochemistry.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Reverse Axillary Mapping in Breast Radiation Treatment Planning	NCT04292860	Breast Cancer Lymphedema		18 Years -	UNC Lineberger Comprehensive Cancer Center
Axillary Reverse Mapping Using Methylene Blue Subcutaneous Injection Can Identify Arm Lymph Nodes and Vessels, Measuring Arm Size for Lymphedema, Histopathological Examination of Arm Lymph Nodes Included With Axillary Lymph Node Dissection	NCT04137744	Arm Lymphedema Lymphatic Sprea... Early Breast Ca...	AXILLARY REVERS...	18 Years -	Zagazig University
Axillary Node Dissection w or w/o LVB in Node Positive Breast Cancer Patients	NCT05970107	Node-positive B...	Axillary Lymph ... Axillary Revers... Lymphaticovenou...	18 Years - 75 Years	Case Comprehensive Cancer Center
Nomogram to Predict Breast Cancer Related Lymphedema	NCT04665882	Breast Cancer Axillary Lymph ... Breast Cancer R... Axillary Revers...	Axillary surger...	18 Years - 80 Years	Wuhan University
Axillary Reverse Mapping	NCT00572481	Cancer of the B...	Axillary Revers...	18 Years -	University of Arkansas
Axillary Reverse Mapping	NCT00572481	Cancer of the B...	Axillary Revers...	18 Years -	University of Arkansas
Axillary Reverse Mapping Using Methylene Blue Subcutaneous Injection Can Identify Arm Lymph Nodes and Vessels, Measuring Arm Size for Lymphedema, Histopathological Examination of Arm Lymph Nodes Included With Axillary Lymph Node Dissection	NCT04137744	Arm Lymphedema Lymphatic Sprea... Early Breast Ca...	AXILLARY REVERS...	18 Years -	Zagazig University
Axillary Reverse Mapping for Invasive Carcinoma of the Breast	NCT00645541	Breast Cancer	Axillary Revers...	18 Years -	M.D. Anderson Cancer Center
Axillary Reverse Mapping	NCT00572481	Cancer of the B...	Axillary Revers...	18 Years -	University of Arkansas
Axillary Reverse Mapping	NCT00572481	Cancer of the B...	Axillary Revers...	18 Years -	University of Arkansas

Spots Global Cancer Trial Database for axillary reverse mapping