Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Technetium Tc 99m Sulfur Colloid

Each patient will receive an injection of technetium-99m sulfur colloid directed subareolar or around the tumor. The material will be prepared as per manufacturer's specifications. The dose will be 20mBq given the same day of 80mBq given the day before. The Nuclear Medicine Department at St Paul's Hospital will perform the injection as per normal sentinel lymph node mapping protocol.

1. Inject radioactive isotope and scan for sentinel node (SLN) using gamma probe
2. Pre-incision: SLN is identified
3. Inject blue dye into patient's arm
4. Complete procedure (SLNB and/or ALND)

Isosulfan Blue (Patent Blue Dye V)

1. Inject radioactive isotope and scan for sentinel node (SLN) using gamma probe
2. Pre-incision: SLN is not identified (No localization)
3. Inject blue dye into breast (nothing in arm)

i. No localization: Inject blue dye into arm and perform ALND ii. Localization: Complete procedure (SLNB and/or ALND)

Sam Wiseman, MD, FRCSC, FACS

Urve Kuusk, MD, FRCSC

Carolyne Dingee, MD,FRCSC

Elaine McKevitt, MD, FRCSC

The purpose of this study is to map the arm lymphatic drainage system in the axilla with blue dye and the breast drainage system with a radioactive material. By identifying the arm lymphatics they can be protected during surgery and this may decrease the occurrence of lymphedema. The information obtained in this study may provide us with better surgical techniques to identify and protect the arm lymphatic drainage system in the axilla.

This study is a non-randomized Phase II study of the Axillary Reverse Mapping (ARM) procedure for patients presenting with breast cancer requiring lymph node evaluation. The study will enroll 100 subjects, and will have two study arms: one for patients requiring only the SLNB procedure (roughly 67% of enrollees), and one for patients requiring a full ALND (roughly 33% of enrollees). For the analysis of study efficacy, each arm will be compared to its procedure-appropriate historical control for evidence of decrease in the 1-year lymphedema rate among patients undergoing SLNB or ALND.

Additional data will be collected on the treatment population's (a) variability in location of arm lymphatics, and (b) incidence of SLN crossover with arm lymphatics, along with success-rate data for identifying SLNs and arm lymphatics during SLNB and/or ALND. This additional data will add to our level of knowledge and experience regarding lymph node surgery.

Breast Lymph Node Mapping

Axillary Reverse Mapping in Breast Cancer

University of British Columbia

Blood and Lymph Conditions

Carcinoma

Carcinoma, Ductal

Lymphedema

Carcinoma in Situ

Carcinoma, Intraductal, Noninfiltrating

Breast Carcinoma In Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Axillary reverse mapping and sentinel lymph node biopsy (ARM/SLNB) or Axillary reverse mapping and axillary lymph node dissection (ARM/ALND)

The control group will have standard sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) without identifying or sparing upper-limb lymphatics and nodes (blue dye is not injected).

ARM/SLNB: patient will be injected with technetium-99 radiolabelled colloid (Tc-99) into the subareolar area of breast, then 1-2 mls of blue dye (patent blue dye) injected subcutaneously into the medial ipsilateral arm, just proximal to the medial epicondyle of the elbow, at the start of the surgical procedure. the SLN(s) will be identified ("hot node") and removed, and any blue lymph nodes and lymphatics will be preserved intact, and only removed or disrupted if there is 'crossover" (i.e. the blue node is also the SLN) or if clinically suspicious for metastatic disease. ARM/ALND: 1-2 mls of blue dye will be injected subcutaneously into the medial ipsilateral arm at the start of the surgical procedure. Surgeons will perform a standard level I and II axillary dissection and any blue lymph nodes or lymphatics will be preserved intact, and only removed or disrupted if blue nodes are suspicious for metastatic disease.

axillary reverse mapping (ARM)

The control group will have standard SLNB or ALND surgery without identifying or sparing upper-limb lymphatics and nodes (blue dye is not injected).

Standard axillary surgery (SLNB or ALND)

Peter Lovrics, MD

Nicole Hodgson, MD, MSc

The purpose of this pilot study is to compare a new surgical technique (axillary reverse mapping) to standard axillary surgery in patients diagnosed with invasive or in situ breast cancer.

Lymphedema is a major chronic morbidity that occurs in patients undergoing treatment for breast cancer (BC). Surgery for BC includes axillary surgery with either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Lymphedema occurs due to removal or disruption of lymphatic drainage of the arm that overlaps with drainage of the breast. The risk of lymphedema increases significantly with adjuvant radiation. 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 either SLNB or ALND. This allows preservation of arm lymphatics unless there is suspicion of metastatic disease in ARM lymphatics or if the ARM node is/are also the sentinel lymph node. Studies to date have largely been observational cohort studies, and mainly with low risk patients undergoing SLNB only. There is only one published randomized controlled trial, and this included only patients undergoing modified radical mastectomy.Our proposal is a prospective randomized pilot study. The study population includes patients undergoing axillary surgery (SLNB with mastectomy or ALND with either BCS or mastectomy or completion ALND after positive SLNB). The intervention group will undergo ARM; the control will undergo standard surgical treatment. Both groups will undergo standardized baseline and postoperative arm measurements and patients will complete symptom and quality of life questionnaires. The purpose is to determine the feasibility of the ARM technique, its accuracy in identifying and sparing arm lymphatics, and its ability to reduce the risk of lymphedema.

Axillary Reverse Mapping (ARM) Technique

A Pilot Randomized Controlled Trial Comparing the Axillary Reverse Mapping (ARM) Technique to Standard Axillary Surgery in Breast Cancer Patients.

Arm circumference measurements of both arms. An arm volume difference of \> 10% will be considered clinically significant lymphedema

infection, hematoma, problems with wound healing

Hamilton Health Sciences Corporation

St. Joseph's Healthcare Hamilton

McMaster University

Principal Investigator

Surgery: For patients randomized to axillary lymph node dissection (ALND), it is recommended that a complete level I and II dissection with resection of minimum of a total of 8 lymph nodes (SLN and ALND together) be done. Level III dissection is not required, but may be performed at the discretion of the surgeon. If fewer than 8 lymph nodes (SLN and ALND together) are resected, then the patient will discontinue protocol treatment.

Radiation Therapy: Radiation is delivered to the breast/chest wall, undissected axilla, supraclavicular nodes and internal mammary nodes in the first 3 intercostal spaces. Treatment will be given 5 days a week over 5-6 weeks.

Radiation Therapy: Radiation is delivered to the breast/chest wall, full axilla including Levels I, II, III, supraclavicular nodes and internal mammary nodes in the first 3 intercostal spaces. Treatment will be given 5 days a week over 5-6 weeks.

Axillary Lymph Node Dissection (ALND)

Nodal Radiation Therapy

Axillary Radiation Therapy

Judy Boughey, MD

This randomized phase III trial studies lymph node dissection and radiation therapy to see how well it works compared to radiation therapy alone in treating patients with breast cancer previously treated with chemotherapy and surgery. Lymph node dissection may remove cancer cells that have spread to nearby lymph nodes in patients with breast cancer. Radiation therapy uses high-energy x rays or protons to kill tumor cells. It is not yet known if radiation therapy works better alone or with lymph node dissection in treating patients with breast cancer previously treated with chemotherapy and surgery.

PRIMARY OBJECTIVE:

I. To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of invasive breast cancer recurrence-free interval in patients with positive sentinel lymph node(s) (SLN\[s\]) after completion of neoadjuvant chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in patients with a positive SLN(s) after completion of neoadjuvant chemotherapy.

II. To obtain an estimate of the distribution of residual disease burden scores.

III. To estimate the distribution of overall survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo axillary lymph node dissection. Beginning 3-12 weeks following surgery, patients undergo nodal radiation therapy comprising 3-dimensional (3D) conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton radiation therapy (PRT) 5 days a week for 5-6 weeks.

ARM II: Patients undergo axillary and nodal radiation therapy comprising 3D-CRT, IMRT, or PRT 5 days a week for 5-6 weeks.

After completion of study treatment, patients are followed up at least every 6 months for 2 years and then annually for 3 years.

Comparison of Axillary Lymph Node Dissection With Axillary Radiation for Patients With Node-Positive Breast Cancer Treated With Chemotherapy

A Randomized Phase III Trial Comparing Axillary Lymph Node Dissection to Axillary Radiation in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy

National Cancer Institute (NCI)

Canadian Cancer Trials Group

Alliance for Clinical Trials in Oncology

Coagulants

Thrombin

After axillary lymph node dissection no surgical sealing patch (TachoSil®) is applied.

After axillary lymph node dissection, 3 large TachoSil® patches in the dissected axilla are positioned to cover as much of the axillary walls as possible.

TachoSil® is a sterile, ready-to-use, absorbable surgical patch and consists of an equine collagen sponge coated with human fibrinogen and human thrombin.

TachoSil® patches

Walter Weber, MD

Christoph Tausch, MD

Axillary lymph node dissection remains an integral part of surgical treatment of primarily node-positive invasive breast cancer. In order to reduce the incidence of clinically relevant seroma, a suction drain is routinely placed into the axillary cavity after axillary lymph node dissection (ALND) by a separate stab incision. The pathogenesis of seroma involves the collection of lymph fluid caused by dissection of lymph vessels and exudate. All coagulation and fibrinolytic factors are produced and secreted by lymphatic endothelial cells and are involved in the sealing of lymphatic capillaries. Local hemostyptic agents may therefore reduce postoperative secretion from lymphatic fistulas caused by ALND.

We propose to conduct a multicenter prospective randomized control trial in Switzerland to evaluate the impact of TachoSil®, a ready-to-use, absorbable surgical patch (consisting of an equine collagen sponge coated with human fibrinogen and human thrombin) on axillary drainage after ALND for breast cancer. We hypothesize that the use of TachoSil® significantly and relevantly reduces the volume and duration of axillary drainage after ALND. This has the potential to increase patients' quality of life, as well as to shorten the length of hospital stay and reduce hospital costs.

DISEASE BACKGROUND

In Switzerland, 5'500 women and 30 to 40 men are diagnosed with breast cancer every year. It accounts for one third of all cancer diagnoses among women, and causes approximately 1'350 deaths per year. Around 1'200 patients per year need axillary lymph node dissection (ALND) as part of their surgical treatment. ALND is indicated primarily for node-positive breast cancer. Patients are identified either by pre-operative evaluation of the axilla or by intraoperative sentinel lymph node biopsy (SLNB).

THERAPY BACKGROUND

During axillary lymph node dissection for breast cancer, standard techniques for prevention of leakage of dissected lymphatic vessels include the application of suture ligaments and the use of bipolar electrocautery. Seroma prevention after ALND is achieved by placement of a closed suction drain through the skin into the axillary cavity.

Closed axillary suction drains are archaic tools to prevent seroma after ALND by simple mechanical drainage at the cost of significant patient discomfort and increased length of hospital stay. The sealing agent TachoSil® (consists of an equine collagen sponge coated with human fibrinogen and human thrombin) allows a more nuanced approach to the management of axillary seroma prevention and may support ongoing and decades-old efforts of the professional breast cancer community to decrease the duration of axillary drainage and finally, to abandon the drain from routine clinical practice.

RATIONALE FOR PERFORMING THE TRIAL

Axillary lymph node dissection remains an integral part of surgical treatment of primarily node-positive invasive breast cancer. In order to reduce the incidence of clinically relevant seroma, a suction drain is routinely placed into the axillary cavity after ALND by a separate stab incision. Indeed, a recent meta-analysis of 6 randomized controlled trials (RCT's) on axillary drainage versus no axillary drainage and a similar meta-analysis of 6 RCT's on volume-controlled versus no/short-term drainage demonstrated a significant reduction of seroma risk with the use of axillary drainage. Importantly, however, the majority of patients in these trials did not develop seroma even in the absence of axillary drainage.

The reduction of seroma risk by axillary drainage in these trials was achieved at the expense of a prolonged hospital stay and significant patient discomfort caused by the drain. During the past 4 decades at least 50 RCT's have been performed on various interventions to reduce axillary drainage with the aim of abandoning the axillary drain from clinical practice. The interventions ranged from surgical dead space reduction, use of various surgical equipment, shoulder immobilization, compression dressing, to the application of somatostatin analogons and other medication. Due to the overall limited success of these trials axillary drainage is still standard of care after ALND.

The pathogenesis of seroma involves the collection of lymph fluid caused by dissection of lymph vessels and exudate. All coagulation and fibrinolytic factors are produced and secreted by lymphatic endothelial cells and are involved in the sealing of lymphatic capillaries. Local hemostyptic agents may therefore reduce postoperative secretion from lymphatic fistulas caused by ALND. However, the results of the trials on the use of fibrin sealant in the axillary cavity after ALND were conflicting. While some showed no favorable impact of fibrin sealant, others demonstrated promising results when using fibrin glue. Consequently, a meta-analysis of 11 RCT's with 632 patients showed no impact of the use of fibrin glues after ALND on the risk of seroma or the length of hospital stay, but revealed a trend toward less drainage volume (weighted mean difference - 117.7, 95 per cent confidence interval - 259.2 to 23.8 ml). In all these studies, however, the liquid form of fibrin sealant was used.

The use of TachoSil®, which is a non-liquid surgical patch, has been shown to strongly reduce the lymphatic drainage after lymphadenectomy in gynecologic and urologic procedures and prevented the development of chylothorax in patients who underwent heart surgery with intraoperative lymphatic leakage.

We propose to conduct a multicenter prospective RCT in Switzerland to evaluate the impact of TachoSil® on axillary drainage after ALND for breast cancer. We hypothesize that the use of TachoSil® significantly and relevantly reduces the volume and duration of axillary drainage after ALND. This has the potential to increase patients' quality of life, as well as to shorten the length of hospital stay and reduce hospital costs, and provides the rationale and the clinical relevance for the proposed RCT. If the proposed RCT shows a minimum of 33% relative drainage reduction, a follow-up trial is justified. The follow-up trial will be conducted with all patients receiving TachoSil® and randomization with versus without axillary drainage. Therefore, the final goal is the omission of axillary drainage after ALND in the future.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After ALND for Breast Cancer

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Lymph Node Dissection for Breast Cancer. A Multicenter Randomized Phase III Trial.

Total volume of axillary drainage in ml until drain removal.

Volume of axillary drainage per 24 hours in ml will be calculated as the total volume of axillary drainage in ml until drain removal divided by the total duration of axillary drainage in days

Total duration of axillary drainage in days will be calculated from the date of surgery to the date of axillary drain removal

Duration of postoperative hospital stay in days will be calculated from the date of surgery to the date of hospital discharge.

Clinically relevant seroma is defined as either causing discomfort or requiring aspiration.

Number of clinically relevant seroma aspirations until 24 weeks after surgery

Total volume of all clinically relevant seroma aspirations in ml until 24 weeks after surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Breast Lymph Node Mapping	NCT01038908	Breast Cancer	Isosulfan Blue ... Isosulfan Blue ...	19 Years -	University of British Columbia
Breast Lymph Node Mapping	NCT01038908	Breast Cancer	Isosulfan Blue ... Isosulfan Blue ...	19 Years -	University of British Columbia
Axillary Reverse Mapping (ARM) Technique	NCT03109522	Invasive Breast... Ductal Carcinom...	axillary revers... Standard axilla...	18 Years -	McMaster University
Comparison of Axillary Lymph Node Dissection With Axillary Radiation for Patients With Node-Positive Breast Cancer Treated With Chemotherapy	NCT01901094	Stage II Breast... Stage IIIA Brea...	Axillary Lymph ... Nodal Radiation... Axillary Radiat...	18 Years -	Alliance for Clinical Trials in Oncology
Axillary Reverse Mapping (ARM) Technique	NCT03109522	Invasive Breast... Ductal Carcinom...	axillary revers... Standard axilla...	18 Years -	McMaster University
Axillary Reverse Mapping (ARM) Technique	NCT03109522	Invasive Breast... Ductal Carcinom...	axillary revers... Standard axilla...	18 Years -	McMaster University
Impact of a Surgical Sealing Patch on Lymphatic Drainage After ALND for Breast Cancer	NCT02311543	Breast Cancer	TachoSil® patch...	18 Years -	Swiss Group for Clinical Cancer Research

Spots Global Cancer Trial Database for axillary lymph node dissection (alnd)