Use of Superparamagnetic Iron Oxide (SPIO) in Sentinel Lymph Node Detection for Breast Cancer

Study Overview
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Brief Summary
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Sentinel lymph node biopsy is mandatory during breast cancer operation for disease staging and treatment. The localization of sentinel lymph node is by the injection of radioisotope and blue dye, which is the gold standard. However the use of radioisotope and blue dye are associated with specific drawbacks. Superparamagnetic iron oxide is a magnetic tracer which is FDA-approved for sentinel lymph node localization. The hypothesis of this study is superparamagnetic iron oxide can replace the conventional dual mapping of radioisotope and blue dye in the detection of sentinel lymph nodes for early breast cancers.

Detailed Description
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Sentinel lymph node biopsy has replaced axillary dissection as the standard of care in clinically node negative breast cancer. Lymphatic mapping with radioisotope and blue dye were most studied tracer agents and their combination was shown to give the highest nodal identification rate and lowest false negative rate. However the use of radioisotope is strictly monitored due to its radioactivity and blue dye is associated with potential allergic reactions and skin tattoo. Superparamagnetic iron oxide is non-radioactive. It gives an audible signal with the magnetometer and a brown color as visual cue. It has demonstrated comparable nodal identification rate with the conventional method in multiple non-inferiority trials in Europe and the USA. There was no randomized controlled trial for a head-to-head comparison between these mapping technique. The hypothesis of this study is superparamagnetic iron oxide alone can replace the conventional dual mapping of radioisotope and blue dye. Previous literature suggested the nodal detection rate for conventional method and SPIO was around 97%. Assuming a non-inferiorly limit of 5%, with a power of 80% and 5% significance level, the number of patients per treatment arm should be 144. We will need a sample size of 300 patients, taking into account a loss to follow-up of <5%. All patients recruited will be provided full explanation of the study and written voluntary consents will be obtained before randomization. All data will be prospectively collected by dedicated research assistant and computerized into a database. All statistical analysis will be performed with Statistical Product and Service Solution (SPSS) version 24. Missing information will be marked and significant missing data will be excluded from analysis. Chi-square test will be used to compare discrete variables and student T test or Mann Whitney U test for continuous variables. P value less than 0.05 will be considered statistically significant. Personal data will be obtained by principal investigator and dedicated research assistant to allow analysis of the results. These data will be anonymous, only identified by the first three letters of patient's name. The file will be encrypted and stored in the study institution. All the information will be solely for research purpose and kept strictly confidential. Research subjects will be provided with phone contacts for any questions or emergency related to the study.

Official Title
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Use of Superparamagnetic Iron Oxide (SPIO) Versus Conventional Radioisotope and Patent Blue Dye in Sentinel Lymph Node Detection for Breast Cancer: a Randomized Controlled Trial

Conditions
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Breast Cancer, Sentinel Lymph Node

Intervention / Treatment
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* Procedure: sentinel lymph node biopsy procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients with clinical T1-3N0 invasive ductal carcinoma or invasive lobular carcinoma planned for breast conservative surgery or mastectomy, with sentinel lymph node biopsy Patients planned for upfront operation or neoadjuvant chemotherapy are allowed Exclusion Criteria: Patients with hypersensitivity to dextran compounds, iron or blue dye Patients with iron overload disease Pregnant or lactating patients Patients with pacemaker or other implantable metallic devices in chest wall or prosthesis in shoulder Mentally incompetent patients

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPIO arm<br>Superparamagnetic iron oxide guided sentinel lymph node mapping | Procedure: sentinel lymph node biopsy procedure<br>* Patient received respective tracer injection and sentinel lymph node biopsy was performed in the operation theatre with the corresponding device.<br>|
| Active Comparator: Control arm<br>Conventional radioisotope and blue dye guided sentinel lymph node mapping | Procedure: sentinel lymph node biopsy procedure<br>* Patient received respective tracer injection and sentinel lymph node biopsy was performed in the operation theatre with the corresponding device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sentinel lymph node detection rate per patient | Successful sentinel lymph node localization for each arm | At the time of operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of sentinel lymph nodes detected | Number of sentinel lymph nodes detected in each arm | At the time of operation | 
| Duration of sentinel lymph node biopsy | Duration of sentinel lymph node biopsy procedure in each arm | Duration of the operation from incision of axillary fascia to satisfactory nodal basin count | 
| Detection rate of pathologically involved sentinel lymph nodes | Detection rate of malignant sentinel lymph nodes in each arm | At operation | 
| Duration of skin stain | Duration of blue stain (from blue dye) and brown stain (from SPIO) in respective arm | post-operative 3 month, 6 month, 12 month and 18 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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superparamagnetic iron oxide, sentinel lymph node detection rate