Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique

A Prospective Multicenter Clinical Trial of Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique for Early Breast Cancer

Internal Mammary Lymph Node (IMLN) and Axillary Lymph Node (ALN) are regarded as "the first station" of lymphatic drainage in breast cancer, serving as an important reference for lymph staging and decision-making. Although the concept of Internal Mammary Sentinel Lymph Node Biopsy (IM-SLNB) has been included in the AJCC guidelines since the 6th edition, technical bottlenecks and clinical benefits still remained to be the main reasons limiting its clinical application:

Technical bottlenecks: In previous clinical practice, the internal mammary visualization rate was very low (13% on average, 0% -37%) under the guidance of the traditional radionuclide injection technique, which became a technology bottleneck restricting the widespread of IM-SLNB. After continuous exploration, our center invented the "modified injection technique" of injecting the nuclide tracer into the mammary gland layer at 6 and 12 o'clock around the areolar under the guidance of ultrasound, as well as increasing the injection volume to increase the local tension. A high internal mammary imaging rate of 71% was obtained, which laid a foundation for the further study and clinical application of IM-SLNB.

Clinical benefits: The IM-SLNB is a method to assess IMLN metastatic status in a minimally invasive way, which may improve the system of regional staging and guide precise IMLN treatment. However, based on the current IM-SLNB indication, the internal mammary metastasis rate was only 8%-15%, and it only had little influence on treatment strategy, which led to the controversy of its clinical application. Previous studies of extended radical mastectomy showed that in ALN positive patients the IMLN metastasis rate was 28-52%, while in ALN negative patients the metastasis rate was only 5-17%. Therefore, the continuation of the previous A-SLNB indication (clinical ALN negative) to IM-SLNB is apparently not in line with the current clinical practice, but further evaluation of internal mammary metastasis status in clinical ALN positive patients may receive greater benefit.

This prospective multicenter study attempted to perform IM-SLNB with our modified injection technique both in clinical ALN negative and positive patients for the first time. Through analyzing metastasis rate of IMLN as well as the influences it had on decision making, we hoped to develop more accurate indication for IM-SLNB and guide the individualized precise treatment of IMLN.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: MIT; Procedure: IM-SLNB

Detailed Description

Tracer injection and Lymphatic imaging: The radionuclide tracer (99mTc-Sulfur colloid) was prepared by the Nuclear Medicine Department and the sulfur colloid kit (equipped with a filter of 220 nm in diameter to control the size of colloidal particles) was prepared by Beijing Xinkesida company. All patients were injected with 99mTc-Sulfur colloid (1.0~1.2ml/29.6~55.5MBq) in periareolar parenchyma gland under the guidance of ultrasound using the "new injection technique" 3-18h before surgery. SPECT / CT lymphoscintigraphy was performed 30 min before surgery, and the radioactive concentration ("hot spot") near the sternum was defined as IMSLN positive.

IM-SLNB: After modified radical mastectomy / breast-conserving radical surgery, intraoperative γ-detector (Neoprobe 2000, Johnson& Johnson Company) was used to locate IM-SLN, and intercostal IM-SLNB was performed: open pectoralis major muscle, expose the parasternal intercostal space at the corresponding intercostal level (if the patient underwent breast-conserving surgery and the tumor was located in the lateral quadrant, an additional 3 cm of skin incision was required), cut the intercostal muscle at radioactive concentration site parallel to the rib, search and locate IMSLN with gamma detector, dissect precisely to avoid injury of internal mammary arteries and veins, and then sent the removed tissue to routine pathological examination.

Pathologic diagnosis: IMSLN was divided into 2mm tissue fragments according to the long axis (short diameter < 2 mm, no division), every tissue fragment required one layer of routine HE staining pathological examination. In this study, metastasis > 0.2mm was defined as IMSLN positive, while solitary tumor cell was defined as IMSLN negative. Further IHC detection of CK-9 was required if the IMSLN was HE staining negative to exclude micrometastasis.

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peng-Fei Qiu, MD; Phone Number: +8618615205204; Email: qiupengfei2002@aliyun.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital and Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients with preoperative pathology confirmed invasive breast cancer;
• Clinical T1-3 N0-3 M0 (with positive fine-needle aspiration result in their clinical or ultrasonic suspicious axillary lymph node ; no clinical or radiologic evidence of distant metastases);
• Be able and willing to sign informed consent forms.

Exclusion Criteria:

• Patients with enlarged internal mammary nodes by imaging;
• Patients who have received neoadjuvant therapy (including neoadjuvant chemotherapy and / or endocrine therapy);
• Patients with a previous history of breast cancer (recurrence of breast cancer and contralateral breast cancer);
• Patients with a history of other malignancies;
• Patients who have had previous surgery in axillary or internal mammary;
• Patients in pregnancy and lactation;
• Patients participant in other clinical trials that will have an impact on the results of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IM-SLNB with MIT; The radiotracer was injected with our modified injection technique (MIT) (periareolar intraparenchymal, high volume and ultrasonographic guidance). Internal mammary sentinel lymph node biopsy (IM-SLNB) was performed for patients with internal mammary visualized.	Procedure: MIT; periareolar intraparenchymal, high volume and ultrasonographic guidance; Other Names: Modified Injection Technique; Procedure: IM-SLNB; IM-SLNB was performed for IMLN visualized patients; Other Names: Internal Mammary Sentinel Lymph Node Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visualization Rate	The internal mammary sentinel lymph node visualization rate with our modified injection techniques	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate of IM-SLNB	Success rate of IM-SLNB in the IMSLN visualization patients who receive IM-SLNB	2 year
Frequency and Severity of Complications with IM-SLNB	IM-SLNB complications in the patients who receive IM-SLNB	2 year
Metastasis Rate of IMSLN	Metastasis rate of IMSLN in clinically axillary node-negative and clinically axillary node-positive patients	2 year
Clinical Benefits	staging and treatment change rate	2 year

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute
• Collaborators: Henan Cancer Hospital; The Affiliated Hospital of Qingdao University
• Investigators: Study Chair: Yong-Sheng Yong-Sheng, MD, Shandong Cancer Hospital and Institute

Publications and helpful links

General Publications

• Qiu PF, Liu JJ, Liu YB, Yang GR, Sun X, Wang YS. A modified technology could significantly improve the visualization rate of the internal mammary sentinel lymph nodes in breast cancer patients. Breast Cancer Res Treat. 2012 Nov;136(1):319-21. doi: 10.1007/s10549-012-2203-5. Epub 2012 Sep 6. No abstract available.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2018
• Primary Completion (ANTICIPATED): June 30, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: May 18, 2018
• First Posted (ACTUAL): May 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 30, 2018
• Last Update Submitted That Met QC Criteria: May 18, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Breast Cancer; Internal Mammary Lymph Node; Internal Mammary Sentinel Lymph Node Biopsy; Detection Rate
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: PMCT-IMSLNB-MIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No