Clinical trial NCT03541278: Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique
Official title: A Prospective Multicenter Clinical Trial of Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique for Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer
Keywords: Breast Cancer
Internal Mammary Lymph Node
Internal Mammary Sentinel Lymph Node Biopsy
Detection Rate
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
Collaborators: name: The Affiliated Hospital of Qingdao University
name: Henan Cancer Hospital
First posted: 2018-05-30
Enrollment: 350
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Visualization Rate
timeFrame: 2 year
Secondary outcomes:
measure: Success rate of IM-SLNB
timeFrame: 2 year
measure: Frequency and Severity of Complications with IM-SLNB
timeFrame: 2 year
measure: Metastasis Rate of IMSLN
timeFrame: 2 year
measure: Clinical Benefits
timeFrame: 2 year
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Yong-Sheng Yong-Sheng, MD
role: STUDY_CHAIR
References:
citation: 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.