<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03024463</url>
  </required_header>
  <id_info>
    <org_study_id>IMLN-VS</org_study_id>
    <nct_id>NCT03024463</nct_id>
  </id_info>
  <brief_title>The Multi-center Validation Study of Internal Mammary Lymph Biopsy With Modified Injection Technique in Breast Cancer Patients</brief_title>
  <official_title>The Multi-center Validation Study of Breast Cancer Internal Mammary Lymph Biopsy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shandong Cancer Hospital and Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shandong Cancer Hospital and Institute</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In addition to axillary lymph node (ALN), internal mammary lymph node (IMLN) chain is also&#xD;
      the first-echelon nodal drainage site for metastasis and it provides important prognostic&#xD;
      information in breast cancer patients. However, decision about local treatment of IMLN is&#xD;
      still being made based on ALN status. The 2016 National Comprehensive Cancer Network&#xD;
      Guidelines recommend internal mammary lymph node irradiation for patients with more than 4&#xD;
      positive ALNs (category 1), and strongly consider irradiation for patients with 1 to 3&#xD;
      positive ALNs (category 2A). Therefore, there will be patients in positive ALN subgroup who&#xD;
      just face complications of an unnecessary radiation to IMLN and there will be patients in&#xD;
      negative ALN subgroup who do not receive adjuvant radiation therapy they really need. Thus,&#xD;
      these inclusion criteria of National Comprehensive Cancer Network might lead to&#xD;
      over-treatment and under-treatment. Internal mammary sentinel lymph node biopsy (IM-SLNB)&#xD;
      provides a less invasive method of assessing the IMLN than surgical dissection. However, low&#xD;
      visualization rate of IM-SLN has been a restriction of IM-SLNB. A modified radiotracer&#xD;
      injection technique was established in our previous study. This technique could significantly&#xD;
      improve the IM-SLN detection rate. The investigators have validated the accurate of the&#xD;
      hypothesis and the modified radiotracer injection technique in the previous study.&#xD;
&#xD;
      For axillary sentinel lymph node biopsy, the success rate and the accuracy are the most&#xD;
      important technical indicators. The relatively lower false-negative rate is a precondition&#xD;
      for the widely application of SLNB. Axillary SLNB needs to be accomplished with the&#xD;
      cooperation of multi-disciplinary teamwork, including the breast surgery, the radiologist,&#xD;
      the nuclear medicine doctor and the pathologist, in order to obtain a better success rate and&#xD;
      a lower false-negative rate. Our previous studies confirmed that the modified radiotracer&#xD;
      injection technique can greatly improve the IM-SLN detection rate. However, whether the&#xD;
      IM-SLNB based on the modified radiotracer injection technique has a low false negative rate&#xD;
      or not still need to be confirmed by a further validation research.&#xD;
&#xD;
      Furthermore，recently, the investigators propose that if IM-SLN is the only metastatic lymph&#xD;
      node and there would be no positive node else in IMLN chain, the radiotherapy and its&#xD;
      associated complications could be avoided in these patients. On the other hand, if there is&#xD;
      the presence of metastatic non-sentinel lymph node (NSLN) in IMLN chain after IM-SLNB, it is&#xD;
      important to predict the risk of IM-NSLN metastasis in IM-SLN positive patients. As there is&#xD;
      currently no such model, a predictive model for IM-SLN positive patients to avoid&#xD;
      radiotherapy is needed in this situation. Therefore, a new study will be conducted to verify&#xD;
      the issues above.&#xD;
&#xD;
      In the current study, all the participants (18~70 years of age) would have the preoperative&#xD;
      pathology of invasive breast cancer and positive fine-needle aspiration result in their&#xD;
      clinical or ultrasonic suspicious axillary lymph node. 99mTc-labeled sulfur colloid was&#xD;
      injected into the parenchyma under the ultrasound guidance 3 to 18 hours before surgery. Two&#xD;
      syringes of 9.25 to 18.5MBq 99mTc-labeled sulfur colloid in 0.5 to 0.7mL volume were injected&#xD;
      at the 6 and 12 o'clock positions 0.5 to 1.0 cm from areola (about 2.0~4.0 cm from the&#xD;
      nipple). IM-SLNB was performed in all participants with IMSLN visualized on preoperative&#xD;
      lymphoscintigraphy and/or detected by the intra-operative gamma probe. All hotspots in the&#xD;
      internal mammary basin were harvested and intra-operative identification of the IM-SLN was&#xD;
      based on gamma probe detection. The IM-SLN was sectioned along the long axis into two blocks&#xD;
      and all blocks were tested by the frozen section and the touch imprint cytology&#xD;
      intra-operatively. Those participants with positive intra-operative results received IMLN&#xD;
      dissection. Finally, all the IM-SLN blocks and IM-NSLN dissected were assessed&#xD;
      post-operatively by H&amp;E and Cytokeratin 19 stained immunohistochemistry. The conclusion would&#xD;
      be drawn through the results mentioned above.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Anticipated">August 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The accuracy (false negative rate) of internal mammary sentinel lymph node biopsy</measure>
    <time_frame>Two years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of internal mammary non-sentinel lymph node metastases in patients with positive axillary node and internal mammary sentinel lymph node</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Factors influencing the number of internal mammary non-sentinel lymph node metastases in patients with positive axillary node and internal mammary sentinel lymph node</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Breast Neoplasm</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>IM-SLNB and IMLN dissection</intervention_name>
    <description>Internal mammary sentinel lymph node biopsy followed by internal mammary lymph node dissection</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        200 patients with positive axillary node&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with preoperative pathology confirmed invasive breast cancer;&#xD;
&#xD;
          -  Clinical N1-3 M0 (with positive fine-needle aspiration result in their clinical or&#xD;
             ultrasonic suspicious axillary lymph node ; no clinical or radiologic evidence of&#xD;
             distant metastases);&#xD;
&#xD;
          -  Be able and willing to sign informed consent forms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have received neoadjuvant therapy (including neoadjuvant chemotherapy and&#xD;
             / or endocrine therapy);&#xD;
&#xD;
          -  Patients with a previous history of breast cancer (recurrence of breast cancer and&#xD;
             contralateral breast cancer);&#xD;
&#xD;
          -  Patients with a history of other malignancies;&#xD;
&#xD;
          -  Patients who have had previous surgery in axillary or internal mammary;&#xD;
&#xD;
          -  Patients in pregnancy and lactation;&#xD;
&#xD;
          -  Patients participant in other clinical trials that will have an impact on the results&#xD;
             of this study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shandong Cancer Hospital and Institute</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250117</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yong-sheng Wang, MD</last_name>
      <phone>+8613505409989</phone>
      <email>wangysh2008@aliyun.com</email>
    </contact>
    <investigator>
      <last_name>Yong-sheng Wang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>May 17, 2018</last_update_submitted>
  <last_update_submitted_qc>May 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shandong Cancer Hospital and Institute</investigator_affiliation>
    <investigator_full_name>Yongsheng Wang</investigator_full_name>
    <investigator_title>Director of Breast Cancer Center</investigator_title>
  </responsible_party>
  <keyword>Breast Neoplasm; Internal Lymph Node; Sentinel Lymph Node Biospy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03024463
org study id: IMLN-VS
nct id: NCT03024463
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
In addition to axillary lymph node (ALN), internal mammary lymph node (IMLN) chain is also
      the first-echelon nodal drainage site for metastasis and it provides important prognostic
      information in breast cancer patients. However, decision about local treatment of IMLN is
      still being made based on ALN status. The 2016 National Comprehensive Cancer Network
      Guidelines recommend internal mammary lymph node irradiation for patients with more than 4
      positive ALNs (category 1), and strongly consider irradiation for patients with 1 to 3
      positive ALNs (category 2A). Therefore, there will be patients in positive ALN subgroup who
      just face complications of an unnecessary radiation to IMLN and there will be patients in
      negative ALN subgroup who do not receive adjuvant radiation therapy they really need. Thus,
      these inclusion criteria of National Comprehensive Cancer Network might lead to
      over-treatment and under-treatment. Internal mammary sentinel lymph node biopsy (IM-SLNB)
      provides a less invasive method of assessing the IMLN than surgical dissection. However, low
      visualization rate of IM-SLN has been a restriction of IM-SLNB. A modified radiotracer
      injection technique was established in our previous study. This technique could significantly
      improve the IM-SLN detection rate. The investigators have validated the accurate of the
      hypothesis and the modified radiotracer injection technique in the previous study.

      For axillary sentinel lymph node biopsy, the success rate and the accuracy are the most
      important technical indicators. The relatively lower false-negative rate is a precondition
      for the widely application of SLNB. Axillary SLNB needs to be accomplished with the
      cooperation of multi-disciplinary teamwork, including the breast surgery, the radiologist,
      the nuclear medicine doctor and the pathologist, in order to obtain a better success rate and
      a lower false-negative rate. Our previous studies confirmed that the modified radiotracer
      injection technique can greatly improve the IM-SLN detection rate. However, whether the
      IM-SLNB based on the modified radiotracer injection technique has a low false negative rate
      or not still need to be confirmed by a further validation research.

      Furthermore，recently, the investigators propose that if IM-SLN is the only metastatic lymph
      node and there would be no positive node else in IMLN chain, the radiotherapy and its
      associated complications could be avoided in these patients. On the other hand, if there is
      the presence of metastatic non-sentinel lymph node (NSLN) in IMLN chain after IM-SLNB, it is
      important to predict the risk of IM-NSLN metastasis in IM-SLN positive patients. As there is
      currently no such model, a predictive model for IM-SLN positive patients to avoid
      radiotherapy is needed in this situation. Therefore, a new study will be conducted to verify
      the issues above.

      In the current study, all the participants (18~70 years of age) would have the preoperative
      pathology of invasive breast cancer and positive fine-needle aspiration result in their
      clinical or ultrasonic suspicious axillary lymph node. 99mTc-labeled sulfur colloid was
      injected into the parenchyma under the ultrasound guidance 3 to 18 hours before surgery. Two
      syringes of 9.25 to 18.5MBq 99mTc-labeled sulfur colloid in 0.5 to 0.7mL volume were injected
      at the 6 and 12 o'clock positions 0.5 to 1.0 cm from areola (about 2.0~4.0 cm from the
      nipple). IM-SLNB was performed in all participants with IMSLN visualized on preoperative
      lymphoscintigraphy and/or detected by the intra-operative gamma probe. All hotspots in the
      internal mammary basin were harvested and intra-operative identification of the IM-SLN was
      based on gamma probe detection. The IM-SLN was sectioned along the long axis into two blocks
      and all blocks were tested by the frozen section and the touch imprint cytology
      intra-operatively. Those participants with positive intra-operative results received IMLN
      dissection. Finally, all the IM-SLN blocks and IM-NSLN dissected were assessed
      post-operatively by H&E and Cytokeratin 19 stained immunohistochemistry. The conclusion would
      be drawn through the results mentioned above.
observational model: Case-Only
time perspective: Prospective
measure: The accuracy (false negative rate) of internal mammary sentinel lymph node biopsy
time frame: Two years
measure: The number of internal mammary non-sentinel lymph node metastases in patients with positive axillary node and internal mammary sentinel lymph node
time frame: Two years
measure: Factors influencing the number of internal mammary non-sentinel lymph node metastases in patients with positive axillary node and internal mammary sentinel lymph node
time frame: Two years
intervention type: Procedure
intervention name: IM-SLNB and IMLN dissection
description: Internal mammary sentinel lymph node biopsy followed by internal mammary lymph node dissection
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shandong Cancer Hospital and Institute
investigator full name: Yongsheng Wang
investigator title: Director of Breast Cancer Center
mesh term: Breast Neoplasms