<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/NCT03033030</url>
  </required_header>
  <id_info>
    <org_study_id>102REG2016</org_study_id>
    <nct_id>NCT03033030</nct_id>
  </id_info>
  <brief_title>Tomosynthesis (TS) or Ultrasound (US) in Mammography-negative Dense Breasts (TOMUS). National Multicenter Trial</brief_title>
  <acronym>TOMUS</acronym>
  <official_title>Tomosynthesis (TS) or Ultrasound (US) in Mammography-negative Dense Breasts (TOMUS). National Multicenter Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Genova</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Genova</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Breast cancer remains a worldwide big killer with a rate of deaths compared with newly&#xD;
      diagnosed cases not lower than 20%. Mammography is the primary imaging modality for the early&#xD;
      detection of clinically occult breast cancer. Mammography is established as the primary&#xD;
      investigation for population-based breast cancer screening. Advances in mammographic&#xD;
      technique regarding both hardware and software applications are still not sufficient to&#xD;
      overcome mammography's limitation with regard to both sensitivity and specificity. Depending&#xD;
      on several factors, such as age and breast density, mammography screening is associated with&#xD;
      a false-negative rate of 10-20 %.&#xD;
&#xD;
      Digital Breast Tomosynthesis (TS) is a novel technique that is able to study the breast using&#xD;
      3D reconstructions of the tissue from multiple low-dose digital mammographic images acquired&#xD;
      in several planes in a 15 to 50 degree angle. This process aims at a increasing the number of&#xD;
      lesion visible due to the reduction of overlapping breast tissue.&#xD;
&#xD;
      In TS, to overcome these limitations, a digital mammography (DM) unit is modified to allow&#xD;
      the X-ray tube to move through a proscribed arc of excursion acquiring a fixed number of&#xD;
      discrete projection images while the breast remains in compression. The individual projection&#xD;
      images are extremely low in dose, so the composite dose incurred during a TS acquisition may&#xD;
      be similar to that of a standard 2D mammography. The radiologically dense breasts are&#xD;
      associated with decreased sensitivity of mammography, both in the clinical and screening&#xD;
      setting as well as its established association with breast cancer risk. The systematic&#xD;
      application of ultrasound (US) in women with radiologically dense breasts and negative&#xD;
      mammogram has been shown to be associated with an additional cancer detection rate [7,8,9].&#xD;
      Incremental ultrasound detection of cancer may be considered in the range of 0.27% to 0.52%&#xD;
      of ultrasound-screened women in different density categories [10]. In addition, the main&#xD;
      limitation of US in breast screening is represented by false- positive findings. These&#xD;
      findings result in additional investigation or unnecessary surgical biopsy [10].&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Breast cancer remains a worldwide big killer with a rate of deaths compared with newly&#xD;
      diagnosed cases not lower than 20%. Mammography is the primary imaging modality for the early&#xD;
      detection of clinically occult breast cancer. Mammography is established as the primary&#xD;
      investigation for population-based breast cancer screening. Advances in mammographic&#xD;
      technique regarding both hardware and software applications are still not sufficient to&#xD;
      overcome mammography's limitation with regard to both sensitivity and specificity. Depending&#xD;
      on several factors, such as age and breast density, mammography screening is associated with&#xD;
      a false-negative rate of 10-20 %.&#xD;
&#xD;
      Digital Breast Tomosynthesis (TS) is a novel technique that is able to study the breast using&#xD;
      3D reconstructions of the tissue from multiple low-dose digital mammographic images acquired&#xD;
      in several planes in a 15 to 50 degree angle. This process aims at a increasing the number of&#xD;
      lesion visible due to the reduction of overlapping breast tissue.&#xD;
&#xD;
      In TS, to overcome these limitations, a digital mammography (DM) unit is modified to allow&#xD;
      the X-ray tube to move through a proscribed arc of excursion acquiring a fixed number of&#xD;
      discrete projection images while the breast remains in compression. The individual projection&#xD;
      images are extremely low in dose, so the composite dose incurred during a TS acquisition may&#xD;
      be similar to that of a standard 2D mammography. The radiologically dense breasts are&#xD;
      associated with decreased sensitivity of mammography, both in the clinical and screening&#xD;
      setting as well as its established association with breast cancer risk. The systematic&#xD;
      application of ultrasound (US) in women with radiologically dense breasts and negative&#xD;
      mammogram has been shown to be associated with an additional cancer detection rate.&#xD;
      Incremental ultrasound detection of cancer may be considered in the range of 0.27% to 0.52%&#xD;
      of ultrasound-screened women in different density categories [10]. In addition, the main&#xD;
      limitation of US in breast screening is represented by false- positive findings. These&#xD;
      findings result in additional investigation or unnecessary surgical biopsy.&#xD;
&#xD;
      The study aims to demonstrate at least statistical equivalence, or non-significant difference&#xD;
      between TS and US in women with dense breasts.&#xD;
&#xD;
      If the equivalence between TS and US will be demonstrated, US may be substituted by TS with&#xD;
      great benefits for the patients and for the healthcare resources we aim to:&#xD;
&#xD;
        1. Assess if TS may detect additional cancers in dense breasts that approximate US&#xD;
           detection capability but with less false positive findings than US.&#xD;
&#xD;
        2. If TS detects new cancers in dense breasts similarly to US (approximate rate or&#xD;
           marginally lower rate), evaluate the true positive/false positive ratio.&#xD;
&#xD;
        3. Cost-analysis. In case of less false positives detected by TS, the TP/ FP trade-off&#xD;
           might be strongly in favour of TS with a great potential of costs reduction.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 2014</start_date>
  <completion_date type="Anticipated">September 2021</completion_date>
  <primary_completion_date type="Anticipated">September 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incremental Cancer Detection Rate or Area Under the Curve</measure>
    <time_frame>2 years</time_frame>
    <description>The study aims to demonstrate at least statistical equivalence, or non-significant difference between TS and US in women with dense breasts.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>TP/FP rate</measure>
    <time_frame>2 years</time_frame>
    <description>If the equivalence between TS and US will be demonstrated, US may be substituted by TS with great benefits for the patients and for the healthcare resources we aim to:&#xD;
Assess if TS may detect additional cancers in dense breasts that approximate US detection capability but with less false positive findings than US.&#xD;
If TS detects new cancers in dense breasts similarly to US (approximate rate or marginally lower rate), evaluate the true positive/false positive ratio.&#xD;
Cost-analysis. In case of less false positives detected by TS, the TP/ FP trade-off might be strongly in favour of TS with a great potential of costs reduction.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">8000</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Tomosynthesis</arm_group_label>
    <description>Patients undergoing Digital Breast Tomosynthesis</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Ultrasound</intervention_name>
    <description>Ultrasound examination</description>
    <arm_group_label>Tomosynthesis</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Women who undergo breast TS and Mammography&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Asymptomatic subjects &lt;50 years of age presenting for mammography, with the exception&#xD;
             of those that, on previous mammograms are found to have breast density BI- RADS D1-2.&#xD;
&#xD;
          -  Asymptomatic subjects ≥ 50 years of age who request mammography and have breast&#xD;
             density BI-RADS 3-4.&#xD;
&#xD;
          -  Written Informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and breast feeding women&#xD;
&#xD;
          -  Unable to tolerate breast compression&#xD;
&#xD;
          -  Breast implants&#xD;
&#xD;
          -  Unable to understand or execute written informed consent&#xD;
&#xD;
          -  Unable or unwilling to agree to follow-up during observation period&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UNIGE</name>
      <address>
        <city>Genova</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alberto S Tagliafico, MD</last_name>
      <phone>+390103637873</phone>
      <email>alberto.tagliafico@unige.it</email>
    </contact>
    <investigator>
      <last_name>Alberto S Tagliafico, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>January 25, 2017</last_update_submitted>
  <last_update_submitted_qc>January 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Genova</investigator_affiliation>
    <investigator_full_name>Alberto Tagliafico</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Ultrasound</keyword>
  <keyword>Digital Breast Tomosynthesis</keyword>
  <keyword>Cancer Detection rate</keyword>
  <keyword>Sensitivity</keyword>
  <keyword>Specificity</keyword>
  <keyword>Breast density</keyword>
  <!-- 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/NCT03033030
org study id: 102REG2016
nct id: NCT03033030
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Breast cancer remains a worldwide big killer with a rate of deaths compared with newly
      diagnosed cases not lower than 20%. Mammography is the primary imaging modality for the early
      detection of clinically occult breast cancer. Mammography is established as the primary
      investigation for population-based breast cancer screening. Advances in mammographic
      technique regarding both hardware and software applications are still not sufficient to
      overcome mammography's limitation with regard to both sensitivity and specificity. Depending
      on several factors, such as age and breast density, mammography screening is associated with
      a false-negative rate of 10-20 %.

      Digital Breast Tomosynthesis (TS) is a novel technique that is able to study the breast using
      3D reconstructions of the tissue from multiple low-dose digital mammographic images acquired
      in several planes in a 15 to 50 degree angle. This process aims at a increasing the number of
      lesion visible due to the reduction of overlapping breast tissue.

      In TS, to overcome these limitations, a digital mammography (DM) unit is modified to allow
      the X-ray tube to move through a proscribed arc of excursion acquiring a fixed number of
      discrete projection images while the breast remains in compression. The individual projection
      images are extremely low in dose, so the composite dose incurred during a TS acquisition may
      be similar to that of a standard 2D mammography. The radiologically dense breasts are
      associated with decreased sensitivity of mammography, both in the clinical and screening
      setting as well as its established association with breast cancer risk. The systematic
      application of ultrasound (US) in women with radiologically dense breasts and negative
      mammogram has been shown to be associated with an additional cancer detection rate [7,8,9].
      Incremental ultrasound detection of cancer may be considered in the range of 0.27% to 0.52%
      of ultrasound-screened women in different density categories [10]. In addition, the main
      limitation of US in breast screening is represented by false- positive findings. These
      findings result in additional investigation or unnecessary surgical biopsy [10].
Breast cancer remains a worldwide big killer with a rate of deaths compared with newly
      diagnosed cases not lower than 20%. Mammography is the primary imaging modality for the early
      detection of clinically occult breast cancer. Mammography is established as the primary
      investigation for population-based breast cancer screening. Advances in mammographic
      technique regarding both hardware and software applications are still not sufficient to
      overcome mammography's limitation with regard to both sensitivity and specificity. Depending
      on several factors, such as age and breast density, mammography screening is associated with
      a false-negative rate of 10-20 %.

      Digital Breast Tomosynthesis (TS) is a novel technique that is able to study the breast using
      3D reconstructions of the tissue from multiple low-dose digital mammographic images acquired
      in several planes in a 15 to 50 degree angle. This process aims at a increasing the number of
      lesion visible due to the reduction of overlapping breast tissue.

      In TS, to overcome these limitations, a digital mammography (DM) unit is modified to allow
      the X-ray tube to move through a proscribed arc of excursion acquiring a fixed number of
      discrete projection images while the breast remains in compression. The individual projection
      images are extremely low in dose, so the composite dose incurred during a TS acquisition may
      be similar to that of a standard 2D mammography. The radiologically dense breasts are
      associated with decreased sensitivity of mammography, both in the clinical and screening
      setting as well as its established association with breast cancer risk. The systematic
      application of ultrasound (US) in women with radiologically dense breasts and negative
      mammogram has been shown to be associated with an additional cancer detection rate.
      Incremental ultrasound detection of cancer may be considered in the range of 0.27% to 0.52%
      of ultrasound-screened women in different density categories [10]. In addition, the main
      limitation of US in breast screening is represented by false- positive findings. These
      findings result in additional investigation or unnecessary surgical biopsy.

      The study aims to demonstrate at least statistical equivalence, or non-significant difference
      between TS and US in women with dense breasts.

      If the equivalence between TS and US will be demonstrated, US may be substituted by TS with
      great benefits for the patients and for the healthcare resources we aim to:

        1. Assess if TS may detect additional cancers in dense breasts that approximate US
           detection capability but with less false positive findings than US.

        2. If TS detects new cancers in dense breasts similarly to US (approximate rate or
           marginally lower rate), evaluate the true positive/false positive ratio.

        3. Cost-analysis. In case of less false positives detected by TS, the TP/ FP trade-off
           might be strongly in favour of TS with a great potential of costs reduction.
observational model: Cohort
time perspective: Prospective
measure: Incremental Cancer Detection Rate or Area Under the Curve
time frame: 2 years
description: The study aims to demonstrate at least statistical equivalence, or non-significant difference between TS and US in women with dense breasts.
measure: TP/FP rate
time frame: 2 years
description: If the equivalence between TS and US will be demonstrated, US may be substituted by TS with great benefits for the patients and for the healthcare resources we aim to:
Assess if TS may detect additional cancers in dense breasts that approximate US detection capability but with less false positive findings than US.
If TS detects new cancers in dense breasts similarly to US (approximate rate or marginally lower rate), evaluate the true positive/false positive ratio.
Cost-analysis. In case of less false positives detected by TS, the TP/ FP trade-off might be strongly in favour of TS with a great potential of costs reduction.
arm group label: Tomosynthesis
description: Patients undergoing Digital Breast Tomosynthesis
intervention type: Diagnostic Test
intervention name: Ultrasound
description: Ultrasound examination
arm group label: Tomosynthesis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
investigator: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Genova
investigator full name: Alberto Tagliafico
investigator title: Assistant Professor