<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/NCT02247713</url>
  </required_header>
  <id_info>
    <org_study_id>M14PRI</org_study_id>
    <nct_id>NCT02247713</nct_id>
  </id_info>
  <brief_title>An International Study on the Use of PET/CT in Radiotherapy Planning in Low and Middle Income Countries</brief_title>
  <acronym>PERTAIN</acronym>
  <official_title>An International Study on the Use of PET/CT in Radiotherapy Planning in Low and Middle Income Countries</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Netherlands Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>International Atomic Energy Agency</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Netherlands Cancer Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A part retrospective, part prospective cohort study to assess the difference in 2-year&#xD;
      overall survival in patients with stage III NSCLC receiving chemoradiotherapy with curative&#xD;
      intent in low and middle income countries before and after a training intervention on the use&#xD;
      of PET/CT for radiotherapy treatment planning.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Over the years, the incidence of lung cancer has risen in some low and middle income&#xD;
      countries due to the rise in tobacco use. Patients commonly present with lung cancer in an&#xD;
      advanced stage (stage III and IV) are not suitable for surgical resection, but may be&#xD;
      considered for radiotherapy. For patients in those countries who are not suitable for&#xD;
      surgical resection, radiotherapy offers the best chance of cure, best improvement in local&#xD;
      cancer control, best palliation and fewest side-effects. For accurate patient selection for&#xD;
      curative treatment and accurate staging of lung cancer, the use of fused&#xD;
      18F-fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography (FDG PET/CT) imaging&#xD;
      has been shown to be superior to CT alone. It has also been shown to have a significant&#xD;
      impact when used in the radiation treatment planning process and in particular for when used&#xD;
      for target volume delineation, where a significant reduction in interobserver variation has&#xD;
      been noted.&#xD;
&#xD;
      In recent years, many health care institutions in low and middle income countries have&#xD;
      established Nuclear Medicine (NM) imaging in routine clinical practice in conjunction with&#xD;
      modern Radiation Oncology (RO) facilities. The installation of hybrid PET/CT systems in these&#xD;
      countries permits more the increased use of PET/CT for both staging and radiotherapy&#xD;
      planning. However the successful implementation of PET/CT for radiotherapy planning (RTP)&#xD;
      requires a degree of expertise to safely and accurately implement this imaging technique. A&#xD;
      recently published review by the International Atomic Energy Agency (IAEA), about current&#xD;
      trends in NM in developing countries showed there is still lack of expertise, equipment and&#xD;
      human resources to gain benefit from this imaging technique. In RO, difficulties in the&#xD;
      implementation of this technique are mainly related to inadequate training of staff and lack&#xD;
      of local expertise.&#xD;
&#xD;
      Quality assurance of the PET/CT scanners might be compromised when not performed according to&#xD;
      accepted nuclear medicine quality assurance standards. Therefore, there is a concern that, if&#xD;
      used without appropriate training or expertise, suboptimal image quality may result and&#xD;
      inappropriate interpretation of the PET/CT for RTP may occur. In this study to help provide&#xD;
      PET Quality Control will be executed to aim for a standardized PET image quality that meets&#xD;
      the minimum requirements of European Association of Nuclear Medicine standards. Participating&#xD;
      centers will be assisted to earn the European Association of Nuclear Medicine (EANM) Research&#xD;
      Ltd (EARL) accreditation. The quality of the imaging can be influenced by physiological and&#xD;
      technical factors. The Standardized Uptake Value (SUV) allows for semi quantitative&#xD;
      evaluation in PET imaging, and is influenced by these factors. Spatial resolution affects SUV&#xD;
      values significantly and this parameter can differ a lot between multiple centers. The EANM&#xD;
      NEMA NU 2001/2007 2 Image Quality Phantom allows for standardization of PET imaging between&#xD;
      centers with different scanners, using the activity coefficient recovery curve (ACRC) as a&#xD;
      parameter for quantification of this spatial resolution.&#xD;
&#xD;
      It is already known that FDG PET/CT based RTP enables appropriate selection of patients who&#xD;
      will benefit from curative radiation therapy. One possible cause of failure in radiotherapy&#xD;
      is the inability to accurately define the tumor edges. In these patients there are no other&#xD;
      possible curative salvage treatment options and the disease is incurable. It is hoped that&#xD;
      FDG PET/CT based RTP will improve tumor volume delineation (TVD) and hence improve outcomes&#xD;
      following curative radiotherapy. There is also clear evidence that PET/CT standardizes TVD in&#xD;
      patients with NSCLC. However, what is not known is the impact of PET/CT based TVD on patient&#xD;
      outcomes such as survival as distinct from the benefit of PET/CT for patient selection for&#xD;
      curative treatment. Furthermore, the impact of a training intervention on the use of PET/CT&#xD;
      RTP in 2-year overall survival has not been studied to the best of our knowledge.&#xD;
&#xD;
      This study will evaluate the possible impact of the use of PET/CT for TVD on 2-year overall&#xD;
      survival in patients with stage III NSCLC referred for curative intent radiotherapy with&#xD;
      chemotherapy in low and middle income countries, this study involves a retrospective cohort&#xD;
      study, a training intervention, and a prospective cohort study. The training intervention&#xD;
      will focus on standard FDG PET/CT acquisition, FDG PET/CT image quality, staging procedure&#xD;
      for FDG PET/CT acquisition and FDG PET/CT for RTP acquisition and Tumor Volume Delineation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
  </study_design_info>
  <primary_outcome>
    <measure>2-year overall survival</measure>
    <time_frame>the included patients will be followed for a maximum of 2 years</time_frame>
    <description>Determine the impact of PET/CT in RTP on 2-year overall survival rates for patients with stage III NSCLC receiving chemoradiotherapy with curative intent. Patients from the retrospective cohort will be selected from the institutional database and were treated between 2010 to 2013. Patients from the prospective cohort will be selected until the end of 2015.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Observer agreement with expert contours as a measure of the effect of a training intervention on tumor volume delineation</measure>
    <time_frame>up to 5 months</time_frame>
    <description>Determine the impact of a PET/CT in RTP training intervention on tumor volume delineation for stage III NSCLC radiotherapy. Different parameters are used to determine the observer variation: Dice Index, median surface distances</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline PET/CT characteristics as a measure for PET/CT scanner performance</measure>
    <time_frame>up to 8 months</time_frame>
    <description>Determine the quality of PET/CT scanners. Study baseline PET/CT imaging protocols and image acquisition characteristics with the following parameters: recovery coefficients, spatial resolution measurement, and calibration of SUV determination. All centers will participate in the EARL accreditation programme.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">520</enrollment>
  <condition>Non Small Cell Lung Cancer Stage III</condition>
  <arm_group>
    <arm_group_label>Retrospective cohort</arm_group_label>
    <description>Participating centers will retrospectively provide demographic, tumor, treatment and follow-up details on at least 25 consecutive patients with stage III NSCLC previously treated with curative intent chemoradiotherapy (concurrent or sequential) in the period between 2010 and 2013.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prospective cohort</arm_group_label>
    <description>Participating centers will provide prospective data on patients with stage III NSCLC treated with curative intent concurrent chemoradiotherapy. Centers will be asked to include at least 25 consecutive cases following the training intervention and the successful local implementation of PET/CT for RTP in NSCLC.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The retrospective cohort study includes at least 250 patientswith stage III NSCLC with&#xD;
        curative intent chemoradiotherapy (sequential or concurrent), 125 patients in the first arm&#xD;
        (non PET staged) and 125 patients (PET staged) in the second arm. The prospective cohort&#xD;
        study includes at least 250 patients (PET staged) receiving concurrent chemoradiotherapy&#xD;
        based on PET/CT RTP. In total, we aim to include a number of 519 patients.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pathologically confirmed NSCLC&#xD;
&#xD;
          -  stage III as per local diagnostic protocol or agreement of local multidisciplinary&#xD;
             team&#xD;
&#xD;
          -  available for clinical follow-up for at least 2 years&#xD;
&#xD;
          -  suitable for treatment with a radical target volume in the opinion of a radiation&#xD;
             oncologist&#xD;
&#xD;
          -  ECOG performance 0 or 1&#xD;
&#xD;
          -  signed informed consent&#xD;
&#xD;
          -  ability to commence radiation therapy within 4 weeks of acquisition of the RTP PET/CT&#xD;
&#xD;
          -  suitable for concurrent chemoradiotherapy (prospective cohort only)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  other neoplasms in the last 5 years except non-melanoma skin cancer&#xD;
&#xD;
          -  stage IV disease diagnosed before acquisition of staging PET/CT&#xD;
&#xD;
          -  inability to provide informed consent&#xD;
&#xD;
          -  uncontrolled diabetes mellitus&#xD;
&#xD;
          -  pregnant or breast feeding mothers&#xD;
&#xD;
          -  tuberculosis&#xD;
&#xD;
          -  neo-adjuvant chemotherapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wouter V Vogel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Antoni van Leeuwenhoek - Netherlands Cancer Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gerard G Hanna, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for Cancer Research and Cell Biology, Queen's University Belfast</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tom Konert, BSc</last_name>
    <phone>0031205127954</phone>
    <email>t.konert@nki.nl</email>
  </overall_contact>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>September 19, 2014</last_update_submitted>
  <last_update_submitted_qc>September 19, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PET</keyword>
  <keyword>radiotherapy</keyword>
  <keyword>international</keyword>
  <keyword>NSCLC</keyword>
  <keyword>overall survival</keyword>
  <keyword>low and middle income countries</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</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/NCT02247713
org study id: M14PRI
nct id: NCT02247713
lead sponsor: 
collaborator: 
has dmc: No
A part retrospective, part prospective cohort study to assess the difference in 2-year
      overall survival in patients with stage III NSCLC receiving chemoradiotherapy with curative
      intent in low and middle income countries before and after a training intervention on the use
      of PET/CT for radiotherapy treatment planning.
Over the years, the incidence of lung cancer has risen in some low and middle income
      countries due to the rise in tobacco use. Patients commonly present with lung cancer in an
      advanced stage (stage III and IV) are not suitable for surgical resection, but may be
      considered for radiotherapy. For patients in those countries who are not suitable for
      surgical resection, radiotherapy offers the best chance of cure, best improvement in local
      cancer control, best palliation and fewest side-effects. For accurate patient selection for
      curative treatment and accurate staging of lung cancer, the use of fused
      18F-fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography (FDG PET/CT) imaging
      has been shown to be superior to CT alone. It has also been shown to have a significant
      impact when used in the radiation treatment planning process and in particular for when used
      for target volume delineation, where a significant reduction in interobserver variation has
      been noted.

      In recent years, many health care institutions in low and middle income countries have
      established Nuclear Medicine (NM) imaging in routine clinical practice in conjunction with
      modern Radiation Oncology (RO) facilities. The installation of hybrid PET/CT systems in these
      countries permits more the increased use of PET/CT for both staging and radiotherapy
      planning. However the successful implementation of PET/CT for radiotherapy planning (RTP)
      requires a degree of expertise to safely and accurately implement this imaging technique. A
      recently published review by the International Atomic Energy Agency (IAEA), about current
      trends in NM in developing countries showed there is still lack of expertise, equipment and
      human resources to gain benefit from this imaging technique. In RO, difficulties in the
      implementation of this technique are mainly related to inadequate training of staff and lack
      of local expertise.

      Quality assurance of the PET/CT scanners might be compromised when not performed according to
      accepted nuclear medicine quality assurance standards. Therefore, there is a concern that, if
      used without appropriate training or expertise, suboptimal image quality may result and
      inappropriate interpretation of the PET/CT for RTP may occur. In this study to help provide
      PET Quality Control will be executed to aim for a standardized PET image quality that meets
      the minimum requirements of European Association of Nuclear Medicine standards. Participating
      centers will be assisted to earn the European Association of Nuclear Medicine (EANM) Research
      Ltd (EARL) accreditation. The quality of the imaging can be influenced by physiological and
      technical factors. The Standardized Uptake Value (SUV) allows for semi quantitative
      evaluation in PET imaging, and is influenced by these factors. Spatial resolution affects SUV
      values significantly and this parameter can differ a lot between multiple centers. The EANM
      NEMA NU 2001/2007 2 Image Quality Phantom allows for standardization of PET imaging between
      centers with different scanners, using the activity coefficient recovery curve (ACRC) as a
      parameter for quantification of this spatial resolution.

      It is already known that FDG PET/CT based RTP enables appropriate selection of patients who
      will benefit from curative radiation therapy. One possible cause of failure in radiotherapy
      is the inability to accurately define the tumor edges. In these patients there are no other
      possible curative salvage treatment options and the disease is incurable. It is hoped that
      FDG PET/CT based RTP will improve tumor volume delineation (TVD) and hence improve outcomes
      following curative radiotherapy. There is also clear evidence that PET/CT standardizes TVD in
      patients with NSCLC. However, what is not known is the impact of PET/CT based TVD on patient
      outcomes such as survival as distinct from the benefit of PET/CT for patient selection for
      curative treatment. Furthermore, the impact of a training intervention on the use of PET/CT
      RTP in 2-year overall survival has not been studied to the best of our knowledge.

      This study will evaluate the possible impact of the use of PET/CT for TVD on 2-year overall
      survival in patients with stage III NSCLC referred for curative intent radiotherapy with
      chemotherapy in low and middle income countries, this study involves a retrospective cohort
      study, a training intervention, and a prospective cohort study. The training intervention
      will focus on standard FDG PET/CT acquisition, FDG PET/CT image quality, staging procedure
      for FDG PET/CT acquisition and FDG PET/CT for RTP acquisition and Tumor Volume Delineation.
observational model: Cohort
measure: 2-year overall survival
time frame: the included patients will be followed for a maximum of 2 years
description: Determine the impact of PET/CT in RTP on 2-year overall survival rates for patients with stage III NSCLC receiving chemoradiotherapy with curative intent. Patients from the retrospective cohort will be selected from the institutional database and were treated between 2010 to 2013. Patients from the prospective cohort will be selected until the end of 2015.
measure: Observer agreement with expert contours as a measure of the effect of a training intervention on tumor volume delineation
time frame: up to 5 months
description: Determine the impact of a PET/CT in RTP training intervention on tumor volume delineation for stage III NSCLC radiotherapy. Different parameters are used to determine the observer variation: Dice Index, median surface distances
measure: Baseline PET/CT characteristics as a measure for PET/CT scanner performance
time frame: up to 8 months
description: Determine the quality of PET/CT scanners. Study baseline PET/CT imaging protocols and image acquisition characteristics with the following parameters: recovery coefficients, spatial resolution measurement, and calibration of SUV determination. All centers will participate in the EARL accreditation programme.
arm group label: Retrospective cohort
description: Participating centers will retrospectively provide demographic, tumor, treatment and follow-up details on at least 25 consecutive patients with stage III NSCLC previously treated with curative intent chemoradiotherapy (concurrent or sequential) in the period between 2010 and 2013.
arm group label: Prospective cohort
description: Participating centers will provide prospective data on patients with stage III NSCLC treated with curative intent concurrent chemoradiotherapy. Centers will be asked to include at least 25 consecutive cases following the training intervention and the successful local implementation of PET/CT for RTP in NSCLC.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wouter V Vogel, MD
role: Principal Investigator
affiliation: Antoni van Leeuwenhoek - Netherlands Cancer Institute
last name: Gerard G Hanna, MD
role: Principal Investigator
affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast
last name: Tom Konert, BSc
phone: 0031205127954
email: t.konert@nki.nl
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung