xml: <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/NCT06029140</url>
    </required_header>
    <id_info>
      <org_study_id>29BRC23.0143 - POSTPONE</org_study_id>
      <nct_id>NCT06029140</nct_id>
    </id_info>
    <brief_title>Stereotactic Radiotherapy Management of Brain Metastases: the Value of a Longitudinal Multimodal Approach (POSTPONE)</brief_title>
    <acronym>POSTPONE</acronym>
    <official_title>Stereotactic Radiotherapy Management of Brain Metastases: the Value of a Longitudinal Multimodal Approach</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Brest</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital, Brest</source>
    <oversight_info>
      <has_dmc>No</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>
        The management of brain metastases has evolved́ rapidly in recent years. It is estimated that&#xD;
        20% to 40% of cancer patients will develop brain metastases (BM) during the course of their&#xD;
        disease. Whole-brain radiotherapy has long been the first-line treatment for brain&#xD;
        metastases. However, large-scale international clinical trials conducted over the past decade&#xD;
        have established stereotactic radiotherapy (SR) as the treatment of choice for the management&#xD;
        of brain metastases (BM). However, even though the method of radiation delivery has evolved&#xD;
        considerably, the problem of monitoring and managing brain metastases remains unresolved.&#xD;
  &#xD;
        This study therefore has several focuses:&#xD;
  &#xD;
          1. Evaluation of the benefit of early remnographic assessment (6 weeks): impact on&#xD;
             recurrence-free survival and overall survival.&#xD;
  &#xD;
          2. Evaluation of a diagnostic approach to radionecrosis: complementarity of DOPA PET and&#xD;
             multimodal MRI.&#xD;
  &#xD;
          3. The benefits of longitudinal remnographic monitoring with the development of&#xD;
             segmentation and automated follow-up tools&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The management of brain metastases has evolved́ rapidly in recent years. It is estimated that&#xD;
        20% to 40% of cancer patients will develop brain metastases (BM) during the course of their&#xD;
        disease. Whole-brain radiotherapy has long been the first-line treatment for brain&#xD;
        metastases. However, large-scale international clinical trials conducted over the past decade&#xD;
        have established stereotactic radiotherapy (SRT) as the treatment of choice for the&#xD;
        management of brain metastases (BM). However, even though the method of radiation delivery&#xD;
        has evolved considerably, the problem of monitoring and managing brain metastases remains&#xD;
        unresolved. Indeed, BM patients constitute a growing population due to the increased efficacy&#xD;
        of systemic treatments, making the occurrence of BM higher. Management of the disease is not&#xD;
        only aimed at alleviating symptoms and, initially, improving survival, but must also take&#xD;
        into account patients' quality of life. Patients with a poor prognosis should not be&#xD;
        over-treated, while those with a more favorable prognosis should not be under-treated.&#xD;
  &#xD;
        With this in mind, a number of tools were rapidly developed to grade the prognosis of&#xD;
        patients with BM. Recursive partitioning analysis (RPA) and Graded Prognostic Assessment&#xD;
        (GPA) are the main ones. They are based on prognostic factors that include age, Karnofsky&#xD;
        index, primary tumor control, presence of extracerebral localization, histological type and&#xD;
        presence of genetic mutations for each primary. Finally, we must also take into account the&#xD;
        growing involvement of systemic treatments in the control of brain disease when the&#xD;
        blood-brain barrier (BBB) is crossed.&#xD;
  &#xD;
        Several studies have shown that patients with symptomatic cerebral recurrences have poorer&#xD;
        survival and generate higher costs for the healthcare system than asymptomatic patients whose&#xD;
        recurrences have been detected by routine surveillance imaging. The importance of frequent&#xD;
        surveillance imaging is therefore essential. National Comprehensive Cancer Network (NCCN)&#xD;
        recommendations include MRI every 2-3 months for the first year, then every 4-6 months&#xD;
        indefinitely. The recommendations of the Association des Neuro-Oncologues d'Expression&#xD;
        Française (ANOCEF) recommend brain MRI at least every 3 months for the first year (9),&#xD;
        RECORAD recommends MRI surveillance every 3 months for the first 2 years, then every 6 months&#xD;
        (10), and Cancer Care Ontario Organization (CCO) recommends a 1st follow-up MRI 2 to 3 months&#xD;
        after the end of treatment, followed by MRI surveillance every 2 to 3 months for 1 year, and&#xD;
        MRI surveillance every 3 to 4 months for 2 to 3 years. Given the heterogeneity of follow-up&#xD;
        modalities, and the absence of any recommendation for surveillance MRI imaging earlier than 3&#xD;
        months after treatment, the Brest University Hospital decided to carry out an early&#xD;
        remnographic reassessment of patients treated with intracerebral stereotactic radiotherapy 6&#xD;
        weeks after the end of treatment, and then every 3 months for a minimum of 2 years.&#xD;
  &#xD;
        After SRT for brain metastases, the median time to development of a radiation-induced adverse&#xD;
        event or radionecrosis is 7 to 11 months. Similarly, the risk of local tumor recurrence after&#xD;
        SR is &lt; 5% after 18 months. In terms of complications, improvements in systemic therapy mean&#xD;
        that patients are living longer and are at greater risk of tumour recurrence later than&#xD;
        previously (defined as &gt; 18 months after SRT). Radionecrosis may therefore occur in up to 50%&#xD;
        of patients several months to several years after irradiation, depending on several factors,&#xD;
        including dose fractionation patterns and the volume of normal brain receiving high-dose&#xD;
        irradiation.&#xD;
  &#xD;
        Radionecrosis can produce symptoms difficult to distinguish from those of local progression&#xD;
        and, if left untreated, can lead to significant morbidity and mortality. Correct differential&#xD;
        diagnosis between radionecrosis and local progression is extremely important, as the two&#xD;
        situations must be managed differently. Surgery or re-irradiation is generally proposed as&#xD;
        salvage therapy in patients with local progression, whereas radionecrosis is most often&#xD;
        treated with corticosteroids.&#xD;
  &#xD;
        Differential diagnosis between radiation-induced changes and brain tumor recurrence is a&#xD;
        challenge in the treatment of brain metastases. The RANO (Response Assessment in&#xD;
        Neuro-Oncology) group has recognized that an approach based on a single imaging modality is&#xD;
        insufficient to establish a correct diagnosis. It recommends the use of advanced imaging&#xD;
        techniques, such as MRI with diffusion sequence and perfusion map, spectroscopy and PET.&#xD;
  &#xD;
        Several radiopharmaceuticals, including the amino acid tracers&#xD;
        O-(2-[18F]fluoroethyl)-L-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro- l-phenylalanine&#xD;
        (F-DOPA), have proved useful in distinguishing radionecrosis from local progression in&#xD;
        patients with brain metastases.&#xD;
  &#xD;
        Several observations can therefore be made:&#xD;
  &#xD;
          -  Heterogeneity of practices concerning remnographic surveillance, particularly at an&#xD;
             early stage.&#xD;
  &#xD;
          -  Heterogeneity in practices concerning suspicion of radionecrosis&#xD;
  &#xD;
        This study therefore has several focuses:&#xD;
  &#xD;
          1. Evaluation of the benefit of early remnographic assessment (6 weeks): impact on&#xD;
             recurrence-free survival and overall survival.&#xD;
  &#xD;
          2. Evaluation of a diagnostic approach to radionecrosis: complementarity of DOPA PET and&#xD;
             multimodal MRI.&#xD;
  &#xD;
          3. The benefits of longitudinal remnographic monitoring with the development of&#xD;
             segmentation and automated follow-up tools&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">July 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">July 1, 2024</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>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Risk factors of radionecrosis</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>The main objective is to identify risk factors for cerebral radionecrosis after stereotactic radiotherapy in patients treated for brain metastases.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Risk factors of local relapse</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>Clinical, dosimetric and radiological factors influencing local control</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Post-SRT follow-up</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>Practical analysis of the benefits of performing MRI 6 weeks after the end of stereotactic radiotherapy treatment, and determining precise criteria to better target patients who would benefit most from it.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Automatic segmentation of brain metastasis</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>Development of a deep-learning algorithm for the automatic segmentation on MRI, CT and CT scanners</description>
    </other_outcome>
    <other_outcome>
      <measure>Automatic follow-up</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>Development of a deep-learning algorithm for the automatic longitudinal follow-up</description>
    </other_outcome>
    <enrollment type="Anticipated">700</enrollment>
    <condition>Brain Metastases, Adult</condition>
    <eligibility>
      <study_pop>
        <textblock>
          Patient treated with intracerebral stereotactic radiotherapy at the Brest University&#xD;
          Hospital as part of the management of a secondary localization of a primary solid cancer.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age ≥ 18 years&#xD;
  &#xD;
            -  Patients with solid cancer with brain metastases treated by hypofractionated external&#xD;
               stereotactic radiotherapy at the CHRU de Brest between 01/01/2014 and 31/12/2022&#xD;
  &#xD;
            -  Patient affiliated to a social security scheme&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with primary brain tumors&#xD;
  &#xD;
            -  Patients treated with normofractionated external cerebral radiotherapy&#xD;
  &#xD;
            -  Age &lt; 18 years&#xD;
  &#xD;
            -  Patients under legal protection (guardianship, curatorship, etc.)&#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>Vincent Bourbonne, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Radiation Oncology Department, Brest University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Vincent BOURBONNE, MD, PhD</last_name>
      <phone>+33298223398</phone>
      <email>vincent.bourbonne@chu-brest.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>Chu Brest</name>
        <address>
          <city>Brest</city>
          <zip>29609</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Vincent Bourbonne, MD, PhD</last_name>
        <email>vincent.bourbonne@chu-brest.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>stereotactic radiotherapy</keyword>
    <keyword>radionecrosis</keyword>
    <keyword>local relapse</keyword>
    <keyword>PET DOPA</keyword>
    <keyword>Multimodal MRI</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasm Metastasis</mesh_term>
      <mesh_term>Brain Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>All collected data that underlie results in a publication</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>Data will be available beginning three years and ending fifteen years following the final study report completion</ipd_time_frame>
      <ipd_access_criteria>Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06029140
  org study id: 29BRC23.0143 - POSTPONE
  nct id: NCT06029140
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The management of brain metastases has evolved́ rapidly in recent years. It is estimated that
        20% to 40% of cancer patients will develop brain metastases (BM) during the course of their
        disease. Whole-brain radiotherapy has long been the first-line treatment for brain
        metastases. However, large-scale international clinical trials conducted over the past decade
        have established stereotactic radiotherapy (SR) as the treatment of choice for the management
        of brain metastases (BM). However, even though the method of radiation delivery has evolved
        considerably, the problem of monitoring and managing brain metastases remains unresolved.
  
        This study therefore has several focuses:
  
          1. Evaluation of the benefit of early remnographic assessment (6 weeks): impact on
             recurrence-free survival and overall survival.
  
          2. Evaluation of a diagnostic approach to radionecrosis: complementarity of DOPA PET and
             multimodal MRI.
  
          3. The benefits of longitudinal remnographic monitoring with the development of
             segmentation and automated follow-up tools
  The management of brain metastases has evolved́ rapidly in recent years. It is estimated that
        20% to 40% of cancer patients will develop brain metastases (BM) during the course of their
        disease. Whole-brain radiotherapy has long been the first-line treatment for brain
        metastases. However, large-scale international clinical trials conducted over the past decade
        have established stereotactic radiotherapy (SRT) as the treatment of choice for the
        management of brain metastases (BM). However, even though the method of radiation delivery
        has evolved considerably, the problem of monitoring and managing brain metastases remains
        unresolved. Indeed, BM patients constitute a growing population due to the increased efficacy
        of systemic treatments, making the occurrence of BM higher. Management of the disease is not
        only aimed at alleviating symptoms and, initially, improving survival, but must also take
        into account patients' quality of life. Patients with a poor prognosis should not be
        over-treated, while those with a more favorable prognosis should not be under-treated.
  
        With this in mind, a number of tools were rapidly developed to grade the prognosis of
        patients with BM. Recursive partitioning analysis (RPA) and Graded Prognostic Assessment
        (GPA) are the main ones. They are based on prognostic factors that include age, Karnofsky
        index, primary tumor control, presence of extracerebral localization, histological type and
        presence of genetic mutations for each primary. Finally, we must also take into account the
        growing involvement of systemic treatments in the control of brain disease when the
        blood-brain barrier (BBB) is crossed.
  
        Several studies have shown that patients with symptomatic cerebral recurrences have poorer
        survival and generate higher costs for the healthcare system than asymptomatic patients whose
        recurrences have been detected by routine surveillance imaging. The importance of frequent
        surveillance imaging is therefore essential. National Comprehensive Cancer Network (NCCN)
        recommendations include MRI every 2-3 months for the first year, then every 4-6 months
        indefinitely. The recommendations of the Association des Neuro-Oncologues d'Expression
        Française (ANOCEF) recommend brain MRI at least every 3 months for the first year (9),
        RECORAD recommends MRI surveillance every 3 months for the first 2 years, then every 6 months
        (10), and Cancer Care Ontario Organization (CCO) recommends a 1st follow-up MRI 2 to 3 months
        after the end of treatment, followed by MRI surveillance every 2 to 3 months for 1 year, and
        MRI surveillance every 3 to 4 months for 2 to 3 years. Given the heterogeneity of follow-up
        modalities, and the absence of any recommendation for surveillance MRI imaging earlier than 3
        months after treatment, the Brest University Hospital decided to carry out an early
        remnographic reassessment of patients treated with intracerebral stereotactic radiotherapy 6
        weeks after the end of treatment, and then every 3 months for a minimum of 2 years.
  
        After SRT for brain metastases, the median time to development of a radiation-induced adverse
        event or radionecrosis is 7 to 11 months. Similarly, the risk of local tumor recurrence after
        SR is < 5% after 18 months. In terms of complications, improvements in systemic therapy mean
        that patients are living longer and are at greater risk of tumour recurrence later than
        previously (defined as > 18 months after SRT). Radionecrosis may therefore occur in up to 50%
        of patients several months to several years after irradiation, depending on several factors,
        including dose fractionation patterns and the volume of normal brain receiving high-dose
        irradiation.
  
        Radionecrosis can produce symptoms difficult to distinguish from those of local progression
        and, if left untreated, can lead to significant morbidity and mortality. Correct differential
        diagnosis between radionecrosis and local progression is extremely important, as the two
        situations must be managed differently. Surgery or re-irradiation is generally proposed as
        salvage therapy in patients with local progression, whereas radionecrosis is most often
        treated with corticosteroids.
  
        Differential diagnosis between radiation-induced changes and brain tumor recurrence is a
        challenge in the treatment of brain metastases. The RANO (Response Assessment in
        Neuro-Oncology) group has recognized that an approach based on a single imaging modality is
        insufficient to establish a correct diagnosis. It recommends the use of advanced imaging
        techniques, such as MRI with diffusion sequence and perfusion map, spectroscopy and PET.
  
        Several radiopharmaceuticals, including the amino acid tracers
        O-(2-[18F]fluoroethyl)-L-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro- l-phenylalanine
        (F-DOPA), have proved useful in distinguishing radionecrosis from local progression in
        patients with brain metastases.
  
        Several observations can therefore be made:
  
          -  Heterogeneity of practices concerning remnographic surveillance, particularly at an
             early stage.
  
          -  Heterogeneity in practices concerning suspicion of radionecrosis
  
        This study therefore has several focuses:
  
          1. Evaluation of the benefit of early remnographic assessment (6 weeks): impact on
             recurrence-free survival and overall survival.
  
          2. Evaluation of a diagnostic approach to radionecrosis: complementarity of DOPA PET and
             multimodal MRI.
  
          3. The benefits of longitudinal remnographic monitoring with the development of
             segmentation and automated follow-up tools
  observational model: Cohort
  time perspective: Retrospective
  measure: Risk factors of radionecrosis
  time frame: Through study completion, an average of 1 year
  description: The main objective is to identify risk factors for cerebral radionecrosis after stereotactic radiotherapy in patients treated for brain metastases.
  measure: Risk factors of local relapse
  time frame: Through study completion, an average of 1 year
  description: Clinical, dosimetric and radiological factors influencing local control
  measure: Post-SRT follow-up
  time frame: Through study completion, an average of 1 year
  description: Practical analysis of the benefits of performing MRI 6 weeks after the end of stereotactic radiotherapy treatment, and determining precise criteria to better target patients who would benefit most from it.
  measure: Automatic segmentation of brain metastasis
  time frame: Through study completion, an average of 1 year
  description: Development of a deep-learning algorithm for the automatic segmentation on MRI, CT and CT scanners
  measure: Automatic follow-up
  time frame: Through study completion, an average of 1 year
  description: Development of a deep-learning algorithm for the automatic longitudinal follow-up
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Vincent Bourbonne, MD, PhD
  role: Principal Investigator
  affiliation: Radiation Oncology Department, Brest University Hospital
  last name: Vincent BOURBONNE, MD, PhD
  phone: +33298223398
  email: vincent.bourbonne@chu-brest.fr
  facility: 
  status: Recruiting
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Neoplasm Metastasis
  mesh term: Brain Neoplasms
  sharing ipd: Yes
  ipd description: All collected data that underlie results in a publication
  ipd info type: Study Protocol
  ipd time frame: Data will be available beginning three years and ending fifteen years following the final study report completion
  ipd access criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement