<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/NCT03771404</url>
  </required_header>
  <id_info>
    <org_study_id>CT/17.01</org_study_id>
    <nct_id>NCT03771404</nct_id>
  </id_info>
  <brief_title>NSCLC Heterogeneity in Early Stage Patients and Prediction of Relapse Using a Personalized &quot;Liquid Biopsy&quot;</brief_title>
  <official_title>Evaluation of Non-small Cell Lung Carcinoma Genetic Heterogeneity in Patients With Operable Early Stage Disease and Prediction of Clinical Relapse Using a Personalized &quot;Liquid Biopsy&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hellenic Oncology Research Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hellenic Oncology Research Group</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 purpose of his study is to investigate the intra tumor heterogeneity of the primary tumor&#xD;
      and the involved lymph nodes from patients with resectable NSCLC, to detect primary tumor&#xD;
      genetic alternations using &quot;liquid biopsy&quot; during the patients' clinical follow up and to&#xD;
      correlate the &quot;liquid biopsy&quot; information with the disease recurrence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lung cancer is the most common cancer in the world. In operable early stage patients NSCLS&#xD;
      can be curable, but even after complete primary tumor resection, about 45% of early stage&#xD;
      patients develop local or distant recurrence within 8-18 months. Recent studies have&#xD;
      established that targeted therapies may fail to cure the disease because of tumor&#xD;
      heterogeneity. The presence of genetic heterogeneity in different portions of a tumor have&#xD;
      demonstrated its importance in tumor biology suggesting that pre-existing genetically&#xD;
      different sub clones may be selected by therapy or differentially involved in the metastatic&#xD;
      process, leading to treatment failure.&#xD;
&#xD;
      The relationship of tumor heterogeneity with the poor clinical outcome suggests that its&#xD;
      assessment could provide interesting and useful clinical information, especially, in terms of&#xD;
      prognosis and treatment selection. It is now, well established that during the evolution of&#xD;
      tumor new cellular clones could be emerged which differ genetically from the molecular&#xD;
      signature of tumor cells evaluated at the time of initial diagnosis. This molecular evolution&#xD;
      may further contribute to the tumor heterogeneity during the disease progression. The&#xD;
      evaluation of the real-time molecular tumor heterogeneity requires repeated re-biopsies&#xD;
      during the different clinical phases of NSCLC which, however, are invasive and not, always,&#xD;
      feasible. This problem can be by-passed by the use of tumor-originating elements in the&#xD;
      plasma and among these cellular products the isolation and analysis of cell tumor DNA (ctDNA)&#xD;
      and the characterization of Circulating Tumor Cells (CTCs) represent important tools for&#xD;
      identification and monitoring of molecular tumor alterations in cancer patients, representing&#xD;
      what the investigators call &quot;liquid biopsy&quot;. ctDNA is originated from cellular necrosis due&#xD;
      to increased tumoral cellular turnover and cellular ischemia as well as from apoptosis of&#xD;
      tumor cells or lysis of Circulating Tumor Cells (CTCs). On the other hand, the CTCs, which&#xD;
      designate the cells circulating in the blood, can be detected in several tumor types,&#xD;
      irrespectively of the clinical phase, and their detection has been correlated with disease&#xD;
      progression and treatment resistance. Therefore, the concomitant analysis of both ctDNA and&#xD;
      CTCs could permit to better evaluate the genetic heterogeneity of the tumor since they&#xD;
      continuously released from tumor cells throughout the clinical course of the disease and is&#xD;
      considered to be proportional to tumor burden and tumor progression at each time-point.&#xD;
&#xD;
      This is a multicenter, single arm, non-randomized translational research study. Patients with&#xD;
      operable NSCLC will be enrolled in the study. Patients' peripheral blood will be obtained&#xD;
      before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6&#xD;
      months thereafter until disease progression and upon disease relapse for the evaluation of&#xD;
      ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph&#xD;
      nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as&#xD;
      well.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 5, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate whether the individual patient's molecular landscape of ctDNA and CTCs could be reliable biomarkers for the early prediction of disease relapse.</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by ddPCR, for a 2-year period or until PD. For each subject, molecular analysis results will be correlated with its clinical outcome in terms of time to disease progression (PFS). CTCs will be isolated based on the cell's size. CTCs isolated by ISET will be phenotypically characterized to define their proliferative, apoptotic, EMT status as well as their immune profile using antibodies and immunofluorescent staining. CTCs isolated by PARSORTIX will be analyzed for the detection of specific genetic changes present in the primary tumor (see NGS analysis of primary tumor) using either qRT-PCR or FISH analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To investigate the genetic heterogeneity in resectable NSCLC</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To monitor using &quot;liquid biopsy&quot; the tumor clonal evolution during the post operation period and define a correlation between the genotype of the primary tumor and the emergence of molecularly different clones</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by droplet digital Polymerase Chain Reaction (ddPCR), for a 2-year period or until PD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To investigate the potential of longitudinal &quot;liquid biopsy&quot; to predict the genetic profile of metastasis</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by droplet digital Polymerase Chain Reaction (ddPCR), for a 2-year period or until PD. Moreover, in patients where metastasis re-biopsy is feasible the metastasis tumor will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the set of genes mentioned above. Correlation between the molecular analysis of the primary tumor, the ctDNA and the metastasis tumor will reveal whether longitudinal liquid biopsy can predict the metastasis genetic profile.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Operable (stages I-IIIA) NSCLC</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>For Operable (stages I-IIIA) NSCLC Patients, blood sampling and tissue samples of the primary tumor as well as the regional involved lymph nodes and, in selected patients, from biopsies from metastasis</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood sampling</intervention_name>
    <description>Patients' peripheral blood will be obtained before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6 months thereafter until disease progression and upon disease relapse for the evaluation of ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as well.</description>
    <arm_group_label>Operable (stages I-IIIA) NSCLC</arm_group_label>
    <other_name>primary tumor sampling after surgery</other_name>
    <other_name>biopsy from metastatic sites in selected patetients</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed NSCLC (adenocarcinoma and squamous cell carcinoma).&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Operable (stages I-IIIA) NSCLC&#xD;
&#xD;
          -  Patients with signed written informed consent obtained according to local guidelines&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients &lt; 18 years&#xD;
&#xD;
          -  Patients with non operable NSCLC (regardless of disease stage)&#xD;
&#xD;
          -  Patients who have any current or prior medical condition that may interfere with the&#xD;
             conduct of the study or the evaluation of its results in the opinion of the&#xD;
             Investigator&#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>Athanasios Kotsakis, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chairman of the Lung Cancer Working Group of the HORG</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Vassilis Georgoulias, MD, PhD</last_name>
    <phone>+302106448450</phone>
    <email>georgulv@otenet.gr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Efthimios Prinarakis, PhD</last_name>
    <phone>+302106448450</phone>
    <email>eprinarakis@horg.gr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>2nd Pneumological Dept, GNA &quot;Sotiria&quot;</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aggeliki Rapti, MD</last_name>
    </contact>
    <investigator>
      <last_name>Aggeliki Rapti, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>7th Pneumological Dept, GNA &quot;Sotiria&quot;</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mina Gaga, MD</last_name>
    </contact>
    <investigator>
      <last_name>Mina Gaga, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Thoracic Surgery Dept, GNA &quot;Sotiria&quot;</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Evaggelos Sepsas, MD</last_name>
    </contact>
    <investigator>
      <last_name>Evaggelos Sepsas, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Thoracic Surgery Clinic, &quot;Hygeia&quot; Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>15123</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Kosmas Iliadis, MD</last_name>
    </contact>
    <investigator>
      <last_name>Kosmas Iliadis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oncology Unit, 3rd Department of Medicine Athens University School of Medicine Athens, GNA &quot;Sotiria&quot;</name>
      <address>
        <city>Athens</city>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Konstantinos Syrigos, MD,PhD,FCCP</last_name>
    </contact>
    <investigator>
      <last_name>Konstantinos Syrigos, MD,PhD,FCCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>IASO General Hospital</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vassilis Georgoulias, MD, PhD</last_name>
      <phone>+302106502639</phone>
    </contact>
    <investigator>
      <last_name>Vassilis Georgoulias, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>November 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>December 7, 2018</last_update_submitted>
  <last_update_submitted_qc>December 7, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NSCLC</keyword>
  <keyword>Tumor heterogeneity</keyword>
  <keyword>liquid biopsy</keyword>
  <keyword>CTCs</keyword>
  <keyword>ctDNA</keyword>
  <keyword>NGS</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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03771404
org study id: CT/17.01
nct id: NCT03771404
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of his study is to investigate the intra tumor heterogeneity of the primary tumor
      and the involved lymph nodes from patients with resectable NSCLC, to detect primary tumor
      genetic alternations using "liquid biopsy" during the patients' clinical follow up and to
      correlate the "liquid biopsy" information with the disease recurrence.
Lung cancer is the most common cancer in the world. In operable early stage patients NSCLS
      can be curable, but even after complete primary tumor resection, about 45% of early stage
      patients develop local or distant recurrence within 8-18 months. Recent studies have
      established that targeted therapies may fail to cure the disease because of tumor
      heterogeneity. The presence of genetic heterogeneity in different portions of a tumor have
      demonstrated its importance in tumor biology suggesting that pre-existing genetically
      different sub clones may be selected by therapy or differentially involved in the metastatic
      process, leading to treatment failure.

      The relationship of tumor heterogeneity with the poor clinical outcome suggests that its
      assessment could provide interesting and useful clinical information, especially, in terms of
      prognosis and treatment selection. It is now, well established that during the evolution of
      tumor new cellular clones could be emerged which differ genetically from the molecular
      signature of tumor cells evaluated at the time of initial diagnosis. This molecular evolution
      may further contribute to the tumor heterogeneity during the disease progression. The
      evaluation of the real-time molecular tumor heterogeneity requires repeated re-biopsies
      during the different clinical phases of NSCLC which, however, are invasive and not, always,
      feasible. This problem can be by-passed by the use of tumor-originating elements in the
      plasma and among these cellular products the isolation and analysis of cell tumor DNA (ctDNA)
      and the characterization of Circulating Tumor Cells (CTCs) represent important tools for
      identification and monitoring of molecular tumor alterations in cancer patients, representing
      what the investigators call "liquid biopsy". ctDNA is originated from cellular necrosis due
      to increased tumoral cellular turnover and cellular ischemia as well as from apoptosis of
      tumor cells or lysis of Circulating Tumor Cells (CTCs). On the other hand, the CTCs, which
      designate the cells circulating in the blood, can be detected in several tumor types,
      irrespectively of the clinical phase, and their detection has been correlated with disease
      progression and treatment resistance. Therefore, the concomitant analysis of both ctDNA and
      CTCs could permit to better evaluate the genetic heterogeneity of the tumor since they
      continuously released from tumor cells throughout the clinical course of the disease and is
      considered to be proportional to tumor burden and tumor progression at each time-point.

      This is a multicenter, single arm, non-randomized translational research study. Patients with
      operable NSCLC will be enrolled in the study. Patients' peripheral blood will be obtained
      before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6
      months thereafter until disease progression and upon disease relapse for the evaluation of
      ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph
      nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as
      well.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: To evaluate whether the individual patient's molecular landscape of ctDNA and CTCs could be reliable biomarkers for the early prediction of disease relapse.
time frame: Up to 2 years
description: The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by ddPCR, for a 2-year period or until PD. For each subject, molecular analysis results will be correlated with its clinical outcome in terms of time to disease progression (PFS). CTCs will be isolated based on the cell's size. CTCs isolated by ISET will be phenotypically characterized to define their proliferative, apoptotic, EMT status as well as their immune profile using antibodies and immunofluorescent staining. CTCs isolated by PARSORTIX will be analyzed for the detection of specific genetic changes present in the primary tumor (see NGS analysis of primary tumor) using either qRT-PCR or FISH analysis.
measure: To investigate the genetic heterogeneity in resectable NSCLC
time frame: Up to 2 years
description: The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63.
measure: To monitor using "liquid biopsy" the tumor clonal evolution during the post operation period and define a correlation between the genotype of the primary tumor and the emergence of molecularly different clones
time frame: Up to 2 years
description: The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by droplet digital Polymerase Chain Reaction (ddPCR), for a 2-year period or until PD.
measure: To investigate the potential of longitudinal "liquid biopsy" to predict the genetic profile of metastasis
time frame: Up to 2 years
description: The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by droplet digital Polymerase Chain Reaction (ddPCR), for a 2-year period or until PD. Moreover, in patients where metastasis re-biopsy is feasible the metastasis tumor will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the set of genes mentioned above. Correlation between the molecular analysis of the primary tumor, the ctDNA and the metastasis tumor will reveal whether longitudinal liquid biopsy can predict the metastasis genetic profile.
arm group label: Operable (stages I-IIIA) NSCLC
arm group type: Other
description: For Operable (stages I-IIIA) NSCLC Patients, blood sampling and tissue samples of the primary tumor as well as the regional involved lymph nodes and, in selected patients, from biopsies from metastasis
intervention type: Other
intervention name: blood sampling
description: Patients' peripheral blood will be obtained before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6 months thereafter until disease progression and upon disease relapse for the evaluation of ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as well.
arm group label: Operable (stages I-IIIA) NSCLC
other name: primary tumor sampling after surgery
other name: biopsy from metastatic sites in selected patetients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Athanasios Kotsakis, MD, PhD
role: Principal Investigator
affiliation: Chairman of the Lung Cancer Working Group of the HORG
last name: Vassilis Georgoulias, MD, PhD
phone: +302106448450
email: georgulv@otenet.gr
last name: Efthimios Prinarakis, PhD
phone: +302106448450
email: eprinarakis@horg.gr
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Greece
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No