title: A randomized phase II study of radiation induced immune boost in operable non-small cell lung cancer (RadImmune trial).
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer deaths worldwide. Surgery, radiotherapy at conventional and high dose and chemotherapy are the mainstay for lung cancer treatment. Insufficient migration and activation of tumour specific effector T cells seem to be important reasons for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer.
  
  
  METHODS
  This trial has been designed as an investigator-initiated, prospective, randomized, 2-armed phase II trial. Patients who are candidates for elective resection of early stage non-small cell lung cancer will be randomized into 2 arms. A total of 36 patients will be enrolled. The patients receive either 2 Gy or no radiation prescribed to their primary tumour. Radiation will be delivered by external beam radiotherapy using 3D radiotherapy or intensity-modulated radiation technique (IMRT) 7 days prior to surgical resection. The primary objective is to compare CD8+ T cell counts detected by immunohistochemistry in resected tumours following preoperative radiotherapy versus no radiotherapy. Secondary objectives include the association between CD8+ T cell counts and progression free survival, the correlation of CD8+ T cell counts quantified by immunohistochemistry and flow cytometry, local tumour control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality. Further, frequencies of tumour reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome.
  
  
  CONCLUSIONS
  This unique intervention combining preoperative low dose radiation and surgical removal of early stage non-small cell lung cancer is designed to address the problem of inadequate host anti-tumour immune response. If successful, this study may affect the role of radiotherapy in lung cancer treatment.
  
  
  BACKGROUND
  NCT02319408;
  
  
  BACKGROUND
  December 29, 2014.
authors.affiliation: Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany. seyer.safi@med.uni-heidelberg.de.
authors.forename: Seyer
authors.initials: S
authors.lastname: Safi
authors.affiliation: Translational Immunology Unit, German Cancer Research Center, Heidelberg, Germany. p.beckhove@dkfz.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
authors.affiliation: Division of Thoracic Pathology, Institute of Pathology, Heidelberg, Germany. arne.warth@med.uni-heidelberg.de.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany. a.benner@dkfz.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.affiliation: Departments of Molecular and Radiation Oncology, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany. Falk.Roeder@med.uni-muenchen.de.|Present address: Department Radiation Oncology, University Hospital Munich (LMU), Munich, Germany. Falk.Roeder@med.uni-muenchen.de.
authors.forename: Falk
authors.initials: F
authors.lastname: Roeder
authors.affiliation: Departments of Molecular and Radiation Oncology, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany. stefan.rieken@med.uni-heidelberg.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rieken
authors.affiliation: Departments of Molecular and Radiation Oncology, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany. juergen.debus@med.uni-heidelberg.de.
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
authors.affiliation: Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany. hendrik.dienemann@med.uni-heidelberg.de.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.affiliation: Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany. hans.hoffmann@med.uni-heidelberg.de.
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
authors.affiliation: Departments of Molecular and Radiation Oncology, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany. p.huber@dkfz.de.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000532:radiotherapy*; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000532:radiotherapy*; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods