title: A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer.
abstract: BACKGROUND
  Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases.
  
  
  METHODS
  This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome.
  
  
  CONCLUSIONS
  This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01191632.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Reissfelder
authors.forename: Carmen
authors.initials: C
authors.lastname: Timke
authors.forename: Hubertus
authors.initials: H
authors.lastname: Schmitz-Winnenthal
authors.forename: Nuh N
authors.initials: NN
authors.lastname: Rahbari
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
authors.forename: Felix
authors.initials: F
authors.lastname: Klug
authors.forename: Falk
authors.initials: F
authors.lastname: Roeder
authors.forename: Lutz
authors.initials: L
authors.lastname: Edler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology* / Q000532:radiotherapy*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000532:radiotherapy* / Q000556:secondary*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000528:radiation effects*; D008875:Middle Aged; D011879:Radiotherapy Dosage