A randomized phase II study of radiation induced immune boost in operable non-small cell lung cancer (RadImmune trial)

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/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: NCT02319408; Registration: December 29, 2014.