Multimodal Hypoxia Imaging and Intensity Modulated Radiotherapy for Inoperable Non-small-cell Lung Cancer

Radiotherapy, preferably combined with chemotherapy, is the treatment standard for locally advanced, unresectable non-small cell lung cancer (NSCLC). The tumor response to different therapy protocols is variable, with hypoxia known to be a major factor that negatively influences treatment effectiveness. Visualisation of tumor hypoxia prior to the use of modern radiation therapy strategies, such as intensity modulated radiation therapy (IMRT), might allow higher dose applications to the target volume, leading to improvement of therapy outcome. 18F-fluoromisonidazole dynamic positron emission tomography and computed tomography (18F-FMISO dPET-CT) and functional magnetic resonance imaging (functional MRI) are attractive strategies for imaging tumor hypoxia. The HIL trial is a single centre pilot study combining multimodal hypoxia imaging with 18F-FMISO dPET-CT and functional MRI and intensity modulated radiation therapy (IMRT) in patients with inoperable stage III NSCLC. 15 patients are recruited in the study. All patients undergo serial 18F-FMISO dPET-CT and functional MRI before treatment, at week 5 of radiotherapy and 6 weeks post treatment. Radiation therapy is performed as inversely planned IMRT after four dimensional computed tomography (4D-CT) based target volume definition. Hypoxia imaging is not included in target volume definition or IMRT dose prescription. Objectives of the trial are to characterize the correlation of 18F-FMISO dPET-CT and functional MRI for tumor hypoxia imaging in NSCLC and evaluate possible effects of radiation therapy on tumor re-oxygenation. Further objectives include the generation of data regarding the prognostic value of 18F-FMISO dPET-CT and functional MRI for locoregional control, progression free survival and overall survival of NSCLC treated with IMRT, which will form the basis for larger clinical trials focusing on possible interactions between tumor oxygenation and radiation outcome.