Multimodal Hypoxia Imaging and Intensity Modulated Radiotherapy for Inoperable Non-small-cell Lung Cancer (HIL)
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
- Standard uptake value (SUV) of 18F-FMISO and k1 and k2 parameters [ Time Frame: 3 months ] [ Designated as safety issue: No ]Primary aim of the study is to assess the correlation between measurements of the standard uptake value (SUV) of 18F-FMISO, as well as measurements of the parameters k1 and k2, which reflect the influx and efflux of FMISO into and out of the cells with functional MRI parameters, such as diffusion coefficients in matched regions of interest in patients with stage III NSCLC treated with intensity modulated radiation therapy (IMRT).
- Local recurrence rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessement of the prognostic value of serial 18F-FMISO dPET-CT and functional MRI for 1-year and 2-year local recurrence rate.
- Progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessement of the prognostic value of serial 18F-FMISO dPET-CT and functional MRI for 1-year and 2-year progression free survival.
- Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessement of the prognostic value of serial 18F-FMISO dPET-CT and functional MRI for overall survival.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Other: Multimodal hypoxia imaging
|Contact: Christian Thieke, Dr. med. Dr. rer. nat.||0049 (0) 6221 firstname.lastname@example.org|
|Contact: Vasileios Askoxylakis, Dr. med.||0049 (0) 6221 email@example.com|
|German Cancer Research Center||Recruiting|
|Heidelberg, Baden-Württemberg, Germany, 69120|
|Contact: Christian Thieke, Dr. med. Dr. rer. nat. 0049 (0) 6221 422544 firstname.lastname@example.org|
|Contact: Vasileios Askoxylakis, Dr. med. 0049 (0) 6221 422616 email@example.com|
|Principal Investigator: Jürgen Debus, Professor|
|Principal Investigator:||Jürgen Debus, Professor||University Clinic Heidelberg and German Cancer Research Center|