Multimodal Hypoxia Imaging and Intensity Modulated Radiotherapy for Inoperable Non-small-cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Standard uptake value (SUV) of 18F-FMISO and k1 and k2 parameters
研究概览
简要总结
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.
详细描述
The HIL-trial has been designed by the study initiators at the Clinical Cooperation Unit Radiation Oncology at the German Cancer Research Center (DKFZ), the Clinical Cooperation Unit Nuclear Medicine at DKFZ, the Department of Radiology at DKFZ and the Department of Radiation Oncology at the University Clinic Heidelberg. The trial is carried out at DKFZ in co-operation with the Department of Radiation Oncology at the University Clinic Heidelberg.
Aim of the study is to characterize the correlation of 18F-FMISO dPET-CT and functional MRI for tumor hypoxia imaging in patients with stage III NSCLC, treated with intensity modulated radiotherapy (IMRT) and evaluate changes in tumor oxygenation during radiation treatment. Objectives include the evaluation of the prognostic value of multimodal hypoxia imaging for locoregional control, progression free survival and overall survival of patients with NSCLC treated with IMRT.
The study is designed as a single centre pilot trial with an accrual of 15 patients with inoperable stage III NSCLC. Patients fulfilling the inclusion criteria are treated with intensity modulated radiation therapy (IMRT). All patients undergo serial 18F-FMISO dPET-CT and functional MRI before treatment, at week 5 of radiotherapy and 6 weeks post treatment.
Eligible patients are informed about participation in the trial with possible benefits and risks, and written informed consent is obtained. Staging is completed through performance of thoracic CT scan, abdominal ultrasound and 18F-FDG dPET-CT scan.
After immobilization in a vacuum mattress a contrast-enhanced thoracic CT scan including four dimensional respiratory triggering is carried out. CT data are synchronized with the recorded respiratory signal and four-dimensional reconstructions are performed to evaluate the motion of the thoracic organs and the tumor during the breathing cycle. Based on the 4D-CT data set, radiation treatment planning is carried out as inverse planning.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented inoperable, histologically confirmed NSCLC stage III
- •Sufficient remaining lung function (FeV1>1.5 l/s or at least 50 % of the respective individual norm value)
- •Karnofsky Performance Score of 70 % or higher.
- •Patients > 18 years of age.
- •Adequate haematological function (wbc>3000 x 10^3 /ml, thc >100 ×10^6 /ml, Hb>10 g/dl)
- •Adequate hepatic and renal function
- •Written informed consent
排除标准
- •Patient refusal
- •Severe concurrent systemic disease
- •Claustrophobia
- •Cardiac pacemaker
- •Other malignancies
- •Hypersensitivity to x-ray contrast medium or 18F-FMISO
- •Severe renal or hepatic insufficiency
- •NSCLC stage I, II or IV
- •Pregnancy or lactation
结局指标
主要结局
Standard uptake value (SUV) of 18F-FMISO and k1 and k2 parameters
时间窗: 3 months
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).
次要结局
- Local recurrence rate(2 years)
- Progression free survival(2 years)
- Overall survival(2 years)