Image-derived Prediction of Response to Chemo-radiation in Glioblastoma

Study Overview
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Brief Summary
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This study seeks to investigate if advanced image-analysis of diagnostic scans, can be used to predict how aggressive brain tumors (glioblastoma) respond to standard chemo- and radiation treatment.

Detailed Description
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Generally, response prediction models seeks to predict time to an event, e.g. time-to-progression and/or overall survival. The aim of this study is to explore the feasibility of establishing an individualized response model, that, based on several morphologic, physiologic and metabolic parameters extracted from computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI), is able to predict the tumor response at the level of an imaging voxel, using machine learning techniques. Imaging modalities include MRI, PET/CT with 18F-fluroethyltyrosine (18F-FET), and PET/MRI with 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM).

Official Title
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Image-derived Prediction of Response to Chemo-radiation in Patients With Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Radiation: Radiotherapy
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, primary supratentorial glioblastoma (WHO grade IV). Exclusion Criteria: No informed consent can be obtained Inability to undergo MRI examination, due to metal implants, pacemaker etc. Not eligible for Stupp-regimen

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Standard chemoradiotherapy<br>Group to receive 60 Gy radiotherapy in 30 fractions with concomitant and adjuvant temozolomide. | Radiation: Radiotherapy<br>* 60 Gy in 30 fractions, 5 days a week, modulated arc therapy.<br>Drug: Temozolomide<br>* Concomitant: 75 mg/m2 5 days a week from start of radiotherapy. Adjuvant: 150/200 mg/m2 in 5 days per 28 days in 6 months.<br>* Other names: Temodar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of predicted response | Tumor response is measured as contrast-enhancing tumor on T1-weighted MRI and by metabolic active tumor using 18F-fluroethyl-tyrosine (FET)-PET. Pre-treatment risk map is constructed using machine learning methods and compared to post-treatment scans. | 3 months post radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DICE-similarity coefficient and percentage overlap of 64Cu-ATSM and contrast-enhanced T1-weighted MRI | Pre-chemoradiotherapy 64Cu-ATSM-PET is used as a surrogate marker for hypoxia and compared to treatment response, measured as contrast-enhancing tumor on T1-weighted MRI | 3 months post radiotherapy | 
| Correlation (volume and maximum values) between lactate and hypoxia | Lactate measured by MR spectroscopy is compared to metabolic uptake of 64Cu-ATSM-PET | 1 week before start of chemoradiotherapy |