Non-Contrast Perfusion Using Arterial Spin Labeled MR Imaging for Assessment of Therapy Response in Glioblastoma

Glioblastoma Clinical Trial

Official title: A Prospective Study to Evaluate Quantitative Non-Contrast Perfusion Using Arterial Spin Labeled Magnetic Resonance (MR) Imaging for Assessment of Therapy Response in Glioblastoma

Status Recruiting

Clinical Trial Summary

MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first.

Clinically, GBM patients are imaged every 8-weeks, beginning at 10 weeks after the completion of chemoradiation, since morphological (i.e. size) changes are not anticipated earlier. However, our preliminary experience and others have shown functional changes including perfusion and diffusion as early as 3-weeks after the initiation of the treatment . Thus, our T10, T18, T26 and T34 MRI sessions will be performed along with the clinical imaging sessions, while the T3 and T6 MRI sessions will be performed additionally for this proposal. All MR imaging sessions will be scheduled within ±1 or ±2 weeks of the target time period, as indicated in the table.

MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. The research MR imaging may take approximately an additional 15 minutes per each imaging session. However, the T3, and T6 MR imaging sessions will be performed additionally for the purpose of this study, with each taking approximately one hour. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first.

Clinical Trial Description

Glioblastoma (GBM) represents about 15% of all primary brain tumors with approximately 19,000 new cases diagnosed annually. The one-, five- and ten-year survival rates for patients with GBM is 37.2%, 5.1% and 2.6% from diagnosis respectively, making it one of the most lethal cancers known, among all cancers. GBMs can be challenging to treat and new cancer therapies are continuously being developed for GBM treatment.

The high cost and potential risks associated with human trials for these experimental therapies have emphasized the need for sensitive monitoring of tumor response. Imaging approaches can play an important role in the evaluation and selection of potential new therapies with non-invasive longitudinal monitoring of treatment response. Currently, the radiological assessment of treatment outcomes predominantly relies on morphological (i.e. size) changes using the Response Evaluation Criteria in Solid Tumors (RECIST) and other similar scores. This is a major limiting factor as the effects of many therapeutic agents at the microscopic level precede the eventual changes in tumor size. One such tumor property that has gained increased attention is angiogenesis, which has been shown to support tumor proliferation and infiltration. Increasing numbers of clinical trials have begun targeting tumor vascular supplies either directly inhibiting angiogenesis (e.g. antiangiogenic therapy) or indirectly disrupting cell proliferation and eventually angiogenesis (e.g. cytotoxic chemoradiation). Such clinical trials and the eventual clinical use of these therapies would be greatly assisted by the availability of robust imaging indicators of angiogenesis (i.e. tissue perfusion).

Positron Emission Tomography (PET) using 15O-labeled water (15O-PET) is considered the gold standard for non-invasive measurement of tissue perfusion. However, the use of 15O-PET requires a cyclotron in close proximity to PET to produce short lived 15O-water (half life 2.4 min), limiting its applicability in clinical settings. Alternative imaging techniques include ultrasound using microbubbles, perfusion computed tomography (CT) using iodinated contrast agent and perfusion MRI using gadolinium based contrast agents. All of these techniques require exogenous agents, restricting their use in longitudinal monitoring of treatment response.

Arterial spin labeled (ASL) MRI has recently emerged as a quantitative imaging (QI) method to measure perfusion (or capillary blood flow) without the administration of exogenous contrast agents. ASL magnetically "labels" the highly permeable water in the blood as a tracer and measures their accumulation in the tissue of interest, without injecting any exogenous contrast. Various versions of ASL have been validated in animals using microspheres, and in humans using 15O-PET in the brain. ASL also has a number of advantages compared to dynamic contrast enhanced (DCE) and dynamic susceptibility contrast (DSC) based MR perfusion measurements. Specifically, ASL does not require exogenous agent alleviating the concerns of gadolinium accumulation or nephrogenic systemic fibrosis (NSF) in patients with impaired renal function and, unlike DCE/DSC, the contribution of vascular permeability to ASL measured perfusion is negligible enabling absolute perfusion quantification in physiological units (ml/100g/min). ;

Related Conditions & MeSH terms

• Glioblastoma

• NCT number: NCT03922984
• Study type: Interventional
• Source: University of Texas Southwestern Medical Center
• Contact: Kelli Key, PhD
• Phone: 214-648-8152
• Email: Kelli.Key@UTSouthwestern.edu
• Status: Recruiting
• Phase: N/A
• Start date: April 16, 2019
• Completion date: April 16, 2027