Developing a Pipeline for Multiparametric MRI-Guided Radiation Therapy: Initial Results from a Phase II Clinical Trial in Newly Diagnosed Glioblastoma

Abstract

Quantitative mapping of hyperperfused and hypercellular regions of glioblastoma has been proposed to improve definition of tumor regions at risk for local recurrence following conventional radiation therapy. As the processing of the multiparametric dynamic contrast-enhanced (DCE-) and diffusion-weighted (DW-) magnetic resonance imaging (MRI) data for delineation of these subvolumes requires additional steps that go beyond the standard practices of target definition, we sought to devise a workflow to support the timely planning and treatment of patients. A phase II study implementing a multiparametric imaging biomarker for tumor hyperperfusion and hypercellularity consisting of DCE-MRI and high b-value DW-MRI to guide intensified (75 Gy/30 fractions) radiation therapy (RT) in patients with newly diagnosed glioblastoma was launched. In this report, the workflow and the initial imaging outcomes of the first 12 patients are described. Among all the first 12 patients, treatment was initiated within 6 weeks of surgery and within 2 weeks of simulation. On average, the combined hypercellular volume and high cerebral blood volume/tumor perfusion volume were 1.8 times smaller than the T1 gadolinium abnormality and 10 times smaller than the FLAIR abnormality. Hypercellular volume and high cerebral blood volume/tumor perfusion volume each identified largely distinct regions and showed 57% overlap with the enhancing abnormality, and minimal-to-no extension outside of the FLAIR. These results show the feasibility of implementing a workflow for multiparametric magnetic resonance-guided radiation therapy into clinical trials with a coordinated multidisciplinary team, and the unique and complementary tumor subregions identified by the combination of high b-value DW-MRI and DCE-MRI.

Keywords: MRI; glioblastoma; multiparametric; pipeline; workflow.

Figure 1.

Integrated workflow diagram for the implementation of an advanced dynamic contrast-enhanced (DCE)- and high b-value magnetic resonance (MR) imaging signature to guide dose-intensified radiotherapy. TPS = treatment planning system; Gd = T1-Gd-enhanced MRI; GTV = gross tumor volume; CTV = clinical target volume; PTV = planning target volume.

Figure 2.

The averaged CBV values in the hCBV tumor volumes, normal frontal white matter (WM) and normal frontal gray matter (GM) in the 12 study patients. The error bars depict the averaged standard deviations of cerebral blood volume (CBV) in the 3 volumes of interest across the 12 patients. Note that the mean CBV value + 2SDs in the frontal WM is smaller than the mean value in the frontal GM, and thus, it cannot be used as a threshold value to define the elevated CBV in the tumor volume.

Figure 3.

An example of a patient with largely nonoverlapping hypercellular tumor regions (TV_HCV) identified by high b-value diffusion-weighted (DW)-magnetic resonance imaging (MRI) (cyan, left panel) and hyperperfused tumor regions (TV_HCBV) identified by DCE-MRI (red, middle panel). Significant extension of TV_HCV is showed beyond the T1 Gd-enhanced region (overlay on T1 Gd-enhanced image, right panel).

Figure 4.

Representative images from radiation plans from 2 different patients. The top row depicts images of radiation plans using advanced MRI to boost tumor subregions to 75 Gy. High-risk tumor targets are identified by advanced MRI (cyan) beyond the abnormal regions seen on T1 Gd-enhanced conventional MRI (green). The conformal 75-Gy isodose line targeting the advanced imaging tumor volume is depicted in red, and the larger 60-Gy isodose line targeting the anatomic T1-Gd-enhanced region with standard clinical margins is depicted in gray-white. The bottom row depicts images of comparison standard radiation plans for the same patients based on anatomic T1-Gd-enhanced MRI with standard clinical margins prescribed to 60 Gy. As showed, advanced MRI-identified boost regions prescribed to 75 Gy were often contained within standard anatomic MRI regions prescribed to 60 Gy.