The purpose of this study is to evaluate the use of dynamic contrast-enhanced MRI (DSC-MRI) to identify and target hypoxic tumor regions in glioblastoma (GBM). The study is divided into two phases: Phase 1 will focus on biologic validation in newly diagnosed GBM patients, while Phase 2 will assess the clinical implementation of DSC-MRI-guided radiotherapy in recurrent or postoperative GBM patients. The primary endpoints are the validation of DSC-MRI in identifying hypoxic regions and assessing the safety and efficacy of radiation therapy based on these findings.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Non-invasively characterize tumor perfusion and derive imaging surrogates of hypoxia that inform tissue sampling (Phase 1) and radiotherapy planning (Phase 2). DSC-MRI is an advanced perfusion technique that acquires rapid, repeated gradient-echo echo-planar images during intravenous administration of a gadolinium-based contrast agent which will aid in the generation of parametric maps.
In Phase 1, these maps will guide neuro-navigation for intra-operative sampling of imaging-defined hypoxic and normoxic subregions to enable biologic and spatial transcriptomic validation. In Phase 2, DSC-MRI-derived hypoxia maps will be rigidly co-registered to planning MRI/CT datasets and imported into the treatment planning system to define hypoxic subvolumes eligible for a conformal radiotherapy boost, delivered with contemporary inverse-planned techniques while respecting all organ-at-risk constraints and standard-of-care dose limits.
NYU Langone Health
New York, New York, United States
Proportion of participants with successful acquisition and processing of interpretable hypoxia maps
Time frame: Up to 3 months
Proportion of participants in whom DSC-MRI hypoxia maps are successfully incorporated into radiotherapy planning and the hypoxia-targeted boost is delivered while meeting organ-at-risk constraints.
Time frame: Up to 3 months
Incidence of treatment-related toxicities
According to CTCAE v6.0, with particular focus on Grade ≥3 treatment-related toxicities.
Time frame: Up to 3 months
Progression-free survival (PFS)
PFS is defined as the time from initiation of hypoxia-guided radiotherapy to disease progression or death from any cause.
Time frame: Up to 5 years
Overall survival (OS)
OS is defined as the time from initiation of hypoxia-guided radiotherapy to death from any cause.
Time frame: Up to 5 years
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Radiotherapy will be delivered using the Varian TrueBeam system. All participants will receive dynamic susceptibility contrast (DSC)-MRI-informed radiotherapy incorporating an integrated boost to imaging-defined hypoxic tumor subvolumes. Radiotherapy will be delivered using inverse-planned intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT), once daily, five fractions per week, with daily volumetric image guidance.