Imaging-computational framework for guiding treatment of HGG: an ohsv clinical trial

The National Cancer Institute awarded the University of Alabama at Birmingham $643,827 on September 3, 2026, under the Cancer Detection and Diagnosis Research program (CFDA 93.394) to develop an imaging-computational framework integrating molecular and functional imaging with computational modeling to guide treatment planning for patients with high-grade gliomas treated with oncolytic herpes simplex virus immunotherapy. The project will leverage an ongoing FDA-approved clinical trial (NCT03657576) to apply advanced PET and MRI imaging simultaneously to provide biologically relevant information on tumor microenvironment factors including hypoxia, amino acid utilization, cellularity, and perfusion. These imaging data will guide placement of intratumoral catheters for oncolytic herpes simplex virus administration, identify factors contributing to intratumor heterogeneity, and inform mathematical models that computationally predict tumor growth and treatment response. The award funds work performed in Birmingham, Alabama, with a period of performance through August 31, 2031. The assistance type is a project grant.

Abstract

The overall objective of this proposal is to integrate molecular and functional imaging with computational modeling to guide treatment planning to optimize tumor response for patients with high grade gliomas (hggs) treated with intratumorally delivered novel oncolytic herpes simplex virus (ohsv) immunotherapy. Hggs, including glioblastomas (gbms), are highly heterogenous, and patients have dire outcomes with low rates of survival. This is partially due to tumor heterogeneity and resistance to currently available treatment strategies. Leveraging an ongoing FDA-approved novel clinical trial, NCT03657576, we can apply advanced, clinically relevant imaging to guide and predict early response to an intratumorally injected novel ohsv in combination with standard-of-care therapies. Pet and MRI simultaneously can provide biologically relevant tumor microenvironment information on hypoxia, amino acid utilization, cellularity, and perfusion that can guide placement of intratumoral catheters, identify factors intratumor heterogeneity, and inform mathematical models that can computationally predict forward the growth of the tumor. We posit that pet/MRI can define the regional tumor biology to direct the sites of ohsv administration and provide an earlier assessment of response than conventional imaging. Our initial clinically trial with this ohsv significantly extended the survival in patients with recurrent HGG compared to standard-of-care. Further, with multiparametric MRI, we identified that tumors with lower perfusion in areas of high cellularity had decreased survival. These complimentary pieces of data provide rationale to expand the ohsv clinical trial to include pet/MRI which will use FET-pet to identify biological tumor volume (BTV) during the course of therapy in addition to fmiso-pet to evaluate regions of hypoxia for catheter placement. Furthermore, we propose pairing the pet/MRI data with an image-based computational model to optimize, on a patient-specific basis, catheter selection for enhanced delivery strategy and predicting the tumor recurrence. Our study will be the first to assess the ability of quantitative FET/fmiso- pet/MRI to guide an interventional strategy, and paired with computational modeling, to monitor and predict changes in hggs. We will test this through the following aims: aim 1) utilize pre-treatment imaging features to guide location of catheter placement for intra-cranial injection of ohsv and biologically validate distinct tumor habitats; aim 2) quantify longitudinal pet/MRI metrics that have favorable response to ohsv.; aim 3) use an image-based computational model to predict the spatio-temporal response and guide which catheters should be utilized for subsequent injections ohsv-IOT. New methods for predicting and optimizing responses for HGG are desperately needed. Our project will develop rigorous-but practical- approaches to optimize a novel ohsv intervention for HGG. This paradigm is adaptable to multicenter trials and other immune- and spatially-directed therapies for brain tumors.