Multiparametric MRI assessment of response to convection-enhanced intratumoral delivery of MDNA55, an interleukin-4 receptor targeted immunotherapy, for recurrent glioblastoma
- Department of Radiology, Division of Neuroradiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
- Department of Neurosurgery, University of Texas-Southwestern Medical Center, Dallas, Texas, United States.
- Department of Medicine Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
- Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Suyash Mohan, Department of Radiology, Division of Neuroradiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
DOI:10.25259/SNI_353_2021Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Suyash Mohan1, Sumei Wang1, Sanjeev Chawla1, Kalil Abdullah2, Arati Desai3, Eileen Maloney4, Steven Brem4. Multiparametric MRI assessment of response to convection-enhanced intratumoral delivery of MDNA55, an interleukin-4 receptor targeted immunotherapy, for recurrent glioblastoma. 06-Jul-2021;12:337
How to cite this URL: Suyash Mohan1, Sumei Wang1, Sanjeev Chawla1, Kalil Abdullah2, Arati Desai3, Eileen Maloney4, Steven Brem4. Multiparametric MRI assessment of response to convection-enhanced intratumoral delivery of MDNA55, an interleukin-4 receptor targeted immunotherapy, for recurrent glioblastoma. 06-Jul-2021;12:337. Available from: https://surgicalneurologyint.com/surgicalint-articles/10941/
Background: Glioblastoma (GBM) is the most common malignant brain tumor and carries a dismal prognosis. Attempts to develop biologically targeted therapies are challenging as the blood–brain barrier can limit drugs from reaching their target when administered through conventional (intravenous or oral) routes. Furthermore, systemic toxicity of drugs often limits their therapeutic potential. To circumvent these problems, convection-enhanced delivery (CED) provides direct, targeted, intralesional therapy with a secondary objective to alter the tumor microenvironment from an immunologically “cold” (nonresponsive) to an “inflamed” (immunoresponsive) tumor.
Case Description: We report a patient with right occipital recurrent GBM harboring poor prognostic genotypes who was treated with MRI-guided CED of a fusion protein MDNA55 (a targeted toxin directed toward the interleukin-4 receptor). The patient underwent serial anatomical, diffusion, and perfusion MRI scans before initiation of targeted therapy and at 1, 3-month posttherapy. Increased mean diffusivity along with decreased fractional anisotropy and maximum relative cerebral blood volume was noted at follow-up periods relative to baseline.
Conclusion: Our findings suggest that diffusion and perfusion MRI techniques may be useful in evaluating early response to CED of MDNA55 in recurrent GBM patients.
Keywords: Diffusion tensor imaging dynamic susceptibility contrast, Multiparametric MRI, Recurrent glioblastoma, Response assessment
Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a miserable prognosis.[
A 57-year-old female with the right occipital recurrent GBM (IDH-1 wild-type, MGMT promoter methylated, with EGFR amplification) was treated with MRI-guided convection-enhanced intratumoral delivery of MDNA55. She underwent initial resection 32 months before this presentation followed by standard-of-care chemoradiation therapy. Her follow-up MRI demonstrated increasing size of enhancing lesion along the anteroinferior aspect of the right occipital resection cavity with elevated relative cerebral blood volume (rCBV), consistent with progressive recurrent malignant glial neoplasm. At this time, her presenting symptoms included memory deficits, confusion, persistent fatigue, and worsening gait instability.
Placement of catheters and infusion of MDNA55
CED catheters were precisely placed under stereotactic guidance after importing the neuronavigation sequences to Brainlab Curve-100 workstation. Two entry points were planned for the minimally invasive trajectory using the “Overview” view to develop a 3D model of the target recurrent tumor and surrounding neural and vascular structures. The catheters were secured in a 14 French Foley catheter (red rubber tubing), stab wounds were then closed with 3-0 Nylon (Neurolon) sutures and the patient was transferred, intubated to the MRI suite [
Intraoperative neuronavigation (Brainlab®, Munich, Germany) demonstrating lesion mapping and trajectory planning through topographic, axial, sagittal, and coronal views (clockwise, left panel). Postoperative wound dressing and secured drug delivery catheter, reflecting the right occipital-parietal entry point (right panel).
Imaging response assessment
The patient underwent serial MRI scans including a baseline and 1, 3-month follow-up MRI on a 3T scanner using a 12-channel, phased array head coil. The MRI protocol included anatomical images, diffusion tensor imaging (DTI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) using parameters as described previously.[
Axial coregistered postcontrast T1-weighted image (PC T1), T2-FLAIR, and corresponding mean diffusivity (MD), fractional anisotropy (FA), and cerebral blood volume (CBV) maps are shown at baseline, 1-month, and at 3-month follow-up periods. There was a striking reduction of contrast enhancement, and CBV (white arrows), more apparent at 1-month follow-up compared to the baseline, with increased MD and decreased FA.
She did well immediately after the infusion, was neurologically intact, and discharged to a rehabilitation facility on day 2 after the procedure. She was readmitted after approximately 1½ months with declining Karnofsky performance score (KPS of 50), persistent nausea and vomiting, unsteadiness of gait, and somnolence, and was found to have hydrocephalus for which a ventriculoperitoneal shunt was placed. She eventually experienced tumor progression and was not considered a candidate for additional treatment, and hence, was transferred to hospice for palliative care.
We demonstrated imaging findings suggestive of a positive early response to convection-enhanced intratumoral delivery of MDNA55, an IL-4 receptor targeted immunotherapy, in a patient with recurrent GBM. Reduced tumor volume, increased MD, decreased FA, and markedly reduced rCBV were observed from contrast enhancing regions of neoplasm. As tissue immunophenotyping was not performed, it is speculative whether the favorable local response was due to a direct pharmacological effect, or an induced immunomodulatory effect, or a combination of these.
The IL-4R is highly expressed in multiple tumor types including 76% of GBMs, spurring tumor growth.[
Conventional MRI is limited in evaluating treatment response in GBM patients, due to lack of specificity, especially in the setting of immunotherapy.[
Neovascularization (formation of new blood vessels) is a common feature of GBMs that account for high tumor perfusion as seen on DSC-PWI-derived CBV maps.[
Despite showing promising findings, clinical utility of CBV maps sometimes may be constrained by limitations that include susceptibility artifacts caused by microhemorrhages present within the tumor bed.[
We believe that multiparametric analysis combining the unique strengths of DTI and DSC-MRI techniques, as performed in the present case, could contribute to a more comprehensive assessment of treatment response in these patients.
Advanced MRI techniques could be a useful adjunct in assessing early response to CED of MDNA55 in recurrent GBM patients. However, this promising finding warrants further validation in future, larger clinical trials.
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