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Multiparametric MRI assessment of response to convection-enhanced intratumoral delivery of MDNA55, an interleukin-4 receptor targeted immunotherapy, for recurrent glioblastoma

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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.
Title: Multiparametric MRI assessment of response to convection-enhanced intratumoral delivery of MDNA55, an interleukin-4 receptor targeted immunotherapy, for recurrent glioblastoma
Description:
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.

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