Response Assessment of GBM During Immunotherapy by Delayed Contrast Treatment Response Assessment Maps

Overview

Journal Front Neurol

Specialty Neurology

Date 2024 Apr 23

PMID 38651109

Authors

Valeria Cuccarini

Filippo Savoldi

Yael Mardor

David Last

Serena Pellegatta

Federica Mazzi

Maria Grazia Bruzzone

Elena Anghileri

Bianca Pollo

Luisa Maddaloni

Camilla Russo

Elisa Bocchi

Valentina Pinzi

Marica Eoli

Domenico Aquino

Affiliations

Soon will be listed here.

Abstract

Introduction: Assessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish true tumor progression (TTP) and pseudoprogression (PsP) in this setting.

Methods: We recruited 16 naïve glioblastoma patients enrolled in a phase II trial consisting of the Stupp protocol (a standardized treatment for glioblastoma involving combined radiotherapy and chemotherapy with temozolomide, followed by adjuvant temozolomide) plus IT with dendritic cells. Patients were followed up till progression or death; seven underwent a second surgery for suspected progression. Clinical, immunological, and MRI data were collected from all patients and histology in case of second surgery. Patients were classified as responders (progression-free survival, PFS > 12 months), and non-responders (PFS ≤ 12), HIGH-NK (natural killer cells, i.e., immunological responders), and LOW-NK (immunological non-responders) based on immune cell counts in peripheral blood. TRAMs differentiate contrast-enhancing lesions with different washout dynamics into hypothesized tumoral (conventionally blue-colored) vs. treatment-related (red-colored).

Results: Using receiver operating characteristic (ROC) curves, a threshold of -0.066 in VV (volume of the blue portion of tumoral area/volume of contrast enhancement) variation between values obtained in the MRI performed before PsP/TTP and at TTP/PSP allowed to discriminate TTP from PsP with a sensitivity of 71.4% and a specificity of 100%. Among HIGH-NK patients, at month 6 there was a significant reduction compared to baseline and month 2 in median "blue" volumes.

Discussion: In conclusion, in our pilot study TRAMs support the discrimination between tumoral and treatment-related enhancing features in immunological responders vs. non-responders, the distinction between PsP and TTP, and might provide surrogate markers of immunological response.

Citing Articles

Comparison of a new MR rapid wash-out map with MR perfusion in brain tumors.

Khadhraoui E, Schmidt L, Klebingat S, Schwab R, Hernandez-Duran S, Gihr G BMC Cancer. 2024; 24(1):1139.

PMID: 39267002 PMC: 11395865. DOI: 10.1186/s12885-024-12909-z.

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