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22.07.2024 | Research

Effects of PreOperative radiotherapy in a preclinical glioblastoma model: a paradigm-shift approach

verfasst von: Beatriz I. Fernandez-Gil, Paula Schiapparelli, Juan P. Navarro-Garcia de Llano, Andrea Otamendi-Lopez, Maria Jose Ulloa-Navas, Loizos Michaelides, Carla A. Vazquez-Ramos, Steven M. Herchko, Melissa E. Murray, Yesesri Cherukuri, Yan W. Asmann, Daniel M. Trifiletti, Alfredo Quiñones-Hinojosa

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2024

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Abstract

Purpose

PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model.

Methods

Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle.

Results

PreOperative RT group median survival was significantly higher than PostOperative RT (p < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors (p < 0.001) and induced senescence in PostOperative RT recurrent tumors (p < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors (p < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group.

Conclusions

This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.

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Titel: Effects of PreOperative radiotherapy in a preclinical glioblastoma model: a paradigm-shift approach
verfasst von: Beatriz I. Fernandez-Gil
Paula Schiapparelli
Juan P. Navarro-Garcia de Llano
Andrea Otamendi-Lopez
Maria Jose Ulloa-Navas
Loizos Michaelides
Carla A. Vazquez-Ramos
Steven M. Herchko
Melissa E. Murray
Yesesri Cherukuri
Yan W. Asmann
Daniel M. Trifiletti
Alfredo Quiñones-Hinojosa
Publikationsdatum: 22.07.2024
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2024
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-024-04765-5

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25.04.2025
Karotisstenose
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Die medikamentöse Therapie für Menschen mit Karotisstenosen hat sich in den vergangenen Dekaden verbessert. Braucht es also noch einen invasiven Eingriff zur Revaskularisation der Halsschlagader bei geringem bis moderatem Risiko für einen ipsilateralen Schlaganfall?

Neuartige Antikörpertherapie bremst MS über zwei Jahre hinweg

18.04.2025
AAN-Jahrestagung 2025
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Eine Therapie mit dem C40-Ligand-Blocker Frexalimab kann MS-Schübe und neue MRT-Läsionen über zwei Jahre hinweg verhindern. Dafür spricht die Auswertung einer offen fortgeführten Phase-2-Studie.

Therapiestopp bei älteren MS-Kranken kann sich lohnen

17.04.2025
AAN-Jahrestagung 2025
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Eine Analyse aus Kanada bestätigt: Setzen ältere MS-Kranke die Behandlung mit Basistherapeutika ab, müssen sie kaum mit neuen Schüben und MRT-Auffälligkeiten rechnen.

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Springer Medizin

Effects of PreOperative radiotherapy in a preclinical glioblastoma model: a paradigm-shift approach