ESTRO 2024 - Abstract Book

S5198

Radiobiology - Microenvironment

ESTRO 2024

3. Zandberg DP, Menk AV, Velez M, Normolle D, DePeaux K, Liu A, et al. Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck. J Immunother Cancer. 2021;9(5).

4. Secomb TW, Hsu R, Ong ET, Gross JF, Dewhirst MW. Analysis of the effects of oxygen supply and demand on hypoxic fraction in tumors. Acta Oncol. 1995;34(3):313-6.

5. Boreel DF, Span PN, Heskamp S, Adema GJ, Bussink J. Targeting Oxidative Phosphorylation to Increase the Efficacy of Radio- and Immune-Combination Therapy. Clin Cancer Res. 2021;27(11):2970-8.

6. Yap TA, Daver N, Mahendra M, Zhang J, Kamiya-Matsuoka C, Meric-Bernstam F, et al. Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials. Nat Med. 2023.

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Poster Discussion

Activation of STAT3 in Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastases

Paola Anna Jablonska 1 , Nuria Galán 2 , Jennifer Barranco 2 , Sergio Leon 2 , Ramón Robledano 3 , José Ignacio Echeveste 3 , Alfonso Calvo 2,4,5 , Javier Aristu 6 , Diego Serrano 2,4,5 1 Hospital Universitario de Navarra, Radiation Oncology, Pamplona, Spain. 2 Center for Applied Medical Research, IDISNA and Program in Solid Tumors, Pamplona, Spain. 3 Clinica Universidad de Navarra, Department of Pathological Anatomy, Pamplona, Spain. 4 University of Navarra, Department of Pathology, Anatomy and Physiology, School of Medicine, Pamplona, Spain. 5 ISCIII, CIBERONC, Madrid, Spain. 6 Clinica Universidad de Navarra, Radiation Oncology, Madrid, Spain

Purpose/Objective:

The risk of brain radiation necrosis (RN) following stereotactic radiosurgery (SRS) as part of brain metastases (BMs) treatment has been a subject of recent investigation. The etiopathology of RN is not fully understood, but direct and indirect effects of radiation on vascular, neuronal, and immune cells seem to play a key role in its development. The signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in inflammatory responses, immune disorders, and carcinogenesis. STAT3 signaling has been described in a subpopulation of reactive astrocytes (RA) associated with BMs, promoting tumor growth and contributing to neurovascular dysfunction. As the development of RN is highly influenced by immuno-inflammatory cascade and neurovascular alteration, we hypothesized that phosphorylation of STAT3 contributes to the pathogenesis of RN following SRS treatment of BMs. We aimed to test this hypothesis in an animal model, followed by validation in a series of human RN specimens.

Material/Methods:

We developed a mouse model of RN using clinical LINAC-based SRS to perform an in-depth characterization of the processes of immune cell infiltration and angiogenesis by immunohistochemistry (IHC) and multispectral immunophenotyping. Ten Balb/c mice were selected for brain SRS with a total dose of 50 Gy in 1 fraction delivered to the left hemisphere using a circular collimator of 5mm diameter and flattening filter-free 6 MV photon beams. Irradiated brain hemispheres were compared to the contralateral, non-irradiated ones. Five Balb/c mice did not undergo brain SRS and their non-irradiated brains were included as healthy controls. IHC and multiplex staining