ESTRO 2023 - Abstract Book

S690

Monday 15 May 2023

ESTRO 2023

PD-0819 Radiosurgery inhibits tumor softening in glioma mouse model:first findings from in vivo elastography G. Acker 1,2,3 , A. Janas 1 , G. Bertalan 4 , A. Kluge 2,5 , I. Sack 4 , D. Zips 2 , P. Vajkoczy 1 , C. Senger 2,6 1 Charité - Universitätsmedizin Berlin, Department of Neurosurgery, Berlin, Germany; 2 Charité - Universitätsmedizin Berlin, Department of Radiation Oncology, Berlin, Germany; 3 Berlin Institute of Health, Clinician Scientist Program, Berlin, Germany; 4 Charité - Universitätsmedizin Berlin, Department of Radiology, Berlin, Germany; 5 Charité - Universitätsmedizin Berlin, Cyberknife Center, Berlin, Germany; 6 Charité - Universitätsmedizin Berlin, CyberKnife Center, Berlin, Germany Purpose or Objective CyberKnife stereotactic radiosurgery (CK-SRS) precisely delivers high irradiation doses to intracranial tumors. The underlying radiobiology is however not fully understood. Furthermore, whilst it is known that malignant gliomas present with softer tissue properties than healthy brain tissue, the influence of irradiation on tumor biomechanical properties is still unknown. Therefore, our aim was to (1) validate the recently established tomoelastography modality known as magnetic resonance elastography (MRE) for deployment in tumor bearing mouse brain followed by (2) investigation of the alterations of glioma stiffness after CK-SRS. Materials and Methods GL261 cells (20.000) were implanted into striatum of C57BL6/N mice (d0). Animals received either 20 (n=24) or 40 Gy (n=25) CK-SRS in a single dose on day 15, non-irradiated GL261 mice served as controls (n=13). MRI investigations were carried out prior (d13) and longitudinally after irradiation (timepoints: d22, d45, d105, d195 after tumor cell implantation) using a 7T MRI scanner. The protocol included T1-weighted imaging with contrast agent followed by multifrequency MRE with mechanical vibrations of 1000, 1200, 1400 Hz generated by a nonmagnetic piezoceramic actuator [1]. 3D wave fields in a coronal view of the mouse brain were acquired using a modified single shot spin echo echo-planar imaging sequence with a sinusoidal motion-encoding gradient and sample interval modulation acquisition strategy [2]. In total eight time points, equally spaced over an oscillation period, were measured to assess the dynamics of the wave field. Total acquisition time per measurement with 11 contiguous slices, three wave field components, 8 wave dynamics, 3 averages and 3 frequencies was 12 min. The calculated shear wave speed (SWS) of generated elastograms served as surrogate for tissue stiffness. For statistical analysis one way Anova with Bonferroni correction was used (significance: p ≤ 0.05). Results Mean tumor volume significantly decreased by ≈ 60 to 65% after CK-SRS after 40 and 20 Gy SRS, respectively. Analysis of MRE data in the non-irradiated control group revealed a significant decrease of SWS on d22 compared to d13 indicating increasing softness of the growing tumors. In the irradiated group, the SWS of tumors remained comparable at all investigation timepoints after 20 Gy treatment without significant alterations. In the cohort treated with 40 Gy a significant softening process was observed up to d45 that was followed by tumor stiffening in the long term. Conclusion The increasing softness of the non-irradiated tumors is due to the well-known soft tissue properties of malignant gliomas [3-5]. We successfully validated the suitability of tomoelastography of the mouse brain for stiffness mapping within only 12 min per animal. The data obtained indicate that irradiation has an impact on the biomechanics of the tumor. The results are to be further elucidated with other MRI sequences, longer observation period and histological appraisal. PD-0820 Fractionated radiotherapy to temporally modulate the tumour microenvironment for immunotherapy M. Ebert 1 , S. Keam 2 , R. D'Alonzo 3 , S. Gill 1 , A. Nowak 2 , A. Cook 2 1 Sir Charles Gairdner Hospital, Radiation Oncology, Perth, Australia; 2 University of Western Australia, Medical School, Perth, Australia; 3 University of Western Australia, School of Physics, Mathematics and Computing, Perth, Australia Purpose or Objective Effective immunotherapy requires a tumour microenvironment (TME) that can enable effective invasion of and reception to immune cells. Abnormal blood vessel architecture, low perfusion, hypoxia and an immunologically “cold” nature may restrict the efficacy of immunotherapy and account for the relatively low proportion of patients in which immunotherapy has high efficacy. This study aimed to determine the changes in TME following low-dose fractionated radiotherapy in order to capitalise on their temporal nature for optimising subsequent immunotherapy. Materials and Methods This work examined subcutaneous flank tumours comprising AB-1 murine mesothelioma cells in BALB/c mice. Tumour irradiations were performed using a PXi XRAD Smart small animal image-guided radiotherapy system when tumours were approximately 20-30 mm2, with mice receiving 5 daily doses of either 0 Gy (sham) or 2 Gy. Animals were euthanised in groups of 4 on either the final day of 5-fraction radiotherapy, the day after or every subsequent 3 days for up to 14 days. Tumours were excised and cut onto slides for immunohistochemistry (IHC) staining of blood vessel markers, hypoxia and the presence/nature of T cells. Samples were also processed for RNA sequencing and network analysis. Results Vessel density, assessed via staining of CD31+ cells, did not vary between groups, however vessel length and diameter decreased in the irradiated group. Vessel perfusion, assessed by tracing lectin, increased dramatically in the irradiated