TGM2 Novel Biomarker Of Radiation Response After Neo-Adjuvant TMZ In Glioblastoma

Abstract

Purpose/Objective(s): Frameless stereotactic radiosurgery (SRS) has become a preferred supplement to frame-based Gamma Knife SRS due to its non-invasive nature and allowance for fractionation. To account for intra-fraction motion, radiation is automatically gated whenever a real-time tracking system detects patient displacement larger than a user-specified threshold. Treatment delivery pauses and a cone-beam CT is acquired to verify patient position if the excess displacement persists. This gating technique, although effective with high accuracy, is sensitive to patient's involuntary motions. Overall treatment duration is increased with each pause, and this can result in a prolonged treatment duration. The purpose of this study is to investigate whether active coaching during frameless SRS can reduce overall treatment duration. Materials/Methods: Patients treated at a single institution with frameless SRS on a Gamma Knife Icon from 2017 to 2020 were retrospectively identified. Beginning in January 2019, all patients treated with frameless SRS were actively coached: Prior to treatment, each patient was instructed on how to adjust his/her head position following prompts from staff. During treatment, the patient motion was closely monitored. Once a large displacement was observed, the patient was instructed to gently tuck/ untuck or tilt his/her chin to reduce the displacement. Patient characteristics and treatment plans were compared between the cohorts of patients treated with and without active coaching. Linear regressions between the planned and overall treatment duration were performed on either cohort. ANOVA and Wilcoxon tests were used with a p-value less than 0.05 considered as significant. Results: A total of 45 patients and 107 frameless SRS treatment sessions were identified, 27 (60.0%) of which underwent 51 (47.7%) frameless SRS treatment sessions with active coaching. There was no significant difference in patient characteristics or treatment plans between two cohorts (p<0.001). Patients treated with active coaching underwent significantly fewer CBCTs during sessions (Median: 1 vs. 2; p<0.01). The median planned and overall treatment durations were 27.1 min (range: 12.2-110.9) and 41.3 min (range: 13.7-202.2) for the non-coached cohort, and 30.9 min (range: 10.6-89.5) and 41.6 min (range: 10.6-144.4) for the coached cohort. Linear regressions analysis revealed that the overall treatment duration was 1.29 times longer than the planned beam-on duration with active coaching (R 2 Z 0.95) and 1.60 times without (R 2 Z 0.75). The difference between the slopes was statistically significant (p<0.001), which indicated a significant reduction in the overall treatment duration with active coaching. Conclusion: Our results suggested that active coaching was associated with significant reductions of overall treatment duration. This simple intervention can be clinically implemented to improve clinical efficiency and possibly patient comfort during frameless Gamma Knife SRS.

Exploring the Role of Transglutaminase in Patients with Glioblastoma: Current Perspectives

“…Daniel and coworkers demonstrated that tTG enhances radio-resistance in glioblastoma both in vitro and in vivo by repressing the expression of the DNA damage repair protein RAD51. 55 They and others have also noted that radiation treatment of glioblastomas frequently resulted in upregulation of tTG. 55,56 Interestingly, Berg demonstrated that irradiation of healthy astrocytes caused tTG to be secreted into the extracellular matrix, which in turn generated a supportive microenvironment for implanted glioma cells, leading to more rapid tumor growth in mouse models.…”

“…55 They and others have also noted that radiation treatment of glioblastomas frequently resulted in upregulation of tTG. 55,56 Interestingly, Berg demonstrated that irradiation of healthy astrocytes caused tTG to be secreted into the extracellular matrix, which in turn generated a supportive microenvironment for implanted glioma cells, leading to more rapid tumor growth in mouse models. This modified extracellular matrix supported stemness and radio-resistance.…”