Purpose: Clinicians know that there is individual variability among the same tumour type to radiotherapy. Glioblastoma (GBM) is relatively radioresistant and can have a variable response despite identical treatment. Using Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) intra-cellular Manganese (Mn) been shown to be related to radiosensitivity in tissue arrays. Our objective was to identify a predictive biomarker of radioresistance in GBM.
Methods and Materials: Using ethics-approved pilot and full study protocols [2024/ETH01069; 2025/PID00420], up to 60 GBM patients’ data were extracted across two institutions, according to strict, pre-defined eligibility criteria. All patients were deceased, had complete or near complete (>90%) resection, had high Karnofsky scores (80-100), had IDH negative tumours, and received standard Stupps protocol treatment (ie 60 Gray RT in 30 fractions with Temozolomide). Histopathology slides were analysed using LA-ICP-MS, measuring intra-tumoural Mn, iron (Fe), copper (Cu) and zinc (Zn). The association between the intra-tumoural metal concentrations, overall survival (OS) and age using linear regression, Kaplan-Meier method, and Cox regression, were evaluated. Known prognostic molecular markers were evaluated in all patients.
Results: Only the Mn score (measured in parts per million ppm) was statistically significantly associated with OS. Preliminary data showed those patients with low Mn score ≤ 0.3279 ppm had a median survival 21.7 months, compared to those with higher Mn score > 0.3279 ppm had a median survival 10.7 months. In the preliminary data, MGMT promoter methylated patients did better with MGMT promoter methylation correlating with intra-tumoural Mn (p = 0.05). All patients who underwent a second surgical procedure for recurrence exhibited a higher Mn score.
Conclusion: An intra-tumoural Mn threshold has been identified in GBM, this may guide clinical decision-making. Further studies are underway to extend these findings in in other solid cancers. Analysis continues and more data will be presented.