Mayo Clinic College of Medicine and Science Jacksonville Jacksonville, FL
D. J. Crompton1, S. Kern2, A. W. Bogan3, B. Do2, S. A. Vora4, A. Quinones-Jinojosa5, T. Burns2, K. Jaeckle5, P. D. Brown6, N. N. Laack II6, J. L. Peterson1, J. H. Uhm7, M. Ruff7, U. Sener7, W. Breen6, and D. M. Trifiletti1; 1Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, 2Mayo Clinic, Rochester, MN, 3Department of Qualitative Health Sciences, Section of Biostatistics, Mayo Clinic, Scottsdale, AZ, 4Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, 5Mayo Clinic, Jacksonville, FL, 6Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 7Mayo Clinic, Department of Neurology, Rochester, MN
Purpose/Objective(s): Glioblastoma (GBM) is the most aggressive primary brain tumor, with inevitable recurrence despite trimodality therapy, and an overall survival of approximately 15 months. Historic series suggest local progression comprises approximately 80% of treatment failures with this disease, but little is known regarding patterns of failure in a modern cohort. In this large multicenter retrospective review we sought to explore the modern patterns of failure of patients with GBM.Materials/
Methods: We obtained institutional review board approval for this retrospective study. We identified patients with newly diagnosed GBM between 2014-2023 who received external beam radiotherapy (EBRT) at a large multisite academic institution. Data collected included extent of resection, radiotherapy dose, radiotherapy modality, utilization of tumor treating fields (TTF), and presence and location of progression (in-field, marginal, or distant). In-field was defined as =80% recurrence volume within the 95% isodose volume, marginal as 20-80% recurrence volume within the 95% isodose volume, and distant as a recurrence <20% within the 95% isodose volume. Chi-square tests were performed to evaluate patient and disease characteristics in relation to location of failure. Results: Six-hundred and seventy (670) patients were included in this retrospective study, with 447 demonstrating radiographic progression at the time of the analysis. Of the patients with progression, 393 (87.9%), 32 (7.2%), and 22 (4.9%) demonstrated in-field, marginal, and distant progression, respectively. Location of progression was not statistically associated with MGMT status (p=0.65), resection extent (p=0.16), IDH status (p=0.32), concurrent TMZ (p=0.20), adjuvant TMZ (p=0.914), or radiation dose/fractionation [60Gy/30Fx, 40Gy/15Fx, 25Gy/5Fx, or >60Gy] (p=0.51). Tumor treating fields (TTF) was associated with decreased in-field and increased marginal failures (p=0.002). Proton treatment was associated with decreased marginal failures and increased distant failures as compared to photon treatment (p=0.025). Temporal and parietal tumors were associated with lower rates of marginal and distant failure as compared to frontal and occipital tumors (p=0.04). Conclusion: In this large modern cohort, over 80% of tumor progression occurred locally, despite modern neurosurgical and radiotherapeutic techniques. In contrast to other published data, we found no association between pattern of progression and MGMT methylation. The relationship between pattern of progression and TTF suggests that may play a clinically significant role in DNA damage response. Despite modern aggressive therapy, these findings suggest that improvements in local therapy continue to be desperately needed in GBM.
