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- Title
MGMT promotor methylation status and implications for weekly adaptive radiotherapy for glioblastoma.
- Authors
Liang Zeng, K.; Saghal, Arjun; Myrehaug, Sten; Soliman, Hany; Tseng, Chia-Lin; Ruschin, Mark; Perry, James; Lim-Fat, Mary Jane; Das, Sunit; Detsky, Jay
- Abstract
Purpose: Integrated MRI-linear accelerator (MR-Linac) technology allows for daily soft tissue visualization, online adaptive replanning and potential for safe margin reduction. We report preliminary findings of weekly tumor reduction in a consecutive series of MGMTmethylated glioblastoma (GBM) patients treated on the MR-Linac (MRL). Methods and materials: UNITED (NCT04726397) is a phase II trial investigating the safety and feasibility of margin reduced MR-guided adaptive radiotherapy in GBM using the MRL. Patients treated with 60 Gy in 30 fractions or 40 Gy in 15 fractions with concomitant temolozomide (TMZ) are eligible. A 5 mm clinical target volume (CTV) expansion is applied to the gross tumor volume (GTV), which is extended to include abnormal T2-FLAIR. Patients undergo weekly on-line adaptive replanning based on a contrast-enhanced T1 and T2- FLAIR MRL-MRI taken in the treatment position. Results: The first five consecutive MGMT-methylated patients are reported. All patients had IDH wild-type GBM and the mean age was 60 years (range: 44- 76 years). Compared to the Day 1 MRL plan, weekly average GTV changes at fraction 6, 11, 16, 21, and 26 were -7.8% (range, +1.1% to -14.0%), -17.6% (range, -3.7% to -24.3%), -15.5% (range, -5.8% to -25.0%), -20.4% (range, -7.4% to -38.1%) and -22.0% (range, -3.6% to -35.7%), respectively. Average CTV reductions were 4.3%, 11.6%, 7.6%, 14.0% and 14.0% at the same respective time points. In comparison, the first five treated unmethylated patients exhibited consistent weekly growth patterns in the GTV during RT. Conclusions: Our preliminary findings support a treatment adaptation protocol for GBM, in particular for patients with methylated GBM, given the volume reductions observed. Clinical outcomes from the UNITED clinical trial will inform endpoints including failure patterns, quality of life, and treatment tolerance.
- Subjects
O6-Methylguanine-DNA Methyltransferase; GLIOBLASTOMA multiforme; METHYLATION; RADIOTHERAPY; MEDICAL protocols
- Publication
Journal of Radiosurgery & SBRT, 2022, Vol 8, p175
- ISSN
2156-4639
- Publication type
Article