Temozolomide use in elderly patients with MGMT promoter unmethylated glioblastoma: Is it finally time to dismount a dead horse?
Bibliographic record
Abstract
Temozolomide (TMZ) remains the only chemotherapy agent associated with a survival benefit in glioblastoma (GBM).In the landmark "Stupp" study, the median overall survival (mOS) was 14.6 months for patients treated with radiation therapy (RT) and TMZ compared to 12.1 months for patients treated with RT alone. 1 Epigenetic silencing via methylation within the CpG island of the promoter region of the O6-methylguanine DNA methyltransferase (MGMT) gene was associated with significantly improved outcomes in the RT/TMZ arm.Patients with MGMT promoter methylated tumors treated with RT/TMZ had an mOS of 21.7 months as compared with 15.6 months for those treated with RT alone, while those with MGMT promoter unmethylated tumors had a marginal survival benefit (12.7 vs. 11.8 months, respectively; P = .06). 2 However, in this trial, 10% of patients with MGMT unmethylated tumors treated with RT/TMZ were alive at 3 years.Coupled with the mild toxicities and absence of compelling alternatives, these data have driven the routine use of TMZ in clinical practice regardless of MGMT status.Treatment of elderly and frail GBM patients represents a special clinical challenge where toxicity must be balanced with potential benefits.Due to poor tolerance of standard RT (60 Gy in 30 fractions) among elderly patients, hypofractionated RT (34 Gy in 3.4 fractions) was evaluated in the Nordic study, in which hypofractionated RT was associated with improved mOS compared to standard RT (7.0 vs. 5.2 months, respectively). 3TMZ alone compared to radiotherapy alone was studied among elderly patients in the German Neuro-oncology Working Group NOA-08 study.TMZ was noninferior to RT alone with an mOS of 8.6 versus 9.6 months, respectively. 4Combinatorial therapy was studied in the Canadian CE.6 study.mOS was longer with the addition of TMZ compared to hypofractionated RT (40 Gy in 15 fractions) alone (9.3 vs. 7.6 months, respectively), and patients with MGMT methylated tumors treated with TMZ had the greatest benefit (13.5 vs. 7.6 months). 5mOS also was modestly prolonged among patients with MGMT promoter unmethylated tumors who received TMZ (10.0 vs. 7.9 months).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".