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September 10, 2025Open Access

Survival in MGMT-Methylated GBM Treated With Combined Temozolomide/ Lomustine in Routine Care: A Uk Retrospective Multi-Centre Cohort Study

MWMatthew WilliamsThe University of Texas MD Anderson Cancer Center ELElizabeth LimUniversity Hospitals Plymouth NHS Trust LPLillie Pakzad-ShahabiImperial College Healthcare NHS Trust

Puntos clave

Median survival for patients with mgmt methylated glioblastoma treated with temozolomide and lomustine was 33.9 months.
Patients treated in routine care had significantly better survival rates than those in the Stupp trial, which reported median OS of 23.4 months.
Data were collected from three centres on patients receiving combined chemo-radiotherapy with temozolomide and lomustine.
This approach highlights the feasibility of combined temozolomide and lomustine treatment in improving outcomes for gbm patients.

Resumen

Abstract AIMS Glioblastoma (GBM) continues to have a poor prognosis. In 2019, the NOA-09 trial suggested that in patients with MGMT methylated GBM, chemo-radiotherapy with combined Temozolomide and Lomustine (TELOM) was superior to chemo-radiotherapy with temozolomide alone. However, there was a signiﬁcant selection effect and outcomes in routine care are rarely reported, with only one published case series. The NRG BN-011 trial is exploring the same question in the USA, and NIHR recently declined to fund a phase 3 UK RCT. We therefore collected data on outcomes in routine care. METHODS We collected retrospective data on outcomes in patients with MGMT methylated GBM treated at three insti- tutions with TELOM. To be eligible, patients had to have a histological diagnosis of newly diagnosed GBM or IDH-mutant Grade 4 astrocytoma, and have received chemo-radiotherapy (40Gy/15# or greater) with TELOM in either the adjuvant or concurrent and adjuvant setting. We extracted data on demographics, histological subtype, survival and other treatments. Patients treated between Jan 2021 and April 2024 were included, with follow-up until January 2025. RESULTS We identiﬁed 23 patients from 3 centres (17, 5, 1 pts respectively). Median age was 55, and 65% were male. 3 were IDH-mut, 17 received 59.4-60Gy of radiotherapy. 16 patients completed 6 cycles of chemotherapy; 13 had at least one cycle delayed. At time of analysis, 10 patients had died, with a median survival of 33.9 months. CONCLUSION Combined TELOM is feasible to deliver in the UK, with reasonable survival and toxicity rates. For practical reasons, many patients received concurrent RT & TMZ, and have adjuvant TELOM. Survival is signiﬁcantly better than patients with MGMT-methylated GBM in the Stupp trial (median OS of 23.4 months). We continue to update data, would encourage others to contribute and continue to develop a prospective multi-centre trial.

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