Multifocal Glioblastoma Managed With Primary Temozolomide as a Strategy to Delay Radiation Therapy: Clinical and Radiological Outcomes

Abstract

Abstract Aim To evaluate the clinical and radiological outcomes of upfront temozolomide (TMZ) monotherapy in deferring radiotherapy for multifocal glioblastoma (GBM). Methods We analysed 18 consecutive adult patients with newly diagnosed, multifocal GBM treated with upfront TMZ monotherapy between 2016 and 2024. The primary endpoint was a 6‐month progression‐free survival (PFS). Secondary endpoints were overall survival (OS) and radiological tumor response. Results The median age of the cohort was 69 years. The median follow‐up was 12 months. Thirteen (72.2%) patients had O⁶‐methylguanine‐DNA methyltransferase (MGMT)‐methylated tumors. Bi‐hemispheric disease was present in 16 patients (88.9%) at baseline. Patients received a median of six TMZ cycles. Disease relapse occurred in 94.4% ( n = 17) of cases, with 47.0% of failures involving distant sites. The 6‐month PFS was 61% (95% CI: 42.3%–88.3%), and the median OS was 12.2 months (95% CI: 11.2–31.1). MGMT‐methylated tumors demonstrated a significant volumetric reduction at 3 months compared to unmethylated cases (median −34.2% vs. +114.0%; p = 0.007). Survival outcomes trended in favour of the methylated cohort (6‐month PFS 69.2% vs. 40.0%; median OS 12.3 vs. 11.2 months), though these associations did not reach statistical significance ( p = 0.480). Conclusion This study provides valuable insights into the use of primary TMZ as an exploratory strategy for short‐term modulation in highly selected patients with extensive multifocal GBM. Whilst this approach facilitates a strategic delay in large‐volume radiation, the high relapse rate underscores that upfront TMZ serves as a temporary window for deferring neurotoxicity rather than achieving durable disease control.