Prospective randomized trial of tumor-treating fields with chemoradiation in newly diagnosed glioblastoma

Dror Limon; Felix Bokstein; Deborah T Blumenthal; Zvi Ram; Rachel Grossman

doi:10.1093/noajnl/vdag106

Prospective randomized trial of tumor-treating fields with chemoradiation in newly diagnosed glioblastoma

Neurooncol Adv. 2026 Apr 24;8(1):vdag106. doi: 10.1093/noajnl/vdag106. eCollection 2026 Jan-Dec.

Authors

Dror Limon¹, Felix Bokstein², Deborah T Blumenthal², Zvi Ram³, Rachel Grossman⁴

Affiliations

¹ Radiation Oncology Unit, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
² Department of Oncology, Tel-Aviv Medical Center, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
³ Department of Neurosurgery, Tel-Aviv Medical Center, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
⁴ Department of Neurosurgery, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion, Haifa, Israel.

Abstract

Background: Tumor-treating fields (TTFields) have demonstrated efficacy in newly diagnosed glioblastoma (ndGBM) when combined with adjuvant temozolomide (TMZ). Preclinical studies suggest that TTFields enhance the therapeutic effect of radiotherapy (RT), providing a rationale for concurrent administration with radiotherapy (RT). This phase 2 randomized trial evaluated the addition of TTFields to standard RT and TMZ, followed by adjuvant TMZ with TTFields, in patients with ndGBM.

Methods: Patients were randomized prior to chemoradiation to receive RT and TMZ with or without concurrent TTFields, followed by maintenance TMZ with TTFields in both groups. The evaluable cohort, defined as an exploratory analysis, included patients who completed at least 4-weeks of RT (≥40Gy) and TTFields in the experimental arm the primary endpoint, based on the intention-to-treat (ITT) population, was 1-year progression-free survival (PFS12). Secondary endpoints included PFS, overall survival (OS) and safety.

Results: Sixty-six patients were randomized (experimental n = 32; control n = 34). In the ITT population, PFS12 favored the experimental group (28.7% vs 17.3%) but did not reach statistical significance (P = .146). Median PFS was 5.4 vs 4.13 months (P = .14) and median OS was 18.5 vs 16.5 months (P = .95) respectively. In the evaluable cohort (n = 54), PFS12 favored experimental group (37.5% vs 17.3%, P = .06), with a significantly longer median PFS (9.9 vs 4.1 months, P = .016). Median OS favored the experimental group (25.9 vs 16.6 months, P = .308). Treatment was well tolerated, with adverse events similar between groups.

Conclusions: Early integration of TTFields with chemoradiation in ndGBM is safe, feasible. Although the primary endpoint was not met, observed survival trends support further evaluation in larger multicenter trials to confirm the potential benefit of concurrent TTFields with chemoradiation.

Keywords: newly diagnosed glioblastoma; randomized clinical trial; survival; tumor treating fields.