Long-term results in recurrent glioblastoma

By Huma Chaudhry, MD, National Institutes of Health

Presenting author: Maciej Harat, MD, PhD

Given that nearly 90% of glioblastomas will recur despite aggressive management, the optimal treatment of recurrent GBM (rGBM) remains to be defined.¹ Maciej Harat, MD, PhD, and colleagues presented long term results from their prospective phase II trial, TTaRGeT, combining tumor treating fields (TTF) and 18F-FET PET-guided stereotactic radiosurgery (SRS) in recurrent IDH wild-type GBM.

FET-PET was uniquely included in this phase II trial, building upon previously published prospective work by Dr. Harat. Early FET-PET universally identified uptake beyond MRI contrast enhancement and biopsied FET-positive sites upgraded to a higher grade tumor in 30% of cases.²

In the presented TTaRGeT study at this year’s ASTRO Annual Meeting, treatment schema included either 18-20 Gy in a single fraction or 25-30 Gy in 5-6 fractions, based on tumor volume, location and interval from prior radiation. The primary endpoint of the study was one-year overall survival. In this study, 35 patients with rGBM, IDH wild-type (WHO 2021) were included in the long-term survival analysis. The results demonstrate an impressive and durable survival, with a median OS of 16.8 months from enrollment, and five-year OS of 20.9% (95% CI, 7.3-39.2%). Median PFS was 5.9 months. Importantly, durable survival was also noted in the MGMT-unmethylated tumors with 30-month OS of 29.2%, though given the small patient numbers for comparison, the difference did not reach statistical significance. Further work is needed to determine the true prognostic implication of MGMT promoter methylation status in this setting.

Device compliance with TTF has been reported as a potential prognostic factor, suggesting at least 75% daily compliance may improve survival.³ In the TTaRGeT study, TTF compliance was high with a median usage of 83.2% and 27 of 40 patients using it at least 75% of the time. The treatment was well tolerated, with only one grade 3 radiation-induced contrast enhancement (RICE) event.

Existing dose-response literature suggests a survival benefit in reirradiation for rGBM with dose above BED10 of 40 Gy.⁴ In the TTaRGeT study presented here, the authors evaluated BED and the impact on survival in exploratory analyses. When grouped by radiation regimen: single fraction (1 x 18 Gy and 1 x 20 Gy) or 5 x 5 Gy and 5 x 6 Gy, median OS nearly doubled in the single fraction group at 30.4 months vs 12.7 and 15.3 months, respectively, however it did not reach statistical significance (p=0.073).

Higher BED (i.e. > 48 Gy, delivered as 5x6 Gy, 1x18Gy, or 1x20 Gy) was compared with 5 x 5 Gy (BED10 = 37.5 Gy), with median OS of 24.9 vs 12.7 months, but did not reach statistical significance (p=0.149). However, patients treated with a single fraction (18 Gy x 1 BED10 = 50.4 Gy) had significantly longer OS compared to those treated with 5 x 6 Gy (BED10 = 48.0 Gy) (p = 0.039). Given the limitations of delivering higher BED to larger volumes, the authors regard these dose-survival results as hypothesis-generating.

The 30-month survival rate was improved in smaller PTV <10cm 3, 50.3% vs. 15%, (p = 0.016). Dr. Harat and his team are further investigating the association between PTV volumes and survival in the randomized Tarrget 2.0 trial (NCT07668869) comparing TTFields plus FET-PET-guided stereotactic radiosurgery with TTFields alone in recurrent IDH-wildtype glioblastoma. This trial is sponsored by the Oncology Center in Bydgoszcz and funded by the Polish Medical Research Agency (Agencja Badań Medycznych, ABM).

TTaRGeT was investigator-initiated with external monitoring by a contract research organization, and was conducted in compliance with Good Clinical Practice.

The full TTaRGeT manuscript is currently under peer review to the International Journal of Radiation Oncology, Biology, Physics. We eagerly await its full publication and Dr. Harat’s future work to advance the treatment of recurrent GBM.

References

1. Minniti, G., et al., Current status and recent advances in reirradiation of glioblastoma. Radiat Oncol, 2021. 16(1): p. 36.
2. Harat, M., et al., Combining amino acid PET and MRI imaging increases accuracy to define malignant areas in adult glioma. Nature Communications, 2023. 14(1): p. 4572.
3. Regev, O., et al., Tumor-Treating Fields for the treatment of glioblastoma: a systematic review and meta-analysis. Neurooncol Pract, 2021. 8(4): p. 426–440.
4. Andratschke, N., et al., ESTRO/EANO recommendation on reirradiation of glioblastoma. Radiotherapy and Oncology, 2025. 204: p. 110696.

Abstract 238, Targeting Recurrent Glioblastoma with Stereotactic Radiosurgery and Tumor Treating Fields Guided by 18F-FET-PET: Long-Term Results from a Prospective Phase 2 Trial (TTaRGeT), was presented during SS 27: Advances in Multimodal Therapy for Glioblastoma: From Phase I to Phase III Trials, at ASTRO's 68th Annual Meeting.

Published on: September 30, 2026