Purpose: Dual timepoint FET-PET acquisition (10 and 60 minutes after FET injection) improves the definition of glioblastoma location and shape. Here we evaluated the safety and efficacy of simultaneous integrated boost (SIB) planned using dual FET-PET for postoperative glioblastoma treatment. Experimental Design: In this prospective pilot study (March 2017-December 2020), 17 patients qualified for FET-PET-based SIB intensity-modulated radiotherapy after resection. The prescribed dose was 78 and 60 Gy (2.6 and 2.0 Gy per fraction, respectively) for the FET-PET- and MR-based target volumes. Eleven patients had FET-PET within nine months to precisely define biological responses. Progression-free survival (PFS), overall survival (OS), toxicities, and radiation necrosis were evaluated. Six patients (35%) had tumors with MGMT promoter methylation. Results: The one- and two-year OS and PFS rates were 73% and 43% and 53% and 13%, respectively. The median OS and PFS were 24 (95%CI 9-26) and 12 (95%CI 6-18) months, respectively. Two patients developed uncontrolled seizures during radiotherapy and could not receive treatment per protocol. In patients treated per protocol, 7/15 presented with new or increased neurological deficits in the first month after irradiation. Radiation necrosis was diagnosed by MRI three months after SIB in five patients and later in another two patients. In two patients, the tumor was larger in FET-PET images after six months. Conclusions: Survival outcomes using our novel dose escalation concept (total 78 Gy) were promising, even within the MGMTunmethylated subgroup. Excessive neurotoxicity was not observed, but radionecrosis was common and must be considered in future trials.

Glioblastoma multiforme (GBM) is highly invasive. Despite irradiation with wide margins, GBM usually recurs in-field. Recent in vitro data have suggested that progression might be promoted by sublethal irradiation. Fluoroethylthyrosine-PET (FET-PET) can be used to detect glioblastoma invasion not apparent on MRI. We therefore performed a retrospective analysis of a prospective clinical study to examine whether glioblastoma outcomes depend on dose volume parameters measured by MRI and FET-PET. Twenty-three patients were prospectively recruited to a study examining the role of dual time point FET-PET in the treatment planning of GBM radiotherapy. The dose delivered to the site of recurrence was subdivided into suboptimal-dose (SOD) and high-dose (HD) areas. Types of progression were defined for correlation with dosimetric parameters including V100% of gross tumor volume (GTV)PET, GTVPETMRI, and GTVMRI. The HD area did not cover the entire GTVPETMRI in any case. Recurrences were significantly more frequent in the SubD area (chi-squared test, p = 0.004). There was no relationship between increasing dose volume and progression. The V100% for GTVPET and progression-free survival (PFS) was positively correlated (Spearman’s rho 0.417; p = 0.038). Progression is more common in areas with suboptimal dosing. Dose heterogeneity within GTVPET may be responsible for shorter PFS.

Supplementary Table from Safety and Efficacy of Irradiation Boost Based on ¹⁸F-FET-PET in Patients with Newly Diagnosed Glioblastoma

Supplementary Table from Safety and Efficacy of Irradiation Boost Based on ¹⁸F-FET-PET in Patients with Newly Diagnosed Glioblastoma