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.

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