The role of reoperation for recurrent glioblastoma (GBM) remains unclear. Prospective studies are lacking. Here, we studied the association of clinical outcome with extent of resection upon surgery for recurrent GBM in the patient cohort of DIRECTOR, a prospective randomized multicenter trial comparing 2 dose-intensified temozolomide regimens at recurrence of GBM. We analyzed prospectively collected clinical and imaging data from the DIRECTOR cohort (N = 105). Volumetric analysis was performed on gadolinium contrast-enhanced MRI as well as fluid attenuated inversion recovery/T2 MRI and correlated with PFS after initial progression (PFS₂) and post-recurrence survival (PRS). Quality of life was monitored by the EORTC QLQ-C30 and QLQ-BN20 questionnaires at 8-week intervals. Seventy-one patients received surgery at first recurrence. Prognostic factors, including age, MGMT promoter methylation, and Karnofsky performance score, were balanced between patients with and without reoperation. Outcome in patients with versus without surgery at recurrence was similar for PFS₂ (2.0 mo vs 1.9 mo, P = .360) and PRS (11.4 mo vs 9.8 mo, P = .633). Among reoperated patients, post-surgery imaging was available in 59 cases. In these patients, complete resection of contrast-enhancing tumor (N = 40) versus residual detection of contrast enhancement (N = 19) was associated with improved PRS (12.9 mo [95% CI: 11.5–18.2] vs 6.5 mo [95% CI: 3.6–9.9], P < .001) and better quality of life. Incomplete tumor resection was associated with inferior PRS compared with patients who did not undergo surgery (6.5 vs 9.8 mo, P = .052). Quality of life was similar in these 2 groups. Surgery at first recurrence of GBM improves outcome if complete resection of contrast-enhancing tumor is achieved.

Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health Organization (WHO) classification. Parameters derived from uptake dynamics of ¹⁸F-fluoro-ethyl-tyrosine PET (¹⁸F-FET-PET) such as minimal time-to-peak (TTP_min) allow discrimination between different prognostic glioma subgroups, too. The present study is aimed at exploring whether TTP_min analysis provides prognostic information beyond the WHO classification. Three hundred patients with newly diagnosed WHO 2007 grades II–IV gliomas with ¹⁸F-FET-PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut–1p/19q codel; IDH1/2 mut–1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and glioblastoma). Clinical and imaging factors such as age, Karnofsky performance score, treatment, TTP_min, and maximal tumor-to-brain ratio (TBR_max) were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis. PFS and OS were longest in the IDH1/2 mut–1p/19q codel subgroup, followed by IDH1/2 mut–1p/19q non-codel, IDH1/2 wildtype, and GBM (P < 0.001). Further, outcome stratified by TTP_min with a cutoff of 17.5 minutes revealed significantly longer PFS and OS in patients with TTP_min >17.5 minutes (P < 0.001 for PFS and OS). Lower TBR_max values or the absence of ¹⁸F-FET uptake was also associated with favorable outcome in the entire group. In the subgroup analyses, longer median TTP_min was associated with improved outcome specifically in the IDH1/2 mut–1p/19q non-codel group. ¹⁸F-FET-PET–derived dynamic analysis defines prognostically distinct subgroups of IDH1/2 mutant–1p/19q non-codel gliomas which cannot be distinguished as yet by molecular marker analysis.

Aim: The aim of the current study was to enlighten the evolution of prostate-specific membrane antigen (PSMA) expression in glioblastoma between initial diagnosis and recurrence in order to provide preliminary insight for further clinical investigations into innovative PSMA-directed treatment concepts in neuro-oncology.Methods: Patients who underwent resection for de-novo glioblastoma (GBM) and had a re-resection in case of a recurrent tumor following radiochemotherapy and subsequent chemotherapy were included (n = 16). Histological and immunohistochemical stainings were performed at initial diagnosis and at recurrence (n = 96 tissue specimens). Levels of PSMA expression both in endothelial and non-endothelial cells as well as vascular density (CD34) were quantified via immunohistochemistry and changes between initial diagnosis and recurrence were determined. Immunohistochemical findings were correlated with survival and established clinical parameters.Results: PSMA expression was found to be present in all GBM tissue samples at initial diagnosis as well as in all but one case of recurrent tumor samples. The level of PSMA expression in glioblastoma varied inter-individually both in endothelial and non-endothelial cells. Likewise, the temporal evolution of PSMA expression highly varied in between patients. The level of vascular PSMA expression at recurrence and its change between initial diagnosis and recurrence was associated with post recurrence survival time: Patients with high vascular PSMA expression at recurrence as well as patients with increasing PSMA expression throughout the disease course survived shorter than patients with low vascular PSMA expression or decreasing vascular PSMA expression. There was no significant correlation of PSMA expression with MGMT promoter methylation status or Ki-67 labelling index.Conclusion: PSMA is expressed in glioblastoma both at initial diagnosis and at recurrence. High vascular PSMA expression at recurrence seems to be a negative prognostic marker. Thus, PSMA expression in GBM might present a promising target for theranostic approaches in recurrent glioblastoma. Especially PSMA PET imaging and PSMA-directed radioligand therapy warrant further studies in brain tumor patients.

This review provides an overview of current applications and perspectives of PET imaging in neuro-oncological surgery. The past and future of PET imaging in the management of patients with glioma and brain metastases are elucidated with an emphasis on amino acid tracers, such as O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (¹⁸F-FET). The thematic scope includes surgical resection planning, prognostication, non-invasive prediction of molecular tumor characteristics, depiction of intratumoral heterogeneity, response assessment, differentiation between tumor progression and treatment-related changes, and emerging new tracers. Furthermore, the role of PET using specific somatostatin receptor ligands for the management of patients with meningioma is discussed. Further advances in neuro-oncological imaging can be expected from promising new techniques, such as hybrid PET/MR scanners and the implementation of artificial intelligence methods, such as radiomics.