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BackgroundDiagnostic accuracy in previous studies of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in patients with suspected recurrent glioma may be influenced by prolonged dynamic PET acquisitions, heterogeneous populations, different non–standard-of-care therapies, and PET scans performed at different time points post radiotherapy. We investigated the diagnostic accuracy of a 20-minute 18F-FET PET scan in MRI-suspected recurrent glioblastoma 6 months after standard radiotherapy and its ability to prognosticate overall survival (OS).MethodsIn total, 146 glioblastoma patients with 168 18F-FET PET scans were reviewed retrospectively. Patients with MRI responses to bevacizumab or undergoing re-irradiation or immunotherapy after 18F-FET PET were excluded. Maximum and mean tumor-to-background ratios (TBRmax, TBRmean) and biological tumor volume (BTV) were recorded and verified by histopathology or clinical/radiological follow-up. Thresholds of 18F-FET parameters were determined by receiver operating characteristic (ROC) analysis. Prognostic factors were investigated in Cox proportional hazards models.ResultsSurgery was performed after 104 18F-FET PET scans, while clinical/radiological surveillance was used following 64, identifying 152 glioblastoma recurrences and 16 posttreatment changes. ROC analysis yielded thresholds of 2.0 for TBRmax, 1.8 for TBRmean, and 0.55 cm3 for BTV in differentiating recurrent glioblastoma from posttreatment changes with the best performance of TBRmax (sensitivity 99%, specificity 94%; P < 0.0001) followed by BTV (sensitivity 98%, specificity 94%; P < 0.0001). Using these thresholds, 166 18F-FET PET scans were correctly classified. Increasing BTV was associated with shorter OS (P < 0.0001).ConclusionA 20-minute 18F-FET PET scan is a powerful tool to distinguish posttreatment changes from recurrent glioblastoma 6-month postradiotherapy, and predicts OS.

BACKGROUND We conducted a phase 1 dose-escalation study of RO5323441, a novel antiplacental growth factor (PlGF) monoclonal antibody, to establish the recommended dose for use with bevacizumab and to investigate the pharmacokinetics, pharmacodynamics, safety/tolerability, and preliminary clinical efficacy of the combination. METHODS Twenty-two participants with histologically confirmed glioblastoma in first relapse were treated every 2 weeks with RO5323441 (625 mg, 1250 mg, or 2500 mg) plus bevacizumab (10 mg/kg). A standard 3 + 3 dose-escalation trial design was used. RESULTS RO5323441 combined with bevacizumab was generally well tolerated, and the maximum tolerated dose was not reached. Two participants experienced dose-limiting toxicities (grade 3 meningitis associated with spinal fluid leak [1250 mg] and grade 3 cerebral infarction [2500 mg]). Common adverse events included hypertension (14 participants, 64%), headache (12 participants, 55%), dysphonia (11 participants, 50%) and fatigue (6 participants, 27%). The pharmacokinetics of RO5323441 were linear, over-the-dose range, and bevacizumab exposure was unaffected by RO5323441 coadministration. Modulation of plasmatic angiogenic proteins, with increases in VEGFA and decreases in FLT4, was observed. Dynamic contrast-enhanced/diffusion-weighted MRI revealed large decreases in vascular parameters that were maintained through the dosing period. Combination therapy achieved an overall response rate of 22.7%, including one complete response, and median progression-free and overall survival of 3.5 and 8.5 months, respectively. CONCLUSION The toxicity profile of RO5323441 plus bevacizumab was acceptable and manageable. The observed clinical activity of the combination does not appear to improve on that obtained with single-agent bevacizumab in patients with recurrent glioblastoma.

BACKGOUND: Patients with glioblastoma (GBM) show a variable disease course ranging from rapid progression to prolonged progression free survival (PFS). Despite aggressive standard therapy consisting of radiotherapy plus concomitant and adjuvant temozolomide (RCX) the prognoses is poor with a median overall survival (OS) less than 15 months and 5-year overall survival less than 10%. To maximize patient survival and optimize quality of life, it is relevant to identify prognostic biomarkers for treatment stratification. Positron emission tomography (PET) scanning using radiolabeled amino acids has been introduced in the radiation therapy planning of GBM. Therefore this study will evaluate whether postoperative FET PET in newly diagnosed GBM can provide additional prognostic information on outcome. MATERIALS AND METHODS: 147 patients from our GBM database treated with RCX and evaluated with FET PET postoperatively (1-2 weeks) in the period November 2011 - February 2014 were included retrospectively. With OS as the primary endpoint, and PFS as a secondary endpoint, the prognostic value of postoperative biological tumor volume (BTV) in FET PET, mean tumor to background ratio (TBRmean) and maximum tumor to background ratio (TBRmax) was estimated using Cox proportional hazards model. The analysis was adjusted for the known prognostic factors, performance status (PS), age and corticosteroid therapy status, by multivariate analysis. RESULTS: Median OS and PFS were 14.0 and 6.54 months respectively. In the univariate analysis, increasing BTV and higher values of TBRmean and TBRmax correlated significantly (