Imaging biomarkers correlate with efficacy of bevacizumab combined with conventional therapy in newly diagnosed glioblastoma: an open-label, single arm trial

Purpose: To investigate the ability of potential imaging biomarkers to predict the response of bevacizumab (known as Avastin) combined with conventional therapy in newly diagnosed glioblastoma. Materials and Methods: Patients newly diagnosed with glioblastoma after surgery were enrolled to receive Avastin plus conventional concurrent radiotherapy and temozolomide. ¹⁸F-AlF-NOTA-PRGD2 positron emission tomography/computed tomography (¹⁸F-RGD PET/CT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed at baseline, week 3, and week 10 for each patient. Molecular information was assessed in patients’ tumor tissue. Statistical methods included the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard models. This trial was registered with Clinicaltrials.gov, number NCT01939574, ID ML28676.

Results: Twenty patients were prospectively enrolled, and the median follow-up time was 16 months (range, 4-42 months). The median progression-free survival (PFS) was 9.66 months (95% confidence interval [CI], 6.20-13.12 months). Parameters on ¹⁸F-RGD PET/CT and DCE MRI at baseline and changes from baseline to week 10 were found not to be predictive of PFS. However, a greater decrease in the mean standard uptake value (SUV_mean) from week 3 to week 10 was associated with better PFS (12.3 vs. 7.5 months, log rank p=0.009). In addition, low expression levels of epidermal growth factor receptor and vascular endothelial growth factor (VEGFA) were significantly associated with a longer PFS (7.46 vs. 11.40 months, p=0.045; high vs. low, 8.02 vs. 11.40 months, p=0.028). Isocitrate dehydrogenase 1 appeared to prolong PFS, but the association was not statistically significant (mutation vs. non-mutation, 4.2 vs. 10.8 months, p=0.065). Multivariate Cox hazard models were derived for PFS initially using clinical factors such as age, gender, smoking history, Karnofsky performance status, and parameters for which p<0.1. A greater decrease in SUV_mean before and after Avastin treatment remained a signficant predictor of better PFS independent of VEGFA expression (95% CI, 1.82-11575.72, p=0.026).

Conclusions: ¹⁸F-RGD PET/CT may be valuable in assessing the response of glioblastoma to treatment with the combination of Avastin and CCRT, with a greater decrease in SUV_mean predicting better PFS.