Volumetric study reveals the relationship between outcome and early radiographic response during bevacizumab-containing chemoradiotherapy for unresectable glioblastoma

Abstract

Purpose Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBM), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of early radiographic responses in nd-GBM treated with BEV. Methods Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. An experienced neuroradiologist interpreted early responses on fluid-attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI). Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response Assessment in Neuro-Oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan–Meier analysis. Results The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (p = 0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologist’s interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in the RANO criteria. However, even less stringent neuroradiologist interpretation could successfully predict OS prolongation (improved vs. non-improved: p = 0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20–50% (20%, p = 0.0315; 30%, p = 0.087; 40%, p = 0.0456). Conclusions Early response during BEV-containing chemoradiation can be a predictive indicator of patient outcome in unresectable nd-GBM.

An exploratory prospective phase II study of preoperative neoadjuvant bevacizumab and temozolomide for newly diagnosed glioblastoma

“…Because the volume reduction of FLAIR abnormality is likely to be susceptible to pseudoresponse, our results might provide evidence that tumor volume on T1CE is more reliable indicator of response to Bev that could be associated with patient OS, than that on FLAIR. Indeed, previous reports have supported our results, demonstrating that early progression on T1CE but not FLAIR after Bev-containing chemoradiotherapy offers a prognostic indicator for OS in recurrent and newly diagnosed GB [ 21 , 22 ].…”

Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study

“…The patients were treated as previously described. 25 ) Patients were excluded based on previously described criteria. 26 ) Patients with BRAF mutations were also excluded because they comprise a distinct biological subgroup of GBM.…”

Imposing Phase II and Phase III Clinical Trials of Targeted Drugs for Glioblastoma: Current Status and Progress

“…This is because a pseudoresponse may occur in the early stage of treatment and such a "response" will also be present on MRI. At this point, if clinicians use MRI to assess the efficacy of BEV, the disease progression cannot be recognized (8).Thus, the phase III evidence for BEV is still disappointing.…”