Johanna Heugenhauser

Background: This retrospective study used volumetric MRI assessment to compare 3 response assessment criteria, namely, RANO (response assessment in neuro-oncology), mRANO (modified response assessment in neuro-oncology), and RANO 2.0, in patients with newly diagnosed glioblastoma (GB) treated with standard-of-care therapy. We evaluated whether progression-free survival (PFS), defined by each criterion, serves as a prognostic marker for overall survival (OS), and evaluated the impact of progression on patient outcome using landmark analyses. Methods: A total of 137 GB patients were included. Tumor volumes were assessed using semiautomatic 3D segmentation of contrast-enhancing and T2/fluid-attenuated inversion recovery lesions on serial MRI. The PFS was determined using RANO, mRANO, and RANO 2.0 criteria. Correlation between PFS and OS was evaluated using Spearman rank test. Differences in PFS and postprogression survival were tested with the Kruskal-Wallis test and corrected for multiple testing. Landmark analyses at 8 and 12 months were conducted to assess the prognostic effect of progression, with hazard ratios (HRs) derived from Cox models. Results: Median PFS differed significantly across criteria: 7.9 months (RANO), 11.3 months (mRANO), and 9.7 months (RANO 2.0). The correlation of PFS with OS was best with mRANO (ρ = 0.70), followed by RANO 2.0 (ρ = 0.66) and RANO (ρ = 0.50). The highest HR for death in patients with progressive disease was seen with RANO 2.0 (HR = 3.6), followed by mRANO (HR = 3.3), and RANO (HR = 3.3) (8-month landmark). Conclusion: mRANO and RANO 2.0 provided strong prognostic value in newly diagnosed GB patients. mRANO and RANO 2.0 showed strong correlation between PFS and OS, while RANO 2.0 demonstrated the strongest stratification of survival risk based on progression status at landmarks.

Introduction: In this post hoc analysis we compared various response-assessment criteria in newly diagnosed glioblastoma (GB) patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression-free survival (PFS) and overall survival (OS). Methods: 76 patients enrolled in a multicenter phase II trial receiving standard of care (SOC, n = 40) or SOC + Audencel vaccine (n = 36) were included. MRI scans were evaluated using MacDonald, RANO, Vol-RANO, mRANO, Vol-mRANO and iRANO criteria. Tumor volumes (T1 contrast-enhancing as well as T2/FLAIR volumes) were calculated by semiautomatic segmentation. The Kruskal-Wallis-test was used to detect differences in PFS among the assessment criteria; for correlation analysis the Spearman test was used. Results: There was a significant difference in median PFS between mRANO (8.6 months) and Vol-mRANO (8.6 months) compared to MacDonald (4.0 months), RANO (4.2 months) and Vol-RANO (5.4 months). For the vaccination arm, median PFS by iRANO was 6.2 months. There was no difference in PFS between SOC and SOC + Audencel. The best correlation between PFS/OS was detected for mRANO (r = 0.65) and Vol-mRANO (r = 0.69, each p < 0.001). A total of 16/76 patients developed a pure T2/FLAIR progressing disease, and 4/36 patients treated with Audencel developed pseudoprogression. Conclusion: When comparing different response-assessment criteria in GB patients treated with dendritic cell-based immunotherapy, the best correlation between PFS and OS was observed for mRANO and Vol-mRANO. Interestingly, iRANO was not superior for predicting OS in patients treated with Audencel.