Session Item

Differentiating early tumor progression (ETP) from pseudoprogression (PSP) in patients with glioblastoma (GBM) is crucial to improve prognosis. Objective of this study was to investigate the ability of multiapproach analysis including clinical data, diffusion weighted imaging (DWI), perfusion magnetic resonance imaging (MRI) and 3D magnetic resonance spectroscopic imaging (MRSI) to distinguish ETP from PSP in patients with GBM.

Among 180 patients included in prospective phase III Randomized SPECTROGLIO trial (NCT01507506)(1), 46 patients were suspected with progression within 6 months after end of radiotherapy. Ratios of choline/creatine (Cho/Cr), choline/N-acetyl aspartate (Cho/NAA) and lactate/N-acetyl aspartate (Lac/NAA) were extracted after co-registration of 3D-MRSI with the FLAIR and T1-weighted images before and after gadolinium administration. Voxels were analysed according to the region to which they belonged: contrast-enhanced (CE) lesion, necrosis and infiltrative oedema. Apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps were calculated and registered to T1 CE MRI. Differences between ETP and PSP were evaluated using Mann-Whitney tests and p-values were adjusted with Bonferroni correction. Logistic regressions with backward elimination procedure and area under receiver operator characteristic curve (AUC) analyses were used to assess the predictive ability of imaging parameters. Overall survival (OS) were calculated from inclusion until death or last-follow-up.

Based on the trial recommendations and RANO criteria on new MRI one month after progression suspicion, 28 patients were classified as PSP and 18 as ETP. After a median follow up of 41 months, OS rate at 2 years was 60.7% in PSP and 19.3% in ETP. Median survival was higher in PSP compared to ETP (25.2 months’ vs 20.3 months p=0.0092). There was no significant difference between groups in terms of gender, arm of treatment, type of surgery and MGMT status. Higher ratios of Lac/NAA and Cho/Cr were observed in ETP compared to those with PSP (median respectively 1.2 vs 0.5, p=0.006 and 3 vs 2.2, p=0.021) within the CE regions. ETP were characterized by Cho/Cr >2.33 with an AUC of 78%, sensibility (se)83%, specificity (sp)64%. Other parameters were Lac/NAA >0.61 and tumor volume (TV) >9.42 cc with respectively AUC of 81% and 81%, se of 100% and 100%, and sp of 63 % and 61%. Within the FLAIR edema, no significant predictor was retained after Bonferroni correction. TV was higher in ETP than in PSP (23.2cc vs 7.2cc p= 0.0075). After multivariable regression analysis, TV was the most significant predictor to classify ETP and PSP and the only one retained in the model (p=0.028). 

In this analysis from a prospective trial including DWI, perfusion and MRSI, we describe significant spectroscopic ratios, particularly surrogate’s markers of hypoxia, i.e. lactate. TV remains the only predictive factor in the multivariate analysis.

1.            Laprie A et al, BMC Cancer 2019