Assessment of Pre-operative Measurements of Tumor Size by MRI Methods as Survival Predictors in Wild Type IDH Glioblastoma

© 2020 Palpan Flores, Vivancos Sanchez, Roda, Cerdán, Barrios, Utrilla, Royo and Gandía González.[Objective]: We evaluate the performance of three MRI methods to determine non-invasively tumor size, as overall survival (OS) and Progression Free Survival (PFS) predictors, in a cohort of wild type, IDH negative, glioblastoma patients. Investigated protocols included bidimensional (2D) diameter measurements, and three-dimensional (3D) estimations by the ellipsoid or semi-automatic segmentation methods. [Methods]: We investigated OS in a cohort of 44 patients diagnosed with wild type IDH glioblastoma (58.2 ± 11.4 years, 1.9/1 male/female) treated with neurosurgical resection followed by adjuvant chemo and radiotherapy. Pre-operative MRI images were evaluated to determine tumor mass area and volume, gadolinium enhancement volume, necrosis volume, and FLAIR-T2 hyper-intensity area and volume. We implemented then multivariate Cox statistical analysis to select optimal predictors for OS and PFS. [Results]: Median OS was 16 months (1–42 months), ranging from 9 ± 2.4 months in patients over 65 years, to 18 ± 1.6 months in younger ones. Patients with tumors carrying O6-methylguanin-DNA-methyltransferase (MGMT) methylation survived 30 ± 5.2 vs. 13 ± 2.5 months in non-methylated. Our study evidenced high and positive correlations among the results of the three methods to determine tumor size. FLAIR-T2 hyper-intensity areas (2D) and volumes (3D) were also similar as determined by the three methods. Cox proportional hazards analysis with the 2D and 3D methods indicated that OS was associated to age ≥ 65 years (HR 2.70, 2.94, and 3.16), MGMT methylation (HR 2.98, 3.07, and 2.90), and FLAIR-T2 ≥ 2,000 mm2 or ≥60 cm3 (HR 4.16, 3.93, and 3.72), respectively. Other variables including necrosis, tumor mass, necrosis/tumor ratio, and FLAIR/tumor ratio were not significantly correlated with OS. [Conclusion]: Our results reveal a high correlation among measurements of tumor size performed with the three methods. Pre-operative FLAIR-T2 hyperintensity area and volumes provided, independently of the measurement method, the optimal neuroimaging features predicting OS in primary glioblastoma patients, followed by age ≥ 65 years and MGMT methylation.This work was supported in part by grants PI 2017/00361 from Instituto de Salud Carlos III to JR, MG, and AP and by grant B2017/BMD3688 from the Community of Madrid to JR, MG, and SC

Assessment of overall survival in glioma patients as predicted by metabolomic criteria

© 2019 Gandía-González, Cerdán, Barrios, López-Larrubia, Feijoó, Palpan, Roda and Solivera.[Objective]: We assess the efficacy of the metabolomic profile from glioma biopsies in providing estimates of postsurgical Overall Survival in glioma patients.[Methods]: Tumor biopsies from 46 patients bearing gliomas, obtained neurosurgically in the period 1992–1998, were analyzed by high resolution 1H magnetic resonance spectroscopy (HR- 1H MRS), following retrospectively individual postsurgical Overall Survival up to 720 weeks.[Results]: The Overall Survival profile could be resolved in three groups; Short (shorter than 52 weeks, n = 19), Intermediate (between 53 and 364 weeks, n = 19) or Long (longer than 365 weeks, n = 8), respectively. Classical histopathological analysis assigned WHO grades II–IV to every biopsy but notably, some patients with low grade glioma depicted unexpectedly Short Overall Survival, while some patients with high grade glioma, presented unpredictably Long Overall Survival. To explore the reasons underlying these different responses, we analyzed HR-1H MRS spectra from acid extracts of the same biopsies, to characterize the metabolite patterns associated to OS predictions. Poor prognosis was found in biopsies with higher contents of alanine, acetate, glutamate, total choline, phosphorylcholine, and glycine, while more favorable prognosis was achieved in biopsies with larger contents of total creatine, glycerol-phosphorylcholine, and myo-inositol. We then implemented a multivariate analysis to identify hierarchically the influence of metabolomic biomarkers on OS predictions, using a Classification Regression Tree (CRT) approach. The CRT based in metabolomic biomarkers grew up to three branches and split into eight nodes, predicting correctly the outcome of 94.7% of the patients in the Short Overall Survival group, 78.9% of the patients in the Intermediate Overall Survival group, and 75% of the patients in the Long Overall Survival group, respectively.[Conclusion]: Present results indicate that metabolic profiling by HR-1H MRS improves the Overall Survival predictions derived exclusively from classical histopathological gradings, thus favoring more precise therapeutic decisions.This work was supported in part by grants PI2017/00361 from Instituto de Investigación Carlos III to JR, grant B2017/BMD-3688 from the Community of Madrid to JR and SC, and grant PI-0143-2016 from the Regional Ministry of Health of the Regional Government of Andalucía to JS