Abstract
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.
Highlights
Glioblastomas are the most aggressive and frequent primary tumors of the central nervous system in adult populations, with an approximate incidence of 3–5/100,000 people [1, 2]
Our pilot study investigates the prognostic value of three different methods of pre-surgical tumor size measurement by Magnetic Resonance Imaging (MRI), combined with relevant clinical and genetic information, as Overall Survival (OS) and Progression Free Survival (PFS) predictors
Summarizing, our study shows that the size of Fluid-Attenuation Inversion Recovery (FLAIR)-T2 hyper-intensity, as measured by the three methods, presents a similar significant impact in the OS and PFS under both, bivariate and multivariate analyses
Summary
Glioblastomas are the most aggressive and frequent primary tumors of the central nervous system in adult populations, with an approximate incidence of 3–5/100,000 people [1, 2]. Glioblastomas are currently classified in primary or secondary subtypes, reflecting either a “de novo” origin without evidence of any preceding lesion or, a “progression from a lower grade astrocytoma,” respectively [5]. Both subtypes have very different OS profiles, with longer survival estimates for the secondary. The molecular signature discriminating between primary (IDH wild type), or secondary subtypes, is the absence or presence, of the isocitrate dehydrogenase (IDH) mutation [5,6,7], respectively. Methylation of the O6 methylguanine DNA Methyltransferase (MGMT) promoter represents the molecular feature in prognostic relevance, predicting a better response to alkylating agents like temozolamide (TMZ), during adjuvant chemotherapy [8, 9]
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