Choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas

Abstract

S. Choline-to-N-acetyl aspartate and lipids-lactate-tocreatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas. Br J Radiol 2016; 89: 20150502. FULL PAPERCholine-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas Objective: A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis. Methods: A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13-85 years). Oedema and viable tumour measurements were acquired using regions of interest in T 1 weighted, T 2 weighted, fluid-attenuated inversion recovery, apparent diffusion coefficient (ADC) and MR spectroscopy (MRS). We calculated Kaplan-Meier curves and obtained Cox's proportional hazards.Results: During the follow-up period (3-98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287-8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: x 2 (3) 5 9.098, p 5 0.028. Conclusion: MRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids-lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM.

Intratumoral Distribution of Lactate and the Monocarboxylate Transporters 1 and 4 in Human Glioblastoma Multiforme and Their Relationships to Tumor Progression-Associated Markers

“…Nevertheless, contamination of the lactate peak with signals of lipids cannot be completely avoided, and the amount remains unclear. Previous studies described a correlation of the progression-free survival with the lactate/creatine ratio [ 15 , 16 ], or the distribution of metabolites with tumor subtypes [ 17 ]. Despite the comparatively low number of patients in this study, the relative changes in the lactate concentrations among the different regions were significant.…”

Correlations between DTI-derived metrics and MRS metabolites in tumour regions of glioblastoma: a pilot study

“…21 Recent studies have shown the importance of Cho/NAA and LL/Cr ratios in assembling significant survival models in glioblastoma. 10 The use of DTI allows diffusion directionality to be quantified as different DTI-derived metrics 21 ; it yields ultrastructural information on cellular density and properties of the extracellular matrix. 22 In 2006, Pena et al expressed that it was not completely understood the magnitudes and associations among DTI measurements observed in the evaluation of brain tumours.…”

“…The results might be compared with previously published models. 10 To simplify the discussion of our findings, we grouped them into four sections:…”

“…9 MRS found that the cholineto-N-acetyl aspartate (Cho/Naa) ratio is the most substantial survival predictor in glioblastoma with a log-hazard function of 2.672 (each unit of increase in the Cho/Naa ratio represents a 267% increase in the risk of death in glioblastoma). 10 The usefulness of DTI-derived biomarkers has been proved in the differentiation of glioblastoma from brain abscesses and metastatic brain tumours 11 and between glioblastoma and healthy brains. 12 Up to 11 DTIderived biomarkers have calculated in brain MRI, each one with different diagnostic performance depending on the selected tumour region.…”

Imaging methods used in the assessment of environmental disease networks: a brief review for clinicians

“…Magnetic resonance spectroscopy (MRS) grant in vivo analysis of cerebral metabolites that establish chemical content in some brain regions, some of the metabolites more frequently studied is choline, N-acetyl aspartate (NAA), creatine and glutamate (Glu) [60]. Although the most common use of MRS has been in the evaluation of glioblastoma's survival [61], and epilepsy [62], recent applications of the MRS for environmental diseases have identified neurodevelopment variations due to prenatal exposure [4]. Studies about prenatal exposition to environmental pollution and the exposition during the first year of life are essential because of the importance of brain development during this time [63].…”