MRI Features and IDH Mutational Status of Grade II Diffuse Gliomas: Impact on Diagnosis and Prognosis

Abstract

BACKGROUND Grade II diffuse gliomas (DGs) with isocitrate dehydrogenase (IDH) mutations are associated with better prognosis than their IDH-wildtype counterparts. We sought to determine MRI characteristics associated with IDH mutational status and whether MRI, combined with IDH mutational status, can better predict clinical outcomes of grade II DGs. METHODS Preoperative MRIs were retrospectively studied for qualitative tumor characteristics including location, extent, cortical involvement, margin sharpness, cystic component, mineralization or hemorrhage, and contrast enhancement. Quantitative diffusion and perfusion metrics were also assessed. Logistic regression and receiver operating characteristic analyses were used to evaluate the relationship between MRI features and IDH mutational status. The association between IDH mutational status, 1p19q co-deletion, MRI features, extent of resection, and clinical outcomes was assessed by Kaplan-Meier and Cox proportional hazards models. RESULTS Of 100 grade II DGs, 78 were IDH-mutant and 22 were IDH-wildtype. IDH-wildtype tumors were associated with older age, multifocality, brainstem involvement, lack of cystic change, and lower ADC. Multivariable regression showed that age >45 years as well as ADCmin, ADCmean, and ADCmax were independently associated with IDH mutational status. Of these, an ADCmin threshold of 0.9 × 10−3 mm2/s provided greatest sensitivity and specificity (91% and 76%, respectively) in defining IDH-wildtype grade II DGs. Combining low ADCmin with IDH-wildtype status conferred worse outcomes than IDH-wildtype status alone. CONCLUSION IDH-wildtype grade II DGs are associated with lower ADC and poor clinical outcomes. Combining IDH mutational status and ADC may allow for more accurate prediction of clinical outcomes in patients with grade II DGs.

T2 mapping of molecular subtypes of WHO grade II/III gliomas

“…Verger et al (2017) for example showed an increased Tracer (F-FDOPA) Bold data shows significant values uptake in PET-CT in IDH-mut and WHO grade III glioma [30]. Even recent studies like Villanueva-Meyer et al (2018) who found significant differences depending on the IDH status of WHO grade II glioma by use of ADC (apparent diffusion coefficient)-maps could not fully meet the expectations in clinical practice [9]. Nevertheless, no technique was valid enough to implement it into the clinical routine.…”

“…Malignant gliomas are the most frequent primary brain tumors in adults [1][2][3][4][5][6]. In 2016 the World Health Organization (WHO) Classification of Tumors of the Central Nervous System initially "integrated" [7] genotypic parameters such as molecular genetic tumor markers in its revised version from 2016 [5,8,9]. This new classification adds the genetic markers and gives a more precise division into molecular subgroups with distinct molecular signatures [5,8,10].…”

“…This new classification adds the genetic markers and gives a more precise division into molecular subgroups with distinct molecular signatures [5,8,10]. These groups may correlate with their histologic subtype and define different patient's prognosis and treatment response [5,[8][9][10][11][12].…”

“…One of the most important markers in gliomas is the isocitrate dehydrogenase (IDH) 1 and 2 [5,9,[11][12][13]. IDH1 and IDH2 are coding for isocitrate dehydrogenase, which catalyzes the conversion of isocitrate to alpha-ketoglutarate (ΑKG), leading to an increased level of D2HG in IDH mutated tumors [3,5,6,[13][14][15].…”

“…Another effect of IDHmutation (IDH-mut) is the inhibition of the PI3K/Akt pathway, which may induce a higher level of apoptosis [16]. IDH mutations in general are associated with a better prognosis by influencing cell proliferation, angiogenesis and vascularization [1,3,5,6,8,9,11,14,[16][17][18].…”