Triple-Negative Glioma: MR Features & Molecular Markers in an Aggressive Subtype of Low-Grade Glioma

Presenting Author Senior Author
Name: Javier Villanueva-Meyer Name: Soonmee Cha
Email: Email:
Presenting Author’s RIG/SRG: Neuroradiology  
Presenting Author's Lab Location: Parnassus   

Abstract Information
Imaging Modality: MR
Disease Application: Brain Cancer
Complete author list: Javier Villanueva Meyer, MD; Byung Se Choi, MD; Matthew Wood, MD, PhD; Tarik Tihan, MD, PhD; Soonmee Cha, MD
Abstract highlights: MR features can be used alongside molecular biomarkers to assess the aggressiveness and prognosis of low grade gliomas and subsequently may provide a means of guiding treatment and follow-up options as patient-tailored therapy.
Low-grade gliomas (LGGs) are a heterogeneous group of tumors with distinct clinical behavior and prognosis. One strategy to improve their characterization is through the use of molecular biomarkers: p53, IDH 1/2, and 1p19q. These objective markers correlate with histologic classification and clinical outcomes. Specifically, the absence of IDH1/2 mutation or 1p19q deletion have been identified as indicative of a poor prognosis relative to LGGs harboring this mutation or loss, respectively. The purpose of our study was to determine MR imaging parameters that can discriminate a, recently-described, aggressive subtype of LGG that is characterized by an absence of these three genetic alterations.
A retrospective review of our electronic medical records from 2010 to 2014 yielded 105 cases of pathologically-confirmed LGG that also had molecular testing for p53 mutation, IDH1/2 mutation, and 1p/19q deletion. The MR imaging characteristics including tumor location, volume, infiltration pattern, cortical involvement, hemorrhage, and contrast-enhancement, and quantitative diffusion and perfusion MRI were assessed in these cases and compared to low-grade gliomas harboring these mutations. Additionally, clinical data of patient treatment, disease course, and survival was collected.
There were 24 diffuse astrocytomas (23%), 36 oligoastrocytomas (34%) and 45 oligodendrogliomas (43%). P53 mutation was found in 21 cases (20%), IDH1/2 mutation was found in 70 cases (67%), and 1p19q deletion was found in 45 cases (43%). Thirteen cases (12%) did not have any of these three genetic alterations. Triple-negative tumors showed a significantly lower incidence of cortical involvement (p<0.05) and lower mean and minimum apparent diffusion coefficient (ADC) values (1.25 vs. 1.45 x 10-3 mm2/s; 0.89 vs. 1.09 x 10-3 mm2/s, p<0.01). Multiple logistic regression analysis showed low ADC value as an independent predictor of triple-negative LGG. With a cut-off of 1.0 x 10-3 mm2/s, the ADC value provided a sensitivity of 73% and a specificity of 72% with an odds ratio of 7.0 (p<0.01). In cases with available clinical follow-up, triple-negative LGGs were found to have disease progression within 2 years in 50% of cases compared to 16% in the non-triple-negative cohort.
Triple-negative LGGs are associated with lower mean ADC values and lack of cortical involvement on MR examination and with a clinically aggressive phenotype.