Apparent Diffusion Coefficient Metrics to Differentiate between Treatment-Related Abnormalities and Tumor Progression in Post-Treatment Glioblastoma Patients: A Retrospective Study.

Distinguishing treatment-related abnormalities (TRA) from tumor progression (TP) in glioblastoma patients is a diagnostic imaging challenge due to the identical morphology of conventional MR imaging sequences. Diffusion-weighted imaging (DWI) and its derived images of the apparent diffusion coefficient (ADC) have been suggested as diagnostic tools for this problem. The aim of this study is to determine the diagnostic accuracy of different cut-off values of the ADC to differentiate between TP and TRA. In total, 76 post-treatment glioblastoma patients with new contrast-enhancing lesions were selected. Lesions were segmented using a T1-weighted, contrast-enhanced scan. The mean ADC values of the segmentations were compared between TRA and TP groups. Diagnostic accuracy was compared by use of the area under the curve (AUC) and the derived sensitivity and specificity values from cutoff points. Although ADC values in TP (mean = 1.32 × 10-3 mm2/s; SD = 0.31 × 10-3 mm2/s) were significantly different compared to TRA (mean = 1.53 × 10-3 mm2/s; SD = 0.28 × 10-3 mm2/s) (p = 0.003), considerable overlap in their distributions exists. The AUC of ADC values to distinguish TP from TRA was 0.71, with a sensitivity and specificity of 65% and 70%, respectively, at an ADC value of 1.47 × 10-3 mm2/s. These findings therefore indicate that ADC maps should not be used in discerning between TP and TRA at a certain timepoint without information on temporal evolution.

Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas.

BACKGROUND: The disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative of aggressive tumor behavior and can thereby complement the prognostically favorable 1p/19q co-deletion. RESULTS: Genome-wide, 50 base pair single-end sequencing was performed to detect CNAs in a clinically well-characterized cohort of 98 formalin-fixed paraffin-embedded low-grade gliomas. CNAs are correlated with overall survival as an endpoint. Seventy-five additional samples from spatially distinct regions and paired recurrent tumors of the discovery cohort were analyzed to interrogate the intratumoral heterogeneity and spatial evolution. Loss of 10q25.2-qter is a frequent subclonal event and significantly correlates with an unfavorable prognosis. A significant correlation is furthermore observed in a validation set of 126 and confirmation set of 184 patients. Loss of 10q25.2-qter arises in a longitudinal manner in paired recurrent tumor specimens, whereas the prognostically favorable 1p/19q co-deletion is the only CNA that is stable across spatial regions and recurrent tumors. CONCLUSIONS: CNAs in low-grade gliomas display extensive intratumoral heterogeneity. Distal loss of 10q is a late onset event and a marker for reduced overall survival in low-grade glioma patients. Intratumoral heterogeneity and higher frequencies of distal 10q loss in recurrences suggest this event is involved in outgrowth to the recurrent tumor.

Health-related quality of life and cognitive functioning in long-term anaplastic oligodendroglioma and oligoastrocytoma survivors.

Overall survival of patients with anaplastic oligodendroglial tumors has been improved due to the addition of procarbazine, lomustine and vincristine (PCV) chemotherapy to radiotherapy (RT), especially in 1p/19q-codeleted tumors. With improved survival, quality of survival becomes pivotal. We evaluated cognitive functioning and health-related quality of life (HRQOL) in a cohort of long-term anaplastic oligodendroglioma survivors. Thirty-two out of 37 long-term survivors included in European Organisation for Research and Treatment of Cancer (EORTC) study 26951 in the Netherlands and France participated. Cognition was assessed using neuropsychological tests for 6 domains, and HRQOL with the EORTC Quality of Life Questionnaire (EORTC QLQ-C30) and Brain Cancer Module (EORTC QLQ-BN20). Fatigue and mood were evaluated. Results were compared to healthy controls and to patients' own HRQOL 2.5 years following initial treatment. At the time of assessment, median survival for the patients was 147 months, 27 were still progression-free since initial treatment. Of progression-free patients, 26% were not, and 30% were severely cognitively impaired; 41% were employed and 81% could live independently. Patients' HRQOL was worse compared to controls, but similar to 2.5 years after initial treatment. Initial treatment (RT versus RT + PCV) was not correlated with cognition or HRQOL. In conclusion, cognitive functioning in long-term anaplastic oligodendroglioma survivors is variable. However, most patients function independently. In progression-free patients, HRQOL is relatively stable during the disease course. In this small sample, no effect of the addition of PCV on cognition or HRQOL was identified.

Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution.

The histopathological diagnosis of diffuse gliomas often lacks the precision that is needed for tailored treatment of individual patients. Assessment of the molecular aberrations will probably allow more robust and prognostically relevant classification of these tumors. Markers that have gained a lot of interest in this respect are co-deletion of complete chromosome arms 1p and 19q, (hyper)methylation of the MGMT promoter and IDH1 mutations. The aim of this study was to assess the prognostic significance of complete 1p/19q co-deletion, MGMT promoter methylation and IDH1 mutations in patients suffering from diffuse gliomas. The presence of these molecular aberrations was investigated in a series of 561 diffuse astrocytic and oligodendroglial tumors (low grade n=110, anaplastic n=118 and glioblastoma n=333) and correlated with age at diagnosis and overall survival. Complete 1p/19q co-deletion, MGMT promoter methylation and/or IDH1 mutation generally signified a better prognosis for patients with a diffuse glioma including glioblastoma. However, in all 10 patients with a histopathological diagnosis of glioblastoma included in this study complete 1p/19q co-deletion was not associated with improved survival. Furthermore, in glioblastoma patients >50 years of age the favorable prognostic significance of IDH1 mutation and MGMT promoter methylation was absent. In conclusion, molecular diagnostics is a powerful tool to obtain prognostically relevant information for glioma patients. However, for individual patients the molecular information should be interpreted with caution and weighed in the context of parameters such as age and histopathological diagnosis.