Radiogenomic Predictors of Recurrence in Glioblastoma-A Systematic Review

Abstract

Glioblastoma, as the most aggressive brain tumor, is associated with a poor prognosis and outcome. To optimize prognosis and clinical therapy decisions, there is an urgent need to stratify patients with increased risk for recurrent tumors and low therapeutic success to optimize individual treatment. Radiogenomics establishes a link between radiological and pathological information. This review provides a state-of-the-art picture illustrating the latest developments in the use of radiogenomic markers regarding prognosis and their potential for monitoring recurrence. Databases PubMed, Google Scholar, and Cochrane Library were searched. Inclusion criteria were defined as diagnosis of glioblastoma with histopathological and radiological follow-up. Out of 321 reviewed articles, 43 articles met these inclusion criteria. Included studies were analyzed for the frequency of radiological and molecular tumor markers whereby radiogenomic associations were analyzed. Six main associations were described: radiogenomic prognosis, MGMT status, IDH, EGFR status, molecular subgroups, and tumor location. Prospective studies analyzing prognostic features of glioblastoma together with radiological features are lacking. By reviewing the progress in the development of radiogenomic markers, we provide insights into the potential efficacy of such an approach for clinical routine use eventually enabling early identification of glioblastoma recurrence and therefore supporting a further personalized monitoring and treatment strategy.

Keywords: GBM; glioblastoma; gliomas; imaging genomics; magnetic resonance imaging; molecular markers; neuro-oncology; radiogenomics; radiology; radiomics; recurrence.

Figure 1

PRISMA flow chart for the systematic review detailing the database searches, the number of records screened, and the studies included.

Figure 2

Tumor localization based on tumor-associated parameters. MGMT-methylated tumors and tumors with a lower Ki-67 value were lateralized to the left hemisphere. In contrast, MGMT-unmethylated tumors and tumors with mutation of IDH1 were found to be lateralized to the right hemisphere. IDH1-mutant tumors were located in the frontal lobe, whereas IDH wild-type tumors were located in the frontal and temporal lobes. Tumors with the proneural gene expression subtype and tumors with an absent loss of PTEN frequently occurred in the frontal lobe. MGMT-methylated tumors were located in the (left) frontal and left temporal lobes. In contrast, MGMT-unmethylated tumors were located in the insular lobe. Tumors revealing EGFR amplification and EGFRvIII-mutated tumors involved the frontal, left temporal and parietal regions. Temporal location was associated with IDH wild-type tumors. Abbreviations: EGFR+, EGFR amplification; EGFRvIII+, EGFRvIII mutation; IDH1+, IDH1 mutation; IDH-wt, IDH wildtype; Ki-67, Kiel-antigen Nr.67; MGMT-, MGMT promotor unmethylated; MGMT+, MGMT promotor methylated.