Dataset Information

MRI Features May Predict Molecular Features of Glioblastoma in Isocitrate Dehydrogenase Wild-Type Lower-Grade Gliomas.

ABSTRACT:

Background and purpose

Isocitrate dehydrogenase (IDH) wild-type lower-grade gliomas (histologic grades II and III) with epidermal growth factor receptor (EGFR) amplification or telomerase reverse transcriptase (TERT) promoter mutation are reported to behave similar to glioblastoma. We aimed to evaluate whether MR imaging features could identify a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.

Materials and methods

In this multi-institutional retrospective study, pathologically confirmed IDH wild-type lower-grade gliomas from 2 tertiary institutions and The Cancer Genome Atlas constituted the training set (institution 1 and The Cancer Genome Atlas, 64 patients) and the independent test set (institution 2, 57 patients). Preoperative MRIs were analyzed using the Visually AcceSAble Rembrandt Images and radiomics. The molecular glioblastoma status was determined on the basis of the presence of EGFR amplification and TERT promoter mutation. Molecular glioblastoma was present in 73.4% and 56.1% in the training and test sets, respectively. Models using clinical, Visually AcceSAble Rembrandt Images, and radiomic features were built to predict the molecular glioblastoma status in the training set; then they were validated in the test set.

Results

In the test set, a model using both Visually AcceSAble Rembrandt Images and radiomic features showed superior predictive performance (area under the curve = 0.854) than that with only clinical features or Visually AcceSAble Rembrandt Images (areas under the curve = 0.514 and 0.648, respectively; P < . 001, both). When both Visually AcceSAble Rembrandt Images and radiomics were added to clinical features, the predictive performance significantly increased (areas under the curve = 0.514 versus 0.863, P < .001).

Conclusions

MR imaging features integrated with machine learning classifiers may predict a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.

SUBMITTER: Park CJ

PROVIDER: S-EPMC7959428 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

MRI Features May Predict Molecular Features of Glioblastoma in Isocitrate Dehydrogenase Wild-Type Lower-Grade Gliomas.

Park C J CJ Han K K Kim H H Ahn S S SS Choi D D Park Y W YW Chang J H JH Kim S H SH Cha S S Lee S-K SK

AJNR. American journal of neuroradiology 20210128 3

<h4>Background and purpose</h4>Isocitrate dehydrogenase (IDH) wild-type lower-grade gliomas (histologic grades II and III) with epidermal growth factor receptor (EGFR) amplification or telomerase reverse transcriptase (TERT) promoter mutation are reported to behave similar to glioblastoma. We aimed to evaluate whether MR imaging features could identify a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.<h4> ...[more]

PMID: 33509914

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Project description:BackgroundMutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lower-grade gliomas that carry IDH2 mutations.MethodsData from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test.ResultsTotally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively).ConclusionsIDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.

Project description:PurposeGlioblastomas (GBM) are the most common malignant primary brain tumors in adults and have a dismal prognosis. Patients frequently suffer from local tumor recurrences, with limited therapeutic options. Re-irradiation represents a possible intervention, but given the recent 5th edition of the World Health Organization classification of central nervous system tumors, studies in isocitrate dehydrogenase wild type (IDH-wt) cohorts undergoing a second course of radiotherapy remain limited. Herein, we sought to describe our institutional experience and outcomes after GBM IDH-wt re-irradiation.Materials and methodsGBM patients with confirmed IDH-wt status undergoing re-irradiation were included in this single-center, retrospective analysis.ResultsA total of 88 patients were analyzed. The median clinical and radiographic follow-up periods were 4.6 months and 4.4 months, respectively. Most patients had a Karnofsky performance status of at least 80% (n = 57). The median biologically effective dose and 2 Gy equivalent dose (EQD2) for re-irradiations, assuming an α/β ratio of 10 Gy for GBM, were 51.4 and 42.8 Gy, respectively. In total, 71 deaths were recorded. The median overall survival (OS) was 8.0 months. Multivariable Cox regression of OS revealed a positive influence of gross total resection vs. biopsy or no resection (hazard ratio: 0.43, p = 0.02). The median progression-free survival (PFS) was 5.9 months. The multivariable Cox regression for PFS did not detect any significant factors. No clear evidence of radiation necrosis was recorded during the available follow-up. However, only a minority (n = 4) of patients underwent surgery after re-irradiation, none showing histopathological proof of radiation necrosis.ConclusionThe prognosis for recurrent IDH-wt GBM after re-irradiation is poor. Patients who are amenable and able to undergo re-resection may have a favorable OS. A second course of radiotherapy with a moderate cumulative EQD2 and small- to medium-sized planning target volumes appeared safe regarding the occurrence of radiation necrosis.

Dataset Information

MRI Features May Predict Molecular Features of Glioblastoma in Isocitrate Dehydrogenase Wild-Type Lower-Grade Gliomas.

Background and purpose

Materials and methods

Results

Conclusions

Publications

MRI Features May Predict Molecular Features of Glioblastoma in <i>Isocitrate Dehydrogenase</i> Wild-Type Lower-Grade Gliomas.

Similar Datasets

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