Dataset Information

Incidence and characteristics of pseudoprogression in IDH-mutant high-grade gliomas: A POLA network study.

ABSTRACT:

Background

Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described.

Methods

We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression.

Results

In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions.

Conclusion

In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered.

SUBMITTER: Seyve A

PROVIDER: S-EPMC10013645 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Incidence and characteristics of pseudoprogression in IDH-mutant high-grade gliomas: A POLA network study.

Seyve Antoine A Dehais Caroline C Chinot Olivier O Djelad Apolline A Cohen-Moyal Elisabeth E Bronnimann Charlotte C Gourmelon Carole C Emery Evelyne E Colin Philippe P Boone Mathieu M Vauléon Elodie E Langlois Olivier O di Stefano Anna-Luisa AL Seizeur Romuald R Ghiringhelli François F D'Hombres Anne A Feuvret Loic L Guyotat Jacques J Capelle Laurent L Carpentier Catherine C Garnier Louis L Honnorat Jérôme J Meyronet David D Mokhtari Karima K Figarella-Branger Dominique D Ducray François F

Neuro-oncology 20230301 3

<h4>Background</h4>Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described.<h4>Methods</h4>We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (r ...[more]

PMID: 35953421

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Project description:Roughly 50% of adult gliomas harbor isocitrate dehydrogenase (IDH) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized. Using bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers. Genes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and single-cell ATAC-seq data demonstrate that genes of myelination regulators and myelin components are hypermethylated and show inaccessible chromatin status, whereas regulators of OPC specification and maintenance are hypomethylated and show open chromatin status. Markers of astrocyte precursors are not enriched in IDH-mutant gliomas. Our studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas.

Project description:BACKGROUND AND PURPOSE:Isocitrate dehydrogenase (IDH)-mutant lower grade gliomas are classified as oligodendrogliomas or diffuse astrocytomas based on 1p/19q-codeletion status. We aimed to test and validate neuroradiologists' performances in predicting the codeletion status of IDH-mutant lower grade gliomas based on simple neuroimaging metrics. MATERIALS AND METHODS:One hundred two IDH-mutant lower grade gliomas with preoperative MR imaging and known 1p/19q status from The Cancer Genome Atlas composed a training dataset. Two neuroradiologists in consensus analyzed the training dataset for various imaging features: tumor texture, margins, cortical infiltration, T2-FLAIR mismatch, tumor cyst, T2* susceptibility, hydrocephalus, midline shift, maximum dimension, primary lobe, necrosis, enhancement, edema, and gliomatosis. Statistical analysis of the training data produced a multivariate classification model for codeletion prediction based on a subset of MR imaging features and patient age. To validate the classification model, 2 different independent neuroradiologists analyzed a separate cohort of 106 institutional IDH-mutant lower grade gliomas. RESULTS:Training dataset analysis produced a 2-step classification algorithm with 86.3% codeletion prediction accuracy, based on the following: 1) the presence of the T2-FLAIR mismatch sign, which was 100% predictive of noncodeleted lower grade gliomas, (n = 21); and 2) a logistic regression model based on texture, patient age, T2* susceptibility, primary lobe, and hydrocephalus. Independent validation of the classification algorithm rendered codeletion prediction accuracies of 81.1% and 79.2% in 2 independent readers. The metrics used in the algorithm were associated with moderate-substantial interreader agreement (κ = 0.56-0.79). CONCLUSIONS:We have validated a classification algorithm based on simple, reproducible neuroimaging metrics and patient age that demonstrates a moderate prediction accuracy of 1p/19q-codeletion status among IDH-mutant lower grade gliomas.

Dataset Information

Incidence and characteristics of pseudoprogression in IDH-mutant high-grade gliomas: A POLA network study.

Background

Methods

Results

Conclusion

Publications

Incidence and characteristics of pseudoprogression in IDH-mutant high-grade gliomas: A POLA network study.

Similar Datasets

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