MRI-Based Radiomic Signature for PI3K/AKT-Activated Glioblastoma

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PURPOSE/OBJECTIVE(S): Prior work has demonstrated that transcriptional signatures and immune cell infiltrates associated with phosphatidylinositol 3-kinase (PI3K) downregulation are able to distinguish glioblastoma patients who respond to immune checkpoint blockade. PI3K/Akt pathway is involved in tumorigenesis, immune microenvironment regulation, and chemo-radiation treatment resistance. We hypothesized that PI3K/Akt-activated glioblastoma may harbor imaging features that would allow for radiomic discrimination. MATERIALS/METHODS: Patients from The Cancer Genome Atlas and the Ivy Glioblastoma Atlas Project who underwent resection and received temozolomide-based chemoradiation from 1996-2003 were included. All tumors underwent RNA-sequencing and had pre-, post-operative and surveillance MRIs. Single sample Gene Set Enrichment Analysis (ssGSEA) was applied to gene expression data to identify samples with PI3K/Akt pathway activation. A programming environment-based machine learning software was used to extract unique quantitative image features from manually segmented pre-operative tumors from post-contrast T1 sequences. Prior to image analysis, all images underwent z-score normalization over all voxels. Extracted features included shape features, first-order statistical, intensity-histogram based, fractal, local intensity, and texture matrix-based features from both unfiltered and filtered images (wavelet decompositions). A threshold of P < 0.05 was used to identify significant radiomic features. Adaptive LASSO-penalized regression was used to develop a radiomic predictor for PI3K-Akt downregulation. Area under the ROC curve (AUC) assessed performance of the model with three-fold internal cross-validation. RESULTS: Twenty-two patients with glioblastoma were included in the analysis. Tumors from 8 of 22 patients (36.4%) had downregulation of PI3K/Akt signaling by ssGSEA. Among tumors with upregulation of PI3K/Akt signaling, 71% had upstream loss or deletion of PTEN. Tumors with downregulated PI3K/AKT signaling were also more likely to have intratumoral B cell lymphocytes identified by ssGSEA. Overall, 2800 radiomic features were extracted from pre-operative, post-contrast MRI images of 22 patients with glioblastoma. 49 features were significantly different between the two groups. Adaptive LASSO regression analysis was performed to develop a 6-feature radiomic signature with an AUC of 0.955 (95% Confidence Interval, 0.862-1.000). CONCLUSION: We identified a radiomic signature comprised of 6 features that classifies PI3K/Akt-activated glioblastoma, which is associated with increased immune cell infiltration and potential response to immunotherapy. This signature may help in identifying patients who may benefit from immunomodulation in glioblastoma.

Original languageEnglish (US)
Pages (from-to)e136-e137
JournalInternational Journal of Radiation Oncology, Biology, Physics
Issue number3
StatePublished - Nov 1 2021

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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