Pre-operative MRI radiomics model non-invasively predicts key genomic markers and survival in glioblastoma patients.

PURPOSE: Although glioblastoma (GBM) is the most common primary brain malignancy, few tools exist to pre-operatively risk-stratify patients by overall survival (OS) or common genetic alterations. We developed an MRI-based radiomics model to identify patients with EGFR amplification, MGMT methylation, GBM subtype, and OS greater than 12 months. METHODS: We retrospectively identified 235 patients with pathologically confirmed GBMs from the Cancer Genome Atlas (88; TCGA) and MD Anderson Cancer Center (147; MDACC). After two neuroradiologists segmented MRI tumor volumes, we extracted first-order and second-order radiomic features (gray-level co-occurrence matrices). We used the Maximum Relevance Minimum Redundancy technique to identify the 100 most relevant features and validated models using leave-one-out-cross-validation and validation on external datasets (i.e., TCGA). Our results were reported as the area under the curve (AUC). RESULTS: The MDACC patient cohort had significantly higher OS (22 months) than the TCGA dataset (14 months). On both LOOCV and external validation, our radiomics models were able to identify EGFR amplification (all AUCs > 0.83), MGMT methylation (all AUCs > 0.85), GBM subtype (all AUCs > 0.92), and OS (AUC > 0.91 on LOOCV and 0.71 for TCGA validation). CONCLUSIONS: Our robust radiomics pipeline has the potential to pre-operatively discriminate common genetic alterations and identify patients with favorable survival.

Endovascular Stroke Interventions: Procedural Complications and Management.

Endovascular mechanical thrombectomy has evolved significantly and has become the mainstay and most effective currently available treatment for acute ischemic stroke patients due to large vessel occlusion. Mechanical thrombectomy is presently performed using a stent retriever or stent-like device, an aspiration catheter, or a combination of the two. Much of the literature has focused on the benefits of endovascular mechanical thrombectomy with only limited data about procedural complications and management. Awareness of risk factors and early recognition of these complications can potentially reduce complication rates, improve management, and yield better overall outcomes. In this review, the authors present a description of intraprocedural complications and strategies to prevent and treat these complications.

Durability of partial splenic artery embolization on platelet counts for cancer patients with hypersplenism-related thrombocytopenia.

PURPOSE: Partial splenic artery embolization (PSAE) has shown promise in increasing platelet counts in cancer patients with hypersplenism-related thrombocytopenia. The purpose of this study was to identify response predictors and to longitudinally evaluate PSAE efficacy and durability in a large cohort of cancer patients with hypersplenism-related thrombocytopenia. METHODS: A single-institution, IRB-approved, HIPAA-compliant retrospective review of all PSAEs for thrombocytopenia between 2012 and 2015 was performed. Patients were classified as complete responders (CR, no platelet value < 100 × 109/L following PSAE), partial responders (PR, initial increase in platelets but subsequent decrease in platelets < 100 × 109/L), and non-responders (NR, platelets never > 100 × 109/L following PSAE). RESULTS: Of the 98 patients included in the study, 58 had CR (59%), 28 had PR (29%), and 12 patients had NR (12%). The percent splenic tissue embolized was significantly greater in the CR group compared to the PR group (P = 0.001). The percent volume of splenic tissue embolized was linearly correlated with the magnitude of platelet increase without a minimum threshold. At least one line of chemotherapy was successfully restarted in 97% of patients, and 41% of patients did not experience recurrence of thrombocytopenia for the duration of their survival. The major complication rate was 8%, with readmission following initial hospitalization for persistent "post-embolization syndrome" symptoms the most common. CONCLUSIONS: In cancer patients with hypersplenism-related thrombocytopenia, PSAE is a safe intervention that effects a durable elevation in platelet counts across a range of malignancies and following the re-initiation of chemotherapy.

Styloid Process Osteoradionecrosis: Report of 3 Cases.

We report the imaging and clinical findings in 3 patients with osteoradionecrosis of the styloid process, an uncommon consequence of radiation therapy for head and neck malignancy.

A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models.

PURPOSE: Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma. EXPERIMENTAL DESIGN: Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data glioblastoma patients (n = 93) and orthotopic xenografts (OX; n = 40). Tumor phenotypes were segmented, and radiomic-features extracted using the developed radiome-sequencing pipeline. Patients and animals were dichotomized on the basis of Periostin (POSTN) expression levels. RNA and protein levels confirmed RNAi-mediated POSTN knockdown in OX. Total RNA of tumor cells isolated from mouse brains (knockdown and control) was used for microarray-based expression profiling. Radiomic-features were utilized to predict POSTN expression status in patient, mouse, and interspecies. RESULTS: Our robust pipeline consists of segmentation, radiomic-feature extraction, feature normalization/selection, and predictive modeling. The combination of skull stripping, brain-tissue focused normalization, and patient-specific normalization are unique to this study, providing comparable cross-platform, cross-institution radiomic features. POSTN expression status was not associated with qualitative or volumetric MRI parameters. Radiomic features significantly predicted POSTN expression status in patients (AUC: 76.56%; sensitivity/specificity: 73.91/78.26%) and OX (AUC: 92.26%; sensitivity/specificity: 92.86%/91.67%). Furthermore, radiomic features in OX were significantly associated with patients with similar POSTN expression levels (AUC: 93.36%; sensitivity/specificity: 82.61%/95.74%; P = 02.021E-15). CONCLUSIONS: We determined causality between radiomic texture features and POSTN expression levels in a preclinical model with clinical validation. Our biologically validated radiomic pipeline also showed the potential application for human-mouse matched coclinical trials.

Multi-center study finds postoperative residual non-enhancing component of glioblastoma as a new determinant of patient outcome.

INTRODUCTION: The aim of the present study is to assess whether postoperative residual non-enhancing volume (PRNV) is correlated and predictive of overall survival (OS) in glioblastoma (GBM) patients. METHODS: We retrospectively analyzed a total 134 GBM patients obtained from The University of Texas MD Anderson Cancer Center (training cohort, n = 97) and The Cancer Genome Atlas (validation cohort, n = 37). All patients had undergone postoperative magnetic resonance imaging immediately after surgery. We evaluated the survival outcomes with regard to PRNV. The role of possible prognostic factors that may affect survival after resection, including age, sex, preoperative Karnofsky performance status, postoperative nodular enhancement, surgically induced enhancement, and postoperative necrosis, was investigated using univariate and multivariate Cox proportional hazards regression analyses. Additionally, a recursive partitioning analysis (RPA) was used to identify prognostic groups. RESULTS: Our analyses revealed that a high PRNV (HR 1.051; p-corrected = 0.046) and old age (HR 1.031; p-corrected = 0.006) were independent predictors of overall survival. This trend was also observed in the validation cohort (higher PRNV: HR 1.127, p-corrected = 0.002; older age: HR 1.034, p-corrected = 0.022). RPA analysis identified two prognostic risk groups: low-risk group (PRNV < 70.2 cm3; n = 55) and high-risk group (PRNV ≥ 70.2 cm3; n = 42). GBM patients with low PRNV had a significant survival benefit (5.6 months; p = 0.0037). CONCLUSION: Our results demonstrate that high PRNV is associated with poor OS. Such results could be of great importance in a clinical setting, particularly in the postoperative management and monitoring of therapy.

Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype.

Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.