The spectrum of rare central nervous system (CNS) tumors with EWSR1-non-ETS fusions: experience from three pediatric institutions with review of the literature.

The group of CNS mesenchymal (non-meningothelial) and primary glial/neuronal tumors in association with EWSR1-non-ETS rearrangements comprises a growing spectrum of entities, mostly reported in isolation with incomplete molecular profiling. Archival files from three pediatric institutions were queried for unusual cases of pediatric (≤21 years) CNS EWSR1-rearranged tumors confirmed by at least one molecular technique. Extra-axial tumors and cases with a diagnosis of Ewing sarcoma (EWSR1-ETS family fusions) were excluded. Additional studies, including anchored multiplex-PCR with next-generation sequencing and DNA methylation profiling, were performed as needed to determine fusion partner status and brain tumor methylation class, respectively. Five cases (median 17 years) were identified (M:F of 3:2). Location was parenchymal (n = 3) and undetermined (n = 2) with topographic distributions including posterior fossa (n = 1), frontal (n = 1), temporal (n = 1), parietal (n = 1) and occipital (n = 1) lobes. Final designation with fusion findings included desmoplastic small round cell tumor (EWSR1-WT1; n = 1) and tumors of uncertain histogenesis (EWSR1-CREM, n = 1; EWSR1-CREB1, n = 1; EWSR1-PLAGL1, n = 1; and EWSR1-PATZ1, n = 1). Tumors showed a wide spectrum of morphology and biologic behavior. For EWSR1-CREM, EWSR1-PLAGL1 and EWSR1-PATZ1 tumors, no significant methylation scores were reached in the known brain tumor classes. Available outcome (4/5) was reported as favorable (n = 2) and unfavorable (n = 2) with a median follow-up of 30 months. In conclusion, we describe five primary EWSR1-non-ETS fused CNS tumors exhibiting morphologic and biologic heterogeneity and we highlight the clinical importance of determining specific fusion partners to improve diagnostic accuracy, treatment and monitoring. Larger prospective clinicopathological and molecular studies are needed to determine the prognostic implications of histotypes, anatomical location, fusion partners, breakpoints and methylation profiles in patients with these rare tumors.

Immunotherapy and Response Assessment in Malignant Glioma: Neuro-oncology Perspective.

Glioblastoma (GBM) is the deadliest form of brain cancer and recurs uniformly. Despite aggressive treatment with maximal safe surgical resection, adjuvant radiation with temozolomide chemotherapy, and alternating electrical field therapy, median survival for newly diagnosed GBM remains <2 years. Novel therapies are desperately needed. Immunotherapy, which has led to significant improvement in patient outcomes across many tumor types, is currently being studied in a large number of GBM clinical trials. One of the biggest challenges in immunotherapy trials in GBM has been accurate response assessment using currently available imaging modalities, including magnetic resonance imaging. In this review, we will discuss the rationale for immunotherapy for GBM, immunotherapeutic modalities currently under clinical evaluation in GBM, and the challenges and recent advances in imaging response assessment in GBM immunotherapy.

Cancer Imaging Phenomics via CaPTk: Multi-Institutional Prediction of Progression-Free Survival and Pattern of Recurrence in Glioblastoma.

PURPOSE: To construct a multi-institutional radiomic model that supports upfront prediction of progression-free survival (PFS) and recurrence pattern (RP) in patients diagnosed with glioblastoma multiforme (GBM) at the time of initial diagnosis. PATIENTS AND METHODS: We retrospectively identified data for patients with newly diagnosed GBM from two institutions (institution 1, n = 65; institution 2, n = 15) who underwent gross total resection followed by standard adjuvant chemoradiation therapy, with pathologically confirmed recurrence, sufficient follow-up magnetic resonance imaging (MRI) scans to reliably determine PFS, and available presurgical multiparametric MRI (MP-MRI). The advanced software suite Cancer Imaging Phenomics Toolkit (CaPTk) was leveraged to analyze standard clinical brain MP-MRI scans. A rich set of imaging features was extracted from the MP-MRI scans acquired before the initial resection and was integrated into two distinct imaging signatures for predicting mean shorter or longer PFS and near or distant RP. The predictive signatures for PFS and RP were evaluated on the basis of different classification schemes: single-institutional analysis, multi-institutional analysis with random partitioning of the data into discovery and replication cohorts, and multi-institutional assessment with data from institution 1 as the discovery cohort and data from institution 2 as the replication cohort. RESULTS: These predictors achieved cross-validated classification performance (ie, area under the receiver operating characteristic curve) of 0.88 (single-institution analysis) and 0.82 to 0.83 (multi-institution analysis) for prediction of PFS and 0.88 (single-institution analysis) and 0.56 to 0.71 (multi-institution analysis) for prediction of RP. CONCLUSION: Imaging signatures of presurgical MP-MRI scans reveal relatively high predictability of time and location of GBM recurrence, subject to the patients receiving standard first-line chemoradiation therapy. Through its graphical user interface, CaPTk offers easy accessibility to advanced computational algorithms for deriving imaging signatures predictive of clinical outcome and could similarly be used for a variety of radiomic and radiogenomic analyses.

Perilesional Hyperintensity on T1-Weighted Images in Intra-Axial Brain Masses other than Cavernous Malformations.

BACKGROUND AND PURPOSE: Hyperintensity on T1-weighted imaging in perilesional vasogenic edema has been reported as a useful sign for differentiating cavernous malformation from other hemorrhagic intra-axial masses. In this study, we investigated the frequency of perilesional hyperintensity on T1-weighted imaging in patients with intra-axial hemorrhagic and nonhemorrhagic brain masses. METHODS: The study was performed with the approval of the institutional review board. Magnetic resonance images of 218 patients with 282 intra-axial brain masses (129 metastases, 46 gliomas, 18 primary central nervous system lymphomas [PCNSLs], 25 intracerebral hemorrhages, 50 cavernous malformations, and 14 patients with brain abscesses) were evaluated. The signal intensity in perilesional area was qualitatively evaluated on T1-weighted sequences. In addition, signal intensity in perilesional area was quantitatively measured on T1-weighted sequences and normalized to the contralateral white matter. RESULTS: Hyperintensity on T1-weighted imaging in perilesional vasogenic edema was found in 12 (9%) of 129 metastases, 8 (16%) of 50 cavernous malformations, 1 (4%) in 25 nonneoplastic intracerebral hemorrhages, and none of the patients with high-grade glioma, PCNSL, or abscess. All of the lesions with perilesional hyperintensity showed either acute or subacute hemorrhage. Pairwise comparison of qualitative hyperintensity on T1-weighted imaging demonstrated no significant difference between the groups. Perilesional hyperintensity on T1-weighted imaging showed high specificity in both metastasis and cavernous malformation groups (94%). CONCLUSION: Perilesional hyperintensity on T1-weighted imaging is not limited to cavernous malformations and frequently evident with melanoma and other hemorrhagic metastasis to the brain. In our experience, it was not seen in high-grade glioma, PCNSL, and brain abscess.