PATZ1-Rearranged Tumors of the Central Nervous System: Characterization of a Pediatric Series of Seven Cases.

PATZ1-rearranged sarcomas are well-recognized tumors as part of the family of round cell sarcoma with EWSR1-non-ETS fusions. Whether PATZ1-rearranged central nervous system (CNS) tumors are a distinct tumor type is debatable. We thoroughly characterized a pediatric series of PATZ1-rearranged CNS tumors by chromosome microarray analysis (CMA), DNA methylation analysis, gene expression profiling and, when frozen tissue is available, optical genome mapping (OGM). The series consisted of 7 cases (M:F=1.3:1, 1-17 years, median 12). On MRI, the tumors were supratentorial in close relation to the lateral ventricles (intraventricular or iuxtaventricular), preferentially located in the occipital lobe. Two major histologic groups were identified: one (4 cases) with an overall glial appearance, indicated as "neuroepithelial" (NET) by analogy with the corresponding methylation class (MC); the other (3 cases) with a predominant spindle cell sarcoma morphology, indicated as "sarcomatous" (SM). A single distinct methylation cluster encompassing both groups was identified by multidimensional scaling analysis. Despite the epigenetic homogeneity, unsupervised clustering analysis of gene expression profiles revealed 2 distinct transcriptional subgroups correlating with the histologic phenotypes. Interestingly, genes implicated in epithelial-mesenchymal transition and extracellular matrix composition were enriched in the subgroup associated to the SM phenotype. The combined use of CMA and OGM enabled the identification of chromosome 22 chromothripsis in all cases suitable for the analyses, explaining the physical association of PATZ1 to EWSR1 or MN1. Six patients are currently disease-free (median follow-up 30 months, range 12-92). One patient of the SM group developed spinal metastases at 26 months from diagnosis and is currently receiving multimodal therapy (42 months). Our data suggest that PATZ1-CNS tumors are defined by chromosome 22 chromothripsis as causative of PATZ1 fusion, show peculiar MRI features (eg, relation to lateral ventricles, supratentorial frequently posterior site), and, although epigenetically homogenous, encompass 2 distinct histologic and transcriptional subgroups.

Radiation-induced intracranial rhabdomyosarcoma- A rare complication: Report of a case with literature review.

Radiation-induced sarcoma (RIS) of the central nervous system is an uncommon late complication of radiation therapy. We report a case of a 47-year-old male patient who underwent surgery followed by irradiation and chemotherapy with temozolomide for a frontal lobe gliosarcoma and presented 43 months later with a recurrent tumor in the same location with interval growth in the size of the lesion. Histology from surgical resection of the recurrent tumor revealed embryonal rhabdomyosarcoma (RMS). Adjacent brain parenchyma showed radiation-induced changes. There was no evidence of gliosarcoma at recurrence. In addition to the rarity of sarcomas arising following irradiation for glial tumors, this case represents one of the first reports of an intracerebral RMS arising in this setting.

Oligosarcomas, IDH-mutant are distinct and aggressive.

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.

Chasing a rarity: a retrospective single-center evaluation of prognostic factors in primary gliosarcoma.

BACKGROUND AND PURPOSE: Primary gliosarcoma (GS) is a rare variant of IDH-wildtype glioblastoma multiforme. We performed a single-center analysis to identify prognostic factors. PATIENTS AND METHODS: We analyzed the records of 26 patients newly diagnosed with primary WHO grade IV GS. Factors of interest were clinical and treatment data, as well as molecular markers, time to recurrence, and time to death. RESULTS: Median follow-up was 9 months (range 5-21 months). Gross total resection did not lead to improved survival, most likely due to the relatively small sample size. Low symptom burden at the time of diagnosis was associated with longer PFS (P = 0.023) and OS (P = 0.018). Median OS in the entire cohort was 12 months. Neither MGMT promoter hypermethylation nor adjuvant temozolomide therapy influenced survival, consistent with some previous reports. CONCLUSION: In this retrospective study, patients exhibiting low symptom burden at diagnosis showed improved survival. None of the other factors analyzed were associated with an altered outcome.

Primary versus secondary gliosarcoma: a systematic review and meta-analysis.

INTRODUCTION: Gliosarcomas are extremely rare malignant brain tumors, which can be classified as primary gliosarcoma (PGS) if the tumors arise de novo or secondary gliosarcoma (SGS) in patients who had previously been treated for glioblastoma. Given their rarity, it is unclear if PGS is clinically and genetically different from SGS. This meta-analysis aimed to investigate the clinicopathological features, prognostic survivals, and molecular profiles of these rare tumors. METHODS: We searched PubMed and Web of Science for relevant studies. Odds ratio (OR), hazard ratio (HR), and their 95% confidence intervals (CI) were pooled using the random-effect model. RESULTS: We included eight studies with 239 PGS and 79 SGS for meta-analyses. Compared to PGS, SGS occurred at a younger age and had lower rates of gross total resection and radiation therapy. Bevacizumab was more commonly administered in SGS. SGS patients had a significantly worse PFS (HR 0.60; 95% CI 0.40-0.89) and OS (HR 0.46; 95% CI 0.31-0.68) in comparison to PGS. The incidences of EGFR mutation, IDH mutation, and MGMT methylation were not statistically different between PGS and SGS. CONCLUSION: Our results demonstrated that PGS and SGS had distinct clinicopathological profiles and prognoses but shared similar genetic profiles. This study facilitates our understanding of how these two malignant brain tumors behave clinically, but future studies will be required to elucidate the genetic pathways of PGS and SGS.

Survival outcomes associated with MGMT promoter methylation and temozolomide in gliosarcoma patients.

PURPOSE: Gliosarcoma is an uncommon glioblastoma subtype, for which MGMT promoter methylation's relationship with response to temozolomide chemotherapy is unclear. We therefore examined this question using a national cohort. METHODS:  The National Cancer Database was queried for patients histopathologically diagnosed with gliosarcoma between 2010 and 2019. The associations between MGMT promoter methylation, first-line single-agent chemotherapy-presumed to be temozolomide herein-and overall survival (OS) were examined using log-rank tests and Cox regression, with correction for multiple testing (p < 0.01 was significant). RESULTS: 580 newly-diagnosed gliosarcoma patients with MGMT status were available, among whom 33.6% were MGMT promoter methylated. Median OS for gliosarcoma patients that received standard-of-care temozolomide and radiotherapy was 12.1 months (99% confidence interval [CI] 10.8-15.1) for MGMT promoter unmethylated and 21.4 months (99% CI 15.4-26.2) for MGMT promoter methylated gliosarcomas (p = 0.003). In multivariable analysis of gliosarcoma patients-which included the potential confounders of age, sex, maximal tumor size, extent of resection, and radiotherapy-receipt of temozolomide was associated with improved OS in both MGMT promoter methylated (hazard ratio [HR] 0.23 vs. no temozolomide, 99% CI 0.11-0.47, p < 0.001) and unmethylated (HR 0.50 vs. no temozolomide, 99% CI 0.29-0.89, p = 0.002) gliosarcomas. MGMT promoter methylation was associated with improved OS among temozolomide-treated gliosarcoma patients (p < 0.001), but not in patients who did not receive chemotherapy (p = 0.35). CONCLUSION: In a national analysis of gliosarcoma patients, temozolomide was associated with prolonged OS irrespective of MGMT status. These results provide support for the current practice of trimodal therapy for gliosarcoma.

A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib.

Herein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor. A comprehensive molecular analysis on the tumor tissue showed a TPR-NTRK1 gene fusion. The patient was treated with a TRK inhibitor, larotrectinib, and exhibited a stable disease with residual lesion following 8 months of target therapy. The present study is the first report of an infantile gliosarcoma harboring NTRK1 rearrangement treated with larotrectinib.

Gliosarcoma with unusual glial components: Two case reports.

Gliosarcoma is characterized by the presence of alternating lesions of glial and mesenchymal components. Although many mesenchymal components have been reported, there are few reports on glial components. We here report two cases of gliosarcoma. Case 1 was a 42-year-old woman with right hemiparesis and motor aphasia. Magnetic resonance imaging (MRI) identified a tumor in the left frontal lobe. Pathological analysis of the tumor removal specimen revealed gliosarcoma, with a glial component resembling pleomorphic xanthoastrocytoma. Postoperatively, radiotherapy and chemotherapy were conducted, and the patient was symptom-free over 12 months after surgery. Case 2 was a 67-year-old woman with a consciousness disorder and left hemiparesis. MRI revealed a tumor in the right frontal lobe. Pathological analysis of the first tumor removal specimen identified gliosarcoma, with a glial component characterized by large tumor cells. Additionally, the Ki-67 labeling index of the glial component was greater than that of the mesenchymal component, and molecular genetic analysis disclosed a mutation in the telomerase reverse transcriptase (TERT) gene (TERT). Chemotherapy and radiotherapy were performed. Four months later, MRI revealed recurrence, and the second surgery was performed. Pathological analysis revealed giant cell glioblastoma without TERT mutation. The patient died due to tumor progression 12 months after the first surgery. It is essential to continue histopathological evaluation of glial components, and further genetic evaluation on gliosarcoma is required.

Secondary gliosarcoma: the clinicopathological features and the development of a patient-derived xenograft model of gliosarcoma.

BACKGROUND: Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM. METHODS: Tissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared. RESULTS: In explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors. CONCLUSIONS: Our PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.

Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling.

BACKGROUND: Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. METHODS: Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. RESULTS: Potentially meaningful associations (p<0.1, Fisher's exact test (FET)) were found for 14 of these tests in GS vs. GB. A novel finding was higher levels of proteins mediating immuno-evasion (PD-1, PD-L1) in GS. All of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11. CONCLUSIONS: GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB.

Gliosarcoma in patients under 20 years of age. A clinicopathologic study of 11 cases and detailed review of the literature.

BACKGROUND: Gliosarcoma is a rare variant of IDH- wild type glioblastoma with both glial and mesenchymal differentiation. It accounts for approximately 2% of glioblastomas and has a poor prognosis similar to that of classic glioblastoma. It is seen mostly between 40 and 60 years of age with a mean age over 50 years. Pediatric gliosarcoma is even rarer than gliosarcoma in adults. We describe the clinicopathological features of gliosarcoma in patients under 20 years of age and determine whether there are significant differences from gliosarcoma in adults. We also present detailed review of published literature on pediatric gliosarcoma. METHODS: Slides of gliosarcomas in patients under 20 years of age were reviewed. Clinicopathological features were noted in detail and follow up was obtained. RESULTS: Eleven cases of gliosarcoma were reported in patients under 20 years of age. Ages ranged from three to 19 years (mean age 13 years). Frontal, parietal and temporal lobes were the commonest locations. Mean and median tumor size was six and five cm respectively. All 11 cases demonstrated the classic biphasic pattern. In 10 cases, glial component was astrocytic and was highlighted on GFAP. Sarcomatous component in most cases resembled fibrosarcoma and was high grade in 72.7%. Glial areas were reticulin poor while sarcomatous areas were reticulin rich. In over 45% cases, bizarre tumor giant cells were seen in the sarcomatous areas. In 1 case, sarcomatous areas showed extensive bone and cartilage formation. Other histologic features included hyalinized blood vessels, hemorrhage, infarction, gemistocytic cells, rhabdoid cells etc. Follow up was available in nine patients, five received chemoradiation post resection while three received radiotherapy only. Prognosis was dismal and eight patients died within one to 14 months following resection. CONCLUSIONS: Gliosarcomas in patients under 20 comprised 13% of all gliosarcomas reported during the study period. Frequency and mean age were higher compared to other published reports. Pathological features were similar to those described in literature. Clinicopathological features and prognosis of pediatric gliosarcomas were similar to adult gliosarcomas.

The clinical, radiological, and immunohistochemical characteristics and outcomes of primary intracranial gliosarcoma: a retrospective single-centre study.

Primary intracranial gliosarcoma is a rare malignant brain tumour, and the most effective treatment for gliosarcoma remains unclear. This study aimed to identify risk factors for progression-free survival (PFS) and overall survival (OS) in these cases. This retrospective single-centre study evaluated 103 patients (median age, 51 years; 67 men [65%]) with primary intracranial gliosarcoma between 2006 and 2017. Treatments included surgery (GTR, 63 patients; STR, 39 patients; biopsy, 1 patient), radiotherapy (adjuvant, 76 patients; exclusive treatment, 1 patient), and chemotherapy (adjuvant temozolomide, 52 patients; adjuvant nimustine/teniposide, 19 patients; adjuvant bevacizumab, 1 patient; exclusive nimustine/teniposide treatment, 1 patient). The median OS was 13.3 months, and the median PFS was 9.1 months. In the multivariate analyses, the poor prognostic factors were ependymal lining enhancement of the lateral ventricle (PFS, HR 2.406, p = 0.005; OS, HR 2.946, p = 0.009) and enhancement in the motor functional cortex (PFS, HR 2.892, p = 0.002; OS, HR 2.639, p = 0.009). Good OS was predicted by adjuvant radiotherapy alone (HR 0.071, p < 0.001), adjuvant temozolomide-based chemotherapy alone (HR 0.063, p = 0.005), adjuvant temozolomide-based chemotherapy with concurrent radiotherapy (HR 0.056, p < 0.001), and salvage surgery at recurrence (HR 0.449, p = 0.031). The present study revealed that, in patients with primary intracranial gliosarcoma, enhancement in the functional motor cortex and ependymal lining enhancement of the lateral ventricle were both poor prognostic factors. Survival was optimized in cases treated using maximal safe resection followed by adjuvant temozolomide-based chemotherapy with concurrent radiotherapy. Furthermore, salvage surgery provided meaningful therapeutic benefits for recurrent gliosarcoma.

Primary and secondary gliosarcoma: differences in treatment and outcome.

INTRODUCTION: There are only few studies comparing differences in the outcome of primary versus secondary gliosarcoma. This study aimed to review the outcome and survival of patients with primary or secondary gliosarcoma following surgical resection and adjuvant treatment. The data were also matched with data of patients with primary and secondary glioblastoma (GBM). PATIENTS AND METHODS: Treatment histories of 10 patients with primary gliosarcoma and 10 patients with secondary gliosarcoma were analysed and compared. Additionally, data of 20 patients with primary and 20 patients with secondary GBM were analysed and compared. All patients underwent surgical resection of the tumour in our department. Follow-up data, progression-free survival (PFS), and median overall survival (mOS) were evaluated. RESULTS: The median PFS in patients with primary gliosarcoma was significantly higher than in patients with secondary gliosarcoma (p = 0.037). The 6-month PFS rates were 80.0% in patients with primary and 30.0% in patients with secondary gliosarcoma. Upon recurrence, five patients with primary gliosarcoma and four patients with secondary gliosarcoma underwent repeat surgical resection. The mOS of patients with primary gliosarcoma was significantly higher than that of patients with secondary gliosarcoma (p = 0.031). The percentage of patients surviving at 1-year/2-year follow-up in primary gliosarcoma was 70%/20%, while it was only 10%/10% in secondary gliosarcoma. When PFS and mOS of primary gliosarcoma was compared to primary GBM, there were no statistically differences (p = 0.509; p = 0.435). The PFS and mOS of secondary gliosarcoma and secondary GBM were also comparable (p = 0.290 and p = 0.390). CONCLUSION: Patients with primary gliosarcoma have a higher PFS and mOS compared to those with secondary gliosarcoma. In the case of tumour recurrence, patients with secondary gliosarcoma harbour an unfavourable prognosis with limited further options. The outcome of patients with primary or secondary gliosarcoma is comparable to that of patients with primary or secondary GBM.

Spinal metastasis of glioblastoma multiforme before gliosarcomatous transformation: a case report.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumors. Intracranial GBM metastases to the spine are rarely detected clinically. Secondary gliosarcomas after treatment of primary GBM are rarely described. CASE PRESENTATION: Herein, we report the case of a 53-year-old woman who presented to our emergency room with progressive headache and weakness on the left side. Plain computed tomography and contrast magnetic resonance imaging of the brain revealed an approximately 6.8 cm × 4.5 cm right temporoparietooccipital intraaxial cystic tumor with surrounding diffuse perifocal edema that caused midline shift toward the left. Emergency craniotomy was performed to remove the tumor, and pathological examination revealed GBM. The patient received proton beam therapy, Gliadel implantation, and oral temozolomide chemotherapy as well as targeted therapy with bevacizumab. Approximately 15 months after diagnosis, she underwent surgical resection of the right temporal recurrent tumor and was newly diagnosed as having a metastatic spinal tumor. Pathologically, the right temporal and metastatic spinal tumors were gliosarcoma and GBM, respectively. CONCLUSIONS: Concurrent spinal metastasis and gliosarcomatous transformation, which are two types of GBM complications, are rare. To our knowledge, this is the first report of a case of recurrent GBM with gliosarcoma after proton bean therapy.

Clinical implications of multiple glioblastomas: An analysis of prognostic factors and survival to distinguish from their single counterparts.

PURPOSE: Glioblastoma (GBM) has the highest fatality rate among primary malignant brain tumors. GBMs with synchronous multiple foci (multiple GBMs) is rarely diagnosed in the clinical scenario. This study aims to compare the clinical characteristics between multiple and single GBMs and to identify factors associated with the survival of GBM and evaluate their effects. METHODS: We retrospectively reviewed the medical records of patients with primary GBM in a referral medical center in Taiwan who were diagnosed between 2005 and 2016. They were identified from the cancer registry database of the center and followed from the date of diagnosis to october 2018. The primary endpoint of this study was overall survival (OS), and the independent factors for survival were identified through Cox regressions. RESULTS: A total of 48 patients were identified, of whom 44 GBM (92%) and 4 gliosarcoma (GSM) (8%). Preoperative images showed five (10%) patients had multiple brain lesions. GSM showed a high ratio of multiple lesions (50%) than patients with GBM (5%) (p = 0.05). Those with multiple lesions had significantly worse median OS of 8.2 months compared to patients with a single lesion (16 months, p = 0.03). We found that multiple GBMs was a predictor of worse survival (hazard ratio [HR] = 3.57, 95% confidence interval [95%CI]: 1.26-10.13) after adjusting for other significant predictor of radiotherapy (HR = 0.47, 95%CI: 0.23-0.96). CONCLUSION: Patients with multiple GBMs had worse survival compared to those with single GBM. GBM patients without post-operative radiotherapy were also a predictor of worse survival.

Prognostic factors and clinical outcomes in adult primary gliosarcoma patients: a Surveillance, Epidemiology, and End Results (SEER) analysis from 2004 to 2015.

Objective: Gliosarcoma (GSC), a rare malignant brain tumor, is considered as a variant of isocitrate dehydrogenase 1 wild type (IDH1-WT) glioblastoma (GBM). This study aimed to retrospectively analyze the clinical characteristics of GSC and compare whether there are some differences of treatment strategies and outcomes between GSC and GBM patients through Surveillance, Epidemiology, and End Results (SEER) database.Patients and methods: The clinical data of adults diagnosed with primary GSC between 2004 and 2015 were queried from SEER database. The Kaplan-Meier curve and the Cox model were performed to analyze the relationships between clinical parameters and patients' prognosis. Similar analyses were conducted for all primary GBM patients of SEER.Results: In total, 527 GSC and 20,541 GBM patients with complete and valid clinical information were finally enrolled for further analysis. Compared with GBM, GSC owned a proclivity to temporal lobe rather than frontal lobe (p < 0.001), a less conservative extension of resection (EOR) (p < 0.001), and a higher sensitivity to radiotherapy (p < 0.001). As shown by univariate analysis, surgery, radiotherapy and chemotherapy could prolong the overall survival (OS) time of GSC, but EOR did not confer an advantage to the outcomes of patients, no matter whether combined radio/chemotherapy was given. In multivariate analysis, age more than 60 and lack of radio/chemotherapy were identified as independent risk factors for OS of GSC patients.Conclusions: Our study found that although EOR seemed to be important to GBM, the extent of surgery did not show a clear relationship with the improved prognosis of GSC. Additionally, radiotherapy and chemotherapy could prolong patients' survival time significantly, which suggests a more positive role of them in treating GSC and needs further investigations.

Gliosarcoma: distinct molecular pathways and genomic alterations identified by DNA copy number/SNP microarray analysis.

PURPOSE: Gliosarcoma is a histologic variant of glioblastoma (GBM), and like GBM carries a poor prognosis. Median survival is less than one (1) year with less than 5% of patients alive after 5 years. Although there is no cure, standard treatment includes surgery, radiation and chemotherapy. While very similar to GBM, gliosarcoma exhibits several distinct differences, morphologically and molecularly. Therefore, we report a comprehensive analysis of DNA copy number changes in gliosarcoma using a cytogenomic DNA copy number (CN) microarray (OncoScan®). METHODS: Cytogenomic DNA copy number microarray (OncoScan®) was performed on 18 cases of gliosarcoma. MetaCore™ enrichment was applied to the array results to detect associated molecular pathways. RESULTS: The most frequent alteration was copy number loss, comprising 57% of total copy number changes. The number of losses far exceeded the number of amplifications (***, < 0.001) and loss of heterozygosity events (***, < 0.001). Amplifications were infrequent (4.6%), particularly for EGFR. Chromosomes 9 and 10 had the highest number of losses; a large portion of which correlated to CDKN2A/B loss. Copy number gains were the second most common alteration (26.2%), with the majority occurring on chromosome 7. MetaCore™ enrichment detected notable pathways for copy number gains including: HOXA, Rho family of GTPases, and EGFR; copy number loss including: WNT, NF-kß, and CDKN2A; and copy number loss of heterozygosity including: WNT and p53. CONCLUSIONS: The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.

Racial/ethnic differences in survival for patients with gliosarcoma: an analysis of the National cancer database.

PURPOSE: Gliosarcoma is characterized by the World Health Organization as a Grade IV malignant neoplasm and a variant of glioblastoma. The association of race and ethnicity with survival has been established for numerous CNS malignancies, however, no epidemiological studies have reported these findings for patients with gliosarcoma. The aim of this study was to examine differences by race and ethnicity in overall survival, 30-day mortality, 90-day mortality, and 30-day readmission. METHODS: Data were obtained by query of the National Cancer Database (NCDB) for years 2004-2014. Patients with gliosarcoma were identified by International Classification of Diseases for Oncology, Third Edition (ICD-O-3)-Oncology morphologic code 9442/3 and topographical codes C71.0-C71.9. Differences in survival by race/ethnicity were examined using univariable and multivariable Cox proportional hazards models. Readmission and mortality outcomes were examined with univariable and multivariable logistic regression. RESULTS: A total of 1988 patients diagnosed with gliosarcoma were identified (White Non-Hispanic n = 1,682, Black Non-Hispanic n = 165, Asian n = 40, Hispanic n = 101). There were no differences in overall survival, 30- and 90-day mortality, or 30-day readmission between the races and ethnicities examined. Median survival was 10.4 months for White Non-Hispanics (95% CI 9.8, 11.2), 10.2 months for Black Non-Hispanics (95% CI 8.6, 13.1), 9.0 months for Asian Non-Hispanics (95% CI 5.1, 18.2), and 10.6 months for Hispanics (95% CI 8.3,16.2). 7.3% of all patients examined had an unplanned readmission within 30 days. CONCLUSION: Race/ethnicity are not associated with differences in overall survival, 30-day mortality, 90-day mortality, or 30-day readmission following surgical intervention for gliosarcoma.

Management and survival trends for adult patients with malignant gliomas in the setting of multiple primary tumors: a population based analysis.

INTRODUCTION: The impact of multiple primary tumors, in the setting of malignant glioma (MG), has not been heavily explored. METHODS: We extracted demographics and clinical data from the SEER-18 registry for adult patients with MGs. The cases were separated based on the sequence of MG diagnosis relative to the other primary tumors: Group (A) One primary only or first primary of multiple primaries and Group (B) second primary or subsequent primary tumor. Incidences, frequencies, and glioma-related survivals were analyzed. RESULTS: Group B constituted 12.8% of new MG. The incidences of group B, relative to those of all new MG, range from 0.14 to 0.18. Compared to group A, group B exhibited an older age. Moreover, group B exhibited a higher proportion of females, Caucasians, smaller tumors, non-operative cases, and those receiving radiation (p < 0.05); the proportion with GTR remained comparable. Multiple groupings (oral cavity, digestive system, respiratory system, skin, breast, genital systems, urinary system, lymphoma) exhibited lower glioma-related observed survival (p < 0.05) compared to Group A. An active diagnosis of "leukemia" appears to confer longer glioma-related survival while a history of "breast" or "digestive system" malignancies portends a shorter glioma-related survival. CONCLUSION: For newly diagnosed MG, a high proportion does have history of extra-CNS primary tumors. Generally, these patients appear to have worse glioma-related observed survival compare to those with malignant glioma as the only primary or the first of multiple primary tumors. Knowledge regarding epidemiology, clinical factors, and observed survival can help guide clinical management/consultation for this subset of patients.

Gliosarcoma: a clinical and radiological analysis of 48 cases.

OBJECTIVES: To retrospectively review the radiological and clinicopathological features of gliosarcoma (GSM) and differentiate it from glioblastoma multiforme (GBM). METHODS: The clinicopathological data and imaging findings (including VASARI analysis) of 48 surgically and pathologically confirmed GSM patients (group 1) were reviewed in detail, and were compared with that of other glioblastoma (GBM) cases in our hospital (group 2). RESULTS: There were 28 men and 20 women GSM patients with a median age of 52.5 years (range, 24-80 years) in this study. Haemorrhage (n = 21), a salt-and-pepper sign on T2-weighted images (n = 36), unevenly thickened wall (n = 36) even appearing as a paliform pattern (n = 32), an intra-tumoural large feeding artery (n = 32) and an eccentric cystic portion (ECP) (n = 19) were more commonly observed in the GSM group than in GBM patients. Based on our experience, GSM can be divided into four subtypes according to magnetic resonance imaging (MRI) features. When compared to GBM (group 2), there were more patients designated with type III lesions (having very unevenly thickened walls) and IV (solid) lesions among the GSM cases (group 1). On univariate prognostic analysis, adjuvant therapy (radiotherapy, chemotherapy, and radiochemotherapy) and existence of an eccentric cyst region were prognostic factors. However, Cox's regression model showed only adjuvant therapy as a prognostic factor for GSM. CONCLUSIONS: When compared to GBM, certain imaging features are more likely to occur in GSM, which may help raise the possibility of this disease. All GSM patients are recommended to receive adjuvant therapy to achieve a better prognosis with radiotherapy, chemotherapy or radiochemotherapy all as options. KEY POINTS: • Diagnosis of gliosarcoma can be suggested preoperatively by imaging. • Gliosarcoma can be divided into four subtypes based on MRI. • Paliform pattern and ECP tend to present in gliosarcoma more than GBM. • The cystic subtype of gliosarcoma may predict a more dismal prognosis. • All gliosarcoma patients should receive adjuvant therapy to achieve better prognosis.