Gliosarcoma Patients Research Articles

PATH-05. PRIMARY AND SECONDARY GLIOSARCOMA: RADIOLOGICAL AND PROGNOSTIC DIFFERENCES USING COMPREHENSIVE MULTI-OMICS ANALYSIS

Abstract Purpose Gliosarcoma (GS), a rare variant of glioblastoma (GB), is further classified into primary (de novo) gliosarcoma (PGS), and secondary gliosarcoma (SGS), which is defined as recurrence after a diagnosis of diffuse glioma. Poorer survival of SGS than PGS has been reported, however, the detailed mechanism remains unknown. METHODS: A retrospective retrieval of pathological confirmed GS was performed. All the clinical, radiological, and pathological comparisons were based on the diagnosis of GS. A multi-omics, including whole exome sequencing, transcriptome, proteome and phosphoproteome, approach was used to acquire the molecular profiles of these specimens. RESULTS: From 2003 to 2020, a total of 28 GSs were identified, including 19 PGSs and 9 SGSs. The age tended to be younger in SGS group than PGS group (52.1 ± 10.9 vs. 60.8 ± 11.5, p=0.069). SGSs tended to present with dural attachment (p=0.071) and were significantly associated with major vessel encasement (p=0.002) than PGSs. The Ki-67 index tended to be higher in SGSs than PGSs (p=0.081). The GS survival was significantly shorter in SGS group than PGS group (median: 7.9 vs. 32.4 months, p< 0.001). The multi-omics analysis demonstrated SGSs had significantly higher expression of negative regulation of megakaryocyte differentiation, telomere capping, and DNA replication nucleosome assembly pathways than PGSs. Next, using proteome / phosphoproteome nonnegative matrix factorization analysis, PGS was categorized into two clusters (PGS_C1 versus PGS_C2) with distinct multi-omics features. Of which, PGS_C1 (n=4) tended to have shorter survival than PGS_C2 (n=15, p=0.054). Notably, the survival of patients in PGS_C1, who had similar multi-omics signature to SGS, were as poor as those of SGSs. CONCLUSIONS: In summary, this study provides, for the first time, in depth evidence for understanding GS and presents multi-omics biomarkers with prognostic significance. Further therapeutic translation should based on current findings to benefit GS patients.

Clinicopathological and Neuroimaging Features of Primary Gliosarcoma: A Case Series and Review of Literature

Gliosarcoma (GS) is a rare primary high-grade brain neoplasm with a poor prognosis and challenging surgical resection. Although it is now considered a morphologic variant of IDH-wildtype glioblastoma (World Health Organization Classification of Tumours 2021), GS may display peculiarities that hamper both surgical and oncological management. In this retrospective study, we searched our registry for histologically confirmed GS patients between 2006 and 2020. Cases were reviewed for clinical information, pathologic characteristics, imaging findings, management, and outcome. 21 patients with histologically confirmed GS were identified with a median age of 62years. Twelve were men and 9 women. The temporal lobe was the most common location (9 patients, 42.9%). Nineteen patients underwent surgical resection, and only 4 (19%) demonstrated gross total resection on postsurgical MRI, with an overall median survival of 7months (range, 0.5-37). Diagnostic MRI demonstrated heterogenous lesions with necrotic-cystic areas and a ring-enhancement pattern. Only 1 case of extracranial extension was seen in our sample, and no patient showed distant metastases. The rarity of primary GS and the absence of specific therapeutic guidelines represent a significant clinical challenge. Our study provides a comprehensive analysis of clinical and neuroimaging characteristics in a real-world patient cohort and compares our findings with the available literature.

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

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. 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). 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 12.1months (99% confidence interval [CI] 10.8-15.1) for MGMT promoter unmethylated and 21.4months (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). 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.

Clinical and survival characteristics of primary and secondary gliosarcoma patients

PurposeGliosarcoma (GS) is classified by the World Health Organization as a subtype of glioblastoma with sarcomatous features. GS have a propensity to metastasize, as opposed to other gliomas, with lower 5-year survival rates than GBM patients. In this study, we identified differences in survival between patients with primary and secondary GS. MethodsWe retrospectively identified patients who presented at the MD Anderson Cancer Center with a pathology-confirmed diagnosis of GS. We defined overall survival (OS) from the date of pathological diagnosis of primary GS (from sarcomatous change for secondary GS). We defined progression-free survival (PFS) from the date of GS chemoradiation completion to radiographic disease progression. We used Kaplan-Meier survival estimates and the log-rank test to compare OS and PFS between primary and secondary GS. We used univariable Cox proportional hazard regression to assess differences in OS & PFS by various characteristics. ResultsWe identified 94 GS patients; 70 had primary disease and 24 secondary. Molecular analysis of GS tumor samples revealed that 47.1% were GFAP positive, 38.5% S-100 positive, and 83.7% reticulin-positive. Among the tested samples, 3.8% had IDH and 73.1% had TP53 mutations. The median OS for all patients was 16.8 months. Median OS from the pathological diagnosis of GS was 17.3 months for primary and 10.2 months for secondary GS. Median OS for secondary GS was 28.9 months from initial diagnosis of the primary neoplasm. ConclusionsOur study is the largest single institution evaluation of GS and provides insight into patterns of survival for GS.

Genomic landscape of gliosarcoma: distinguishing features and targetable alterations

Gliosarcoma is an aggressive brain tumor with histologic features of glioblastoma (GBM) and soft tissue sarcoma. Despite its poor prognosis, its rarity has precluded analysis of its underlying biology. We used a multi-center database to characterize the genomic landscape of gliosarcoma. Sequencing data was obtained from 35 gliosarcoma patients from Genomics Evidence Neoplasia Information Exchange (GENIE) 5.0, a database curated by the American Association of Cancer Research (AACR). We analyzed genomic alterations in gliosarcomas and compared them to GBM (n = 1,449) and soft tissue sarcoma (n = 1,042). 30 samples were included (37% female, median age 59 [IQR: 49–64]). Nineteen common genes were identified in gliosarcoma, defined as those altered in > 5% of samples, including TERT Promoter (92%), PTEN (66%), and TP53 (60%). Of the 19 common genes in gliosarcoma, 6 were also common in both GBM and soft tissue sarcoma, 4 in GBM alone, 0 in soft tissue sarcoma alone, and 9 were more distinct to gliosarcoma. Of these, BRAF harbored an OncoKB level 1 designation, indicating its status as a predictive biomarker of response to an FDA-approved drug in certain cancers. EGFR, CDKN2A, NF1, and PTEN harbored level 4 designations in solid tumors, indicating biological evidence of these biomarkers predicting a drug-response. Gliosarcoma contains molecular features that overlap GBM and soft tissue sarcoma, as well as its own distinct genomic signatures. This may play a role in disease classification and inclusion criteria for clinical trials. Gliosarcoma mutations with potential therapeutic indications include BRAF, EGFR, CDKN2A, NF1, and PTEN.

Clinical and Survival Characteristics of Gliosarcoma Patients (1986)

Clinical and Survival Characteristics of Gliosarcoma Patients (1986)

Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma.

Introduction: Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited.Methods: Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions.Results: Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], p = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001–0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02–0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001–0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1–79.6] months vs. 5.45 [1.8–26.3], p = 0.0092) and OS (median 56.73 months [7.8–104.5] vs. 14.83 [3.8 to 29.1], p = 0.0252).Conclusion: Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.

Clinical Characteristics of Gliosarcoma and Outcomes From Standardized Treatment Relative to Conventional Glioblastoma.

Background: Gliosarcoma (GS) is a rare histopathologic variant of glioblastoma (GBM) characterized by a biphasic growth pattern consisting of both glial and sarcomatous components. Reports regarding its relative prognosis compared to conventional GBM are conflicting and although GS is treated as conventional GBM, supporting evidence is lacking. The aim of this study was to characterize demographic trends, clinical outcomes and prognostic variables of GS patients receiving standardized therapy and compare these to conventional GBM.Methods: Six hundred and eighty GBM patients, treated with maximal safe resection followed by radiotherapy with concomitant and adjuvant temozolomide at a single institution, were retrospectively reevaluated by reviewing histopathological records and tumor tissue for identification of GS patients. Clinico-pathological- and tumor growth characteristics were obtained via assessment of medical records and imaging analysis. Kaplan-Meier survival estimates were compared with log-rank testing, while Cox-regression modeling was tested for prognostic factors in GS patients.Results: The cohort included 26 primary gliosarcoma (PGS) patients (3.8%) and 7 secondary gliosarcoma (SGS) patients (1.0%). Compared to conventional GBM tumors, PGS tumors were significantly more often MGMT-unmethylated (73.9%) and located in the temporal lobe (57.7%). GS tumors often presented dural contact, while extracranial metastasis was only found in 1 patient. No significant differences were found between PGS and conventional GBM in progression-free-survival (6.8 and 7.6 months, respectively, p = 0.105) and in overall survival (13.4 and 15.7 months, respectively, p = 0.201). Survival following recurrence was not significantly different between PGS, SGS, and GBM. Temporal tumor location and MGMT status were found associated with PGS survival (p = 0.036 and p = 0.022, respectively).Conclusion: Despite histopathological and location difference between GS and GBM tumors, the patients present similar survival outcome from standardized treatment. These findings support continued practice of radiation and temozolomide for GS patients.

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: a clinical and radiological analysis of 48 cases.

To retrospectively review the radiological and clinicopathological features of gliosarcoma (GSM) and differentiate it from glioblastoma multiforme (GBM). 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). 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. 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. • 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.

Assessment of treatment approach and survival outcomes in a modern cohort of patients with primary gliosarcoma using the national cancer database

// Lu Deng 1 , Allison Cheung 2 , Harrison X. Bai 3 , Xuejun Li 4 , Weihua Liao 5 , Ya Cao 6 , Giorgos Karakousis 7 , Paul J. Zhang 8 , Bo Xiao 9 and Li Yang 1 1 Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China 2 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, 06511, United States 3 Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States 4 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China 5 Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China 6 Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China 7 Department of Surgery, Hospital of the University of Pennsylvania, Silverstein, Philadelphia, Pennsylvania, 19104, United States 8 Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States 9 Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China Correspondence to: Li Yang, email: yangli762@csu.edu.cn Bo Xiao, email: Xiaobo_xy@126.com Keywords: age, gliosarcoma, national cancer database, survival, trimodality therapy Received: April 11, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: August 26, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: January 12, 2018 ABSTRACT Background: Primary gliosarcoma is a rare malignant brain tumor with dismal prognosis. Previous reports are limited to case reports and small retrospective case series. Objective: To evaluate treatment and survival outcomes in a large cohort of primary gliosarcoma patients treated in the United States. Results: 1622 patients met the inclusion criterion. Median age was 63 years. The 3-year OS rate for the entire cohort was 11.9%. Patients aged 18 to 60 years were significantly more likely to receive trimodality therapy (defined as the use of surgery, radiotherapy [RT] and chemotherapy [CT]) than patients older than 60 (68.1% vs. 56.7%, p &lt; 0.001). The utilization of trimodality therapy significantly increased during the study period (57.5% in 2004&ndash;2008 vs. 65.1% in 2009&ndash;2013; p = 0.002). On multivariate Cox regression analysis, GTR, surgery followed by RT and the use of trimodality therapy were associated with longer OS, while older age, Charlson-Deyo score &ge; 1 and multi-focal tumor were associated with shorter OS. The use of trimodality therapy was consistently associated with longer OS in subgroup analyses based on age and extent of resection. Materials and Methods: The National Cancer Database was used to identify all primary gliosarcoma patients aged 18 to 90 years who were diagnosed between 2004 and 2013. Overall survival (OS) was evaluated by Kaplan-Meir analysis, univariate and multivariate Cox proportional hazard regression analysis. Conclusions: The use of trimodality therapy significantly increased during the study period and was associated with improved outcomes regardless of age and extent of resection.

Patterns of care and outcomes in gliosarcoma: an analysis of the National Cancer Database.

OBJECTIVE The authors compared presenting characteristics and survival for patients with gliosarcoma (GS) and glioblastoma (GBM). Additionally, they performed a survival analysis for patients who underwent GS treatments with the hypothesis that trimodality therapy (surgery followed by radiation and chemotherapy) would be superior to nontrimodality therapy (surgery alone or surgery followed by chemotherapy or radiation). METHODS Adults diagnosed with GS and GBM between the years 2004 and 2013 were queried from the National Cancer Database. Chi-square analysis was used to compare presenting characteristics. Kaplan-Meier, Cox regression, and propensity score analyses were employed for survival analyses. RESULTS In total, data from 1102 patients with GS and 36,658 patients with GBM were analyzed. Gliosarcoma had an increased rate of gross-total resection (GTR) compared with GBM (19% vs 15%, p < 0.001). Survival was not different for patients with GBM (p = 0.068) compared with those with GS. After propensity score analysis for GS, patients receiving trimodality therapy (surgery followed by radiation and chemotherapy) had improved survival (12.9 months) compared with those not receiving trimodality therapy (5.5 months). In multivariate analysis, GTR, female sex, fewer comorbidities, trimodality therapy, and age < 65 years were associated with improved survival. There was a trend toward improved survival with MGMT promoter methylation (p = 0.117). CONCLUSIONS In this large registry study, there was no difference in survival in patients with GBM compared with GS. Among GS patients, trimodality therapy significantly improved survival compared with nontrimodality therapy. Gross-total resection also improved survival, and there was a trend toward increased survival with MGMT promoter methylation in GS. The major potential confounder in this study is that patients with poor functional status may not have received aggressive radiation or chemotherapy treatments, leading to the observed outcome. This study should be considered hypothesis-generating; however, due to its rarity, conducting a clinical trial with GS patients alone may prove difficult.

High prevalence of TP53 mutations is associated with poor survival and an EMT signature in gliosarcoma patients

Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.

Therapeutic management of gliosarcoma in the temozolomide era.

Gliosarcoma (GS) is a malignant, uncommon variant of high-grade glioma comprised of infiltrative glial and atypical sarcomatous cells, identified in adult and pediatric populations. GS has been subcategorized into primary (de novo) and secondary tumors, with the latter typically arising in the setting of prior glioblastoma. Due to its rarity, the pathogenesis, epidemiology and optimal therapy of GS have been based on small retrospective cohort studies, with treatment presently utilizing regimens established for other high-grade gliomas, including combination of resection, radiotherapy and temozolomide-based chemotherapy. As more information is gathered about GS molecular profiles, novel treatment strategies may be developed to improve outcomes of GS patients. Here we summarize results of GS management with focus on the temozolomide era.

An individual patient data meta-analysis on characteristics, treatments and outcomes of glioblastoma/ gliosarcoma patients with metastases outside of the central nervous system.

PurposeTo determine the characteristics, treatments and outcomes of patients with glioblastoma multiforme (GBM) or gliosarcoma (GS) and metastases outside of the central nervous system (CNS).MethodsPubMed and Web of Science searches for peer-reviewed articles pertaining to GBM/ GS patients with metastatic dissemination were conducted using the keywords gliosarcoma, glioblastoma, GBM, metastasis, metastases and metastatic. Additionally, we performed hand search following the references from the selected papers. Cases with metastases to the CNS were excluded and evaluated in a separate study.Results109 articles published between 1928 and 2013 were eligible. They reported on 150 patients. We observed a remarkable increase in the number of cases per decade over time. Median overall survival from diagnosis of metastasis (OSM+) was 6.0 ± 0.8 months and median overall survival from initial diagnosis (OSID) 13 ± 2.4 months. On univariate analyses, gender, age, the histological subtype, the time interval between initial diagnosis and diagnosis of metastasis and pulmonary involvement did not influence OSM+. We did not observe any substantial treatment progress. A comparison of the present cohort with 84 GBM/ GS patients with exclusive CNS dissemination suggests that metastases outside the CNS are related to a slightly more favorable outcome.ConclusionsThe occurrence of extra-CNS metastasis from GBM/ GS is associated with a dismal prognosis, however it seems to compare slightly favorable to CNS dissemination. Crucial treatment progress has not been achieved over recent decades. A central registry should be considered to consecutively gain more information about the ideal therapeutic approach.

Primary Gliosarcoma of the Brain: Radiologic and Histopathologic Features

Gliosarcoma is a rare central nervous system (CNS) neoplasm with biphasic glial and non-glial malignant components. Here we describe the radiologic and histopathologic features observed in five cases of primary gliosarcoma. The mean age at diagnosis in the studied patients was 54.2 years; these patients were predominantly males (male:female ratio = 4:1). At diagnosis all patients had several clinical deterioration. The most common symptoms of presentation were: headache (5/5 cases), seizures (4/5 cases) and hemiparesis (1/5 cases). All the tumors were large (mean major diameter= 4.12±1.64 cm) at diagnosis as evidenced in computer tomography (CT) scans and magnetic resonance images (MRIs), with preferential involvement of the temporal lobe and frequent associated deviation of the midline structures. Other common characteristics identified on CT scans and MRIs were partial contrast medium uptake with annular pattern (5/5 cases), peripheral edema (5/5 cases), and central calcification (3/5 cases). In additional a peak of dye uptake was observed (4/5 cases) on MRI spectrometry. In the histopathology, the glial component showed malignant astrocytes, with high Ki67 (>60%) and p53 positivity; the sarcomatous components displayed pleomorphic spindle cells similarly with p53 positivity and high Ki67 (75-90%) in all cases. Dedifferentiation to pleomorphic sarcoma (two cases), fibrosarcoma (one case), leiomyosarcoma (one case) and MPNST (one case) were documented. All patients received radiotherapy/chemotherapy and had a median overall survival of ten months. The study of radiologic and histopathologic features in primary gliosarcomas of the brain is a priority to achieve early diagnosis that can be translated to better outcomes. Here we describe the radiologic and histopathologic features observed in a group of gliosarcoma patients with variable histopathologic dedifferentiation.

O6-methylguanine DNA methyltransferase status determined by promoter methylation and immunohistochemistry in gliosarcoma and their clinical implications

O(6)-methylguanine-DNA methyltransferase (MGMT) is known as a DNA repair protein, and loss of function in MGMT is related to an increase in survival in patients with malignant gliomas treated with alkylating agents. In the present study, we determined the status of MGMT using methylation-specific polymerase chain reaction (PCR) and immunohistochemistry on paraffin-embedded specimens in 12 human gliosarcomas, and these results were then related to overall survival (OS) and response to alkylating agents. The MGMT promoter was methylated in six patients. Immunostaining of MGMT was positive in 58.3% of patients. MGMT methylation status was correlated with immunostaining results in five patients (41.7%). The median OS and progression-free survival (PFS) of the whole population were 13.4 months [95% confidence interval (CI), 12.3-14.5 months] and 8.3 months (95% CI, 7.4-9.2 months), respectively. In patients with methylated MGMT promoter, median OS was 15.0 months, compared with 11.3 months in the unmethylated group. Median PFS of gliosarcoma patients was 10.3 months for the methylated group, whereas it was 7.3 months for the unmethylated group. On multivariate analysis, patients with methylated MGMT promoter had better prognosis than patients with unmethylated MGMT promoter with respect to OS and PFS (P = 0.045 and 0.034, respectively). However, there was no statistical significance between MGMT protein expression and survival. The results show that a significant fraction of gliosarcomas have MGMT promoter methylation and protein expression, and suggest that patient survival is associated with MGMT methylation status.

Clinical characteristics and outcomes for a modern series of primary gliosarcoma patients

Primary gliosarcoma (PGS) is a rare central nervous system tumor with limited experience reported in the literature. In the current study, the authors present a modern series of confirmed PGS cases treated in the era of magnetic resonance imaging (MRI), after the accepted glioblastoma management of resection, radiation, and temozolomide. Using a retrospective review, patients with confirmed PGS were identified (1996-2008). Cases were determined to be PGS by central pathology review using the 2007 World Health Organization criteria. Extensive chart review was performed to gather clinical and pathologic data on these cases. All but 1 patient had undergone a preoperative MRI, with 1 patient receiving a computed tomography scan due to a cardiac pacemaker. A total of 10 patients received radiotherapy with concurrent and adjuvant temozolomide chemotherapy, and 8 patients received radiotherapy alone or in combination with other chemotherapeutic agents. In 2 patients, the history of adjuvant treatment could not be confirmed. The overall median survival was 13.9 months (range, 2.2-22.9 months). Patients with gliosarcomas resembling meningioma were found to have a significantly prolonged median survival compared with patients harboring gliosarcoma resembling glioblastoma multiforme (16 months vs 9.6 months; P = .011). However, no difference in survival was noted between patients who received concurrent radiotherapy and temozolomide compared with those who did not (10.4 months vs 13.9 months; P = .946). The results of the current study support previous hypotheses that there are 2 distinct types of PGS. The type mimicking the appearance of a meningioma appears to carry a significantly more favorable prognosis, most likely due to an increased chance at achieving macroscopic total resection.

Clinicopathological Characteristics and Outcomes of Gliosarcoma: Analysis using the Surveillance, Epidemiology, and End Results (SEER) Registry Data

Clinicopathological Characteristics and Outcomes of Gliosarcoma: Analysis using the Surveillance, Epidemiology, and End Results (SEER) Registry Data

Clinical and epidemiological characteristics of pediatric gliosarcomas

Gliosarcoma (GS) is a glioblastoma with a sarcomatous component that is presumed to be a metaplastic differentiation of glioma cells. We studied the clinical relevance of this histological glioblastoma subentity within the pediatric population. We obtained patient data from the German HIT-GBM database, which contains clinical data for more than 600 pediatric patients with centrally reviewed high-grade gliomas. By applying defined inclusion criteria (diagnosis of GS proven by central neuropathological review; patient age 0 to 21 years), four patients were identified. In addition, after a review of the English medical scientific literature, 19 additional cases were found. The relative frequency of GS in the German HIT-GBM database was only 1.9%. In the whole series of 23 pediatric GS patients, including previously reported cases, the male-to-female-ratio was 1.2:1. GS was found in all pediatric age groups with a median age of 11 years, but there was an unexpectedly high accumulation in infants (6 of 23 <3 years of age, 26%). GS showed a strong predilection of the cerebral hemispheres (22 out of 23 cases). Increased intracranial pressure was the leading symptom of a short clinical history with a median duration of 0.7 month. Interestingly, six patients (26%) were reported with a history of cranial radiotherapy prior to GS diagnosis. In 60% of the GS patients in our series, gross total resection was achieved. Median overall (OS) and event-free survivals (EFS) of the total cohort were 12.1 and 9.8 months, respectively. In conclusion, GS is a very rare tumor entity in children. Literature review suggests a relatively higher incidence in infants and in patients with a previous history of radiotherapy.