IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy

ObjectiveIsocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an established association with preoperative seizures in patients with grades II–IV diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of postoperative seizure frequency.MethodsThis was a retrospective study. Patients with grades II–IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included. The primary outcome was seizure frequency over the first 12 postoperative months: Group A — postoperative seizure freedom; Group B — 1–11 seizures over 12 months (less than one seizure per month); and Group C — greater than one seizure per month. Rates of IDH1-R132H mutation were compared between the three outcome groups in univariate and multivariate analyses. Subgroup analysis was performed in 64 patients with IDH1/2 pyrosequencing data.ResultsOne hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III, and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12 months, compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and 70.0% (14/20) of Group C patients (p = 0.001). On multivariate analysis, after controlling for preoperative seizure, grade, and temporal tumor location, IDH1-R132H was associated with Group C when compared with both Group A (RR 4.75, p = 0.032) and Group B (RR 9.70, p = 0.012). In the subgroup with IDH1/2 molecular data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of Group C, and 87.5% (14/16) of Group C patients (p = 0.004).SignificanceIn patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated with a more severe phenotype of postoperative epilepsy. These findings support further research into IDH mutations, and the potential for an antiepileptic therapeutic effect of their inhibitors, in patients with glioma-associated epilepsy.     

BRAF V600E mutation is a significant prognosticator of the tumour regrowth rate in brainstem gangliogliomas

BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma’s clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma’s clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p = 0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p = 0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR = 1.027, p = 0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery.     

An analysis of 170 glioma patients and systematic review to investigate the association between IDH-1 mutations and preoperative glioma-related epilepsy

Seizure is a common presenting symptom of glioma, and many biomarkers have been suggested to be associated with preoperative seizure; however, the relationships between IDH (isocitrate dehydrogenase) mutations and glioma-related epilepsy only recently been studied. The authors aimed to examine the correlations between IDH mutations in glioma patients with preoperative seizures and tumor location. A series of 170 glioma samples were analyzed for IDH1 R132H mutations (amino acid change from arginine to histidine at codon 132) with immunohistochemistry (IHC) staining and for IDH mutations with direct DNA sequencing when the IHC results were negative. If either the IHC or direct DNA sequencing result was positive, the IDH status was defined as mutated. The results of the IDH mutation examinations were used to analyze the relationship between mutations and glioma-related epilepsy. The study population consisted of 64 (37.6%) World Health Organization (WHO) grade II gliomas, 58 (34.1%) grade III, and 48 (28.3%) grade IV gliomas. A total of 84 samples with IDH1 mutations were observed in our study, and 54 of these presented with seizures as the initial symptoms, whereas 28 of the patients with wild-type IDH status presented with seizures (p = 0.043 for the WHO grade II gliomas, p = 0.002 for the grade III gliomas and p = 0.942 for the grade IV gliomas, chi-squared tests). Among the WHO grade II and III gliomas, IDH1 mutations were significantly associated with preoperative seizures, but no significant relationship between IDH mutations and preoperative seizures was found with glioblastoma multiforme.     

Prognostic factors and treatment options for paediatric ependymomas

The aim of this study was to determine factors of prognostic relevance for paediatric ependymomas, and evaluate the efficacy of treatment modalities. This is a retrospective study of 43 patients with ependymoma (<18 years) who underwent a combination of surgical excision, chemotherapy, and/or radiotherapy treatment at The Prince of Wales Cancer Centre between 1969 and 2009. Statistical analysis was performed to assess the prognostic relevance of various parameters affecting the two-year and five-year overall survival (OS) and progression-free survival (PFS). The five-year OS and PFS were 50.3% and 44.8% respectively (median follow-up 50 months). Eighteen patients (41.9%) experienced tumour recurrence: 13 had a local recurrence (LR) and five had both LR and distant recurrence. On univariate analysis, a more favourable prognosis in terms of both OS and PFS was evident for supratentorial tumours compared to infratentorial tumours (OS p = 0.007, PFS p = 0.045), stereotactic radiosurgery/ fractionated stereotactic radiotherapy compared to craniospinal irradiation or local posterior fossa/local brain ± boost radiotherapy modalities (OS p = 0.047, PFS p = 0.031), total radiotherapy dose >50 Gy compared to ?50 Gy (OS p = 0.008, PFS p = 0.005), and in patients with no tumour recurrence compared to those with recurrence (OS p = 0.03, PFS p < 0.001). Although not statistically significant, a more favourable multivariate outcome was evident in patients who underwent complete surgical resection. Chemotherapy treatment and histopathological grade, however, were not relevant to prognosis. This study supports the need to pursue more aggressive treatment for infratentorial and/or recurrent tumours. Ideal treatment involves maximal surgical resection, followed by adjuvant radiotherapy (>50 Gy).     

Early adjuvant radiotherapy in the treatment of atypical meningioma

Atypical meningiomas have a greater propensity to recur than benign meningiomas and the benefits of early adjuvant radiotherapy are unclear. Existing studies report conflicting results. This retrospective cohort study evaluated the role of early adjuvant radiotherapy following surgical resection of atypical meningioma. A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I–III) or subtotal resection (STR; Simpson Grade IV–V). Survival analysis was performed using the Kaplan–Meier method. One hundred thirty-three patients were identified with a median age of 62 years (range 22–86 years) and median follow-up of 57.4 months (range 0.1–152.2 months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5 year PFS 81.2% versus 40.08%, log-rank = 11.117, p = 0.001) but not overall survival (OS) (5 year OS 76.6% versus 39.7%, log-rank = 3.652, p = 0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5 year OS 77.0% versus 75.7%, log-rank = 0.075, p = 0.784) or PFS (5 year PFS 82.0% versus 79.3%, log-rank = 0.059, p = 0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned.     

IDH1 mutation may not be prognostically favorable in glioblastoma when controlled for tumor location: A case-control study

Isocitrate dehydrogenase 1 (IDH1) mutation is a known prognostic factor in glioblastoma multiforme (GBM). It has been well documented that patients with IDH1 mutant (IDH1-mu) GBM have a better outcome compared to patients with IDH1 wild-type (IDH1-WT) GBM. IDH1-mu tumors have been shown to be more commonly located in the frontal lobe, and less likely to be in multiple lobes. It is unclear whether differential location is part of the prognostically favorable profile of these tumors. We performed a case-control study, matching IDH1-mu GBMs to IDH1-WT GBMs that are controlled for age, sex and tumor location. There were 21 IDH1-mu tumors and 21 matched IDH1-WT tumors. Age, sex and tumor location were matched between the two groups. After controlling for the factors described, the IDH1-mu tumors were more likely to be secondary GBM (61.9% secondary vs. 14.3%, p = 0.004). There was an insignificant trend towards smaller tumor volume in the IDH1-mu group (28.13 ± 6.56 vs. 41.8 ± 7.33 cm³, p = 0.173). Extent of surgical resection was similar in both groups (mean 84.49% vs. 89.89%, p = 0.419). There was no survival advantage for IDH1-mu tumors when controlled for location: 25.2 months overall survival for IDH1-mu patients and 23.6 for IDH1-WT patients, p = 0.794. IDH1 mutation may provide part of its prognostic significance by differential localization of tumor, both making IDH1-mu tumors more amenable to gross total resection and placing these tumors in less eloquent areas, thereby lowering neurological morbidity.     

Pleomorphic xanthoastrocytomas: Institutional experience of 18 patients

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade glioma (World Health Organization Grade II) that most often presents in the first two decades of life. We summarize and present our institutional experience in the management of these tumors. All patients managed for PXA at the University of California San Francisco were retrospectively identified through chart review. Patient demographics, tumor characteristics, management, and follow-up were extracted using medical records. Primary endpoints were overall (OS) and progression-free survival (PFS). In total, nineteen patients were treated for PXA from 1993–2011. Clinical data were available for analysis in 18 patients. Median OS was 209.0 months after date of surgery, with both 5 year and 10 year survival rates of 94%. In this patient cohort, tumor grade (p = 0.07), age (p = 0.32), and extent of resection (p = 0.58) did not predict OS. The majority of tumors (78%) recurred. Median PFS was 21.7 months, with 5 year and 10 year recurrence-free rates of 28% and 22%. On univariate analysis, tumor grade (p = 0.01), but not age (p = 0.51), size (p = 0.30), or extent of resection (p = 0.21), was the only covariate predictive of PFS. In patients presenting with higher tumor grade, however, earlier recurrence was demonstrated. Furthermore, the majority of recurrences (36%) occurred within the first 6 months post-operatively, which indicates the need to closely follow patients for that time.     

Survival outcomes of giant cell glioblastoma: Institutional experience in the management of 20 patients

Giant cell glioblastoma (GCG) is a rare subtype of glioblastoma (GBM) that is believed to carry an improved prognosis. However, given the rarity of this tumor, best management practices for GCG have yet to be ascertained. Here, we present our experience in managing GCG tumors at the University of California, San Francisco. Patients were retrospectively identified through chart review, and data pertaining to patient demographics, treatment plans, and follow-up were extracted from existing medical records. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. In sum, we identified 22 patients who were managed or followed for GCG. Most patients (78%) initially underwent subtotal resection as primary treatment for their tumor, and most also received post-operative adjuvant therapy (90%), with radiation being the most frequently administered modality (85%). Within this institutional cohort, median OS and PFS were 15.4 months and 5.7 months, respectively. On multivariate survival analysis, age (p = 0.84), sex (p = 0.05), and adjuvant radiation plus temozolomide (p = 0.12) were not associated with prolonged OS. However, adjuvant radiation plus temozolomide was associated with longer PFS (p = 0.01), and patients receiving this therapy demonstrated a median PFS of 32.9 months versus 13.1 months. These findings confirm the comparatively improved prognosis of GCG over GBM. Moreover, they suggest that extent of resection may not significantly delay recurrence or extend survival, and that combination radiation with temozolomide may represent the optimum adjuvant paradigm to delay tumor progression.     

Reliability of noncontrast-enhancing tumor as a biomarker of IDH1 mutation status in glioblastoma

Isocitrate dehydrogenase 1 (IDH1) mutations in gliomas have been associated with a frontal lobe location and a greater proportion of noncontrast-enhancing tumour (nCET). The purpose of our study was to validate the utility of MRI imaging features in predicting IDH1 mutations in glioblastomas. Pre-operative MRIs of new glioblastoma patients, consisting of at least FLAIR and T1-weighted post-contrast sequences, were reviewed by a neuroradiologist based primarily on the VASARI feature set. IDH1 mutation testing was performed on all patients using immunohistochemistry. 153 patients met the inclusion criteria, of whom five had IDH1 mutations (3.3%). A frontal lobe location had equivalent frequency in both the IDH1-mutated and IDH1-wildtype cohorts (p = 1.000). Three (60%) of the IDH1-mutated tumours had >33% nCET, compared to 21% of IDH1-wildtype (p = 0.073). 12 tumours had a frontal lobe epicentre and >33% nCET, all being IDH1-wildtype. All five IDH1-mutated tumours had either a frontal lobe epicentre or >33% nCET, but none had both these features. Our results question the strength of the association between frontal lobe glioblastomas with substantial nCET and IDH1 mutations, as these features are also relatively frequent in IDH1-wildtype tumours, which are much more common. MRI is thus more useful for ruling out an IDH1 mutation rather than strongly suggesting its presence: if a particular glioblastoma does not have a frontal lobe epicentre and has less than 33% nCET, it can be predicted to be IDH1-wildtype with a high degree of confidence.     

IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom

IntroductionSeizures are the most common initial symptom in patients with low-grade glioma and their occurrence strongly depends on the tumor location. The majority of low-grade gliomas reveal mutations in the genes encoding isocitrate-dehydrogenase 1 (IDH1) or 2 (IDH2). These mutations are associated with metabolic changes that are potentially epileptogenic. We investigated the correlation between IDH1/2 mutations and tumor localization and seizure as the initial symptom.Materials and methodsThis retrospective study included patients with a diagnosis of WHO grade II astrocytoma and cortical infiltration and in whom initial symptoms were documented and biopsy tissue was available for IDH1/2 analysis. IDH1/2 mutation analysis was performed by direct sequencing or by immunohistochemistry with an antibody which detects mutated protein IDH1 R132H. Sequencing was carried out if immunohistochemistry was negative. IDH1/2 status was defined as mutated if either of these investigations were positive.ResultsSeventy-nine patients were included. IDH1 or IDH2 mutation was present in 63 (80%) patients who on average were younger than patients without IDH1/2 mutation (40 vs. 47 years, p = 0.0331, t-test). IDH1/2 mutations were associated with frontal tumor location (p = 0.0202). All 12 tumors in the insula revealed IDH1/2 mutations. Seizure as the initial symptom was recorded in 57 (72%) patients and was associated with IDH1 or IDH2 mutation by multivariate analysis (OR 22.563, p = 0.0019).ConclusionIn WHO grade II astrocytomas, IDH1/2 mutations mostly occur in tumors infiltrating the frontal lobe. Seizure as the initial symptom is associated with IDH1 or IDH2 mutation.     

Co-expression of midkine and pleiotrophin predicts poor survival in human glioma

The aim of this study was to investigate whether co-expression of midkine (MK) and pleiotrophin (PTN) has prognostic relevance in human gliomas. Immunohistochemistry was used to investigate the expression of MK and PTN proteins in 168 patients with gliomas. The levels of MK and PTN mRNA in glioma tissues and paratumor tissues were evaluated in 45 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan–Meier survival analysis was performed to assess prognostic significance. The expression levels of MK and PTN proteins in glioma tissue were both significantly higher (both p < 0.001) than those in paratumor tissues on immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of either MK or PTN was significantly associated with the World Health Organization Grade (p = 0.001 and 0.034, respectively), low Karnofsky Performance Status (KPS) score (p = 0.022 and 0.001, respectively), time to recurrence (p = 0.043 and 0.011, respectively) and poor overall survival (p = 0.018 and 0.001, respectively). Multivariate Cox proportional-hazards regression analysis revealed that increased expressions of MK and PTN were both independent prognostic factors for poor overall survival (p = 0.030 and 0.022, respectively). Furthermore, the co-expression of MK and PTN was more significantly (p = 0.003) associated with adverse prognosis in patients with gliomas than the respective expression of MK or PTN alone. To our knowledge, these findings are the first to indicate that the co-expression of MK and PTN is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker.     

The influence of carmustine wafer implantation on tumor bed cysts and peritumoral brain edema

The development of perifocal edema and tumor bed cyst has been reported after implantation of biodegradable carmustine wafers for the treatment of malignant gliomas. We retrospectively evaluated these changes in a series of patients; 19 consecutive patients with malignant glioma who received carmustine wafer implantation at our hospital from January 2013 through July 2013, and 28 patients who underwent surgery prior to our institution’s initiation of carmustine wafer implantation, as historical controls. The volume of the tumor bed cyst and perifocal edema was calculated on MRI acquired at four time points: ⩽72 hours after surgery for baseline, and at 1–4, 5–8, and 9–12 weeks after surgery. The volume of the tumor bed cyst in the wafer group increased significantly relative to the control group at all time points (p = 0.04). Opening of the ventricle was inversely correlated with enlargement of the tumor bed cyst in the wafer group (p = 0.04). The change in the volume of perifocal edema in the wafer group was not significantly different (p = 0.48), but exhibited a considerable increase in patients with anaplastic oligodendroglioma relative to glioblastoma patients in the wafer group (p = 0.01). We demonstrated significant enlargement of the tumor bed cyst volume after carmustine wafer implantation, as well as the development of marked perifocal edema in patients with anaplastic oligodendroglioma.     

Impact of prognostic nutritional index on survival in recurrent glioblastoma

BackgroundPrimary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment.MethodsData of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10 × serum albumin (g/dL)) + (0.005 × total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes.ResultsMedian value of PNI was 45.7, and median follow-up duration was 9 months (1–68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5–10.4). Median OS was significantly longer in patients with PNI > 45.7 compared to patients with PNI ≤ 45.7 (13.9 months (95%CI: 10.5–17.4), and 4.6 months (95%CI: 2.5–6.8), p < 0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22–0.74), p = 0.03)].ConclusionIn our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.     

Response and habituation of pro- and anti-inflammatory gene expression to repeated acute stress

IntroductionAcute stress induces increases in plasma inflammatory mediators, which do not habituate to repeated stress. Inflammation is a risk factor for age-related illnesses, highlighting the need to understand factors controlling inflammation. No studies have examined changes in pro- and anti-inflammatory gene expression in response to repeated acute stress in humans.MethodsRNA was isolated from peripheral blood before, 30 and 120 min after exposure of n = 32 healthy human participants to the Trier Social Stress Test (TSST) on two days. Gene expression of interleukin (IL)-6, IL-1β, nuclear factor (NF)-κB and IκB was measured repeatedly on both days. We further assessed leukocyte numbers, plasma IL-6, and salivary cortisol.ResultsStress induced IL-6 (F = 44.7; p < 0.001) and cortisol responses (F = 18.6; p < 0.001). Cortisol responses habituated (F = 5.1, p = 0.003), but IL-6 responses did not (n.s.). All genes increased in response to initial stress (IL-6: F = 3.8; p = 0.029; IL-1β: F = 7.1; p = 0.008; NF-κB: F = 5.1; p = 0.009; IκB: F = 4.7; p = 0.013) and showed habituation to repeated stress (IL-6: t = 2.3; p = 0.03; IL-1β: t = 3.9; p = 0.001; NF-κB: t = 2.1; p = 0.041; IκB: t = 3.1; p = 0.005). Day 1 responses of IL-1β and IκB were not explained by changes in leukocyte populations, but IL-6 and NF-κB, as well as most day 2 changes were not independent of leukocyte populations.ConclusionsStress response and habituation of pro- and anti-inflammatory gene expression as found here might indicate that even on an intracellular level, inflammatory responses to acute stress are adaptive in that they respond to initial, but habituate to repeated, similar stress. Future studies will need to test whether non-habituation is predictive of disease.     

The use of isoflurane and desflurane as inhalational agents for glioblastoma surgery. A survival analysis

BackgroundSeveral studies have examined the impact of anesthetics on cancer recurrence. Isoflurane but not desflurane has protumoral effects. We hypothesize the use of isoflurane but not desflurane during surgery for primary GBM is an independent predictor of disease progression and mortality.Methods378 adult patients were included in the study. The progression free survival (PFS) and overall survival (OS) rates at 1 and 5 years were compared in patients who had either desflurane or isoflurane alone or in combination with propofol infusion. Multivariate analyses were conducted to test the association between preoperative, intraoperative and postoperative hyperglycemia with PFS and OS.ResultsKaplan–Meier curves demonstrated similar survival in patients who had either desflurane or isoflurane. The use of a propofol infusion during surgery did not affect survival. Univariate analysis demonstrated that age, body mass index and the adjusted Charlson comorbidity score were associated with reduced survival. The multivariate analysis confirmed that age and BMI but not the type volatile anesthetic use were independent prognostic factors for PFS (HR, 95%CI: 1.07, 0.85–1.37, 9 = 0.531) and OS (HR, 95%CI: 1.13, 0.86–1.48, p = 0.531).ConclusionThe use of isoflurane or desflurane during GBM surgery is not associated with reduced PFS or OS.     

Downregulation of chromatin remodeling factor CHD5 is associated with a poor prognosis in human glioma

Chromodomain helicase DNA-binding protein 5 (CHD5), a member of the CHD family, is involved in key cellular processes including chromatin remodeling, cell cycle regulation, and cellular adhesion. Recent studies have demonstrated that CHD5 is the product of a novel tumor suppressor gene and is implicated in certain tumor types. However, the clinicopathological significance of CHD5 expression in human malignant gliomas remains unclear. To address this problem, CHD5 expression in human gliomas and non-neoplastic brain tissues was measured using real-time quantitative polymerase chain reaction (RT–PCR) assay, Western blot, and immunohistochemistry. The association of CHD5 immunostaining with clinicopathological factors or prognosis of glioma patients was statistically analyzed. Genetic and protein expression of CHD5 were downregulated in glioma tissues compared to corresponding non-neoplastic brain tissues (both p < 0.001). Additionally, decreased expression of CHD5 in glioma was significantly associated with pathological grade (p = 0.007); high pathological grade was associated with low CHD5 expression. Loss of CHD5 protein expression was also significantly correlated with a low Karnofsky performance scale score (p = 0.01). Moreover, overall survival of patients with low CHD5 protein expression was dramatically shorter than those of patients with high CHD5 protein expression (p = 0.003). Multivariate Cox regression analysis indicated that CHD5 expression was an independent prognostic factor for patients with gliomas (p = 0.01). In conclusion, these data offer convincing evidence for the first time that CHD5 might act as a tumor suppressor in glioma, may act as a regulator of aggressive development, and is a candidate prognostic marker for this malignancy.     

Effectiveness of radiotherapy for elderly patients with anaplastic gliomas

Postoperative radiotherapy (RT) is utilized routinely in the management of anaplastic World Health Organization Grade III gliomas (AG), including anaplastic astrocytoma (AA) and anaplastic oligodendroglioma (AO). However, the optimal role of RT in elderly AG patients remains controversial. We evaluated the effectiveness of RT in elderly AG patients using a national cancer registry. The USA Surveillance, Epidemiology, and End Results database (1990–2008) was used to query patients over 70 years of age with AA or AO. Independent predictors of overall survival were determined using a multivariate Cox proportional hazards model. Among 390 elderly patients with AG, 333 (85%) had AA and 57 (15%) had AO. Approximately two-thirds of AA patients (64%) and AO patients (65%) received RT. Most AO patients (58%) and many AA patients (41%) underwent surgical resection; the remainder had biopsy. The median overall survival for all patients who underwent RT was 6 months (95% confidence interval [CI], 5–7 months) versus 2 months (95% CI 1–6) in patients who did not have RT. Patients who had gross total resection (GTR) plus RT had a median overall survival of 11 months (95% CI 7–14). Multivariate analysis for all patients showed that undergoing RT was significantly associated with improved survival (hazard ratio [HR] 0.52, p < .0001). AA tumor type (HR 1.37, p = .03) was associated with worse survival than AO tumor type; female sex (HR 0.59, p < .0001) and being married (HR 0.66, p = .002) significantly improved survival. Patients that underwent GTR had a significant reduction in the hazards of mortality compared to biopsy (HR 0.72, p = .04). Elderly AG patients undergoing RT had better overall survival compared to patients who did not receive RT. Treatment strategies involving maximal safe resection plus RT should be considered in the optimal management of AG in elderly patients.     

Clinical management and survival of patients with central nervous system hemangiopericytoma in the National Cancer Database

Purpose/objectivesHemangiopericytomas are rare central nervous system (CNS) tumors. We sought to investigate existing clinical management strategies and overall survival (OS) among patients with hemangiopericytomas of the CNS.Methods/materialsAll patients diagnosed with CNS hemangiopericytoma from 2004 to 2014 in the National Cancer Database were included. Clinical and treatment-related characteristics were analyzed for an association with OS following diagnosis using univariable and multivariable analyses.ResultsNine-hundred and eighty-one patients were included (0.22% of all CNS tumors). At diagnosis, 22 patients had spinal tumors (2%), 21 patients had multifocal tumors (2%) 28 had disseminated disease (3%), and the remainder were unifocal intracranial tumors. Patients either underwent surgical resection and radiation (48%), surgery alone (37%), radiation alone (6%), or biopsy alone (9%). Of patients with known extent of resection, 53% underwent gross total resection, and, of patients with known radiation modality, 15% received stereotactic radiosurgery. Among the total cohort, 3 and 10 year OS was 87% and 59%, respectively. On multivariable analysis, factors associated with inferior OS included age (HR = 1.05, p < 0.001), WHO grade (p < 0.001), multifocal disease (HR = 2.59, p = 0.04), disseminated disease (HR = 2.67, p = 0.01), and chemotherapy (HR = 2.66, p = 0.01). Patients receiving surgery alone or surgery and radiation demonstrated improved OS compared to biopsy alone (HR = 0.45, p = 0.01 and HR = 0.47, p = 0.02, respectively). However radiation utilization did not impact OS (p = 0.691).ConclusionsThe present data provide large-scale prognostic information from a contemporary cohort of patients with hemangiopericytoma and support an initial attempt at surgical extirpation. The benefits of ionizing radiation are likely limited to improved local control and neurologic function.