Primary intracranial haemangiopericytoma: Comparison of survival outcomes and metastatic potential in WHO grade II and III variants

Primary intracranial haemangiopericytomas (HPC) are rare, highly vascular tumours with a high propensity for local recurrence and distant metastasis. Optimal treatment includes maximal surgical resection followed by adjuvant radiotherapy. In 2007, new histopathological grading criteria were introduced to differentiate between high grade (World Health Organization [WHO] grade III) and low grade (WHO grade II) tumours. Given the rarity of this tumour, there is a paucity of information regarding the prognostic significance of histological grade. We conducted a retrospective review of our 20 year experience in treating 27 patients with HPC at our institution. Statistical analysis to compare overall survival, local recurrence rate and metastatic potential between the two grades were conducted using Kaplan–Meier analysis. The estimated median survival for grade II HPC was 216 months and for grade III tumours was 142 months. On multivariate analysis, grade II tumours were associated with better survival than grade III lesions (hazard ratio = 0.16, 95% confidence interval 0.26–0.95; p = 0.044). During the study period, 33% of grade III tumours developed local recurrence compared to 21% of grade II tumours. Metastases were found in 36% of grade II patients and 25% of grade III patients. There was no significant statistical difference in local recurrence rate and metastasis between the two grades. Higher histological grading in HPC is associated with worse overall survival. However based on our series higher histological grading is not associated with higher local recurrence or distant metastatic rates.     

Spinal ependymomas: Benefits of extent of resection for different histological grades

Although the World Health Organization (WHO) categorizes spinal ependymomas into three histological grades, difference in surgical outcomes between WHO grades I and II tumors are unclear. For these benign tumors, prognosis may be best determined by factors other than tumor grade alone, such as extent of resection. To analyze the effects of the extent of resection on different grades of spinal ependymomas, we performed a comprehensive literature review to identify adult spinal ependymoma patients who received surgical resection with a clearly identifiable WHO grade. A total of 175 patients were identified. While grade III tumors carried the worst prognosis as expected (p < 0.001), grade I and II tumors did not differ significantly in outcomes following surgery. Overall, gross total resection (GTR, 68.7%, 114/166) provided significantly improved progression-free survival (PFS, p < 0.001) and overall survival (OS, p = 0.022) compared to the subtotal resection group. Surprisingly, the highest GTR rate was achieved for grade II tumors (78.8%, 78/99; p < 0.001) followed by grade I (58.9%, 33/56) and grade III tumors (27.3%, 3/11). Interestingly, PFS was significantly improved by GTR for grade II tumors (p < 0.001), but not for grade I (p = 0.705). Similar trends, although not statistically significant, were found for OS. Our results show that while GTR provides the best overall outcomes, GTR is most effective for classic grade II ependymomas, but not for grade I ependymomas. Despite having a lower WHO grade, myxopapillary ependymomas have a lower GTR rate, and benefit less from GTR.     

Resultados en el tratamiento de los hemangiopericitomas intracraneanos. Serie de casos

ObjectiveIntracranial hemangiopericytoma (HPC) is a rare central nervous system tumor characterized by its low incidence, high rate of local recurrence and risk of metastasis. The main objectives of this paper are two: to show the results in the treatment of HPC in our institution in the last 20 years and to make a review of the literature on this topic.MethodsRetrospective review that includes patients diagnosed with intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) that have undergone surgery from 1997 to 2017. It includes patients that had nuclear expression of STAT-6 (detected by immunohistochemistry) and grade II/III histopathological diagnosis (defined by the World Health Organization in 2016). We collected demographic data, tumor characteristics, treatment and survival of these patients.ResultsA total of 19 patients fulfilled inclusion criteria. The median follow up was 96 months (12-230). The mortality rate was 21% (n = 4). 57.9% of patients presented at least one tumor recurrence (n = 11) (recurrences of 6%, 67% y 90% at 1, 5 and 10 years). Five patients presented extracranial metastasis. Patients with tumors < 6 cm had greater survival (P < .05).ConclusionsA series of patients undergoing SFT/HPC were presented according to the new WHO criteria. Size is a predictor of survival. Currently there are no validated criteria for surgical resection in this pathology. A classification with surgical guidance would be useful.     

Outcome of resection of WHO Grade II meningioma and correlation of pathological and radiological predictive factors for recurrence

This study investigated whether extent of surgical resection (Simpson and Shinshu grade) along with pathological and radiological factors influence the tumor control and recurrence-free survival (RFS) of patients with World Health Organization (WHO) grade II meningiomas. The clinical, radiological and surgical notes on the 59 patients with WHO grade II meningioma managed at our institution over 20 years were retrospectively reviewed. In this study, median survival time was 41 months. The overall recurrence rate in Simpson grades I and II resection was 31%. In grades III and IV, the overall recurrence rate was 73%, and this high recurrence rate in these groups was confined within 5 years. In Cox regression analysis, combined data of grades (I and II)/complete resection showed a significant difference in RFS compared to grades (III and IV)/subtotal resection (p = 0.0001). A similar trend of RFS (p = 0.0001) was observed with the Shinshu grading system of resection. In addition, a Ki-67% marker for proliferation less than 15% (p = 0.029), absence of certain radiological features including heterogeneous enhancement, cyst formation and peritumoral edema (p = 0.006), and repeat surgery for recurrent meningioma was associated with better survival (p = 0.014). However, radiosurgery did not have a beneficial role in the treatment of recurrence of atypical meningioma. The Simpson grading system is the primary predictor of recurrence of WHO grade II meningioma after resection. In addition, certain pathological and radiological features need to be considered as possible factors of recurrence after resection. Lastly, depending on the likely risks and surgical morbidity, repeat surgical resection should be performed for recurrent atypical meningioma.     

Reirradiation of recurrent meningioma

Management of meningioma includes observation, resection, and radiation therapy (RT). For patients with recurrent disease, similar options exist. However, the control rate following a second course of RT for recurrent disease is unknown. We reviewed an institutional database of patients with meningioma treated with stereotactic radiosurgery or fractionated stereotactic RT who underwent a second course for recurrent disease. Cox regression model was used for analysis. Variables tested included tumor volume, RT type, tumor grade, age at diagnosis, time to progression, and interval between RT. Eleven of 19 patients (58%) experienced disease progression. Median time to second progression was 10 months. Freedom from progression at one year was lower in patients with grade II or III tumors compared to those with grade 1 or unknown histology (17% compared to 92%, p = 0.0054). Cox regression showed that a grade II–III tumor affects progression-free survival (PFS), with a hazard ratio of 5.37 (p = 0.011). Median time to progression (MTP) for patients with grade II–III tumors was eight months. MTP was not reached for patients with grade 1/unknown tumors. Reirradiation for recurrent meningioma yields modest tumor control rates but for patients with grade II or III tumors, outcomes are poor.     

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.     

Treatment and survival of supratentorial and posterior fossa ependymomas in adults

Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan–Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3 years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p < 0.0001), high tumor grade (HR 1.82, p = 0.005), and large tumor size (HR 1.66, p = 0.008) were associated with poor survival. Females compared to males (HR 0.67, p = 0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p = 0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location.     

Treatment of atypical meningioma

The aim of this study was to review the outcome after multimodality therapy in atypical meningiomas using the 2000 World Health Organization (WHO) classification system, and to suggest a logical therapeutic approach. Between April 1997 and February 2008, 35 patients with atypical meningiomas were managed in our hospital. All surgical specimens were reviewed according to the 2000 WHO classification system. The median follow-up was 40 months (range: 6–97 months). Radical extirpation surgery (Simpson grade I) was performed in 11 (31%) patients, and there was no tumor recurrence for these patients. For patients who underwent incomplete resection, the median interval to recurrence was increased from 17 months for surgery alone to 39 months for surgery with adjuvant radiation therapy (p = 0.138). Age, MIB-l labeling index, and tumor location had no significant effect on either progression-free survival or overall survival. Atypical meningiomas are difficult to manage and have high recurrence and poor survival rates. In our series, complete resection of the tumor is a key determinant for a better outcome. Adjuvant radiation therapy is recommended if incomplete surgical excision is performed.     

Overexpression of tissue microRNA10b may help predict glioma prognosis

We investigated the relationship between microRNA-10b (miR-10b) expression and prognosis in human glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-10b in 128 glioma and 20 normal brain tissues. Clinical information – age, sex, Karnofsky Performance Status (KPS) and World Health Organization (WHO) grade – were also collected. The associations between miR-10b expression and the clinicopathological factors and outcome of glioma patients were statistically analyzed. Expression levels of miR-10b in glioma tissue were significantly higher than in normal brain tissue (P < 0.001). High-grade glioma (WHO grade III and IV) had much higher miR-10b expression levels than low-grade tumors (WHO grade I and II). Additionally, the increased miR-10b expression in the glioma tissues was significantly associated with a low KPS (P = 0.03). Kaplan–Meier survival curves and Cox regression analyses showed that overexpression of miR-10b (P = 0.01) and high grade (P = 0.02) were independent factors predicting poor outcome for glioma patients. Furthermore, subgroup analyses showed that the miR-10b expression level was significantly associated with poor overall survival in glioma patients with high grades (P < 0.001). Up-regulation of miR-10b may have value in predicting clinical outcome in glioma patients, particularly for those with high pathological grades.     

Reduced expression of LC3B-II and Beclin 1 in glioblastoma multiforme indicates a down-regulated autophagic capacity that relates to the progression of astrocytic tumors

The aim of this study was to investigate the expression of microtubule-associated protein 1 light chain 3B (LC3B) and the autophagy-related gene Beclin 1 in astrocytic tumors and to analyze their expression profiles with respect to the development of astrocytic tumors. The expression patterns of LC3B and Beclin 1 were analyzed by immunohistochemistry and/or western blotting in tumor samples from 62 patients with different grades of astrocytic tumor. The expression patterns of LC3B and Beclin 1 were correlated with the pathological and clinical characteristics of the patients. Western blot analysis indicated that the average optical densitometry (OD) ratio of Beclin 1 in high-grade astrocytic tumors (World Health Organization [WHO] grade III/IV) was lower than in low-grade astrocytic tumors (WHO grade I/II, p = 0.036). The expression of LC3B-I exhibited no significant difference among the various grades of astrocytic tumor. However, the average OD ratio of LC3B-II was lower in glioblastoma multiforme (GBM) than in other grades of astrocytic tumor (p = 0.030). The expression levels of Beclin 1 and LC3B-II were related to survival time and they were also correlated with each other (p = 0.035). In addition, down-regulation of LC3B-II and Beclin 1 expression was associated with GBM. The progression of astrocytic tumors was related to a decrease in autophagic capacity represented by the loss of LC3B-II and Beclin 1 expression.     

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.     

Prognostic factors and survival in primary adult high grade brainstem astrocytoma: A population based study from 1973–2008

Adult brainstem astrocytomas are a rare and heterogeneous group of malignancies. Most reports represent low-grade gliomas. This study used the Surveillance, Epidemiology and End Results (SEER) database to analyze the association between survival and demographic factors, tumor histology, and treatment characteristics among adult patients with high-grade brainstem astrocytoma (HGBSA). Adult patients with histologically confirmed diagnoses of primary HGBSA were studied. In univariate and multivariate analysis, we investigated the effect of demographics, tumor histology and treatment modality on survival. Overall median survival in the cohort of 240 adult patients was 7 months, with 1, 2, 5 and 10 year survival rates of 33.2%, 19.7%, 10.1%, and 8.3%, respectively. Age >50 years (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.45–2.70, p < 0.001) and grade IV versus grade III tumor (HR 1.61, 95% CI 1.15–2.26, p = 0.006) were associated with statistically significant increased mortality in multivariate analyses. Surgical intervention trended toward association with lower mortality (HR 0.68, 95% CI 0.47–1.01, p = 0.055). Our findings suggest that in patients with HGBSA, younger age and lower-grade histology are associated with better prognosis. Surgical intervention trended towards a significant association with better outcome, while radiation treatment was not associated with a statistically significant benefit in survival.     

Ganglioglioma of brain stem and cervicomedullary junction: A 50 years review of literature

Gangliogliomas are rare low-grade brain tumors composed of both neoplastic glial and neuronal cell elements. The treatment modalities are relatively different in this location and hence factors affecting outcome are poorly understood. We identified 142 brain stem GG patients across 46 studies. The average age was 11.4 years with significant difference b/w males and females under the age of 20 (p = 0.001). 100% of tumors in the CMJ while, 72% of type I and 86% of type II tumors demonstrated contrast enhancement. 72% of type I and 86% of type II tumors demonstrated contrast enhancement. All BRAF mutation positive tumors demonstrated contrast enhancement. Medulla and pons was the most favorable location followed by medulla alone, and the CMJ. In all tumors “gross total resection” (GTR, 16%), “subtotal resection” (STR, 48%) or “partial resection” (PR, 36%) was achieved. Most subtypes II and III were partially resected (86% and 66%), while, subtype I underwent STR (66%). Only 55% of the patients were positive for the BRAF V600E mutation. The overall survival dropped from 50% at 24 to 10% at 60 months, postoperatively. Through this review, we found that an early diagnosis, location, and with the imaging characteristics are vital part of the preoperative planning. Surgical resection is highly dependent on location in the brain stem with radical resection only limited to the most contrast enhancing portion of these tumors. BRAF V600E mutation status should be considered to allow the possibility of targeted therapy in case of a residual tumor and/or regrowth.     

Hippocampal-sparing radiotherapy: The new standard of care for World Health Organization grade II and III gliomas?

The neurocognitive effects of cranial radiotherapy in patients with gliomas are well-recognised and may be related to the dose delivered to the hippocampi. Intensity modulated radiotherapy (IMRT) is a radiotherapy technique that can be used to selectively spare the hippocampi without compromising the dose delivered to the tumour. This study aimed to evaluate if hippocampal-sparing IMRT is achievable in patients with World Health Organization (WHO) grade II and III gliomas. A retrospective review of consecutive patients with WHO grade II and III gliomas treated with IMRT at our institution between January 2009 and August 2012 was performed. Hippocampal-sparing was defined as a mean dose to at least one hippocampus of less than 30 Gy. The dose delivered to the tumour was never compromised to achieve the hippocampal dose constraint. Logistic regression analyses were performed to identify predictive factors for achieving hippocampal-sparing treatment. Eighteen patients were identified and hippocampal-sparing was achieved in 14 (78%). The median dose prescribed was 59.4 Gy in 33 fractions and 11 patients had WHO grade III gliomas. The mean dose to the contralateral hippocampus was 24.9 Gy. Planning target volumes less than 420.5 cm³ were more likely to enable hippocampal-sparing treatment to be given (hazard ratio 1.7, p = 0.03) and there was a trend with oligodendrogliomas and anaplastic oligodendrogliomas. Hippocampal-sparing radiotherapy is feasible in patients with WHO grade II and III gliomas. Oncologic outcomes are yet to be assessed prospectively. The relationship between hippocampal dose and neurocognitive function in adults is currently under investigation.     

Clinicopathologic analysis of rhabdoid meningioma

Rhabdoid meningioma is an uncommon variant of meningioma, and was classified separately for the first time in the 2000 World Health Organization’s classification of tumors of the nervous system. Because it often shows malignant histological features and follows an aggressive clinical course, it has been classified as a grade III neoplasm. We describe the clinicopathologic features of 13 patients with this rare tumor. From 13 patients (seven male, six female), 19 specimens of rhabdoid meningioma were obtained between 2001 and 2009. The mean age of patients was 50.4 years at their first operation. The mean postoperative follow-up period was 35.7 months. Five patients experienced tumor recurrence, and two patients died from the disease. The mean time to first recurrence was 36.1 months. The recurrence-free survival rates at 1 and 5 years were 62% and 23%, respectively. Immunohistochemically, all tumors were positive for vimentin and epithelial membrane antigen. MIB-1 labeling indices were higher following tumor recurrence. Close follow-up and aggressive treatment of these tumors is warranted.     

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.     

Ki-67 overexpression in WHO grade II gliomas is associated with poor postoperative seizure control

PurposeSeizures are the most common initial symptom in patients with low-grade gliomas, and approximately 30% of these patients still suffer from epilepsy after gross-total resection of the tumour. We examined the relationship between the overexpression of ki-67 in WHO grade II gliomas and seizure control.MethodsA series of 93 histologically confirmed WHO grade II glioma tissues were analysed through immunohistochemical staining for ki-67 expression. Follow-up visits regarding seizure control were scheduled at 12 months. The Engel classification was used to categorise patients’ seizure status.ResultsOf the 93 patients analysed, 65 (66.3%) patients initially presented with seizures. A total of 36 patients were diagnosed with WHO grade II oligodendrogliomas, 29 patients had oligoastrocytomas and 28 patients had astrocytomas. Ki-67 was over-expressed in 15 patients. One year after surgery poor seizure control was observed in 11 of these patients. In contrast, low ki-67 expression (<10%) was found in 78 patients. Poor seizure control was observed in 36 patients (difference between ki-67 over- and low expression groups P = 0.002). Logistic regression analysis revealed that patients with gross-total resection achieved better seizure control while ki-67 overexpression and age below 38 years were poor seizure control factors explained of the variance of seizure outcome (OR: 0.382, 4.354 and 1.822, respectively).ConclusionsIn WHO grade II gliomas, Ki-67 is a molecular marker which predicts poor seizure control of glioma patients after the resection of the tumour. Gross-total resection, ki-67 overexpression and age below 38 years significantly affect seizure prognosis.