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Gliomatosis cerebri: clinical characteristics, management, and outcomes.

ABSTRACT: Gliomatosis cerebri is a rare diffusely infiltrating primary neoplastic glial process of the brain. Our objective is to review clinical presentation, management, and outcome in a large single institution series of gliomatosis cerebri patients. 54 consecutive gliomatosis cerebri cases presenting to Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Inclusion criteria included involvement of at least three cerebral lobes, lack of a single discrete mass and pathological confirmation of diffuse glioma. Median overall survival (OS) was 18.5 months. Age, gender, presenting symptoms, and contrast enhancement did not correlate significantly with survival, though there was a trend toward decreased overall survival in patients above the median age of 46 years. Karnofsky performance score <70 was associated with poor OS (median 9.5 vs. 20.5 months, p = 0.02). Higher histologic grade was associated with poor progression-free survival (PFS; median for WHO grades II, III, and IV: 21.5, 6.5, and 4 months; p = 0.03) and OS (median 34, 15.5, and 8.5 months; p < 0.05). Radiation therapy was strongly associated with better prognosis (PFS 16.5 vs. 4.5 months, p < 0.01; OS 27.5 vs. 6.5, p < 0.01), but chemotherapy was not. Gliomatosis cerebri patients have a poor prognosis. Lower KPS upon presentation and higher histologic grade predict decreased survival. Surgery's role is limited beyond biopsy for diagnostic purposes. Radiotherapy appears beneficial, although selection bias could be present in this retrospective study. Chemotherapy's value is not as clear but this must be interpreted with caution given variable treatment regimens in this series.

SUBMITTER: Chen S

PROVIDER: S-EPMC3907195 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Gliomatosis cerebri: clinical characteristics, management, and outcomes.

Chen Selby S Tanaka Shota S Giannini Caterina C Morris Jonathan J Yan Elizabeth S ES Buckner Jan J Lachance Daniel H DH Parney Ian F IF

Journal of neuro-oncology 20130123 2

Gliomatosis cerebri is a rare diffusely infiltrating primary neoplastic glial process of the brain. Our objective is to review clinical presentation, management, and outcome in a large single institution series of gliomatosis cerebri patients. 54 consecutive gliomatosis cerebri cases presenting to Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Inclusion criteria included involvement of at least three cerebral lobes, lack of a single discrete mass and pathological conf ...[more]

PMID: 23341100

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Project description:Gliomatosis cerebri (GC), a rare and deadly CNS neoplasm characterized by involvement of at least three cerebral lobes, predominantly affects adults. While a few small series have reported its occurrence in children, little is known about the molecular characteristics of pediatric GC. We reviewed clinical, radiological, and histological features of pediatric patients with primary GC treated at our institution over 15 years. Targeted sequencing of mutational hotspots in H3F3A, IDH1/2, and BRAF, and genome-wide analysis of DNA methylation and copy number abnormalities was performed in available tumors. Thirty-two patients [23 (72 %) with type 1 and 9 (28 %) with type 2 GC] were identified. Median age at diagnosis was 10.2 years (range 1.5-19.1). A median of 4 cerebral lobes (range 3-8) was affected at diagnosis. In addition, symmetrical bithalamic involvement was observed in 9 (28 %) patients. Twenty-two patients (69 %) had an anaplastic astrocytoma. Despite aggressive therapy, only two patients younger than 3 years at diagnosis are long-term survivors. Clustering analysis of methylation array data from 18 cases classified tumors as IDH (n = 3, 17 %), G34 (n = 4, 22 %), mesenchymal (n = 3, 17 %), and RTK I 'PDGFRA' (n = 8, 44 %). No tumors were classified as K27 subgroup. PDGFRA was the most commonly amplified oncogene in 4 of 22 tumors (18 %). H3F3A p.G34 occurred in all cases classified as G34. Two of 3 cases in the IDH subgroup had IDH1 p.R132H. No H3F3A p.K27 M, IDH2 p.R172, or BRAF p.V600E mutations were observed. There was a trend towards improved survival in the IDH subgroup (P = 0.056). Patients with bithalamic involvement had worse outcomes (P = 0.019). Despite some overlap, the molecular features of pediatric GC are distinct from its adult counterpart. Like in adults, the similarity of genetic and epigenetic characteristics with other infiltrative high-grade gliomas suggests that pediatric GC does not represent a distinct molecular entity.

Project description:In modern clinical neuro-oncology the pathological diagnoses are very challenging creating significant clinical confusion and affecting therapeutic decisions and prognostic estimation. We investigated whether gene expression profiling, coupled with class prediction methodology, could be used to predict prognosis of gliomatosis cerebri in a more consistent manner then standard pathology. We report the results of a molecular study in fifty-nine cases of gliomatosis cerebri, correlating these results with prognosis. TP53 and PTEN gene sequences were analyzed and microarray expression profiling were also performed. At the 24 month follow-up, 17 patients were alive, while 42 patients were died. We identified a 23 gene signature able to predict patient prognosis with microarray gene expression profiling. With the aim to produce a prognostication tool useful in clinical investigation we studied the expression of this 23 gene signature by RT-qPCR. Real time expression values relative to these 23 gene features were used to built a prediction method able to distinguish patients with good prognosis (more likely responsive to therapy) from patients with a bad prognosis (more likely irresponsive to therapy). These results demonstrated not only strong association of gene expression patterns with the survival of the patients but also a robust reproducibility of these gene expressionâ?? based predictors. We have analyzed 59 gliomatosis cerebri bioptic tissue comparing them with normal brain tissue derived by non-tumor surrounding tissue or commercial brain tissue. We alternatively labeled test sample and reference with Cy3 and Cy5 so to avoid a systematic bias due to label efficiency. Since the aim of the work was to find a correlation between prognosis and expression profile we considered each sample of a one prognosis group like a replicate of that group. Median survival data allowed us to distinguish 59 gliomatosis cerebri patients in two group: bad prognosis group, counting 42 patients, with a median survival of 14.58 months and good prognosis group with a median survival of 41.20 months. Moreover TP53 and PTEN mutation analysis was performed on this patients. Kaplan-Meier survival curve with log-rank test showed like each prognosis group can be furthermore divided in 2 groups where bad prognosis group patients bringing a mutation in one of the two gene analized or both genes showed the wrong survival. Microarray expression profile follwed by average linkage clustering analysis based on Pearson correlation coefficients was applied to all tissues on the basis of similarity in the expression pattern over all genes. As expected, it yielded two major clusters, one representing the good prognosis group and the other the bad prognosis one. Interesting these cluster are identical to cluster based on survival. Tumour classification based upon WHO 2007.

Project description:We report the results of a molecular study in thirty-seven cases of gliomatosis cerebri, correlating these results with prognosis. The well-known prognostic factors of gliomas, i.e., age, KPS, histology (Grade 2 vs. 3), or contrast enhancement, was predictive of response or outcome only in a percentage of patients but not in all patients. We identified an 8 miRNA signature able to predict patient prognosis with microarray gene expression profiling. The 8 gene features were used to built a prediction method able to distinguish patients with good prognosis (more likely to be responsive to therapy) from patients with a poor prognosis (less likely to be responsive to therapy). Keywords: miRNA expression profile Fifty-nine patients, between 12- and 73-years-old, with clinical signs of increased intracranial pressure were admitted to our institutions between January 2000 to September 2005. Pre-operative neuroradiological studies (CT scan and MRI) showed diffuse infiltrative processes involving more than two different lobes, no identifiable focal mass, and contrast enhancement absent or less than 1 cm in diameter. Written informed consent and tumour DNA were obtained for molecular analysis. Other eligibility criteria included a Karnofsky Performance Scale index (KPS) >50, normal bone marrow function (white blood cell count >3.0X109/l, neutrophil count >1.5X109/l, platelet count >100X109/l, and haemoglobin >10g/dL), normal liver function (aspartate aminotransferase or alanine aminotransferase <2 times the upper limit of laboratory normal, normal bilirubin, and alkaline phosphatase < 2 times the upper limit of normal), and normal renal function (serum creatinine <1.5 mg/dL). The patients received chemotherapy with temozolamide and radiotherapy. The TMZ schedule consisted of 150 to 200 mg/m2 was orally administered once daily on days 1 to 5. Treatment cycles were repeated every 28 days, with a maximum of 24 months. All patients had a monthly neurological and performance status evaluation and a radiological (MRI) evaluation every 2 to 3 months. Responses were evaluated according to previously described criteria (8): a clinical response was defined as an improvement of a neurological deficit or cognitive function evaluated by Mini-Mental Status Examination, an improvement of at least 75% in seizure frequency, or the disappearance of intracranial hypertension. When radiological MRI scans showed a reduction of more than 50% in the hyper intense area it was considered a partial response (PR), and a <50% regression or an objective regression of mass effect, was considered a minor response (MR). Disease was considered as stable when no clinical or radiological changes were seen for at least 6 months, whereas neurological deterioration, a need to increase corticosteroids, or evidence of tumour progression on MRI (an increase in the T2 or the appearance of contrast enhancement) indicated tumour progression.

Dataset Information

Gliomatosis cerebri: clinical characteristics, management, and outcomes.

Publications

Gliomatosis cerebri: clinical characteristics, management, and outcomes.

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