Gliomatosis cerebri: a consensus summary report from the Second International Gliomatosis cerebri Group Meeting, June 22-23, 2017, Bethesda, USA.
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ABSTRACT:
SUBMITTER: Morales La Madrid A
PROVIDER: S-EPMC6301002 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Publications
Gliomatosis cerebri: a consensus summary report from the Second International Gliomatosis cerebri Group Meeting, June 22-23, 2017, Bethesda, USA.
Morales La Madrid Andres A Ranjan Surabhi S Warren Katherine E KE
Journal of neuro-oncology 20180711 1
Gliomatosis cerebri (GC) is an aggressive glioma characterized by an invasive growth pattern and a dismal prognosis. The low incidence and non-specific symptoms at presentation pose unique challenges for early diagnosis and disease-specific research. There is no standard of care for the treatment of patients with a GC phenotype. Understanding the biology of this entity is a critical step in determining effective treatments. Toward this end, the Second International GC Group convened at National ...[more]
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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 expression– based predictors.
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Project description:Gliomatosis cerebri (GC) is a rare, extensively infiltrating glioma involving multiple contiguous lobes of the brain. This lethal disease affects all age groups, and the majority of patients have a poor outcome despite aggressive treatment. Despite its initial recognition in 1938, GC remains a controversial entity with little consensus in its definition, histology, or treatment. The majority of GC tumors are astrocytic, although mixed phenotypes have been identified. Treatment of GC is challenging as surgery is generally not an option due to the extensive areas of brain involved, the benefit of radiation therapy is unclear, and no chemotherapy has proven efficacy. Due to the rarity of the disease and its heterogeneity, both at histopathological and molecular levels, it is difficult to conduct clinical trials tailored for this diagnosis. This review summarizes our current knowledge, examines clinical studies focusing on the treatment of GC, highlights ongoing challenges, and discusses the recent molecular insights into adult and pediatric GC. We conclude that, although no longer recognized as a distinct pathological entity, GC represents a unique disease phenotype. Given the histologic and molecular overlap with other diffuse gliomas, the research emphasis should be on investigating its unique invasive biology.
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2010-05-18 | E-GEOD-11822 | biostudies-arrayexpress
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.
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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.
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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.
2011-01-07 | E-GEOD-19870 | biostudies-arrayexpress
Project description:The extremely invasive phenotypes and genotypes related to progression of gliomatosis cerebri (GC) remain unclear although GC has been removed as an independent entity from the 2016 WHO classification. Hence, categorization of GC under the current WHO molecular classification is essential, and the molecular subgroups that might contribute to GC progression should be compared with the histopathological differences between initial and new lesions identified during follow-up. Analyses of IDH1/2 and TERTp mutations and 1p/19q co-deletion, and immunohistochemistry of IDH1-R132H, ATRX, p53 and galectin-3 were performed. Anaplastic astrocytoma, IDH-wildtype (AA-IDHwt) was the common molecular subgroup (52.8%), followed by diffuse astrocytoma, IDH-wildtype (DA-IDHwt) and AA, IDH-mutant (AA-IDHmt) (each 16.9%), DA-IDHmt (7.9%), glioblastoma (GBM)-IDHwt (3.3%) and GBM-IDHmt (2.2%). Approximately 92% of the AA-IDHwt lesions progressed to histologically confirmed GBM in the newly enhanced lesions harboring the TERTp mutation and expressing galectin-3. Similar to primary GBMs, GC-related GBMs that progressed from the IDHwt subgroups showed microvascular proliferation, palisading necrosis or thrombotic occlusion, implying that a subset of IDHwt subgroups may evolve to overt GBM. Molecular subgrouping did not provide the perfect prediction for the survival of GC patients. The AA-IDHwt group showed worse overall and progression-free survival (PFS) than the AA-IDHmt group. Biopsy plus radiotherapy, chemotherapy and temozolomide treatment for DA-IDHwt, and resection plus radiotherapy and temozolomide treatment for AA-IDHwt prolonged PFS. In conclusions, majority of GC was of the AA-IDHwt subgroup, which progressed to GBM. Molecular subgroups may assist in the selection of treatment modalities, because "GC pattern" still remains as a special growth of gliomas in WHO 2016 classification without established treatment guideline.
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