Dataset Information

Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma.

ABSTRACT: We investigate the differences in molecular signature and clinical outcomes between multiple lesion glioblastoma (GBM) and single focus GBM in the modern treatment era. Between August 2000 and May 2010, 161 patients with GBM were treated with modern radiotherapy techniques. Of this group, 33 were considered to have multiple lesion GBM (25 multifocal and 8 multicentric). Patterns of failure, time to progression and overall survival were compared based on whether the tumor was considered a single focus or multiple lesion GBM. Genomic groupings and methylation status were also investigated as a possible predictor of multifocality in a cohort of 41 patients with available tissue for analysis. There was no statistically significant difference in overall survival (p < 0.3) between the multiple lesion tumors (8.2 months) and single focus GBM (11 months). Progression free survival was superior in the single focus tumors (7.1 months) as compared to multi-focal (5.6 months, p = 0.02). For patients with single focus, multifocal and multicentric GBM, 81, 76 and 88 % of treatment failures occurred in the 60 Gy volume (p < 0.5), while 54, 72, and 38 % of treatment failures occurred in the 46 Gy volume (p < 0.4). Out of field failures were rare in both single focus and multiple foci GBM (7 vs 3 %). Genomic groupings and methylation status were not found to predict for multifocality. Patterns of failure, survival and genomic signatures for multiple lesion GBM do not appreciably differ when compared to single focus tumors.

SUBMITTER: Paulsson AK

PROVIDER: S-EPMC4146694 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

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Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma.

Paulsson Anna K AK Holmes Jordan A JA Peiffer Ann M AM Miller Lance D LD Liu Wennuan W Xu Jianfeng J Hinson William H WH Lesser Glenn J GJ Laxton Adrian W AW Tatter Stephen B SB Debinski Waldemar W Chan Michael D MD

Journal of neuro-oncology 20140703 2

We investigate the differences in molecular signature and clinical outcomes between multiple lesion glioblastoma (GBM) and single focus GBM in the modern treatment era. Between August 2000 and May 2010, 161 patients with GBM were treated with modern radiotherapy techniques. Of this group, 33 were considered to have multiple lesion GBM (25 multifocal and 8 multicentric). Patterns of failure, time to progression and overall survival were compared based on whether the tumor was considered a single ...[more]

PMID: 24990827

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Project description:Congenital glioblastoma multiforme (cGBM) historically has been considered an aggressive tumor of infancy requiring extensive chemotherapy to achieve cure. We report on 4 patients at our institution with cGBMs who were treated with surgery and chemotherapy (carboplatin and etoposide every 21 days for 2-6 cycles). Four of four patients are progression free at a median time of 27.5 months (22-103 months). To characterize the molecular biology of cGBM, we compared the gene expression profiles of 3 cGBMs to 12 pediatric and 6 primary adult glioblastomas collected at our institution. Unsupervised hierarchical clustering showed cGBMs grouped together with other high-grade gliomas. cGBMs demonstrated marked similarity to both pediatric and adult GBMs, with only a total of 31 differentially expressed genes identified (FDR < 0.05). Unique molecular features of congenital GBMs identified included over-expression of multiple genes involved in glucose metabolism and tissue hypoxia pathways. Four tyrosine kinases were also mong the up-regulated genes (RET, RASGRF2, EFNA5, ALK). Thus, at our institution congenital GBMs, while similar both histologically and molecularly to other GBMs, appear to have a good prognosis with surgery in combination with relatively moderate chemotherapy. Further study is needed to determine if the few gene expression differences that were identified may contribute to the better survival seen in these tumors compared to pediatric or adult GBMs. Key Words: glioblastoma; congenital; pediatric; gene expression; microarray Molecular profiling of 18 AT/RT patient tumor samples was performed using Affymetrix U133 Plus2 GeneChips. Data were background corrected and normalized using gcRMA (as implemented in Bioconductor). Unsupervised agglomerative hierarchical clustering was performed to identify subsets of AT/RTs with similar gene expression. Limma (moderated t-tests; Bioconductor) was used to identify signature genes for each cluster. Bioinformatics web tool DAVID was used to identify enriched biological processes for each cluster. Survival was analyzed using Kaplan-Meier curves and Cox Hazard Ratio. Bioinformatics tools Gene Set Enrichment (GSEA) and Ingenuity Pathways Analysis were also used to gain further insight into cluster differences.

Project description: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.

Dataset Information

Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma.

Publications

Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma.

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