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

Paulsson, Anna K.; Holmes, Jordan A.; Peiffer, Ann M.; Miller, Lance D.; Liu, Wennuan; Xu, Jianfeng; Hinson, William H.; Lesser, Glenn J.; Laxton, Adrian W.; Tatter, Stephen B.; Debinski, Waldemar; Chan, Michael D.

doi:10.1007/s11060-014-1515-1

Cited by 34 publications

(32 citation statements)

References 19 publications

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“…Our data are in agreement with existing findings in that uGBMs and mGBMs tend to most frequently recur in-field, 14 although that publication found a PFS but not an OS difference, contrary to our findings. Moreover, we could also confirm the two most established therapy – independent prognostic factors age and KPS score – in the univariate and multivariate analyses.…”

Section: Discussionsupporting

confidence: 90%

Survival and recurrence patterns of multifocal glioblastoma after radiation therapy

Syed¹,

Liermann²,

Verma³

et al. 2018

CMAR

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PurposeIt is hypothesized that multifocal glioblastoma (mGBM) is associated with worse prognosis compared to unifocal disease (uGBM). This study aims to investigate the differences in survival rates and progression patterns of patients between these two groups after radiation therapy.Patients and methodsWe retrospectively analyzed 265 patients with primary GBM undergoing radiation therapy at the Department of Radiation Oncology, University Hospital Heidelberg, Germany, between 2004 and 2013. Of these, 202 (76%) were uGBMs and 63 (24%) were mGBMs. First, progression-free survival (PFS) and overall survival (OS) between groups were compared using the Kaplan–Meier method. Second, univariate and multivariate Cox proportional hazards regression was applied to discern prognostic and predictive factors with PFS and OS in the cohorts. Third, recurrence patterns of uGBMs and mGBMs were assessed on follow-up MRIs and compared using the chi-squared test.ResultsAs compared to patients with uGBM, patients with mGBM experienced significantly worse median OS (11.5 vs 14.8 months, P=0.032). Overall, 195 (73.0%) patients experienced tumor progression: 153 (75.7%) patients with uGBM and 46 (73.0%) patients with mGBM. There were no significant differences in PFS between the respective groups (6.5 vs 6.6 months, P=0.750). Of note, concomitant temozolomide treatment was associated with an OS benefit in both uGBM and mGBM by about five months (P=0.006 and P<0.001). Furthermore, there were no significant differences in progression patterns of uGBM and mGBM. Both recurred as unifocal and multifocal disease (P=0.51), and local vs distant brain recurrences occurred similarly in both groups (OR=1.33, P=0.53).ConclusionMultifocality is an independent predictor of survival in GBM. Concomitant temozolomide treatment improved OS of patients with mGBM and uGBM. Both disease types showed similar patterns of progression. Current target volume concepts seem to be adequate in both unifocal and multifocal GBMs. GBM, the most common primary brain tumor in adults, is associated with poor survival. We show herein that multifocality is an independent prognostic factor for survival. We also illustrate that the progression patterns of both unifocal and multifocal GBM are similar.

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Section: Discussionsupporting

confidence: 90%

Survival and recurrence patterns of multifocal glioblastoma after radiation therapy

Syed¹,

Liermann²,

Verma³

et al. 2018

CMAR

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“…No M-GBMs belonged to the G-CIMP subgroup. Paulsson et al [19] reported a similar classification trend in the eight M-GBMs among the 41 GBM patients in their study. In their cohort, five (63%) were of the mesenchymal subtype, and none were of the G-CIMP subtype.…”

Section: Discussionsupporting

confidence: 63%

Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma

Liu

et al. 2015

Acta Neuropathol

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Ten to twenty percent of newly diagnosed glioblastoma (GBM) patients initially present with multiple lesions, termed multifocal or multicentric GBM (M-GBM). The prognosis of these patients is poorer than is that of solitary GBM (S-GBM) patients. However, it is unknown whether multifocality has a genetic, epigenetic, or molecular basis. Here, we identified the genetic and epigenetic characteristics of M-GBM by performing a comprehensive analysis of multidimensional data, including imaging, genetic, epigenetic, and gene expression profiles, from 30 M-GBM cases in The Cancer Genome Atlas (TCGA) database and comparing the results with those of 173 S-GBM cases. We found that M-GBMs had no IDH1, ATRX, or PDGFRA mutations and were significantly associated with the mesenchymal subtype. We also identified the CYB5R2 gene to be hypo-methylated and overexpressed in M-GBMs. The expression level of CYB5R2 was significantly associated with patient survival in two major independent GBM cohorts, totaling 758 cases. The IDH1 mutation was markedly associated with CYB5R2 promoter methylation, but the survival influence of CYB5R2 was independent of IDH1 mutation status. CYB5R2 expression was significantly associated with collagen maturation and the catabolic process and immunoregulation pathways. These results reveal that M-GBMs have some underlying genetic and epigenetic characteristics that are associated with poor prognosis and that CYB5R2 is a new epigenetic marker for GBM prognosis.

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“…Other clinical behaviors that may be affected include multifocality [20], the presence of satellite nodules [21], and the likelihood of pseudoprogression [22]. A major disadvantage of genomic analyses of GBM behavior is that they are generally underpowered studies because of the expense and availability of fresh frozen tissue in a tumor bank.…”

Section: Discussionmentioning

confidence: 99%

Genomic predictors of patterns of progression in glioblastoma and possible influences on radiation field design

et al. 2015

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We present a retrospective investigation of the role of genomics in the prediction of central versus marginal disease progression patterns for glioblastoma (GBM). Between August 2000 and May 2010, 41 patients with GBM and gene expression and methylation data available were treated with radiotherapy with or without concurrent temozolomide. Location of disease progression was categorized as within the high dose (60 Gy) or low dose (46 Gy) volume. Samples were grouped into previously described TCGA genomic groupings: Mesenchymal (m), classical (c), proneural (pn), and neural (n); and were also classified by MGMT-Methylation status and G-Cimp methylation phenotype. Genomic groupings and methylation status were investigated as a possible predictor of disease progression in the high dose region, progression in the low dose region, and time to progression. Based on TCGA category there was no difference in OS (p = 0.26), 60 Gy progression (PN: 71 %, N: 60 %, M: 89 %, C: 83 %, p = 0.19), 46 Gy progression (PN: 57 %, N: 40 %, M: 61 %, C: 50 %, p = 0.8) or time to progression (PN: 9 months, N:15 months, M: 9 months, C: 7 months, p = 0.58). MGMT methylation predicted for improved OS (median 25 vs. 13 months, p = 0.01), improved DFS (median 13 vs. 8 months, p = 0.007) and decreased 60 Gy (p = 0.003) and 46 Gy (p = 0.006) progression. There was a cohort of MGMT methylated patients with late marginal disease progression (4/22 patients, 18 %). TCGA groups demonstrated no difference in survival or progression patterns. MGMT methylation predicted for a statistically significant decrease in in-field and marginal disease progression. There was a cohort of MGMT methylated patients with late marginal progression. Validations of these findings would have implications that could affect radiation field size.

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

Cited by 34 publications

References 19 publications

Survival and recurrence patterns of multifocal glioblastoma after radiation therapy

Survival and recurrence patterns of multifocal glioblastoma after radiation therapy

Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma

Genomic predictors of patterns of progression in glioblastoma and possible influences on radiation field design

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