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

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

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy

Multi-Omics Analysis of Brain Metastasis Outcomes Following Craniotomy

Background: The incidence of brain metastasis continues to increase as therapeutic strategies have improved for a number of solid tumors. The presence of brain metastasis is associated with worse prognosis but it is unclear if distinctive biomarkers can separate patients at risk for CNS related death. Methods: We executed a single institution retrospective collection of brain metastasis from patients who were diagnosed with lung, breast, and other primary tumors. The brain metastatic samples were sent for RNA sequencing, proteomic and metabolomic analysis of brain metastasis. The primary outcome was distant brain failure after definitive therapies that included craniotomy resection and radiation to surgical bed. Novel prognostic subtypes were discovered using transcriptomic data and sparse non-negative matrix factorization. Results: We discovered two molecular subtypes showing statistically significant differential prognosis irrespective of tumor subtype. The median survival time of the good and the poor prognostic subtypes were 7.89 and 42.27 months, respectively. Further integrated characterization and analysis of these two distinctive prognostic subtypes using transcriptomic, proteomic, and metabolomic molecular profiles of patients identified key pathways and metabolites. The analysis suggested that immune microenvironment landscape as well as proliferation and migration signaling pathways may be responsible to the observed survival difference. Conclusion: A multi-omics approach to characterization of brain metastasis provides an opportunity to identify clinically impactful biomarkers and associated prognostic subtypes and generate provocative integrative understanding of disease

CT-only planning for Gamma Knife radiosurgery in the treatment of trigeminal neuralgia: methodology and outcomes from a single institution

INTRODUCTION: Gamma Knife radiosurgery (GKRS) has been established as a safe and effective treatment option for trigeminal neuralgia. Some patients have contraindications to magnetic resonance imaging (MRI), the standard stereotactic imaging used for GKRS treatment planning. Computerized tomography (CT) imaging may be used as an alternative in this scenario. We sought to evaluate the outcomes of our patients treated using this technique. METHODS: Between August 2001 and November 2009, 19 patients with trigeminal neuralgia were treated with GKRS using CT-only planning. The course of the trigeminal nerve was determined based upon anatomical landmarks when the nerve was not directly visualized on the treatment-planning CT. Median dose used was 90 Gy (range 85-90 Gy). Follow-up data based on Barrow Neurological Institute (BNI) pain score and toxicity were obtained using electronic medical records and by telephone interview. RESULTS: With median follow-up time of 18 months (range 4-36 months), improvement in quality of life after GKRS was reported in 17 of 19 patients. Freedom from BNI IV-V pain relapse was 82% at 24 months. By 3 months post-GKRS, 50% of patients were able to discontinue medications completely. Three patients reported numbness after GKRS; none of these patients described bothersome numbness. Use of contrast did not affect treatment outcome (P = 0.31). CONCLUSIONS: Stereotactic CT-only treatment planning of GKRS for the treatment of trigeminal neuralgia is feasible and safe. Further studies are necessary to determine if the long-term durability of pain relief is comparable to that of MRI-based GKRS planning