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  • American Society of Clinical Oncology (ASCO)  (4)
  • 1
    Online Resource
    Online Resource
    Optimizing the identification of anaplastic oligodendroglioma patients that benefit from adjuvant PCV chemotherapy using the Illumina platform: A further report from EORTC study 26951.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 2011-2011
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 2011-2011
    Abstract: 2011 Background: Adjuvant PCV chemotherapy improves overall survival (OS) in 1p/19q co-deleted grade 3 gliomas. Analyses of EORTC 26951 and RTOG 9402 suggest that other molecularly defined subsets of grade III tumors benefit as well. We previously identified a CpG-Island Hypermethylated Phenotype (CIMP+) as a candidate biomarker. This was further explored in a larger series using snap frozen (SF) or formalin fixed paraffin embedded (FFPE) tumor material, and compared to the value of 1p/19q, IDH1/2 and MGMT status. Methods: Methylation profiles were assessed using the Infinium HumanMethylation 27 or 450 BeadChip (Illumina). MGMT promoter methylation was re-assessed with a logistic regression model (MGMT-STP27) using probes cg1243587 and cg12981137 of the platform as described (Bady et al, Acta Neuropathol 2012;124:547-60). These probes correspond to area’s of the promoter correlated to MGMT protein expression. Previously, MGMT promoter methylation had been assessed using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA). Results: Methylation profiling was conducted in 115 patients. CIMP status correlation between FFPE and SF was excellent (R 2 0.96). In multivariate analysis, 1p/19q co-deletion and CIMP status were independent prognostic factors. Although 1p/19q status and IDH mutational status identify subgroups with more benefit of PCV chemotherapy, tests for interaction remain negative (p 0.25 and 0.33 respectively); MGMTstatus (MS-MLPA) had no impact (p = 0.70). However, CIMP status was of borderline predictive significance (p= 0.07), and MGMT-STP27 was of statistical significance (p = 0.003; HR unmethylated 1.61, 95% CI [0.71, 3.66], HR methylated 0.37, 95% CI 0.23, 0.61] . Conclusions: CIMP status and MGMT promoter methylation assessed with Illumina HumanMethylation BeadChips appear the most informative tests for identifying grade III glioma patients benefitting from the addition of PCV to RT. Validation in an independent dataset is required. Clinical trial information: NCT00002840.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.2011
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 2
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    MGMT Promoter Methylation Is Prognostic but Not Predictive for Outcome to Adjuvant PCV Chemotherapy in Anaplastic Oligodendroglial Tumors: A Report From EORTC Brain Tumor Group Study 26951
    American Society of Clinical Oncology (ASCO) ; 2009
    In:  Journal of Clinical Oncology Vol. 27, No. 35 ( 2009-12-10), p. 5881-5886
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 35 ( 2009-12-10), p. 5881-5886
    Abstract: O6-methylguanine-methyltransferase (MGMT) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy (RT). It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT). Patients and Methods In the European Organisation for the Research and Treatment of Cancer study 26951, 368 patients with AOT were randomly assigned to either RT alone or to RT followed by adjuvant PCV. From 165 patients of this study, formalin-fixed, paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis. This was investigated with methylation specific multiplex ligation-dependent probe amplification. Results In 152 cases, an MGMT result was obtained, in 121 (80%) cases MGMT promoter methylation was observed. Methylation strongly correlated with combined loss of chromosome 1p and 19q loss (P = .00043). In multivariate analysis, MGMT promoter methylation, 1p/19q codeletion, tumor necrosis, and extent of resection were independent prognostic factors. The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival. In tumors diagnosed at central pathology review as glioblastoma, no prognostic effect of MGMT promoter methylation was observed. Conclusion In this study, on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy. The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2009.24.1034
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2009
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    One year experience of MET gene exon 14 skipping analysis in lung cancer: Identification of 18 cases by NGS.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e20055-e20055
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e20055-e20055
    Abstract: e20055 Background: Lung adenocarcinoma (LAC) is the most common histological type of non-small-cell lung cancer and is one of the malignancies with the most evolved personalized treatments based on molecular characteristics of the tumor. Mutations in EGFR, HER2 and BRAF, specific translocations of ALK, ROS1, RET and amplification of MET all have standard diagnostic importance and lead to specific treatment options for the individual LAC patients. Recently, in 2-4% of LAC MET gene mutations leading to skipping of exon 14 were found. These mutations were described to occur more frequently in tumors with sarcomatoid histology. LAC with MET exon 14 skipping mutations showed impressive, although temporary, responses to MET tyrosine kinase inhibitors (TKI) crizotinib, cabozantinib and capmatinib. We will present our experience with routine molecular diagnostic detection of the most common MET exon 14 skipping mutations. Methods: In January 2016 we included in our standard, DNA based, molecular diagnostics custom-made NGS analyses 4 amplicons for detection of MET skipping mutations. The analyses were performed on microdissected FFPE tissue sections or routine histology or cytology stained preparations. Nine different mutations were validated for their effect on splicing by RT-PCR on RNA isolated from the same tissue samples. Results: Between January 2016 and January 2017 676 routine molecular diagnostic analyses on LAC were performed. In 18 (2.7%) cases MET mutations were detected possibly resulting in exon 14 skipping. Nine out of 16 different mutations were tested by RT-PCR and all 9 were demonstrated to result in MET exon 14 skipping. Conclusions: MET exon 14 skipping mutations can reliably be detected in routine pathology tissue samples. These analyses can easily be included in routine molecular diagnostic NGS. When necessary, confirmation of the mutational effect on RNA splicing can be implemented as well. Routine identification of MET skipping mutations (2.7% of cases) adds substantially to the personalized targeted treatment strategies for LAC patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e20055
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Novel EGFR V834L Germline Mutation Associated With Familial Lung Adenocarcinoma
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  JCO Precision Oncology , No. 2 ( 2018-11), p. 1-5
    Details
    In: JCO Precision Oncology, American Society of Clinical Oncology (ASCO), , No. 2 ( 2018-11), p. 1-5
    Type of Medium: Online Resource
    ISSN: 2473-4284
    URL: Article
    DOI: 10.1200/PO.17.00266
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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