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rdf:type |
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lifeskim:mentions |
umls-concept:C0004114,
umls-concept:C0013216,
umls-concept:C0076080,
umls-concept:C0080103,
umls-concept:C0205329,
umls-concept:C0871261,
umls-concept:C1521970,
umls-concept:C1521991,
umls-concept:C1522449,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
2
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pubmed:dateCreated |
2011-1-18
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pubmed:abstractText |
Only a few studies examined the effect of temozolomide (TMZ) in recurrent low-grade astrocytoma (LGA) after surgery, none of which included a homogeneous and sufficiently sized group of patients with progression after radiotherapy (RT). We evaluated a cohort of 58 patients treated with TMZ for progression after RT of a previous LGA and investigated the relation between outcome and mutations in the IDH1, IDH2, and TP53 genes, O?-methylguanine-methyltransferase (MGMT) promoter methylation, trisomy of chromosome 7, and loss of chromosomes 1p and 19q. All patients received first-line TMZ 200 mg/m²/day on days 1-5 every 4 weeks for a progressive LGA with a contrast-enhancing lesion on MRI after RT. Six months progression-free survival (PFS) was 67%, and the median overall survival was 14 months. An objective response was obtained in 54%. TP53 mutations and loss of chromosome 19q showed a borderline association with PFS, but none of the other molecular characteristics were correlated with the outcome to TMZ. Both a methylated MGMT promoter gene and IDH1 mutations were found in 86% of the tumor samples. A correlation was found between IDH1 mutations and MGMT promoter methylation (P < .001). Neither MGMT promoter methylation nor IDH1 mutations correlated with PFS, but the interval between the very first symptom of the LGA and the start of the TMZ was significantly longer in the patients with IDH1 mutations (P = .01) and a methylated MGMT promoter (P = .02). We conclude that MGMT promoter methylation and IDH1 mutations seem to predict survival from the time of diagnosis, but not PFS to TMZ.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Alkylating,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Dacarbazine,
http://linkedlifedata.com/resource/pubmed/chemical/IDH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Isocitrate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/O(6)-Methylguanine-DNA...,
http://linkedlifedata.com/resource/pubmed/chemical/TP53 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/isocitrate dehydrogenase 2, human,
http://linkedlifedata.com/resource/pubmed/chemical/temozolomide
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1523-5866
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pubmed:author |
pubmed-author:BoogerdWillemW,
pubmed-author:BrombergJacoline E CJE,
pubmed-author:DinjensWinand N MWN,
pubmed-author:DubbinkHendrikus JHJ,
pubmed-author:Dutch Society for Neuro-Oncology,
pubmed-author:GijtenbeekJohanna M MJM,
pubmed-author:GroenendijkFloris HFH,
pubmed-author:KouwenhovenMathilde C MMC,
pubmed-author:KrosJohan MJM,
pubmed-author:PostmaTjeerd JTJ,
pubmed-author:Sillevis SmittPeter A EPA,
pubmed-author:TaalWalterW,
pubmed-author:ZonnenbergBernard ABA,
pubmed-author:ZonnenbergChris B LCB,
pubmed-author:van HeuvelIreneI,
pubmed-author:van MarionRonaldR,
pubmed-author:van den BentMartin JMJ,
pubmed-author:van der HoltBronnoB
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pubmed:issnType |
Electronic
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
235-41
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pubmed:meshHeading |
pubmed-meshheading:21177338-Adult,
pubmed-meshheading:21177338-Antineoplastic Agents, Alkylating,
pubmed-meshheading:21177338-Astrocytoma,
pubmed-meshheading:21177338-Brain Neoplasms,
pubmed-meshheading:21177338-Chromosome Deletion,
pubmed-meshheading:21177338-Chromosomes, Human, Pair 1,
pubmed-meshheading:21177338-Chromosomes, Human, Pair 19,
pubmed-meshheading:21177338-DNA, Neoplasm,
pubmed-meshheading:21177338-DNA Methylation,
pubmed-meshheading:21177338-Dacarbazine,
pubmed-meshheading:21177338-Female,
pubmed-meshheading:21177338-Follow-Up Studies,
pubmed-meshheading:21177338-Humans,
pubmed-meshheading:21177338-Immunoenzyme Techniques,
pubmed-meshheading:21177338-Isocitrate Dehydrogenase,
pubmed-meshheading:21177338-Male,
pubmed-meshheading:21177338-Middle Aged,
pubmed-meshheading:21177338-Mutation,
pubmed-meshheading:21177338-Neoplasm Staging,
pubmed-meshheading:21177338-O(6)-Methylguanine-DNA Methyltransferase,
pubmed-meshheading:21177338-Polymerase Chain Reaction,
pubmed-meshheading:21177338-Promoter Regions, Genetic,
pubmed-meshheading:21177338-Radiotherapy Dosage,
pubmed-meshheading:21177338-Survival Rate,
pubmed-meshheading:21177338-Treatment Outcome,
pubmed-meshheading:21177338-Trisomy,
pubmed-meshheading:21177338-Tumor Markers, Biological,
pubmed-meshheading:21177338-Tumor Suppressor Protein p53
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pubmed:year |
2011
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pubmed:articleTitle |
First-line temozolomide chemotherapy in progressive low-grade astrocytomas after radiotherapy: molecular characteristics in relation to response.
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pubmed:affiliation |
Department of Neuro-oncology/Neurology, Erasmus MC, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands. w.taal@erasmusmc.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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