title: IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy.
abstract: Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8-63.2) and 38% (95 % CI, 25.7-50.7%), and median and 5-year progression-free survival rates were 36 months (95% CI, 28.5-44.0) and 22 % (95 % CI, 10-34%), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60% of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age < 50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated.
authors.affiliation: Radiation Oncology Unit, Sant'Andrea Hospital, University Sapienza, Via di Grottarossa 1035, 00189, Rome, Italy. giuseppe.minniti@ospedalesantandrea.it.|IRCCS Neuromed, Pozzilli, IS, Italy. giuseppe.minniti@ospedalesantandrea.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Minniti
authors.affiliation: Radiation Oncology Unit, Sant'Andrea Hospital, University Sapienza, Via di Grottarossa 1035, 00189, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Scaringi
authors.affiliation: IRCCS Neuromed, Pozzilli, IS, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Arcella
authors.affiliation: IRCCS Neuromed, Pozzilli, IS, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lanzetta
authors.affiliation: Pathology Unit, Sant'Andrea Hospital, University Sapienza, Rome, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Di Stefano
authors.affiliation: Pathology Unit, Sant'Andrea Hospital, University Sapienza, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Scarpino
authors.affiliation: Neuroradiology Unit, Sant'Andrea Hospital, University Sapienza, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bozzao
authors.affiliation: Neurology Unit, Regina Elena Institute, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.affiliation: Neurology Unit, Regina Elena Institute, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Villani
authors.affiliation: Neurosurgery Unit, Policlinico Umberto I, University Sapienza, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Salvati
authors.affiliation: IRCCS Neuromed, Pozzilli, IS, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Esposito
authors.affiliation: IRCCS Neuromed, Pozzilli, IS, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.affiliation: Radiation Oncology Unit, Sant'Andrea Hospital, University Sapienza, Via di Grottarossa 1035, 00189, Rome, Italy.
authors.forename: Riccardo Maurizi
authors.initials: RM
authors.lastname: Enrici
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001254:Astrocytoma / Q000235:genetics / Q000628:therapy*; D015415:Biomarkers; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D059248:Chemoradiotherapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012189:Retrospective Studies; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
references.citation: J Clin Oncol. 2001 Jan 15;19(2):509-18
references.pmid: 11208845
references.citation: J Neurooncol. 2014 Jan;116(2):275-82
references.pmid: 24162810
references.citation: J Neurooncol. 2011 Apr;102(2):311-6
references.pmid: 20686820
references.citation: N Engl J Med. 2005 Mar 10;352(10):997-1003
references.pmid: 15758010
references.citation: Int J Clin Oncol. 2012 Dec;17(6):551-61
references.pmid: 21971842
references.citation: J Neurooncol. 2011 Nov;105(2):325-35
references.pmid: 21523485
references.citation: Acta Neuropathol. 2010 Dec;120(6):707-18
references.pmid: 21088844
references.citation: Neuro Oncol. 2012 Nov;14 Suppl 5:v1-49
references.pmid: 23095881
references.citation: J Neurooncol. 2013 Aug;114(1):85-91
references.pmid: 23681562
references.citation: Neuro Oncol. 2010 May;12(5):500-7
references.pmid: 20406900
references.citation: Eur J Cancer. 2008 Jun;44(9):1210-6
references.pmid: 18248979
references.citation: J Clin Oncol. 2010 Apr 10;28(11):1963-72
references.pmid: 20231676
references.citation: J Natl Cancer Inst. 1993 May 5;85(9):704-10
references.pmid: 8478956
references.citation: Lancet Oncol. 2008 May;9(5):453-61
references.pmid: 18452856
references.citation: Neuro Oncol. 2013 Jun;15(6):775-82
references.pmid: 23486687
references.citation: J Neurooncol. 2009 Mar;92(1):57-63
references.pmid: 19011763
references.citation: Radiother Oncol. 2008 Aug;88(2):177-82
references.pmid: 18395280
references.citation: J Neurooncol. 2011 Jul;103(3):503-12
references.pmid: 20862518
references.citation: J Clin Oncol. 2013 Jan 20;31(3):337-43
references.pmid: 23071247
references.citation: Neurol Clin. 2007 Nov;25(4):1111-39, x
references.pmid: 17964028
references.citation: Neurosurgery. 2004 Feb;54(2):349-57; discussion 357
references.pmid: 14744281
references.citation: Cochrane Database Syst Rev. 2002;(4):CD003913
references.pmid: 12519620
references.citation: J Clin Oncol. 2009 Dec 10;27(35):5874-80
references.pmid: 19901110
references.citation: Lancet Oncol. 2009 May;10(5):459-66
references.pmid: 19269895
references.citation: Cancer. 2004 Nov 1;101(9):2079-85
references.pmid: 15372474
references.citation: J Neurooncol. 2011 Feb;101(3):457-62
references.pmid: 20556480
references.citation: J Clin Oncol. 2013 Jan 20;31(3):344-50
references.pmid: 23071237
references.citation: Neurology. 2013 Oct 22;81(17):1515-22
references.pmid: 24068788
references.citation: J Neurooncol. 2013 Jun;113(2):305-11
references.pmid: 23526410