title: Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers.
abstract: Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA.
authors.affiliation: Department of Radiation Oncology, Sant'Andrea Hospital, University Sapienza, Via di Grottarossa 1035, 00189, Rome, Italy, gminniti@ospedalesantadrea.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Minniti
authors.forename: Antonella
authors.initials: A
authors.lastname: Arcella
authors.forename: Claudia
authors.initials: C
authors.lastname: Scaringi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lanzetta
authors.forename: Domenica
authors.initials: D
authors.lastname: Di Stefano
authors.forename: Stefania
authors.initials: S
authors.lastname: Scarpino
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Mattia Falchetto
authors.initials: MF
authors.lastname: Osti
authors.forename: Riccardo Maurizi
authors.initials: RM
authors.lastname: Enrici
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000532:radiotherapy*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes