PURPOSE: To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. PATIENTS AND METHODS: From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. RESULTS: The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). CONCLUSION: TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.
PURPOSE: To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. PATIENTS AND METHODS: From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. RESULTS: The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). CONCLUSION:TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.
Authors: Alba A Brandes; Enrico Franceschi; Mario Ermani; Alicia Tosoni; Fiorenzo Albani; Roberta Depenni; Marina Faedi; Anna Pisanello; Girolamo Crisi; Benedetta Urbini; Claudio Dazzi; Luigi Cavanna; Claudia Mucciarini; Giuseppe Pasini; Stefania Bartolini; Gianluca Marucci; Luca Morandi; Elena Zunarelli; Serenella Cerasoli; Giorgio Gardini; Giovanni Lanza; Enrico Maria Silini; Silvio Cavuto; Agostino Baruzzi; A Baruzzi; F Albani; F Calbucci; R D'Alessandro; R Michelucci; A Brandes; V Eusebi; S Ceruti; E Fainardi; R Tamarozzi; E Emiliani; M Cavallo; E Franceschi; A Tosoni; M Cavallo; F Fiorica; A Valentini; R Depenni; C Mucciarini; G Crisi; E Sasso; C Biasini; L Cavanna; D Guidetti; N Marcello; A Pisanello; A M Cremonini; G Guiducci; S de Pasqua; S Testoni; R Agati; G Ambrosetto; A Bacci; E Baldin; A Baldrati; E Barbieri; S Bartolini; E Bellavista; F Bisulli; E Bonora; F Bunkheila; V Carelli; M Crisci; P Dall'Occa; D de Biase; S Ferro; C Franceschi; G Frezza; V Grasso; M Leonardi; G Marucci; V Mazzocchi; L Morandi; B Mostacci; G Palandri; E Pasini; M Pastore Trossello; A Pession; M Ragazzi; P Riguzzi; R Rinaldi; S Rizzi; G Romeo; F Spagnolli; P Tinuper; C Trocino; S Cerasoli; M Dall'Agata; M Faedi; M Frattarelli; G Gentili; A Giovannini; P Iorio; U Pasquini; G Galletti; C Guidi; W Neri; A Patuelli; S Strumia; M Casmiro; A Gamboni; F Rasi; G Cruciani; P Cenni; C Dazzi; Ar Guidi; F Zumaglini; A Amadori; G Pasini; M Pasquinelli; E Pasquini; A Polselli; A Ravasio; B Viti; M Sintini; A Ariatti; F Bertolini; G Bigliardi; P Carpeggiani; F Cavalleri; S Meletti; P Nichelli; E Pettorelli; G Pinna; E Zunarelli; F Artioli; I Bernardini; M Costa; G Greco; R Guerzoni; C Stucchi; C Iaccarino; R Rizzi; G Zuccoli; P Api; F Cartei; E Fallica; E Granieri; F Latini; G Lelli; C Monetti; V Ramponi; A Saletti; R Schivalocchi; S Seraceni; M R Tola; B Urbini; C Giorgi; E Montanari; D Cerasti; P Crafa; I Dascola; I Florindo; S Mazza; F Servadei; Em Silini; P Torelli; P Immovilli; N Morelli; C Vanzo Journal: Neurooncol Pract Date: 2014-08-28
Authors: Andrew L Lin; Jingxia Liu; John Evans; Eric C Leuthardt; Keith M Rich; Ralph G Dacey; Joshua L Dowling; Albert H Kim; Gregory J Zipfel; Robert L Grubb; Jiayi Huang; Clifford G Robinson; Joseph R Simpson; Gerald P Linette; Michael R Chicoine; David D Tran Journal: Neuro Oncol Date: 2013-11-26 Impact factor: 12.300
Authors: Martin J van den Bent; Hendrikus J Dubbink; Marc Sanson; Cathleen R van der Lee-Haarloo; Monika Hegi; Judith W M Jeuken; Ahmed Ibdaih; Alba A Brandes; Martin J B Taphoorn; Marc Frenay; Denis Lacombe; Thierry Gorlia; Winand N M Dinjens; Johan M Kros Journal: J Clin Oncol Date: 2009-11-09 Impact factor: 44.544