TY - JOUR
T1 - First-line temozolomide chemotherapy in progressive low-grade astrocytomas after radiotherapy: molecular characteristics in relation to response
AU - Taal, Walter
AU - Dubbink, Erik jan
AU - Zonnenberg, CBL
AU - Zonnenberg, BA
AU - Postma, TJ
AU - Gijtenbeek, JMM
AU - Boogerd, W
AU - Groenendijk, Floris
AU - Kros, J.M.
AU - Kouwenhoven, Mathilde
AU - van Marion, Ronald
AU - Heuvel, null
AU - van der Holt, Ronnie
AU - Bromberg, Jacoline
AU - Sillevis Smitt, Peter
AU - Dinjens, Winand
AU - van den Bent, Martin
PY - 2011
Y1 - 2011
N2 - Only a few studies examined the effect of temozolomidc (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 TPS3 genes, O-6-methylguanine-methyltransferase (MGMT) promoter methylation, trisomy of chromosome 7, and loss of chromosomes 1 p and 19q. All patients received first-line TMZ 200 mg/m(2)/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 IDHI 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.
AB - Only a few studies examined the effect of temozolomidc (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 TPS3 genes, O-6-methylguanine-methyltransferase (MGMT) promoter methylation, trisomy of chromosome 7, and loss of chromosomes 1 p and 19q. All patients received first-line TMZ 200 mg/m(2)/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 IDHI 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.
U2 - 10.1093/neuonc/noq177
DO - 10.1093/neuonc/noq177
M3 - Article
C2 - 21177338
SN - 1522-8517
VL - 13
SP - 235
EP - 241
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - 2
ER -