TY - JOUR
T1 - Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors
T2 - A report from EORTC study 26951
AU - Erdem-Eraslan, Lale
AU - Gravendeel, Lonneke A.
AU - De Rooi, Johan
AU - Eilers, Paul H.C.
AU - Idbaih, Ahmed
AU - Spliet, Wim G.M.
AU - Den Dunnen, Wilfred F.A.
AU - Teepen, Johannes L.
AU - Wesseling, Pieter
AU - Smitt, Peter A.E.Sillevis
AU - Kros, Johan M.
AU - Gorlia, Thierry
AU - Van Den Bent, Martin J.
AU - French, Pim J.
PY - 2013/1/20
Y1 - 2013/1/20
N2 - Purpose: Intrinsic glioma subtypes (IGSs) are molecularly similar tumors that can be identified based on unsupervised gene expression analysis. Here, we have evaluated the clinical relevance of these subtypes within European Organisation for Research and Treatment of Cancer (EORTC) 26951, a randomized phase III clinical trial investigating adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study includes gene expression profiles of formalin-fixed, paraffin-embedded (FFPE) clinical trial samples Patients and Methods: Gene expression profiling was performed in 140 samples, 47 fresh frozen samples and 93 FFPE samples, on HU133-Plus-2.0 and HuEx-1.0-st arrays, respectively. Results: All previously identified six IGSs are present in EORTC 26951. This confirms that different molecular subtypes are present within a well-defined histologic subtype. Intrinsic subtypes are highly prognostic for overall survival (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance status, and tumor location), molecular (1p/19q loss of heterozygosity [LOH], IDH1 mutation, and MGMTmethylation), and histologic parameters Combining known molecular (1p/19q LOH, IDH1) prognostic parameters with intrinsic subtypes mproves outcome prediction (proportion of explained variation, 30% v 23% for each individua group of factors). Specific genetic changes (IDH1, 1p/19q LOH, and EGFRamplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p/19q LOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone versus 12.8 years after RT/PCV (P =.0349; hazard ratio, 2.18; 95% CI, 1.06 to 4.50) Conclusion: Intrinsic subtypes are highly prognostic in EORTC 26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV.
AB - Purpose: Intrinsic glioma subtypes (IGSs) are molecularly similar tumors that can be identified based on unsupervised gene expression analysis. Here, we have evaluated the clinical relevance of these subtypes within European Organisation for Research and Treatment of Cancer (EORTC) 26951, a randomized phase III clinical trial investigating adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study includes gene expression profiles of formalin-fixed, paraffin-embedded (FFPE) clinical trial samples Patients and Methods: Gene expression profiling was performed in 140 samples, 47 fresh frozen samples and 93 FFPE samples, on HU133-Plus-2.0 and HuEx-1.0-st arrays, respectively. Results: All previously identified six IGSs are present in EORTC 26951. This confirms that different molecular subtypes are present within a well-defined histologic subtype. Intrinsic subtypes are highly prognostic for overall survival (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance status, and tumor location), molecular (1p/19q loss of heterozygosity [LOH], IDH1 mutation, and MGMTmethylation), and histologic parameters Combining known molecular (1p/19q LOH, IDH1) prognostic parameters with intrinsic subtypes mproves outcome prediction (proportion of explained variation, 30% v 23% for each individua group of factors). Specific genetic changes (IDH1, 1p/19q LOH, and EGFRamplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p/19q LOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone versus 12.8 years after RT/PCV (P =.0349; hazard ratio, 2.18; 95% CI, 1.06 to 4.50) Conclusion: Intrinsic subtypes are highly prognostic in EORTC 26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV.
UR - http://www.scopus.com/inward/record.url?scp=84873362485&partnerID=8YFLogxK
U2 - 10.1200/JCO.2012.44.1444
DO - 10.1200/JCO.2012.44.1444
M3 - Article
C2 - 23269986
AN - SCOPUS:84873362485
SN - 0732-183X
VL - 31
SP - 328
EP - 336
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -