Hailong Li1, Jiye Li2, Gang Cheng1, Jianning Zhang1, Xuezhen Li3. 1. Department of Neurosurgery, Navy General Hospital, Beijing 100048, China. 2. Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. 3. Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China. Electronic address: hjzyysw@163.com.
Abstract
PURPOSE: This study aimed to investigate the potential association between IDH mutation and O6-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy. METHODS: A total of 157 GBM patients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis. RESULTS: Of the 157 GBM patients, 145 (92.36%) patients, including 38 patients with psPD, 38 patients with early progression (ePD), and 69 patients with non-progression (non-PD), were followed up for six to 56 months. We identified a higher rate of MGMT promoter methylation and IDH1 mutation in psPD patients compared with ePD patients (P=0.002). In addition, MGMT promoter methylation and IDH1 mutation predicted a high probability of psPD development in GBM patients (P=0.001 and P<0.001, respectively). MGMT promoter methylation, IDH1 mutation, Karnofsky performance score (KPS) ≥70, and psPD were associated with a significantly longer overall survival of GBM patients (P=0.001, 0.001, 0.002, and P<0.001, respectively). Both of MGMT promoter methylation and IDH mutation had a cumulative effect on the OS of GBM patients. GBM patients with psPD (39.2±2.1months, P<0.001) had a longer median survival (MS) than GBM patients with ePD (11.9±1.1months) or with non-PD (24.4±2.4months). CONCLUSION: MGMT promoter methylation and IDH1 mutation were associated with PsPD and predicted a longer median survival in GBM patients after TMZ-based chemoradiotherapy. Genetic analyses of the MGMT promoter and IDH1 may allow us to effectively treat GBM patients. Copyright Â
PURPOSE: This study aimed to investigate the potential association between IDH mutation and O6-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy. METHODS: A total of 157 GBMpatients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis. RESULTS: Of the 157 GBMpatients, 145 (92.36%) patients, including 38 patients with psPD, 38 patients with early progression (ePD), and 69 patients with non-progression (non-PD), were followed up for six to 56 months. We identified a higher rate of MGMT promoter methylation and IDH1 mutation in psPD patients compared with ePD patients (P=0.002). In addition, MGMT promoter methylation and IDH1 mutation predicted a high probability of psPD development in GBMpatients (P=0.001 and P<0.001, respectively). MGMT promoter methylation, IDH1 mutation, Karnofsky performance score (KPS) ≥70, and psPD were associated with a significantly longer overall survival of GBMpatients (P=0.001, 0.001, 0.002, and P<0.001, respectively). Both of MGMT promoter methylation and IDH mutation had a cumulative effect on the OS of GBMpatients. GBMpatients with psPD (39.2±2.1months, P<0.001) had a longer median survival (MS) than GBMpatients with ePD (11.9±1.1months) or with non-PD (24.4±2.4months). CONCLUSION:MGMT promoter methylation and IDH1 mutation were associated with PsPD and predicted a longer median survival in GBMpatients after TMZ-based chemoradiotherapy. Genetic analyses of the MGMT promoter and IDH1 may allow us to effectively treat GBMpatients. Copyright Â
Authors: R F Barajas; D Schwartz; H L McConnell; C N Kersch; X Li; B E Hamilton; J Starkey; D R Pettersson; J P Nickerson; J M Pollock; R F Fu; A Horvath; L Szidonya; C G Varallyay; J J Jaboin; A M Raslan; A Dogan; J S Cetas; J Ciporen; S J Han; P Ambady; L L Muldoon; R Woltjer; W D Rooney; E A Neuwelt Journal: AJNR Am J Neuroradiol Date: 2020-06-11 Impact factor: 3.825
Authors: Panagiotis Korfiatis; Timothy L Kline; Daniel H Lachance; Ian F Parney; Jan C Buckner; Bradley J Erickson Journal: J Digit Imaging Date: 2017-10 Impact factor: 4.056
Authors: Ramon F Barajas; Bronwyn E Hamilton; Daniel Schwartz; Heather L McConnell; David R Pettersson; Andrea Horvath; Laszlo Szidonya; Csanad G Varallyay; Jenny Firkins; Jerry J Jaboin; Charlotte D Kubicky; Ahmed M Raslan; Aclan Dogan; Justin S Cetas; Jeremy Ciporen; Seunggu J Han; Prakash Ambady; Leslie L Muldoon; Randy Woltjer; William D Rooney; Edward A Neuwelt Journal: Neuro Oncol Date: 2019-03-18 Impact factor: 12.300
Authors: Lindsay S Rowe; John A Butman; Megan Mackey; Joanna H Shih; Theresa Cooley-Zgela; Holly Ning; Mark R Gilbert; DeeDee K Smart; Kevin Camphausen; Andra V Krauze Journal: J Neurooncol Date: 2018-05-16 Impact factor: 4.130
Authors: Homan Mohammadi; Kevin Shiue; G Daniel Grass; Vivek Verma; Kay Engellandt; Dirk Daubner; Gabriele Schackert; Mercia J Gondim; Dibson Gondim; Alexander O Vortmeyer; Aaron P Kamer; William Jin; Timothy J Robinson; Gordon Watson; Hsiang-Hsuan M Yu; Tim Lautenschlaeger Journal: Neurooncol Pract Date: 2019-10-10