Showing papers by "Barbara Fisher published in 2018"

Association of MGMT Promoter Methylation Status With Survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An Analysis From the NRG Oncology/RTOG 0424 Trial.

Abstract: Importance The initial report of NRG Oncology/Radiation Therapy Oncology Group (RTOG) 0424 demonstrated a 3-year overall survival benefit with the addition of temozolomide to radiotherapy compared with a historical control. However, an important end point of the trial—evaluation of the association between O6-methylgaunine-DNA-methyltransferase (MGMT) promoter methylation and survival outcomes—was not previously reported. Objective To examine the proportion of patients in NRG Oncology/RTOG 0424 withMGMTpromoter methylation and its association with survival outcomes. Design, Setting, and Participants Specimens collected were analyzed after trial completion to determineMGMTpromoter methylation andIDH1/2status and the association betweenMGMTstatus and survival outcomes. A model derived from logistic regression (MGMT-STP27) was used to calculateMGMTpromoter methylation status. Univariate and multivariable analyses were performed using the Cox proportional hazards regression model to determine the association ofMGMTstatus with survival outcomes. Patient pretreatment characteristics were included as covariates in multivariable analyses. Main Outcomes and Measures Progression-free survival (PFS) and overall survival (OS). Results Of all 129 eligible patients in NRG Oncology/RTOG 0424, 75 (58.1%) hadMGMTstatus available (median age, 48 years; age range, 20-76 years; 42 [56.0%] male): 57 (76.0%) methylated and 18 (24.0%) unmethylated. A total of 13 unmethylated patients (72.2%) had astrocytoma as opposed to oligoastrocytoma or oligodendroglioma, whereas 23 methylated patients (40.4%) had astrocytoma. On univariate analyses, an unmethylatedMGMTpromoter was significantly associated with worse OS (hazard ratio [HR], 3.52; 95% CI, 1.64-7.56;P Conclusions and Relevance In this study,MGMTpromoter methylation was an independent prognostic biomarker of high-risk, low-grade glioma treated with temozolomide and radiotherapy. This is the first study, to our knowledge, to validate the prognostic importance ofMGMTpromoter methylation in patients with grade II glioma treated with combined radiotherapy and temozolomide and highlights its potential prognostic value beyondIDH1/2mutation status. Trial Registration ClinicalTrials.gov Identifier:NCT00114140

Actr-02. nrg oncology/rtog 0424: long-term results of a phase ii study of temozolomide-based chemoradiotherapy regimen for high-risk low-grade gliomas

Abstract: PURPOSE: To report the long-term outcomes and MGMT analysis of temozolomide (TMZ) and radiotherapy (RT) in a high-risk low-grade gliomas (LGG) population. PATIENTS/ METHODS For this single-arm phase II study, LGG patients with ≥3 risk factors (age ≥40, astrocytoma, bi-hemispheric tumor, size ≥6 cm or preoperative neurologic function status >1) received RT (54 Gy/30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The primary endpoint was overall survival (OS) at 3 years after registration. A one-sided Z-test was used to test the hazard rate based on the observed 3-year OS rate versus a prespecified historical control from the EORTC high-risk LGG population. Secondary endpoints included progression-free survival (PFS), and the association of survival outcomes with MGMT methylation status, for which the MGMT-STP27 prediction model was used based on 450k data. The initial report of this study was published in 2015, when the results of the MGMT analysis were unavailable.