演題抄録

International Session

開催概要
開催回
第54回・2016年・横浜
 

A mutation and prognostic biomarker study in grade Ⅱ and Ⅲ gliomas utilizing a combined cohort of NRG oncology/RTOG 9802 and NRG oncology/RTOG 9813

演題番号 : IS7-3

[筆頭演者]
Chakravarti Arnab:1 
[共同演者]
Bell Erica H.:1、Mcelroy Joseph P.:1、Fleming Jessica:1、Timmers Cynthia:1、Chakraborty Arup R.:1、Salavaggione Andrea L.:1、Chang Susan M.:1,2、Shaw Edward G.:3、Aldape Kenneth D.:4、Brachman David G.:5、Schultz Christopher J.:6、Shih Helen A.:7、Curtis Mark:8、Hunter Grant K.:9、Murtha Albert D.:10、Zhang Peixin:11,12、Won Minhee Ma.:11,12、Mehta Minesh P.:12

1:The Ohio State University, USA、2:UCSF Medical Center、3:Wake Forest University Health Sciences、4:University of Texas MD Anderson、5:Arizona Oncology Services Foundation、6:Medical College of Wisconsin、7:Massachusetts General Hospital、8:Thomas Jefferson University Hospital、9:Intermountain Medical Center、10:Cross Cancer Institute、11:NRG Oncology Statistics and Data Management Center、12:University of Maryland

 

BACKGROUND: This study examined the prognostic significance of mutations within IDH1/2, ATRX, CIC, FUBP1, and the TERT promoter using a combined cohort of two prospective phase III studies of high-risk grade II and III gliomas using multivariate analyses (MVAs).
METHODS: IDH mutation status was determined by immunohistochemistry and/or next-generation sequencing. A custom Ion AmpliSeq™ DNA panel was used for mutation analysis; TERT promoter mutations were detected by Sanger sequencing. Overall survival (OS) was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated and tested using the Cox proportional hazard model and the log-rank test. MVAs were performed incorporating clinical variables.
RESULTS: Mutations were found within IDH1/2 in 65% (142/219), ATRX in 34% (44/128), the TERT promoter in 32% (43/135), CIC in 18% (23/130), and FUBP1 in 6% (8/130) of analyzed cases. In the univariate analyses on OS, IDH1/2 mutations (HR=0.38; p<0.001) and CIC mutations (HR= 0.48; p=0.04) significantly associated with better OS. Upon MVA, IDH1/2 mutations were significantly associated with OS (HR=0.50; p<0.001), whereas CIC mutations trended toward significance for OS (HR=0.47; p=0.073).
CONCLUSIONS: This study highlights the prognostic value of IDH mutations independent of age, treatment, surgery, histology, and performance status. In addition, this study provides evidence that CIC may provide prognostic information independent of grade/histology. Most importantly, this is the first study to examine the prognostic effects of these mutations using rigorous MVA in a combined cohort of grade II and III gliomas with prospectively-collected, well-annotated clinical data.
FUNDING: U10CA21661, U10CA180868, U10CA180822, U10CA37422 (NCI), Bristol Myers Squibb and Merck &Co. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).

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