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• W3094346075 abstract "Low-grade gliomas (LGGs) comprise about 15% of all gliomas and exhibit variable clinical behavior. Standard of care is maximum safe resection with or without adjuvant radiotherapy and chemotherapy. For patients deemed to benefit from adjuvant radiotherapy (RT), we sought to identify genomic predictors that influence overall survival (OS) and progression-free survival (PFS). Level 3 data for 474 patients with LGG were downloaded from The Cancer Genome Atlas (TCGA). Among patients who underwent surgery and RT, genome-wide association tests of mutations and RNA-Seq by Expectation-Maximization (RSEM) expression levels with OS were performed using univariate and multivariate Cox proportional hazards regression. Covariates included age, sex, glioma histology, WHO grade, IDH mutant and 1p/19q co-deletion status, and chemotherapy. To meet significance criteria under multiple hypothesis testing, genomic markers had to pass Bonferroni correction, P < 0.05 association with PFS, and matching direction of effect size on PFS. This TCGA cohort study consists of 259 males and 215 females with LGG. There were 291 patients treated by surgery and RT, of whom 224 also received chemotherapy. Median follow-up was 23 months. RT delivery was associated with older age, astrocytomas, and IDH wild-type disease (P < 0.005). Increased expression of USP28, ISL2, IGF2BP3, RTTN, and LRRK2 was found to confer shorter PFS and OS (P < 0.005) among patients who received RT. We were able to successfully stratify these patients into low, medium, and high risk categories using a Genomic Score (GS) defined as the sum of expression values for the 5 aforementioned genes; GS categories were strongly associated with PFS and OS, independent of age, histology, grade, IDH mutant, and 1p/19q co-deletion status (Table). This relationship was not observed for the 183 patients treated by surgery without RT. Adjuvant RT is generally added to surgery for LGG with poorer prognostic features. Expression of several genes related to neuronal differentiation and projection morphogenesis as part of a GS may help further guide outcomes expectation and individualized care for these patients. Additional prospective genomic interrogation and functional studies are warranted.Abstract 3728; TableMultivariate Cox proportional hazards regression variablePFS HR (95% CI)OS HR (95% CI)Age, years1.01 (1.00–1.03)1.04 (1.02–1.06)Sex • Female—— • Male0.90 (0.63–1.29)1.34 (0.88–2.06)Glioma histology • Astrocytoma—— • Oligoastrocytoma0.52 (0.31–0.87)1.04 (0.59–1.84) • Oligodendroglioma0.89 (0.54–1.44)1.06 (0.61–1.85)WHO grade • 2—— • 30.78 (0.48–1.27)1.41 (0.79–2.51)Mutation status • IDH mutant and 1p/19q co-deletion—— • IDH mutant, no 1p/19q co-deletion1.35 (0.69–2.64)1.22 (0.56–2.65) • IDH wildtype6.69 (3.29–13.60)4.87 (2.26–10.47)Chemotherapy • No—— • Yes1.12 (0.68–1.83)0.64 (0.35–1.19)Genomic Score • Low—— • Medium1.86 (1.10–3.17)4.15 (2.06–8.35) • High3.10 (1.59–6.04)11.61 (5.01–26.87) Open table in a new tab" @default.
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• W3094346075 date "2020-11-01" @default.
• W3094346075 modified "2023-09-26" @default.
• W3094346075 title "Genomics-Stratified Survival For Adult Low-Grade Glioma Treated By Surgery And Radiotherapy" @default.
• W3094346075 doi "https://doi.org/10.1016/j.ijrobp.2020.07.152" @default.
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