Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Oct 27;6(33):34414-22.
doi: 10.18632/oncotarget.5437.

The radiosensitivity index predicts for overall survival in glioblastoma

Kamran A Ahmed  1 , Prakash Chinnaiyan  2 , William J Fulp  3 , Steven Eschrich  4 , Javier F Torres-Roca  1 , Jimmy J Caudell  1
Affiliations

The radiosensitivity index predicts for overall survival in glioblastoma

Kamran A Ahmed et al. Oncotarget. .

Abstract

We have previously developed a multigene expression model of tumor radiosensitivity (RSI) with clinical validation in multiple cohorts and disease sites. We hypothesized RSI would identify glioblastoma patients who would respond to radiation and predict treatment outcomes. Clinical and array based gene expression (Affymetrix HT Human Genome U133 Array Plate Set) level 2 data was downloaded from the cancer genome atlas (TCGA). A total of 270 patients were identified for the analysis: 214 who underwent radiotherapy and temozolomide and 56 who did not undergo radiotherapy. Median follow-up for the entire cohort was 9.1 months (range: 0.04-92.2 months). Patients who did not receive radiotherapy were more likely to be older (p < 0.001) and of poorer performance status (p < 0.001). On multivariate analysis, RSI is an independent predictor of OS (HR = 1.64, 95% CI 1.08-2.5; p = 0.02). Furthermore, on subset analysis, radiosensitive patients had significantly improved OS in the patients with high MGMT expression (unmethylated MGMT), 1 year OS 84.1% vs. 53.7% (p = 0.005). This observation held on MVA (HR = 1.94, 95% CI 1.19-3.31; p = 0.008), suggesting that RT has a larger therapeutic impact in these patients. In conclusion, RSI predicts for OS in glioblastoma. These data further confirm the value of RSI as a disease-site independent biomarker.

Keywords: glioblastoma; radiosensitivity; signature.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

JTR and SE hold an awarded patent and two pending patents on the technology described in this manuscript. In addition, they are co-founders and officers of Cvergenx, Inc a company that holds the exclusive commercial rights to the assay described.

Figures

Figure 1
Figure 1. Overall survival in radioresistant and radiosensitive patients with high MGMT expression treated with radiation and temozolomide
See this image and copyright information in PMC

References

    1. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. The Lancet Oncology. 2009;10:459–466. - PubMed
    1. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. The New England journal of medicine. 2005;352:997–1003. - PubMed
    1. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, et al. IDH1 and IDH2 mutations in gliomas. The New England journal of medicine. 2009;360:765–773. - PMC - PubMed
    1. Eschrich S, Zhang H, Zhao H, Boulware D, Lee JH, Bloom G, Torres-Roca JF. Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform. International journal of radiation oncology, biology, physics. 2009;75:497–505. - PMC - PubMed
    1. Eschrich SA, Fulp WJ, Pawitan Y, Foekens JA, Smid M, Martens JW, Echevarria M, Kamath V, Lee JH, Harris EE, Bergh J, Torres-Roca JF. Validation of a radiosensitivity molecular signature in breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2012;18:5134–5143. - PMC - PubMed

Publication types

MeSH terms