Oncotarget

Research Papers:

The radiosensitivity index predicts for overall survival in glioblastoma

Kamran A. Ahmed _, Prakash Chinnaiyan, William J. Fulp, Steven Eschrich, Javier F. Torres-Roca and Jimmy J. Caudell

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Oncotarget. 2015; 6:34414-34422. https://doi.org/10.18632/oncotarget.5437

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Abstract

Kamran A. Ahmed1, Prakash Chinnaiyan4, William J. Fulp2, Steven Eschrich3, Javier F. Torres-Roca1,*, Jimmy J. Caudell1,*

1Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA

2Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA

3Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA

4Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA

*Senior authors

Correspondence to:

Jimmy J. Caudell, e-mail: [email protected]

Javier F. Torres-Roca, e-mail: [email protected]

Keywords: radiosensitivity, signature, glioblastoma

Received: July 15, 2015     Accepted: September 21, 2015     Published: October 03, 2015

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.


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