A Gene Expression Model of Intrinsic Tumor Radiosensitivity: Prediction of Response and Prognosis After Chemoradiation

Steven A. Eschrich, Jimmy Pramana, Hongling Zhang, Haiyan Zhao, David Boulware, Ji Hyun Lee, Gregory Bloom, Caio Rocha-Lima, Scott Kelley, Douglas P. Calvin, Timothy J. Yeatman, Adrian C. Begg, Javier F. Torres-Roca

Research output: Contribution to journalArticle

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Abstract

Purpose: Development of a radiosensitivity predictive assay is a central goal of radiation oncology. We reasoned a gene expression model could be developed to predict intrinsic radiosensitivity and treatment response in patients. Methods and Materials: Radiosensitivity (determined by survival fraction at 2 Gy) was modeled as a function of gene expression, tissue of origin, ras status (mut/wt), and p53 status (mut/wt) in 48 human cancer cell lines. Ten genes were identified and used to build a rank-based linear regression algorithm to predict an intrinsic radiosensitivity index (RSI, high index = radioresistance). This model was applied to three independent cohorts treated with concurrent chemoradiation: head-and-neck cancer (HNC, n = 92); rectal cancer (n = 14); and esophageal cancer (n = 12). Results: Predicted RSI was significantly different in responders (R) vs. nonresponders (NR) in the rectal (RSI R vs. NR 0.32 vs. 0.46, p = 0.03), esophageal (RSI R vs. NR 0.37 vs. 0.50, p = 0.05) and combined rectal/esophageal (RSI R vs. NR 0.34 vs. 0.48, p = 0.001511) cohorts. Using a threshold RSI of 0.46, the model has a sensitivity of 80%, specificity of 82%, and positive predictive value of 86%. Finally, we evaluated the model as a prognostic marker in HNC. There was an improved 2-year locoregional control (LRC) in the predicted radiosensitive group (2-year LRC 86% vs. 61%, p = 0.05). Conclusions: We validate a robust multigene expression model of intrinsic tumor radiosensitivity in three independent cohorts totaling 118 patients. To our knowledge, this is the first time that a systems biology-based radiosensitivity model is validated in multiple independent clinical datasets.

Original languageEnglish
Pages (from-to)489-496
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume75
Issue number2
DOIs
StatePublished - Oct 1 2009

Fingerprint

prognosis
gene expression
Radiation Tolerance
radiation tolerance
tumors
Gene Expression
predictions
cancer
Neoplasms
Radiation Oncology
Systems Biology
transponders
Esophageal Neoplasms
Rectal Neoplasms
Head and Neck Neoplasms
Linear Models
biology
cultured cells
genes
markers

Keywords

  • Chemoradiation
  • Gene expression
  • Intrinsic radiosensitivity
  • Predictive assay
  • Systems biology

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

A Gene Expression Model of Intrinsic Tumor Radiosensitivity : Prediction of Response and Prognosis After Chemoradiation. / Eschrich, Steven A.; Pramana, Jimmy; Zhang, Hongling; Zhao, Haiyan; Boulware, David; Lee, Ji Hyun; Bloom, Gregory; Rocha-Lima, Caio; Kelley, Scott; Calvin, Douglas P.; Yeatman, Timothy J.; Begg, Adrian C.; Torres-Roca, Javier F.

In: International Journal of Radiation Oncology Biology Physics, Vol. 75, No. 2, 01.10.2009, p. 489-496.

Research output: Contribution to journalArticle

Eschrich, SA, Pramana, J, Zhang, H, Zhao, H, Boulware, D, Lee, JH, Bloom, G, Rocha-Lima, C, Kelley, S, Calvin, DP, Yeatman, TJ, Begg, AC & Torres-Roca, JF 2009, 'A Gene Expression Model of Intrinsic Tumor Radiosensitivity: Prediction of Response and Prognosis After Chemoradiation', International Journal of Radiation Oncology Biology Physics, vol. 75, no. 2, pp. 489-496. https://doi.org/10.1016/j.ijrobp.2009.06.014
Eschrich, Steven A. ; Pramana, Jimmy ; Zhang, Hongling ; Zhao, Haiyan ; Boulware, David ; Lee, Ji Hyun ; Bloom, Gregory ; Rocha-Lima, Caio ; Kelley, Scott ; Calvin, Douglas P. ; Yeatman, Timothy J. ; Begg, Adrian C. ; Torres-Roca, Javier F. / A Gene Expression Model of Intrinsic Tumor Radiosensitivity : Prediction of Response and Prognosis After Chemoradiation. In: International Journal of Radiation Oncology Biology Physics. 2009 ; Vol. 75, No. 2. pp. 489-496.
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AU - Zhang, Hongling

AU - Zhao, Haiyan

AU - Boulware, David

AU - Lee, Ji Hyun

AU - Bloom, Gregory

AU - Rocha-Lima, Caio

AU - Kelley, Scott

AU - Calvin, Douglas P.

AU - Yeatman, Timothy J.

AU - Begg, Adrian C.

AU - Torres-Roca, Javier F.

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