The Radiosensitivity Index Predicts for Overall Survival in Glioblastoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Oct 10

PMID 26451615

Citations 61

Authors

Kamran A Ahmed

Prakash Chinnaiyan

William J Fulp

Steven Eschrich

Javier F Torres-Roca

Jimmy J Caudell

Affiliations

Soon will be listed here.

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.

Citing Articles

Evaluating the Radiation Sensitivity Index and 12-Chemokine Gene Expression Signature for Clinical Use in a CLIA Laboratory.

Berglund A, Puskas J, Yoder S, Smith A, Marchion D, Qin D Cancer Res Commun. 2025; 5(3):389-397.

PMID: 39932296 PMC: 11873780. DOI: 10.1158/2767-9764.CRC-24-0534.

Establishment of cancer cell radiosensitivity database linked to multi-layer omics data.

Oike T, Kambe R, Darwis N, Shibata A, Ohno T Cancer Sci. 2024; 116(3):690-697.

PMID: 39668120 PMC: 11875790. DOI: 10.1111/cas.16334.

Point/Counterpoint: The role of reirradiation in recurrent glioblastoma.

Rahman R, Preusser M, Tsien C, Le Rhun E, Sulman E, Wen P Neuro Oncol. 2024; 27(1):7-12.

PMID: 39527460 PMC: 11726241. DOI: 10.1093/neuonc/noae209.

Evaluating the Radiation Sensitivity Index and 12-chemokine gene expression signature for clinical use in a CLIA laboratory.

Berglund A, Puskas J, Yoder S, Smith A, Marchion D, Qian D bioRxiv. 2024; .

PMID: 39345465 PMC: 11429982. DOI: 10.1101/2024.09.19.613957.

Validation of a genome-based model for adjusting radiotherapy dose (GARD) in patients with locally advanced rectal cancer.

Xia H, Li Z, Lin Y, Lin Y, Zeng L, Xu B Sci Rep. 2024; 14(1):21572.

PMID: 39284851 PMC: 11405410. DOI: 10.1038/s41598-024-72818-w.

References

Gilbert M, Wang M, Aldape K, Stupp R, Hegi M, Jaeckle K . Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013; 31(32):4085-91. PMC: 3816958. DOI: 10.1200/JCO.2013.49.6968. View

Eschrich S, Fulp W, Pawitan Y, Foekens J, Smid M, Martens J . Validation of a radiosensitivity molecular signature in breast cancer. Clin Cancer Res. 2012; 18(18):5134-43. PMC: 3993974. DOI: 10.1158/1078-0432.CCR-12-0891. View

Chinot O, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R . Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014; 370(8):709-22. DOI: 10.1056/NEJMoa1308345. View

Meng J, Li P, Zhang Q, Yang Z, Fu S . A radiosensitivity gene signature in predicting glioma prognostic via EMT pathway. Oncotarget. 2014; 5(13):4683-93. PMC: 4148091. DOI: 10.18632/oncotarget.2088. View

Ahmed K, Fulp W, Berglund A, Hoffe S, Dilling T, Eschrich S . Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection. Int J Radiat Oncol Biol Phys. 2015; 92(4):837-42. PMC: 4481172. DOI: 10.1016/j.ijrobp.2015.01.036. View

Torres-Roca J, Fulp W, Caudell J, Servant N, Bollet M, Van de Vijver M . Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer. Int J Radiat Oncol Biol Phys. 2015; 93(3):631-8. PMC: 5811194. DOI: 10.1016/j.ijrobp.2015.06.021. View

Sultanem K, Patrocinio H, Lambert C, Corns R, LeBlanc R, Parker W . The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial. Int J Radiat Oncol Biol Phys. 2003; 58(1):247-52. DOI: 10.1016/s0360-3016(03)00819-8. View

Chan J, Lee S, Fraass B, Normolle D, Greenberg H, Junck L . Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol. 2002; 20(6):1635-42. DOI: 10.1200/JCO.2002.20.6.1635. View

Strom T, Hoffe S, Fulp W, Frakes J, Coppola D, Springett G . Radiosensitivity index predicts for survival with adjuvant radiation in resectable pancreatic cancer. Radiother Oncol. 2015; 117(1):159-64. PMC: 7771365. DOI: 10.1016/j.radonc.2015.07.018. View

10.

Floyd N, Woo S, Teh B, Prado C, Mai W, Trask T . Hypofractionated intensity-modulated radiotherapy for primary glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2004; 58(3):721-6. DOI: 10.1016/S0360-3016(03)01623-7. View

11.

Roa W, Brasher P, Bauman G, Anthes M, Bruera E, Chan A . Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004; 22(9):1583-8. DOI: 10.1200/JCO.2004.06.082. View

12.

Hegi M, Diserens A, Gorlia T, Hamou M, De Tribolet N, Weller M . MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005; 352(10):997-1003. DOI: 10.1056/NEJMoa043331. View

13.

Torres-Roca J, Eschrich S, Zhao H, Bloom G, Sung J, McCarthy S . Prediction of radiation sensitivity using a gene expression classifier. Cancer Res. 2005; 65(16):7169-76. DOI: 10.1158/0008-5472.CAN-05-0656. View

14.

Phillips H, Kharbanda S, Chen R, Forrest W, Soriano R, Wu T . Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006; 9(3):157-73. DOI: 10.1016/j.ccr.2006.02.019. View

15.

Iuchi T, Hatano K, Narita Y, Kodama T, Yamaki T, Osato K . Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT. Int J Radiat Oncol Biol Phys. 2006; 64(5):1317-24. DOI: 10.1016/j.ijrobp.2005.12.005. View

16.

Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G . Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007; 356(15):1527-35. DOI: 10.1056/NEJMoa065901. View

17.

. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008; 455(7216):1061-8. PMC: 2671642. DOI: 10.1038/nature07385. View

18.

Panet-Raymond V, Souhami L, Roberge D, Kavan P, Shakibnia L, Muanza T . Accelerated hypofractionated intensity-modulated radiotherapy with concurrent and adjuvant temozolomide for patients with glioblastoma multiforme: a safety and efficacy analysis. Int J Radiat Oncol Biol Phys. 2008; 73(2):473-8. DOI: 10.1016/j.ijrobp.2008.04.030. View

19.

Tsien C, Moughan J, Michalski J, Gilbert M, Purdy J, Simpson J . Phase I three-dimensional conformal radiation dose escalation study in newly diagnosed glioblastoma: Radiation Therapy Oncology Group Trial 98-03. Int J Radiat Oncol Biol Phys. 2008; 73(3):699-708. PMC: 2913423. DOI: 10.1016/j.ijrobp.2008.05.034. View

20.

Yan H, Parsons D, Jin G, McLendon R, Rasheed B, Yuan W . IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009; 360(8):765-73. PMC: 2820383. DOI: 10.1056/NEJMoa0808710. View