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NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients

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Abstract

From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1–3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity. Out of the 712 patients accrued, 694 (97.5%) were analyzable cases (350 HFX, 344 standard arm). There was no significant difference between the arms on overall acute or late treatment-related toxicity. No statistically significant effect for HFX, as compared to standard therapy, was found on either OS, with a median survival time (MST) of 11.3 versus 13.1 months (p = 0.20) or PFS, with a median PFS time of 5.7 versus 6.9 months (p = 0.18). The treatment effect on OS remained insignificant based on the multivariate analysis (hazard ratio 1.16; p = 0.0682). When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme (MST: 10.3 vs. 11.2 months; p = 0.34), anaplastic astrocytoma (MST: 69.8 vs. 50.0 months; p = 0.91) or anaplastic oligodendroglioma (MST: 92.1 vs. 66.5 months; p = 0.33). Though this trial provided many invaluable secondary analyses, there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients.

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Funding

This study was supported by grants U10CA21661 (RTOG-Ops-Stat), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U10CA37422 (CCOP), from the National Cancer Institute (NCI).

Author information

Authors and Affiliations

  1. Emory University/Winship Cancer Institute, 1365 Clifton Rd NE, Atlanta, GA, 30322, USA

    Arif N. Ali & Walter J. Curran Jr

  2. NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA

    Peixin Zhang & Minhee Won

  3. The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    W. K. Alfred Yung & Marta Penas-Prado

  4. University of Rochester Medical Center, Rochester, NY, USA

    Yuhchyau Chen

  5. Henry Ford Hospital accruals Fox Chase Cancer Center, Detroit, MI, USA

    Benjamin Movsas

  6. Cross Cancer Institute, Edmonton, AB, Canada

    Raul C. Urtasun

  7. Sutter General Hospital accruals Radiological Associates of Sacramento, Sacramento, CA, USA

    Christopher U. Jones

  8. State University of New York Downstate Medical Center, Brooklyn, NY, USA

    Kwang N. Choi

  9. Washington University School of Medicine, St. Louis, MO, USA

    Jeff M. Michalski

  10. Intermountain Medical Center accruals LDS Hospital, Murray, UT, USA

    A. Jennifer Fischbach

  11. Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

    Arnold M. Markoe

  12. Froedtert and the Medical College of Wisconsin, Milwaukee, WI, USA

    Christopher J. Schultz

  13. Montefiore Medical Center, Moses Campus, Bronx, NY, USA

    Madhur K. Garg

  14. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA

    Alan C. Hartford

  15. Wayne State University, Detroit, MI, USA

    Harold E. Kim

Authors
  1. Arif N. Ali
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  2. Peixin Zhang
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  3. W. K. Alfred Yung
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  4. Yuhchyau Chen
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  5. Benjamin Movsas
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  6. Raul C. Urtasun
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  7. Christopher U. Jones
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  8. Kwang N. Choi
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  9. Jeff M. Michalski
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  10. A. Jennifer Fischbach
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  11. Arnold M. Markoe
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  12. Christopher J. Schultz
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  13. Marta Penas-Prado
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  14. Madhur K. Garg
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  15. Alan C. Hartford
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  16. Harold E. Kim
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  17. Minhee Won
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  18. Walter J. Curran Jr
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Corresponding author

Correspondence to Arif N. Ali.

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Conflict of interest

Dr. Movsas reports research grants from Varian, Inc. and Philips, Inc. Drs. Chen and Penas-Prado report grants from NCI. Dr. Jones reports receiving speaker fees from Lilly. Dr. Yung reports research grant to his institution from RTOG and fees for serving on scientific advisory board of DNAtrix.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Ali, A.N., Zhang, P., Yung, W.K.A. et al. NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients. J Neurooncol 137, 39–47 (2018). https://doi.org/10.1007/s11060-017-2558-x

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  • DOI: https://doi.org/10.1007/s11060-017-2558-x

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