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Outcome of Adult Brain Tumor Consortium (ABTC) prospective dose-finding trials of I-125 balloon brachytherapy in high-grade gliomas: challenges in clinical trial design and technology development when MRI treatment effect and recurrence appear similar

  • Original Research
  • Published:
Journal of Radiation Oncology

Abstract

Objectives

The aim of this study is to define the maximal safe radiation dose to guide further study of the GliaSite balloon brachytherapy (GSBT) system in untreated newly diagnosed glioblastoma (NEW-GBM) and recurrent high-grade glioma (REC-HGG). GBST is a balloon placed in the resection cavity and later filled through a subcutaneous port with liquid I-125 Iotrex, providing radiation doses that diminish uniformly with distance from the balloon surface.

Methods

The Adult Brain Tumor Consortium initiated prospective dose-finding studies to determine maximum tolerated dose in NEW-GBM treated before standard RT or after surgery for REC-HGG. Patients were inevaluable if there was progression before the 90-day posttreatment toxicity evaluation point.

Results

Ten NEW-GBM patients had the balloon placed, and 2/10 reached the 90 day timepoint. Five REC-HGG enrolled and two were assessable at the 90-day evaluation endpoint. Imaging progression occurred before 90-day evaluation in 7/12 treated patients. The trials were closed as too few patients were assessable to allow dose escalation, although no dose-limiting toxicities (DLTs) were observed. Median survival from treatment was 15.3 months (95 % CI 7.1–23.6) for NEW-GBM and 12.8 months (95 % CI 4.2–20.9) for REC-HGG.

Conclusion

These trials failed to determine a maximum tolerated dose (MTD) for further testing as early imaging changes, presumed to be progression, were common and interfered with the assessment of treatment-related toxicity. The survival outcomes in these and other related studies, although based on small populations, suggest that GSBT may be worthy of further study using clinical and survival endpoints, rather than standard imaging results. The implications for local therapy development are discussed.

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Funding

This study was funded by the National Cancer Institute Grants CA62-475 and CA137443 and by Proxima Therapeutics, Alpharetta, GA.

Ethical standards statement

All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Cancer Center, Johns Hopkins University, 401 North Broadway, Suite 1440, Baltimore, MD, 21231, USA

    L. R. Kleinberg, J. Weingart, S. Desideri, X. Ye & S. Grossman

  2. Piedmont Radiation Oncology, Winston-Salem, NC, USA

    V. Stieber

  3. Henry Ford Hospital, Detroit, MI, USA

    T. Mikkelsen

  4. Thomas Jefferson University Hospital, Philadelphia, PA, USA

    K. Judy

  5. Cleveland Clinic, Cleveland, OH, USA

    G. Barnett

  6. Emory University, Atlanta, USA

    J. Olson

Authors
  1. L. R. Kleinberg
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  2. V. Stieber
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  3. T. Mikkelsen
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  4. K. Judy
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  5. J. Weingart
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  6. G. Barnett
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  7. J. Olson
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  8. S. Desideri
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  9. X. Ye
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  10. S. Grossman
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Corresponding author

Correspondence to L. R. Kleinberg.

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Kleinberg, L.R., Stieber, V., Mikkelsen, T. et al. Outcome of Adult Brain Tumor Consortium (ABTC) prospective dose-finding trials of I-125 balloon brachytherapy in high-grade gliomas: challenges in clinical trial design and technology development when MRI treatment effect and recurrence appear similar. J Radiat Oncol 4, 235–241 (2015). https://doi.org/10.1007/s13566-015-0210-y

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  • DOI: https://doi.org/10.1007/s13566-015-0210-y

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