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Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma

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Abstract

We investigate the differences in molecular signature and clinical outcomes between multiple lesion glioblastoma (GBM) and single focus GBM in the modern treatment era. Between August 2000 and May 2010, 161 patients with GBM were treated with modern radiotherapy techniques. Of this group, 33 were considered to have multiple lesion GBM (25 multifocal and 8 multicentric). Patterns of failure, time to progression and overall survival were compared based on whether the tumor was considered a single focus or multiple lesion GBM. Genomic groupings and methylation status were also investigated as a possible predictor of multifocality in a cohort of 41 patients with available tissue for analysis. There was no statistically significant difference in overall survival (p < 0.3) between the multiple lesion tumors (8.2 months) and single focus GBM (11 months). Progression free survival was superior in the single focus tumors (7.1 months) as compared to multi-focal (5.6 months, p = 0.02). For patients with single focus, multifocal and multicentric GBM, 81, 76 and 88 % of treatment failures occurred in the 60 Gy volume (p < 0.5), while 54, 72, and 38 % of treatment failures occurred in the 46 Gy volume (p < 0.4). Out of field failures were rare in both single focus and multiple foci GBM (7 vs 3 %). Genomic groupings and methylation status were not found to predict for multifocality. Patterns of failure, survival and genomic signatures for multiple lesion GBM do not appreciably differ when compared to single focus tumors.

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Acknowledgements

The investigators responsible for this manuscript would like to sincerely thank Marlene Pratto and the Pratto Fund for Brain Tumor Research for the generous gift which helped to fund this research. We would like to thank Dr. Thomas L. Ellis, who contributed significantly to this work until his untimely death in 2012. We would also like to thank our patients as they are the inspiration behind our work. This work has previously been presented at the ASTRO 2012 National Meeting in Boston, MA.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

Pratto Fund for Brain Tumor Research; Dalton McMichael Fund in Cancer Research (to A.M.P); Comprehensive Cancer Center of Wake Forest University supported by the National Cancer Institute Cancer Center Support Grant [P30CA012197].

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Authors and Affiliations

  1. Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Anna K. Paulsson

  2. Department of Radiation Oncology, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Jordan A. Holmes, Ann M. Peiffer, William H. Hinson & Michael D. Chan

  3. Department of Neurosurgery, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Adrian W. Laxton, Stephen B. Tatter & Waldemar Debinski

  4. Department of Cancer Biology, Wake Forest Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Lance D. Miller

  5. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Wennuan Liu & Jianfeng Xu

  6. Department of Medicine (Hematology & Oncology), Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Glenn J. Lesser

  7. Brain Tumor Center of Excellence, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Ann M. Peiffer, Glenn J. Lesser, Stephen B. Tatter, Waldemar Debinski & Michael D. Chan

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  1. Anna K. Paulsson
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  2. Jordan A. Holmes
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  3. Ann M. Peiffer
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  4. Lance D. Miller
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  5. Wennuan Liu
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  6. Jianfeng Xu
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  7. William H. Hinson
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  8. Glenn J. Lesser
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  9. Adrian W. Laxton
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  10. Stephen B. Tatter
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  11. Waldemar Debinski
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  12. Michael D. Chan
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Corresponding author

Correspondence to Michael D. Chan.

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11060_2014_1515_MOESM1_ESM.ppt

Supplementary material 1 (PPT 339 kb) Supplementary Fig. 1. Using the predictive 840 gene list published in the TCGA GBM samples [6], we created a heat map while maintaining the previously published TCGA gene order

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Paulsson, A.K., Holmes, J.A., Peiffer, A.M. et al. Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma. J Neurooncol 119, 429–435 (2014). https://doi.org/10.1007/s11060-014-1515-1

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  • DOI: https://doi.org/10.1007/s11060-014-1515-1

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