Skip to main content
Log in

Multilesion glioblastoma multiforme in the modern chemo-radiotherapy era: an analysis of pattern of failure and overall survival

  • Original Research
  • Published:
Journal of Radiation Oncology

Abstract

Purpose/objectives

We sought to evaluate the pattern of disease progression and survival of patients with multilesion glioblastoma (GBM) in a modern patient cohort.

Methods/materials

We retrospectively collected the clinical data of patients over 2004–2014 with newly diagnosed GBM. Following resection (or biopsy), all patients received radiotherapy to 60 Gy in 30 fractions with concurrent and adjuvant temozolomide. Preoperative MRIs were reviewed by a single diagnostic radiologist blinded to treatment outcomes and categorized as single focus or multilesion (multifocal/multicentric). Multifocal tumors were defined as noncontiguous enhancement along known neural pathways and multicentric tumors were defined as noncontiguous enhancement along disjointed pathways (i.e., different lobes). Univariate and multivariate (MVA) analyses were performed to investigate factors prognostic of overall survival.

Results

Of 155 eligible patients, 30 presented with a multilesion tumor focus (19.4%). Of the patients that developed recurrent disease before death (n = 123), the predominant pattern of failure was local (80%) and did not differ by focality (p = 0.18). Unifocal, multifocal, and multicentric tumors demonstrated similar actuarial disease progression (p = 0.12). Median survival was inferior in patients with multifocal and multicentric disease compared to unifocal disease (11.5, 7.1, and 18.0 months, respectively, p = 0.009). On MVA, factors prognostic of overall survival included age ≥70 (HR 3.89, p < 0.001), MGMT promoter hypermethylation (HR 0.21, p = 0.004), IDH1/2 mutation status (p = 0.044), and multicentric tumors (HR 7.18, p = 0.002). Extent of tumor resection did not impact OS (p = 0.308).

Conclusions

We identified unifocal, multifocal, and multicentric GBM entities with differing overall survival following modern chemo-radiotherapy techniques despite similar pattern of disease progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466

    Article  CAS  PubMed  Google Scholar 

  2. National Comprehensive Cancer Network Clinical Practice Guidelines: Central Nervous System Cancers v1.2016, Available at: http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf, Accessed 1 Dec. 2016

  3. Paulsson AK, Holmes JA, Peiffer AM et al (2014) Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma. J Neuro-Oncol 119:429–435

    Article  Google Scholar 

  4. Patil CG, Yi A, Elramsisy A et al (2012) Prognosis of patients with multifocal glioblastoma: a case-control study. J Neurosurg 117:705–711

    Article  PubMed  Google Scholar 

  5. Showalter TN, Andrel J, Andrews DW et al (2007) Multifocal glioblastoma multiforme: prognostic factors and patterns of progression. Int J Radiat Oncol Biol Phys 69:820–824

    Article  PubMed  Google Scholar 

  6. Thomas RP, Xu LW, Lober RM et al (2013) The incidence and significance of multiple lesions in glioblastoma. J Neuro-Oncol 112:91–97

    Article  Google Scholar 

  7. Hassaneen W, Levine NB, Suki D et al (2011) Multiple craniotomies in the management of multifocal and multicentric glioblastoma. Clinical article. Journal of Neurosurgery 114:576–584

    Article  PubMed  Google Scholar 

  8. Lawrence YR, Mishra MV, Werner-Wasik M et al (2012) Improving prognosis of glioblastoma in the 21st century: who has benefited most? Cancer 118:4228–4234

    Article  PubMed  Google Scholar 

  9. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  CAS  PubMed  Google Scholar 

  10. Armstrong TS, Wefel JS, Wang M et al (2013) Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma. J Clin Oncol 31:4076–4084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li J, Wang M, Won M et al (2011) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81:623–630

    Article  PubMed  Google Scholar 

  12. Michaelsen SR, Christensen IJ, Grunnet K et al (2013) Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme: an observational study of a cohort of consecutive non-selected patients from a single institution. BMC Cancer 13:402

    Article  PubMed  PubMed Central  Google Scholar 

  13. Stark AM, van de Bergh J, Hedderich J et al (2012) Glioblastoma: clinical characteristics, prognostic factors and survival in 492 patients. Clin Neurol Neurosurg 114:840–845

    Article  PubMed  Google Scholar 

  14. Fekete B, Werlenius K, Orndal C, et al. 2015 Prognostic factors for glioblastoma patients—a clinical population-based study. Acta Neurologica Scandinavica

  15. Tanaka S, Meyer FB, Buckner JC et al (2013) Presentation, management, and outcome of newly diagnosed glioblastoma in elderly patients. J Neurosurg 118:786–798

    Article  PubMed  Google Scholar 

  16. Scott JG, Suh JH, Elson P et al (2011) Aggressive treatment is appropriate for glioblastoma multiforme patients 70 years old or older: a retrospective review of 206 cases. Neuro-Oncology 13:428–436

    Article  PubMed  PubMed Central  Google Scholar 

  17. Shakur SF, Bit-Ivan E, Watkin WG et al (2013) Multifocal and multicentric glioblastoma with leptomeningeal gliomatosis: a case report and review of the literature. Case Rep Med 2013:132679

    PubMed  PubMed Central  Google Scholar 

  18. Lacroix M, Abi-Said D, Fourney DR et al (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198

    Article  CAS  PubMed  Google Scholar 

  19. Itakura H, Achrol AS, Mitchell LA, et al. Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities. Science Translational Medicine 2015;7:303ra138.

Download references

Acknowledgments

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniel M. Trifiletti.

Ethics declarations

Funding

No funding was received for this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This investigation was approved by the institutional ethics review board prior to initiation.

Informed consent

Statement of informed consent was not applicable since the manuscript does not contain any patient data.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Trifiletti, D.M., Hill, C., Garda, A. et al. Multilesion glioblastoma multiforme in the modern chemo-radiotherapy era: an analysis of pattern of failure and overall survival. J Radiat Oncol 6, 57–63 (2017). https://doi.org/10.1007/s13566-017-0297-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13566-017-0297-4

Keywords

Navigation