Journal of Neuro-Oncology

, Volume 109, Issue 1, pp 195–203 | Cite as

Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma?

  • Tejpal Gupta
  • Vimoj Nair
  • Siji Nojin Paul
  • Sadhana Kannan
  • Aliasgar Moiyadi
  • Sridhar Epari
  • Rakesh Jalali
Clinical Study

Abstract

Glioblastoma progenitor or stem cells residing in the stem-cell niche in the subventricular zones (SVZ) can initiate or promote tumorigenesis. They can also migrate throughout the brain, resulting in disease progression. Irradiation of potential cancer stem-cell niche in the SVZ may influence survival. To analyze radiotherapy dose-volume parameters to the SVZ that correlate with survival in adequately treated patients with newly diagnosed glioblastoma, 40 adults with histopathologically proven supratentorial glioblastoma with available baseline imaging treated with postoperative conventionally fractionated focal conformal radiotherapy plus chemotherapy, available radiotherapy planning dataset, and documented event of progression or death or minimum 6-month follow-up were included in this retrospective study. Dose-volume parameters to the SVZ were extracted from treatment planning system and analyzed in relation to survival outcomes. Mean ipsilateral and contralateral SVZ volumes were 5.6 and 6.4 cc, respectively. With median follow-up of 15 months (interquartile range 12–18 months), median [95 % confidence interval (CI)] progression-free survival (PFS) and overall survival (OAS) was 11 months (95 % CI 8.9–13.0 months) and 17 months (95 % CI 11.6–22.4 months), respectively. Older age (>50 years), poor recursive partitioning analysis (RPA) class, and higher than median of mean contralateral SVZ dose were associated with significantly worse PFS and OAS. Multivariate analysis identified RPA class, Karnofsky performance status, and mean ipsilateral SVZ dose as independent predictors of survival. Increasing mean dose to the ipsilateral SVZ was associated with significantly improved OAS. Irradiation of potential cancer stem-cell niche influences survival outcomes in patients with newly diagnosed glioblastoma.

Keywords

Glioblastoma Radiotherapy Stem-cell niche Subventricular zone Survival 

References

  1. 1.
    Wen PY, Kesari S (2008) Malignant gliomas in adults. New Engl J Med 359(5):492–507. doi:10.1056/NEJMra0708126 PubMedCrossRefGoogle Scholar
  2. 2.
    Koshy M, Villano JL, Dolecek TA, Howard A, Mahmood U, Chmura SJ, Weichselbaum RR, McCarthy BJ (2011) Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neurooncol. doi:10.1007/s11060-011-0738-7 Google Scholar
  3. 3.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New Engl J Med 352(10):987–996. doi:10.1056/NEJMoa043330 PubMedCrossRefGoogle Scholar
  4. 4.
    McDonald MW, Shu HK, Curran WJ Jr, Crocker IR (2011) Pattern of failure after limited margin radiotherapy and temozolomide for glioblastoma. Int J Radiat Oncol Biol Phys 79(1):130–136. doi:10.1016/j.ijrobp.2009.10.048 PubMedCrossRefGoogle Scholar
  5. 5.
    Oh J, Sahgal A, Sanghera P, Tsao MN, Davey P, Lam K, Symons S, Aviv R, Perry JR (2011) Glioblastoma: patterns of recurrence and efficacy of salvage treatments. Can J Neurol Sci (Le journal canadien des sciences neurologiques) 38(4):621–625Google Scholar
  6. 6.
    Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (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(5):459–466. doi:10.1016/S1470-2045(09)70025-7 PubMedCrossRefGoogle Scholar
  7. 7.
    Gatenby RA, Vincent TL (2003) An evolutionary model of carcinogenesis. Cancer Res 63(19):6212–6220PubMedGoogle Scholar
  8. 8.
    Moolgavkar SH, Knudson AG Jr (1981) Mutation and cancer: a model for human carcinogenesis. J Natl Cancer Inst 66(6):1037–1052PubMedGoogle Scholar
  9. 9.
    Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111. doi:10.1038/35102167 PubMedCrossRefGoogle Scholar
  10. 10.
    Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMedGoogle Scholar
  11. 11.
    Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64(19):7011–7021. doi:10.1158/0008-5472.CAN-04-1364 PubMedCrossRefGoogle Scholar
  12. 12.
    Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6(6):425–436. doi:10.1038/nrc1889 PubMedCrossRefGoogle Scholar
  13. 13.
    Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4(11):1313–1317. doi:10.1038/3305 PubMedCrossRefGoogle Scholar
  14. 14.
    Alvarez-Buylla A, Garcia-Verdugo JM (2002) Neurogenesis in adult subventricular zone. J Neurosci 22(3):629–634PubMedGoogle Scholar
  15. 15.
    Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250. doi:10.1146/annurev.neuro.28.051804.101459 PubMedCrossRefGoogle Scholar
  16. 16.
    Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, Oh EY, Gaber MW, Finklestein D, Allen M, Frank A, Bayazitov IT, Zakharenko SS, Gajjar A, Davidoff A, Gilbertson RJ (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11(1):69–82. doi:10.1016/j.ccr.2006.11.020 PubMedCrossRefGoogle Scholar
  17. 17.
    Lim DA, Cha S, Mayo MC, Chen MH, Keles E, VandenBerg S, Berger MS (2007) Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro-oncology 9(4):424–429. doi:10.1215/15228517-2007-023 PubMedCrossRefGoogle Scholar
  18. 18.
    Gong X, Schwartz PH, Linskey ME, Bota DA (2011) Neural stem/progenitors and glioma stem-like cells have differential sensitivity to chemotherapy. Neurology 76(13):1126–1134. doi:10.1212/WNL.0b013e318212a89f PubMedCrossRefGoogle Scholar
  19. 19.
    Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760. doi:10.1038/nature05236 PubMedCrossRefGoogle Scholar
  20. 20.
    Glantz M, Kesari S, Recht L, Fleischhack G, Van Horn A (2009) Understanding the origins of gliomas and developing novel therapies: cerebrospinal fluid and subventricular zone interplay. Semin Oncol 36(4 Suppl 2):S17–S24. doi:10.1053/j.seminoncol.2009.05.003 PubMedCrossRefGoogle Scholar
  21. 21.
    Evers P, Lee PP, DeMarco J, Agazaryan N, Sayre JW, Selch M, Pajonk F (2010) Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma. BMC Cancer 10:384. doi:10.1186/1471-2407-10-384 PubMedCrossRefGoogle Scholar
  22. 22.
    Filippini G, Falcone C, Boiardi A, Broggi G, Bruzzone MG, Caldiroli D, Farina R, Farinotti M, Fariselli L, Finocchiaro G, Giombini S, Pollo B, Savoiardo M, Solero CL, Valsecchi MG (2008) Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma. Neuro-oncology 10(1):79–87. doi:10.1215/15228517-2007-038 PubMedCrossRefGoogle Scholar
  23. 23.
    Siker ML, Wang M, Porter K, Nelson DF, Curran WJ, Michalski JM, Souhami L, Chakravarti A, Yung WK, Delrowe J, Coughlin CT, Mehta MP (2011) Age as an independent prognostic factor in patients with glioblastoma: a Radiation Therapy Oncology Group and American College of Surgeons National Cancer Data Base comparison. J Neurooncol 104(1):351–356. doi:10.1007/s11060-010-0500-6 PubMedCrossRefGoogle Scholar
  24. 24.
    Li J, Wang M, Won M, Shaw EG, Coughlin C, Curran WJ Jr, Mehta MP (2011) Validation and simplification of the Radiation Therapy Oncology Group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81(3):623–630. doi:10.1016/j.ijrobp-2010-06-012 PubMedCrossRefGoogle Scholar
  25. 25.
    Wick W, Stupp R, Beule AC, Bromberg J, Wick A, Ernemann U, Platten M, Marosi C, Mason WP, van den Bent M, Weller M, Rorden C, Karnath HO (2008) A novel tool to analyze MRI recurrence patterns in glioblastoma. Neuro-oncology 10(6):1019–1024. doi:10.1215/15228517-2008-058 PubMedCrossRefGoogle Scholar
  26. 26.
    Slotman BJE, Eppinga WSC, de haan PF, Lagerwaard J (2011) Is irradiation of potential cancer stem cell niches in the subventricular zones indicated in GBM? (abstr 1058). Int J Radiat Oncol Biol Phys 81 (2, Suppl 1):S184Google Scholar
  27. 27.
    Nicholas MK, Lukas RV, Chmura S, Yamini B, Lesniak M, Pytel P (2011) Molecular heterogeneity in glioblastoma: therapeutic opportunities and challenges. Semin Oncol 38(2):243–253. doi:10.1053/j.seminoncol.2011.01.009 PubMedCrossRefGoogle Scholar
  28. 28.
    Young GS, Macklin EA, Setayesh K, Lawson JD, Wen PY, Norden AD, Drappatz J, Kesari S (2011) Longitudinal MRI evidence for decreased survival among periventricular glioblastoma. J Neurooncol 104(1):261–269. doi:10.1007/s11060-010-0477-1 PubMedCrossRefGoogle Scholar
  29. 29.
    Bohman LE, Swanson KR, Moore JL, Rockne R, Mandigo C, Hankinson T, Assanah M, Canoll P, Bruce JN (2010) Magnetic resonance imaging characteristics of glioblastoma multiforme: implications for understanding glioma ontogeny. Neurosurgery 67 (5):1319–1327; discussion 1327–1318. doi:10.1227/NEU.0b013e3181f556ab Google Scholar
  30. 30.
    Kappadakunnel M, Eskin A, Dong J, Nelson SF, Mischel PS, Liau LM, Ngheimphu P, Lai A, Cloughesy TF, Goldin J, Pope WB (2010) Stem cell associated gene expression in glioblastoma multiforme: relationship to survival and the subventricular zone. J Neurooncol 96(3):359–367. doi:10.1007/s11060-009-9983-4 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Tejpal Gupta
    • 1
  • Vimoj Nair
    • 1
  • Siji Nojin Paul
    • 1
  • Sadhana Kannan
    • 2
  • Aliasgar Moiyadi
    • 3
  • Sridhar Epari
    • 4
  • Rakesh Jalali
    • 1
  1. 1.Department of Radiation OncologyAdvanced Centre for Treatment, Research and Education in Cancer (ACTREC) and Tata Memorial Hospital, Tata Memorial CentreNavi MumbaiIndia
  2. 2.Department of Epidemiology and Clinical Trials Unit, Clinical Research SecretariatAdvanced Centre for Treatment, Research and Education in Cancer (ACTREC) and Tata Memorial Hospital, Tata Memorial CentreNavi MumbaiIndia
  3. 3.Division of Neuro-surgery, Department of Surgical OncologyAdvanced Centre for Treatment, Research and Education in Cancer (ACTREC) and Tata Memorial Hospital, Tata Memorial CentreNavi MumbaiIndia
  4. 4.Division of Neuro-pathology, Department of PathologyAdvanced Centre for Treatment, Research and Education in Cancer (ACTREC) and Tata Memorial Hospital, Tata Memorial CentreNavi MumbaiIndia

Personalised recommendations