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Journal of Neuro-Oncology

, Volume 133, Issue 1, pp 107–118 | Cite as

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

  • Natsuko Kondo
  • Rolf F. Barth
  • Shin-Ichi Miyatake
  • Shinji Kawabata
  • Minoru Suzuki
  • Koji Ono
  • Norman L. Lehman
Clinical Study
First Online:

Abstract

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients’ tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

Keywords

Boron neutron capture therapy High-grade glioma Cerebrospinal fluid dissemination Small cell glioblastoma Anaplastic oligodendroglioma 
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Notes

Acknowledgements

We thank Dr. Daniel Jones of Ohio State University for performing FISH studies, Dr. Yoshinori Sakurai of Kyoto University Research Reactor Institute for recalculating the DVH of BNCT, and Loretta Bahn for assistance in preparation of this manuscript. Dr. Lehman was supported in part by NIH grant R01 NS081125. Ms. Bahn was partially supported by the Kevin J. Mullin Memorial Fund for Brain Tumor Research. This work was also supported by the Future Development Funding Program of the Kyoto University Research Coordination Alliance.

References

  1. 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 10:459–466CrossRefPubMedGoogle Scholar
  2. 2.
    Kawabata S, Miyatake S, Kuroiwa T et al (2009) Boron neutron capture therapy for newly diagnosed glioblastoma. J Radiat Res 50:51–60CrossRefPubMedGoogle Scholar
  3. 3.
    Miyatake S, Kawabata S, Yokoyama K et al (2009) Survival benefit of boron neutron capture therapy for recurrent malignant gliomas. J Neurooncol 91:199–206. doi: 10.1007/s11060-008-9699-x CrossRefPubMedGoogle Scholar
  4. 4.
    Carson KA, Grossman SA, Fisher JD et al (2007) Prognostic factors for survival in adult patients with recurrent glioma enrolled onto the new approaches to brain tumor therapy CNS consortium phase I and II clinical trials. J Clin Oncol 25:2601–2606. doi: 10.1200/JCO.2006.08.1661 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Barth RF, Coderre JA, Vicente MGH et al (2005) Boron neutron capture therapy of cancer: current status and future prospects. Clin Cancer Res 11:3987–4002CrossRefPubMedGoogle Scholar
  6. 6.
    Barth RF, Vicente MG, Harling OK et al (2012) Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer. Radiat Oncol 7:146–166CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Salazar OM, Rubin P (1976) The spread of glioblastoma multiforme as a determining factor in the radiation treated volume. Int J Radiat Oncol Biol Phys 1:627–637CrossRefPubMedGoogle Scholar
  8. 8.
    Erlich SS, Davis RL (1978) Spinal subarachnoid metastasis from primary intracranial glioblastoma multiforme. Cancer 42:2854–2864CrossRefPubMedGoogle Scholar
  9. 9.
    Hamilton MG, Tranmer BI, Hagen NA (1993) Supratentorial glioblastoma with spinal cord intramedullary metastasis. Can J Neurol Sci 20:65–68CrossRefPubMedGoogle Scholar
  10. 10.
    Engelhard HH, Corsten LA (2005) Leptomeningeal metastases of primary central nervous system (CNS) neoplasms. Cancer Treat Res. 5:71–85.CrossRefGoogle Scholar
  11. 11.
    Mandel JJ, Yust-Katz S, Cachia D et al (2014) Leptomeningeal dissemination in glioblastoma; an inspection of risk factors, treatment, and outcomes at a single institution. J Neurooncol 20:597–605CrossRefGoogle Scholar
  12. 12.
    Lee SW, Fraass BA, Marsh LH et al (1999) Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. Int J Radiat Oncol Biol Phys 43:79–88CrossRefPubMedGoogle Scholar
  13. 13.
    Wallner KE, Galicich JH, Krol G et al (1989) Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 16:1405–1409CrossRefPubMedGoogle Scholar
  14. 14.
    Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Jansen M, Yip S, Louis DN (2010) Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers. Lancet Neurol 9:717–726CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kawabata S, Miyatake S, Kajimoto Y et al (2003) The early successful treatment of glioblastoma patients with modified boron neutron capture therapy. report of two cases. J Neurooncol 65:159–165CrossRefPubMedGoogle Scholar
  18. 18.
    Miyatake S, Kawabata S, Kajimoto Y et al (2005) Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages. J Neurosurg 103:1000–1009CrossRefPubMedGoogle Scholar
  19. 19.
    Imahori Y, Ueda S, Ohmori Y, et al (1998) Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas:Part I. Clin Can Res 4:1825–1832.Google Scholar
  20. 20.
    Imahori Y, Ueda S, Ohmori Y, et al (1998) Positron emission tomography- based boron neutron capture therapy using boronophenylalanine for high-grade gliomas:Part II. Clin Can Res 4:1833–1841Google Scholar
  21. 21.
    Sakurai Y, Ono K, Miyatake S et al (2006) Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours. Phys Med Biol 51:1173–1183CrossRefPubMedGoogle Scholar
  22. 22.
    Sakurai Y, Kobayashi T (2002) The medical-irradiation characteristics for neutron capture therapy at the heavy water neutron irradiation facility of Kyoto university research reactor. Med Phys 29:2328–2337CrossRefPubMedGoogle Scholar
  23. 23.
    Kawabata S, Miyatake S, Hiramatsu R et al (2011) Phase II clinical study of boron neutron capture therapy combined with X-ray radiotherapy/temozolomide in patients with newly diagnosed glioblastoma multiforme–study design and current status report. Appl Radiat Isot 69:1796–1799CrossRefGoogle Scholar
  24. 24.
    Miyashita M, Miyatake SI, Imahori Y et al (2008) Evaluation of fluoride-labeled boronophenylalanine-PET imaging for the study of radiation effects in patients with glioblastomas. J Neurooncol 89:239–246CrossRefPubMedGoogle Scholar
  25. 25.
    Lois DN, Ohgaki H, Wiestler OD, et al. (2016) Chap. 1, Diffuse astrocytic and oligodendroglial tumours, WHO classification of tumors of the Central Nervous System, P36.Google Scholar
  26. 26.
    Joseph NM, Phillips J, Dahiya S et al (2013) Diagnostic implications of IDH1-R132H and OLIG2 expression patterns in rare and challenging glioblastoma variants. Mod Pathol 26:315–326CrossRefPubMedGoogle Scholar
  27. 27.
    Tanaka M, Ino Y, Nakagawa K et al (2005) High-dose conformal radiotherapy for supratentorial malignant glioma: a historical comparison. Lancet Oncol 6:953–960CrossRefPubMedGoogle Scholar
  28. 28.
    Iuchi T, Hatano K, Kodama T et al (2014) Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma. Int J Radiat Oncol Biol Phys 88:793–800CrossRefPubMedGoogle Scholar
  29. 29.
    Nakagawa K, Aoki Y, Fujimaki T et al (1998) High-dose conformal radiotherapy influenced the pattern of failure but did not improve survival in glioblastoma multiforme. Int J Radiat Oncol Biol Phys 40:1141–1149CrossRefPubMedGoogle Scholar
  30. 30.
    Wild-Bode C, Weller M, Rimner A et al (2001) Sublethal irradiation promotes migration and invasiveness of glioma cells: implications for radiotherapy of human glioblastoma. Cancer Res 61:2744–2750PubMedGoogle Scholar
  31. 31.
    Zhai GG, Malhotra R, Delaney M et al (2006) Radiation enhances the invasive potential of primary glioblastoma cells via activation of the Rho signaling pathway. J Neuro-Oncology 76:227–237CrossRefGoogle Scholar
  32. 32.
    Zhao T, Wang H, Ma H et al (2016) Starvation after cobalt-60 γ-ray radiation enhances metastasis in U251 glioma cells by regulating the transcription factor SP1. Int J Mol Sci 17:386CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Hellweg CE, Spitta LF, Henschenmacher B, et al (2016) Transcription factors in the cellular response to charged particle exposure. Front Oncol. doi: 10.3389/fonc.2016.00061 PubMedPubMedCentralGoogle Scholar
  34. 34.
    Ghandhi SA, Yaghoubian B, Amundson SA (2008) Global gene expression analyses of bystander and alpha particle irradiated normal human lung fibroblasts: Synchronous and differential responses. BMC Med Genomics 1:63CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Brennan CW, Verhaak RG, McKenna A et al (2013) The somatic genomic landscape of glioblastoma. Cell 155:462–477CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Talasila KM, Soentgerath A, Euskirchen P et al (2013) EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis. Acta Neuropathol 125:683–698CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lim DA, Cha S, Mayo MC et al (2007) Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. J Neuro-Oncology 9(4):424–429CrossRefGoogle Scholar
  38. 38.
    Kimura M, Lee Y, Miller R et al (2013) Glioblastoma multiforme: relationship to subventricular zone and recurrence. Neuroradiol J 26:542–547CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Roelz R., Reinacher P, Jabbarli R, et al (2015) Surgical ventricular entry is a key risk factor for leptomeningeal metastasis of high grade gliomas. Sci Rep 5:17758CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Perry A, Aldape KD, George DH et al (2004) Small cell astrocytoma an aggressive variant that is clinicopathologically and genetically distinct from anaplastic oligodendroglioma. Cancer 101:2318–2326CrossRefPubMedGoogle Scholar
  41. 41.
    Coderre JA, Chanana AD, Joel DD et al (1998) Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: boron concentration correlates with tumor cellularity. Radiat Res 149:163–170CrossRefPubMedGoogle Scholar
  42. 42.
    Scherer HJ (1940) The forms of growth in gliomas and their practical significance. Brain 63:1–35CrossRefGoogle Scholar
  43. 43.
    Scherer HJ (1938) Structural development in gliomas. Am J Cancer 34:333–351Google Scholar
  44. 44.
    Englehard HH, Stelea A, Mundt A (2003) Oligodendroglioma and anaplastic oligodendroglioma: clinical features, treatment, and prognosis. Surg Neurol 60:443–456CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Natsuko Kondo
    • 1
  • Rolf F. Barth
    • 3
  • Shin-Ichi Miyatake
    • 2
  • Shinji Kawabata
    • 2
  • Minoru Suzuki
    • 1
  • Koji Ono
    • 1
  • Norman L. Lehman
    • 3
  1. 1.Particle Radiation Oncology Research CenterKyoto University Research Reactor InstituteOsakaJapan
  2. 2.Department of NeurosurgeryOsaka Medical CollegeTakatsuki CityJapan
  3. 3.Department of PathologyThe Ohio State University Medical CenterColumbusUSA

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