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Assessment of the results from the phase I/II boron neutron capture therapy trials at the Brookhaven National Laboratory from a clinician’s point of view

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Summary

Boron neutron capture therapy (BNCT) represents a promising modality for a relatively selective radiation dose delivery to the tumor tissue. The key to effective BNCT of tumors such as glioblastoma multiforme (GBM) is the homogeneous preferential accumulation of10B in the tumor, including the infiltrating GBM cells, as compared to that in the vital structures of the normal brain. Provided that sufficiently high tumor10B concentration (∼109 boron-10 atoms/cell) and an adequate thermal neutron fluence (∼ 109 neutrons/cm2) are achieved, it is the ratio of the10B concentration in tumor cells to that in the normal brain cells and the blood that will largely determine the therapeutic gain of BNCT.

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References

  1. Farr LE, Sweet WH, Robertson JS, Foster CG, Locksley HG, Sutherland DL, Mendelsohn ML, Stickley EE: Neutron capture therapy with boron in the treatment of glioblastoma multiforme. Am J Roentgenol 71: 279–291, 1954

    CAS  Google Scholar 

  2. Slatkin DN, Stoner RD, Rosander KM, Kalef-Ezra JA, Laissue JA: Central nervous system radiation syndrome in mice from preferential10B(n,α)7 Li irradiation of brain vasculature. Proc Natl Acad Sci USA 85: 4020–4024, 1988

    Article  PubMed  CAS  Google Scholar 

  3. Sweet WH: Early history of development of boron neutron capture therapy of tumors. J Neuro-Oncol 33: 19–26, 1997

    Article  CAS  Google Scholar 

  4. Asbury AK, Ojemann RG, Nielsen SL, Sweet WH: Neuropathologic study of fourteen cases of malignant brain tumor treated by boron-10 slow neutron capture radiation. J Neuropathol Exp Neurol 31: 278–303, 1972

    Article  PubMed  CAS  Google Scholar 

  5. Godwin JT, Farr LE, Sweet WH, Robertson JS: Pathological study of eight patients with glioblastoma multiforme treated by neutron capture therapy using boron 10. Cancer 8: 601–615, 1955

    Article  Google Scholar 

  6. Slatkin DN: A history of boron neutron capture therapy of brain tumors: postulation of a brain radiation dose tolerance limit. Brain 114: 1609–1629, 1991

    Article  PubMed  Google Scholar 

  7. Nakagawa Y, Hatanaka H: Boron neutron capture therapy: clinical brain tumor studies. J Neuro-Oncol 33: 105–115, 1997

    Article  CAS  Google Scholar 

  8. Laramore GE, Spence AM: Boron neutron capture therapy (BNCT) for high-grade gliomas of the brain: a cautionary note. Int J Radiat Oncol Biol Phys 36: 241–246, 1996

    Article  PubMed  CAS  Google Scholar 

  9. Fairchild RG, Kalef-Ezra J, Saraf SK, Fiarman S, Ramsey E, Wielopolski L, Laster BH, Wheeler FJ: Installation and testing of an optimized epithermal neutron beam at the Brookhaven Medical Research Reactor (BMRR). Basic Life Sci 54: 185–199, 1990

    PubMed  CAS  Google Scholar 

  10. Liu HB, Brugger RM, Greenberg DD, Rorer DC, Hu JP, Hauptman HM: Enhancement of the epithermal neutron beam used for boron neutron capture therapy. Int J Radiat Oncol Biol Phys 28: 1149–1156, 1994

    PubMed  CAS  Google Scholar 

  11. Davis FG, Freels S, Grutsch J, Barlas S, Brem S: Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on surveillance, epidemiology, and end results (SEER) data, 1973–1991. J Neurosurg 88: 1–10, 1998

    PubMed  CAS  Google Scholar 

  12. Mehta MP, Masciopinto J, Rozental J, Levin A, Chappell R, Bastin K, Miles J, Turski P, Kubsad S, Mackie T, Kinsella T: Stereotactic radiosurgery for glioblastoma multiforme: report of a prospective study evaluating prognostic factors and analyzing long-term survival advantage. Int J Radiat Oncol Biol Phys 30: 541–549, 1994

    PubMed  CAS  Google Scholar 

  13. Curran WJ Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE, Nelson DF: Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst 85: 704–710, 1993

    Article  PubMed  Google Scholar 

  14. Scott CB, Scarantino C, Urtasun R, Movsas B, Jones CU, Simpson JR, Fischbach AJ, Curran WJ Jr: Validation and predictive power of radiation therapy oncology group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06. Int J Radiat Oncol Biol Phys 40: 51–55, 1998

    Article  PubMed  CAS  Google Scholar 

  15. Lantos P, Vandenberg SR, Kleihues P: Tumors of the nervous system. In: Graham DI, Lantos PI (eds) Greenfields Neuropathology Oxford University Press Inc., New York pp 612–613, 1997

    Google Scholar 

  16. Halperin EC, Burger PC, Bullard DE: The fallacy of the localized supratentorial malignant glioma. Int J Radiat Oncol Biol Phys 15: 505–509, 1988

    Article  PubMed  CAS  Google Scholar 

  17. Sullivan FJ, Herscher LL, Cook JA, Smith J, Steinberg SM, Epstein AH, Oldfield EH, Goffman TE, Kinsella TJ, Mitchell JB, Glatstein E: National Cancer Institute (phase II) study of high-grade glioma treated with accelerated hyper-fractionated radiation and iododeoxyuridine: results in anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 30: 583–590, 1994

    PubMed  CAS  Google Scholar 

  18. Gabel D, Foster S, Fairchild RG: The Monte Carlo simulation of the biological effect of the10B(n, α)7Li reaction in cells and tissue and its implication for boron neutron capture therapy. Radiat Res 111(1): 14–25, 1987

    Article  PubMed  CAS  Google Scholar 

  19. Thompson CB, Sanders JE, Flournoy N, Buckner CD, Thomas ED: The risks of central nervous system relapse and leukoencephalopathy in patients receiving marrow transplants for acute leukemia. Blood 67: 195–199, 1986

    PubMed  CAS  Google Scholar 

  20. Kemper TL, O’Neil R, Caveness WF: Effects of single dose supervoltage whole brain radiation in macaca mulatta. J Neuropathol Exp Neurol 36: 916–940, 1977

    Article  PubMed  CAS  Google Scholar 

  21. Fike JR, Gobbel GT: Central nervous system radiation injury in large animal models. In: Gutin PH, Leibel SA, Sheline GE (eds) Radiation Injury to the Nervous System. Raven Press, New York, pp 113–135, 1991

    Google Scholar 

  22. Huiskamp R, Gavin PR, Coderre JA, Phillips KHI, Wheeler FJ: Brain tolerance in dogs to boron neutron capture therapy with borocaptate sodium (BSH) or boronophenylalanine (BPA). In: Mishima Y (ed) Cancer Neutron Capture Therapy. Plenum Press, Raven Press, pp 591–598, 1996

    Google Scholar 

  23. Slatkin DN: A history of boron neutron capture therapy of brain tumor, Postulation of a brain radiation dose tolerance limit. Brain 114: 1609–1629, 1991

    Article  PubMed  Google Scholar 

  24. Morris GM, Coderre JA, Hopewell JW, Micca PL, Nawrocky MM, Liu HB, Bywaters A: Response of the central nervous system to boron neutron capture irradiation: evaluation using rat spinal cord model. Radiother Oncol 32(3): 249–255, 1994

    Article  PubMed  CAS  Google Scholar 

  25. Engenhart R, Kimmig BN, Hover K-H, Wowra B, Romahn J, Lorenz WJ, van Kaick G, Wannemacher M: Long-term follow-up brain metastases treated by percutaneous stereotactic single high-dose irradiation. Cancer 71: 1353–1361, 1993

    Article  PubMed  CAS  Google Scholar 

  26. Elowitz EH, Bergland RM, Coderre JA, Joel DD, Chadha M, Chanana AD: Biodistribution of p-boronophenylalanine in patients with glioblastoma multiforme for use in boron neutron capture therapy. Neurosurgery 42(3): 463–469, 1998.

    Article  PubMed  CAS  Google Scholar 

  27. Coderre JA, Chanana AD, Joel DD, Elowitz EH, Micca PL, Nawrocky MM, Chadha M, Gebbers JO, Shady M, Peress NS, Slatkin DN: Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: boron concentration correlates with tumor cellularity. Radiat Res 149(2): 163–170, 1998

    Article  PubMed  CAS  Google Scholar 

  28. Nigg DW, Wheeler FJ, Wessol DE, Capala J, Chadha M: Computational dosimetry and treatment planning for boron neutron capture therapy. J Neuro-Oncol 33: 93–104, 1997

    Article  CAS  Google Scholar 

  29. Nigg DW, Wheeler FJ, Wessol DE, Wemple CA, Babcock R, Capala J: Some recent developments in treatment planning software and methodology for BNCT. Proceedings of the Seventh International Symposium on Neutron Capture Therapy for Cancer, Zurich, CH. September 4–7 1996. In: Larsson B, Crawford J, Weinreich R (eds) Advances in Neutron Capture Therapy Vol I, Medicine and Physics. Elsevier, Amsterdam, pp 91–94, 1997

    Google Scholar 

  30. Wessol DE, Wheeler FJ: Creating and using a type of free-form geometry in Monte Carlo particle transport. Nucl Sci Eng 113: 314–323, 1993

    CAS  Google Scholar 

  31. Wheeler F, Nigg DW: Three-dimensional radiation dose distribution analysis for boron neutron capture therapy. Nucl Sci Eng 110: 16–31, 1992

    CAS  Google Scholar 

  32. Chanana AD, Capala J, Chadha M, Coderre JA, Diaz AZ, Elowitz E H, Iwai J, Joel DD, Liu HB, Ma R, Pendzick N Peress NS, Shady MS, Slatkin DN, Tyson GW, Wielopolski L: Boron neutron capture therapy for glioblastoma multiforme: interim results from the Phase I/II dose-escalation studies. Neurosurgery 44(6): 1182–1192; 1999

    Article  PubMed  Google Scholar 

  33. Cox JD, Stetz J, Pajak TF: Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31(5): 1341–1346, 1995

    Article  PubMed  CAS  Google Scholar 

  34. Diaz AZ, Capala J, Ma R, Chanana AD: Local tumor progression in zone of peritumor vasogenic edema following boron neutron capture therapy for glioblastoma multiforme. Int J Radiat Oncol Biol Phys 42(Suppl 1): 264, 1998

    Google Scholar 

  35. Barker FG, Chang SM, Gutin PH, Malec MK, McDermott MW, Prados MD, Wilson CB: Survival and functional status after resection of recurrent glioblastoma multiforme. Neurosurgery 42(4): 709–720, 1998

    Article  PubMed  Google Scholar 

  36. Diaz AZ, Capala J, Chanana AD, Coderre JA, Ma R: Retrospective review of patients undergoing palliative photon radiotherapy after recurrence following boron neutron capture therapy for glioblastoma multiforme. Radiology 213(Suppl 1): 238, 1999

    Google Scholar 

  37. Aziz T, Peress NS, Diaz A, Capala J, Chanana A: Post-mortem neuropathological features secondary to boron neutron capture therapy for glioblastoma multiforme. J Neuropathol Exp Neurol 59(1): 62–73, 2000

    PubMed  CAS  Google Scholar 

  38. Diaz AZ, Chanana AD, Capala J, Chadha M, Coderre J, Elowitz EH, Iwai J, Joel DD, Liu HB, Ma R, Pendzick N, Preess NS, Shady MS, Slatkin DN, Tyson GW, Wielopolski L: Boron neutron capture therapy for glioblastoma multiforme: results from the initial phase I/II dose escalation studies. In: Hawthorne MF, Shelly K, Wiersima RJ (eds) Frontiers in Neutron Capture Therapy. Kluwer Academic/Plenum Publisher, New York, pp 61–72, 2001

    Google Scholar 

  39. Fitzek MM, Thornton AF, Rabinov JD, Lev MH, Pardo FS, Munzenrider JE, Okunieff P, Bussiere M, Braun I, Hochberg FH, Hedley-Whyte ET, Liebsch NJ, Harsh GR 4th: Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial. J Neurosurg 91(2): 251–260, 1999

    PubMed  CAS  Google Scholar 

  40. Laramore GE, Griffin TW, Gerdes AJ, Parker RG: Fast neutron and mixed (neutron/photon) beam teletherapy for grades III and IV astrocytomas. Cancer 42: 96–103, 1978

    Article  PubMed  CAS  Google Scholar 

  41. Laramore GE, Wheeler FJ, Wessol DE, Stelzer KJ, Griffin TW: A tumor control curve for malignant gliomas derived from fast neutron radiotherapy data: implications for treatment delivery and compound selection. Proceedings of the Seventh International Symposium on Neutron Capture Therapy for Cancer, Zurich, CH, September 4–7, 1996. In: Larsson B, Crawford J, Weinreich R (eds) Advances in Neutron Capture Therapy Vol II, Chemistry and Biology, Elsevier, Amsterdam, pp 580–587, 1997

    Google Scholar 

  42. Jain RK: Vascular and interstitial barriers to delivery of therapeutic agents in tumors. Cancer Metastasis Rev 9(3): 253–266, 1990

    Article  PubMed  CAS  Google Scholar 

  43. Jain RK: Transport of molecules, particles, and cells in solid tumors. Annu Rev Biomed Eng 1 (Review): 241–263, 1999 (Review)

    Article  PubMed  CAS  Google Scholar 

  44. Smith DR, Chandra S, Coderre JA, Morrison GH: Ion microscopy imaging of 10B from p-boronophenylalanine in a brain tumor model for boron neutron capture therapy. Cancer Res 56(19): 4302–4306, 1996

    PubMed  CAS  Google Scholar 

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Correspondence to Aidnag Z. Diaz.

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Diaz, A.Z. Assessment of the results from the phase I/II boron neutron capture therapy trials at the Brookhaven National Laboratory from a clinician’s point of view. J Neuro-Oncol 62, 101–109 (2003). https://doi.org/10.1007/BF02699937

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