Journal of Neuro-Oncology

, Volume 62, Issue 1, pp 87–99 | Cite as

Clinical Review of the Japanese Experience with Boron Neutron Capture Therapy and A Proposed Strategy Using Epithermal Neutron Beams

  • Yoshinobu Nakagawa
  • Kyonghon Pooh
  • Toru Kobayashi
  • Teruyoshi Kageji
  • Shinichi Uyama
  • Akira Matsumura
  • Hiroaki Kumada
Article

Abstract

Our concept of boron neutron capture therapy (BNCT) is selective destruction of tumor cells using the heavy-charged particles yielded through 10 B(n, α)7 Li reactions. To design a new protocol that employs epithermal neutron beams in the treatment of glioma patients, we examined the relationship between the radiation dose, histological tumor grade, and clinical outcome. Since 1968, 183 patients with different kinds of brain tumors were treated by BNCT; for this retrospective study, we selected 105 patients with glial tumors who were treated in Japan between 1978 and 1997. In the analysis of side effects due to radiation, we included all the 159 patients treated between 1977 and 2001.

With respect to the radiation dose (i.e. physical dose of boron n-alpha reaction), the new protocol prescribes a minimum tumor volume dose of 15 Gy or, alternatively, a minimum target volume dose of 18 Gy. The maximum vascular dose should not exceed 15 Gy (physical dose of boron n-alpha reaction) and the total amount of gamma rays should remain below 10 Gy, including core gamma rays from the reactor and capture gamma in brain tissue.

The outcomes for 10 patients who were treated by the new protocol using a new mode composed of thermal and epithermal neutrons are reported.

brain tumor glioblastoma radiation therapy boron neutron capture therapy heavy-charged particle 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    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, 1998Google Scholar
  2. 2.
    Fulton DS, Urtason RC, Scott-Brown I, Johnson ES, Mielke B, Carry B: Increasing radiation dose intensity using hyperfractionation in patients with malignant glioma. J Neuro-Oncol 14: 63–72, 1992Google Scholar
  3. 3.
    Blasberg RG, Groothuis DR: Chemotherapy of brain tumors: physiological and pharmacokinetic considerations. Semin Oncol 13: 70–82, 1986Google Scholar
  4. 4.
    Castro JR, Phillips TL, Prados M, Gutin P, Larson DA, Petti PL, Daftari IK, Collier JM, Lillis-Hearne P: Neon heavy charged particle radiotherapy of glioblastoma of the brain. Int J Radiat Oncol Biol Phys 38: 257–261, 1997Google Scholar
  5. 5.
    Nakagawa Y, Hatanaka H: Boron neutron capture therapy - clinical brain tumor study. J Neuro-Oncol 33: 105–115, 1997Google Scholar
  6. 6.
    Hatanaka H: Clinical experience of boron-neutron capture therapy for glioma - a comparison with conventional chemoimmuno-radiotherapy: boron. In: Hatanaka H (ed) Neutron Capture Therapy forTumors. Nishimura & Co., Niigata City, 1986, pp 349–379Google Scholar
  7. 7.
    Nakagawa Y, Kageji T, Hatanaka H: Thermal neutron capture therapy for brain stem and skull base tumors; heavy water and multiportal neutron delivery. In: Soloway AH, Barth RF, Carpenter DE (eds) Advances in Neutron Capture Therapy. Plenum Press, New York, 1993, pp 671–676Google Scholar
  8. 8.
    Blagojevic N, Storr GJ, Allen B, Hatanaka H, Nakagawa Y: Role of heavy water in boron neutron capture therapy. In: Zammenhof RG (ed) Topics in Dosimetry & Treatment Planning for Boron Neutron Capture Therapy. Advanced Medical Publishing, Madison, 1994, pp 125–134Google Scholar
  9. 9.
    Nakagawa Y: What were important factors in patients treated by BNCT in Japan? In: Larsson B (ed) Neutron Capture Therapy,Vol 1, Medicine and Physics. Elsevier, Amsterdam, 1997, pp 65–70Google Scholar
  10. 10.
    Kageji T, Nakagawa Y, Kitamura K, Matsumoto K, Hatanaka H: Pharmacokinetics and boron uptake of BSH (Na2B12H11SH) in patients with intracranial tumors. J Neuro-Oncol 33: 117–130, 1997Google Scholar
  11. 11.
    Kobayashi T, Sakurai Y, Kanda K, Fujita Y, Ono K: The more modelling and basic characteristics of the heavy water neutron irradiation facility of the Kyoto University research reactor mainly for neutron capture therapy. Nucl Technol 131: 354–378, 2001Google Scholar
  12. 12.
    Holland EC: Glioblastoma multiforme: the terminator. Proc Natl Acad Sci (USA) 97: 6242–6244, 2000Google Scholar
  13. 13.
    Burger P, Vogel S, Green S, Strike T: Glioblastoma multiforme and anaplastic astrocytoma, pathologic criteria and prognostic implications. Cancer 56: 1106–1111, 1985Google Scholar
  14. 14.
    Kitano K: A method for calculating the absorbed dose near interface from 10B(n α)7Li reaction. Radiat Res 61: 304–315, 1975Google Scholar
  15. 15.
    Rydin RA, Deutsch OL, Murray BW: The effect of geometry on capillary wall dose for boron neutron capture therapy. Phys Med Biol 21: 134–138, 1976Google Scholar
  16. 16.
    Kageji T, Nagahiro S, Kitamura K, Nakagawa Y, Hatanaka H, Haritz D, Grochulla F, Haselsberger K, Gabel D: Optimal timing of neutron irradiation for boron neutron capture therapy after intravenous infusion of sodium borocaptate in patients with glioblastoma. Int J Radiat Oncol Biol Phys 51: 120–130, 2001Google Scholar
  17. 17.
    Kumada H, Yamamoto K, Torii Y, Matsumura A, Yamamoto T, Nakagawa Y, Horiguchi Y: Development of computational dosimetry system and measurement of dose distribution in water head phantom for BNCT in JAERI. In: Proceedings of the 2000 Workshop on Utilization of Research Reactors. JAERI-Conf 2001. 17: 357–362, 2001Google Scholar
  18. 18.
    Mehta MP, Masciopinto J, Rozental J, Levin A, Chappel R, Bastine K, Miles J, Turski P, Kubsad S, Mackie T, Kinsella T: Stereotactic radiosurgery for glioblastoma multiforme: report of a postoperative study evaluating prognostic factors and analyzing long-term survival advantage. Int J Radiat Oncol Biol Phys 30: 541–549, 1994Google Scholar
  19. 19.
    Kumar PP, Good RR, Jones EO, Patil AA, Leibrock LG, McComb RD: Survival of patients with glioblastoma multiforme treated by intraoperative high-activity cobalt 60 endocurie therapy. Cancer 64(7): 1409–1413, 1989Google Scholar
  20. 20.
    Tagian A, Ramsay J, Turner JA, Budach W, Gioloso D, Pardo F, Okuniff P, Bleehen N, Urtasun R, Suit H: Int J Radiat Oncol Biol Phys 25: 243–249, 1993Google Scholar
  21. 21.
    Locher GL: Biological effects and therapeutic possibilities of neutrons. Am J Roentgenol 36: 1–13, 1936Google Scholar
  22. 22.
    Sweet WH, Javid M: The possible use of neutron-capturing isotopes such as boron-10 in the treatment of neoplasms. I. Intracranial tumor. J Neurosurg 9: 200–209, 1952Google Scholar
  23. 23.
    Javid M, Brownell GL, Sweet WH: The possible use of neutron-capturing isotopes such as boron-10 in the treatment of neoplasms. II. Computation of the radiation energy and estimates of effects in normal and neoplastic brain. J Clin Invest 31: 603–610, 1952Google Scholar
  24. 24.
    Farr LE, Sweet WH, Robertson JS, Foster CG, Locksley HB, Sutherland DL, Mendelsohn ML, Stickley EE: Neutron capture therapy with boron in the treatment of glioblastoma multiforme. AJR 71: 279–293, 1954Google Scholar
  25. 25.
    Soloway AH, Hatanaka H, Davis MA: Penetration of brain and brain tumor. Tumor-binding sulfhydryl boron compounds. J Med Chem 10: 714–717, 1971Google Scholar
  26. 26.
    Hatanaka H, Amano K, Kanemitsu H, Ikeuchi I, Yoshizaki T: Boron uptake by human brain tumors and quality control of boron compounds. In: Hatanaka H (ed) Neutron Capture Therapy for Tumors. Nishimura & Co., Niigata City, 1986, pp 77–106Google Scholar
  27. 27.
    Nakagawa Y, Pooh K, Sone M, Kageji T, Nakamichi M, Takahashi H, Amemiya K, Gabel D: Determination of BSH absorbed in tumor tissue. In: Hawthorne MF, Shelly K, Wiersema J (eds) Frontiers in Neutron Capture Therapy, Vol 2. Kluwer Acad/Plenum Publishers, New York, 2001, pp 933–937Google Scholar
  28. 28.
    Amemiya K, Takahashi H, Nakazawa M, Shimizu H, Majima T, Nakagawa Y, Yasuda N, Yamamoto M, Kageji T, Nakamichi M, Hasegawa T, Kobayashi T, Sakurai Y, Ogura K: Soft X ray imaging using CR-39 plastics with AFMreadout. Nucl Instrum Meth Phys Res B 187: 361–366, 2002Google Scholar
  29. 29.
    Hatanaka H: Boron-neutron capture therapy for tumors. In: Karim ABM, Laws, ER Jr (eds) Glioma. Springer-Verlag, Berlin, 1991, pp 233–249Google Scholar
  30. 30.
    Laramore GE, Spence AM: Boron neutron capture therapy (BNCT) for high grade glioma of the brain: a cautionary note. Int J Radiat Oncol Biol Phys 36: 241–246, 1996Google Scholar
  31. 31.
    Higashi H, Matsumoto K, Ono Y, Shinohara C, Nakagawa M, Tsuno K, Furuta T, Ohmoto T: Patterns of recurrence in malignant gliomas after brachytherapy. No Shinkei Geka 22(4): 321–326, 1994Google Scholar
  32. 32.
    Coderre JA, Elowitz EH, Chadha M, Bergland R, Capala J, Joel DD, Liu HB, Slatkin DN, Chanana AD: Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: trial design and early results. J Neurosurg 33: 141–152, 1997Google Scholar
  33. 33.
    Sauerwein W: The clinical project at HFR Petten: a status report. In: Larsson B, Crawford J, Weinreich R (eds) Advances in Neutron Capture Therapy: Medicine and Physics. Elsevier, Amsterdam, 1997, pp 77–84Google Scholar
  34. 34.
    Gabel D, Foster S, Fairchild RG: The Monte Carlosimulation of the biological effect of the 10B(n α)7Li reaction in cells and tissue and its implication for boron neutron capture therapy. Radiat Res 111: 25–36, 1987Google Scholar
  35. 35.
    Coderre JA, Makar MA: Radiobiology of boron neutron capture therapy: problems with the concept of relative biological effectiveness. In: Allen B, Moore D, Harrington B (eds) Progress in Neutron Capture Therapy for Cancer. Plenum Press, New York, 1992, pp 463–468Google Scholar
  36. 36.
    Morris GM, Coderre JA, Hopewell JW, Micca PL, Rezvani M: Response of rat skin to boron neutron capture therapy with p-boronophenylalanine or borocaptate sodium. Radiother Oncol 32: 144–153, 1994Google Scholar
  37. 37.
    Broerse JJ, Barendren GW: Relative biological effectiveness of fast neutron for effects on normal tissues. Curr Top Radiat Res Q8: 305–350, 1973Google Scholar
  38. 38.
    Ward JF: The yield of DNA double-strand breaks produced intracellularly by ionizing radiation: a review. Int J Radiat Biol 57(6): 1141–1150, 1990Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Yoshinobu Nakagawa
    • 1
  • Kyonghon Pooh
    • 1
  • Toru Kobayashi
    • 2
  • Teruyoshi Kageji
    • 3
  • Shinichi Uyama
    • 3
  • Akira Matsumura
    • 4
  • Hiroaki Kumada
    • 5
  1. 1.Department of NeurosurgeryNational Kagawa Children's HospitalKagawa
  2. 2.Kyoto University Research Reactor InstituteKyoto
  3. 3.Department of NeurosurgeryUniversity of TokushimaTokushima
  4. 4.Department of Neurosurgery, Institute of Clinical MedicineUniversity of TsukubaJapan
  5. 5.Department of Research Reactor, Tokai Research EstablishmentJapan Atomic Energy Research InstituteJapan

Personalised recommendations