Clinical review of the japanese experience with boron neutron capture therapy and a proposed strategy using epithermal neutron beams

Yoshinobu Nakagawa1, Kyonghon Pooh1, Toru Kobayashi2, Teruyoshi Kageji3, Shinichi Uyama3, Akira Matsumura4, Hiroaki Kumada5
1Department of Neurosurgery, National Kagawa Children's Hospital, Zentsuji City Kagawa, Japan
2Kyoto University Research Reactor Institute, Kyoto
3Department of Neurosurgery, University of Tokushima, Tokushima
4Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Japan
5Department of Research Reactor, Tokai Research Establishment, Japan Atomic Energy Research Institute, Japan

Tóm tắt

Our concept of boron neutron capture therapy (BNCT) is selective destruction of tumor cells using the heavy-charged particles yielded through10B(n, α)7Li 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.

Từ khóa


Tài liệu tham khảo

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

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, 1992

Blasberg RG, Groothuis DR: Chemotherapy of brain tumors: physiological and pharmacokinetic considerations. Semin Oncol 13: 70–82, 1986

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, 1997

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

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 for Tumors. Nishimura & Co., Niigata City, 1986, pp 349–379

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 671–676

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 125–134

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 65–70

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, 1997

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, 2001

Holland EC: Glioblastoma multiforme: the terminator. Proc Natl Acad Sci (USA) 97: 6242–6244, 2000

Burger P, Vogel S, Green S, Strike T: Glioblastoma multiforme and anaplastic astrocytoma, pathologic criteria and prognostic implications. Cancer 56: 1106–1111, 1985

Kitano K: A method for calculating the absorbed dose near interface from 10B(n α)7 Li reaction. Radiat Res 61: 304–315, 1975

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, 1976

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, 2001

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, 2001

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, 1994

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, 1989

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, 1993

Locher GL: Biological effects and therapeutic possibilities of neutrons. Am J Roentgenol 36: 1–13, 1936

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, 1952

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, 1952

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, 1954

Soloway AH, Hatanaka H, Davis MA: Penetration of brain and brain tumor. Tumor-binding sulfhydryl boron compounds. J Med Chem 10: 714–717, 1971

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 77–106

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 933–937

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 AFM readout. Nucl Instrum Meth Phys Res B 187: 361–366, 2002

Hatanaka H: Boron-neutron capture therapy for tumors. In: Karim ABM, Laws, ER Jr (eds) Glioma. Springer-Verlag, Berlin, 1991, pp 233–249

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, 1996

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, 1994

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, 1997

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 77–84

Gabel D, Foster S, Fairchild RG: The Monte Carlo-simulation of the biological effect of the 10B(n α)7 Li reaction in cells and tissue and its implication for boron neutron capture therapy. Radiat Res 111: 25–36, 1987

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 463–468

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, 1994

Broerse JJ, Barendren GW: Relative biological effectiveness of fast neutron for effects on normal tissues. Curr Top Radiat Res Q8: 305–350, 1973

Ward JF: The yield of DNA double-strand breaks produced intracellularly by ionizing radiation: a review. Int J Radiat Biol 57(6): 1141–1150, 1990