Boron neutron capture therapy: The past to the present

Abstract

We appreciate the interest of Dr. Theodore L. Phillips in our recent manuscript and the opportunity to clarify a point that was not clear in our article. We have treated 119 patients with intracranial tumors and one extracranial nerve-related tumor by boron neutron capture therapy (BNCT). These patients included malignant gliomas (grade 3-4) low grade gliomas (grade l-2), PNET, meningioma, sarcomas, and cerebral metastasis. Grade 3-4 gliomas have traditionally been called “glioblastomas,” but now there is a new tendency to call only grade 4 a glioblastoma. Grade 3 gliomas are sometimes referred to as “anaplastic gliomas” and grade 4 gliomas are termed “highly malignant tumors.” To avoid confusion of nomenclature, the authors have made it a rule to use only the term “grade 3-4 gliomas” in accordance with the World Health Organization (WHO) standard. As a new category, we introduced the name of PNET. Most of the patients who had been diagnosed as low grade astrocytoma before BNCT were recurrent cases and malignant change (grade 1-2, grade 3-4) was revealed at BNCT or after post-mortem examination. As for the boron concentration, we have reported on it in clinical cases and experimental studies. We took some samples from different tumor beds during operation to measure boron concentration. However, it is not possible to take all samples at exactly the same time. Another component is contents of the specimens. If the specimen is composed of active tumor cells and necrosis, the boron concentration in the tumor tissue must be demonstrated as lower levels than those in pure active tumor cells. Indeed there were varieties in boron concentration in the tumor tissue of the same patient. In such a case we calculated radiation dose according to most highest level of boron concentration. When we decide the radiation time, neutron fluence is limited below the safety radiation dose at the surface of the brain and to prevent radiation damage to blood vessels in brain (below 2.OE + 13 n/cm* on neutron fluence). If boron-concentration is about 28 ppm in tumor tissue. 15 Gy of physical dose by heavy particles including proton is radiated under neutron fluence 5.5E + 12 n/cm*. Dose at the brain surface excluding boron - 10 (n, alpha) reaction is 1.5-5 Gy. A recent experimental study using prompt gamma spectrometry demonstrated boron concentration in normal rain tissue was 2-5 ppm at 6 h after injection of BSH (50 mg/kg) and below 1.5 ppm at 24 h in live rabbits. The specimens collected at sametime intervals showed boron concentration below 1 ppm. This indicated that boron concentration in the tumor tissue may be more than 10 times of that in the normal brain tissue, which means efficacy and safety of BSH at BNCT. When investigators recall the poor results studied in the 1950s in the United States, they consider most related factors are neutron source and boron compound. Indeed such factors are very important, but we should not forget new diagnostic procedures such as computed tomography (CT) scan and magnetic resonance imaging (MRI). Dr. Hatanaka induced CT scan in 1972. After induction of MRI, we can decide much more correctly the margin of the tumor which shows us correct depth and width of the tumor. We then are able to radiate the tumor more correctly with enough dose of neutron beam even if we use thermal neutron. We believe BNCT is one of the best forms of treatment for malignant brain tumors, however, to treat deep seated brain tumors and recurrent tumors, as Dr. Theodore L. Phillips mentioned, we need further improvement such as a new boron compound and neutron beam.