**3. The practice of neutron capture therapy**

### **3.1 Boron drugs**

In many national and international BNCT clinical studies using BPA, neutron beam irradiation has been performed in many cases during the clearance phase after the intravenous infusion of BPA. This, however, required simulation of the in vivo dynamics of boron concentration during irradiation, resulting in an increased importance of subsequent evaluation. In promoting medical applications based on the idea of prescription dose, the accuracy of pre-prediction was pursued, and it was considered that the continuous intravenous infusion during the irradiation used in the clinical research of head and neck cancer using nuclear reactors could solve this problem, and we have taken this approach in our brain tumor treatment. To maintain the concentration of 10B in the tumor tissue that is expected to have a therapeutic effect during thermal neutron beam irradiation, it has been adopted as a dosage and administration method of BPA to maintain the concentration of 10B in whole blood at 20 ppm or higher.

In 15 patients with recurrent head and neck tumors, BPA (fructose solution) 500 mg/kg (400 mg/kg was administered at a constant rate of 200 mg/kg/hr. for 2 h, followed by reducing the infusion rate of the remaining 100 mg/kg to approximately 100 mg/kg/hr. at a constant rate until the end of the irradiation) was administered at the reactor of the Kyoto University Institute for Integrated Radiation and Nuclear Science [14]. In BNCT of malignant glioma carried out by Osaka Medical University adopting the same protocol, an average result of 27 ppm in the whole blood boron concentration was obtained. On the other hand, the whole blood boron level immediately after irradiation in patients treated with BPA (fructose solution) 250 mg/kg could not be maintained at 20 ppm, and even in patients treated with 500 mg/kg, the mean value of whole blood boron level immediately after irradiation decreased to 19.5 ppm, and the fluctuation before and after irradiation was greater compared with 30.4 ppm before irradiation [14]. These experiences suggest that a dose of BPA 500 mg/kg (200 mg/kg/hr. × 2 hr. + 100 mg/kg of BPA at a constant rate of approximately 100 mg/kg/hr. to match the end of irradiation time) is expected to exceed 20 ppm of whole blood boron concentration during irradiation, and that the method of administration that satisfies the conditions for maintaining stable concentrations before and after irradiation.

In a phase II clinical trial (BNCT) in Sweden, 30 patients with glioblastoma were treated with a 6-hour infusion of 900 mg/kg of BPA followed by irradiation 2 hours later. Although transient serious adverse events have been observed, irreversible events have not been observed, and the tolerability of BNCT at 900 mg/kg BPA and 2 hours after 6 hours of intravenous infusion was confirmed [14].

### **3.2 Dose prescriptions**

Factors on the radiation side that generally govern the effects on normal tissue include radiation quality, distribution of dose in the tissue and size of the irradiated volume, and on the tumor side include the presence of a history of radiotherapy and the effect of the tumor on the surrounding normal tissue. It is required that the dose in the irradiated volume is as uniform as possible in order to accurately evaluate the relationship between the reaction of the tissue and the dose. In conventional X-ray or particle therapy, it is possible to irradiate evenly a certain volume of radiation,

*Boron Compounds for Neutron Capture Therapy in the Treatment of Brain Tumors DOI: http://dx.doi.org/10.5772/intechopen.106202*

#### **Figure 4.**

*Example of dose calculation (dose planning for a simulated brain tumor) using the BNCT dose calculation program (NeuCure® dose engine Sumitomo heavy industries, ltd.) the graphical user Interface (GUI) enables detailed visualization of dose distribution, dose volume histogram (DVH) plotting, and reference and modification of various parameters in one GUI.*

including the normal brain around the brain tumor. However, for neutron radiation, the attenuation of neutron intensity in the tissue is large and delivering a uniform irradiation becomes difficult.

The skin is a thin layer of tissue that is not affected much by neutron attenuation, so it is possible to define the dose at the skin surface. It's also regarded to be more versatile when it comes to expanding its indication to other organs throughout the body.

Skin dose and dose distribution in the normal brain (maximum dose) can also be associated, and the idea of limiting skin dose so that the maximum dose in the normal brain does not exceed the tolerable dose usually obtained from experience and knowledge of radiotherapy has been adapted. In the case of brain tumors, it has been reported by Mayer et al. that necrosis of normal brain tissue develops when the cumulative dose of initial radiotherapy and re-radiotherapy exceeds 100Gy (2Gy

fractionated irradiation) [15]. In clinical practice, the effectiveness and safety of BNCT are considered, and the eligibility is judged, and the plan is made using the skin dose as an index.
