International Journal of Radiation Oncology*Biology*Physics
Physics contributionFeasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma from a viewpoint of dose distribution analysis
Introduction
In Japan, since a major machinery maker announced that >40 people, who worked or often visited a factory in which highly toxic blue asbestos was used, died of mesothelioma in June 2005, malignant pleural mesothelioma (MPM) has become an object of public concern (1). Murayama et al. reported that after World War II, the amount of asbestos consumed in Japan increased to 250,000–350,000 tons per year until 1990, at which time a rapid decrease began, and that there would be about 100,000 deaths as a result of MPM in the next 40 years (2). Western Europe and the USA also face the same critical situation with asbestos-related MPM. In addition, the incidence rate of MPM is predicted to increase dramatically in developing countries because of the poor regulation and proliferation of the industrial use of asbestos (3).
The prognosis of MPM has been dismal, and the median survival length is 9–12 months without intervention (4). Although there is a bias for selecting patients, promising results have been reported by combined therapy of surgery, adjuvant radiotherapy, and chemotherapy—termed trimodality therapy (5). Unfortunately, the candidates for aggressive surgery, such as extrapleural pneumonectomy (EPP), are limited because of advanced disease, advanced age, and medical illness. Although experimental treatments such as immunotherapy or gene therapy have been attempted in patients with advanced MPM, no promising results have been reported (6, 7).
To investigate the new strategy for treating MPM patients who are inoperable, we designed a treatment protocol for boron neutron capture therapy (BNCT). BNCT is based on a nuclear reaction; nonradioactive isotope 10B atoms that have absorbed low energy (<0.5 eV) neutrons disintegrate into alpha (4He) particles and recoiled lithium nuclei (7Li). These particles deposit high energy along their very short paths (<10 μm) (8). Malignant cells with 10B are thus destroyed after thermal neutron irradiation. If a sufficient number of 10B atoms accumulate in the tumor cells, and the gradient of the amount of 10B atoms between the tumor and the surrounding normal tissues is large, then selective boron neutron capture irradiation will be successfully delivered to the tumor. The present study aimed to investigate the feasibility of BNCT for MPM from a viewpoint of dose–distribution analysis.
Section snippets
BNCT treatment planning using the Simulation Environment for Radiotherapy Applications (SERA) system
In the present study, we constructed treatment plans for 3 patients with MPM using SERA, a currently available BNCT treatment planning system (9, 10). The SERA system requires the entry of several user-defined parameters. These parameters include the 10B concentrations in the tumors and the normal lung, the nuclear composition of the tissues, the relative biologic effectiveness (RBE) of each component of the beam, and the compound biologic effectiveness (CBE) factors of the boron compounds. The
DVH analysis
Table 2 summarizes the DVH analysis for the normal lung. When the D05 dose to the normal ipsilateral lung was 5 Gy-Eq, the D95 and mean doses delivered to the normal lung were 2.2–3.6 and 3.5–4.2 Gy-Eq, respectively. Table 3 summarizes the results of the DVH analyses on the D95, D05, and mean doses for the tumors. When the D05 to the normal ipsilateral lung was 5 Gy-Eq, the mean dose delivered to the tumors was 22.4–27.2 Gy-Eq. The D95 and D05 doses were 9.6–15.0 and 31.5–39.5 Gy-Eq,
Discussion
One of the problems in management of MPM is that the proportion of patients who can withstand aggressive surgery is limited because of age, medical illness, and advanced MPM stage. For the patients who can tolerate surgery, trimodality therapy (consisting of aggressive surgery, such as EPP, followed by adjuvant radiotherapy and chemotherapy) has been proposed as a curative treatment, although it needs further improvement to achieve increasing survival rate. Sugarbaker et al. (15) reported that
Conclusions
Most patients with MPM cannot tolerate aggressive surgery because of advanced stage, age, and medical illness. MPM incidence is estimated to be increasing dramatically throughout the world. To overcome this critical situation, BNCT has the possibility of becoming a promising treatment for MPM.
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