Treatment planning system and BNCT system for boron neutron capture therapy (BNCT)

Abstract

To provide a treatment planning system for boron neutron capture therapy.SOLUTION: A treatment planning system for BNCT comprises storage means which stores an ideal patient position that is considered to be a position determined for each patient with respect to a neutron beam irradiation port of a neutron beam irradiation device and an ideal position for a neutron beam treatment for the patient, an estimated gradually-reduced boron concentration value that is estimated from the in-blood boron concentration measurement value right before assumed multiple times of irradiation, and an assumed boron concentration application dose that is calculated by calculation means that calculates the application dose based on each estimated gradually-reduced boron concentration value. The treatment planning system for BNCT selects the estimated gradually-reduced boron concentration value closest to the measurement value upon receiving the in-blood boron concentration measurement value right before irradiation, and transmits the assumed boron concentration application dose based on the boron concentration value to a BNCT system.SELECTED DRAWING: Figure 20

Description

Technical Field

[0001] The present invention relates to a treatment planning system for Boron Neutron Capture Therapy (hereinafter referred to as BNCT), a BNCT system, and BNCT.

Background Art

[0002] The types of radiation are roughly classified into alpha (α) rays, beta (β) rays, gamma (γ) rays, X-rays, charged particle beams such as proton beams and heavy ions, and neutron beams. Among them, the latter ones have a greater ability to penetrate substances (penetrating power).

[0003] A typical example of the effective use of radiation is its application in the medical field. In particular, these radiations are used in cancer treatment, such as X-ray treatment using X-rays and "particle beam therapy" using particles such as protons and carbon. When performing cancer treatment using radiation, radiation is concentrated on the cancer lesion as much as possible, while minimizing the exposure of surrounding normal tissues to radiation. Treatment is carried out by utilizing the difference in the radiation doses applied to the cancer lesion and the normal tissues. In current radiotherapy, in order to obtain a medical effect, in the case of cancers where the cancer lesion and normal tissues are close to each other or cancers where the cancer infiltrates into normal tissues, a large amount of radiation is also applied to the normal tissues, which may cause side effects and late complications.

[0004] In recent years, in order to avoid such side effects and late complications, methods of precisely irradiating radiation to cancer have been studied. Examples include "Intensity Modulated Radiation Therapy (IMRT)", which is high-dose irradiation to the exact cancer site by stereotactic irradiation, "Motion Tracking Radiation Therapy", which irradiates radiation in accordance with the movement inside the body such as the patient's breathing and the movement of the heart, and "Particle Beam Therapy", which intensively applies heavy particle beams and proton beams with high treatment effects.

[0005] In addition to these X-ray and particle beam therapies, one treatment that has attracted particular attention in recent years is "Boron Neutron Capture Therapy (BNCT)," which combines neutron beams with boron compounds to selectively destroy cancer at the cellular level. Neutron beams, which have the greatest penetrating power among all types of radiation, are further classified according to their energy levels, for example, as follows. The values ​​in parentheses indicate the energy of each type of neutron beam; a higher number indicates greater penetrating power.

[0006] Neutrons are classified into four categories based on their penetrating power, from weakest to strongest: cold neutrons (~0.005 eV), thermal neutrons (~0.025 eV), epithermal neutrons (0.025 eV~10 keV), and fast neutrons (10 keV and above). However, there are various theories regarding the classification of neutron radiation, and the energy values ​​in parentheses are not strictly defined. For example, some theories define the energy range of thermal neutrons as below 0.5 eV, and the energy range of epithermal neutrons as between 0.5 eV and 10 keV or below 40 keV.

[0007] Furthermore, neutrons have no electric charge and are therefore easily absorbed when they collide with atomic nuclei. This absorption of neutrons is called neutron capture. In particular, boron-10, an isotope of boron, has the property of having a very high probability (called the cross-sectional area) of capturing thermal neutrons compared to other elements. Boron-10 that has captured a thermal neutron undergoes the following nuclear reaction. 10 B+n→ 7 Li+ 4 He It undergoes a nuclear reaction, releasing helium nuclei (alpha particles) and lithium nuclei, which have a high cell-killing effect. Furthermore, the generated alpha particles and lithium nuclei travel only a few micrometers within normal tissue before stopping.

[0008] BNCT utilizes this physical property. Before treatment, a compound containing boron-10 (hereinafter referred to as boron compound) is introduced into the cancer cells by injection or intravenous drip. Then, thermal neutrons are irradiated onto the cancerous lesion, causing a neutron capture reaction within the cancer cells. The resulting helium nuclei (alpha rays) and lithium nuclei destroy the cancer's DNA. Since cancer cells are only about 10 micrometers in size, the alpha rays and lithium nuclei remain within the cancer cells and do not affect the surrounding normal tissue. Based on this principle, BNCT possesses the extremely advantageous characteristic of being able to destroy cancer at the cellular level while preserving normal tissue.

[0009] Cancer cells readily absorb boron compounds into their cells during their rapid proliferation process, and BNCT utilizes this property to effectively destroy only cancer cells. This principle was proposed by Locher in the United States about 80 years ago and has long been recognized as an extremely superior form of radiotherapy, with minimal impact on the patient's healthy tissues. Research and development have been conducted in various countries. However, there are many important development challenges, such as developing neutron beam generators, selection devices to select neutron beam types effective for treatment, and eliminating the impact on healthy tissue other than the affected area of ​​the patient (i.e., causing boron compounds to form only on cancer cells). As a result, it has not yet become a widely adopted treatment method.

[0010] The following is an example of selecting neutron beam types for effective use in medical applications, particularly in BNCT. First, we will eliminate as much as possible high-energy neutron radiation that has adverse effects on the body (e.g., fast neutron radiation), then reduce low-energy neutron radiation that has little penetration into living organisms (e.g., thermal neutron radiation, cold neutron radiation), and increase the proportion of medium-energy neutron radiation that does penetrate living organisms (e.g., epithermal neutron radiation (0.5eV~10keV)).

[0011] This makes it possible to create medical neutron beams that can be effectively used in BNCT. Epothermic neutron beams have relatively high penetration depth into the patient's tissues, and when the low-energy portion of these medium-velocity neutron beams and epithermic neutron beams are irradiated to the head, for example, unless the cancer is very deep, craniotomy is not required, and effective irradiation of the affected area is possible without craniotomy.

[0012] On the other hand, extremely low-energy neutron beams, such as thermal and cold neutron beams, have poor penetration depth, and surgical treatments using these neutron beams are used for superficial cancers (e.g., skin cancer). Furthermore, when these low-energy neutron beams are used to treat malignant brain tumors, craniotomy is required to deliver the neutrons to the lesion, which places a heavy burden on the patient. In BNCT, to enhance the therapeutic effect, it is considered important to irradiate the affected area with the necessary amount of neutrons, primarily epithermal neutrons, with some thermal neutrons included.

[0013] Specifically, the epithermal neutron flux required for an irradiation time of approximately 1 hour is approximately 0.5 to 1.0 × 10⁻¹⁰ at the irradiation port. 9 [n / cm 2 This will result in [ / sec]. To generate epithermal neutrons of this intensity, the proton emission energy from the accelerator, which is the neutron source, is estimated to be approximately 5-30 MeV when beryllium (Be) is used as the neutron beam target, and the average current is estimated to be approximately 1 mA to several mA. When lithium (Li) is used as the target, the proton emission energy is estimated to be around 2.5 MeV, and the average current is estimated to be around 10 mA to 30 mA.

[0014] In radiation therapy such as X-ray therapy, particle beam therapy, and BNCT, dose evaluation is performed in advance using a treatment planning system to determine the irradiation conditions. Among the irradiation conditions, the patient's position is particularly important, as it defines the patient's position relative to the irradiation beam (irradiation port).

[0015] Generally, in radiation therapy (including BNCT), the patient is fixed in a predetermined position according to the irradiation conditions before treatment, and then the patient is irradiated with radiation. In the case of current radiation therapy, excluding BNCT, the irradiation time is very short (less than 1 minute), so the treatment (irradiation) is performed on the premise that the patient does not move (except for breathing), and the dose administered to the patient is assumed to be the dose calculated in advance during the treatment planning stage.

[0016] Therefore, if the patient moves during irradiation, the radiation may not reach the planned area, the lesion may not receive a sufficient dose for treatment, and the surrounding healthy tissue may receive a dose exceeding the planned dose. Therefore, in X-ray therapy and particle beam therapy, changes in the patient's position during irradiation are monitored by doctors and medical staff using camera monitors. If the patient moves significantly during treatment, the treatment is interrupted, the patient's position is readjusted, and irradiation is resumed. Furthermore, in addition to unexpected positional changes in the patient, for X-ray therapy and proton beam therapy for lung cancer and liver cancer, where organs constantly and periodically change position due to respiration, irradiation accuracy is ensured by turning the beam on and off in accordance with the patient's breathing. For example, in X-ray therapy and particle beam therapy, the movement of the lesion during irradiation is tracked by using fluoroscopic X-rays between beam irradiations to determine the lesion's position and then performing the treatment. In this case, there are two methods: the "ambush irradiation method," which irradiates the lesion when the therapeutic beam enters the target area, and the "dynamic tracking irradiation method," which adjusts the beam irradiation range to irradiate a moving lesion. Furthermore, as a detection method synchronized with respiration, changes in organ position are indirectly measured by monitoring with laser rangefinders. In addition, a technique has been put into practical use in which gold markers are implanted around the lesion to confirm the movement and position of the lesion (due to respiration) before and after beam irradiation.

[0017] On the other hand, in the case of BNCT, the treatment time is about one hour, which is extremely long compared to other radiation therapies. Therefore, the possibility of the patient moving during prolonged irradiation is higher than with other radiation therapies. To avoid this, completely immobilizing the patient would place a great burden on them, so strong immobilization is not performed. In other words, with BNCT, the treatment time is long, about one hour, and since no strong immobilization is performed, there is a very high possibility that the patient's position will change during irradiation. If irradiation is completed while the patient's position has shifted, a significant difference will occur from the dose initially planned. In BNCT, the patient's movement during irradiation is monitored using a camera, and treatment is continued even if there is some movement of the patient (such as positional changes due to respiration, which are within the acceptable range for BNCT). Furthermore, in the case of BNCT, a boron compound is administered to the patient, and since the blood concentration of boron decreases over time, there is a risk that the boron concentration will fall below the level required for treatment if the irradiation time exceeds one hour. Therefore, if neutron irradiation is turned off during irradiation to perform alignment work, the decrease in boron concentration will make it difficult to continue the treatment, and the treatment itself will become impossible. For this reason, neutron irradiation is usually not controlled by turning the neutron output on or off, and irradiation is performed continuously. Therefore, in the case of BNCT, treatment is usually completed in a single continuous irradiation. Consequently, if the irradiation is completed with the target area misaligned, a significant difference will occur from the dose originally planned.

[0018] (BNCT treatment procedure) Figure 1 shows the general treatment procedure for BNCT. Typically, when a patient suitable for BNCT is identified, a treatment plan is first created using a Treatment Planning System (TPS). This plan involves determining the optimal irradiation conditions for the patient, including the beam's position, angle, distance, and duration. This planning process is performed 1-2 weeks before irradiation.

[0019] After formulating an optimal treatment plan using TPS, the actual treatment day arrives. On the day, administration of the boron compound (BPA) is carried out approximately 1 to 2 hours before the actual irradiation. When a certain amount of the boron compound has been administered and the boron compound has accumulated in the cancer lesion, the patient is taken to the irradiation room. In the actual irradiation room, the patient is accurately fixed at the irradiation position. This irradiation position is defined within the irradiation conditions derived by TPS, and the patient is fixed according to those conditions. For BNCT irradiation, depending on the location of the lesion, the patient may be irradiated lying down or sitting.

[0020] Conventional patient alignment methods involve aligning using multiple laser beams or aligning while checking the positional relationships of the eyes, nose, ears, etc. with respect to the beam hole using visual inspection or a ruler (In X-ray therapy and particle beam therapy, etc., since an X-ray fluoroscope can be installed in the irradiation room, the patient fixed roughly at the irradiation position is fluoroscoped with X-rays and an X-ray image is taken to confirm the position of the cancer lesion. However, since BNCT uses neutrons, if an X-ray fluoroscope is installed in the irradiation room, the device will be immediately damaged by the neutrons, so an X-ray fluoroscope cannot be installed and alignment based on confirming the lesion position by conventional X-ray fluoroscopy cannot be performed).

[0021] Before starting the irradiation, blood is drawn several times to measure the boron concentration in the blood. Based on this measurement of the boron concentration, the boron concentration during irradiation is estimated. Here, the ratios of the boron concentration in each organ and tissue such as the brain, skin, mucosa, and cancer lesion to the boron concentration in the blood are known from past research. For example, in the case of BPA, if the boron concentration in the blood is set to 1, the concentration ratio of the skin is 1.2, the brain is 1.0, and cancer cells are 3 to 5. Therefore, by measuring the boron concentration in the blood by blood sampling, the boron concentration accumulated in each tissue can be estimated. During irradiation, the boron concentration in the blood and various organs / tissues changes (decreases) sequentially. However, since the boron concentration cannot be measured during irradiation, based on the measured value just before irradiation, the drug kinetics, and the decay curve of the boron concentration based on past research, the change in the boron concentration is estimated. In actual irradiation, a method is also used where the "average boron concentration" during irradiation is estimated to calculate the "average boron dose" during irradiation (the boron dose per 1 ppm is calculated using TPS). Here, the "boron dose" refers to the dose given to cells by the α-rays and lithium nuclei generated by the reaction of neutrons absorbed by boron and boron-10. The boron dose is also referred to as the boron concentration-imparted dose hereinafter. Since a difference occurs in the boron concentration between cancer cells and normal tissues, a difference also occurs in the boron dose, and this difference in the boron dose becomes the therapeutic effect of BNCT (the difference in dose between cancer cells and normal cells).

[0022] Patient alignment (fixation to the "ideal" irradiation position guided by TPS) is completed, blood sampling is performed to estimate the average boron concentration, the irradiation time is determined, and irradiation is started. However, the temporal change in the blood boron concentration may vary among patients, and the estimation of the average boron concentration during irradiation from the measured value just before irradiation may not be accurate enough. After irradiation, blood sampling is performed again to actually measure the boron concentration after irradiation, and when retrospectively evaluating the average boron concentration during irradiation, it often deviates significantly from the average boron concentration predicted / estimated before irradiation. This deviation error can often reach 10 - 20%.

[0023] The dose rate delivered to cancerous lesions and normal tissue also changes depending on the boron concentration. When the boron concentration is high, the dose rate delivered to that area is also high, so the irradiation time is shorter. Conversely, when the boron concentration is low, the irradiation time is longer. The irradiation time for BNCT is controlled by the maximum neutron dose delivered to normal tissue (for example, 10 Gy). For example, if the boron dose rate is 1 Gy / ppm / hr per 1 ppm of boron concentration, then when the boron concentration is 10 ppm, the boron dose rate will be 10 Gy / hr, meaning that 1 hour is required to deliver the maximum boron dose of 10 Gy. If the boron concentration is 20 ppm, the dose rate will be 20 Gy / hr, so 0.5 hours = 30 minutes of irradiation is sufficient to deliver 10 Gy.

[0024] Since the irradiation time changes depending on the prior estimates of the boron concentration and boron dose, estimating the boron concentration and predicting the boron dose based on it becomes extremely important.

[0025] Regarding patient positioning, conventional methods do not account for patient movement during irradiation. Normally, (1) The patient is fixed in the position specified by TPS. (2) The patient must not move during irradiation. The irradiation will be carried out under the assumption that... If this assumption is guaranteed, then neutrons can be irradiated to the lesion and surrounding organs according to the TPS irradiation plan, meaning that if irradiation is performed for the duration determined by the TPS, the calculated dose can be delivered to each area. However, in reality, (1) In some cases, it may not be possible to align the TPS according to the plan during the pre-irradiation positioning stage. (2) Due to the long irradiation time, the patient may move during irradiation, making it impossible to maintain the irradiation conditions determined by TPS, and neutrons may start hitting areas other than those planned. This situation arises.

[0026] The content of Patent Document 1 below (a prior application by Sumitomo Heavy Industries, Ltd.) is as follows: the discrepancy between the "ideal" irradiation condition position derived by this TPS and the actual position (before irradiation) when the patient is fixed is predicted in advance, and dose calculations are performed (under many positional discrepancy conditions), and the calculation result of the positional condition closest to the discrepancy is adopted from the prior calculations. The irradiation time is also slightly changed to match the positional discrepancy.

[0027] (Treatment planning system) Figure 2 shows the flow of dose calculation applied to a patient under certain irradiation conditions using TPS. Figure 3 shows the flow of treatment planning (determination of optimal irradiation conditions) using TPS. TPS first creates a 3D model of the patient by acquiring CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) data. For this 3D model, the expected irradiation conditions (beam incidence position, angle, distance, etc.), i.e., calculation conditions, are set. Once these calculation conditions are determined, TPS creates a calculation model and inputs it into a Monte Carlo (MC) calculation code to perform the calculation. In the MC calculation, the neutron distribution = dose distribution in the patient's body is calculated under those irradiation conditions (a simulation of irradiation is performed).

[0028] Normally, it's not possible to determine the optimal irradiation conditions with just one calculation (one set of calculation conditions). Therefore, the irradiation conditions are changed, and further calculations are performed under those changed conditions. The results of the previous calculation and the calculation after the change are then compared, and the better condition is selected. This process is repeated many times, the calculation results are compared, and finally, the (optimal irradiation conditions) = (the irradiation conditions that yielded the best results among all the calculations performed) are selected and used as the irradiation conditions for actual irradiation.

[0029] (Changes in dose distribution due to patient positional displacement) Figure 4 shows the procedure during BNCT in a nuclear reactor. Immediately before irradiation, after the patient has been fixed in the irradiation position, a device called a "3D digitizer" is used to measure the positions of the patient's eyes, nose, ears, etc. The positions (coordinates) of the eyes, nose, and ears in the upper middle table of Figure 4 represent the coordinates of each part of the eye, nose, and ears if they had been fixed in the "ideal" irradiation position during the pre-treatment irradiation simulation (treatment planning) using TPS.

[0030] However, the coordinates measured by the 3D digitizer show a deviation from the ideal position (the lower numbers in the table in the middle of Figure 4 indicate the amount of deviation). Traditionally, several measurements using this 3D digitizer were performed to adjust the alignment and confirm that the irradiation conditions were as close as possible to the "ideal" conditions before starting irradiation. Even then, there was still a slight deviation. Figure 4 shows this slight deviation, but irradiation was performed assuming it was OK.

[0031] The lower right image in Figure 5 shows how the actual patient position immediately before irradiation, as measured by this 3D digitizer, was reproduced using TPS. Comparing the upper right image, which shows the irradiation conditions, with the lower right image, which shows (actual fixation) = (actual irradiated patient position), it can be seen that the position of the cancerous lesion (the black area near the center of the beam hole) is set to the center in the irradiation conditions, whereas in the actual patient fixation position, the cancerous lesion is shifted slightly below the center of the beam.

[0032] Thus, with BNCT, it is often difficult to irradiate under ideal conditions during actual treatment. Nevertheless, irradiation is performed under the assumption that the target is "fixed in the ideal position."

[0033] Furthermore, with this reactor-based BNCT, position measurement using the 3D digitizer takes about 5 minutes, and since the measurement is performed while directly touching the patient, measurement cannot be performed during irradiation. In addition, feeding back the coordinate information of the eyes, nose, and ears measured by the 3D digitizer to the TPS is not easy, and the procedure involves performing the work and recalculating on the day after the treatment (irradiation) is completed.

[0034] Therefore, even if the 3D digitizer detects a slight deviation from the ideal irradiation position, it is not possible to immediately feed that information back into the TPS (Total Positioning System). In the invention described in Patent Document 1 below, the dose calculation is performed in advance under numerous positional conditions, taking into account the positional displacement immediately before irradiation. From these calculations, the condition closest to the actual displacement is selected and irradiation is performed.

[0035] (Boron concentration during irradiation) As mentioned above, the boron concentration during BNCT irradiation is constantly changing (decreasing). Figures 6(a) and 6(b) show measured blood boron concentration data for two boron compounds, BPA and BSH. This measured data is from BNCT in a nuclear reactor, and the boron concentration in the blood was measured by taking blood samples from patients several times before irradiation. BPA decreases rapidly immediately after drug administration ends (= when irradiation begins). The characteristics of this phenomenon are characterized by the pharmacokinetics and metabolism of the body. Based on this decay curve, the "average concentration" during irradiation is estimated before the start of irradiation.

[0036] For example, in the case of BPA in Figure 6(a), the blood boron concentration immediately before irradiation is approximately 24 ppm. During irradiation (gray area), it is assumed that the concentration will decrease according to the decay curve (curve line in the figure) estimated from the pharmacokinetics of BPA, and the concentration immediately after the end of irradiation is predicted to be approximately 8 ppm before the start of irradiation. Based on this, the physician determines and decides, for example, that the "average boron concentration" during irradiation is "15 ppm" before irradiation.

[0037] In other words, dose calculations in dose assessment assume that the boron concentration is always 15 ppm during irradiation. For example, if the calculated dose rate for a certain area is 1 Gy / ppm / hr, and the actual concentration is 15 ppm, then it becomes 15 Gy / hr, and if irradiation is to be completed with 10 Gy, the calculation would be (10 / 15) × 60 minutes = 40 minutes. However, in reality, the accuracy of this boron concentration prediction is currently poor.

[0038] Changes in the concentration of boron compounds in living organisms are published in the non-patent literature papers 1 and 2 listed below. Based on these papers and experience, we were able to predict the decay of boron concentration.

[0039] (Differences and changes in dose distribution within the body due to differences in boron concentration) Boron-10 has the property of readily reacting with neutrons (which is why BNCT treatment is effective). However, because boron-10 readily reacts with neutrons, if the concentration of boron-10 in the lesion is high, neutrons can get stuck and have difficulty reaching deeper parts of the tissue. Conversely, if the concentration of boron-10 is low (or if boron-10 is absent), neutrons pass smoothly through the body, forming a normal neutron distribution. In other words, the neutron distribution within the body changes depending on the boron-10 concentration, and consequently, the dose distribution within the body (around the lesion) also changes.

[0040] Figure 7 compares the neutron flux distribution on the beam axis when there is no boron-10 in the cancerous lesion (upper line) and when the boron-10 concentration in the cancerous lesion is 50 ppm (lower line). Figures 8(a) and 8(b) show the two-dimensional distribution of neutrons in the body when there is no boron-10 in the cancerous lesion (white ellipse area) (a) and when the boron-10 concentration is 50 ppm (b).

[0041] Figure 7 shows that the neutron distribution remains unchanged from the time the beam enters the body until it reaches the cancerous lesion. After passing through the cancerous lesion, if there is no boron-10 present, the distribution becomes the upper line (normal distribution). On the other hand, if there is 50 ppm of boron-10 in the cancerous lesion, the distribution becomes the lower line. This indicates that many neutrons are stopped by boron-10 as they pass through the cancerous lesion, resulting in a decrease in the number of neutrons after they have passed through the lesion.

[0042] Figure 8 shows a similar pattern: when boron-10 is not present in the cancerous lesion in (a), the high-neutron region (in the color representation, red line → orange line → yellow line) extends widely and deeply. However, when the boron-10 concentration is 50 ppm, the high-neutron region (red line) stops before reaching the cancerous lesion, indicating that the neutron intensity after passing through the lesion is lower than the distribution in (a).

[0043] In conventional TPS (Therapeutic Production System) dose assessment and treatment planning, the boron concentration in the cancerous lesion is assumed to be a certain concentration (the expected average concentration during irradiation: for example, 15 ppm), and this concentration is set in the calculation model for calculations. In actual treatment, the irradiation time is determined based on the dose assessment of the neutron distribution calculated using that single concentration, and the dose to each site is also evaluated (Figure 9). However, in reality, the neutron distribution differs between the boron concentration at the start of irradiation (e.g., 24 ppm) and the concentration just before the end of irradiation (e.g., 8 ppm), and the dose delivered to each site changes accordingly. Current BNCT methods ignore these differences. If dose evaluation could be performed in accordance with the changes in boron concentration at any given time, more accurate dose evaluation and irradiation control would be possible.

[0044] [Problems the invention aims to solve] As is evident from the background technologies mentioned above, the major challenges in current BNCT are the following three: (1) Even if we try to understand the changes in the patient's position during treatment, currently there is no high-precision patient position measurement system that can withstand neutron irradiation and measure changes in the patient's position in real time. (2) If the patient's position changes during treatment, even if an attempt is made to correct the dose by sequentially performing dose evaluations based on the patient's position change information, the re-evaluation of the dose at the changed position takes time, and the information cannot be effectively utilized within the treatment time. (3) Although the boron concentration is constantly changing during neutron irradiation, the fine changes in boron concentration during irradiation are not measured, and irradiation control based on reassessment of the dose in accordance with changes in boron concentration is not possible.

[0045] As a solution to the problem described in (1) above, the applicants of this case filed a prior application for and recently received patent No. 6591229. This technology uses multiple cameras installed in the irradiation chamber and combines motion capture technology to sequentially measure the patient's position. By using this technology, it is possible to quantitatively measure the patient's position in seconds during irradiation, and the patient's position can be measured in real time with high accuracy even during neutron beam irradiation.

[0046] Furthermore, Japanese Patent No. 6565120 discloses a neutron capture therapy system, which, as a solution to the above problem (2), discloses a technique of pre-evaluating the dose corresponding to the amount of displacement of the patient's position. However, this technology does not include the ability to measure the patient's position with high precision in real time during neutron irradiation. Therefore, it is limited to the patient positioning stage before irradiation and cannot handle cases where the patient moves during neutron irradiation. It can only be used at the start of irradiation.

[0047] Therefore, in the case of slight positional changes, irradiation will continue, accepting that the dose may change. As a result, if the prescribed dose that should be delivered to the lesion is insufficient, recurrence may occur. Conversely, if more dose than necessary is delivered, it can lead to over-irradiation of normal tissue, potentially causing adverse events such as radiation damage.

[0048] Furthermore, even if we were to attempt to correct the assigned dose by sequentially performing dose assessments based on the patient's location information, the current calculation methods would be too time-consuming to implement, posing a significant challenge. [Prior art documents] [Patent Documents]

[0049] [Patent Document 1] Japanese Patent Publication No. 6565120 (Japanese Unexamined Patent Publication No. 2018-47132) [Patent Document 2] Japanese Patent Publication No. 6591229 (Japanese Unexamined Patent Publication No. 2017-35348) [Non-patent literature]

[0050] [Non-Patent Document 1] Effect of Dose and infusion time on the delivery of p-boronophenylalanine for neutron capture therapy, DDJoel, et al, J. Neuro-Oncology, 41, 213-221, 1999 [Non-Patent Document 2] Pharmacokinetics of sodium borocaptate: a critical assessment of dosing paradigms for boron neutron capture therapy, CR Gibson, et al., J. Neuro-Oncology, 62, 157-169, 2003 [Overview of the Initiative] Means for solving the problem and their effects

[0051] The present invention has been made in view of the above problems, and aims to provide a BNCT treatment planning system, a BNCT system, and a BNCT that enable highly accurate treatment without the risk of recurrence due to insufficient prescribed radiation dose to be delivered to the lesion, and conversely, without the risk of over-irradiating normal tissue and causing adverse events such as radiation damage by delivering an excessive dose.

[0052] To achieve the above objective, the BNCT treatment planning system (1) according to the present invention provides an ideal patient position that is ideal for treatment, The expected average boron concentration during treatment, Each patient has at least one hypothetical patient position that is expected to be most likely to occur during treatment, and The system includes a storage means for storing the assumed patient position dose calculated by a calculation means for calculating the dose to be applied at each assumed patient position, During actual treatment, upon receiving a signal of patient position change from the patient position measurement system, the system selects the assumed patient position closest to the actual patient position and transmits this assumed patient position, along with the dose administered at that position and the average boron concentration at irradiation estimated from the measured blood boron concentration immediately before irradiation, to the neutron irradiation control system in the BNCT system.

[0053] According to the BNCT treatment planning system (1) described above, when a signal of patient position change is received from the patient position measurement system during actual treatment, the system can select the assumed patient position closest to the actual patient position, and the dose to be administered to the patient during actual treatment can be immediately determined without delay based on the dose to be administered at the assumed patient position, which has been calculated in advance prior to the actual treatment. As a result, it becomes possible to adjust the dose administered to the patient during actual treatment, making it easier to secure the planned dose during BNCT treatment, which can lead to an improvement in the effectiveness and treatment outcomes of cancer treatment with neutron beam therapy. Moreover, it becomes easier to suppress the dose to normal cells surrounding the lesion, which can lead to a reduction in adverse events (side effects). The planned dose mentioned above refers to the ideal dose for treatment calculated at the ideal patient position.

[0054] Furthermore, the BNCT treatment planning system (2) according to the present invention includes an ideal patient position that is considered ideal for treatment, The estimated progressively decreasing boron concentration value, estimated from multiple assumed blood boron concentration measurements immediately before irradiation, The system includes a storage means for storing the assumed boron concentration dose calculated by a calculation means for calculating the dose based on each estimated stepwise decreasing boron concentration value, The system is characterized by receiving a blood boron concentration measurement taken immediately before irradiation, selecting the estimated progressively decreasing boron concentration value closest to that measurement, and transmitting the assumed boron concentration dose based on that boron concentration value to the neutron irradiation control system in the BNCT system.

[0055] Although the boron concentration is constantly changing during neutron irradiation, the above-mentioned BNCT treatment planning system (2) makes it possible to control irradiation using an assumed boron concentration dose based on the estimated stepwise decreasing boron concentration value that is closest to the measured blood boron concentration. This makes it easier to secure the planned dose during BNCT treatment, leading to improved therapeutic effects and outcomes for cancer treatment with neutron beam therapy.

[0056] Furthermore, the BNCT treatment planning system (3) according to the present invention includes an ideal patient position that is considered ideal for treatment, Each patient has at least one hypothetical patient position that is expected to be most likely to occur during treatment, and The assumed patient position dose calculated by the calculation means for calculating the dose at each assumed patient position, The estimated progressively decreasing boron concentration value, estimated from multiple assumed blood boron concentration measurements immediately before irradiation, The system includes a storage means for storing the assumed boron concentration dose calculated by a calculation means for calculating the dose based on each estimated stepwise decreasing boron concentration value, During actual treatment, when a signal of patient position change is received from the patient position measurement system, the system selects the hypothetical patient position closest to the current patient position, and, along with that hypothetical patient position, the dose applied at that hypothetical position, Furthermore, upon receiving a blood boron concentration measurement taken immediately before irradiation, the system selects the estimated progressively decreasing boron concentration value closest to that measurement and transmits the assumed boron concentration dose based on that boron concentration value to the neutron irradiation control system in the BNCT system.

[0057] According to the BNCT treatment planning system (3) described above, when a signal of patient position change is received from the patient position measurement system during actual treatment, the system can select the assumed patient position closest to the actual patient position, and the dose to be administered to the patient during actual treatment can be immediately determined without delay based on the dose to be administered at the assumed patient position, which has been calculated in advance prior to the actual treatment. Therefore, it is also possible to adjust the dose administered to the patient during actual treatment, making it easier to secure the planned dose during BNCT treatment, which can lead to an improvement in the effectiveness and treatment outcomes of cancer treatment with neutron beam therapy. Moreover, it is also possible to control irradiation using the assumed boron concentration dose based on the estimated stepwise decreasing boron concentration value closest to the measured blood boron concentration, which makes it easier to secure the planned dose during BNCT treatment, which can lead to an even greater improvement in the effectiveness and treatment outcomes of cancer treatment with neutron beam therapy.

[0058] Furthermore, the BNCT system (1) according to the present invention is a BNCT system comprising a neutron beam irradiation device, a patient holding device, a patient position measurement system, a BNCT treatment planning system, and a neutron beam irradiation control system, The neutron irradiation control system is characterized by comprising a storage means for storing information on the assigned dose transmitted from any of the BNCT treatment planning systems (1) to (3), and an irradiation control unit that integrates these assigned doses and performs irradiation termination control when the integrated value reaches the treatment target value.

[0059] According to the above BNCT system (1), it becomes easier to secure the planned dose during BNCT treatment, which can lead to improvements in the effectiveness and outcomes of cancer treatment with neutron beam therapy.

[0060] Furthermore, the BNCT treatment planning system (4) according to the present invention includes a storage means for storing the ideal patient position considered ideal for treatment and the assumed average boron concentration during treatment, and a high-speed dose calculation unit. During actual treatment, when a signal of variation in the patient's position from the ideal patient position is received from the patient position measurement system, the conditions of the calculation model are reproduced at the patient position corresponding to the variation, and the boron concentration is calculated using the average boron concentration at irradiation estimated from the measured blood boron concentration immediately before irradiation. The high-speed dose calculation unit performs dose calculations under the conditions of the reproduced calculation model. It is characterized by transmitting the rapidly calculated assigned dose value to the neutron irradiation control system in the BNCT system.

[0061] According to the BNCT treatment planning system (4) described above, the high-speed dose calculation unit can sequentially reproduce the conditions of the calculation model at the fluctuating patient position even during actual treatment, and perform high-speed dose calculations under the reproduced conditions of the calculation model. In other words, irradiation can be controlled with finer, more accurate assigned dose values, making it easier to secure the planned assigned dose during BNCT treatment, which can lead to further improvements in the therapeutic effect and treatment outcomes of cancer treatment with neutron beam therapy. Moreover, it becomes easier to further suppress the dose to normal cells surrounding the lesion, which can lead to a further reduction in adverse events (side effects).

[0062] Furthermore, the BNCT treatment planning system (5) according to the present invention includes a storage means for storing the ideal patient position considered ideal for treatment, and a high-speed dose calculation unit. During actual treatment, the boron concentration is measured sequentially, and when these measured values ​​are received, The boron concentration is changed to the measured value obtained sequentially, while the patient position is maintained at the ideal patient position, reproducing the conditions of the calculation model. The high-speed dose calculation unit performs dose calculations under the conditions of the reproduced calculation model. It is characterized by transmitting the rapidly calculated assigned dose value to the neutron irradiation control system in the BNCT system.

[0063] According to the BNCT treatment planning system (5) described above, even during actual treatment, the conditions of the calculation model using boron concentration measurements obtained by a sequentially measurable prompt gamma ray measurement method are reproduced, and dose calculations under the conditions of the reproduced calculation model are performed by the high-speed dose calculation unit. In other words, irradiation can be controlled with finer, more accurate assigned dose values ​​that correspond to changes in boron concentration, making it easier to secure the planned assigned dose during BNCT treatment, and leading to further improvements in the therapeutic effect and treatment outcomes of cancer treatment with neutron beam therapy.

[0064] Furthermore, the BNCT treatment planning system (6) according to the present invention includes a storage means for storing the ideal patient position considered ideal for treatment, and a high-speed dose calculation unit. During actual treatment, when a signal of variation in the patient's position from the ideal patient position is received from the patient position measurement system, the conditions of the calculation model are reproduced using the measured values ​​sequentially measured during the actual treatment, at the patient position corresponding to the variation, and the boron concentration. The high-speed dose calculation unit performs dose calculations under the conditions of the reproduced calculation model. It is characterized by transmitting the rapidly calculated assigned dose value to the neutron irradiation control system in the BNCT system.

[0065] According to the above BNCT treatment planning system (6), even during actual treatment, the calculation model is reproduced with conditions changed to sequentially fluctuating patient positions and boron concentration measurements obtained by sequentially measurable prompt gamma ray measurement methods, and high-speed dose calculations are performed under the conditions of the reproduced calculation model. Therefore, irradiation can be controlled with finer, more precise dose values ​​that correspond to both the fluctuating patient position and the changes in boron concentration. Therefore, securing the planned dose during BNCT treatment becomes extremely easy, leading to further improvements in the effectiveness and outcomes of cancer treatment with neutron beam therapy. Moreover, it becomes easier to further suppress the dose to normal cells surrounding the lesion, leading to a further reduction in adverse events (side effects).

[0066] Furthermore, the BNCT system (2) according to the present invention is a BNCT system comprising a neutron beam irradiation device, a patient holding device, a patient position measurement system, a BNCT treatment planning system, and a neutron beam irradiation control system, The neutron beam irradiation control system is characterized by comprising a storage means for storing information on the assigned dose transmitted from any of the BNCT treatment planning systems (4) to (6), and an irradiation control unit that integrates these assigned doses and performs irradiation termination control when the integrated value reaches the treatment target value.

[0067] According to the above BNCT system (2), irradiation can be controlled with finer, more accurate dose values ​​that correspond to both the fluctuating patient position and / or changes in boron concentration. Therefore, securing the planned dose during BNCT treatment becomes extremely easy, leading to further improvements in the effectiveness and outcomes of cancer treatment with neutron beam therapy.

[0068] Furthermore, the BNCT (1) according to the present invention is a BNCT that uses either the BNCT system (1) or (2), This system is characterized by continuously re-evaluating the assigned dose during actual treatment using a calculation model that takes into account changes in the patient's position and / or changes in boron concentration during actual treatment, thereby ensuring highly accurate dose delivery for the patient's treatment.

[0069] According to the above BNCT(1), irradiation can be controlled with finer, more precise dose values ​​that correspond to both the fluctuating patient position and / or changes in boron concentration. Therefore, securing the planned dose during BNCT treatment becomes extremely easy, enabling the implementation of neutron beam therapy for cancer with superior efficacy and treatment outcomes. [Brief explanation of the drawing]

[0070] [Figure 1]This is a schematic diagram illustrating the general treatment procedure for BNCT. [Figure 2] This is a schematic diagram illustrating the flow of dose calculation for a patient under certain irradiation conditions using a Treatment Planning System (TPS). [Figure 3] This is a schematic diagram illustrating the process of treatment planning (determining optimal irradiation conditions) using TPS. [Figure 4] This is a schematic diagram illustrating the process when performing BNCT (Body-Nutritional Coherence Therapy) in a nuclear reactor. [Figure 5] This schematic diagram shows the patient's irradiation position under "ideal" irradiation conditions using TPS (upper right) and the "actual irradiation position" reproduced by measurement using a 3D digitizer (lower right). [Figure 6] This graph shows measured blood boron concentration data for two boron compounds, BPA(a) and BSH(b). [Figure 7] This graph compares the neutron flux distribution on the beam axis when there is no boron-10 in the cancerous lesion (top line) and when the boron-10 concentration in the cancerous lesion is 50 ppm. [Figure 8] This graph compares the two-dimensional distribution of neutrons in the body when there is no boron-10 in the cancerous lesion (white oval area) (a) with the two-dimensional distribution when the boron-10 concentration is 50 ppm (b). [Figure 9] This is a schematic diagram showing the overall configuration of a BNCT system, including a conventional treatment planning system. [Figure 10] This is a schematic external view showing the overall configuration of a BNCT system including a treatment planning system according to an embodiment of the present invention. [Figure 11] This is a functional block diagram schematically showing the overall configuration of a BNCT system including a treatment planning system according to Embodiment 1 of the present invention. [Figure 12] This is a schematic diagram illustrating an example of a situation in which dose evaluation is performed at the assumed patient location using the treatment planning system according to Embodiment 1 of the present invention. [Figure 13]These are external views and schematic diagrams illustrating a method for matching the actual patient position to the ideal patient position in a treatment planning system according to Embodiment 1 of the present invention. [Figure 14] This is a schematic diagram including a table illustrating an example of a patient position during actual treatment according to Embodiment 1 of the present invention, and a method for measuring the deviation from the ideal patient position. [Figure 15] This schematic diagram includes a table illustrating a method for performing dose evaluation, using an example of a patient's position during actual treatment according to Embodiment 1 of the present invention. [Figure 16] This flowchart shows the control operations for performing dose evaluation at the assumed patient position before the start of actual treatment in a treatment planning system according to Embodiment 1 of the present invention. [Figure 17] A flowchart illustrating the control operations after the start of actual treatment in the BNCT system according to Embodiment 1 of the present invention. [Figure 18] This is a schematic external view showing the overall control operation after the start of actual treatment in a BNCT system including a treatment planning system according to Embodiment 1 of the present invention. [Figure 19] This is a schematic diagram showing the overall control operation after the start of actual treatment in a BNCT system including a treatment planning system according to Embodiment 2 of the present invention. [Figure 20] This is a functional block diagram schematically showing the overall configuration of a BNCT system including a treatment planning system according to Embodiment 2 of the present invention. [Figure 21] This flowchart illustrates the control operations before the start of actual treatment in the treatment planning system according to Embodiment 2 of the present invention, and after the start of actual treatment in the BNCT system. [Figure 22] This is a schematic external view showing the overall control operation after the start of actual treatment in a BNCT system including a treatment planning system according to Embodiment 3 of the present invention. [Figure 23] This is a functional block diagram schematically showing the overall configuration of a BNCT system including a treatment planning system according to Embodiment 3 of the present invention. [Figure 24]This flowchart illustrates the control operations before the start of actual treatment in the treatment planning system according to Embodiment 3 of the present invention, and after the start of actual treatment in the BNCT system. [Figure 25] This is a schematic external view showing the overall control operation after the start of actual treatment in a BNCT system including a treatment planning system according to Embodiment 4 of the present invention. [Figure 26] This is a functional block diagram that schematically shows the overall configuration of a BNCT system including a treatment planning system according to Embodiment 4 of the present invention. [Figure 27] This flowchart illustrates the control operations before the start of actual treatment in the treatment planning system according to Embodiment 4 of the present invention, and after the start of actual treatment in the BNCT system. [Figure 28] This is a schematic external view showing the overall control operation after the start of actual treatment in a BNCT system including a treatment planning system according to Embodiment 5 of the present invention. [Figure 29] This is a functional block diagram that schematically shows the overall configuration of a BNCT system including a treatment planning system according to Embodiment 5 of the present invention. [Figure 30] This flowchart illustrates the control operations before the start of actual treatment in the treatment planning system according to Embodiment 5 of the present invention, and after the start of actual treatment in the BNCT system. [Figure 31] This is a schematic external view showing the overall control operation after the start of actual treatment in a BNCT system including a treatment planning system according to Embodiment 6 of the present invention. [Figure 32] This is a functional block diagram schematically showing the overall configuration of a BNCT system including a treatment planning system according to Embodiment 6 of the present invention. [Figure 33] This flowchart illustrates the control operations before the start of actual treatment in the treatment planning system according to Embodiment 6 of the present invention, and after the start of actual treatment in the BNCT system. [Modes for carrying out the invention]

[0071] Hereinafter, embodiments of the boron neutron capture therapy (BNCT) treatment planning system, BNCT system, and BNCT according to the present invention will be described with reference to the drawings. Figure 10 is a schematic external view showing the overall configuration of a BNCT system including a treatment planning system according to an embodiment of the present invention. The BNCT system 1 comprises a BNCT treatment planning system 2 (hereinafter simply referred to as treatment planning system 2), a neutron beam irradiation control system 3, a neutron beam irradiation device 4, a patient position measurement system 5, and a patient holding device 6.

[0072] The neutron irradiation device 4 is positioned with its neutron irradiation port 4A directed towards the neutron irradiation room R. In the case of BNCT, the irradiation port 4A itself is usually not movable, but by equipping this irradiation port 4A with a multi-leaf collimator (not shown), it is configured to be able to follow changes in the patient's position within a certain range by controlling the aperture range of this multi-leaf collimator.

[0073] In one embodiment of the neutron irradiation device 4, a head holding means (not shown) capable of stably holding, for example, the patient's head during treatment is retractably mounted near the irradiation port 4A. In the case of BNCT, the treatment time is about one hour, but by equipping the head holding means, the likelihood of the patient maintaining the ideal patient position in the treatment plan increases, which can lead to an improvement in the effectiveness and outcome of treatment for head cancer. Moreover, it becomes easier to suppress the dose to normal cells surrounding the lesion, which can lead to a reduction in adverse events (side effects).

[0074] The patient position measurement system 5 consists of three visible light cameras C positioned above the patient in the neutron beam therapy room R. Furthermore, the patient position measurement system 5 employs the technology of Patent No. 6591229, which was previously filed and recently granted by the applicants in this case.

[0075] The patient position measurement system 5 is configured to sequentially measure the position of patient M by combining motion capture technology with multiple visible light cameras 5A installed in the radiation therapy room R. By employing this technology, it becomes possible to quantitatively measure the patient's position in seconds during neutron irradiation, and the patient's position can be measured in real time with high accuracy even during neutron irradiation. This invention is based on the premise of employing this technology. In this embodiment, the patient position information calculated by the patient position measurement system 5 is output in DICOM format to the treatment planning system 2 and the drive control unit 6a of the patient holding device 6, and then transmitted.

[0076] In Figure 10, the patient support device 6 is shown as a bed type. However, depending on the location of the lesion, a chair type may be more suitable for treatment than a bed type. For such cases, a chair type (not shown) of the patient support device 6 is also available.

[0077] Regardless of the type of patient holding device 6, in one embodiment, a 6-axis drive device (not shown) is incorporated, which is movable in the X, Y, and Z axes and rotatable around these three axes, so that the patient's position can be moved in any direction. The drive control unit 6a (Figure 11) of the patient holding device 6 receives a patient position change signal 5s (Figure 11) from the patient position measurement system 5 and is configured to drive the patient holding device 6 to move and rotate in any direction.

[0078] Figure 11 is a schematic functional block diagram showing the entire BNCT system 1, including the treatment planning system 2 according to Embodiment 1 of the present invention. The treatment planning system 2 is configured with dedicated software installed on a computer system as shown in Figure 10. It receives patient position information from the patient position measurement system 5, and when patient-specific lesion information is input, it determines ideal treatment conditions for each patient, such as irradiation time, beam irradiation angle, and irradiation time per unit boron concentration, and is configured to create and execute an ideal treatment plan for each patient. The treatment planning system 2 is connected to the drive control unit 4a of the neutron irradiation device 4 via the neutron irradiation control system 3, and is also connected to the patient position measurement system 5 and the drive control unit 6a of the patient holding device 6.

[0079] The treatment planning system 2 comprises a storage means 2A, a means 2B for calculating the assumed patient location dose, and a means 2C for selecting the assumed patient location. The memory means 2A stores the ideal patient position 2Aa, the assumed mean boron concentration value 2Ab, the assumed patient position 2Ac, the assumed patient position dose 2Ad, and the mean boron concentration at the time of irradiation 2Ae.

[0080] The ideal patient position 2Aa, as used here, is the position relative to the neutron beam irradiation port 4A of the neutron beam irradiation device 4, which is determined for each individual patient, and represents the position considered to be the ideal position for neutron beam therapy for that patient. Furthermore, the ideal dose to be administered for treatment, calculated at the ideal patient position 2Aa, is called the planned dose. Assumed patient position 2Ac refers to at least one patient position specific to each patient that is expected to be most likely to occur during treatment, and represents the patient position expected before the start of treatment.

[0081] The assumed average boron concentration of 2Ab refers to the expected average boron concentration during treatment, which is determined for each individual patient before treatment begins, taking into account factors such as the patient's physique. The mean boron concentration value of 2Ae at the time of irradiation is the boron concentration estimated from the measured blood boron concentration immediately before irradiation, and is used in calculating the dose during actual treatment. The assumed patient location dose calculation means 2B is a calculation means that takes in each assumed patient location and calculates the planned dose at each assumed patient location, and the calculated assumed patient location dose 2Ad is stored in the storage means 2A. The Monte Carlo method, which offers high computational accuracy, is used to calculate this assumed patient-positioned dose (2Ad).

[0082] Current Monte Carlo-based dose calculations require approximately 30 minutes even with a parallel computing environment that parallelizes 100 CPUs for a single patient position condition. Considering that actual BNCT irradiation is completed within 30 minutes to 1 hour, attempting to recalculate the dose for fluctuating patient positions using the Monte Carlo method during irradiation would likely result in the irradiation ending before the calculation is complete. Furthermore, there is a high probability that the patient will move to another location during the 30-minute calculation process. Therefore, it was impossible to continue irradiation control even if the dose applied during treatment was recalculated using the Monte Carlo method with fluctuating patient positions.

[0083] In contrast, in this embodiment, the range of patient movement is anticipated in advance, and the planned dose for each of the multiple anticipated patient positions is calculated beforehand. Then, during actual treatment, patient position information is received from the patient position measurement system 5 to obtain the accurate fluctuating patient position, and the acquired fluctuating patient position is compared with the multiple anticipated patient positions to select the anticipated patient position closest to the fluctuating patient position (anticipated patient position selection means 2C).

[0084] Then, the pre-calculated assumed patient position dose (Ad), corresponding to the selected assumed patient position, is used for treatment. This allows treatment to be carried out as if real-time dose evaluation at a fluctuating patient position were achieved and irradiation control were continuously maintained during actual treatment.

[0085] The expected patient position changes are estimated to be around 10 conditions, and are not expected to exceed 20 conditions at most (if the range of variation exceeds this, the patient will deviate significantly from the irradiation position, and in actual treatment, it will be necessary to interrupt the irradiation, return the patient to their original position, and then resume irradiation). If 20 conditions are assumed and calculated in advance, and assuming a calculation time of 30 minutes per condition as described above, the calculation can be completed in approximately 600 minutes = 10 hours. Since the treatment plan is made about a week before the actual treatment is carried out, even if 10 hours of calculation time is required, it is sufficient time to complete the dose evaluation for all assumed patient position conditions and store the assumed patient position dose 2Ad in the storage means 2A in preparation for the day of treatment.

[0086] Figure 12 is a schematic diagram showing the situation in which dose evaluations are performed in advance at assumed patient positions 1 and 2 using the treatment planning system 2. This shows the beam irradiation direction for the ideal patient position 2Aa in the treatment plan, and the resulting dose evaluation graph, as well as the beam irradiation direction for the assumed patient positions 1 and 2, which the patient is likely to occupy during actual treatment, and the resulting dose evaluation graph. Then, dose evaluations are performed in advance for each of the assumed patient positions 1 to 20, and this data is linked and stored in memory device 2A.

[0087] Figure 13 is an external view and schematic diagram illustrating how to match the actual patient position to the ideal patient position 2Aa in the treatment planning system 2.

[0088] Markers are attached to the patient's head. The process of aligning the actual patient's position with the ideal patient position 2Aa using these markers as guides is shown. If the goal is to align all of these markers, even a slight misalignment in the marker positions on the head will make alignment impossible. Therefore, in this embodiment, the method of aligning all of these markers is not employed. Instead, the centroids of these markers are determined, and vectors extending in a predetermined direction from these centroids are generated. By finding the point of agreement between these centroids and vectors, the actual patient's position can be accurately and easily aligned with the ideal patient position 2Aa.

[0089] Figure 14 compares the ideal patient position derived by treatment planning system 2 (left) with the actual patient position measured during treatment (right). In this example, the points used to identify the patient's position are the "right outer canthus," "right external auditory meatus," and "nasal tip." The right-hand side shows the actual treatment measurement, where the same point on the patient was measured, and the difference between the measured coordinates and the coordinates at the ideal irradiation position is displayed.

[0090] Figure 15 is a schematic diagram that includes a table illustrating the method of dose evaluation, using an example of a patient's position during actual treatment. Figure 15 shows the dose rate results for each area irradiated under ideal irradiation conditions determined by the treatment planning system 2 (bottom left), and the dose rate results for each area calculated by loading the measured patient position data shown on the right side of Figure 14 into the treatment planning system 2, moving the actual patient position to the ideal patient position 2Aa, and re-evaluating the dose (bottom right).

[0091] By reproducing the actual positional conditions, it was confirmed that the patient's head was tilted approximately 7 degrees toward the beam relative to the ideal patient position 2Aa, and that the center of the lesion area had shifted approximately 3 millimeters downward relative to the center of the beam.

[0092] Under these conditions, a re-dose assessment was conducted, and it was confirmed that the maximum and average dose rates in the lesion area, skin, and brain decreased by approximately 7 to 14 percent. Under ideal conditions, the treatment was planned to be completed in 45.9 minutes, but under conditions that replicated the actual patient position, the irradiation time required was 48.9 minutes. This indicates that the change in patient position reduced the dose rate to each area, necessitating an additional 3 minutes of irradiation.

[0093] This example demonstrates a single measurement of patient position, re-evaluation of dose, and adjustment of irradiation time. However, in actual treatment, dose evaluation is reproduced each time the patient's position changes, thereby improving the accuracy of dose evaluation.

[0094] Figure 16 is a flowchart showing the control operation of the control unit when performing dose evaluation at the assumed patient position before the start of actual treatment in the treatment planning system 2 according to Embodiment 1 of the present invention.

[0095] First, in step S1, lesion information for each patient is collected, and ideal treatment conditions for each patient, such as irradiation time, beam irradiation angle, and irradiation time per unit boron concentration, are determined to create an ideal treatment plan for each patient.

[0096] Next, in step S2, it is determined whether the number of assumed patient positions n has reached 20. In step S2, if it is determined that the number of assumed patient positions n has reached 20, the process ends. However, if it is determined that the number of assumed patient positions n has not reached 20, the process proceeds to step S3.

[0097] In step S3, the number of assumed patient positions n is set to start from 1. Next, we proceed to step S4, in which the dose rate at the assumed patient position n is calculated. For this calculation, we employ the Monte Carlo method, which has high calculation accuracy, as described above.

[0098] Next, the process proceeds to step S5, in which the assumed patient location, the assigned dose rate at the assumed patient location, and the boron concentration are linked and stored in memory in the memory means 2A.

[0099] Next, in step S6, the number of assumed patient positions n is increased by one, and then the process returns to step S2. This process is repeated until the number of assumed patient positions n reaches 20. Once it is determined that the number of assumed patient positions n has reached 20, the process is terminated.

[0100] Figure 17 is a flowchart showing the control operations performed after the start of actual treatment in the BNCT system according to Embodiment 1 of the present invention.

[0101] First, in step S10, the patient is accurately held in the predetermined ideal patient position 2Aa on the patient holding device 6 using the patient position measurement system 5. Next, in step S11, estimated mean boron concentration information is acquired from the blood boron concentration measurement taken immediately before irradiation.

[0102] Next, in step S12, irradiation with neutron beams is started at the planned dose. Next, the process proceeds to step S13, where it is determined whether or not a patient position change signal 5s from the patient position measurement system 5 has been received. If it is determined that the patient position change signal 5s has been received, the process proceeds to step S14; however, if it is determined that the patient position change signal 5s has not been received, the process returns to step S13.

[0103] In step S14, the current patient position is obtained from the patient position measurement system 5. Next, in step S15, the current patient position at the time of treatment, which was captured in step S14, is compared with the assumed patient position stored in the memory means 2A.

[0104] Next, in step S16, the hypothetical patient position closest to the current patient position, based on the comparison results from the previous step S15, is selected.

[0105] Next, in step S17, the assigned dose rate for the assumed patient position selected in step S16 is retrieved from the storage means 2A. Next, in step S18, the doses irradiated so far are accumulated. Next, in step S19, it is determined whether the accumulated dose has reached the planned dose planned by the treatment planning system. If it is determined that the planned dose has been reached, irradiation is terminated. On the other hand, if it is determined that the planned dose has not yet been reached, the process returns to step S13.

[0106] Figure 18 is a schematic overview showing the overall control operation in a BNCT system including a treatment planning system according to Embodiment 1 of the present invention.

[0107] The patient is precisely held in the ideal patient position on the patient holding device using a patient position measurement system. Immediately before neutron irradiation, the boron concentration in the blood is measured, and the estimated average boron concentration information derived from this measurement is entered into the treatment planning system. The estimated average boron concentration shown in the figure is 15 ppm.

[0108] Once neutron irradiation begins with the planned dose, the patient position measurement system continuously transmits patient position information (center of gravity & vector) to the treatment planning system, allowing the treatment planning system to accurately determine any changes in the patient's position.

[0109] When it is determined that a patient position change signal has been received, the system determines the current value based on the patient position signal from the patient position measurement system and compares it with the assumed patient positions (20 in this embodiment) stored in the storage means 2A. Based on the comparison, the hypothetical patient position closest to the current patient position is selected.

[0110] Next, the assigned dose for the selected assumed patient location, the ratio of the assigned dose to the patient located at the assumed patient location to the planned assigned dose, and the irradiation time obtained by converting the calculated assigned dose rate into irradiation time are retrieved from the storage means 2A.

[0111] Next, the irradiation time in the actual treatment is adjusted based on the recalled irradiation time. The irradiation control system accumulates the irradiation time so far and determines whether the accumulated irradiation time has reached the planned dose planned by the treatment planning system. If it is determined that the planned dose has been reached, it executes a control to terminate the irradiation. On the other hand, if it is determined that the planned dose has not yet been reached, it continues the irradiation.

[0112] As shown in Figure 18, the treatment was completed with a final irradiation time of 62 minutes. This irradiation time was 12 minutes longer than the 50-minute irradiation time shown in Figure 9 of the treatment planning stage, and the result indicates that the planned dose was secured.

[0113] Figure 19 is a schematic external view showing the overall control operation in a BNCT system including a treatment planning system according to Embodiment 2 of the present invention.

[0114] In Embodiment 2, it is assumed that the patient maintains the ideal patient position for treatment during irradiation, while multiple expected boron concentration changes during irradiation are estimated, and dose calculations for each boron concentration are performed in advance and stored in memory before irradiation begins.

[0115] The patient is precisely held in the ideal patient position on the patient holding device using a patient position measurement system. Immediately before neutron irradiation, the boron concentration in the blood is measured (26 ppm), and the estimated progressively decreasing boron concentration values ​​derived from this measurement are entered into the treatment planning system. The estimated progressively decreasing boron concentration values ​​shown in the figure are 25 ppm, 16 ppm, and 12 ppm.

[0116] When neutron irradiation begins at the planned dose, the dose based on the estimated stepwise decreasing boron concentration value, the ratio of the dose to the planned dose, and the irradiation time obtained by converting the calculated dose rate into irradiation time are retrieved from the storage means 2A.

[0117] The irradiation control system adjusts the irradiation time in the actual treatment based on the called irradiation time, accumulates the irradiation time delivered to each boron concentration interval, and determines whether the accumulated irradiation time has reached the planned dose planned by the treatment planning system. If it is determined that the planned dose has been reached, it executes a control to terminate the irradiation; on the other hand, if it is determined that the planned dose has not yet been reached, it continues the irradiation.

[0118] As shown in Figure 19, the treatment was completed with a final irradiation time of 63 minutes. This irradiation time was 13 minutes longer than the 50-minute irradiation time shown in Figure 9 of the treatment planning stage, and the result indicates that the planned dose was secured.

[0119] Figure 20 is a schematic functional block diagram showing the entire BNCT system 1, including the treatment planning system 2 according to Embodiment 2 of the present invention.

[0120] The treatment planning system 2 comprises a memory means 2A, an ideal patient position assignment dose calculation means 2B1, an assumed boron concentration assignment dose calculation means 2B2, and an estimated stepwise decreasing boron concentration selection means 2C1. The memory means 2A stores the ideal patient position 2Aa, the estimated gradually decreasing boron concentration value 2Af, the assumed boron concentration dose 2Ag, and the estimated gradually decreasing boron concentration value 2Ah at the time of irradiation.

[0121] The ideal patient position 2Aa, as used here, is the position relative to the neutron beam irradiation port 4A of the neutron beam irradiation device 4, which is determined for each individual patient, and represents the position considered to be the ideal position for neutron beam therapy for that patient.

[0122] The estimated progressively decreasing boron concentration value 2Af refers to multiple boron concentration values ​​estimated from blood boron concentration measurements immediately before irradiation, based on pharmacokinetic methods and other factors. The assumed boron concentration dose of 2Ag represents the boron concentration dose based on the estimated progressively decreasing boron concentration value that is closest to the blood boron concentration measurement taken immediately before irradiation. The estimated stepwise decreasing boron concentration value of 2Ah during irradiation represents the value selected from among several estimated stepwise decreasing boron concentration values ​​during actual irradiation.

[0123] The ideal patient position dose calculation means 2B1 is a calculation means that takes in the ideal patient position and calculates the planned dose at the ideal patient position, and the calculated ideal patient position dose is stored in the storage means 2A. The Monte Carlo method, which offers high computational accuracy, is used to calculate this ideal patient-positioned dose.

[0124] In this second embodiment, a range of estimated progressively decreasing boron concentration values ​​2Af is assumed in advance, and the planned doses for multiple estimated progressively decreasing boron concentration values ​​2Af are calculated in advance and stored in memory.

[0125] During actual treatment, the estimated progressively decreasing boron concentration value (2Af) closest to the blood boron concentration measurement immediately before irradiation is selected from among several estimated progressively decreasing boron concentration values ​​(2Af). The irradiation time is then controlled based on a pre-calculated planned dose for the selected estimated progressively decreasing boron concentration value.

[0126] As a result, during actual treatment, it becomes possible to perform treatment as if irradiation control were being performed based on real-time dose evaluation using estimated stepwise decreasing boron concentration values.

[0127] The estimated number of boron concentration values ​​for the gradual decrease is expected to be around 10 conditions, and even with more detailed assumptions, it is unlikely to exceed 20 conditions at most. If 20 conditions are assumed and calculated in advance, and assuming a calculation time of 10 minutes per condition, the calculation can be completed in approximately 200 minutes = 3 hours and 20 minutes. Since the treatment plan is made about a week before the actual treatment is carried out, even if the calculation time exceeds 3 hours, it is sufficient time to complete the dose evaluation based on all assumed estimated gradual reduction boron concentration values ​​and store the assumed boron concentration dose 2Ag in the memory means 2A in preparation for the day of treatment.

[0128] Figure 21(a) is a flowchart showing the control operation of the control unit when performing dose evaluation before the start of actual treatment in the treatment planning system 2 according to Embodiment 2 of the present invention.

[0129] First, in step S21, lesion information for each patient is collected, and ideal treatment conditions for each patient, such as irradiation time, beam irradiation angle, and irradiation time per unit boron concentration, are determined to create an ideal treatment plan for each patient. Additionally, the stepwise changes in multiple estimated boron concentration values ​​are incorporated.

[0130] Next, in step S22, the dose rate is calculated based on the boron concentration values ​​at each stage. In step S22, the stepwise boron concentration value is set with an upper limit of 20.

[0131] In step S23, these stepwise boron concentration values, the assigned dose based on each stepwise boron concentration value, and the ratio of the assigned dose to the planned assigned dose are linked and stored in memory in the memory means 2A.

[0132] Figure 21(b) is a flowchart showing the control operations performed after the start of actual treatment in the BNCT system according to Embodiment 2 of the present invention.

[0133] First, in step S25, the patient is accurately held in the predetermined ideal patient position 2Aa on the patient holding device 6 using the patient position measurement system 5. Next, the boron concentration at the start of irradiation is estimated based on the blood boron concentration measurement taken immediately before irradiation.

[0134] Next, in step S26, the boron concentration information is transmitted to the treatment planning system.

[0135] Next, the process proceeds to step S27, in which the boron concentration is estimated by pharmacokinetic analysis, prompt gamma ray measurement, or PG-SPECT method. Next, the process proceeds to step S28, in which a pre-calculated and stored dose value corresponding to the determined boron concentration value is obtained.

[0136] Next, the process proceeds to step S29, where the dose is accumulated. Next, in step S30, it is determined whether the accumulated dose has reached the planned dose planned by the treatment planning system. If it is determined that the planned dose has been reached, irradiation is terminated. On the other hand, if it is determined that the planned dose has not yet been reached, the process returns to step S27.

[0137] Figure 22 is a schematic overview showing the overall control operation in a BNCT system including a treatment planning system according to Embodiment 3 of the present invention.

[0138] In Embodiment 3, the range of patient movement is anticipated in advance, and the planned dose for multiple anticipated patient positions is calculated beforehand. The boron concentration is estimated based on multiple anticipated boron concentration changes during irradiation, and dose calculations for each boron concentration are performed in advance. These calculations are then linked to each of the multiple anticipated patient positions and stored in memory before irradiation begins.

[0139] The patient is precisely held in the ideal patient position on the patient holding device using a patient position measurement system. Immediately before neutron irradiation, the boron concentration in the blood is measured (26 ppm), and the estimated progressively decreasing boron concentration values ​​derived from this measurement are entered into the treatment planning system. The estimated progressively decreasing boron concentration values ​​shown in the figure are 25 ppm, 16 ppm, and 12 ppm.

[0140] Once neutron irradiation begins with the planned dose, the patient position measurement system continuously transmits patient position information (center of gravity & vector) to the treatment planning system, allowing the treatment planning system to accurately determine any changes in the patient's position.

[0141] When it is determined that a patient position change signal has been received, the system determines the current value based on the patient position signal from the patient position measurement system and compares it with the assumed patient positions (20 in this embodiment) stored in the storage means 2A. Based on the comparison, the hypothetical patient position closest to the current patient position is selected.

[0142] Next, the assigned dose for the selected assumed patient location, the ratio of the assigned dose to the patient located at the assumed patient location to the planned assigned dose, and the irradiation time obtained by converting the calculated assigned dose rate into irradiation time are retrieved from the storage means 2A. In addition, the applied dose based on the estimated progressively decreasing boron concentration value, the ratio of the applied dose to the planned applied dose, and the irradiation time obtained by converting the calculated applied dose rate into irradiation time are retrieved from the storage means 2A.

[0143] Next, the irradiation time in the actual treatment is adjusted based on the recalled irradiation time. The irradiation control system calculates the irradiation time, taking into account both the current patient position and the estimated progressively decreasing boron concentration. It then determines whether the accumulated irradiation time has reached the planned dose set by the treatment planning system. If it is determined that the planned dose has been reached, the system executes a control to terminate the irradiation. On the other hand, if it is determined that the planned dose has not yet been reached, the system continues the irradiation.

[0144] As shown in Figure 22, the treatment was completed with a final irradiation time of 64 minutes. This irradiation time was 14 minutes longer than the 50-minute irradiation time shown in Figure 9 for the treatment planning stage, indicating that the planned dose was achieved.

[0145] Figure 23 is a functional block diagram schematically showing the overall configuration of the BNCT system 1, which includes the treatment planning system 2 according to Embodiment 3 of the present invention.

[0146] The treatment planning system 2 comprises a storage means 2A, a means 2B for calculating the assumed patient position dose, a means 2C for selecting the assumed patient position, a means 2B1 for calculating the ideal patient position dose, a means 2B2 for calculating the assumed boron concentration dose, and a means 2C1 for selecting the estimated stepwise decreasing boron concentration.

[0147] The memory means 2A stores the ideal patient position 2Aa, the assumed patient position 2Ac, the assumed patient position dose 2Ad, the estimated gradually decreasing boron concentration value 2Af, the assumed boron concentration dose 2Ag, and the estimated gradually decreasing boron concentration value 2Ah during irradiation.

[0148] Assumed patient position 2Ac refers to at least one patient position specific to each patient that is expected to be most likely to occur during treatment, and represents the patient position expected before the start of treatment. The estimated progressively decreasing boron concentration value 2Af refers to multiple boron concentration values ​​estimated from blood boron concentration measurements immediately before irradiation, based on pharmacokinetic methods and other factors.

[0149] The assumed boron concentration dose of 2Ag represents the boron concentration dose based on the estimated progressively decreasing boron concentration value that is closest to the blood boron concentration measurement taken immediately before irradiation. The estimated stepwise decreasing boron concentration value of 2Ah during irradiation represents the value selected from among several estimated stepwise decreasing boron concentration values ​​during actual irradiation.

[0150] The assumed patient location dose calculation means 2B is a calculation means that takes in each assumed patient location and calculates the planned dose at each assumed patient location, and the calculated assumed patient location dose 2Ad is stored in the storage means 2A. The Monte Carlo method, which offers high computational accuracy, is used to calculate this assumed patient-positioned dose (2Ad).

[0151] In this embodiment 3, the range of patient movement is anticipated in advance, and the planned dose for each of the multiple anticipated patient positions is calculated beforehand. Then, during actual treatment, patient position information is received from the patient position measurement system 5 to obtain the accurate fluctuating patient position, and the acquired fluctuating patient position is compared with the multiple anticipated patient positions to select the anticipated patient position closest to the fluctuating patient position (anticipated patient position selection means 2C).

[0152] Then, the pre-calculated assumed patient position dose (Ad), corresponding to the selected assumed patient position, is used for treatment. This allows treatment to be carried out as if real-time dose evaluation at a fluctuating patient position were achieved and irradiation control were continuously maintained during actual treatment.

[0153] The ideal patient position dose calculation means 2B1 is a calculation means that takes in the ideal patient position and calculates the planned dose at the ideal patient position, and the calculated ideal patient position dose is stored in the storage means 2A. The Monte Carlo method, which offers high computational accuracy, is used to calculate this ideal patient-positioned dose.

[0154] In this third embodiment, a range of estimated progressively decreasing boron concentration values ​​2Af is assumed in advance, and the planned doses for multiple estimated progressively decreasing boron concentration values ​​2Af are calculated in advance and stored in memory.

[0155] During actual treatment, the estimated progressively decreasing boron concentration value (2Af) closest to the blood boron concentration measurement immediately before irradiation is selected from among several estimated progressively decreasing boron concentration values ​​(2Af). The irradiation time is then controlled based on a pre-calculated planned dose for the selected estimated progressively decreasing boron concentration value.

[0156] As a result, during actual treatment, it becomes possible to perform treatment as if irradiation control were being performed based on real-time dose evaluation using estimated stepwise decreasing boron concentration values.

[0157] Figure 24(a) is a flowchart showing the control operation of the control unit when performing dose evaluation in advance before the start of actual treatment in the treatment planning system 2 according to Embodiment 3 of the present invention.

[0158] First, in step S31, lesion information for each patient is taken in, and ideal treatment conditions for each patient, such as irradiation time, beam irradiation angle, and irradiation time per unit boron concentration, are determined to create an ideal treatment plan for each patient.

[0159] Next, in step S32, it is determined whether the number of assumed patient positions n has reached 20. In step S32, if it is determined that the number of assumed patient positions n has reached 20, the process ends. However, if it is determined that the number of assumed patient positions n has not reached 20, the process proceeds to step S33.

[0160] In step S33, the number of assumed patient positions n is set to start from 1. Next, we proceed to step S34, in which the dose rate at the assumed patient position n is calculated. For this calculation, the Monte Carlo method, which has high calculation accuracy as described above, is employed.

[0161] Next, the process proceeds to step S35, in which the ratio of the dose to be administered to a patient located at the assumed patient position to the planned dose is calculated from the ideal patient position 2Aa and the assumed patient position.

[0162] Then, in step S36, the stepwise changes in multiple estimated boron concentration values ​​are incorporated.

[0163] Next, in step S37, the dose rate is calculated based on the boron concentration value at each stage. In step S37, the stepwise boron concentration value is set with an upper limit of 20.

[0164] Next, in step S38, the assumed patient location, boron concentration, and each stepwise boron concentration dose rate are linked and stored in memory in the memory means 2A.

[0165] Next, in step S39, the number of assumed patient positions n is increased by one, and then the process returns to step S32. This process is repeated until the number of assumed patient positions n reaches 20. Once it is determined that the number of assumed patient positions n has reached 20, the process is terminated.

[0166] Figure 24(b) is a flowchart showing the control operations performed after the start of actual treatment in the BNCT system according to Embodiment 3 of the present invention.

[0167] First, in step S41, the patient is accurately held in the predetermined ideal patient position 2Aa on the patient holding device 6 using the patient position measurement system 5. Next, in step S42, the boron concentration at the start of irradiation is estimated from the blood boron concentration measurement taken immediately before irradiation.

[0168] Next, in step S43, irradiation with neutron beams is started at the planned dose. Next, the process proceeds to step S44, where it is determined whether or not a patient position change signal 5s from the patient position measurement system 5 has been received. If it is determined that the patient position change signal 5s has been received, the process proceeds to step S45; however, if it is determined that the patient position change signal 5s has not been received, the process proceeds to step S51.

[0169] In step S45, the current patient position is obtained from the patient position measurement system 5. Next, in step S46, the current patient position at the time of treatment, which was captured in step S45, is compared with the assumed patient position stored in the memory means 2A. Next, in step S47, the hypothetical patient position closest to the current patient position, based on the comparison results from the previous step S46, is selected.

[0170] Next, in step S48, the boron concentration is estimated. Next, in step S49, the selected assumed patient location and the dose rate at the boron concentration at that time are retrieved.

[0171] Next, in step S50, the dose is accumulated. Next, the process proceeds to step S51, where it is determined whether the accumulated dose has reached the planned dose planned by the treatment planning system. If it is determined that the planned dose has been reached, the irradiation is terminated. On the other hand, if it is determined that the planned dose has not yet been reached, the process returns to step S44.

[0172] Figure 25 is a schematic external view showing the overall control operation in the BNCT system 1, which includes the treatment planning system 2 according to Embodiment 4 of the present invention.

[0173] The patient is precisely held in the ideal patient position on the patient holding device using a patient position measurement system. Immediately before neutron irradiation, the boron concentration in the blood is measured, and the estimated average boron concentration information derived from this measurement is entered into the treatment planning system. The estimated average boron concentration shown in the figure is 15 ppm.

[0174] Once neutron irradiation begins with the planned dose, the patient position measurement system continuously transmits patient position information (center of gravity & vector) to the treatment planning system, allowing the treatment planning system to accurately determine any changes in the patient's position.

[0175] Upon detecting a patient position change signal, the system determines the current patient position based on the patient position signal from the patient position measurement system, and then rapidly calculates the dose assessment by reproducing the calculation model conditions based on the current patient position. This rapid calculation uses a supercomputer-level system, as shown in the figure.

[0176] The irradiation control system accumulates the doses irradiated so far and determines whether the accumulated dose has reached the planned dose set by the treatment planning system. If it is determined that the planned dose has been reached, the system executes a control to terminate irradiation. On the other hand, if it is determined that the planned dose has not yet been reached, the system continues irradiation.

[0177] As shown in Figure 25, the treatment was completed with a final irradiation time of 62.5 minutes. This irradiation time was 12.5 minutes longer than the 50-minute irradiation time shown in Figure 9 of the treatment planning stage, and the results indicate that the planned dose was achieved.

[0178] Figure 26 is a schematic functional block diagram showing the entire BNCT system 1, including the treatment planning system 2 according to Embodiment 4 of the present invention.

[0179] The treatment planning system 2 comprises a storage means 2A and a variable patient position-assigned dose high-speed calculation means 2B4. The memory means 2A stores the ideal patient position 2Aa, the assumed average boron concentration value 2Ab, the fluctuating patient position 2Aj, the dose assigned to the fluctuating patient position 2Ak, and the average boron concentration at the time of irradiation 2Ae.

[0180] The ideal patient position 2Aa, as used here, is the position relative to the neutron beam irradiation port 4A of the neutron beam irradiation device 4, which is determined for each individual patient, and represents the position considered to be the ideal position for neutron beam therapy for that patient. Furthermore, the ideal dose to be administered for treatment, calculated at the ideal patient position 2Aa, is called the planned dose.

[0181] The assumed average boron concentration of 2Ab refers to the expected average boron concentration during treatment, which is determined for each individual patient before treatment begins, taking into account factors such as the patient's physique. The mean boron concentration value of 2Ae at the time of irradiation is the boron concentration estimated from the measured blood boron concentration immediately before irradiation, and is used in calculating the dose during actual treatment.

[0182] The variable patient position assigned dose high-speed calculation means 2B4 is a calculation means consisting of a supercomputer or the like that takes in the variable patient position and calculates the assigned dose at each variable patient position at high speed, and the calculated variable patient position assigned dose 2Ak is temporarily stored in the storage means 2A. The calculation of this variable patient position-assigned dose 2Ak is performed by reproducing the calculation model conditions based on the variable patient position and performing a high-speed dose evaluation.

[0183] Figure 27(a) is a flowchart showing the control operation of the control unit when performing dose evaluation at the ideal patient position before the start of actual treatment in the treatment planning system 2 according to Embodiment 4 of the present invention.

[0184] In step S60, lesion information for each patient is taken in, and ideal treatment conditions for each patient, such as irradiation time, beam irradiation angle, and irradiation time per unit boron concentration, are determined to create an ideal treatment plan for each patient. The boron concentration used will be the assumed average boron concentration of 2Ab, as described above.

[0185] Figure 27(b) is a flowchart showing the control operations performed after the start of actual treatment in the BNCT system according to Embodiment 4 of the present invention.

[0186] First, in step S61, the patient is accurately held in the predetermined ideal patient position 2Aa on the patient holding device 6 using the patient position measurement system 5. Next, in step S62, estimated mean boron concentration information is acquired from the blood boron concentration measurement taken immediately before irradiation.

[0187] Next, in step S63, irradiation with neutron beams is started at the planned dose. Next, the process proceeds to step S64, where it is determined whether or not the patient position change signal 5s from the patient position measurement system 5 has been received. If it is determined that the patient position change signal 5s has been received, the process proceeds to step S65; however, if it is determined that the patient position change signal 5s has not been received, the process proceeds to step S68.

[0188] In step S65, the current patient position, i.e., the fluctuating patient position, is acquired from the patient position measurement system 5. Next, in step S66, the current patient position (variable patient position) at the time of treatment, which was acquired in step S65, is transmitted to the treatment planning system.

[0189] The treatment planning system, having received the current patient position (fluctuating patient position) during treatment, then, in step S67, reproduces the calculation model conditions based on the fluctuating patient position and performs a high-speed dose calculation. This high-speed calculation uses a supercomputer-level system, as shown in the figure.

[0190] Next, in step S68, the doses irradiated so far are accumulated. Next, in step S69, it is determined whether the accumulated dose has reached the planned dose planned by the treatment planning system. If it is determined that the planned dose has been reached, irradiation is terminated. On the other hand, if it is determined that the planned dose has not yet been reached, the process returns to step S64.

[0191] Figure 28 is a schematic overview showing the overall control operation in a BNCT system including a treatment planning system according to Embodiment 5 of the present invention.

[0192] In Embodiment 5, it is assumed that the patient maintains the ideal patient position for treatment during irradiation, while the boron concentration is measured sequentially, and dose calculations are performed by changing the boron concentration in the calculation model in accordance with the changes in the measured concentration.

[0193] The patient is precisely held in the ideal patient position on the patient holding device using a patient position measurement system. Immediately before neutron irradiation, the boron concentration in the blood is measured (26 ppm), and the boron concentration at the start of irradiation is estimated from this measurement.

[0194] During actual treatment, measurement values ​​obtained using a measurement method selected from among pharmacokinetic methods, prompt gamma ray measurement, or PG-SPECT are sequentially transmitted to the treatment planning system. In the treatment planning system that incorporates the measured values, the boron concentration in the calculation model is changed in response to the change in measured concentration to perform dose calculations. The measured boron concentration values ​​shown in the figure are 25 ppm, 20 ppm, 17 ppm, 15 ppm, and 13.5 ppm.

[0195] The irradiation control system accumulates the calculated dose and determines whether the accumulated dose has reached the planned dose set by the treatment planning system. If it determines that the planned dose has been reached, it executes a control to terminate the irradiation. On the other hand, if it determines that the planned dose has not yet been reached, it continues the irradiation.

[0196] As shown in Figure 28, the treatment was completed with a final irradiation time of 63.5 minutes. This irradiation time was 13.5 minutes longer than the 50-minute irradiation time shown in Figure 9 of the treatment planning stage, and the results indicate that the planned dose was achieved.

[0197] Figure 29 is a functional block diagram schematically showing the overall configuration of a BNCT system including a treatment planning system according to Embodiment 5 of the present invention.

[0198] The treatment planning system 2 includes a memory means 2A and a high-speed dose calculation means 2B5 that assigns sequentially measured values ​​of the ideal patient position and boron concentration. The memory means 2A stores the ideal patient position 2Aa, sequential measurement values ​​2Am selected from measurement methods such as pharmacokinetics, prompt gamma ray measurement, or PG-SPECT, and high-speed calculated assigned dose values ​​2An.

[0199] The ideal patient position 2Aa, as used here, is the position relative to the neutron beam irradiation port 4A of the neutron beam irradiation device 4, which is determined for each individual patient, and represents the position considered to be the ideal position for neutron beam therapy for that patient. Furthermore, the ideal dose to be administered for treatment, calculated at the ideal patient position 2Aa, is called the planned dose.

[0200] The ideal patient position / boron concentration sequential measurement value assigning dose high-speed calculation means 2B5 is a calculation means consisting of a supercomputer or the like that takes in sequential boron concentration measurements and calculates the assigning dose at high speed based on the sequential boron concentration measurements, and the calculated high-speed calculated assigning dose value 2An is temporarily stored in the storage means 2A. This high-speed calculated dose value 2An is calculated by rapidly calculating the dose evaluation by reproducing the calculation model conditions based on sequentially measured boron concentration values.

[0201] Figure 30(a) is a flowchart showing the control operation of the control unit when performing dose evaluation at the ideal patient position before the start of actual treatment in the treatment planning system 2 according to Embodiment 5 of the present invention.

[0202] In step S70, lesion information for each patient is collected, and ideal treatment conditions for each patient, such as irradiation time, beam irradiation angle, and irradiation time per unit boron concentration, are determined to create an ideal treatment plan for each patient.

[0203] Figure 30(b) is a flowchart showing the control operations performed after the start of actual treatment in the BNCT system according to Embodiment 5 of the present invention.

[0204] First, in step S71, the patient is accurately held in the predetermined ideal patient position 2Aa on the patient holding device 6 using the patient position measurement system 5. In addition, the boron concentration at the start of irradiation is estimated based on the blood boron concentration measurement taken immediately before irradiation.

[0205] Next, in step S72, the estimated boron concentration obtained by pharmacokinetic analysis, prompt gamma ray measurement, or PG-SPECT method is transmitted to the TPS. Next, the process proceeds to step S73, in which the TPS reproduces the calculation model conditions under the conditions of ideal patient position and sequential boron concentration measurements, performs high-speed dose calculation, and transmits the calculation results to the irradiation control system. A supercomputer-level system, as shown in the figure, is used for this high-speed calculation. Next, in step S74, the doses irradiated so far are accumulated.

[0206] Next, in step S75, it is determined whether the accumulated dose has reached the planned dose planned by the treatment planning system. If it is determined that the planned dose has been reached, irradiation is terminated. On the other hand, if it is determined that the planned dose has not yet been reached, the process returns to step S72.

[0207] Figure 31 is a schematic overview showing the overall control operation in a BNCT system including a treatment planning system according to Embodiment 6 of the present invention.

[0208] In Embodiment 6, the patient's position is measured sequentially by a patient position measurement system, and the boron concentration is also measured sequentially. The dose calculation is performed by changing the patient's position and boron concentration in the calculation model.

[0209] The patient is precisely held in the ideal patient position on the patient holding device using a patient position measurement system. Immediately before neutron irradiation, the boron concentration in the blood is measured (26 ppm), and the boron concentration at the start of irradiation is estimated from this measurement.

[0210] When neutron beam irradiation starts with the planned dose, the patient position measurement system always transmits patient position information (center of gravity & vector) to the treatment planning system side, and the treatment planning system side can accurately judge the variation of the patient position.

[0211] On the other hand, the boron concentration is successively transmitted to the treatment planning system as a measured value obtained by a measurement method selected from measurement methods such as the pharmacokinetic method, the prompt gamma ray measurement method, or the PG-SPECT method. In the treatment planning system, based on the current patient position information from the patient position measurement system and corresponding to the measured concentration change, the dose evaluation is calculated at high speed by reproducing the calculation model conditions. For this high-speed calculation, a supercomputer-level one as shown in the figure is used.

[0212] On the irradiation control system side, the dose irradiated so far is integrated, and it is judged whether or not the integrated dose has reached the planned dose planned by the treatment planning system. When it is judged that the planned dose has been reached, the control to end the irradiation is executed. On the other hand, when it is judged that the planned dose has not yet been reached, the irradiation is continued.

[0213] In what is shown in FIG. 31, finally, the irradiation time is 65.0 minutes and the treatment is completed. This irradiation time is 15.0 minutes longer than the irradiation time of 50 minutes at the treatment planning stage shown in FIG. 9, and it is recognized that the planned dose has been ensured.

[0214] FIG. 32 is a functional block diagram schematically showing the overall configuration of a BNCT system including a treatment planning system according to Embodiment Mode 6 of the present invention.

[0215] The treatment planning system 2 is configured to include a storage means 2A and a means 2B6 for high-speed calculation of dose with sequentially measured values of variable patient position and boron concentration. The memory means 2A stores sequential measurement values 2Am obtained by a measurement method selected from measurement methods such as an ideal patient position 2Aa, a variable patient position 2Aj, a pharmacokinetic method, an immediate gamma-ray measurement method, or a PG-SPECT method, a high-speed calculated dose value 2An, and the like.

[0216] The ideal patient position 2Aa mentioned here is the position with respect to the neutron beam irradiation port 4A of the neutron beam irradiation device 4 determined for each patient, and means a position considered to be an ideal position for neutron beam treatment for the patient. Also, the ideal dose to be administered for treatment calculated at the ideal patient position 2Aa is called the planned dose.

[0217] The variable patient position·boron concentration sequential measurement value dose high-speed calculation means 2B6 is a calculation means composed of a supercomputer or the like that takes in the variable patient position and the boron concentration sequential measurement value, reproduces the calculation model conditions corresponding to the variable patient position information and the measured concentration change, and performs high-speed calculation of dose evaluation. The calculated high-speed calculated dose value 2An is temporarily stored in the memory means 2A.

[0218] Figure 33(a) is a flowchart showing the control operation of the control unit when performing dose evaluation at the ideal patient position before the actual treatment starts in the treatment planning system 2 according to Embodiment 6 of the present invention.

[0219] In step S80, lesion information for each patient and the like are taken in, ideal treatment conditions for each patient, such as irradiation time, beam irradiation angle, irradiation time per unit boron concentration, etc. are determined, and an ideal treatment plan for each patient is created.

[0220] Figure 33(b) is a flowchart showing the control operation executed after the actual treatment starts in the BNCT system according to Embodiment 6 of the present invention.

[0221] First, in step S81, while using the patient position measurement system 5, the patient is accurately held at the ideal patient position 2Aa determined on the patient holding device 6. Next, in step S82, the boron concentration at the start of irradiation is estimated based on the blood boron concentration measurement taken immediately before irradiation.

[0222] Next, in step S83, irradiation with neutron beams is started at the planned dose. Next, the process proceeds to step S84, where it is determined whether or not the patient position change signal 5s from the patient position measurement system 5 has been received. If it is determined that the patient position change signal 5s has been received, the process proceeds to step S85; however, if it is determined that the patient position change signal 5s has not been received, the process proceeds to step S87.

[0223] In step S85, the current patient position, i.e., the fluctuating patient position, is acquired from the patient position measurement system 5. Next, in step S86, the current patient position (variable patient position) acquired in step S85 is transmitted to the treatment planning system.

[0224] Next, in step S87, the boron concentration is estimated by pharmacokinetic analysis, prompt gamma ray measurement, or PG-SPECT method. Next, in step S88, the estimated boron concentration is sent to the TPS.

[0225] Next, in step S89, the TPS reproduces the calculation model conditions under the conditions of fluctuating patient position and sequentially measured boron concentration, performs high-speed dose calculation, and transmits the calculation results to the irradiation control system. A supercomputer-level system, as shown in the figure, is used for this high-speed calculation. Next, in step S90, the doses of radiation received up to that point are accumulated.

[0226] Next, in step S91, it is determined whether the accumulated dose has reached the planned dose planned by the treatment planning system. If it is determined that the planned dose has been reached, irradiation is terminated. On the other hand, if it is determined that the planned dose has not yet been reached, the process returns to step S84. Industrial application fields

[0227] Industrial applications include treatment planning systems for boron neutron capture therapy (BNCT), BNCT systems, and external beam radiation therapy such as BNCT. In the field of BNCT where the radiation exposure time is long and the treatment system and treatment method have not been established, it can be a particularly effective technology. [Note] [Claim 4] The system includes a storage means for storing the position of the neutron irradiation device relative to the neutron irradiation port, which is determined for each patient and is considered to be the ideal patient position for neutron therapy for that patient, and the assumed average boron concentration during treatment, and a high-speed dose calculation unit. During actual treatment, when a signal of variation in the patient's position from the ideal patient position is received from the patient position measurement system, the conditions of the calculation model are reproduced at the patient position corresponding to the variation, and the boron concentration is calculated using the average boron concentration at irradiation estimated from the measured blood boron concentration immediately before irradiation. The high-speed dose calculation unit performs dose calculations under the conditions of the reproduced calculation model. A treatment planning system for BNCT, characterized by transmitting the rapidly calculated assigned dose value to the neutron irradiation control system in the BNCT system. [Claim 5] The system includes a storage means for storing the ideal patient position, which is the position of the neutron irradiation device relative to the neutron irradiation port determined for each patient and is considered to be the ideal position for neutron therapy for that patient, and a high-speed dose calculation unit. During actual treatment, the boron concentration is measured sequentially, and when these measured values ​​are received, The boron concentration is changed to the measured value obtained sequentially, while the patient's position is maintained at the ideal patient position, reproducing the conditions of the calculation model. The high-speed dose calculation unit performs dose calculations under the conditions of the reproduced calculation model. A treatment planning system for BNCT, characterized by transmitting the rapidly calculated assigned dose value to the neutron irradiation control system in the BNCT system. [Claim 6] The system includes a storage means for storing the ideal patient position, which is the position of the neutron irradiation device relative to the neutron irradiation port determined for each patient and is considered to be the ideal position for neutron therapy for that patient, and a high-speed dose calculation unit. During actual treatment, when a signal indicating variation in the patient's position from the ideal patient position is received from the patient position measurement system, the conditions of the calculation model are reproduced using the measured values ​​obtained sequentially during the actual treatment by prompt gamma ray measurement, at the patient position corresponding to the variation, and the boron concentration. The high-speed dose calculation unit performs dose calculations under the conditions of the reproduced calculation model. A treatment planning system for BNCT, characterized by transmitting the rapidly calculated assigned dose value to the neutron irradiation control system in the BNCT system. [Claim 7] A BNCT system comprising a neutron beam irradiation device, a patient holding device, a patient position measurement system, a BNCT treatment planning system, and a neutron beam irradiation control system, The BNCT system is characterized in that the neutron beam irradiation control system includes a storage means for storing information on the applied dose transmitted from the BNCT treatment planning system described in any one of claims 4 to 6, and an irradiation control unit that integrates these applied doses and performs irradiation termination control when the integrated value reaches the treatment target value.

Explanation of Symbols

[0228] 1 BNCT system 2 Treatment planning system 2A Storage means 2Aa Ideal patient position 2Ab Assumed average boron concentration 2Ac Assumed patient position 2Ad Dose given at the assumed patient position 2Ae Average boron concentration during irradiation 2Af Estimated stepwise decreasing boron concentration value [[ID=6,8]]2Ag Dose given at the assumed boron concentration Estimated stepwise decrease in boron concentration value during 2Ah irradiation 2Aj Variable patient position 2Ak Variable patient positioning dose Sequentially measured boron concentration in 2Am prompt gamma rays 2An High-Speed ​​Calculation Assigned Dose Value 2B Means for calculating the dose given to the assumed patient position 2B1 Ideal patient positioning dose calculation method 2B2 Calculation method for assuming boron concentration dose 2B4 Rapid calculation method for dose assigned to a variable patient position 2B5 Ideal patient position, sequential boron concentration measurement, and high-speed dose calculation method 2B6 Rapid dose calculation method with sequential measurement values ​​of fluctuating patient position and boron concentration 2C Estimated patient position selection means 2C1 Estimated Stepwise Decreasing Boron Concentration Selection Method 3. Neutron beam irradiation control system 3a Storage means 3b Irradiation control section 4 Neutron beam irradiation equipment 4A Irradiation port 4a Drive control unit 5. Patient Location Measurement System 5A Visible Light Camera 5S Patient position change signal 6 Patient holding device 6a Drive control unit R Neutron Therapy Room M patient

Claims

1. The position of the neutron irradiation device relative to the neutron irradiation port, which is determined for each patient, is the ideal patient position, which is considered to be the ideal position for neutron therapy for that patient, The estimated progressively decreasing boron concentration value, estimated from multiple assumed blood boron concentration measurements immediately before irradiation, The system includes a storage means for storing the assumed boron concentration dose calculated by a calculation means for calculating the dose based on each estimated stepwise decreasing boron concentration value, A BNCT treatment planning system characterized by receiving a blood boron concentration measurement immediately before irradiation, selecting the estimated stepwise decreasing boron concentration value closest to the measurement, and transmitting the assumed boron concentration dose based on that boron concentration value to the neutron irradiation control system in the BNCT system.

2. The position of the neutron irradiation device relative to the neutron irradiation port, which is determined for each patient, is the ideal patient position, which is considered to be the ideal position for neutron therapy for that patient, Each patient has at least one hypothetical patient position that is expected to be most likely to occur during treatment, and The assumed patient position dose calculated by the calculation means for calculating the dose at each assumed patient position, The estimated progressively decreasing boron concentration value, estimated from multiple assumed blood boron concentration measurements immediately before irradiation, The system includes a storage means for storing the assumed boron concentration dose calculated by a calculation means for calculating the dose based on each estimated stepwise decreasing boron concentration value, During actual treatment, when a patient position change signal is received from the patient position measurement system, the system selects the hypothetical patient position closest to the patient's position after the change, and, along with that hypothetical patient position, determines the dose to be administered at that hypothetical position. A BNCT treatment planning system characterized by receiving a blood boron concentration measurement immediately before irradiation, selecting the estimated stepwise decreasing boron concentration value closest to the measurement, and transmitting the assumed boron concentration dose based on that boron concentration value to the neutron irradiation control system in the BNCT system.

3. A BNCT system comprising a neutron beam irradiation device, a patient holding device, a patient position measurement system, a BNCT treatment planning system, and a neutron beam irradiation control system, The BNCT system is characterized in that the neutron beam irradiation control system includes a storage means for storing information on the applied dose transmitted from the BNCT treatment planning system described in claim 1 or claim 2, and an irradiation control unit that integrates these applied doses and performs irradiation termination control when the integrated value reaches the treatment target value.

Images