Devices for providing radiation therapy

Abstract

The present invention relates to a device for providing radiation therapy to a patient, comprising: an electron source for providing an electron beam; a linear accelerator for accelerating said beam to a predetermined energy; and a beam delivery module for delivering the accelerated beam from said linear accelerator towards the patient to treat a target volume with a radiation dose. The device further comprises intensity modulation means configured to modulate the distribution of the radiation dose within the target volume according to a predetermined pattern. The pattern has an area of ​​at least about 50 cm 3 The radiation dose is determined to match the dimensions of a target volume of at least about 5 cm deep within the patient's tissue, and / or a target volume located at a depth of at least about 5 cm deep within the patient's tissue. The delivered radiation dose is up to about 20 Gy delivered during a total treatment time of less than about 50 ms.

Description

Technical Field

[0001] The present invention relates to a device for radiotherapy comprising intensity modulation means, particularly a device for ultra-short time intensity modulated radiotherapy.

Background Art

[0002] Cancer is a globally dominant cause of death, mainly treated by surgery, radiotherapy (RT), and chemotherapy. Its incidence is increasing rapidly, but improvements in the potential for complete cure are slow, despite recent advances, particularly in immunotherapy, robotic surgery, and the introduction of new molecularly targeted drugs.

[0003] Since the pioneering research of Roentgen and Marie Curie in the early 20th century, radiotherapy has remained an essential tool for treating cancer. Recent developments in radiotherapy have made these treatments more accurate and effective, but the remaining side effects, such as damage to healthy tissue, still limit its use.

[0004] Delivering a high therapeutic radiation dose to a tumor depends on the ability to protect normal tissues from the harmful effects of radiation. Over the past few decades, optimizing the accurate dose distribution to the target volume and healthy tissues has emerged as the most powerful tool for obtaining a differential effect between normal tissues and tumors, thereby minimizing side effects.

[0005] One of the most efficient tools for achieving high conformality is intensity-modulated radiotherapy (IMRT), which uses multiple focused beams, each delivering a small portion of the dose, resulting in a highly conformal distribution of the total dose. In conventional radiotherapy, IMRT is planned with a specific inverse treatment planning system and delivered via rotation of the irradiation source along with mechanical modulation of the beam through a multi-leaf collimator. For proton therapy, beam intensity modulation is achieved using a fixed proton source and magnetic scanning, enabling the achievement of optimal proton conformality (intensity-modulated proton therapy, IMPT).

[0006] A complementary new solution to limit radiation-induced damage to normal tissue is to shorten the irradiation time in so-called FLASH radiotherapy (RT) or FLASH therapy. Conventional radiotherapy generally aims to deliver a total dose of 20-70 Gy to each tumor, typically in fractions of 2 Gy, with each fraction delivered over several minutes. In recent years, numerous experiments have demonstrated that RT with very short irradiation times (less than 50 ms) can significantly reduce side effects.

[0007] FLASH radiotherapy is a biological phenomenon that demonstrates that ultra-high dose rates can induce significant preservation of normal tissue, while the effect on tumors is maintained without impairment compared to the same radiation dose at conventional dose rates, resulting in more effective treatment. In published experiments, this biological FLASH effect is observed when ultra-high dose rates (typically exceeding 1.5 Gy per pulse) are used during a pulse, and the average dose rate within the pulse is 10 6 It has been reported that this can be achieved under certain conditions when using several ultra-intense pulses (exceeding Gy) and when a high total radiation dose (>10-20 Gy) is delivered over the entire duration in the range of milliseconds (ms), for example, when the 20 Gy delivery should be performed in less than 50 ms.

[0008] During the ultrashort timescale of flash delivery, it is unknown how intensity modulation of doses within each beam can be used to provide a highly conformal dose distribution in flash therapy. The use of mechanical modulation with multi-leaf collimators is not feasible on the flash timescale.

[0009] In the clinical context of deep-seated tumors within the body, achieving high conformation with IMRT requires multiple beams, typically up to 100 beams, all focused on the target. However, using multiple beams is not suitable for the flash effect, as biological flash sparging in normal tissue is inherently observed when using high single-beam doses of at least 10 Gy to 30 Gy per beam.

[0010] Therefore, existing solutions cannot meet the FLASH requirements when it comes to providing a highly conformal dose distribution to deep tumors and / or large tumors in FLASH treatment. [Overview of the Initiative] [Problems that the invention aims to solve]

[0011] The above-mentioned problems are solved, or at least partially solved, by the device and method according to the present invention. [Means for solving the problem]

[0012] The present invention is a device for providing radiation therapy to a patient, - An electron source for providing an electron beam, - A linear accelerator that accelerates the beam to a predetermined energy, - A beam delivery module for delivering an accelerated beam from the linear accelerator toward the patient in order to treat a target volume with radiation dose. In a device equipped with, The device further comprises intensity modulation means configured to modulate the distribution of radiation dose within a target volume according to a predetermined pattern that matches the target volume, The pattern includes several subsections, each subsection corresponding to a portion of the target volume, allowing the intensity modulation means to set the amount of radiation received by each portion of the target volume. The pattern is at least about 50cm 3 The target volume, and / or the dimensions of the target volume located at a depth of at least 5 cm within the patient's tissue, are determined to match the radiation dose. The present invention relates to a device characterized in that the radiation dose distributed by the intensity modulation means is up to approximately 20 Gy, and the radiation dose is delivered during the total treatment time of less than approximately 50 ms.

[0013] The dimensions of the target volume are preferably at least about 100 cm³, more preferably at least about 250 cm³, more preferably at least about 500 cm³, more preferably at least about 750 cm³, more preferably at least about 1000 cm³, more preferably at least about 2000 cm³, and more preferably at least about 3000 cm³.

[0014] The target volume is located at a depth of at least approximately 5 cm in the patient's tissue, meaning that the entire target volume is at a depth of at least 5 cm in the patient's tissue. Preferably, the target volume is at a depth of at least approximately 10 cm, at least approximately 15 cm, at least approximately 20 cm, or at least approximately 25 cm in the patient's tissue.

[0015] The radiation dose is preferably up to approximately 30 Gy, and more preferably up to approximately 40 Gy.

[0016] Preferably, the overall treatment (i.e., radiation therapy) time is less than about 10 ms, more preferably less than about 1 ms.

[0017] The present invention relates to a device for ultrashort-duration intensity-modulated radiation therapy to induce a flash effect in order to deliver intensity-modulated radiation doses.

[0018] In the present invention, the radiation dose, i.e., the total radiation dose, is delivered at a dose of 20 Gy typically in less than 50 ms on the time scale at which the FLASH effect is observed.

[0019] Intensity modulation describes a technique in which the dose is made to depend on the position within the target volume. The present invention enables the use of intensity modulation means in electron therapy at the FLASH time scale (i.e., the overall treatment time below 50 ms). The clinical objective of intensity modulation is essentially to achieve optimal conformity for optimal coverage of the target volume.

[0020] The claimed solution addresses the combination of FLASH treatment and dose intensity modulation for the purpose of providing a highly conformal FLASH therapy (= intensity modulated FLASH therapy).

[0021] By combining both FLASH conditions and intensity modulation of the dose, two powerful complementary tools are provided for sparing normal tissue while delivering an optimal high curative dose in the tumor. This combination significantly expands the potential applications of radiotherapy for cancer treatment.

[0022] The device of the present invention comprises intensity modulation means configured to modulate the distribution of the radiation dose within the target volume. The target volume is irradiated according to a pattern of subsections each corresponding to a part of the target volume.

[0023] Intensity modulation requires that the parts of the target volume corresponding to the subsections of the pattern are irradiated independently and that the dose of each subsection of the pattern is independently controlled so that each subsection can have its own intensity and energy. In other words, the pattern is a map and each subsection of the pattern corresponds to the coordinates of a part of the target volume. Advantageously, the pattern comprises a shifted bunch train in which the charge and energy are modulated.

[0024] Preferably, in a plane transverse to the beam, subsections are formed by focusing the beam to a size smaller than the target volume cross-section.

[0025] Focusing can be adjusted to a preferred value of 1 / 10, preferably 1 / 100, of the target cross-section per beam, since the entire target cross-section is irradiated.

[0026] The shape of the subsections can be adjusted to any shape, such as from circular to elongated elliptical, and rectangular or hexagonal.

[0027] In the state-of-the-art of clinical radiotherapy, intensity modulation means - changing the position of the leaves of the multi-leaf collimator (VMAT or step & shoot) and the pulse repetition rate during irradiation, or - continuously scanning a pencil beam of constant dose (PBS, e.g., proton pencil beam scanning) is meant.

[0028] Thus, in the above method from the state-of-the-art, the total intensity of the combined field is modulated, and the characteristics (charge, instance energy) of each particle train are not directly modulated. This is completely different in the present invention. In the present invention, the intensity modulation means individually modulates the charge and energy of the bunch trains in order to generate a fully intensity-modulated magnetic field.

[0029] The intensity modulation means of the present invention makes it possible to control the radiation dose in the tumor cross-section (independently for each incident beam line in the case of multiple beam lines) by adjusting the position, total charge and energy of each electron bunch within and between trains of electron bunches.

[0030] The pattern is, for example, at least about 50 cm 3The target volume and / or the dimensions of the target volume located at a depth of at least about 5 cm within the patient's tissue are determined to match the radiation dose. In other words, the present invention can deliver an intensity-modulated radiation dose of at least 20 Gy to a large target volume (e.g., meaning at least 50 cm³) or a deeply seated target volume (e.g., at least 5 cm deep) in an ultrashort time (meaning less than 50 ms), but existing radiotherapy devices cannot achieve all of these requirements simultaneously.

[0031] In this invention, key parameters for intensity-modulated radiation dose, i.e., delivering at least 20 Gy of radiation to a large target volume or deep target volume in an ultra-short time (meaning less than 50 ms), are simultaneously achieved under FLASH conditions.

[0032] In a preferred embodiment, the pattern corresponds to a treatment plan that can be selectively chosen from a uniform to a specified heterogeneous radiation dose distribution, depending on the clinical specifications of each individual patient.

[0033] The pattern preferably corresponds to a dose intensity gradient for gradually distributing the radiation dose within the target volume. The pattern is favorably selected using a treatment planning system specifically designed for FLASH therapy.

[0034] The pattern depends favorably on (one or a combination of the following factors). - Dimensions and / or shape of the target volume, - Proximity of vital organs and / or healthy tissues, - Number and direction of radiation beams, - The required radiation dose within each subsection.

[0035] The accelerated beam contains several trains of particle bunches. Each train and each bunch within a train has a configurable total charge and energy. The dose from each bunch train is determined by the charge of each bunch train. The charge per bunch train can be specified by the number of bunches in the bunch train and the charge per bunch. Setting the number of bunches is a preferred means of specifying the bunch train charge, giving a charge range, and therefore a dose range.

[0036] The intensity of the train is given by the charge per bunch and the number of bunches per train, which gives the dose delivered to a portion of the target volume by each train. The intensity modulation means according to the present invention allows the charge of each train to be set independently and directs each train to a predetermined position that modulates the dose distribution within the target volume.

[0037] The two trains of an electron bunch have the same charge and can be directed to different or the same part of the target volume. Alternatively, the electron bunches of two trains have different charges and can be directed to different or the same part of the target volume.

[0038] In another example, the energy remains fixed, but the charge can be varied for each train. In this example, a 100 MeV train could have a charge of 100 nC or 300 nC, correspondingly giving different doses. By distributing the 100 nC or 300 nC trains within separate subsections, it is possible to achieve intensity modulation, particularly lateral to the beam direction.

[0039] Intensity can also be modulated by changing both the energy of each train and the energy of each bunch within the train. In another example, there are 100 MeV and 102 MeV trains in an accelerating beam, with the 100 MeV having a charge of 300 nC and the 102 MeV having a charge of 100 nC. By setting the energy of the trains, it is possible to achieve intensity modulation lateral to the beam direction and longitudinal to the beam direction, as different energy beams follow different trajectories within the beamline, and the higher the energy, the deeper the train travels. Varying the energy of the trains within the beamline has two effects: 1) the train reaches the patient at different positions (lateral modulation), and 2) the beam transmission changes (longitudinal modulation).

[0040] In one embodiment, each section receives a dose up to the maximum total dose, which is, for example, at least about 20 Gy. The total dose is delivered in less than 50 ms. Therefore, for example, if the total dose is 20 Gy and the pattern includes 10 subsections, each subsection can receive a dose up to 20 Gy. The total dose, also called the prescribed dose, is the total dose that the target volume should receive in a single session of less than 50 ms, preferably less than 50 ms.

[0041] The total dose can preferably be increased to at least 35 Gy, and preferably at least 40 Gy, in less than 50 ms.

[0042] In one embodiment, each part receives at least one train of electron bunches. The electron trains have a specific total charge and energy. This provides a means of profiling the dose within the tumor in three dimensions and offers high conformability to the overall radiotherapy.

[0043] In a preferred embodiment, the electron source is a very high-energy electron beam having a charge of at least about 1000 nC, preferably at least about 1500 nC.

[0044] The electron source is preferably fixed (for example, relative to the patient). This means that during radiation therapy, the electron source is preferably stationary, i.e., not moving or not moving.

[0045] In one embodiment, the electron source is configured to deliver, for example, up to 20 trains of electron bunches, each at least 150 nC, over the entire time. The bunch charge is adjustable to nominally about 0.5 nC, and the trains are 300 bunches.

[0046] In one embodiment, the accelerating beam is composed of multiple electron bunch trains, and the intensity modulation means is configured to modulate the radiation dose by separating the electron bunch trains according to the charge and / or energy of each train. Each subsection of the pattern corresponds to a portion of the target volume that is independently irradiated by at least one train of electron bunches having a determined energy and total charge.

[0047] In one embodiment, the intensity modulation means includes charge variation means for independently setting the charge of each train and directing each train toward a predetermined subsection of the pattern to reach a corresponding portion of the target volume that modulates the distribution of radiation dose within the target volume.

[0048] For example, the intensity modulation means includes a deflection means for deflecting the position of each train of electron bunches in a direction lateral to the accelerating beam direction, wherein the deflection means has a deflection velocity faster than the interval time between two subsequent trains.

[0049] In one embodiment, the deflection means is an electromechanical means.

[0050] In another embodiment, the deflection means is an electromagnetic means such as a magnet or deflection magnet, for example, a dipole magnet or quadrupole magnet having a time-varying magnetic field, or a dipole coil. The magnet of the intensity modulation means is, for example, a high-speed ramping magnet or a magnet capable of high-speed field ramping.

[0051] In another embodiment, the deflection means is a radio frequency deflector. Such a deflector can impose time-varying transverse momentum on different bunches in the train, resulting in complex bunch position patterns at the target, which in turn modulate the intensity. The transverse momentum is changed by giving amplitude and phase variations to the radio frequency pulses that power the deflector. Radio frequency deflectors are typically located at the ends of linear accelerators (linacs).

[0052] Each deflection magnet can be deflected along two orthogonal axes, for example, by a pair of orthogonal dipole coils. A specific setting of the magnetic field gives a specific beam trajectory, and therefore the destination in the target cross-section.

[0053] To direct a series of bunch trains to designated positions in each subsection, the magnetic field of the deflection magnets is set to a specific set of values ​​over the passage time of the series of bunch trains, thus giving a specific sequence of beam trajectories. This is done by adjusting the current in the magnets over the time between bunch train passages. This means that the entire deflection is completed within a specified total treatment time of less than 50 ms, preferably less than 10 ms, and more preferably less than 1 ms (over all beamlines in the case of multiple beamlines). The bunch trains follow the designated trajectories, sequentially irradiating designated portions of the target volume.

[0054] The deflection means may be located at the ends of the linear accelerator (or within the beam delivery lines in the case of multiple beamlines). A preferred solution is a single deflection magnet at the end of each beamline. The deflection means can preferably deflect each train of electron bunch laterally to optimally cover the target volume.

[0055] For example, the deflection mechanism is implemented within a linear accelerator or a delivery module.

[0056] In one embodiment, the intensity modulation means includes energy modulation means for independently setting the energy of each train or each bunch within a train, and directing each train or each bunch (if the energy of each bunch is set) toward a predetermined subsection of the pattern to reach a corresponding portion of the target volume that modulates the distribution of radiation dose along the direction of the accelerating beam passing through the target volume. Specifically, since the longitudinal distribution of dose depends on energy, the greater the energy, the deeper the energy penetrates into the target volume (into the tissue). Therefore, by modulating the energy of the electron bunch train, it becomes possible to modulate the intensity along the direction of the accelerating beam (or along each beamline in the case of multiple beamlines). By irradiating the target volume with a train of electron bunches of a specified energy, longitudinal (beam direction) intensity modulation is generated.

[0057] In one embodiment, an energy variation means is configured to perform a predetermined energy variation between each train of electron bunches, and the energy variation means is preferably operated from a linear accelerator. Preferably, each train has an energy difference of about 1% to about 5%. In the case of multiple beamlines, the energy range between trains within the beamline is limited to less than the beamline selection energy difference.

[0058] For example, energy fluctuation means are operated by controlling the amplitude and phase of the high-frequency pulses in a linear accelerator. The energy of each train in the electron bunch at the end of the linear accelerator is determined by the amplitude of the radio frequency field within the linear accelerator and the relative phase between the beam and the radio frequency pulses.

[0059] The energy of bunches within a train and the entire bunch train can be varied by the specifications of the high-frequency pulses, and the programmed amplitude and phase of the high-frequency pulses supplied to the accelerating structure. Therefore, beam energy can be used for train positioning both between bunches and within bunches. Preferably, the energy variations within each train and within each bunch are used simultaneously to profile the dose distribution specified on both the horizontal and vertical axes within a FLASH timescale (less than 50 ms).

[0060] Increasing energy modulation methods can be clinically interesting because energy variations may provide further degrees of freedom along the direction of the accelerating beam, which can contribute to obtaining an optimal dose distribution (the higher the energy within each subsection, the deeper the beam in that subsection delivers the dose).

[0061] The charge variation means is preferably achieved by changing the number of bunches for each train and / or by changing the charge for each bunch.

[0062] In one embodiment, an accelerated electron beam is separated by separation means into a plurality of beamlines, preferably two or three beamlines, each beamline separated by a predetermined angle, and each of the beamlines is then focused toward the patient to reach the target volume in a total time of less than 50 ms, preferably less than 10 ms, more preferably less than 1 ms, and each beamline further includes independent intensity modulation means.

[0063] For example, the separation means is selected from a list that includes energy-based separation means using magnetic spectrometers and radio frequency deflector-based means.

[0064] Preferably, each beamline has an energy difference of about 10% to about 40%. In the case of multiple beamlines, the beamline selection energy difference is greater than the energy range between trains within the beamline.

[0065] Advantageously, each beamline is equipped with an independent intensity modulation means. This allows the independent intensity modulation of each beam to achieve the optimal conformality required for the delivery dose relative to the target volume.

[0066] Preferably, the target volume is illuminated from two or three beamlines, each having independent intensity modulation. In a preferred embodiment, the intensity modulation means include charge variation means, energy variation means, deflection means, and a combination of multiple beamlines. This combination enables three-dimensional intensity modulation. The optimal intensity modulation is preferably specified depending on the delimitation of the target volume and the nearby organs at risk.

[0067] In one embodiment, the accelerated electron beam has a predetermined energy between about 30 MeV and about 250 MeV, preferably between about 50 MeV and about 250 MeV, and more preferably between about 50 MeV and about 150 MeV.

[0068] The present invention further provides a method for treating a tumor target volume in a patient, - To provide a device according to the present invention, -Using the aforementioned radiation dose, at least about 50 cm 3 Determining the target volume and / or the target volume located at a depth of at least approximately 5 cm within the patient's tissue, - Determining a pattern that matches the dimensions of the target volume, wherein the pattern includes several subsections, each subsection corresponding to a portion of the target volume, so as to enable the intensity modulation means to set the radiation dose received by each portion of the target volume. - The intensity modulation means of the device is configured to modulate the distribution of radiation dose within a portion of the target volume according to a predetermined pattern, - To deliver a dose of radiation to a target volume according to a predetermined pattern, wherein the dose of radiation distributed by the intensity modulation means is a maximum of about 20 Gy, preferably at least about 30 Gy, more preferably at least about 40 Gy, during a total treatment time of less than about 50 ms, preferably less than about 10 ms, more preferably less than about 1 ms. Regarding methods including

[0069] The present invention makes it possible to provide a high dose of radiation (i.e., at least 20 Gy) with a highly conformal modulation intensity delivered under FLASH conditions (i.e., less than 50 ms).

[0070] The specific advantages of this method are the same as those of the devices of the present invention described herein and will not be repeated here.

[0071] The unique combination of high conformation and FLASH conditions allows for an optimal dose distribution. The treatment according to this invention can be used to treat all types of tumors.

[0072] Advantageously, intensity-modulated flash therapy uses high doses per fraction with a high conformity index, and very few fractions for treatment, e.g., 1 to 3 fractions, preferably 1 or 2 fractions, are expected to deliver the total radiation dose to each patient.

[0073] In one embodiment, this method is - Further includes setting up intensity modulation means to modulate the radiation dose by separating trains of electron bunches according to the charge and / or energy of each train.

[0074] In one embodiment, this method is - This includes independently setting the charge of each train and directing each train toward a predetermined subsection of the pattern to reach the corresponding portion of the target volume that modulates the distribution of radiation dose within the target volume.

[0075] In one embodiment, this method is - This includes independently setting the energy of each train and directing each train toward a predetermined subsection of the pattern, so that it reaches the corresponding portion of the target volume that modulates the radiation dose distribution along the direction of the accelerating beam passing through the target volume.

[0076] In one embodiment, this method is - Separating accelerated electrons into a plurality of beamlines, preferably two or three beamlines, by separation means, each beamline being separated by a predetermined angle, and then focusing each of the beamlines toward the patient to reach the target volume in a total time of less than 50 ms, preferably less than 10 ms, more preferably less than 1 ms, each beamline further comprising independent intensity modulation means. Includes.

[0077] Preferably, the pattern includes between 5 and 10 subsections per beam, each subsection having a high dose intensity.

[0078] In a preferred embodiment, the treatment is -Administering at least one train of electron bunches per subsection, preferably one or two trains of electron bunches per subsection, wherein each dose per subsection is modulated to a maximum of approximately 20 Gy per subsection, preferably a maximum of 30 Gy per subsection, and more preferably a maximum of 40 Gy per subsection. Includes.

[0079] In this invention, ultra-high dose-rate radiotherapy or ultra-high dose-rate high-dose irradiation means FLASH radiotherapy or FLASH therapy. FLASH radiotherapy can be defined as a radiotherapy treatment that preserves healthy tissue compared to conventional RT dose rates while maintaining the effect on tumors without compromising it.

[0080] As used herein, the term “extremely high dose rate radiation dose” means the total dose delivered to the target volume of the patient.

[0081] As used herein, the term “about” applies to a number or range of numbers and refers to a range of numbers that a person skilled in the art would consider equivalent to the listed values, i.e., plus or minus 10%. For example, “about 10 cm” refers to 10 cm + / - 10%, i.e., from 9.9 cm to 10.1 cm. In this invention, dose refers to the amount of radiation in Gy units delivered to a patient. The dose may be administered in several fractions.

[0082] As used herein, the term “patient” refers to mammals, including dogs, cats, rats, mice, monkeys, cattle, horses, goats, sheep, pigs, camels, and most preferably humans, as is well understood in the art. In some embodiments, a patient is a patient in need of treatment or a patient suffering from cancer. However, in other embodiments, a patient can be a normal subject. This term is not intended to indicate a specific age or sex. Therefore, adult and neonatal patients, whether male or female, are intended to be covered.

[0083] As used herein, the term "at least maximum X" means a value greater than 0 up to a maximum of X.

[0084] As used herein, the term “radio pulse” refers to a pulse of radio waves used in a linear accelerator. A linear accelerator uses microwave power radio pulses to accelerate a radiation beam from a radiation source, such as an electron beam from an electron source. For example, these radio pulses are about 250 ns long and can repeat in burst mode at a repetition rate of 1 kHz, i.e., a period of 1 ms. For example, the microwave frequency is in the X band, specifically 12 GHz, but can also be in the C (5.7 GHz) or S (3 GHz) band.

[0085] As used herein, the term “radiation pulse” refers to a pulse of particles after a linear accelerator. Each pulse accelerates at least a train of particle bunches, for example, electron bunches if the radiation beam is an electron beam. For example, since a particle bunch is about 1 ps long and comes every 1 ns, a 250 ns radio pulse will have 250 particle bunches. Each particle bunch has a charge of 1 nC, giving a total charge of 2500 nC (before collimation) and an average current of 1 A in the pulse.

[0086] In this specification, the word “means” (singular or plural) preceding or following a function may be replaced with the word “unit” or “module.” For example, “intensity modulation means” may be replaced with “intensity modulation unit” or “intensity modulation module.”

[0087] In this invention, the accelerated beam is composed of multiple trains, each train containing multiple bunches, and each bunch consisting of multiple particles. For example, in a treatment, there are 20 trains, each train comprising 300 bunches, and each bunch having a charge of 1 nC (1 nanocoulomb corresponding to 6.2 × 10^9 electrons). With respect to time, for example, from minimum to maximum, each bunch is approximately 1 ps in length (0.3 mm at the speed of light), with 1 ns between bunches. In this example, with 300 bunches / train, the train is therefore 300 ns in length, and 20 trains, delivered every 2.5 ms, reach the patient over a treatment time of 50 ms.

[0088] The embodiments of the device described herein can also be applied to the methods according to the present invention with necessary modifications.

[0089] The present invention may include one embodiment or a combination of embodiments. [Brief explanation of the drawing]

[0090] Further specific advantages and features of the present invention will become more apparent from the following non-limiting description of at least one embodiment of the invention with reference to the accompanying drawings. [Figure 1] This is an overall view of a first embodiment of the device according to the present invention. [Figure 2] This is a detailed diagram of a beam delivery module according to a first embodiment of the device according to the present invention. [Figure 3] This figure shows an example of a dose distribution using an intensity modulation means within a device according to the first embodiment. [Figure 4] This figure shows another example of a dose distribution using an intensity modulation means within the device according to the first embodiment. [Modes for carrying out the invention]

[0091] The detailed description of the present invention is intended to be non-limiting, as any feature of one embodiment can be advantageously combined with any other feature of a different embodiment.

[0092] Figures 1 and 2 show a device 1 according to the present invention according to a first embodiment, where Figure 1 is an overall overview and Figure 2 is a detailed view of the beam delivery module of the device.

[0093] Device 1 comprises an electron source 2, a linear accelerator 3, and a beam delivery module 4. Device 1 is configured to deliver a dose of radiation to a target volume 5 of a patient.

[0094] Radiation source 2 is a high-current electron source, specifically a high-frequency laser-driven optical injector.

[0095] Linear accelerator 3 is a high-current X-band linac. The linac has parameters of an 8.5-meter-long accelerating structure that operates with a beam load gradient of 35 MV / m. The linac is powered by two 50 MW peak-power X-band klystrons and a radio-frequency pulse compressor.

[0096] Figure 2 is a detailed view of the beam delivery module 4. The role of the beam delivery module 4 is to guide the beam from the electron source 2 to the patient's target volume 5. The beam delivery module 4 includes a separation means 6 and an intensity modulation means 7.

[0097] The accelerating beam is first split by the separation means 6 into two separate beamlines 8 and 9, namely the high-momentum beamline 8 and the low-momentum beamline 9.

[0098] In this example, the separation means 6 is a splitter dipole 10 (separation magnet) for separating the accelerating beam leaving the linear accelerator 3 into two separate beamlines. The splitter dipole 10 has the following parameters: - Size: 1000mm x 850mm x 800mm -Weight: 3000kg -Material: Iron yoke, copper coil - Bending angle: 122 degrees (for low-momentum beams); 65.5 degrees (for high-momentum beams) -Center magnetic field: 1.0T - Effective length: 0.555m (for low-momentum beams); 0.665m (for high-momentum beams)

[0099] Next, the separation means 6 controls each beamline 8 , 9 One of the dipoles 11, 12 above, i.e., high-momentum beamlines. 8 The system further includes a high-momentum dipole 11 on top and a low-momentum dipole 12 on the low-momentum beamline 9.

[0100] The high-momentum dipole 11 has the following parameters. - Size: 700mm x 735mm x 450mm -Weight: 1500kg -Material: Iron yoke, copper coil -Angle of bending: 54.5 degrees -Center magnetic field: 0.95T - Effective length: 0.5m -Current: 22.4A

[0101] The low-momentum dipole 12 has the following parameters. - Size: 700mm x 735mm x 450mm -Weight: 1500kg -Material: Iron yoke, copper coil - Flexion angle: 92.3 degrees -Center field: 1.09T - Effective length: 0.5m -Current: 27.2A

[0102] Device 1 further comprises intensity modulation means 7. In the example shown in Figures 1 and 2, the intensity modulation means 7 comprises deflection means 13 positioned on the respective beamlines 8 and 9 downstream of the high-momentum dipole 11 and the low-momentum dipole 12, respectively.

[0103] The deflection means 13 is a scanning magnet, preferably a high-speed ramping magnet, or a magnet capable of high-speed field ramping with the following parameters. - Size: 290mm x 205mm x 205mm -Weight: 1500kg -Material: Iron yoke, copper coil - Duty cycle: 10% -Integrated magnetic field: 0.034Tm -Maximum deflection angle: 100mrad - Effective length: 0.3m -Current: 5.6kA

[0104] Optionally, intensity modulation means 7 The system may further include energy modulation means (not shown). For example, energy modulation means further deflecting the trajectory of each train in the particle bunch by an angle of 1% to 5%.

[0105] Figures 3 and 4 show two examples of dose distributions that can be achieved using the present invention.

[0106] Figure 3 shows an example of a uniform dose distribution profile for a 100 MeV beam obtained with the intensity modulation described in the present invention. Figure 3 shows a graph of a uniform dose distribution at a depth of 10 cm within a target volume generated by a single beamline. In this example, the beam has an energy of 100 MeV, and the intensity modulation pattern includes five elliptical subsections, each with a cross-section of 10 cm × 3 cm. An average dose of 10 Gy is generated within a portion of the target volume, with each portion having an area of ​​10 × 15 cm² (cross-section) over a total time of 32 ms, using five trains with a duration of 0.3 μs repeated every 8 ms. The graph shows that when 10 Gy (unmodulated) is delivered to each subsection, the lateral superposition of the five adjacent subsections sums up to a uniform total dose.

[0107] Figure 4 shows an example of a heterogeneous dose distribution profile of a 100 MeV beam obtained with the intensity modulation described in the present invention. Figure 4 shows a graph of the heterogeneous dose distribution at a depth of 10 cm within a target volume generated by a single beamline. In this example, the beam has an energy of 100 MeV, and the intensity modulation pattern includes five elliptical subsections, each with a cross-section of 10 cm × 3 cm. An average dose of 10 Gy is generated within a portion of the target volume, and each portion has an area of ​​10 × 15 cm² (cross-section) within a total time of 32 ms, using five trains with a duration of 0.3 μs repeated every 8 ms. In contrast to Figure 3, the graph in Figure 4 shows that when the dose of each subsection is set to different levels from left to right, i.e., 11 Gy, 8 Gy, 10 Gy, 9 Gy, and 12 Gy, using the modulation means of the present invention, the lateral superposition of five adjacent subsections results in an intensity-modulated dose distribution in the range of + / - 20%. To generate other modulation patterns, the subsection charge and spot shape are optimized to produce a specified dose distribution (in this graph, -140nC, 100nC, 120nC, 110nC, and 150nC).

[0108] While embodiments have been described in conjunction with several other embodiments, many alternative, modified, and variant forms are considered, or are obviously, obvious to those skilled in the art in the applicable field. Therefore, this disclosure is intended to encompass all such alternative, modified, equivalent, and variant forms that fall within the scope of this disclosure. This is particularly true, for example, with respect to different available devices. [Explanation of symbols]

[0109] 1. Device according to the first embodiment 2 electron source 3 linear accelerator 4 Beam Delivery Module 5. Target volume of the patient 6 Separation means 7 Intensity modulation means 8 High-momentum beamline 9 Low-momentum beamline 10 Splitter Dipole 11. High-Momentum Dipole 12 Low-Momentum Dipole 13 Deflection means

Claims

1. A device (1) for providing radiation therapy to a patient, An electron source (2) for providing an electron beam, A linear accelerator (3) for accelerating the beam to a predetermined energy, wherein the beam accelerated by the linear accelerator (3) is composed of multiple trains of electron bunches, A beam delivery module (4) for delivering the multiple trains of electron bunches from the linear accelerator (3) toward the patient in order to treat a target volume (5) with radiation dose, and In a device (1) that includes, The beam delivery module (4) further comprises separation means (6) and intensity modulation means (7), wherein the intensity modulation means (7) is configured to generate a predetermined dose distribution within the target volume (5) according to a predetermined modulation pattern of a dose distribution that matches the target volume (5), The intensity modulation means (7) is configured to adjust the position, total charge, and energy of each electron bunch within and between trains of electron bunches, and the separation means (6) is configured to separate the trains of electron bunches according to the total charge and / or energy of each train. The modulation pattern comprises several subsections, each subsection comprising a train of electron bunches having a determined charge and energy, and the intensity modulation means (7) irradiates the corresponding portion of the target volume (5) such that each portion of the target volume (5) receives a set dose of radiation. The modulation pattern is characterized in that the dose distribution is determined to match the location within the patient and the size of each part constituting the target volume (5), wherein the target volume (5) is at least about 50 cm³. ３ and / or located at a depth of at least about 5 cm within the patient's tissue, The device (1) is further characterized in that the radiation dose distributed by the intensity modulation means (7) is at least about 20 Gy, and the radiation dose is delivered during the total irradiation time of radiation less than about 50 ms.

2. The device (1) according to claim 1, wherein the intensity modulation means (7) is configured to further adjust the projection size and arrival angle of each electron bunch within and between trains of electron bunches.

3. The device according to claim 1 or 2, wherein the radiation dose is at least 30 Gy, at least 35 Gy, or at least 40 Gy.

4. The device (1) according to any one of claims 1 to 3, wherein each part of the target volume (5) receives the maximum total radiation dose.

5. The device (1) according to any one of claims 1 to 4, wherein each portion of the target volume (5) receives at least one train of electron bunches.

6. The device (1) according to any one of claims 1 to 5, wherein the intensity modulation means (7) comprises charge variation means for independently setting the charge of each train and modulating the dose distribution inside the target volume (5) by directing each train toward a predetermined subsection of the modulation pattern of the dose distribution.

7. The device (1) according to any one of claims 1 to 6, wherein the intensity modulation means (7) comprises energy variation means for independently setting the energy of each train and directing each train toward a predetermined subsection of the modulation pattern to reach a corresponding portion of the target volume (5) that modulates the dose along the path of the beam accelerated by the linear accelerator (3) inside the target volume (5).

8. The device (1) according to any one of claims 1 to 7, wherein the beam accelerated by the linear accelerator (3) is separated into a plurality of beamlines (8, 9) by the separation means (6), each beamline (8, 9) is separated by a predetermined angle, and after being separated into beamlines (8, 9), each beamline (8, 9) is focused toward the patient and simultaneously reaches and irradiates the target volume (5) during a radiation irradiation time of less than 50 ms, and each beamline (8, 9) further comprises an independent intensity modulation means (7).

9. The device (1) according to any one of claims 1 to 8, wherein the intensity modulation means (7) comprises a deflection means (13) for deflecting the position of each train of the electron bunch in the lateral direction, and the deflection means (13) has a deflection speed faster than the interval time between two subsequent trains.

10. The device (1) according to claim 9, wherein the deflection means (13) includes a dipole magnet quadrupole magnet having a time-varying magnetic field, or a dipole coil, or a high-speed ramping magnet or a magnet capable of high-speed magnetic field ramping.

11. The device (1) according to claim 9 or 10, wherein the deflection means (13) comprises a radio frequency deflector.

12. The device (1) according to claim 7, wherein the energy fluctuation means is configured to perform a predetermined energy fluctuation between each train of electron bunches, and the energy fluctuation means is operated from the linear accelerator (3).

13. The device (1) according to claim 12, wherein the energy fluctuation means is operated by controlling the amplitude and phase of the high-frequency pulses of the linear accelerator (3).

14. The device (1) according to any one of claims 1 to 13, wherein the intensity modulation means (7) comprises a combination of a charge fluctuation means, an energy fluctuation means, a deflection means (13), and a plurality of beamlines (8, 9).

15. The device (1) according to any one of claims 1 to 14, wherein the beam accelerated by the linear accelerator (3) has a predetermined energy between approximately 30 MeV and approximately 250 MeV, between approximately 50 MeV and approximately 250 MeV, or between approximately 50 MeV and approximately 150 MeV.

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