Treatment device for delivering treatment plan for flash deposition with accelerator of charged particles by pencil beam scanning

Abstract

To provide a treatment device for delivering a treatment plan for flash deposition with an accelerator of charged particles by pencil beam scanning.SOLUTION: To shorten the time for depositing a target dose (Dti) into the cells spanned by the flash spots (Si) of the flash volume (Vht), the flash spots are combined into k sets of n flash spots (Si). After depositing a jth pulse dose (Dij) into the cells spanned by an ith flash spot (Si) the beam commutes from the ith flash spot (Si) to a next (i+1)th flash spot according to a flash scanning subsequence to deposit a jth dose into the cells spanned by each of the subsequent flash spots of the flash scanning subsequence, until returning to the ith flash spot to deposit a (j+1)th dose (Di(j+1)), and so on.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present invention relates to a therapeutic apparatus for executing a treatment plan for a therapeutic volume (V) including a flash volume (Vht) containing healthy cells and preferably tumor cells, using a beam of charged particles, preferably protons. To preserve healthy cells and kill tumor cells, the flash volume (Vht) must be dosed at an extremely high dose rate (HDR). The beam is emitted from a pulsed particle accelerator that delivers pulses of charged particles. Several pulses of the pulsed beam are generally required to deliver the target dose to the flash volume (Vht), which can prolong the dose delivery time beyond the limits required to enable HDR. The treatment plan according to the present invention allows for the delivery of a target dose at a predetermined location within the flash volume (Vht) using a pencil beam scan (PBS), with each spot distributed across a single painting layer spread throughout the entire flash volume. [Background technology]

[0002] Radiation therapy using particles or waves such as electron beams, proton beams, heavy ion beams, X-rays, and gamma rays has become an essential means of treating patients with tumors.

[0003] Because such radiation damages both tumor cells and healthy cells within a given volume, a major challenge in cancer treatment is formulating a treatment plan that ensures the effective destruction or death of tumor cells while preserving as many healthy cells, especially those adjacent to the tumor cells, as possible. The first step in treatment planning is imaging the tumor area using a CT scan. Based on these images, the oncologist identifies the appropriate targets and determines where and how much radiation to deliver to kill the tumor cells. Such plans are extremely complex because they must satisfy multiple, often competing, parameters. For this reason, treatment planning systems are generally computer-generated.

[0004] The first criterion that a treatment plan must meet is to ensure that, at the end of treatment, a total target dose sufficient to kill tumor cells is delivered to the volume. Simultaneously, the second criterion that a treatment plan must meet is to minimize the deterioration of healthy cells adjacent to the tumor cells. No matter how precise the dose delivery to the volume containing tumor cells may be, the radiation reaching that volume will almost certainly cross healthy cells and deliver doses to healthy cells surrounded by or contained within that volume. Different types of radiation have different energy delivery patterns. For example, X-rays deliver most of their energy at a depth near the epidermis, and the delivered energy decreases with depth. Therefore, healthy tissue located upstream of the target volume of tumor cells receives a higher dose than the tumor cells in the target volume. In contrast, as shown in Figures 1(a) and 1(c), charged particle beams, especially protons, deliver most of their energy near the end of their beam path, forming the so-called Bragg peak.

[0005] Pencil beam scanning (PBS) is a technique that involves steering a beam of charged particles towards individual spots within a mesh of spots that define a target volume containing tumor cells. This ensures that a predetermined target dose is delivered to the spread cells within each spot. Beam steering and dose delivery are carried out according to a treatment plan that defines the charge to be delivered at each spot and the scanning sequence for that spot. PBS reduces unnecessary radiation exposure to surrounding non-cancerous cells by shaping the treatment area to reflect the geometric shape of the tumor. In addition to the geometric shape of the target, PBS allows for localized adjustment of the beam intensity depending on the location of the spot within the target.

[0006] A mesh generally consists of several painting layers, each consisting of a two-dimensional array of spots positioned on a plane perpendicular to the irradiation axis (X). By sequentially arranging several painting layers, the resulting mesh of spots defines the entire target volume. Using accelerated proton beams, a single beam can continuously impart a predetermined charge to corresponding spots in each painting layer by superimposing several Bragg peaks at shifted depths in each painting layer along the irradiation axis (X). This results in spread-out Bragg peaks (SOBP) that spread across the entire depth of the tumor cell volume, or to a portion of it. This technique allows for the delivery of a target dose to the target volume by PBS in several painting layers with different beam energies. The painting layer (or depth) to which the dose is imparted can be controlled, i.e., controlled by the energy of the accelerated particles. The dose imparted to the cells with spread spots in the above painting layers can be controlled, i.e., controlled by the beam fluence (= number of charges per unit area). Due to the dosing pattern associated with the shape of the Bragg peak, healthy cells located upstream of the target volume traversed by the proton beam receive a lower dose than cells within the volume. However, when designing a treatment plan, it must be noted that each time a spread-out cell in a given painting layer receives a dose, the dose is added to the previously dosed dose each time a corresponding spread-out cell in a painting layer downstream of the given painting layer is dosed. In this specification, the terms “downstream” and “upstream” are used with respect to the direction of beam propagation.

[0007] In SOBP (Surface-Obstructed Proton Therapy) as described above, healthy cells located upstream of the target volume receive a significantly lower dose than cells contained within the target volume. Conversely, healthy cells within or adjacent to the target volume receive a dose similar to that of adjacent tumor cells within the same target volume. One principle of radiotherapy is that healthy cells are generally (somewhat) more resistant to radiation than tumor cells. The key to radiotherapy is "opening the therapeutic window," that is, finding a dose that damages the tumor while preserving healthy tissue. However, this therapeutic window is quite narrow. To minimize the degradation of healthy cells adjacent to tumor cells, the total dose received by healthy cells must not exceed the maximum permissible dose. Since the maximum permissible dose that healthy cells can (relatively) safely receive in one session may be substantially equivalent to the minimum target dose required to destroy tumor cells, there is a trade-off to be found between two conflicting requirements: on the one hand, delivering a dose sufficient to kill tumor cells, and on the other hand, delivering a dose that preserves healthy cells. This problem cannot be solved, but it can be mitigated by spreading the treatment over several sessions.

[0008] The total target dose is often delivered to tumor cells in one or more fractionated doses (or sessions) spaced apart over time. Fractionating dose delivery is one way to further expand the therapeutic range. The sum of the doses delivered in each session must reach the total target dose necessary to kill the tumor cells, taking into account the healing of cells in the time between two sessions. It has been observed that tumor cells have a longer recovery time to recover from damage sustained after a single fractionated irradiation than healthy cells. This suggests that increasing the number of sessions may allow healthy cells to heal better than tumor cells. However, since sessions are quite uncomfortable for patients, reducing the number of sessions is advantageous from the perspective of patient comfort and is more cost-effective.

[0009] Traditionally, radiotherapy treatment plans involved delivering radiation doses to the target cells at conventional dose-delivery rates (CDRs) of less than 1 Gy / s, generally on the order of 0.03 Gy / s. During a single session, the dose-delivery rate on a single cell by all overlapping spots is the ratio (Σ) of the sum of the doses (Dij) delivered to the cell (i) by the spots during the session to the sum of the time (tj) required to deliver the corresponding dose (Dij). j Dij / Σ iIt is defined as tj). With rare exceptions, current radiotherapy facilities deliver dose rates of less than 0.1 Gy / s, preferably on the order of 0.03 Gy / s, and most clinical protocols involve delivering multiple target doses (Dti) of 2-3 Gy per session at regular intervals, which accumulate to reach the total target dose. Since the total target dose is often close to the tolerance limit of normal tissue located in the irradiation field, it can damage normal tissue along with tumor cells. Recently, it has been confirmed that delivering the same dose with an ultra-high dose rate (HDR) has significantly less impact on healthy cells compared to delivering the same total dose with a conventional dose rate (CDR). However, this difference in behavior between CDR and HDR has not been observed in tumor cells. HDR can be more than an order of magnitude larger than the conventional dose rate (CDR) that is usually applied. Dose delivery with an ultra-high dose rate (HDR) is also called FLASH radiotherapy (=FLASH-RT). Dose delivery using HDR significantly preserves healthy tissue compared to the same dose delivery using conventional CDR, and experimental studies in animals and various organs have confirmed that tumor cells respond to HDR delivery as well as or better than those responded to CDR delivery. For example, FLASH-RT has been reported to dramatically reduce the incidence of pulmonary fibrosis, post-irradiation memory impairment, and small intestinal necrosis in mice while maintaining antitumor response rates. Such effective preservation of normal tissue has been confirmed in large animals, and patients with cutaneous lymphoma are already being treated with FLASH-RT. Therefore, a target dose (Dtj) on the order of 10-15 Gy can be delivered in a single FLASH session. FLASH has the advantage of expanding the therapeutic range with fewer sessions or fractions required than conventional dose delivery sessions.

[0010] The particles are accelerated to a speed of 1 / 3 the speed of light (c). As the speed of the charged particles approaches the speed of light, relativistic effects must be compensated for, and either the frequency of the electric field or the magnetic field must be modified to compensate for the increase in the mass of the charged particles as their speed increases. Relativistic effects become significant around v ≈ c / 3, where v is the particle velocity and c is the speed of light. For example, in a synchrocyclotron, the frequency of the driving RF electric field is changed along the acceleration path of the charged particles while keeping the magnetic field constant. Alternatively, in a synchrotron, the magnetic field is increased over time during the acceleration process while keeping the frequency of the driving RF electric field constant. Charged particles can also be accelerated to high speeds in laser-driven ion accelerators.

[0011] In order to allow the RF frequency of the magnetic or electric field to be changed during the acceleration process, charged particles must be accelerated in successive groups such that all charged particles are exposed to a magnetic field or RF frequency corresponding to their velocity. As a result, the charged particles are emitted in pulses (Pij), and each pulse corresponds to a group of charged particles having a pulse charge (Cij) limited to the maximum pulse charge (i.e., Cij ≤ CM). Each pulse has a duration of pulse time (tp), and the pulses are separated from each other by an inter-pulse interval (Δtp). The above parameters depend on the particle accelerator used. The maximum pulse charge (CM), inter-pulse interval (Δtp), and the number of pulses (N) required to impart the target dose to a given subvolume must be ensured to conform to HDR (i.e., the beam current N × CM / [(N-1) × Δtp] is large enough so that the dose rate in the tissue is 1 Gy / s or greater).

[0012] Each spot (Si) in a given painting layer receives a dose that is added to the previously assigned dose each time it is irradiated by a beam of charge (Cij), and the beam of charge (Cij) assigns doses (Dij) along the beam path to various spots located in painting layers downstream of the given painting layer; therefore, it is not possible to assign doses to multiple painting layers in HDR. In fact, the dose assignment ratio (Σ)j Dij / Σ ij The time denominator of tj) grows too rapidly in cells located furthest upstream in a target volume, which repeatedly receive small doses (Dj) during time (tj) each time a downstream spot is targeted. PBS in a single painting layer can be achieved using a proton beam by applying a dose following SOBP with a single beam over an entire subvolume whose cross-section is defined by the spot and which extends over the entire depth of the volume along the irradiation axis (X). The subvolume may be a cylinder with the spot at its base and extending along the irradiation axis (X).

[0013] In a two-dimensional array, depending on the spacing between adjacent spots, a beam targeting a given spot may deliver some dose to the spread cells of adjacent spots. This is because the charge fluence (number of charges per unit area) in the beam can be defined by a Gaussian distribution. Generally, if spots are separated by a distance of approximately 1.5σ of the Gaussian distribution of charge in the beam cross-section, it is thought that the overlap of Gaussian curves on adjacent spots will result in a substantially uniform fluence. The overlap of the Gaussian distribution profiles of the spots is desirable to ensure that no part of the target volume is not receiving the predetermined target dose, and that the fluence is uniform between adjacent spots. However, charge overlap and continuous, long-lasting dose delivery are quite detrimental to FLASH-RT. This is because each time a dose is delivered to the spread cells of adjacent spots due to overlap, the dose delivery rate of the ratio Σ j A larger tj denominator reduces the dose delivery rate to adjacent spots, which can easily become incompatible with HDR. This problem is even more pronounced with PBS delivery, because the target dose to be delivered to each subvolume in HDR generally must be delivered in several pulses. In fact, the target dose is generally greater than the amount that can be delivered by a single pulse of maximum pulse charge (CM). By delivering the target dose in several pulses, the delivery time Σj The length of tj extends not only to subvolumes but also to adjacent subvolumes due to overlap.

[0014] Due to the constraints described above, dose delivery by PBS in HDR becomes extremely complex. The present invention solves the problem of ensuring that the target volume treated by PBS of charged particles is effectively irradiated in HDR as needed, taking into account all overlapping dose delivery distributions of all charges that overlap or leak onto a given spot to be treated. These and other advantages are described in more detail below. [Prior art documents] [Patent Documents]

[0015] [Patent Document 1] European Patent No. 20200183082 [Non-patent literature]

[0016] [Non-Patent Document 1] Bortfeld, T. (1997) An analytical approximation of the Bragg curve for therapeutic proton beams.Med.Phys.,24(12),2024-2033 [Overview of the Initiative]

[0017] The present invention relates to a therapeutic apparatus for performing a treatment plan for a therapeutic volume (V) using a beam of charged particles, preferably protons, wherein the therapeutic volume (V) is • Target volume (Vt) containing virtually only tumor cells, • A flash volume (Vht) containing healthy cells and preferably tumor cells (3t) It consists of.

[0018] For example, the target volume (Vt) can be defined as the gross tumour volume (GTV) mainly containing tumour cells. The treatment volume may include the clinical target volume (CTV) defined as the range where the therapist desires to deliver the required dose. On the other hand, when the treatment volume corresponds to the CTV (i.e., the flash volume (Vht) is included in the CTV), the CTV becomes a combination of the GTV (or target volume (Vt)) and the flash volume (Vht), and thus includes tumour cells and healthy cells. On the other hand, when the treatment volume (V) includes the CTV and the organs to be preserved located upstream of the CTV in the beam path, the flash volume (Vht) includes the above organs, intersects the CTV, and extends beyond the CTV. The object of the present invention is to apply HDR so as to deliver the desired dose necessary for killing tumour cells to the entire CTV and preserve the healthy tissues included in the flash volume (Vht).

[0019] The treatment device is configured to deliver a pulse of charged particles that imparts a dose (Dij) within the treatment volume (V) such that, for each spot (Si, Ri) distributed over a single painting layer that spreads throughout the treatment volume (V) by pencil beam scanning (PBS), the dose is imparted to the spot (Si) whose dose is encapsulated within the flash volume (Vht) at a very high dose rate (HDR), where HDR is defined as a dose rate HDR ≧ 1 Gy / s, and the pulsed particle accelerator has the following characteristics, namely, · charged particles are emitted in pulses (Pij), each pulse having a pulse charge (Cij) below the maximum pulse charge (CM ≧ Cij) and a duration of the pulse time (tp), and the pulses are separated from each other by an inter-pulse interval (Δtp), · the beam of charged particles can be scanned at a maximum scan speed (vs = ds / Δts) from the first flash spot to the second flash spot, where ds is the distance between the first flash spot and the second flash spot, and Δts is the scan time required to scan from the first flash spot to the second flash spot characterized in that.

[0020] The treatment device comprises a computer or processor configured to control a pulsed particle accelerator to implement a treatment plan (TP), the treatment plan being · Defining a mesh of N flash spots (Si) covering the range of the projection of the flash volume (Vht) projected parallel to the irradiation axis (X) on a projection plane (Π) perpendicular to the irradiation axis (X), and being substantially parallel to the beam (100); · For each flash spot (Si), defining a target charge (Cti) necessary to impart a target dose (Dti) to the spread cells of each flash spot (Si); · In determining the theoretical flash charge plan for each flash spot (Si), which defines a theoretical number (mi) of pulse charges (Cij) of a certain number of pulses necessary to impart a target dose (Dti) to the spread cells of each flash spot (Si), the target charge (Cti) is equal to the sum of the theoretical pulse charges (Cij) of the said number (mi) of pulses irradiating the flash spot (i.e., TIFF2023010652000002.tif8170), or the target dose (Dti) is equal to the sum of the said number (mi) of pulse doses (Dij) imparted to the spread cells of the flash spot by each pulse charge (Cij) (i.e., TIFF2023010652000003.tif8170), and · Defining a flash scan sequence of N flash spots, which defines a sequence of flash spots (Si) to which a corresponding number (mi) of pulse doses (Dij) are imparted and including.

[0021] The gist of the present invention relates to a flash scan sequence, the flash scan sequence being · In defining a certain number (k) of sets (5), each set (5) including a certain number n of flash spots (Si), where 1 < n < N, - For each set (5) of n combined flash spots, the flash scan subsequence of n combined flash spots is defined such that the distance (ds) between all consecutive first and second flash spots in the set and ((Si, S(i+1)) and (Sn, S1)) is always less than or equal to the maximum distance (dM) defined as the product of the scan speed (vs) and the dead time (td) (i.e., d ≤ dM = vs × td), wherein the dead time (td) is the time between the end of one pulse and the beginning of the next pulse (i.e., td = Δtp - tp). Includes.

[0022] A processor, for example, (a) Direct the beam to the first flash spot (S1) (i.e., i=1), and deliver a first pulsed charge (C11) (i.e., j=1) to the spread cells of the first flash spot (S1) in the first flash scan subsequence of the first set of n combined flash spots, thereby conferring the corresponding first pulsed dose (D11), (b) Move the beam to the second flash spot (S2) (i.e., i=2) of the flash scan subsequence and deliver the first pulsed charge (C21) to the spread cells of the second flash spot (S2) to impart the first pulsed dose (D21) in order to measure the actual first pulsed charge (C11) actually delivered to the first flash spot (S1) during the treatment session and to calculate the adjusted theoretical second pulsed charge (C12) to be next delivered to the first flash spot (S1) in accordance with the theoretical flash charge plan. (c) If i < n, move the beam to the i-th flash spot (Si) of the flash scan sub-sequence, and during the estimated time required to measure the actual previous pulse charge (C(i-1)1) actually delivered to the previous flash spot (S(i-1)) during the treatment session and to calculate the adjusted theoretical second pulse charge (C(i-1)2) to be delivered next at the previous flash spot (S(i-1)) according to the theoretical flash charge plan, deliver the first pulse charge (Ci1) to the spread cells of the i-th flash spot (Si), (d) Repeat the previous step (n - 3) times until i = n, (e) Return the beam to the first flash spot (S1) of the flash scan sub-sequence (i.e., i = 1), and during the estimated time required to measure the actual first pulse charge (Cn1) delivered to the n-th flash spot (Sn) during the treatment session and to calculate the adjusted theoretical second pulse charge (Cn2) to be delivered next at the n-th flash spot (Sn) according to the theoretical flash charge plan, apply the adjusted theoretical second pulse charge (C12) calculated as above at the first flash spot (S1) (i.e., j = 2), (f) Repeat steps (b) to (e) until j = (mi - 1), and at least repeat steps (b) to (d) for j = mi until the target charge (Cti) is delivered to each of the first flash spots (S1, Sn) of the first set of n combined flash spots, (g) Move the beam to the first flash spot according to the second flash scan sub-sequence of the second set of n combined flash spots, and repeat steps (a) to (f) for the n combined flash spots of the second set of n combined flash spots, (h) Repeat the last step for the remaining (k - 2) sets of flash scan subsequences of the n combined flash spots until the corresponding target charge (Cti) is delivered by HDR to all k sets (5) of n combined flash spots of the mesh. configured to control a pulsed particle accelerator as such.

[0023] The number (n) of combined flash spots in a set (5) is · when tc / td is an integer, the ratio tc / td > 1 (i.e., 0TIFF2023010652000004.tif7170, n = tc / td), and · otherwise, the sum of 1 and the integer part of the ratio (tc / td) (i.e., n = INTEGER(tc / td)+1) can be defined as td is the dead time, and tc is the calculated adjusted theoretical pulse charge (Ci(j + 1)) based on the actual pulse charge (Cij) measured by the first pulse (Pij) preceding the second pulse (Pi(j + 1)), and is the calculation time required by the pulsed particle accelerator to define and prepare the next pulse (P(j + 1)) according to it, and is longer than the dead time (tc > td). The number (k) of sets (5) of n combined flash spots can be defined as the integer part of the ratio (N / n) (i.e., n = INTEGER(N / n)), and an additional set of nR flash spots can be defined and handled as a set of n combined flash spots as defined above, and nR (< n) is the remainder of the ratio N / n until the target charge (Cti) is delivered by HDR to all N flash spots of the mesh.

[0024] In a preferred embodiment, the number (n) of combined flash spots is 2 (i.e., n = 2), · In the first flash scan sub-sequence of the first set of n = 2 flash spots (S1, S2), the second flash spot (S2) must receive a number of pulses (P1 to Pm2) to reach the second target charge (Ct2) that is greater than the number of pulses (m1) required for the first flash spot (S1) to deliver the first target charge (Ct1) to the first flash spot (S1) (i.e., m1 < m2 and Ct1 < Ct2), · When the first flash spot (S1) and the second flash spot (S2) of the first set (5) each receive m1 pulses and the target charge (Ct1) is delivered to the first flash spot (S1), the second flash spot (S2) dissociates from the first flash spot (S1) and combines with the third flash spot (S3) to form a second set of n = 2 flash spots (S2, S3), where the third flash spot (S3) is located at a distance d (d ≦ DM) from the second flash spot (S2), and both the second flash spot (S2) and the third flash spot (S3) each receive (m2 - m1) pulses until the second flash spot (S2) receives the target charge (Ct2), and the third flash spot (S3) must receive a third target charge (Ct3) that is greater than the residual charge (Ct2 - Ct1), · The third flash spot (S3) dissociates from the second flash spot (S2) and combines with the fourth flash spot (S4) to form a third set of n = 2 flash spots (S3, S4), and so on, until all N flash spots of the mesh receive their respective target charges (Cti) in HDR.

[0025] Generally, the calculation time (tc) is at least the following steps, namely, · Measuring the pulse charge (Cij) delivered by the j-th pulse (Pij) applied to the i-th flash spot (Si), and · The accumulated theoretical pulse charge TIFF2023010652000005.tif8170 shows the accumulated pulse charge actually measured at the i-th flash spot (Si) after j pulses. The steps involve calculating the adjusted theoretical pulse charge (Ci(j+1)) that should be applied to the i-th flash spot by the required (j+1) pulse (Pi(j+1)) according to the charge plan by comparing with TIFF2023010652000006.tif8170, The steps include: preparing the pulsed particle accelerator to emit the next pulse (Pi(j+1)) with a tuned value of the theoretical pulse charge (Ci(j+1)); and It may be necessary to complete this.

[0026] In a preferred embodiment, the treatment is - Define a mesh of M normal spots (Ri) that cover the projection range of the target volume (Vt) (i.e., Vt = V - Vht) projected parallel to the irradiation axis (X) onto the projection plane (Π), • Determine a normal charge plan for each normal spot (Ri) that specifies the value of each pulse charge (Cij) to impart a target charge (Cti) using mi pulses, rather than necessarily HDR. • Define a normal scan sequence for assigning a target charge (Cti) to each of the M normal spots (Ri). Includes.

[0027] The present invention also relates to a treatment planning system (TPS) for implementing the treatment plan (TP) defined above, wherein the TPS is A mesh unit configured to define a mesh of N flash spots (Si) covering the projection range of a flash volume (Vht) that is projected parallel to the irradiation axis (X) and approximately parallel to the beam (100) on a projection plane (Π) perpendicular to the irradiation axis (X), • For each flash spot (Si), a target charge unit is configured to define the target charge (Cti) necessary to impart a target dose (Dti) to the cells where each flash spot (Si) has spread, · In a flash plan unit configured to determine a theoretical flash charge plan for each flash spot (Si), which defines the theoretical pulse charge (Cij) of a certain number (mi) of pulses required to impart a target dose (Dti) to the cells where each flash spot (Si) has spread, the target charge (Cti) is equal to the sum of the theoretical pulse charges (Cij) of the above-mentioned number (mi) of pulses irradiating the flash spot (i.e., TIFF2023010652000007.tif8170, or the target dose (Dti) is equal to the sum of the above-mentioned number (mi) of pulse doses (Dij) imparted to the cells where each flash spot has spread by each pulse charge (Cij) (i.e., TIFF2023010652000008.tif8170), a flash plan unit, and · A flash scan sequence unit configured to define a flash scan sequence of N flash spots, which defines a sequence of flash spots (Si) where a corresponding number (mi) of pulse doses (Dij) are imparted to the cells where each flash spot has spread is provided.

[0028] The flash scan sequence unit performs the following operations, that is, · In an operation of defining a certain number (k) of sets (5), each set (5) includes a number n of flash spots (Si), where 1 < n < N, and · For each set (5) of n combined flash spots, the distance (ds) between all consecutive first flash spots and second flash spots ((Si, S(i + 1)) and (Sn, S1)) of the set is always less than or equal to the maximum distance (dM) defined as the product of the scan speed (vs) and the dead time (td) (i.e., d ≤ dM = vs × td). In an operation of defining a flash scan subsequence of n combined flash spots, the dead time (td) is the time between the end of a pulse and the start of the next pulse (i.e., td = Δtp - tp). is configured to plan. [Brief explanation of the drawing]

[0029] [Figure 1] Figure 1(a) shows an example of an expanded Bragg peak (SOBP). Figure 1(b) shows an example of irradiation of a target volume containing tumor cells surrounded by healthy cells. Figure 1(c) shows an SOBP obtained using a proton beam along a given irradiation axis (X). [Figure 2] Figure 2(a) is a schematic perspective view of a system including a target volume with healthy tissue positioned upstream along the irradiation axis (X). The corresponding SOBP along the irradiation axis (X) and the projection of the treatment volume (V) onto a plane (Π) are shown. Figure 2(b) shows a side view of the system in Figure 2(a) (perpendicular to the irradiation axis (X)) along with the corresponding SOBP. Figure 2(c) shows a front view of the system in Figure 2(a) (parallel to the irradiation axis (X)). Figure 2(d) shows details of Figure 2(c) along with the spot. [Figure 3] Figure 3 shows the charge of each pulse of a pulsed beam irradiating a spot (Si) with a continuous pulse of electric charge (Cij) using a particle accelerator, as a function of time (lower graph), and the accumulated dose (ΣjDij) as a function of time (upper graph). [Figure 4] Figure 4(a) illustrates the principle of the present invention as a function of time, through the continuous application of dose to spread cells by the same pair of first spots (S1) and second spots (S2). Figure 4(b) shows a top view of Figure 4(a), illustrating the scan sequence between the first spot (S1) and the second spot (S2). [Figure 5]Figure 5(a) shows the cumulative dose delivered to adjacent spread cells of the first and second spots as a function of time by a conventional treatment plan in which the first and second spots are irradiated sequentially. Figure 5(b) shows the cumulative dose delivered to adjacent spread cells of the first and second spots as a function of time by a first embodiment of the flash scan sequence according to the present invention, where n=2. Figure 5(c) shows the cumulative dose delivered to adjacent spread cells of the first, second, third, and fourth spots as a function of time by a second embodiment of the method according to the present invention, where n=2. [Figure 6] Figure 6(a) shows a sequence of n=2 flash spots, where the same predetermined number of pulses are emitted from each of the two flash spots in a pair. Figure 6(b) shows a sequence of n=2 spots, where different target doses are applied to the spread cells of each of the two flash spots in a pair. [Modes for carrying out the invention]

[0030] The present invention relates to a therapeutic apparatus for the treatment of a therapeutic volume (V) using a beam (100) of charged particles, preferably protons, wherein the therapeutic volume (V) is • Target volume (Vt) containing virtually only tumor cells (3t), • Flash volume (Vht) containing healthy cells (3h) and tumor cells (3t) It consists of.

[0031] The treatment device includes a pulsed particle accelerator and a processor.

[0032] A pulsed particle accelerator is configured to deliver pulses of charged particles. For example, a pulsed particle accelerator can be a synchrocyclotron, a synchrotron, or a laser-driven ion accelerator. A pulsed particle accelerator has the following characteristics, namely: • Charged particles are emitted in pulses (Pij), each pulse having a pulse charge (Cij) (Cij ≤ CM) less than or equal to the maximum pulse charge and a pulse duration (tp), and the pulses are separated from each other by an interpulse interval (Δtp) (see Figures 3, 4(a), and 5(a) to 5(c)). • A beam of charged particles can scan from the first flash spot to the second flash spot at the maximum scan speed (vs = ds / Δts), where ds is the distance between the first and second flash spots, and Δts is the scan time required to scan from the first to the second flash spot (see Figure 4(b)). It is characterized by the following:

[0033] The beam can be defined by the type of charged particle to be irradiated (preferably protons), the maximum pulse charge (CM) of the pulse (Pij), the pulse duration (tp) for delivering the pulse, and the interpulse interval (Δtp) which specifies the time required for the particle accelerator to emit a second pulse (Pi2) after the first pulse (Pi1) has been emitted. The number of beams and the beam direction are important parameters. In this specification, only one beam direction extending along the irradiation axis (X) will be discussed. As will be obvious to those skilled in the art, the same description can be applied to various beam directions with the necessary modifications. SOBP can be obtained by superimposing coaxial beamlets that define the shape of the SOBP. Alternatively, a single beam (100) can be emitted and shaped by interposing a ridge filter. These techniques are well known to those skilled in the art and do not need to be described herein.

[0034] The beam has a diameter. Charged particles are distributed in a Gaussian distribution in the cross-section of the beam perpendicular to the irradiation axis (X). The radius of the beam can be defined as 2σ of the Gaussian distribution.

[0035] The pulsed particle accelerator is configured to deliver dose within the treatment volume (V) for each spot (Si, Ri) distributed over a single painting layer that spreads over the entire treatment volume (V) by means of pencil beam scanning (PBS). The dose must be delivered to the spread cells of the spot (Si) encapsulated within the flash volume (Vht) with a high dose rate (HDR), where HDR is defined as dose rate HDR ≧ 1 Gy / s. The dose can be delivered at any ratio (CDR or HDR) at all normal spots (Ri) of the treatment volume (V) located outside the flash volume (Vht) (see Fig. 2(d)).

[0036] The processor is configured to control the pulsed particle accelerator to implement a treatment plan (TP). The TP includes · specifying a mesh of N flash spots (Si), and · for each flash spot (Si), specifying the target charge (Cti) required to deliver the target dose (Dti) to the spread cells of each flash spot (Si), and · in the specification of the theoretical flash charge plan for each flash spot (Si), including the theoretical pulse charge (Cij) of a certain number (mi) of pulses required to deliver the target dose (Dti) to the spread cells of each flash spot (Si), where the target dose (Dti) is equal to the sum of the above-mentioned number (mi) of pulse doses (Dij) delivered to the spread cells of the flash spot by each pulse charge (Cij) (i.e., TIFF2023010652000009.tif7170), the specification, and · in the specification of the flash scan sequence of N flash spots, where the scan sequence includes ○ in the specification of a certain number (k) of sets (5), each set (5) including a certain number n of flash spots (Si), where 1 < n < N, the specification, and ○For each set (5) of n combined flash spots, the distance (ds) between all consecutive first and second flash spots ((Si, S(i+1)) and (Sn, S1)) of the set is always less than or equal to the maximum distance (dM) defined as the product of the scan speed (vs) and the dead time (td) (i.e., d ≤ dM = vs × td), wherein the dead time (td) is the time between the end of one pulse and the beginning of the next pulse (i.e., td = Δtp - tp), and Regulations and Includes.

[0037] The processor is also configured to control the pulsed particle accelerator to perform, for example, the flash scan sequence described below.

[0038] Spot mesh First, as shown in Figures 2(a) and 2(d), a mesh of N flash spots (Si) is defined on a projection plane (Π) perpendicular to the irradiation axis (X), and the flash spot (Si) is projected parallel to the irradiation axis (X), which is approximately parallel to the beam (100), covering the projection range of the flash volume (Vht).

[0039] Oncologists characterize the geometric shape and topography of a tumor region based on images of the tumor region obtained by computed tomography (CT scan). Figure 2(a) schematically shows an example of a tumor region, where a healthy organ (Vh) containing healthy cells (3h) is located between the patient's skin (3s) and a target volume (Vt) mainly containing tumor cells (3t). In order to reach the target volume (Vt), the beam (100) must traverse the healthy volume (Vh), thus irradiating both the healthy cells (3h) in the healthy volume (Vh) and the tumor cells (3t) in the target volume (Vt). In some embodiments, downstream organs (shaded in Figure 2(a)) contain both healthy cells and tumor cells (3h, 3t), making it impossible to target tumor cells without irradiating healthy cells.

[0040] Pencil beam scanning (PBS) defines a mesh of spots that characterize the entire volume to be irradiated. Because, with currently available instruments, it is impossible to apply FLASH-RT to the entire tumor area in many applications, and in order to take advantage of the benefits of FLASH-RT, the mesh according to the present invention includes flash spots (Si) to be irradiated with HDR and normal spots (Ri) that can be irradiated with CDR. Figure 2(d) shows an example of a mesh that includes both flash spots (Si) (= black dots) contained within a flash volume (Vht) and normal spots (Ri) (white dots) contained within a target volume (Vt). In the embodiment of Figure 2, the flash spots (Si) are spots aligned with the beam that must traverse healthy organ (Vh). As described above, the flash volume (Vht) may include healthy cells (3h) adjacent to tumor cells (3t).

[0041] To achieve HDR application across the entire flash volume (Vht), the treatment plan of the present invention includes a single painting layer. For this reason, it is preferable that the flash spots (Si) contained within the flash volume (Vht) are aligned on the irradiation beam (X) of each beam traversing a two-dimensional array of flash spots. The two-dimensional array is a projection parallel to the irradiation beam (100) onto a plane perpendicular to the irradiation beam. In this way, all flash spots (Si) distributed over a certain depth parallel to the irradiation axis (X) of the flash volume (Vht) are contained within a cylinder composed of a base plane defined by the spots in the two-dimensional array and a generatrix parallel to the irradiation axis (X). The length of these cylinders depends on the position where the cylinders intersect the boundary of the flash volume (Vht).

[0042] The spot has dimensions perpendicular to the irradiation axis (X), which can be equal to the beam diameter mentioned above. The higher the mesh density (i.e., the closer adjacent spots are to each other), the greater the effect of dose overlap from adjacent spots on spread cells; therefore, the distance between adjacent spots, which defines the mesh density, is an important parameter. When the distance between adjacent spots is approximately 1.5σ, a considerable overlap is observed, resulting in a uniform dose distribution in the lateral direction.

[0043] Charge Plan The treatment plan must kill tumor cells present in the tumor area while preserving as many healthy cells as possible that are adjacent to or in the beam's path targeting the tumor cells. The oncologist establishes a table listing the doses to be delivered to each volume. The dose delivered by a beam of a given fluence depends on the type of tissue and how the tissue interacts with the beam. For the same tissue, the dose delivered by a given beam primarily depends on the beam's fluence (= number of charges per unit area (Cij)). To kill tumor cells, a target dose (Dti) is delivered in a session to spread cells in both flash spots (Si) and normal spots (Ri).

[0044] To preserve healthy cells, the treatment plan must meet a target dose rate, at which the dose is locally delivered to the flash volume (Vht) to kill tumor cells while leveraging the FLASH effect to preserve healthy cells as much as possible. These target dose rates are generally determined by an oncologist who identifies one or more flash volumes (Vht) containing healthy cells, based on an image of the tumor region obtained by computed tomography (= CT scan). To achieve the FLASH effect in one or more specific volumes (Vht), the one or more specific volumes (Vht) must be irradiated at an ultra-high dose rate (HDR), where the HDR in each voxel of the volume is defined as the dose rate and HDR (= Σ i,j Dij / Σ j tj≧1 Gy / s) is the ratio of the sum of the doses (Σ i,j Dij) delivered to the specified voxel of the flash volume by each pulse (Pij) over all pulses (Pij) delivered to all flash spots (Si) that deliver dose to that voxel, to the sum (Σ j Dij) of the times (tj) required to deliver the dose (Σ j tj) to one flash spot (Si) (see Figure 3). The sum of the times includes the time during which dose is delivered by the overlap from beams targeting adjacent flash spots. A voxel is a portion of tissue that receives dose from several overlapping spots. The term "voxel" is used in CT scans and can typically have a size of 2×2×2 mm. Thus, a voxel can contain many biological cells. Since oncologists generally rely on the results of CT scans to define the dose to be delivered to cells, it is reasonable to use the same terms and concepts for treatment planning.

[0045] To include dose rates in a treatment plan, the capabilities of the particle accelerator available to execute the plan may be considered. For example, a maximum dose rate (DRmax) can be defined, at which a given pulsed dose (Dij) can be delivered by the beam to a flash spot (Si) as DRmax = Imax.K(E). Imax is the maximum beam current that the proton accelerator nozzle can deliver, and K(E) is the proton fluence (1cm) for different incident energies (E) of the proton beam. 2 It is a known function that relates the number of charge particles (=protons) per unit to the dose delivered to the tissue by the proton beam. For example, in equation 26 of (Non-Patent Literature 1), the factor to the right of φ0 represents K(E).

[0046] According to the present invention, for each flash spot (Si), the target charge (Cti) required to impart a target dose (Dti) to the cells of the voxel spread by each flash spot (Si) is defined at the end of the session. The target charge (Cti) depends on the properties of the beam and the properties of the tissue to which the target dose (Dti) is imparted and to which the beam interacts.

[0047] Once a target charge (Cti) is defined for each flash spot (Si), a charge plan is determined that allocates both the number of pulses (mi) to be delivered and the theoretical pulse charge (Cij) for each flash spot (Si). The charge plan involves defining the theoretical pulse charge (Cij) of a certain number (mi) of pulses necessary to ultimately impart the target dose (Dti) to each voxel in the spread cells of each flash spot (Si). Thus, as shown in Figure 3, the target charge (Cti) is equal to the sum of the above number (mi) of theoretical pulse charges (Cij) that irradiate the flash spot (i.e., TIFF2023010652000010.tif8170). This also means that the target dose (Dti) is equal to the sum of the above number (mi) pulse doses (Dij) that are applied to the cells with a spread flash spot by each pulse charge (Cij) (i.e., It can also be expressed in terms of dose, as shown in TIFF2023010652000011.tif8170. However, due to statistical uncertainty, the pulse charge actually delivered in each pulse by the particle accelerator can only be approximated by the theoretical pulse charge (Cij). Therefore, it is necessary to measure the actual value of the delivered charge and compare it with the theoretical pulse charge value (Cij). If there is a discrepancy between the two values ​​that exceeds a predetermined tolerance, the theoretical pulse charge (Ci(j+1)) for the next pulse can be corrected to a new value of the adjusted theoretical pulse charge to match the (theoretical) charge plan.

[0048] Next, a flash scan sequence of N flash spots is established, which defines a sequence of flash spots (Si) to which a corresponding number (mi) pulse dose (Dij) is applied to the spread cells of each flash spot. The flash scan sequence is defined as follows:

[0049] Flash scan sequence A set of n flash spots (5) A number (k) of sets (5) of combined flash spots (Si) are defined, each set (5) containing a number n of flash spots (Si), where 1 < n < N. Preferably, n = 2. For each set (5) of n combined flash spots, the distance (ds) between every consecutive first and second flash spots of the set ((Si, S(i + 1)) and (Sn, S1)) is always less than or equal to the maximum distance (dM) defined as the product of the scan speed (vs) and the dead time (td) (i.e., d ≤ dM = vs × td). Thus, a flash scan sub - sequence of n combined flash spots is defined, and the dead time (td) is the time required by the particle accelerator to emit the second pulse (Pi2) after the first pulse (Pi1) has been emitted (i.e., td = Δtp - tp). Since the beam takes time (Δts) to move from the first spot to the second spot, all pairs of flash spots in the scan sub - sequence must be spaced such that they require a scan time (Δts) that is not longer than the dead time (td) to scan from the first flash spot to the next flash spot in the scan sub - sequence (i.e., Δts ≤ td, ∀(Si, S(i + 1))). The scan sub - sequence proceeds as follows, as shown in FIGS. 4(a) and 4(b).

[0050] In a preferred embodiment, the number (n) of combined flash spots in the set (5) is determined as follows, that is, · when tc / td is an integer, the ratio tc / td > 1 (i.e., in the case of TIFF2023010652000012.tif7170, n = tc / td), and · otherwise, the sum of 1 and the integer part of the ratio (tc / td) (i.e., n = INTEGER(tc / td)+1) is defined, As shown in FIGS. 3, 4(a), 4(b), 5(a), and 5(b), td is the dead time, and tc is the calculation time required by a pulse particle accelerator that includes defining and preparing the next pulse (P(j+1)) according to an adjusted theoretical pulse charge (Ci(j+1)) calculated based on the actual pulse charge (Cij) measured by the first pulse (Pij) that executes the calculation operation detailed below and precedes the second pulse (Pi(j+1)), and tc is longer than the dead time (tc > td). For example, when t / Δtp is included in 1.5 to 2.0, or 1.6 to 1.8, the number of flash spots per set (5) can be equal to n = 2.

[0051] The number (k) of sets (5) of n combined flash spot sets can be the integer part of the ratio (N / n) (i.e., n = INTEGER(N / n)), and an additional set of nR flash spots can be defined and handled as n combined flash spot sets as defined below, where nR (<n) is the remainder of the ratio N / n until the target charge (Cti) is delivered in HDR to all N flash spots of the mesh in the flash volume.

[0052] Flash scan subsequence The first pulse (P1) of a pulsed charge (C11) is delivered to the spread cells of the first flash spot (S1) of the first flash scan subsequence of a first set of n combined flash spots to impart the corresponding first pulsed dose (D11). The actual first pulsed charge (C11) actually delivered at the first flash spot (S1) is measured and compared to the theoretical first pulsed charge to ensure that each spot receives the target charge (Cti) as planned. If there is a discrepancy between the actual and theoretical values ​​of the first pulsed charge (C11), an adjusted theoretical second pulsed charge (C12) to be next delivered to the first flash spot (S1) is calculated to match the theoretical flash charge plan. The measurement, comparison, and calculation of the adjusted values ​​are collectively referred to as the “calculation operation” and require computation time (tc) to complete. The computation time (tc) is generally greater than the interpulse interval (Δtp) that separates two consecutive pulses of charged particles emitted by the accelerator (i.e., tc > Δtp).

[0053] After delivering the first pulse of charge (C11) to the first spot, i.e., after pulse time (tp), the beam is moved to the second flash spot (S2) according to a flash scan subsequence, and the first pulsed charge (C21) is delivered to impart the first pulsed dose (D21) to the spread cells of the second flash spot (S2). Meanwhile, during time (tc), a calculation operation is performed for the first pulsed charge (C11) for the first flash spot (S1). The beam must reach the second spot (S2) by the time the second pulse (P2) becomes ready to emit, i.e., by the end of the interpulse interval (Δtp) between the first pulse (P1) and the second pulse (P2). In line with the theoretical flash charge plan, a computational operation is performed to measure the actual first pulse charge (C21) delivered to the second flash spot (S2), compare it to the theoretical first pulse charge (C21), and calculate the adjusted theoretical second pulse charge (C22) that should be delivered next to the second flash spot.

[0054] After delivering the first pulse of charge (C21) to the second spot (S2), the beam is moved to the next flash spot (Si) in the flash scan subsequence, and then moved to the nth flash spot (Sn) in the flash scan subsequence, and the previous step is repeated (n-2) times until the first pulsed charge (Cn1) is delivered to the spread cells of the nth flash spot, thereby conferring the first dose (Dn1). Each time, the calculation operation is repeated for the first dose delivered to each of the set (5) flash spots (S1~Sn).

[0055] During a treatment session, the actual first pulsed charge (Cn1) delivered at the nth flash spot (Sn) is measured, and the beam is returned to the first flash spot (S1) of the flash scan subsequence for an estimated time required to calculate the adjusted theoretical second pulsed charge (Cn2) to be delivered next at the nth flash spot (Sn) in accordance with the theoretical flash charge plan. The adjusted theoretical second pulsed dose (D12) is then applied to the spread cells of the first flash spot (S1) as calculated above. The same process is repeated for the n flash spots, applying the adjusted theoretical second pulsed dose (Di2) to the spread cells of each flash spot. These operations are repeated until the target charge (Cti) is delivered to the spread cells of each flash spot (S1, Sn) in the first set of n combined flash spots and the corresponding target dose (Dti) is applied. When n=2, the beam travels back and forth between the first spot and the second spot (S1-S2-S1-...) as shown in Figures 4(a) and 4(b), delivering pulses each time. In Figure 4(b), the accumulated dose Deq is the average dose. Cumulative dose for TIFF2023010652000013.tif7170 (Σ j It is normalized by adding the ratio of Dij (i.e., TIFF2023010652000014.tif7170).

[0056] The beam is then moved to the first flash spot according to a second flash scan subsequence of a second set of n combined flash spots, and the corresponding target dose is repeated for all n combined flash spots of the second set of n combined flash spots until they all receive it.

[0057] k-group scan sequence Each set (5) of n flash spots (Si) can be irradiated with an ultra-high dose rate (HDR) as described above. When irradiating already irradiated flash spots (Si) onto spots in another set, it is important not to excessively extend the irradiation time. Therefore, the sequence of k sets must also be considered to ensure that the dose (Dij) is actually delivered with an ultra-high dose rate (HDR) at the end of the irradiation session. Methods for optimizing the sequence of spots to be irradiated with HDR are known in the art, such as those described in (Patent Document 1). Any of these methods described for the spot sequence can be applied to the sequence of k sets. For example, the unit cells of the scarf sequence can be defined as described in (Patent Document 1).

[0058] Calculation time longer than the interpulse interval (tc > Δtp) The interpulse interval (Δtp) depends solely on the particle accelerator used to execute the treatment plan. In some accelerators, several pulses may be accelerated simultaneously, separated from one another, and passing through different sections of the acceleration path under different electromagnetic conditions to account for relativistic effects. In other accelerators, pulses must leave the accelerator before a second pulse is emitted and accelerated. These differences can have a significant impact on the value of (Δtp).

[0059] On the other hand, the computation time (tc) depends on the entire processing unit. For example, the computation time (tc) involves at least the following steps, namely: · Measuring the actual pulse charge (Cij) delivered by the jth pulse (Pij) applied to the ith flash spot (Si); · Comparing the accumulated theoretical pulse charge with the accumulated actual pulse charge actually measured at the ith flash spot (Si) after j pulses TIFF2023010652000015.tif9170 to calculate the adjusted theoretical pulse charge (Ci(j + 1)) to be applied to the ith flash spot by the (j + 1)th pulse (Pi(j + 1)) required to conform to the charge plan; · Preparing the pulse particle accelerator to emit the next pulse (Pi(j + 1)) with the adjusted value of the theoretical pulse charge (Ci(j + 1)); may need to be completed.

[0060] The calculation time can only start after the pulse time (tp) of the pulse duration. Therefore, for the accelerator to emit pulses at a full nominal pulse rate of 1 pulse per Δtp, the calculation time should be shorter than the dead time (td = Δtp - tp) required by the accelerator to emit the second pulse. This is impossible, and the calculation time (tc) is greater than the free time (td) and generally greater than the inter-pulse interval (Δtp), i.e., (td < Δtp < tc). Therefore, the calculation time (tc) is a factor that prolongs the treatment plan because it cannot operate the accelerator at its highest nominal pulse rate of 1 pulse / Δtp and instead has to operate at a low rate of 1 pulse / Δtt, where Δtt = (tp + tc) > Δtp (see Fig. 5(a)).

[0061] According to the present invention, the accelerator can be operated at a fairly high rate close to the nominal pulse rate of 1 pulse / Δtp at the same value as the calculation time (tc).

[0062] When the sets are composed of the same flash spots In one embodiment shown in Figure 6(a), all flash spots in a group (5) must receive the same target dose (Dti) in HDR. This applies, for example, to the middle of a flash volume (Vht) that has similar characteristics, is far from any boundaries, or is separated from each other by a distance greater than 1.5σ, and has little overlap between adjacent flash spots. In either of these cases, all n flash spots in a group can receive the same number of pulses. Under these conditions, the composition of all groups within a group is constant, and the groups consist of the same flash spots throughout the treatment session.

[0063] Figure 6(a) shows an example of a mesh of flash spots (Si) (= black dots) and normal spots (Ri) (= white dots) projected onto a plane (Π). The flash spots (Si) are combined into sets (5) of n=2 flash spots each. The spread cells of each flash spot (Si, S(i+1)) in the same set receive the target dose (Dti, Dt(i+1)) delivered with the same number of pulses (i.e., mi=m(i+1)). However, the flash spots of two different sets (5) do not necessarily have to receive the same number (mi) of pulses. The first set (5) consists of a first flash spot (S1) and a second flash spot (S2). As shown in Figures 4(a) and 4(b), for each pulse (Pij), the beam (100) makes several (mi) round trips between the first and second flash spots of the first set (5), each time imparting a charge that accumulates after (mi = m(i+1) pulses) until the target dose (Dti, Dt(i+1)) is reached. At this stage, the spread cells of the flash spots in the first set (5) have received the target dose (Dti) planned for the session, and the beam can move to the second set (5), consisting of the third flash spot (S3) and the fourth flash spot (S4), and repeat the dose-imparting operation between the two spots as described above. A similar operation is repeated up to the last set (5), consisting of the (N-1) flash spot (S(N-1)) and the Nth flash spot (SN), completing the treatment of the flash spots contained within the flash volume. If the flash volume contains an odd number (N) flash spots, the last set (5) of n=2 flash spots consists of the (N-2)th flash spot and the (N-1)th flash spot. The Nth flash spot is treated alone as an additional set of nR=1 flash spots, and is treated as part of the previous k (=(N-1) / 2) sets of n=2 combined flash spots. A normal spot (Ri) (=white dot) can be treated in the usual way and with CDRs that are well known to those skilled in the art.

[0064] The advantages of the present invention are shown by comparing FIG. 5(a) (prior art) and FIG. 5(b) (present invention), which show the cumulative dose imparted by pulses (Pij, P(i + 1)j) (mi, m(i + 1) of them) to the expanded cells of adjacent first flash spot (Si) and second flash spot (S(i + 1)) as a function of time. The dose accumulated in the first spot (Si) is represented by a solid line, and the dose accumulated in the second spot (S(i + 1)) is represented by a dashed line. In the embodiments shown in FIGS. 5(a) and 5(b), the first and second spots of the set (5) are close enough so that a part of the dose imparted to the expanded cells of one of the first spot (Si) or the second spot (S(i + 1)) overlaps with the other adjacent spot (S(i + 1), Si). The dose imparted by the overlap is shown by the portion of the curve labeled (S). The dose imparted by the pulse (Pij) targeting the first or second spot is shown by the portion of the curve labeled (P).

[0065] FIG. 5(a) shows the irradiation treatment of adjacent first and second spots as conventionally performed, where the first and second spots are irradiated continuously. The expanded cells of the first spot (Si) receive (mi) pulses (Pij) that impart a cumulative dose (Σ j Dij). Considering the portion of the dose to be imparted to the expanded cells of the second spot (S(i + 1)) that overlaps with the dose imparted to the expanded cells of the first spot (Si), the mi pulses (Pij) delivered to the expanded cells of the first flash spot (Si) impart a cumulative dose Σ j Dij (< Dti) that is less than the target dose (Dti), for example, so as to reach the target dose (Dti) after receiving the overlapping dose from the second spot (S(i + 1)). When all (mi) pulses are delivered to the first flash spot (Si), the cumulative dose (Σ jDij<Dti) is assigned to the first spot, and the overlapping dose (Ds(i+1)) is assigned to the adjacent second flash spot (S(i+1)). The beam moves to the second spot (S(i+1)) and delivers successive doses (D(i+1)j) in (m(i+1) number of) successive pulses until the target dose (Dt(i+1)) is assigned to the second flash spot. During this operation, the overlapping dose (Dsi) is delivered by overlapping with the first spot (Si), and thus this also reaches the target dose (Dti).

[0066] In this example, it can be seen that it takes a total of 25 time units (=t / Δtp) of time to assign the target doses (Dti, Dt(i+1)) to the adjacent first and second spots, respectively. Each of the 25 time units corresponds to the time during which the particle accelerator used can emit one pulse. In this example, during the period of 25 time units, the accelerator has only emitted 12 pulses (mi = 6 pulses on the first spot, m(i+1) = 6 pulses on the second spot) out of the 25 pulses it could have emitted during that time. As a result, the effectiveness with respect to the nominal rate of the accelerator is less than 50% (=12 / 25). This discrepancy is due to the need for a long calculation time (tc) with respect to the inter-pulse interval (Δtp) to measure the actual pulse charge (Cij) of each emitted pulse, compare this with the theoretical charge, and prepare the accelerator to emit the next pulse (Pi(j+1)) with the adjusted theoretical pulse charge. This long time (Δt, tot(Si)) for delivering the target doses (Di, D(i+1)) by successive irradiation of the first spot (Si) and the second spot (S(i+1)) is detrimental to achieving HDR and, in some cases, can make FLASH-RT impossible.

[0067] The present invention allows for a significant reduction in total irradiation time compared to the conventional treatment plan described above. Figure 5(b) shows a treatment plan for a set (5) of n=2 flash spots (Si, S(i+1)) that must receive the same target dose (Dti, Dt(i+1)) and the same number of pulses (mi, m(i+1)) as the conventional embodiment shown in Figure 5(a) above. As shown in Figures 4(a) and 4(b), the beam delivers a first dose (D11) to the spread cells of the first flash spot (S1), moves to the second flash spot (S2) and delivers a first dose (D21), and returns to the first flash spot (S1) and delivers a second dose (D12) according to a adjusted theoretical second pulse charge determined and prepared during the calculation time (tc) when the first dose (C21) is delivered to the second flash spot (S2). The same applies thereafter. Due to the overlap of charges from the spread cells of the two flash spots, the total time (Δt, tot(Si)) required to deliver the target dose (Dti, Dt(i+1)) is approximately 13 unit hours, which is about half the time required according to the conventional treatment plan discussed with reference to Figure 5(a). This results in a charge delivery rate twice that achieved with the conventional treatment plan, increasing the possibility of treating the entire flash volume with HDR. Furthermore, the total time (Δt, tot(Si)) required to treat both of the flash spots (Si, S(i+1)) of pair (5) was also about half the time required with the conventional treatment plan. Regardless of whether there is dose overlap between the spread cells of two adjacent spots, this significantly reduces the duration of treatment sessions, which is beneficial for both patients and hospitals / treatment centers. Hospitals / treatment centers can plan more treatments per unit hour, optimizing the frequency of particle accelerator use.

[0068] Compared to conventional treatment planning techniques, the acceleration of treatment planning with the present invention increases when the ratio of calculation time (tc) to dead time (td = Δtp - tp) (tc / td) is greater than 1. The present invention shortens treatment time by selecting the number of flash spots in each set such that the ratio (tc / (td×n)) approaches 1, preferably does not fall below 1 (i.e., tc / (td×n) ≥ 1 and tc / (td×n) → 1).

[0069] If the set consists of different flash spots In some cases, all flash spots in a given set (5) may not be able to deliver the same number of pulses (mi) to the spread cells of the flash spots in order to reach their respective target doses (Dti). This can occur, for example, when flash spots are close to the boundary, or when the mesh is dense and there is considerable overlap between adjacent flash spots. Thus, the spread cells of flash spots designed to receive the fewest pulses will reach their target dose (Dti) before the spread cells of adjacent flash spots in the same set. These flash spots must not be irradiated further and must be prevented from being irradiated, but the spread cells of other flash spots in the same set will still receive some dose. Taking into consideration the need to prevent uncontrollable dose overlaps toward flash spots where cells have already received their target doses (Dti) or their planned number of pulses (Pij), dose delivery may continue in that set with flash spots such as (n-1), (n-2), where cells have not yet received their target doses (Dti) or their planned number of pulses (Pij). As all flash spots except the two remaining in the set receive their corresponding target doses and move away from the irradiation field, the flash spot that must receive the most pulses among the remaining two will soon be alone in the set (or irradiation field). If the same thing happens with multiple sets, and many single flash spots remain, it can become difficult to guarantee HDR across the entire flash volume.

[0070] In the preferred embodiment of the present invention shown in FIG. 6(b), the set includes a combination of n = 2 flash spots, and the spread cells of the second flash spot (S(i + 1)) of the set must receive a number of pulses (m(i + 1)) greater than the number of pulses (mi) that the spread cells of the first spot (Si) must receive to reach their respective target doses (Dti, Dt(i + 1)) (i.e., mi < m(i + 1)). This applies when the set initially includes n = 2 flash spots at the beginning of the treatment session, or when, as described above, only 2 flash spots remain for each cell to receive the pulses required to reach the corresponding target dose (Dti). In this case, different sets are permeable and can evolve over the course of the treatment by accepting new flash spots and removing other flash spots where the cells have reached the target dose (Dti). This situation can be defined as follows. The number of pulses (m2) of the second target dose (Dt2) that the cells of the second flash spot (S2) in the first set of flash scan subsequences of n = 2 flash spots (S1, S2) must receive to reach the second target dose (Dt2) is greater than the number of pulses (m1) of the first target dose (Dt1) that the spread cells of the first flash spot (S1) must receive to deliver the first target dose (Dt1) (i.e., m1 < m2). This embodiment of the present invention proceeds as follows, as shown in FIG. 6(b). ·The first flash spot (Si) and the second flash spot (S(i+1)) of the first pair (5) (see the solid and dashed lines in Figure 5(c)) each receive (mi) pulses (and if there is no substantial overlap, the target dose (Dti) is applied to the cells where the first flash spot (Si) has spread), the second flash spot (S(i+1)) dissociates from the first flash spot (Si) and combines with the third flash spot (S(i+2)) to form n=2 flash spots (S(i+1), S( A second set of i+2)) is formed, and the third flash spot (S(i+2)) is located at a distance d (≤DM) from the second flash spot (S(i+1)), and both the second flash spot (S(i+1)) and the third flash spot (S(i+2)) receive (m(i+1)-mi) pulses, and the second flash spot (S(i+1)) must receive a third target charge (Ct(i+2)) greater than the residual charge (Ct(i+1)-Cti) until it receives the target charge (Ct(i+1)), The third flash spot (S(i+2)) (see the long dashed line in Figure 5(c)) dissociates from the second flash spot (S(i+1)) and combines with the fourth flash spot (S(i+3)) (see the mixed line in Figure 5(c)) to form a third pair of n=2 flash spots (S(i+2), S(i+3)), and so on, until all N flash spots in the mesh receive their respective target charges (Cti) in HDR.

[0071] A similar analysis can be performed with respect to Figure 5(a) by comparing the time series of the conventional treatment plan with the time series of this embodiment shown in Figure 5(c). First, the same flash scan sequence discussed with respect to Figure 5(b) is applied here, and the beam moves between the first flash spot (Si) and the second flash spot (S(i+1)). However, in this embodiment, the spread cells of the first flash spot (Si) reach the target dose (Dti) before the spread cells of the second flash spot (S(i+1)). For clarity, it is assumed that there is no substantial overlap between adjacent flash spots in Figure 5(c). The second flash spot (S(i+1)) dissociates from the first flash spot (Si) and forms a new pair with the third flash spot (S(i+2)), and the beam oscillates between the second flash spot (S(i+1)) and the third flash spot (S(i+2)) until the second flash spot (S(i+1)) receives the corresponding number of pulses (m(i+1)). The third flash spot (S(i+2)) dissociates from the second flash spot (S(i+1)) and combines with the fourth flash spot (S(i+3)) to form a third pair (5) of n=2 flash spots, and so on. As can be seen in Figure 5(c), the treatment time is optimized to the same amount of time required by the conventional treatment plan in Figure 5(a) to deliver the target dose (Dti, Dt(i+1)) to the spread cells of the first and second spots (which carries a high risk of being too slow for HDR), and the target dose is delivered to the spread cells of the three flash spots (Si~S(i+2)), and partially to the spread cells of the fourth flash spot (S(i+3)) in this embodiment of Figure 5(c).

[0072] As described above in relation to the embodiment shown in Figure 5(b), the present invention shortens the treatment time by selecting the number of flash spots in each set such that the ratio (tc / (td×n)) approaches 1 and does not fall below 1 (i.e., tc / (td×n) ≥ 1 and tc / (td×n) → 1).

[0073] Regular Spot (Ri) This invention focuses on delivering a target dose (Dti) to a flash volume (Vht) using HDR. However, the treatment volume (V) also includes a target volume (Vt) primarily containing tumor cells (3t), and tumor cells (t) can be killed by CDR because the tumor cells (3t) are not adjacent to healthy cells (3h) or the beam does not cross healthy cells to reach the target volume (Vt). The target volume (Vt) can also be treated with PBS without concern for charge delivery rate, except to shorten the session for patient comfort. Developing a treatment plan for the target volume (Vt) involves the following steps: The steps include defining a mesh of M normal spots (Ri) that cover the projection range of the target volume (Vt) (i.e., Vt = V - Vht) projected parallel to the irradiation axis (X) onto the projection plane (Π), The steps include: determining a normal charge plan for each normal spot (Ri), which specifies the value of each pulse charge (Cij) to impart a target charge (Cti) with mi pulses, not necessarily HDR; The steps include defining a normal scan sequence for assigning a target charge (Cti) to each of M normal spots (Ri), and Includes.

[0074] Figures 6(a) and 6(b) show the treatment volume (V), which includes the flash volume (Vht) defined by the mesh of flash spots (Si) represented by black dots (as described above) and the target volume (Vt) defined by the mesh of normal spots (Ri) represented by white dots. The treatment plan of the present invention treats flash spots and normal spots sequentially in any order, but preferably, as shown in Figures 6(a) and 6(b), the flash spots are treated first, followed by the normal spots.

[0075] Conclusion The present invention provides a therapeutic apparatus comprising a pulsed particle accelerator and a processor for controlling the pulsed particle accelerator, for delivering charged particles to a flash volume (Vht) in HDR by PBS according to a treatment plan. Due to dose delivery by continuous pulses and statistical uncertainty regarding the charge (Cij) actually emitted by the particle accelerator in each pulse, a given target dose is delivered only to cells with a spread flash spot (Si) over a total time Δtt = mix(tp + tc) and a maximum dose delivery rate Σ j It can be applied in Dij / mix(tp+tc) (which is often too slow to obtain FLASH-RT). Furthermore, in the case of a sufficiently dense mesh, the overlap of doses (Dij) applied to cells covered by a first flash spot (Si) on an adjacent flash spot further prolongs the application time and further reduces the dose application rate.

[0076] By combining flash spots (Si) into sets of n flash spots and moving the beam (100) according to the flash scan subsequence described above, the time required to deliver the target dose (Dti) to the spread cells of the flash spots (Si) is significantly reduced, and the dose delivery rate is improved accordingly. This is even more advantageous when there is considerable dose overlap between adjacent flash spots. In all cases, the session duration is significantly reduced by the treatment plan described herein rather than by conventional plans, and the target dose (Dti) is delivered continuously to the spread cells of each spot (see Figures 5(a) (Prior Art), 5(b), and 5(c) (Invention)). [Explanation of Symbols]

[0077] 3h Healthy cells 3t tumor cells 3s Patient's skin 5. Combinations of flash spots 100 beams Charge of a Cij pulse (Pij) CDR Conventional dose assignment rate Maximum pulse charge of the CM pulse Di dose applied to cells affected by a spread of flash spots TIFF2023010652000016.tif8170Dij Dose imparted by pulse Pij of charge Cij d Distance between the two spots Maximum distance between two consecutive flash spots in a dM scan subsequence DS scan distance Target dose in cells with spread Dti spots (Si, Ri) HDR ultra-high dose rate Number of k pairs M: Number of regular spots (Ri) mi: Number of pulses required to deliver the target dose (Dti) Number of flash spots in n sets N is the number of flash spots (Si). nR Number of flash spots in the additional set (= remaining ratio N / n) Pij charge (Cij) pulse Ri Regular Spot i Si Flash Spoti SOBP (Sum of Bragg Peak) tc calculation time td dead time (=Δtp-tp) tp pulse time V Treatment area VHT flash volume vs scan speed Vt Target Volume X irradiation axis Δtp Interpulse interval Δts scan time

Claims

1. A treatment device for the treatment of a treatment volume (V) with a beam (100) of charged particles, preferably protons, said treatment volume (V) comprising: a target volume (Vt) that contains substantially only tumor cells (3t); a flush volume (Vht) containing healthy cells (3h) and preferably tumor cells (3t); It is composed of The treatment device comprises: a pulsed particle accelerator configured to deliver pulses of charged particles to deposit a dose (Dij) in the treatment volume (V) such that for each spot (Si, Ri) distributed over a single painting layer spanning the entire treatment volume (V), the dose (Dij) is deposited at a very high dose deposition rate (HDR) to the spot (Si) contained within the flash volume (Vht) by pencil beam scanning (PBS), the HDR being defined as a dose rate HDR ≧ 1 Gy / s; the charged particles are emitted in pulses (Pij), each pulse having a pulse charge (Cij) less than or equal to a maximum pulse charge (C) (i.e. C > Cij) and a duration of a pulse time (tp), the pulses being separated from each other by an interpulse interval (Δtp); The beam of charged particles can be scanned from a first flash spot to a second flash spot with a maximum scan speed (vs = ds / Δts), where ds is the distance between the first flash spot and the second flash spot, and Δts is the scan time required to scan from the first flash spot to the second flash spot. A pulsed particle accelerator; A processor configured to control the pulsed particle accelerator to implement a treatment plan (TP), the treatment plan comprising: definition of a mesh of N flash spots (Si) covering the range of projection of the flash volume (Vht) projected parallel to the irradiation axis (X), which is approximately parallel to the beam (100), on a projection plane (Π) perpendicular to the irradiation axis (X); the definition of the target charge (Cti) necessary for each flash spot (Si) to impart a target dose (Dti) to said cell over which each flash spot (Si) extends; - definition of a theoretical flash charge plan for each flash spot (Si), comprising the theoretical pulse charges (Cij) of a certain number (mi) of pulses necessary to deliver the target dose (Dti) to the cells spread of each flash spot (Si), said target charge (Cti) being equal to the sum of the theoretical pulse charges (Cij) of said number (mi) of flash spots irradiating (i.e. ), or the target dose (Dti) is equal to the sum of the number (mi) of pulse doses (Dij) delivered to the cells spread by the flash spot by each pulse charge (Cij) (i.e., ) provisions, definition of a flash scan sequence of said N flash spots, comprising a sequence of flash spots (Si) in which said corresponding number (mi) of pulse doses (Dij) are applied to said cells spread over each flash spot; Includes Processor and Equipped with The flash scan sequence includes: the prescription of a certain number (k) of sets (5), each set (5) containing a number n of flash spots (Si), 1<n<N; a definition of a flash scan subsequence of n combined flash spots such that for each set (5) of n combined flash spots, the distance (ds) between all successive first and second flash spots ((Si, S(i+1)) and (Sn, S1)) of the set is always less than or equal to a maximum distance (dM) defined as the product of the scan speed (vs) and a dead time (td), i.e. d≦dM=vs×td, the dead time (td) being the time between the end of a pulse and the beginning of the next pulse (i.e. td=Δtp−tp); and The processor, for example, (a) directing the beam to a first flash spot (S1) (i.e., i=1) and delivering a corresponding first pulse dose (D11) to the cells spread in the first flash spot (S1) of a first flash scan subsequence of a first set of n combined flash spots; (b) moving the beam to a second flash spot (S2) (i.e., i=2) of the flash scan subsequence and delivering a first pulse charge (C21) to the cells spread in the second flash spot (S2) to provide a first pulse dose (D21) during an estimated time required to measure an actual first pulse charge (C11) actually delivered to the first flash spot (S1) during a treatment session and to calculate an adjusted theoretical second pulse charge (C12) to be subsequently delivered at the first flash spot (S1) in accordance with the theoretical flash charge plan; (c) if i<n, moving the beam to the i-th flash spot (Si) of the flash scan subsequence and delivering a first pulse charge (Ci1) to the cells spread across the i-th flash spot (Si) during an estimated time required to measure an actual previous pulse charge (C(i-1)1) actually delivered to a previous flash spot (S(i-1)) during a treatment session and to calculate an adjusted theoretical second pulse charge (C(i-1)2) to be next delivered at the previous flash spot (S(i-1)) to fit the theoretical flash charge plan; (d) repeating the previous step (n-3) times until i=n; (e) returning the beam to the first flash spot (S1) (i.e., i=1) of the flash scan sub-sequence and applying the adjusted theoretical second pulse charge (C12) (i.e., j=2) calculated as above to the first flash spot (S1) during an estimated time required to measure the actual first pulse charge (Cn1) delivered to the nth flash spot (Sn) during a treatment session and to calculate the adjusted theoretical second pulse charge (Cn2) to be next delivered at the nth flash spot (Sn) in accordance with the theoretical flash charge plan; (f) repeating steps (b)-(e) for j=(mi-1), and repeating steps (b)-(d) for j=mi at least until the target charge (Cti) is delivered to each flash spot (S1, Sn) of the first set of n combined flash spots; (g) moving the beam to a first flash spot according to a second flash scan subsequence of a second set of n combined flash spots and repeating steps (a)-(f) for the n combined flash spots of the second set of n combined flash spots; (h) repeating the last step for the flash scan sub-sequences of the remaining (k-2) sets of n combined flash spots until the corresponding target charge (Cti) is delivered with HDR to the n combined flash spots of all k sets (5) of the mesh. The treatment device is configured to control the pulsed particle accelerator so as to

2. 2. The treatment device of claim 1, wherein the number (n) of combined flash spots in a set (5) is: If tc / td is an integer, the ratio tc / td>1 (i.e., where n=tc / td, otherwise, n=1 plus the integer part of the ratio (tc / td) (i.e., n=INTEGER(tc / td)+1); A treatment device characterized in that td is the dead time, tc is the calculated time required by the pulsed particle accelerator to define and prepare the next pulse (P(j+1)) according to the adjusted theoretical pulse charge (Ci(j+1)) calculated based on the actual pulse charge (Cij) measured in the first pulse (Pij) preceding the second pulse (Pi(j+1)), and is longer than the dead time (tc>td).

3. 3. The treatment device according to claim 2, wherein the calculation time (tc) is calculated by at least the following steps: - measuring the pulse charge (Cij) delivered by the jth pulse (Pij) applied to the ith flash spot (Si); Accumulated theoretical pulse charge is the accumulated pulse charge actually measured in the i flash spot (Si) after j pulses. calculating an adjusted theoretical pulse charge (Ci(j+1)) to be delivered to the i flash spot by the (j+1)th pulse (Pi(j+1)) required to meet the charge plan by comparing Preparing the pulsed particle accelerator to emit the next pulse (Pi(j+1)) at the adjusted value of the theoretical pulse charge (Ci(j+1)); A treatment device characterized in that the above steps are required to be completed.

4. 4. The therapeutic device according to claim 1, wherein the number (k) of sets of n combined flash spots (5) is an integer part of the ratio (N / n) (i.e., n=INTEGER(N / n)), and additional sets of nR flash spots are defined and treated as the sets of n combined flash spots according to claim 1, with nR (<n) being the remainder of the ratio N / n until the target charge (Cti) is delivered in HDR to all N flash spots of the mesh.

5. 4. The treatment device according to claim 1, wherein the flash scan sequence comprises: the number (n) of flash spots combined for all of the k sets (5) is 2 (i.e., n=2); the second flash spot (S2) in the flash scan subsequence of the first set of n=2 flash spots (S1, S2) must receive a number (m2) of pulses (P1-Pm2) to reach a second target charge (Ct2) that is greater than the number (m1) of pulses (P1-Pm1) required to deliver a first target charge (Ct1) to the first flash spot (S1) (i.e., m1<m2 and Ct1<Ct2); Including, The processor, for example, - decoupling the second flash spot (S2) from the first flash spot (S1) when the first flash spot (S1) and the second flash spot (S2) of the first set (5) each receive m1 pulses and the target charge (Ct1) is delivered to the first flash spot (S1); a third flash spot (S3) is combined with said second flash spot (S2) to form a second set of n=2 flash spots (S2, S3), said third flash spot (S3) being located at a distance d (≦DM) from said second flash spot (S2), both the second flash spot (S2) and the third flash spot (S3) each receive (m2-m1) pulses, and until said second flash spot (S2) receives said target charge (Ct2), it must receive a third target charge (Ct3) greater than the residual charge (Ct2-Ct1); Dissociating the third flash spot (S3) from the second flash spot (S2) and combining the third flash spot with a fourth flash spot (S4) to form a third set of n=2 flash spots (S3, S4), and so on until all N flash spots of the mesh have received their respective target charges (Cti) in the HDR. The treatment device is configured to control the pulsed particle accelerator so as to

6. 4. The treatment device according to claim 1, wherein the treatment plan comprises: - definition of a mesh of M normal spots (Ri) covering the area of ​​the projection of the target volume (Vt) (i.e. Vt=V-Vht) projected parallel to the irradiation axis (X) onto the projection plane (Π); a normal charge plan for each normal spot (Ri) defining the value of each pulse charge (Cij) for applying said target charge (Cti) with mi pulses, not necessarily HDR; - defining a normal scan sequence for applying said target charge (Cti) to each one of said M normal spots (Ri); A treatment device comprising:

7. A treatment planning system (TPS) for implementing a treatment plan (TP) according to any one of claims 1 to 3, comprising: a mesh unit configured to define, on a projection plane (Π) perpendicular to an irradiation axis (X), a mesh of N flash spots (Si) covering a range of projection of the flash volume (Vht) projected parallel to the irradiation axis (X), which is substantially parallel to the beam (100); a target charge unit configured to define for each flash spot (Si) a target charge (Cti) required to deliver a target dose (Dti) to the cells spread over each flash spot (Si); a flash planning unit configured to determine a theoretical flash charge plan for each flash spot (Si), defining the theoretical pulse charge (Cij) of a certain number (mi) of pulses necessary to deliver the target dose (Dti) to the cells spread of each flash spot (Si), said target charge (Cti) being equal to the sum of the theoretical pulse charges (Cij) of said number (mi) of flash spots irradiating the flash spot (i.e. ), or the target dose (Dti) is equal to the sum of the number (mi) of pulse doses (Dij) delivered to the cells spread by the flash spot by each pulse charge (Cij) (i.e., ), a flash planning unit, a flash scan sequence unit configured to define a flash scan sequence of said N flash spots defining a sequence of flash spots (Si) in which said corresponding number (mi) of pulse doses (Dij) are applied to said cells spread over each flash spot; Equipped with The flash scan sequence unit performs the following operations: - defining a number (k) of sets (5), each set (5) comprising a number n of flash spots (Si), 1<n<N; - defining a flash scan subsequence of n combined flash spots such that for each set (5) of n combined flash spots, the distance (ds) between all successive first and second flash spots ((Si, S(i+1)) and (Sn, S1)) of the set is always less than or equal to a maximum distance (dM) defined as the product of the scan speed (vs) and a dead time (td), i.e., d≦dM=vs×td, the dead time (td) being the time between the end of a pulse and the beginning of the next pulse (i.e., td=Δtp−tp); 23. A treatment planning system (TPS) configured to plan a treatment for a patient.

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