Treatment device for carrying out a treatment plan for flash delivery by pencil beam scanning using a charged particle accelerator - Patent Application 20070122963

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 treatment device for implementing a plan for treating a treatment volume (V) including a flash volume (Vht) containing healthy cells and preferably tumor cells using a beam of charged particles, preferably protons. To spare healthy cells and kill tumor cells, the flash volume (Vht) must be dosed with a very high dose rate (HDR). The beam is emitted from a pulsed particle accelerator that delivers pulses of charged particles. To deliver a target dose to the flash volume (Vht), several pulses of the pulsed beam are generally required, which can prolong the delivery time beyond the limits for enabling HDR. Treatment planning according to the present invention allows for the delivery of a target dose with HDR to predetermined locations within the flash volume (Vht) by pencil beam scanning (PBS), spot by spot, distributed across a single painting layer spanning 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 for treating patients suffering from tumors.

[0003] Because such radiation damages both tumor cells and healthy cells contained within the volume, a major challenge in cancer treatment is to define a treatment plan that ensures effective destruction or death of tumor cells while sparing as many healthy cells as possible, especially those adjacent to the tumor cells. The first step in treatment planning is to obtain images of the tumor area via CT scan. Based on these images, the oncologist identifies appropriate targets and determines the location and dose to be administered to kill tumor cells. Such plans are highly complex because they must satisfy multiple, often competing, parameters. For this reason, treatment planning systems are typically computer-generated.

[0004] The first criterion 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. At the same time, the second criterion a treatment plan must meet is to minimize the degradation of healthy tissue adjacent to the tumor cells. Regardless of how precisely the dose is delivered to a volume containing tumor cells, radiation reaching the volume will almost inevitably traverse healthy tissue and also deliver dose to healthy cells surrounded or contained within that volume. Different radiation sources deposit different energy patterns. For example, X-rays deposit most of their energy at depths near the epidermis, and the deposited energy decreases with depth. Therefore, healthy tissue located upstream of a tumor cell target volume receives a higher dose than tumor cells in the target volume. In contrast, as shown in Figures 1(a) and 1(c), charged particle beams, particularly protons, deposit 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 consists of steering a beam of charged particles toward individual spots within a mesh of spots that defines a target volume containing tumor cells. This delivers a predetermined target dose to the cells spread across each spot. Beam steering and dose delivery proceed according to a treatment plan that defines the charge to be delivered at each spot and the scanning sequence of the spots. PBS reduces unnecessary radiation exposure to surrounding non-cancerous tissue by shaping the treatment area to reflect the geometry of the tumor. In addition to the target geometry, PBS allows for localized adjustment of the beam intensity depending on the location of the spot within the target.

[0006] A mesh typically includes several painting layers, each consisting of a two-dimensional array of spots arranged 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 an accelerated proton beam, a single beam can sequentially deposit a predetermined charge at corresponding spots in each painting layer by overlapping several Bragg peaks at different depths in each painting layer along the irradiation axis (X). This results in spread-out Bragg peaks (SOBPs) that extend across the entire depth of the tumor cell volume or across a portion of that volume. This technique allows for the delivery of a targeted dose to a target volume by PBS in several painting layers with different beam energies. The painting layer (or depth) to which the dose is deposited can be controlled, i.e., by the energy of the accelerated particles. The dose deposited in the spread-out cells in the painting layers can be controlled, i.e., by the beam fluence (= number of charges per unit area). Due to the deposition 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 should be noted that each time a dose is delivered to a cell in a spot of a given painting layer, the cell receives a dose that is additive to the dose previously delivered to the cell in a corresponding spot of a painting layer downstream of the given painting layer. In this specification, the terms "downstream" and "upstream" are used relative to the direction of beam propagation.

[0007] In the SOBP described above for proton beams, healthy cells located upstream of the target volume receive a significantly lower dose than cells contained within the target volume. Meanwhile, 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 radiation therapy is that healthy cells are generally (slightly) more resistant to radiation than tumor cells. A key goal in radiation therapy is to "open the therapeutic window," i.e., to find a dose that damages the tumor while sparing 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 tissue must not exceed the maximum tolerated dose. Because the maximum tolerated dose that healthy tissue can (relatively) safely receive in a single session can be substantially the same as the minimum target dose required to destroy tumor cells, a trade-off must 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 spares healthy tissue. This problem is alleviated, though not solved, by spreading the treatment over several sessions.

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

[0009] Traditionally, radiotherapy treatment planning involves delivering radiation doses to treated cells at conventional dose rates (CDR) that are less than 1 Gy / s, typically on the order of 0.03 Gy / s. The dose rate at a cell by all spots overlapping that cell during a session is defined as the ratio (Σ j Dij / Σ iThe dose rate is defined as the dose rate (Dtj). With rare exceptions, current radiotherapy facilities deliver dose rates below 0.1 Gy / s, preferably on the order of 0.03 Gy / s. Most clinical protocols involve the delivery of multiple target doses (Dtj) of 2–3 Gy per session at regular intervals, which accumulate to reach a total target dose. This total target dose is often close to the tolerance limit of normal tissue located in the irradiation field, potentially damaging normal tissue along with tumor cells. Recently, it has been confirmed that the same dose delivered at an ultra-high dose delivery rate (HDR) significantly reduces the impact on healthy tissue compared with the same total dose delivered at a conventional dose delivery rate (CDR). However, such differences in behavior between CDR and HDR have not been observed in tumor cells. HDR can be more than an order of magnitude greater than the commonly applied conventional dose delivery rate (CDR). Dose delivery at an ultra-high dose delivery rate (HDR) is also known as flash-activated radiotherapy (FLASH-RT). Experimental studies in animals and various organs have demonstrated that HDR-based radiation delivery significantly spares healthy tissue compared with conventional CDR-based radiation delivery of the same dose, while tumor cell responses to HDR-based radiation delivery are comparable to or even superior to those achieved with CDR-based radiation delivery. For example, FLASH-RT has been reported to dramatically reduce the incidence of pulmonary fibrosis, memory impairment after brain irradiation, and small intestinal necrosis in mice while maintaining antitumor response rates. Such specific normal tissue sparing has been confirmed in large animals, and patients with cutaneous lymphoma have already been treated with FLASH-RT. Thus, target doses (Dtj) on the order of 10–15 Gy can be delivered in a single FLASH session. FLASH has the advantage of requiring fewer sessions or fractions than conventional radiation-based radiation delivery, thereby expanding the therapeutic window.

[0010] Particles are accelerated to one-third the speed of light (c). As the velocity of a charged particle 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 charged particle's mass as its velocity increases. Relativistic effects become significant at approximately v ≈ c / 3, where v is the particle velocity and c is the speed of light. For example, in a synchrocyclotron, the magnetic field is held constant while the frequency of the driving RF field is varied during the acceleration path the charged particle follows. In a synchrotron, on the other hand, the frequency of the driving RF field is held constant while the magnetic field is increased over time during the acceleration process. Charged particles can also be accelerated to high velocities in laser-driven ion accelerators.

[0011] To allow for the RF frequency of the magnetic or electric field to be changed during the acceleration process, the charged particles must be accelerated in successive batches so that all charged particles are exposed to the magnetic or RF frequency corresponding to their velocity. Consequently, the charged particles are released in pulses (Pij), each corresponding to a batch of charged particles with a pulse charge (Cij) limited to the maximum pulse charge (i.e., Cij ≤ CM). Each pulse has a pulse time (tp) duration, and the pulses are separated from each other by an interpulse interval (Δtp). These parameters depend on the particle accelerator used. It must be ensured that the maximum pulse charge (CM), interpulse interval (Δtp), and number of pulses (N) required to deliver the target dose to a given subvolume are compatible with HDR (i.e., the beam current N × CM / [(N-1) × Δtp] is large enough to ensure a tissue dose rate of 1 Gy / s or greater).

[0012] Since each spot (Si) of a given painting layer receives a dose that is added to the dose previously applied each time it is irradiated by a beam of charges (Cij), which deposit doses (Dij) along their path at various spots located in painting layers downstream of the given painting layer, it is not possible to deposit doses in HDR for multiple painting layers. In fact, the dose deposition rate is a ratio (Σj Dij / Σ ij The time denominator of (tj) rapidly becomes too large for the cells located most upstream in the 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 by using a proton beam to deliver a dose according to the SOBP with a single beam throughout a subvolume whose cross section is defined by the spot and extends throughout the depth of the volume along the irradiation axis (X). The subvolume can be a cylinder whose base is the spot and extends along the irradiation axis (X).

[0013] Depending on the spacing between adjacent spots in a two-dimensional array, a beam aimed at a given spot may also deliver some dose to cells spread across adjacent spots. This is because the charge fluence (= number of charges per unit area) in the beam can be defined by a Gaussian distribution. It is generally believed that if the spots are separated by a distance of approximately 1.5σ of the Gaussian distribution of the charge in the beam cross section, the overlap between the 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 left untreated and that the fluence is uniform between adjacent spots. However, charge overlap and continuous, long-term dose delivery durations are quite detrimental to FLASH-RT because this increases the dose delivery rate by a factor of Σ, which is the ratio of the dose delivery rate, each time a dose is delivered to cells spread across adjacent spots due to overlap. j This is because the larger tj denominator reduces the rate of dose delivery to adjacent spots, which can easily be incompatible with HDR. This problem is exacerbated in PBS delivery, because the target dose to be delivered to each subvolume in HDR must generally be delivered in several pulses. In fact, the target dose is generally larger than can be delivered by a single pulse of maximum pulse charge (CM). By delivering the target dose in several pulses, the delivery time Σj tj is lengthened not only for the subvolume but also for adjacent subvolumes due to overlap.

[0014] The above constraints make HDR dose delivery with PBS extremely complicated. The present invention solves the problem of ensuring that a target volume treated with a PBS of charged particles is effectively irradiated with 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 Summary of the Invention

[0017] The present invention relates to a treatment device for carrying out a plan for the treatment of a treatment volume (V) with a beam of charged particles, preferably protons, the treatment volume (V) comprising: a target volume (Vt) containing essentially only tumor cells; a flush volume (Vht) containing healthy cells and preferably tumor cells (3t); It consists of:

[0018] For example, the target volume (Vt) may be defined as the gross tumor volume (GTV) that primarily contains tumor cells. The treatment volume may include the clinical target volume (CTV), defined as the area to which the therapist desires to deliver the required dose. On the other hand, if the treatment volume corresponds to the CTV (i.e., the flash volume (Vht) is contained within the CTV), the CTV is a combination of the GTV (or target volume (Vt)) and the flash volume (Vht), and therefore includes tumor cells and healthy tissue. On the other hand, if the treatment volume (V) includes the CTV and an organ to be spared that is located upstream of the CTV on the beam path, the flash volume (Vht) intersects with the CTV and extends beyond the CTV by including the organ. The objective of the present invention is to apply HDR to deliver the desired dose required to kill tumor cells throughout the CTV while sparing healthy tissue contained in the flash volume (Vht).

[0019] The treatment device comprises a pulsed particle accelerator configured to deliver pulses of charged particles that impart a dose (Dij) within a treatment volume (V) by pencil beam scanning (PBS) such that for each spot (Si, Ri) distributed over a single painting layer spanning the entire treatment volume (V), the dose is imparted to spots (Si) contained within a flash volume (Vht) at a very high dose deposition rate (HDR), where HDR is defined as a dose rate HDR≧1 Gy / s, and the pulsed particle accelerator has the following characteristics: Charged particles are emitted in pulses (Pij), each pulse having a pulse charge (Cij) less than or equal to a maximum pulse charge (CM≧Cij) and a pulse time (tp) duration, the pulses being separated from one another by an interpulse interval (Δtp); The beam of charged particles can be scanned from the first flash spot to the second flash spot at a maximum scanning speed (vs = ds / Δts), where ds is the distance between the first and second flash spots, and Δts is the scanning time required to scan from the first flash spot to the second flash spot. It is characterized by:

[0020] The treatment device comprises a computer or processor configured to control the pulsed particle accelerator to implement a treatment plan (TP), the treatment plan comprising: defining, on a projection plane (Π) perpendicular to the irradiation axis (X), a mesh of N flash spots (Si) covering the projection range of the flash volume (Vht) projected parallel to the irradiation axis (X), which is substantially parallel to the beam (100); - for each flash spot (Si), determining the target charge (Cti) required to deliver the target dose (Dti) to the cells spread by each flash spot (Si); determining 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 deliver a target dose (Dti) to the spread cells of each flash spot (Si), wherein the target charge (Cti) is equal to the sum of the theoretical pulse charges (Cij) of the number (mi) of pulses irradiating the flash spot (i.e., TIFF0007762632000001.tif8170), or the target dose (Dti) is equal to the sum of the above number (mi) of pulse doses (Dij) given to the cells in the spread of the flash spot by each pulse charge (Cij) (i.e., TIFF0007762632000002.tif8170), and defining a flash scan sequence of N flash spots (Si), which defines a sequence of flash spots (Si) in which a corresponding number (mi) of pulse doses (Dij) is applied to each flash spot; Includes.

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

[0022] The processor may, for example, (a) directing a beam to a first flash spot (S1) (i.e., i=1) and delivering a first pulse charge (C11) (i.e., j=1) to the spread cells of the first flash spot (S1) of the first flash scan subsequence of the first set of n combined flash spots to impart a corresponding first pulse dose (D11); (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 spread cells of the second flash spot (S2) to impart a first pulse dose (D21) during an estimated time required to measure the actual first pulse charge (C11) actually delivered to the first flash spot (S1) during the treatment session and to calculate an adjusted theoretical second pulse charge (C12) to be delivered next at 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 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 for the estimated time required 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), measure the actual first pulse charge (Cn1) delivered to the n-th flash spot (Sn) during the treatment session, and apply the adjusted theoretical second pulse charge (C12) calculated as above at the first flash spot (S1) (i.e., j = 2) for the estimated time required 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, (f) Repeat steps (b) to (e) until j = (mi - 1), and at least until the target charge (Cti) is delivered to each flash spot (S1, Sn) of the first set of n combined flash spots, and repeat steps (b) to (d) for j = mi, (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., in the case of TIFF0007762632000003.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 second flash scan sub-sequence of the first set of two flash spots (S1, S2), the second flash spot (S2) must receive a number of pulses (m2) to reach a second target charge (Ct2) that is greater than the number of pulses (m1) required to deliver a 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 a third flash spot (S3) to form a second set of two flash spots (S2, S3). The third flash spot (S3) is located at a distance d (d ≦ DM) from the second flash spot (S2). Both the second flash spot (S2) and the third flash spot (S3) each receive (m2 - m1) pulses and the second flash spot (S2) must receive a third target charge (Ct3) that is greater than the residual charge (Ct2 - Ct1) until the second flash spot (S2) receives the target charge (Ct2). · The third flash spot (S3) dissociates from the second flash spot (S2) and combines with a fourth flash spot (S4) to form a third set of two flash spots (S3, S4). Similarly, it continues 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); · The accumulated theoretical pulse charge TIFF0007762632000004.tif8170 is the accumulated pulse charge actually measured at the ith flash spot (Si) after j pulses. calculating an 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 fit the charge plan by comparing it with the calculated theoretical pulse charge (Ci(j+1)) to the calculated theoretical pulse charge (Ci(j+1)) required to fit the charge plan; preparing the pulsed particle accelerator to emit a next pulse (Pi(j+1)) at an adjusted value of theoretical pulse charge (Ci(j+1)); may be required to complete

[0026] In a preferred embodiment, the treatment comprises: defining, on the projection plane (Π), a mesh of M normal spots (Ri) covering the projection of the target volume (Vt) (i.e. Vt = V - Vht), projected parallel to the irradiation axis (X); determining a normal charge plan for each normal spot (Ri), defining the value of each pulse charge (Cij) for applying a target charge (Cti) with mi pulses, not necessarily HDR; defining a normal scan sequence for applying a target charge (Cti) to each one of the M normal spots (Ri); Includes.

[0027] The present invention also relates to a Treatment Planning System (TPS) for implementing a Treatment Plan (TP) as defined above, the TPS comprising: a mesh unit configured to define, on a projection plane (Π) perpendicular to the irradiation axis (X), a mesh of N flash spots (Si) covering a projection range 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 impart a target dose (Dti) onto the spread cells of each flash spot (Si); · 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 spread by each flash spot (Si). In this unit, the target charge (Cti) is equal to the sum of the theoretical pulse charges (Cij) of the above-mentioned number (mi) of pulses for irradiating the flash spots (i.e., TIFF0007762632000006.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 spread by the flash spots by each pulse charge (Cij) (i.e., TIFF0007762632000007.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 spread by each flash spot. It comprises.

[0028] The flash scan sequence unit performs the following operations, i.e., · 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)) in 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). It is configured to plan. [Brief explanation of the drawings]

[0029] [Figure 1] Figure 1(a) shows an example of a spread-out 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 the SOBP obtained with 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 located upstream along the irradiation axis (X). The corresponding SOBP along the irradiation axis (X) and the projection of the treatment volume (V) onto the plane (Π) are depicted. Figure 2(b) shows a side view (perpendicular to the irradiation axis (X)) of the system of Figure 2(a) along with the corresponding SOBP. Figure 2(c) shows a front view (parallel to the irradiation axis (X)) of the system of Figure 2(a). Figure 2(d) shows a detail 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 successive pulses of charge (Cij) using a particle accelerator as a function of time (bottom graph) and the accumulated dose (ΣjDij) as a function of time (top graph). [Figure 4] Figure 4(a) illustrates the principle of the present invention by sequential application of doses to a spread of cells of the same pair of first spot (S1) and second spot (S2) as a function of time, while Figure 4(b) shows a top view of Figure 4(a) illustrating the scanning sequence between the first spot (S1) and the second spot (S2). [Figure 5]Figure 5(a) shows the accumulated dose delivered to the spread cells of adjacent first and second spots as a function of time by a conventional treatment plan in which the first and second spots are sequentially irradiated. Figure 5(b) shows the accumulated dose delivered to the spread cells of adjacent first and second spots as a function of time by a first embodiment of a flash scan sequence in accordance with the present invention, where n=2. Figure 5(c) shows the accumulated dose delivered to the spread cells of adjacent first, second, third, and fourth spots as a function of time by a second embodiment of a method in accordance with the present invention, where n=2. [Figure 6] Figure 6(a) shows a sequence of n=2 sets of flash spots where the same predetermined number of pulses are emitted at each of the two flash spots in a set, and Figure 6(b) shows a sequence of n=2 sets of spots where different target doses are delivered to the spread cells of each of the two flash spots in a set. DETAILED DESCRIPTION OF THE INVENTION

[0030] The present invention relates to a treatment device for the treatment of a treatment volume (V) with a beam (100) of charged particles, preferably protons, the treatment volume (V) comprising: a target volume (Vt) containing essentially only tumor cells (3t); A flush 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] The pulsed particle accelerator is configured to deliver pulses of charged particles. For example, the pulsed particle accelerator can be a synchrocyclotron, a synchrotron, or a laser-driven ion accelerator. The pulsed particle accelerator has the following characteristics: Charged particles are emitted in pulses (Pij), each pulse having a pulse charge (Cij) less than or equal to a maximum pulse charge (Cij≦CM) and a duration of a pulse time (tp), the pulses being separated from each other by an interpulse interval (Δtp) (see Figures 3, 4(a), and 5(a)-5(c)); The beam of charged particles can be scanned from the first flash spot to the second flash spot at a maximum scanning speed (vs = ds / Δts), where ds is the distance between the first and second flash spots, and Δts is the scanning time required to scan from the first flash spot to the second flash spot (see Figure 4(b)). It is characterized by:

[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 time (tp) for delivering the pulse, and the interpulse interval (Δtp), which defines the time required by the particle accelerator to emit the second pulse (Pi2) after the first pulse (Pi1) is emitted. The number of beams and the beam direction are important parameters. Only one beam direction extending along the irradiation axis (X) is discussed herein. Those skilled in the art will understand that the same description can be applied mutatis mutandis to various beam directions. The SOBP can be obtained by superposition of coaxial beamlets, which define the shape of the SOBP. Alternatively, a single beam (100) can be emitted and shaped by the interposition of a ridge filter. These techniques are well known to those skilled in the art and need not be described here.

[0034] The beam has a diameter. The charged particles are distributed according to a Gaussian distribution in the cross section of the beam perpendicular to the illumination 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 extending over the entire treatment volume (V) by pencil beam scanning (PBS). The dose must be delivered to the spread cells of the spot (Si) encapsulated within the flash volume (Vht) at 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 · Specification of a mesh of N flash spots (Si), and · Specification of the target charge (Cti) required to deliver the target dose (Dti) to the spread cells of each flash spot (Si) for 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), 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., TIFF0007762632000008.tif7170), specification, and · In the specification of the flash scan sequence of N flash spots, the scan sequence is ○ In the specification of a certain number (k) of sets (5), each set (5) includes a certain number n of flash spots (Si), where 1 < n < N, specification, and Provision 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 consecutive first and second flash spots of the set ((Si, S(i+1)) and (Sn, S1)) is always less than or equal to a maximum distance (dM) defined as the product of the scan speed (vs) and the dead time (td), i.e., d≦dM=vs×td, where the dead time (td) is the time between the end of a pulse and the beginning of the next pulse (i.e., td=Δtp-tp). Including provisions and Includes.

[0037] The processor is also configured to control the pulsed particle accelerator, for example, to perform 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) covering the projection range of the flash volume (Vht) projected parallel to the irradiation axis (X), which is approximately parallel to the beam (100), is defined on a projection plane (Π) perpendicular to the irradiation axis (X).

[0039] Oncologists characterize the geometry and topography of tumor regions based on images of the tumor region obtained by computed tomography (CT scan). Figure 2(a) shows a schematic diagram of an example tumor region, in which a healthy organ (Vh) containing healthy cells (3h) is located between the patient's skin (3s) and a target volume (Vt) containing primarily tumor cells (3t). To reach the target volume (Vt), the beam (100) must traverse the healthy volume (Vh), thereby 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 and tumor cells (3h, 3t), making it impossible to target tumor cells without irradiating healthy cells.

[0040] In pencil beam scanning (PBS), a mesh of spots is defined that characterizes the entire volume to be irradiated. Because currently available equipment makes it impossible to apply FLASH-RT to the entire tumor region in many applications, and to take advantage of the benefits of FLASH-RT at all, the mesh according to the present invention includes flash spots (Si) that should be irradiated with HDR and regular 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 the flash volume (Vht) and regular spots (Ri) (=white dots) contained within the target volume (Vt). In the embodiment of Figure 2, the flash spots (Si) are aligned with the beam that must traverse healthy organs (Vh). As mentioned above, the flash volume (Vht) may include healthy tissue (3h) adjacent to tumor cells (3t).

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

[0042] The spot has a dimension perpendicular to the irradiation axis (X), which may be equal to the beam diameter mentioned above. The distance between adjacent spots, which defines the mesh density, is an important parameter because the denser the mesh (i.e., the closer the adjacent spots are to each other), the greater the impact of dose overlap on the spread of cells from adjacent spots. When the distance between adjacent spots is approximately 1.5σ, significant overlap is observed, confirming a uniform lateral dose distribution.

[0043] Charge Plan The treatment plan must kill tumor cells present in the tumor area while sparing as many healthy cells as possible that are adjacent to the tumor cells or in the path of the beam aimed at the tumor cells. The oncologist defines a table that lists the dose to be delivered to each volume. The dose delivered by a beam of a given fluence depends on the type of tissue and how it interacts with the beam. For the same tissue, it can be said that the dose delivered by a beam depends primarily 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 the spread cells of both the flash spot (Si) and the normal spot (Ri).

[0044] To spare healthy cells, the treatment plan must meet a target dose rate, where the dose is delivered locally to the flash volume (Vht) to kill tumor cells while sparing as many healthy cells as possible by utilizing the FLASH effect. These target dose rates are generally determined by an oncologist who identifies one or more flash volumes (Vht) containing healthy cells based on images of the tumor area obtained by computed tomography (=CT scan). To reach the FLASH effect in one or more specific volumes (Vht), the one or more specific volumes (Vht) must be irradiated with a very high dose delivery rate (HDR), where HDR at each voxel of the volume is defined as the dose delivery rate, and HDR (=Σ i,j Dij / Σ j tj ≥ 1 Gy / s) is the sum of the dose (Σ i,j Dij) to one flash spot (Si), j The sum of the time (tj) required to give Dij j tj) (see Figure 3). The sum of the times includes the time during which the dose is delivered by overlapping beams aimed at 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 dimensions of 2 x 2 x 2 mm. Thus, a voxel can contain many biological cells. Since oncologists commonly rely on the results of CT scans to prescribe the dose to be delivered to cells, it is reasonable to use the same terminology and concepts for treatment planning.

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

[0046] According to the invention, for each flash spot (Si), a target charge (Cti) is defined at the end of the session that is required to deposit a target dose (Dti) on the cells of the voxel that spans each flash spot (Si). The target charge (Cti) depends on the properties of the beam and the properties of the tissue with which the beam interacts and to which the target dose (Dti) is to be deposited.

[0047] Once the 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 required to deliver the target dose (Dti) to the spread cells of each flash spot (Si), and ultimately to each voxel. Thus, as shown in FIG. 3, the target charge (Cti) is equal to the sum of the theoretical pulse charges (Cij) of the number (mi) of pulses that irradiate the flash spot (i.e., TIFF0007762632000009.tif8170). This also means that the target dose (Dti) is equal to the sum of the above number (mi) of pulse doses (Dij) given to the cells in the spread of the flash spot by each pulse charge (Cij) (i.e., It can also be expressed in terms of dose as (TIFF0007762632000010.tif8170). However, due to statistical uncertainties, the pulse charge actually delivered in each pulse by a particle accelerator can only approximate the theoretical pulse charge (Cij). Therefore, it is necessary to measure the actual delivered charge value and compare it with the theoretical pulse charge value (Cij). If there is a discrepancy between the two values ​​beyond a predetermined tolerance, the theoretical pulse charge of the next pulse (Ci(j+1)) can be corrected to the new value of the adjusted theoretical pulse charge to match the (theoretical) charge plan.

[0048] A flash scan sequence of N flash spots is then established, defining a sequence of flash spots (Si) in which a corresponding number (mi) of pulse doses (Dij) are delivered to the spread cells of each flash spot. The flash scan sequence is defined as follows:

[0049] Flash Scan Sequence 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 all successive 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 subsequence of n combined flash spots is defined, and the dead time (td) is the time required by the particle accelerator to emit a second pulse (Pi2) after a 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 subsequence must be spaced such that they require no more scan time (Δts) than the dead time (td) to scan from the first flash spot to the next flash spot in the scan subsequence (i.e., Δts ≤ td, ∀(Si, S(i + 1))). The scan subsequence 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 defined as follows, namely · when tc / td is an integer and the ratio tc / td > 1 (i.e., TIFF0007762632000011.tif7170), n = tc / td, · otherwise, the sum of 1 and the integer part of the ratio (tc / td) (i.e., n = INTEGER(tc / td)+1) is defined as 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 to all N flash spots of the mesh in the flash volume by HDR.

[0052] Flash scan subsequence A first pulse (P1) of pulse charge (C11) is delivered to the spread cells of the first flash spot (S1) of the first flash scan subsequence of the first set of n combined flash spots to impart a corresponding first pulse dose (D11). The actual first pulse charge (C11) actually delivered at the first flash spot (S1) is measured and compared to the theoretical first pulse charge to ensure that each spot receives the target charge (Cti) as planned. If there is a discrepancy between the actual and theoretical first pulse charge (C11), an adjusted theoretical second pulse charge (C12) to be delivered next to the first flash spot (S1) is calculated to match the theoretical flash charge plan. The measurement, comparison, and calculation of the adjusted value are collectively referred to as "calculation operations" and require a calculation time (tc) to complete. The computation time (tc) is generally greater than the interpulse interval (Δtp) separating two successive 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 the flash scan subsequence, and a first pulse charge (C21) is delivered to impart a first pulse dose (D21) to the spread cells of the second flash spot (S2). Meanwhile, during time (tc), a calculation operation for the first pulse charge (C11) for the first flash spot (S1) is performed. The beam must reach the second spot (S2) by the time the second pulse (P2) is ready to be discharged, i.e., by the end of the interpulse interval (Δtp) between the first pulse (P1) and the second pulse (P2). A calculation operation is performed to measure the actual first pulse charge (C21) delivered to the second flash spot (S2) in accordance with the theoretical flash charge plan, compare it with the theoretical first pulse charge (C21), and calculate an adjusted theoretical second pulse charge (C22) to 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 (S1) in the flash scan subsequence, and the previous step is repeated (n-2) times until the beam is moved to the nth flash spot (Sn) in the flash scan subsequence and a first pulse of charge (Cn1) is delivered to the extended cells of the nth flash spot, imparting a first dose (Dn1). Each time, the calculation operation is repeated for the first dose delivered to each of the set (5) of flash spots (S1-Sn).

[0055] The beam is then returned to the first flash spot (S1) of the flash scan subsequence for the estimated time required to measure the actual first pulse charge (Cn1) delivered at the nth flash spot (Sn) during the treatment session and calculate the adjusted theoretical second pulse charge (Cn2) to be delivered next at the nth flash spot (Sn) based on the theoretical flash charge plan. The adjusted theoretical second pulse dose (D12) is then delivered to the cells in the first flash spot (S1) calculated as above. The same process is repeated for the nth flash spot, delivering the adjusted theoretical second pulse dose (D12) to the cells in the first flash spot. These operations are repeated until the target charge (Cti) and the corresponding target dose (Dti) are delivered to the cells in the first set of n combined flash spots (S1, Sn). For n=2, the beam shuttles between the first and second spots (S1-S2-S1-...) and delivers a pulse each time, as shown in Figure 4(a) and Figure 4(b). In Figure 4(b), the accumulated dose Deq is calculated as the average dose Accumulated dose (Σ j Dij) (i.e., TIFF0007762632000013.tif7170).

[0056] The beam is then moved to the first flash spot according to a second flash scan subsequence of the second set of n combined flash spots, and the above steps are repeated until the corresponding target doses for all n combined flash spots of the second set of n combined flash spots have been received.

[0057] k sets of scan sequences The n flash spots (Si) of each set (5) can be irradiated with a very high dose rate (HDR), as explained above. It is important not to excessively extend the irradiation time when irradiating spots of another set with already irradiated flash spots (Si). Therefore, the sequence of the k sets must also be taken into consideration to ensure that at the end of the irradiation session, the dose (Dij) has actually been delivered with a very high dose rate (HDR). Methods for optimizing the sequence of spots to be irradiated with HDR are known in the art, for example, as described in U.S. Pat. No. 6,273,139. ​​Any of these methods described for the sequence of spots can be applied to the sequence of the k sets. For example, the unit cell of the scarf sequence can be defined as described in U.S. Pat. No. 6,273,139.

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

[0059] On the other hand, the calculation time (tc) depends on the entire processing unit. For example, the calculation time (tc) includes at least the following steps: · Measuring the actual pulse charge (Cij) delivered by the j-th pulse (Pij) applied to the i-th flash spot (Si); · Comparing the cumulative theoretical pulse charge with the cumulative actual pulse charge actually measured at the i-th flash spot (Si) after j pulses TIFF0007762632000014.tif9170 to calculate the adjusted theoretical pulse charge (Ci(j + 1)) to be applied to the i-th flash spot by the (j + 1)-th pulse (Pi(j + 1)) required to conform to the charge plan; · Preparing the pulsed 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), 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, but 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 of sets (5) must receive the same target dose (Dti) in HDR. This applies, for example, to mid-portions of flash volumes (Vht) with similar characteristics, away from any boundaries, or separated by a distance greater than 1.5σ, with 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 sets in a group of sets is constant, and the sets are composed of the same flash spots throughout a 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 flash spots, each set consisting of n = 2 flash spots. The spread cells of each flash spot (Si, S(i+1)) of 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 receive the same number of pulses (mi). 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) shuttles between the first and second flash spots of the first set (5) several times (m), depositing an accumulated charge each time until it reaches the target dose (Dti, Dt(i+1)) after (m(i+1)) pulses. At this stage, the cells covered by the flash spots of 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 deposition operation between the two spots as described above. Similar operations are repeated until the final set (5) consisting of the (N-1)th flash spot (S(N-1)) and the Nth flash spot (SN) to complete the treatment of the flash spots contained within the flash volume. If the flash volume contains an odd number (N) of flash spots, then the final 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. The normal spots (Ri) (=white spots) can be treated as normal and with CDR as 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) (the 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 such that a portion 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 pulses (Pij) targeting the first or second spot is shown by the portion of the curve labeled (P).

[0065] Fig. 5(a) shows 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, such that the target dose (Dti) is reached 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 a continuous dose (D(i+1)j) in (m(i+1) number of) consecutive 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) each to deliver the target doses (Dti, Dt(i+1)) to the adjacent first and second spots respectively. Each of these 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, and 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 fact that it requires 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 consecutive 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 significantly reduces total irradiation time compared to the prior art treatment plans described above. Figure 5(b) shows a treatment plan for a set (5) of n=2 flash spots (S, S(i+1)) that must receive the same target doses (Dt, Dt(i+1)) and the same number of pulses (m, m(i+1)) as the prior art 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 tissue at the first flash spot (S1), moves to the second flash spot (S2) to deliver a first dose (D21), returns to the first flash spot (S1) to deliver a second dose (D12) according to the adjusted theoretical second pulse charge determined and prepared during the calculated time (tc) when the first dose (C21) was delivered to the second flash spot (S2), and so on. Due to the charge overlap 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 time units, or approximately half the time required according to the prior art treatment plan discussed with reference to FIG. 5(a). This results in a charge deposition rate that is twice as high as that achieved with prior art treatment plans, increasing the likelihood of treating the entire flash volume with HDR. Furthermore, the total time (Δt, tot(Si)) required to treat both flash spots (Si, S(i+1)) of set (5) is also approximately half the time required with prior art treatment plans. Regardless of whether there is dose overlap between the spread cells of the two adjacent spots, this significantly reduces the duration of the treatment session, benefiting both the patient and the hospital or treatment center, allowing them to plan more treatments per unit time and optimizing the frequency of particle accelerator use.

[0068] Compared to prior art treatment planning, the acceleration of treatment planning according to the present invention increases when the ratio (tc / td) of calculation time (tc) to dead time (td=Δtp-tp) is greater than 1. The present invention reduces treatment time by selecting the number of flash spots in each set so that the ratio (tc / (td×n)) approaches 1 and preferably does not become less than 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 irradiate the same number of pulses (m) to the cells in the spread of the flash spots in order to reach their respective target doses (Dti). This can occur, for example, when the flash spots are close to a boundary or when the mesh is dense and there is significant overlap between adjacent flash spots. Therefore, the cells in the spread of the flash spots designed to receive the fewest number of pulses will reach the target dose (Dti) before the cells in the spread of adjacent flash spots in the same set. These flash spots must not be further irradiated and must therefore be prevented from being irradiated, while the cells in the spread of other flash spots in the same set must still receive some dose. To prevent uncontrolled dose overlap toward flash spots whose cells have already received their target doses (Dti) or their planned number of pulses (Pij), dose delivery can continue with flash spots (n-1), (n-2), etc. in the set whose cells have not yet received their target doses (Dti) or their planned number of pulses (Pij). All flash spots except the two remaining in the set receive their corresponding target doses and leave the irradiation field, so that of the two remaining flash spots, the one that has to receive the most pulses will soon be alone in the set (or irradiation field). If the same thing happens with multiple sets, leaving many single flash spots, it may become difficult to guarantee HDR throughout the entire flash volume.

[0070] In the preferred embodiment of the present invention shown in FIG. 6(b), the set includes n = 2 combined flash spots, and the expanded 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 expanded 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 only 2 flash spots remain for each cell to receive the pulses necessary to reach the corresponding target dose (Dti), as explained above. 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 is greater than the number of pulses (m1) of the first target dose (Dt1) that the expanded 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 set (5) (see the solid and dashed lines in FIG. 5(c)) each receive (mi) pulses (and if there is no substantial overlap, the target dose (Dti) is delivered to the spread cells of the first flash spot (Si)), and 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 flash spots (S(i+2)), wherein a 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)) each receive (m(i+1)-mi) pulses, until the second flash spot (S(i+1)) receives a target charge (Ct(i+1)) that must be greater than the residual charge (Ct(i+1)-Ct(i), · The third flash spot (S(i+2)) (see 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 mixed line in Figure 5(c)) to form a third set of n = 2 flash spots (S(i+2), S(i+3)), and so on until all N flash spots of the mesh have received their respective target charges (Cti) in the HDR.

[0071] A similar analysis can be performed with respect to Figure 5(a) by comparing the time sequence of the prior art treatment plan with the time sequence of this embodiment shown in Figure 5(c). First, the same flash scan sequence as discussed with respect to Figure 5(b) is applied here, with the beam moving 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 in Figure 5(c) that there is no substantial overlap between adjacent flash spots. The second flash spot (S(i+1)) dissociates from the first flash spot (S) and forms a new set 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)) has received 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 set (5) of n=2 flash spots, and so on. As can be seen from Figure 5(c), the treatment time is optimized to be the same time required by the prior art treatment plan of Figure 5(a) to deliver the target dose (Dti, Dt(i+1)) to the spread cells of the first and second spots (high risk of being too slow for HDR), and the target dose is delivered to the spread cells of three flash spots (Si to S(i+2)), and partially to the spread cells of the fourth flash spot (S(i+3)) in the present embodiment of Figure 5(c).

[0072] As discussed above in connection with the embodiment of FIG. 5(b), the present invention reduces treatment time by selecting the number of flash spots in each set so that the ratio (tc / (td×n)) approaches, but does not become less than, 1 (i.e., tc / (td×n)≧1 and tc / (td×n)→1).

[0073] Normal spot (Ri) The present 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) that mainly contains tumor cells (3t), and the 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 worrying about the charge delivery rate, except for shortening the session for patient comfort. Developing a treatment plan for the target volume (Vt) involves the following steps: defining, on the projection plane (Π), a mesh of M normal spots (Ri) covering the projection of the target volume (Vt) (i.e. Vt=V-Vht), projected parallel to the irradiation axis (X); determining a normal charge plan for each normal spot (Ri), defining a value of each pulse charge (Cij) for applying a target charge (Cti) with mi pulses, not necessarily HDR; defining a normal scan sequence for applying a target charge (Cti) to each one of the M normal spots (Ri); Includes.

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

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

[0076] By combining the flash spots (Si) into sets of n flash spots and moving the beam (100) according to the flash scan subsequence described above, the time to deliver the target dose (Dti) to the spread cells of the flash spots (Si) is significantly reduced, and the dose delivery rate is correspondingly improved. This is even more advantageous when there is significant dose overlap between adjacent flash spots. In all cases, the session duration is significantly reduced by the treatment planning described herein as opposed to conventional planning, where the target dose (Dti) is delivered sequentially to the spread cells of each spot (see FIG. 5(a) (prior art) and FIGS. 5(b) and 5(c) (present invention)). [Explanation of symbols]

[0077] 3h Healthy cells 3t tumor cells 3s Patient's skin 5 Combined flash spot set 100 beams Cij Charge of pulse (Pij) CDR Conventional Dose Delivery Rate Maximum pulse charge of CM pulse Di Dose delivered to cells with spread of flash spot TIFF0007762632000015.tif8170Dij Dose deposited by pulse Pij of charge Cij d distance between two spots dM is the maximum distance between two consecutive flash spots in a scan subsequence ds scan distance Dti Target dose in the spread cell of the spot (Si, Ri) HDR Ultra-high dose rate The number of k pairs M Number of normal spots (Ri) mi is the number of pulses required to deliver the target dose (Dti). Number of flash spots in n sets N Number of flash spots (Si) nR Number of flash spots in the additional set (= remainder of the ratio N / n) Pij charge (Cij) pulse Ri Normal Spot i Si Flash Spot i SOBP Bragg peak sum tc calculation time td dead time (=Δtp-tp) tp Pulse time V treatment volume 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, said treatment volume (V) comprising: a target volume (Vt) containing substantially only tumor cells (3t); - flush volume (Vht) containing healthy cells (3h) It consists 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), wherein HDR is 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 one another 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 scanning speed (vs = ds / Δts), where ds is the distance between the first and second flash spots and Δts is the scanning 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 projection of the flash volume (Vht) 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); - defining for each flash spot (Si) the target charge (Cti) necessary to impart a target dose (Dti) to the cell in 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), wherein the target charge (Cti) is equal to the sum of the theoretical pulse charges (Cij) of the number (mi) of pulses irradiating the flash spot (i.e. ), or the target dose (Dti) is equal to the sum of the number (mi) of pulse doses (Dij) imparted to the cells in the spread of 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 a corresponding number (mi) of pulse doses (Dij) is applied to said cell in the extent of each flash spot; Contains Processor and Equipped with the flash scan sequence: the definition of a certain number (k) of sets (5), each set (5) containing a number n of flash spots (Si), 1<n<N; - defining a flash scan subsequence of the n combined flash spots such that 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 a maximum distance (dM) defined as the product of the maximum scan speed (vs) and a dead time (td), i.e., d≦dM=vs×td, wherein the dead time (td) is the time between the end of a pulse and the beginning of the next pulse (i.e., td=Δtp−tp); and the processor: (a) directing the beam to a first flash spot (S1) (i.e., i=1) and delivering a corresponding first pulse dose (D11) to the spread cell of the first flash spot (S1) of a first flash scan sub-sequence 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 spread cells of 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 sub-sequence and delivering a first pulse charge (Ci) to the spread cells of the i-th flash spot (Si) during an estimated time required to measure the actual previous pulse charge (C(i-1)) actually delivered to the previous flash spot (S(i-1)) during a treatment session and to calculate an adjusted theoretical second pulse charge (C(i-1)) to be delivered next at the previous flash spot (S(i-1)) in accordance with the theoretical flash charge plan; (d) repeating step (c) (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 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 delivered next at the nth flash spot (Sn) in accordance with the theoretical flash charge plan; (f) repeating steps (b) through (e) until j=(mi-1), and repeating steps (b) through (d) for j=mi at least until the target charge (Cti) is delivered to each flash spot (S1, Sn) in 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) through (f) for the n combined flash spots of the second set of n combined flash spots; (h) repeating step (g) for the flash scan sub-sequences of the remaining (k-2) sets of n combined flash spots until a corresponding target charge (Cti) is delivered with HDR to the n combined flash spots of all k sets (5) of the mesh; a pulsed particle accelerator configured to control the pulsed particle accelerator by

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 is 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, and tc is the calculation 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 at the i flash spot (Si) after j pulses. calculating an adjusted theoretical pulse charge (Ci(j+1)) to be applied to the i flash spot by the (j+1)th pulse (Pi(j+1)) required to conform to the theoretical flash 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 it is required to complete the following.

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

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). This includes: the processor: - separating 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 the second flash spot (S2) to form a second set of n=2 flash spots (S2, S3), the third flash spot (S3) being located at a distance d (≦DM) from the second flash spot (S2), and both the second flash spot (S2) and the third flash spot (S3) are subjected to (m2-m1) pulses each, until the second flash spot (S2) receives the target charge (Ct2), which must be 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 projection of the target volume (Vt) (i.e. Vt=V-Vht) projected onto the projection plane (Π) parallel to the irradiation axis (X); 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, wherein the TPS comprises: 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 the range of the 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 impart a target dose (Dti) to the cells encompassed by 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 required to deliver the target dose (Dti) to the cells spread of each flash spot (Si), wherein said target charge (Cti) is equal to the sum of the theoretical pulse charges (Cij) of said number (mi) of pulses irradiating the flash spot (i.e. ), or the target dose (Dti) is equal to the sum of the number (mi) of pulse doses (Dij) imparted to the cells in the spread of the flash spot by each pulse charge (Cij) (i.e., ), flash planning unit, a flash scan sequence unit configured to define a flash scan sequence of said N flash spots (Si) defining a sequence of flash spots (Si) in which a corresponding number (mi) of pulse doses (Dij) is applied to said cell in the extent of each flash spot; Equipped with The flash scan sequence unit performs the following operations: - defining a certain 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 the n combined flash spots (5) such that for each set 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 maximum scan speed (vs) and a dead time (td), i.e., d≦dM=vs×td, wherein the dead time (td) is the time between the end of a pulse and the beginning of the next pulse (i.e., td=Δtp−tp); A treatment planning system (TPS) configured to plan a treatment.

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