The use of radiation therapy to treat cancer is well known. Radiation therapy (radiotherapy) involves directing a beam of high energy particles such as electrons, protons, or heavy ions into a target volume (e.g., a tumor or lesion) in a patient.
Before the patient is treated with radiation, a treatment plan specific to that patient is developed. The plan defines various aspects of the radiotherapy using simulations and optimizations based on past experiences. For example, for intensity modulated particle therapy (IMPT), the plan can specify the appropriate beam type and the appropriate beam energy. Other parts of the plan can specify, for example, the angle of the beam relative to the patient/target volume, the beam shape, and the like. In general, the purpose of the treatment plan is to deliver sufficient radiation to the target volume while minimizing the exposure of surrounding healthy tissue to radiation.
Existing IMPT dose delivery techniques utilize raster scanning that takes advantage of the well-known Bragg peak characteristic of a mono-energetic particle (e.g., proton) beam. By scanning the beam in the X and Y directions, a “layer” of dose can be “painted” within the target volume. Subsequent layers are painted in overlapping raster scan patterns using particles with a different energy that would thus stop at a different range (distance). Such scan patterns usually start at the most distal edge of the planning target volume and each subsequent layer is delivered, after a pause to change the beam energy, to a lesser range thus creating a Spread Out Bragg Peak (SOBP), until the final layer is delivered to the proximal edge of the planning target volume.
A fundamental concern during radiation therapy is that the target volume might move during dose delivery (e.g., due to the patient moving, breathing, etc.). Movement during dose delivery can inadvertently place healthy tissue in the path of the radiation intended for the target volume. Although it is theoretically possible for the raster scan pattern to track in-plane motion of the target volume, by superimposing the raster scan pattern with the instantaneous two-dimensional (X-Y) vector corresponding to that motion, any out-of-plane motions (particularly those of normal healthy structures proximal to the target) can introduce motion-related uncertainties that in turn can create dose overlaps (“hot spots”) or, even worse, gaps (“cold spots”) within the target volume.
A recent radiobiology study has demonstrated an advantageous effectiveness in sparing normal, healthy tissue from damage by delivering an entire, relatively high therapeutic radiation dose within a single short period of time (e.g., less than one second). However, in conventional raster-scanned IMPT, because dose delivery along each ray passing through the patient occurs successively at different points in time in the scan pattern and is thus spread out over time, the unavoidable dose that is delivered to the normal healthy structures is also spread out over time. Therefore, the radiobiological tissue-sparing effects reported in the aforementioned study are not realized using existing IMPT techniques.
Furthermore, contemporary radiation therapy delivery systems include dipole electromagnets and scanning magnets. The dipole magnets (often referred to as “bending magnets”) direct (e.g., bend) the particle beam in a direction toward a nozzle, and the scanning magnets steer (deflect or scan) the beam in the X and Y directions. The dipole magnets typically utilize massive ferromagnetic return paths and therefore have a much slower magnetic hysteresis relative to the scanning magnets. That is, it takes much longer to change (increase or decrease) the level of magnetism in the dipole bending magnets than it does to steer the beam using the scanning magnets during IMPT delivery. Also, the relative slowness of varying the magnetic fields of the dipole bending magnets is the primary reason that existing IMPT systems utilize a method of scanning dose one layer at a time. The time spent changing the magnetic strength of the dipole magnets in order to change the incident beam energy constitutes a significant portion of the time required to deliver an IMPT therapy dose. Considering the comfort of the patient, for example, shorter radiotherapy sessions are highly preferred. Thus, the reliance on magnets, particularly the use of the dipole bending magnets, for adjusting particle beams is an obstacle to realizing the benefits of using relatively high therapeutic radiation doses within a very short period of time for dose delivery in radiotherapy.
In an embodiment according to the present disclosure, a radiation therapy system includes an accelerator and beam transport system and a nozzle that can be aimed toward an object. The nozzle includes at least one scanning magnet that guides (e.g., steers, deflects, or scans) the beam toward various locations within a target volume within the object. The nozzle also includes a beam energy adjuster configured to adjust the beam by, for example, placing different thicknesses of material in the path of the beam to affect the energies of the particles in the beam. The beam energy adjuster may include one or both of a range shifter and a range modulator. In an embodiment, the range shifter is configured to place different thicknesses of material in the path of the beam to affect the distance that the particles penetrate into the object. In an embodiment, the range modulator is configured to place different thicknesses of material in the path of the beam to decrease the energies of at least a portion of the particles by varying the exiting beam particle energy over time, to spread out the Bragg peak.
Significantly, the range shifter and/or range modulator, placed in the nozzle as described in this disclosure, are “dynamically variable” (e.g., faster acting than the dipole magnets in the beam transport system). Consequently, a nozzle according to the present disclosure is capable of quickly adjusting the particles in the beam to create a scanned beam (as opposed to a scattered beam) that delivers an entire, relatively high therapeutic radiation dose in the target volume. For example, a dose of four grays can be delivered along a specified beam direction (e.g., a given ray) in less than one second.
Each ray is a part of a scan pattern and irradiates tissue along a different line segment through the target volume (a “target line segment”). A high dose that can be delivered in a short period of time along a target line segment may be referred to herein as a “shot.” In an embodiment, a shot can be adjusted in energy (intensity) or range and delivered to the target volume with a Spread Out Bragg Peak (SOBP) that provides a uniform and otherwise suitably modified dose to an entire target line segment.
The intensity of the dose delivered in a shot can be adjusted to match the prescribed dose for a particular target line segment. Shots can be delivered using, for example, a predefined scanning pattern to irradiate different target line segments: a first adjusted beam that delivers a first dose with a SOBP along a first target line segment in a target volume can be created, and a second adjusted beam that delivers a second dose with a second SOBP along a second target line segment in the target volume can be created, where the second target line segment is displaced from the first target line segment. Each shot can be triggered in time and/or aimed in position to coincide with the position of a moving target within a patient based on, for example, a motion tracking system. Subsequent shots can be independently adjusted in intensity, in range, and with a suitable SOBP, and can also be triggered or aimed to coincide with the 4D (three dimensions plus time) position of each target line segment in the scan pattern until the entire target volume has been irradiated to the prescribed dose.
In an embodiment, a range shifter is in the nozzle, downstream of the scanning magnet(s). In another embodiment, the range shifter is in the nozzle, upstream of the scanning magnet(s). The range shifter provides a rapid means of quickly varying the range of the Bragg peak to match the distal edge of the planning target volume.
In an embodiment, the nozzle includes both a range modulator and a range shifter. The range modulator is downstream of the scanning magnet(s); the range shifter can be downstream or upstream of the scanning magnet(s). In an embodiment, the range modulator includes a number of arms extending from a hub. In an embodiment, each of the arms has a non-uniform thickness and a non-uniform width (and therefore a non-uniform amount of space between adjacent arms). The range modulator can rotate about the hub, so that the beam will pass through at least one of the arms and also can pass through the space between adjacent arms.
In an embodiment, the range modulator can be moved in a first direction (e.g., laterally, transverse to the path of the beam) so that it is either completely out of the path of the beam or is in the path of the beam. In an embodiment, the range modulator can also be moved in a second direction different from (e.g., perpendicular to) the first direction and transverse to the path of the beam.
The range modulator provides a means of quickly varying the energy in a scanned beam to create the desired extent of SOBP in a dynamically variable manner. By adjusting the position of the range modulator and rotating the range modulator, the beam can pass through different parts of at least one of its arms and therefore through different thicknesses of material and also through different amounts of space between adjacent arms, and therefore the extent of spread of the SOBP can be rapidly varied over a useful range.
The range modulator and/or the range shifter match the SOBP (distally and proximally) to the target volume (the planning target volume). Because the range modulator and the range shifter can achieve these effects quickly, a shot can advantageously be used for dose delivery. Thus, using shots, the entire target volume can be irradiated to the dose prescribed by the treatment plan while exposing healthy tissue to only a single, very short burst of radiation. Also, by delivering the entire dose within a short period of time, movement of the target volume becomes much less of an issue. Likewise, delivering a pattern of shots with varying intensity from a single beam direction quickly results in intensity-modulated radiation therapy delivery. Further, by delivering patterns of shots from multiple beam directions, a more refined intensity modulation can be achieved with lower dose delivered to healthy tissues. Importantly, because no dose is delivered distally to the Bragg peak, the dose delivered in this manner to any healthy tissue, outside the target volume, can thus be limited to a single very short burst of low dose radiation.
In summary, embodiments according to the present disclosure provide spatially and temporally precise, modulated irradiation of a moving target in a patient and take advantage of the tissue-sparing effects of the study mentioned above. Embodiments according to the present disclosure provide a more direct method for target volume scanning than the use of the conventional raster scanning technique described above. Each shot is aimed directly to coincide with the in-plane motion of the target using the scanning magnet(s), rather than having to distort the raster scan pattern. Aiming subsequent shots thusly avoids creating motion artifacts such as those caused by the interplay between the target motion of sequential raster scan patterns. Likewise, target motion in the distal-to-proximal direction can be compensated for by varying the range shifter accordingly between shots. Quality assurance is also made easier because the tracking and scanning processes are more independent of one another. Significantly, because a SOBP covering the entire length of each target line segment (from the distal edge to the proximal edge of the planning target volume) is delivered in a short burst, motion-induced uncertainties do not create gaps or overlaps (cold spots or hot spots) within the target volume.
These and other objects and advantages of the various embodiments of the present disclosure will be recognized by those of ordinary skill in the art after reading the following detailed description of the embodiments that are illustrated in the various drawing figures.
This summary is provided to introduce a selection of concepts in a simplified form that is further described below in the detailed description that follows. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.
The accompanying drawings, which are incorporated in and form a part of this specification and in which like numerals depict like elements, illustrate embodiments of the present disclosure and, together with the detailed description, serve to explain the principles of the disclosure.
Reference will now be made in detail to the various embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings. While described in conjunction with these embodiments, it will be understood that they are not intended to limit the disclosure to these embodiments. On the contrary, the disclosure is intended to cover alternatives, modifications and equivalents, which may be included within the spirit and scope of the disclosure as defined by the appended claims. Furthermore, in the following detailed description of the present disclosure, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure. However, it will be understood that the present disclosure may be practiced without these specific details. In other instances, well-known methods, procedures, components, and circuits have not been described in detail so as not to unnecessarily obscure aspects of the present disclosure.
A “ray” is a part of a scan pattern and irradiates tissues along a different line segment through the target volume (a “target line segment”). A high dose that can be delivered in a short period of time along a target line segment may be referred to herein as a “shot.”
The accelerator and beam transport system 104 generates and accelerates a beam of charged particles, such as electrons, protons, and heavy ions, and contains the particles in a well-defined beam. In an embodiment, the accelerator is an isochronous cyclotron capable of continuous wave output. The accelerator (e.g., the cyclotron) extracts particles with a specified energy. This provides a high, continuous wave beam current for the high dose rate per shot. Other types of accelerators can be used, such as a pulsed proton accelerator such as a synchrocyclotron or a synchrotron. The accelerator (e.g., cyclotron) can be a lower power output cyclotron, such as a cyclotron that accelerates particles to the range of 70-300 MeV.
The accelerator and beam transport system 104 includes components (e.g., dipole magnets, also known as bending magnets) that direct (e.g., bend, steer, or guide) the beam through the accelerator and beam transport system in a direction toward and into the nozzle 106. The accelerator and beam transport system 104 may also include components that are used to adjust the beam energy entering the nozzle 106 so that it is different from the beam energy extracted from the accelerator. In an embodiment, sets of quadrupole magnets are located along the beam paths in the accelerator and beam transport system 104.
The nozzle 106 is used to aim the beam toward various locations within an object (e.g., a patient) supported on the supporting device 108 (e.g., a chair or table) in a treatment room. The nozzle 106 may be mounted on or a part of a gantry (not shown) so that it can be moved relative to the supporting device 108; the supporting device may also be moveable. In an embodiment, the accelerator and beam transport system 104 is also mounted on or is a part of the gantry; in another embodiment, the accelerator and beam transport system is separate from (but in communication with) the gantry.
A control system 110 receives and implements a prescribed treatment plan. In an embodiment, the control system 110 includes a computer system having a processor, memory, an input device (e.g., a keyboard), and perhaps a display in well-known fashion. The control system 110 can receive data regarding operation of the system 100. The control system 110 can control parameters of the accelerator and beam transport system 104, nozzle 106, and supporting device 108, including parameters such as the energy, intensity, direction, size, and/or shape of the beam, according to data it receives and according to the prescribed treatment plan.
As noted above, the particles entering the nozzle 106 have a specified energy. Thus, in embodiments according to the present disclosure, the nozzle 106 includes one or more components that affect (e.g., decrease, modulate) the energy of the particles in the beam. In an embodiment, the nozzle 106 also includes components (e.g., X-Y scanning magnets) that steer (e.g., guide, deflect, or scan) the beam particles in the X and Y directions, to scan a target volume in a patient on the supporting device 108.
The term “beam energy adjuster” is used herein as a general term for a component or components that affect the energy of the particles in the beam. In various embodiments, the beam energy adjuster 107 includes a range modulator, a range shifter, or both a range modulator and a range shifter. That is, when the term “beam energy adjuster” is used, then the element being discussed may be a range modulator, a range shifter, or both a range modulator and a range shifter. Note that, in an embodiment in which the beam energy adjuster includes both a range modulator and a range shifter, the range modulator and the range shifter may be separated from each other by other nozzle components. This is illustrated in further detail in
In an embodiment, the nozzle 106A includes a vacuum chamber 208 and monitor chambers 210. The monitor chambers 210 monitor the radiation exiting from the vacuum chamber 208.
In the
As noted above, the initial energies of the particles within the beam 101 are determined by the acceleration provided to the particles by the accelerator and beam transport system 104 (
Continuing with reference to
The range modulator 212 rapidly varies the exiting beam particle energy to create the desired extent of SOPB in a dynamic manner. Also, the range modulator 212 is moveable, so that it can be moved into and out of the beam path and to change the thickness of material exposed to the beam, thereby also changing the extent of the SOBP. This is further discussed below in conjunction with
In the embodiment of
The range shifter 214 is configured to change (e.g., decrease) the energies of the particles in the particle beam to affect the distance that the particles penetrate into the target volume; the range shifter affects the range of the beam. More specifically, the range shifter 214 provides a rapid means of varying the range of the Bragg peak so that the Bragg peak occurs at the distal edge of the planning target volume for each shot. An embodiment of the range shifter 214 is described further below in conjunction with
In the
Each of the arms 404 has a non-uniform thickness. In an embodiment, the thicknesses of the arms 404 decrease as the distance from the hub increases.
In an embodiment, the lengths of the chords of the arms 404 decrease as the distance from the hub 402 increases; that is, the widths of the arms decrease as the distance from the hub increases (where width, W, is the dimension facing the incident particle beam). Thus, in an embodiment, the amount of space, S, between the arms 404 increases as the distance from the hub 402 increases. While the arms 404 are illustrated as being semi-elliptical in shape, the present disclosure is not so limited; the arms may be more rectangular in shape, with rounded corners, for example. Generally speaking, the shapes of the arms 404 can be optimized to achieve design objectives with regard to, for example, selecting and controlling the extent of the SOBP.
The range modulator 212 can rotate clockwise and/or counter-clockwise about an axis 420 through the center of the hub 402 in order to place the arms 404 (one arm at a time) into the path of the scanned beam (into the beam line). The range modulator 212 can also rotate to a position that allows the beam to pass through the space between two adjacent arms. The range modulator 212 can rotate continuously to allow the beam to pass through a varying thickness/width of a combination of at least one arm and at least one amount of space; the varying material thickness due to that rotation creates a desired SOBP. As will be described further below, the range modulator 212 can be moved in the horizontal direction so that the incident particle beam will pass through a different part of an arm and hence through a different thickness and width of material and also through a different amount of space when the range modulator is rotated. The range modulator 212 can also be moved to a position so that it is entirely outside of the beam. In an embodiment, the range modulator 212 can also be moved in the vertical direction, allowing the range modulator to be placed virtually anywhere in or out of the beam.
The shape (profile and cross-sections) of the arms 404 is not limited to the examples of
With reference to
Any of a number of different mechanisms can be used to move the range modulator 212 horizontally and/or vertically. For example, the range modulator 212 can be mounted on a sliding stage or assembly that allows it to be moved in either or both directions, depending on the embodiment.
In
When the range modulator 212 is rotating in the beam path, the beam passes through at least one of the arms 404 and at least one space between adjacent arms. The speed of rotation of the range modulator 212 can be varied such that a beam shot passes through more than one arm 404 and more than one space between adjacent arms. The rotation speed of the range modulator 212 can also be adjusted so that it is synchronized with the operation of the accelerator. Any of a number of different mechanisms can be used to rotate the range modulator 212. For example, the range modulator 212 can be driven directly or indirectly by a motor connected to the hub 402.
In an embodiment, when the range modulator 212 is rotating in the beam path, the position of the range modulator in the beam path is chosen (and the range modulator is moved to that position) so that the varying material thickness due to the varying thicknesses/widths of the arms 404 and the amount of space between the arms results in the desired SOBP. At any point in time, the Bragg peak is a function of the radial distance of the beam from the hub 402. The extent of SOBP can be varied continuously from having no particle beam impingement and thus no SOBP (a pristine Bragg peak) when the beam is beyond the tip of one of the arms 404 (such as the position indicated by the dashed circle 412), to creating a maximum SOBP when the beam passes through the thickest part of one of the arms, for example, near the hub 402. The desired extent of SOBP can be achieved by moving the range modulator 212 so that the beam passes through the range modulator at a radial distance from the hub 402 corresponding to the desired SOBP. By moving the range modulator 212 rotationally and/or radially (in a horizontal and/or vertical direction), any desired SOBP can be achieved.
The range modulator 212 can be quickly positioned (rotationally and radially) and thus can be used to quickly change the SOBP, much more quickly than could be achieved using magnets. Consequently, a dose of four grays can be delivered along a target line segment in less than one second. Moreover, a dose of at least 20 grays can be delivered along a target line segment in less than 500 milliseconds.
In an embodiment, the wedges 502 and 504 can be rapidly adjusted, moving along a programmed motion profile. When placed downstream of the X-Y scanning magnets 204 and 206 (
The range shifter 214 is not limited to the embodiment of
For example, the wedges 502 and 504 may be made of the same material or combination of materials, or the wedges may be made of different materials or combinations of material; that is, one wedge may be made of one material or combination of materials, and another wedge may be made of a different material or materials. The materials may have different densities. Accordingly, the range shifter 214 may be made with components that are other than wedge-shaped. For example, the components may be block-shaped. The density of each block may be non-uniform such that an incident beam will pass through different densities of material depending on where and how the blocks are placed in the path of the beam and where and how the blocks are placed relative to one another. Also, different densities and thicknesses of material can be used; for example, wedge-shaped components that also have non-uniform densities can be used. The range shifter 214 can be implemented using more than two components (e.g., more than two wedges or blocks).
As mentioned above, in an embodiment, an isochronous cyclotron capable of continuous wave output can be used to generate a particle beam. In an embodiment, movement (e.g., rotational, radial, lateral) of the range modulator 212 can be synchronized with the beam source or generator (e.g., with the isochronous cyclotron). For example, sensors can be used to monitor the speed, position, and phase of the range modulator 212 and that information can be used (e.g., by the control system 110) to synchronize the movement of the range modulator to compensate for variations in the intensity of the beam output by the isochronous cyclotron or to compensate for effects of the X-Y scanning magnets 204 and 206. Then, the range shifter 214 is used to “trim” the distal edge of the planning target volume, thus reducing scatter.
In block 702, a beam of particles is received into a nozzle.
In block 704, the beam is scanned (raster scanned) using a number of X-Y scanning magnets.
In block 706, in an embodiment, the distance that the particles penetrate into a target volume is adjusted with a range shifter that is configured to place different thicknesses of material in the path of the beam. In an embodiment, the range shifter is in the nozzle, downstream of the scanning magnets and can act as a range modulator; in another embodiment, the range shifter is in the nozzle, upstream of the scanning magnets.
In block 708, in an embodiment, the energies of at least a portion of the particles in the beam are also adjusted with a range modulator that is in the nozzle and downstream of the scanning magnets (thus the range modulator is exposed to a scanned beam).
Thus, the nozzle can be used to create an adjusted beam that delivers a dose with a SOBP along a target line segment (a shot) in a target volume aligned with the nozzle. The intensity of the dose delivered in a shot can be adjusted to match the prescribed dose for a particular target line segment. Shots can be delivered using, for example, a predefined scanning pattern to irradiate different target line segments; a first adjusted beam that delivers a first dose with a SOBP along a first target line segment in a target volume can be created, and a second adjusted beam that delivers a second dose with a second SOBP along a second target line segment in the target volume can be created, where the second target line segment is displaced from the first target line segment.
The range shifter and/or range modulator placed in the nozzle as described in this disclosure are dynamically variable (e.g., faster acting than the dipole bending magnets in the beam transport system). In an embodiment, the dose delivered along the target line segment is at least four grays and is delivered in less than one second. In another embodiment, the dose delivered along the target line segment is at least 20 grays and is delivered in less than 500 milliseconds.
In an embodiment, treatment planning and dose delivery are performed using multiple beams from different directions and nozzles, instead of using a single nozzle as described above. Each beam can be delivered at a separate time with obtuse or large acute angles between each direction. Because of the fundamental property of a particle beam in which no dose is delivered distally to the Bragg peak, no normal, healthy tissue along a ray beyond that point will receive an unwanted dose. Also, the proximal portions of any rays aimed from different beam directions do not overlap each other for directions that have an obtuse angle relative to each other. Even for beam directions at large acute angles, the extent of overlap is small. Any such overlap outside the target would reduce the positive effects attributable to the use of shots as described herein, so it is desirable to minimize any overlap.
Multiple beam directions are beneficial for at least two reasons. First, scanning dose through the target from multiple directions will greatly reduce the extent and magnitude of any dose inhomogeneity caused by the scan pattern or motion-induced range uncertainty from any one direction, as any of these effects (if present) would be overlapped within the target volume from separate directions. Second, scanning from multiple directions provides significantly greater independent degrees of freedom that can be utilized in treatment plan optimization while also significantly reducing the dose level to any normal, healthy tissue; the entrance dose is spread out over a larger volume of normal tissue.
Two nozzles, each as described above, can be placed coaxially and opposite each other with both aimed at the isocenter. A fast “kicker” magnet in a fixed beam would direct the beam back-and-forth between separate gantry-mounted paths feeding each nozzle. Scanning within each nozzle would be such that beams from both nozzles would both strike the same tissue sequentially or otherwise as close to each other in time as practical (e.g., within one second or within 500 milliseconds of each other), thus taking advantage of the positive radiobiological effects attributable to the use of shots as described herein. Because the planning target volume is typically not at the precise center of the patient, a range shifter such as the range shifter 214 described above can be employed in each nozzle to bring the SOBP from both nozzles into spatial coincidence. Because a very similar SOBP is delivered to the same target line segment from both directions, the magnitude of dose delivered to any normal, healthy tissue along the same line (proximal to the target from each direction) is reduced by half. Another advantage is that this arrangement of nozzles allows a treatment planner to independently optimize the shape and intensity of the scan pattern delivered from each direction to beneficially trade off different dose objectives or constraints during planning. For example, paired nozzles can be used to limit the dose to a specific organ-at-risk that is partially overlapping the planning target volume. No dose is delivered distally to the target beyond the Bragg peak, and this characteristic can be taken advantage of during treatment planning, especially when proton beams are to be used.
Fixed beams can also be employed rather than gantry-mounted beams, either singly or as an opposed pair as described above. The inability to preferentially aim the beam in an ideal direction is offset by a significantly lower capital expenditure. Some disease sites may not require a rotating gantry in order to be effectively treated with IMPT. For example, a pair of fixed nozzles placed in a vertical plane can be arranged to simultaneously deliver an AP/PA (anteroposterior/posteranterior) pair of opposing beams to treat a lung tumor. Similarly, a bilateral beam arrangement with opposing nozzles in a horizontal plane may be useful for other disease sites such as sites in the head and neck.
Other relative beam orientations in a multiple nozzle system (such as orthogonal) could be used, or additional nozzle beam lines and nozzles could be added (e.g., to implement three or four beam directions simultaneously).
In summary, embodiments according to the present disclosure provide spatially and temporally precise, modulated irradiation of a moving target in a patient and take advantage of the tissue-sparing effects of the study mentioned above. Embodiments according to the present disclosure provide a more direct method for target volume scanning than the use of the conventional raster scanning technique described above. Each shot is aimed directly to coincide with the in-plane motion of the target using the X-Y scanning magnets, rather than having to distort the raster scan pattern. Quality assurance is also made easier because the tracking and scanning processes are more independent of one another. Significantly, because a SOBP covering the entire length of each target line segment (from the distal edge to the proximal edge of the planning target volume) is delivered in a short burst, motion-induced uncertainties do not create gaps or overlaps (cold spots or hot spots) within the target volume.
Embodiments according to the present invention can be used to with types of external beam radiotherapy other than IMPT such as, for example, intensity modulated radiation therapy (IMRT), image-guided radiotherapy (IGRT), RapidArc™ radiotherapy, stereotactic body radiotherapy (SBRT), and stereotactic ablative radiotherapy (SABR). Embodiments according to the present disclosure can be incorporated into methods and systems used for planning radiotherapy treatments based on IMPT and other types of radiotherapy. A shot—a high dose that can be delivered in a short period of time along a target line segment—can be adjusted in energy (intensity) or range and delivered to the target volume with a SOBP that provides a uniform and otherwise suitably modified dose to an entire target line segment. The intensity of the dose delivered in a shot can be adjusted to match the prescribed dose for a particular target line segment. Subsequent shots can be independently adjusted in intensity, in range, and with a suitable SOBP, and can also be triggered or aimed to coincide with the 4D (three dimensions plus time) position of each target line segment in the scan pattern until the entire target volume has been irradiated to the prescribed dose. Radiotherapy treatments can be improved by taking advantage of this capability to quickly and accurately vary energy and range on the fly (dynamically). Treatment planning can also be improved because planners are presented with the capability to precisely control dose delivery.
Although the subject matter has been described in language specific to structural features and/or methodological acts, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are disclosed as example forms of implementing the claims.
This application is a continuation of the application with Ser. No. 16/401,387, entitled “Radiation Therapy Systems and Methods,” by S. Mansfield, filed May 2, 2019, which is a continuation of the application with Ser. No. 15/850,472, now U.S. Pat. No. 10,307,618, entitled “Radiation Therapy Systems and Methods,” by S. Mansfield, filed Dec. 21, 2017, which is a continuation of the application with Ser. No. 15/089,330, now U.S. Pat. No. 9,855,445, entitled “Radiation Therapy Systems and Methods,” by S. Mansfield, filed Apr. 1, 2016, all of which are hereby incorporated by reference in their entirety. This application is related to the U.S. application with Ser. No. 15/087,292, entitled “Adaptive Pencil Beam Scanning,” by J. Wulff, filed Mar. 31, 2016, now U.S. Pat. No. 10,912,953, and hereby incorporated by reference in its entirety.
Number | Name | Date | Kind |
---|---|---|---|
4163901 | Azam | Aug 1979 | A |
4914681 | Klingenbeck et al. | Apr 1990 | A |
5153900 | Nomikos et al. | Oct 1992 | A |
5267294 | Kuroda | Nov 1993 | A |
5550378 | Skillicorn et al. | Aug 1996 | A |
5610967 | Moorman et al. | Mar 1997 | A |
5625663 | Swerdloff et al. | Apr 1997 | A |
5682412 | Skillicorn et al. | Oct 1997 | A |
5757885 | Yao et al. | May 1998 | A |
6198802 | Elliott et al. | Mar 2001 | B1 |
6222544 | Tarr et al. | Apr 2001 | B1 |
6234671 | Solomon et al. | May 2001 | B1 |
6260005 | Yang et al. | Jul 2001 | B1 |
6328395 | Kitahara | Dec 2001 | B1 |
6379380 | Satz | Apr 2002 | B1 |
6411675 | Llacer | Jun 2002 | B1 |
6445766 | Whitham | Sep 2002 | B1 |
6504899 | Pugachev et al. | Jan 2003 | B2 |
6580940 | Gutman | Jun 2003 | B2 |
6777700 | Yanagisawa et al. | Aug 2004 | B2 |
6993112 | Hesse | Jan 2006 | B2 |
7268358 | Ma et al. | Sep 2007 | B2 |
7385203 | Nakayama et al. | Jun 2008 | B2 |
7453983 | Schildkraut et al. | Nov 2008 | B2 |
7515681 | Ebstein | Apr 2009 | B2 |
7522706 | Lu et al. | Apr 2009 | B2 |
7560715 | Pedroni | Jul 2009 | B2 |
7590219 | Maurer, Jr. et al. | Sep 2009 | B2 |
7616735 | Maciunas et al. | Nov 2009 | B2 |
7623623 | Raanes et al. | Nov 2009 | B2 |
7778691 | Zhang et al. | Aug 2010 | B2 |
7807982 | Nishiuchi et al. | Oct 2010 | B2 |
7831289 | Riker et al. | Nov 2010 | B2 |
7835492 | Sahadevan | Nov 2010 | B1 |
7907699 | Long et al. | Mar 2011 | B2 |
8284898 | Ho et al. | Oct 2012 | B2 |
8306184 | Chang et al. | Nov 2012 | B2 |
8401148 | Lu et al. | Mar 2013 | B2 |
8406844 | Ruchala et al. | Mar 2013 | B2 |
8559596 | Thomson et al. | Oct 2013 | B2 |
8600003 | Zhou et al. | Dec 2013 | B2 |
8613694 | Walsh | Dec 2013 | B2 |
8636636 | Shukla et al. | Jan 2014 | B2 |
8644571 | Schulte et al. | Feb 2014 | B1 |
8716663 | Brusasco et al. | May 2014 | B2 |
8836332 | Shvartsman et al. | Sep 2014 | B2 |
8847179 | Fujitaka et al. | Sep 2014 | B2 |
8903471 | Heid | Dec 2014 | B2 |
8917813 | Maurer, Jr. | Dec 2014 | B2 |
8948341 | Beckman | Feb 2015 | B2 |
8958864 | Amies et al. | Feb 2015 | B2 |
8983573 | Carlone et al. | Mar 2015 | B2 |
8986186 | Zhang et al. | Mar 2015 | B2 |
8992404 | Graf et al. | Mar 2015 | B2 |
8995608 | Zhou et al. | Mar 2015 | B2 |
9018603 | Loo et al. | Apr 2015 | B2 |
9033859 | Fieres et al. | May 2015 | B2 |
9079027 | Agano et al. | Jul 2015 | B2 |
9149656 | Tanabe | Oct 2015 | B2 |
9155908 | Meltsner et al. | Oct 2015 | B2 |
9233260 | Slatkin et al. | Jan 2016 | B2 |
9258876 | Cheung et al. | Feb 2016 | B2 |
9283406 | Prieels | Mar 2016 | B2 |
9308391 | Liu et al. | Apr 2016 | B2 |
9330879 | Lewellen et al. | May 2016 | B2 |
9333374 | Iwata | May 2016 | B2 |
9468777 | Fallone et al. | Oct 2016 | B2 |
9517358 | Velthuis et al. | Dec 2016 | B2 |
9526918 | Kruip | Dec 2016 | B2 |
9545444 | Strober et al. | Jan 2017 | B2 |
9583302 | Figueroa Saavedra et al. | Feb 2017 | B2 |
9636381 | Basile | May 2017 | B2 |
9636525 | Sahadevan | May 2017 | B1 |
9649298 | Djonov et al. | May 2017 | B2 |
9656098 | Goer | May 2017 | B2 |
9694204 | Hardemark | Jul 2017 | B2 |
9776017 | Flynn et al. | Oct 2017 | B2 |
9786054 | Taguchi et al. | Oct 2017 | B2 |
9786093 | Svensson | Oct 2017 | B2 |
9786465 | Li et al. | Oct 2017 | B2 |
9795806 | Matsuzaki et al. | Oct 2017 | B2 |
9801594 | Boyd et al. | Oct 2017 | B2 |
9844358 | Wiggers et al. | Dec 2017 | B2 |
9854662 | Mishin | Dec 2017 | B2 |
9855445 | Mansfield | Jan 2018 | B2 |
9884206 | Schulte et al. | Feb 2018 | B2 |
9931522 | Bharadwaj et al. | Apr 2018 | B2 |
9962562 | Fahrig et al. | May 2018 | B2 |
9974977 | Lachaine et al. | May 2018 | B2 |
9987502 | Gattiker et al. | Jun 2018 | B1 |
10007961 | Grudzinski et al. | Jun 2018 | B2 |
10022564 | Thieme et al. | Jul 2018 | B2 |
10071264 | Liger | Sep 2018 | B2 |
10080912 | Kwak et al. | Sep 2018 | B2 |
10092774 | Vanderstraten | Oct 2018 | B1 |
10183179 | Smith | Jan 2019 | B1 |
10188875 | Kwak et al. | Jan 2019 | B2 |
10206871 | Lin et al. | Feb 2019 | B2 |
10212800 | Agustsson et al. | Feb 2019 | B2 |
10232193 | Iseki | Mar 2019 | B2 |
10258810 | Zwart et al. | Apr 2019 | B2 |
10272264 | Ollila et al. | Apr 2019 | B2 |
10279196 | West et al. | May 2019 | B2 |
10293184 | Pishdad et al. | May 2019 | B2 |
10307614 | Schnarr | Jun 2019 | B2 |
10307615 | Ollila et al. | Jun 2019 | B2 |
10307618 | Mansfield | Jun 2019 | B2 |
10315047 | Glimelius et al. | Jun 2019 | B2 |
10413755 | Sahadevan | Sep 2019 | B1 |
10449389 | Ollila et al. | Oct 2019 | B2 |
10485988 | Kuusela et al. | Nov 2019 | B2 |
10525285 | Friedman | Jan 2020 | B1 |
10549117 | Vanderstraten et al. | Feb 2020 | B2 |
10603514 | Grittani et al. | Mar 2020 | B2 |
10609806 | Roecken | Mar 2020 | B2 |
10636609 | Bertsche et al. | Apr 2020 | B1 |
10646728 | Zwart | May 2020 | B2 |
10660588 | Boyd et al. | May 2020 | B2 |
10661100 | Shen | May 2020 | B2 |
10682528 | Ansorge et al. | Jun 2020 | B2 |
10702716 | Heese | Jul 2020 | B2 |
10758746 | Kwak et al. | Sep 2020 | B2 |
10870018 | Bartkoski et al. | Dec 2020 | B2 |
10960231 | Mansfield | Mar 2021 | B2 |
20040104354 | Haberer et al. | Jun 2004 | A1 |
20060226372 | Yanagisawa et al. | Oct 2006 | A1 |
20070287878 | Fantini et al. | Dec 2007 | A1 |
20080023644 | Pedroni | Jan 2008 | A1 |
20090063110 | Failla et al. | Mar 2009 | A1 |
20090287467 | Sparks et al. | Nov 2009 | A1 |
20100119032 | Yan et al. | May 2010 | A1 |
20100177870 | Nord et al. | Jul 2010 | A1 |
20100178245 | Arnsdorf et al. | Jul 2010 | A1 |
20100260317 | Chang et al. | Oct 2010 | A1 |
20110006224 | Maltz et al. | Jan 2011 | A1 |
20110091015 | Yu et al. | Apr 2011 | A1 |
20110135058 | Sgouros et al. | Jun 2011 | A1 |
20110240874 | Iwata | Oct 2011 | A1 |
20120076271 | Yan et al. | Mar 2012 | A1 |
20120157746 | Meltsner et al. | Jun 2012 | A1 |
20120171745 | Itoh | Jul 2012 | A1 |
20120197058 | Shukla et al. | Aug 2012 | A1 |
20130116929 | Carlton et al. | May 2013 | A1 |
20130150922 | Butson et al. | Jun 2013 | A1 |
20130177641 | Ghoroghchian | Jul 2013 | A1 |
20130231516 | Loo et al. | Sep 2013 | A1 |
20140091734 | Gall et al. | Apr 2014 | A1 |
20140177807 | Lewellen et al. | Jun 2014 | A1 |
20140185776 | Li et al. | Jul 2014 | A1 |
20140206926 | van der Laarse | Jul 2014 | A1 |
20140275706 | Dean et al. | Sep 2014 | A1 |
20140369476 | Harding | Dec 2014 | A1 |
20150011817 | Feng | Jan 2015 | A1 |
20150202464 | Brand et al. | Jul 2015 | A1 |
20150306423 | Bharat et al. | Oct 2015 | A1 |
20160279444 | Schlosser | Sep 2016 | A1 |
20160310764 | Bharadwaj et al. | Oct 2016 | A1 |
20170128746 | Zwart | May 2017 | A1 |
20170157422 | Zwart | Jun 2017 | A1 |
20170189721 | Sumanaweera et al. | Jul 2017 | A1 |
20170203129 | Dessy | Jul 2017 | A1 |
20170281973 | Allen et al. | Oct 2017 | A1 |
20170281981 | Mansfield | Oct 2017 | A1 |
20180021594 | Papp et al. | Jan 2018 | A1 |
20180043183 | Sheng et al. | Feb 2018 | A1 |
20180056090 | Jordan et al. | Mar 2018 | A1 |
20180099154 | Prieels | Apr 2018 | A1 |
20180099155 | Prieels et al. | Apr 2018 | A1 |
20180099159 | Forton et al. | Apr 2018 | A1 |
20180133514 | Mansfield | May 2018 | A1 |
20180154183 | Sahadevan | Jun 2018 | A1 |
20180197303 | Jordan et al. | Jul 2018 | A1 |
20180207425 | Carlton et al. | Jul 2018 | A1 |
20180236268 | Zwart et al. | Aug 2018 | A1 |
20190022407 | Abel | Jan 2019 | A1 |
20190022422 | Trail | Jan 2019 | A1 |
20190054315 | Isola et al. | Feb 2019 | A1 |
20190070435 | Joe Anto et al. | Mar 2019 | A1 |
20190168027 | Smith | Jun 2019 | A1 |
20190255361 | Mansfield | Aug 2019 | A1 |
20190299027 | Fujii et al. | Oct 2019 | A1 |
20190299029 | Inoue | Oct 2019 | A1 |
20190351259 | Lee et al. | Nov 2019 | A1 |
20200001118 | Snider, III et al. | Jan 2020 | A1 |
20200022248 | Yi et al. | Jan 2020 | A1 |
20200030633 | Van Heteren et al. | Jan 2020 | A1 |
20200035438 | Star-Lack | Jan 2020 | A1 |
20200069818 | Jaskula-Ranga et al. | Mar 2020 | A1 |
20200164224 | Vanderstraten et al. | May 2020 | A1 |
20200178890 | Otto | Jun 2020 | A1 |
20200197730 | Safavi-Naeini et al. | Jun 2020 | A1 |
20200254279 | Ohishi | Aug 2020 | A1 |
20200269068 | Abel | Aug 2020 | A1 |
20200276456 | Swerdloff | Sep 2020 | A1 |
20200282234 | Folkerts et al. | Sep 2020 | A1 |
20210170202 | Mansfield | Jun 2021 | A1 |
Number | Date | Country |
---|---|---|
104001270 | Aug 2014 | CN |
106730407 | May 2017 | CN |
107362464 | Nov 2017 | CN |
109966662 | Jul 2019 | CN |
111481840 | Aug 2020 | CN |
111481841 | Aug 2020 | CN |
010207 | Jun 2008 | EA |
0979656 | Feb 2000 | EP |
3338858 | Jun 2018 | EP |
3384961 | Oct 2018 | EP |
3421087 | Jan 2019 | EP |
3453427 | Mar 2019 | EP |
3586920 | Jan 2020 | EP |
2617283 | Jun 1997 | JP |
2019097969 | Jun 2019 | JP |
2007017177 | Feb 2007 | WO |
2010018476 | Feb 2010 | WO |
2013081218 | Jun 2013 | WO |
2013133936 | Sep 2013 | WO |
2014139493 | Sep 2014 | WO |
2015038832 | Mar 2015 | WO |
2015102680 | Jul 2015 | WO |
2016122957 | Aug 2016 | WO |
2017156316 | Sep 2017 | WO |
2017174643 | Oct 2017 | WO |
2018137772 | Aug 2018 | WO |
2018152302 | Aug 2018 | WO |
2019097250 | May 2019 | WO |
2019103983 | May 2019 | WO |
2019164835 | Aug 2019 | WO |
2019166702 | Sep 2019 | WO |
2019185378 | Oct 2019 | WO |
2019222436 | Nov 2019 | WO |
2020018904 | Jan 2020 | WO |
2020064832 | Apr 2020 | WO |
2020107121 | Jun 2020 | WO |
2020159360 | Aug 2020 | WO |
Entry |
---|
M. McManus et al., “The challenge of ionisation chamber dosimetry in ultra-short pulsed high dose-rate Very High Energy Electron beams,” Sci Rep 10, 9089 (2020), published Jun. 3, 2020, https://doi.org/10.1038/S41598-020-65819-y. |
Ibrahim Oraiqat et al., “An Ionizing Radiation Acoustic Imaging (iRAI) Technique for Real-Time Dosimetric Measurements for FLASH Radiotherapy,” Medical Physics, vol. 47, Issue10, Oct. 2020, pp. 5090-5101, First published: Jun. 27, 2020, https://doi.org/10.1002/mp.14358. |
K. Petersson et al., “Dosimetry of ultra high dose rate irradiation for studies on the biological effect induced in normal brain and GBM,” ICTR-PHE 2016, p. S84, Feb. 2016, https://publisher-connector.core.ac.uk/resourcesync/data/elsevier/pdf/14c/aHR0cDovL2FwaS5lbHNIdmllci5jb20vY29udGVudC9hcnRpY2xIL3BpaS9zMDE2NzgxNDAxNjMwMTcyNA==.pdf. |
Susanne Auer et al., “Survival of tumor cells after proton irradiation with ultra-high dose rates,” Radiation Oncology 2011, 6:139, Published Oct. 18, 2011, DOI: https://doi.org/10.1186/1748-717X-6-139. |
Cynthia E. Keen, “Clinical linear accelerator delivers FLASH radiotherapy,” Physics World, Apr. 23, 2019, IOP Publishing Ltd, https://physicsworld.com/a/clinical-linear-accelerator-delivers-flash-radiotherapy/. |
Fan et al., “Emission guided radiation therapy for lung and prostate cancers: A feasibility study on a digital patient,” Med Phys. Nov. 2012; 39(11): 7140-7152. Published online Nov. 5, 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505203/doi: 10.1118/1.4761951. |
Favaudon et al., “Ultrahigh dose-rate, “flash” irradiation minimizes the side-effects of radiotherapy,” Cancer / Radiotherapy, vol. 19, Issues 6-7 , Oct. 2015 , pp. 526-531, Available online Aug. 12, 2015, https://doi.org/10.1016/j.canrad.2015.04.006. |
O. Zlobinskaya et al., “The Effects of Ultra-High Dose Rate Proton Irradiation on Growth Delay in the Treatment of Human Tumor Xenografts in Nude Mice,” Radiation Research, 181(2):177-183. Published Feb. 13, 2014, DOI: http://dx.doi.org/10.1667/RR13464.1. |
Bjorn Zackrisson, “Biological Effects of High Energy Radiation and Ultra High Dose Rates,” Umea University Medical Dissertations, New series No. 315—ISSN 0346-6612, From the Department of Oncology, University of Umea, Umea, Sweden, ISBN 91-7174-614-5, Printed in Sweden by the Printing Office of Umea University, Umea, 1991. |
P. Montay-Gruel et al., “Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s,” Radiotherapy and Oncology, vol. 124, Issue 3, Sep. 2017, pp. 365-369, Available online May 22, 2017, doi: 10.1016/j.radonc.2017.05.003. |
BW Loo et al., “Delivery of Ultra-Rapid Flash Radiation Therapy and Demonstration of Normal Tissue Sparing After Abdominal Irradiation of Mice,” International Journal of Radiation Oncology, Biology, Physics, vol. 98, Issue 2, p. E16, Supplement: S Meeting Abstract: P003, Published: Jun. 1, 2017, DOI: https://doi.org/10.1016/j.ijrobp.2017.02.101. |
Bhanu Prasad Venkatesulu et al., “Ultra high dose rate (35 Gy/sec) radiation does not spare the normal tissue in cardiac and splenic models of lymphopenia and gastrointestinal syndrome,” Sci Rep 9, 17180 (2019), Published Nov. 20, 2019, DOI: https://doi.org/10.1038/s41598-019-53562-y. |
P. Montay-Gruel et al., “Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species,” PNAS May 28, 2019, vol. 116, No. 22, pp. 10943-10951; first published May 16, 2019, https://doi.org/10.1073/pnas.1901777116. |
Peter G. Maxim et al., “FLASH radiotherapy: Newsflash or flash in the pan?”, Medical Physics, 46 (10), Oct. 2019, pp. 4287-4290, American Association of Physicists in Medicine, First published: Jun. 27, 2019, https://doi.org/10.1002/mp.13685. |
Andrei Pugachev et al., “Pseudo beam's-eye-view as applied to beam orientation selection in intensity-modulated radiation therapy,” Int. J. Radiation Oncology Biol. Phys., vol. 51, Issue 5, p. 1361-1370, Dec. 1, 2001, DOI: https://doi.org/10.1016/S0360-3016(01)01736-9. |
Xiaodong Zhang et al., “Intensity-Modulated Proton Therapy Reduces the Dose to Normal Tissue Compared With Intensity-Modulated Radiation Therapy or Passive Scattering Proton Therapy and Enables Individualized Radical Radiotherapy for Extensive Stage IIIB Non-Small-Cell Lung Cancer: A Virtual Clinical Study,” Int. J. Radiation Oncology Biol. Phys., vol. 77, No. 2, pp. 357-366, 2010, Available online Aug. 5, 2009, DOI: https://doi.org/10.1016/j.ijrobp.2009.04.028. |
A. J. Lomax et al., “Intensity modulated proton therapy: A clinical example,” Medical Physics, vol. 28, Issue 3, Mar. 2001, pp. 317-324, First published: Mar. 9, 2001, https://doi.org/10.1118/1.1350587. |
Lamberto Widesott et al., “Intensity-Modulated Proton Therapy Versus Helical Tomotherapy in Nasopharynx Cancer: Planning Comparison and NTCP Evaluation,” Int. J. Radiation Oncology Biol. Phys., vol. 72, No. 2, pp. 589-596, Oct. 1, 2008, Available online Sep. 13, 2008, DOI: https://doi.org/10.1016/j.ijrobp.2008.05.065. |
Andrei Pugachev et al., “Role of beam orientation optimization in intensity-modulated radiation therapy,” Int. J. Radiation Oncology Biol. Phys., vol. 50, No. 2, pp. 551-560, Jun. 1, 2001, Available online May 10, 2001, DOI: https://doi.org/10.1016/S0360-3016(01)01502-4. |
Damien C. Weber et al., “Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview,” Radiat Oncol. 2006; 1: 22. Published online Jul. 20, 2006, doi: 10.1186/1748-717X-1-22. |
RaySearch Laboratories, “Leading the way in cancer treatment, Annual Repod 2013,” RaySearch Laboratories (publ), Stockholm, Sweden, 94 pages, Apr. 2014, https://www.raysearchlabs.com/siteassets/about-overview/media-center/wp-re-ev-n-pdfs/brochures/raysearch-ar-2013-eng-pdf. |
Fredrik Carlsson, “Utilizing Problem Structure in Optimization of Radiation Therapy,” KTH Engineering Sciences, Doctoral Thesis, Stockholm, Sweden, Apr. 2008, Optimization and Systems Theory, Department of Mathematics, Royal Institute of Technology, Stockholm, Sweden, ISSN 1401-2294, https://www.raysearchlabs.com/globalassets/about-overview/media-center/wp-re-ev-n-pdfs/publications/thesis-fredrik_light.pdf. |
Chang-Ming Charlie Ma, “Physics and Dosimetric Principles of SRS and SBRT,” Mathews J Cancer Sci. 4(2): 22, 2019, published: Dec. 11, 2019, ISSN: 2474-6797, DOI: https://doi.org/10.30654/MJCS.10022. |
Alterego-Admin, “Conventional Radiation Therapy May Not Protect Healthy Brain Cells,” International Neuropsychiatric Association—INA, Oct. 10, 2019, https://inawebsite.org/conventional-radiation-therapy-may-not-protect-healthy-brain-cells/. |
Aafke Christine Kraan, “Range verification methods in particle therapy: underlying physics and Monte Carlo modeling,” Frontiers in Oncology, Jul. 7, 2015, vol. 5, Article 150, 27 pages, doi: 10.3389/fonc.2015.00150. |
Wayne D. Newhauser et al., “The physics of proton therapy,” Physics in Medicine & Biology, Mar. 24, 2015, 60 R155-R209, Institute of Physics and Engineering in Medicine, IOP Publishing, doi: 10.1088/0031-9155/60/8/R155. |
S E McGowan et al., “Treatment planning optimisation in proton therapy,” Br J Radiol, 2013, 86, 20120288, The British Institute of Radiology, 12 pages, DOI: 10.1259.bjr.20120288. |
Steven Van De Water et al., “Towards FLASH proton therapy: the impact of treatment planning and machine characteristics on achievable dose rates,” Acta Oncologica, Jun. 26, 2019, vol. 58, No. 10, p. 1462-1469, Taylor & Francis Group, DOI: 10.1080/0284186X.2019.1627416. |
J. Groen, “FLASH optimisation in clinical IMPT treatment planning,” MSc Thesis, Jul. 1, 2020, Erasmus University Medical Center, department of radiotherapy, Delft University of Technology, 72 pages. |
Muhammad Ramish Ashraf et al., “Dosimetry for FLASH Radiotherapy: A Review of Tools and the Role of Radioluminescence and Cherenkov Emission,” Frontiers in Oncology, Aug. 21, 2020, vol. 8, Article 328, 20 pages, doi: 10.3389/fphy.2020.00328. |
Emil Schuler et al., “Experimental Platform for Ultra-high Dose Rate FLASH Irradiation of Small Animals Using a Clinical Linear Accelerator,” International Journal of Radiation Oncology, Biology, Physics, vol. 97, No. 1, Sep. 2016, pp. 195-203. |
Elette Engels et al., “Toward personalized synchrotron microbeam radiation therapy,” Scientific Reports, 10:8833, Jun. 1, 2020, 13 pages, DOI: https://doi.org/10.1038/s41598-020-65729-z. |
P-H Mackeprang et al., “Assessing dose rate distributions in VMAT plans” (Accepted Version), Accepted Version: https://boris.unibe.ch/92814/8/dose_rate_project_revised_submit.pdf Published Version: 2016, Physics in medicine and biology, 61(8), pp. 3208-3221. Institute of Physics Publishing IOP, published Mar. 29, 2016, https://boris.unibe.ch/92814/. |
Xiaoying Liang et al., “Using Robust Optimization for Skin Flashing in Intensity Modulated Radiation Therapy for Breast Cancer Treatment: A Feasibility Study,” Practical Radiation Oncology, vol. 10, Issue 1, p. 59-69, Published by Elsevier Inc., Oct. 15, 2019. |
Alexei Trofimov et al., “Optimization of Beam Parameters and Treatment Planning for Intensity Modulated Proton Therapy,” Technology in Cancer Research & Treatment, vol. 2, No. 5, Oct. 2003, p. 437-444, Adenine Press. |
Vladimir Anferov, “Scan pattern optimization for uniform proton beam scanning,” Medical Physics, vol. 36, Issue 8, Aug. 2009, pp. 3560-3567, First published: Jul. 2, 2009. |
Ryosuke Kohno et al., “Development of Continuous Line Scanning System Prototype for Proton Beam Therapy,” International Journal of Particle Therapy, Jul. 11, 2017, vol. 3, Issue 4, p. 429-438, DOI: 10.14338/IJPT-16-00017.1. |
Wenbo Gu et al., “Integrated Beam Orientation and Scanning-Spot Optimization in Intensity Modulated Proton Therapy for Brain and Unilateral Head and Neck Tumors,” Med Phys. Author manuscript; available in PMC Apr. 1, 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904040/Published in final edited form as: Med Phys. Apr. 2018; 45(4): 1338-1350. Published online Mar. 1, 2018. doi: 10.1002/mp.12788 Accepted manuscript online: Feb. 2, 2018. |
Paul Morel et al., “Spot weight adaptation for moving target in spot scanning proton therapy,” Frontiers in Oncology, May 28, 2015, vol. 5, Article 119, 7 pages, doi: 10.3389/fonc.2015.00119. |
Simeon Nill et al., “Inverse planning of intensity modulated proton therapy,” Zeitschrift fur Medizinische Physik, vol. 14, Issue 1, 2004, pp. 35-40, https://doi.org/10.1078/0939-3889-00198. |
A. Lomax, “Intensity modulation methods for proton radiotherapy,” Physics in Medicine & Biology, Jan. 1999, vol. 44, No. 1, pp. 185-205, doi: 10.1088/0031-9155/44/1/014. |
M Kramer et al., “Treatment planning for heavy-ion radiotherapy: physical beam model and dose optimization,” Physics in Medicine & Biology, 2000, vol. 45, No. 11, pp. 3299-3317, doi: 10.1088/0031-9155/45/11/313. |
Harald Paganetti, “Proton Beam Therapy,” Jan. 2017, Physics World Discovery, IOP Publishing Ltd, Bristol, UK, 34 pages, DOI: 10.1088/978-0-7503-1370-4. |
Shinichi Shimizu et al., “A Proton Beam Therapy System Dedicated to Spot-Scanning Increases Accuracy with Moving Tumors by Real-Time Imaging and Gating and Reduces Equipment Size,” PLoS One, Apr. 18, 2014, vol. 9, Issue 4, e94971, https://doi.org/10.1371/journal.pone.0094971. |
Heng Li et al., “Reducing Dose Uncertainty for Spot-Scanning Proton Beam Therapy of Moving Tumors by Optimizing the Spot Delivery Sequence,” International Journal of Radiation Oncology, Biology, Physics, vol. 93, Issue 3, Nov. 1, 2015, pp. 547-556, available online Jun. 18, 2015, https://doi.org/10.1016/j.ijrobp.2015.06.019. |
Ion Beam Applications SA, “Netherlands Proton Therapy Center Delivers First Clinical Flash Irradiation,” Imaging Technology News, May 2, 2019, Wainscot Media, https://www.itnonline.com/content/netherlands-proton-therapy-center-delivers-first-clinical-flash-irradiation. |
R. M. De Kruijff, “FLASH radiotherapy: ultra-high dose rates to spare healthy tissue,” International Journal of Radiation Biology, 2020, vol. 96, No. 4, pp. 419-423, published online: Dec. 19, 2019, https://doi.org/10.1080/09553002.2020.1704912. |
Mevion Medical Systems, “Focus on the Future: Flash Therapy,” Press Releases, Sep. 16, 2019, https://www.mevion.com/newsroom/press-releases/focus-future-flash-therapy. |
Joseph D. Wilson et al., “Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?”, Frontiers in Oncology, Jan. 17, 2020, vol. 9, Article 1563, 12 pages, doi: 10.3389/fonc.2019.01563. |
David P. Gierga, “Is Flash Radiotherapy coming?”, International Organization for Medical Physics, 2020, https://www.iomp.org/iomp-news2-flash-radiotherapy/. |
Abdullah Muhammad Zakaria et al., “Ultra-High Dose-Rate, Pulsed (FLASH) Radiotherapy with Carbon Ions: Generation of Early, Transient, Highly Oxygenated Conditions in the Tumor Environment,” Radiation Research, Dec. 1, 2020, vol. 194, Issue 6, pp. 587-593, Radiation Research Society, Published: Aug. 27, 2020, doi: https://doi.org/10.1667/RADE-19-00015.1. |
Yusuke Demizu et al., “Carbon Ion Therapy for Early-Stage Non-Small-Cell Lung Cancer,” BioMed Research International, vol. 2014, Article ID 727962, 9 pages, Hindawi Publishing Corporation, published: Sep. 11, 2014, https://doi.org/10.1155/2014/727962. |
Ivana Dokic et al., “Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams,” Oncotarget, Aug. 30, 2016, vol. 7, No. 35, pp. 56676-56689, published online: Aug. 1, 2016, doi: 10.18632/oncotarget.10996. |
Aetna Inc., “Proton Beam, Neutron Beam, and Carbon Ion Radiotherapy,” 2020, No. 0270, http://www.aetna.com/cpb/medical/data/200_299/0270.html. |
Nicholas W. Colangelo et al., “The Importance and Clinical Implications of FLASH Ultra-High Dose-Rate Studies for Proton and Heavy Ion Radiotherapy,” Radiat Res. Author manuscript; available in PMC Jan. 1, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949397/Published in final edited form as: Radiat Res. Jan. 2020; 193(1): 1-4. Published online Oct. 28, 2019. doi: 10.1667/RR15537.1. |
Vincent Favaudon et al., “Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice,” Science Translational Medicine, Jul. 16, 2014, vol. 6, Issue 245, 245ra93, American Association for the Advancement of Science, DOI: 10.1126/scitranslmed.3008973. |
“FlashRad: Ultra-high dose-rate FLASH radiotherapy to minimize the complications of radiotherapy,” 2014, https://siric.curie.fr/sites/default/files/atoms/files/flashrad.pdf. |
Tami Freeman, “FLASH radiotherapy: from preclinical promise to the first human treatment,” Physics World, Aug. 6, 2019, IOP Publishing Ltd, https://physicsworld.com/a/flash-radiotherapy-from-preclinical-promise-to-the-first-human-treatment/. |
IntraOp Medical, Inc., “IntraOp and Lausanne University Hospital Announce Collaboration in FLASH radiotherapy,” Jun. 18, 2020, https://intraop.com/news-events/lausanne-university-flash-radiotherapy-collaboration/. |
M.-C. Vozenin et al., “Biological Benefits of Ultra-high Dose Rate FLASH Radiotherapy: Sleeping Beauty Awoken,” Clin Oncol (R Coll Radiol). Author manuscript; available in PMC Nov. 12, 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850216/Published in final edited form as: Clin Oncol (R Coll Radiol). Jul. 2019; 31(7): 407-415. Published online Apr. 19, 2019. doi: 10.1016/j.clon.2019 04.001. |
Efstathios Kamperis et al., “A FLASH back to radiotherapy's past and then fast forward to the future,” J Cancer Prev Curr Res. 2019;10(6):142-144. published Nov. 13, 2019, DOI: 10.15406/jcpcr.2019.10.00407. |
P. Symonds et al., “FLASH Radiotherapy: The Next Technological Advance in Radiation Therapy?”, Clinical Oncology, vol. 31, Issue 7, p. 405-406, Jul. 1, 2019, The Royal College of Radiologists, Published by Elsevier Ltd., DOI: https://doi.org/10.1016/j.clon.2019.05.011. |
Swati Girdhani et al., “Abstract LB-280: FLASH: A novel paradigm changing tumor irradiation platform that enhances therapeutic ratio by reducing normal tissue toxicity and activating immune pathways,” Proceedings: AACR Annual Meeting 2019; Mar. 29-Apr. 3, 2019; Atlanta, GA, published Jul. 2019, vol. 79, Issue 13 Supplement, pp. LB-280, American Association for Cancer Research, DOI: https://doi.org/10.1158/1538-7445.AM2019-LB-280. |
Bazalova-Carter et al., “On the capabilities of conventional x-ray tubes to deliver ultra-high (FLASH) dose rates,” Med. Phys. Dec. 2019; 46 (12):5690-5695, published Oct. 23, 2019, American Association of Physicists in Medicine, doi: 10.1002/mp.13858. Epub Oct. 23, 2019. PMID: 31600830. |
Manuela Buonanno et al., “Biological effects in normal cells exposed to FLASH dose rate protons,” Radiother Oncol. Author manuscript; available in PMC Oct. 1, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728238/Published in final edited form as: Radiother Oncol. Oct. 2019; 139: 51-55. Published online Mar. 5, 2019. doi: 10.1016/j.radonc.2019.02 009. |
N. Rama et al., “Improved Tumor Control Through T-cell Infiltration Modulated by Ultra-High Dose Rate Proton FLASH Using a Clinical Pencil Beam Scanning Proton System,” International Journal of Radiation Oncology, Biology, Physics, vol. 105, Issue 1, Supplement , S164-S165, Sep. 1, 2019, Mini Oral Sessions, DOI: https://doi.org/10.1016/j.ijrobp.2019.06.187. |
Inserm Press Office, “Radiotherapy ‘flashes’ to reduce side effects,” Press Release, Jul. 16, 2014, https://presse.inserm.fr/en/radiotherapy-flashes-to-reduce-side-effects/13394/. |
Eric S. Diffenderfer et al., “Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System,” International Journal of Radiation Oncology, Biology, Physics, vol. 106, Issue 2, Feb. 1, 2020, pp. 440-448, Available online Jan. 9, 2020, Published by Elsevier Inc., DOI: https://doi.org/10.1016/j.ijrobp.2019.10.049. |
Valerie Devillaine, “Radiotherapy and Radiation Biology,” Institut Curie, Apr. 21, 2017, https://institut-curie.org/page/radiotherapy-and-radiation-biology. |
Imaging Technology News, “ProNova and medPhoton to Offer Next Generation Beam Delivery, Advanced Imaging for Proton Therapy,” Oct. 6, 2014, Wainscot Media, Link: https://www.itnonline.com/content/pronova-and-medphoton-offer-next-generation-beam-delivery-advanced-imaging-proton-therapy. |
OncoLink Team, “Radiation Therapy: Which type is right for me?”, OncoLink Penn Medicine, last reviewed Mar. 3, 2020, Trustees of the University of Pennsylvania, https://www.oncolink.org/cancer-treatment/radiation/introduction-to-radiation-therapy/radiation-therapy-which-type-is-right-for-me. |
Marco Durante et al., “Faster and safer? FLASH ultra-high dose rate in radiotherapy,” Br J Radiol 2018; 91(1082):Jun. 28, 2017, British Institute of Radiology, Published Online: Dec. 15, 2017, https://doi.org/10.1259/bjr.20170628. |
John R. Fischer, “PMB launches FLASH radiotherapy system for use in clinical trials,” HealthCare Business News, Jun. 29, 2020, DOTmed.com, Inc., https://www.dotmed.com/news/story/51662. |
Marie-Catherine Vozenin et al., “The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients,” Clinical Cancer Research, Author Manuscript Published OnlineFirst Jun. 6, 2018, https://clincancerres.aacrjournals.org/content/clincanres/early/2018/06/06/1078-0432.CCR-17-3375.full.pdf. |
Number | Date | Country | |
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20210170202 A1 | Jun 2021 | US |
Number | Date | Country | |
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Parent | 16401387 | May 2019 | US |
Child | 17182031 | US | |
Parent | 15850472 | Dec 2017 | US |
Child | 16401387 | US | |
Parent | 15089330 | Apr 2016 | US |
Child | 15850472 | US |