AU2017208222B2 - Auto-updated and implemented radiation treatment plan apparatus and method of use thereof - Google Patents

Abstract

AUTO-UPDATED AND IMPLEMENTED RADIATION TREATMENT PLAN APPARATUSANDMETHODOFUSETHEREOF 5 The invention comprises a method and apparatus for treating a tumor, comprising the steps of: (1) a main controller implementing an initial radiation treatment plan, as a current radiation treatment plan, using positively charged particles delivered from a synchrotron, along a beam transport line, through a nozzle system proximate the treatment room, and into the tumor; (2) concurrent 10 with the step of implementing, imaging the tumor, such as with protons, to generate a current image; (3) upon detection of movement of the tumor relative to surrounding constituents of the patient using the current image, the main controller, using computer implemented code, automatically generating an updated treatment plan, the updated treatment plan becoming the current 15 radiation treatment plan; and (4) repeating the steps of implementing, imaging, and generating an updated treatment plan at least n times, where n is a positive integer of at least one.

Description

This application is a divisional of AU 2017203110 filed on 10 May 2017, which claims priority to the continuation-in-part of U.S. patent application no. 15/467,840 filed March 23, 2017, which is a continuation-in-part of U.S. patent application no. 15/402,739 filed January 10, 2017, which is a continuation-in-part of U.S. patent application no. 15/348,625 filed November 10, 2016, which is a continuation-in-part of U.S. patent application no. 15/167,617 filed May 27, 2016.

BACKGROUND OF THE INVENTION

FIELD OF THE INVENTION

The invention relates generally to imaging and treating a tumor.

DISCUSSION OF THE PRIOR ART

Cancer Treatment

Proton therapy works by aiming energetic ionizing particles, such as protons accelerated with a particle accelerator, onto a target tumor. These particles damage the DNA of cells, ultimately causing their death. Cancerous cells, because of their high rate of division and their reduced ability to repair damaged DNA, are particularly vulnerable to attack on their DNA.

Patents related to the current invention are summarized here.

Proton Beam Therapy System

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F. Cole, et.al. of Loma Linda University Medical Center “Multi-Station Proton Beam Therapy System”, U.S. patent no. 4,870,287 (September 26, 1989) describe a proton beam therapy system for selectively generating and transporting proton beams from a single proton source and accelerator to a 5 selected treatment room of a plurality of patient treatment rooms.

Problem

There exists in the art of charged particle cancer therapy a need for accurate, precise, and rapid imaging of a patient and/or treatment of a tumor using charged 10 particles.

SUMMARY OF THE INVENTION

The invention comprises an automated updated and optionally auto-implemented cancer treatment plan apparatus and method of use thereof.

DESCRIPTION OF THE FIGURES

A more complete understanding of the present invention is derived by referring to the detailed description and claims when considered in connection with the Figures, wherein like reference numbers refer to similar items throughout the 20 Figures.

Figure 1A illustrate component connections of a charged particle beam therapy system, Figure 1B illustrates a charged particle therapy system;

Figure 2 illustrates a tomography system;

Figure 3 illustrates a beam path identification system;

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Figure 4A illustrates a beam path identification system coupled to a beam transport system and a tomography scintillation detector and Figure 4B illustrates the scintillation detector rotating with the patient and gantry nozzle;

Figure 5 illustrates a treatment delivery control system;

Figure 6A illustrates a two-dimensional - two-dimensional imaging system relative to a cancer treatment beam, Figure 6B illustrates multiple gantry 10 supported imaging systems, and Figure 6C illustrates a rotatable cone beam;

Figure 7A illustrates a process of determining position of treatment room objects and Figure 7B illustrates an iterative position tracking, imaging, and treatment system;

Figure 8 illustrates a fiducial marker enhanced tomography imaging system;

Figure 9 illustrates a fiducial marker enhanced treatment system;

Figures 10(A-C) illustrate isocenterless cancer treatment systems;

Figure 11 illustrates a transformable axis system for tumor treatment;

Figure 12 illustrates a semi-automated cancer therapy imaging/treatment system;

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Figure 13 illustrates a system of automated generation of a radiation treatment plan;

Figure 14 illustrates a system of automatically updating a cancer radiation 5 treatment plan during treatment; and

Figure 15 illustrates an automated radiation treatment plan development and implementation system.

Elements and steps in the figures are illustrated for simplicity and clarity and have not necessarily been rendered according to any particular sequence. For example, steps that are performed concurrently or in different order are illustrated in the figures to help improve understanding of embodiments of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention comprises a method and apparatus for treating a tumor of a patient with positively charged particles in a treatment room, comprising the steps of: (1) 20 providing an initial radiation treatment plan; (2) a main controller implementing the initial radiation treatment plan, as a current radiation treatment plan, using the positively charged particles delivered from a synchrotron, along a beam transport line, through a nozzle system proximate the treatment room, and into the tumor;

(3) concurrent with the step of implementing, imaging the tumor, such as with 25 protons, to generate a current image; (4) upon detection of movement of the tumor relative to surrounding constituents of the patient using the current image, the main controller, using computer implemented code, automatically generating an updated treatment plan, the updated treatment plan becoming the current radiation treatment plan; and (5) repeating the steps of implementing, imaging,

2017208222 24 Jul 2017 and generating an updated treatment plan at least n times, where n is a positive integer of at least one. Optionally, the step of automatically generating an updated treatment plan further comprising the step of an unsupervised computer implemented algorithm using a set of computer coded inputs to automatically 5 generate the updated treatment plan.

In combination, the above described embodiment is used with: (1) a proton therapy cancer treatment system integrated with a proton tomography imaging system using one or more coated layers designed to emit photons upon 10 interaction with a charged particle beam and/or (2) a set of fiducial marker detectors that detect photons emitted from and/or are reflected off of a set of fiducial markers positioned on one or more objects in a treatment room, where resultant determined distances and/or calculated angles are used to determine relative positions of multiple objects or elements in the treatment room. 15 Generally, in the proton tomography imaging system, one or more detectors imaging photons emitted from the coated layers, also referred to as imaging sheets or layers, are used to determine one or more point positions of the charged particle beam at a given time. Combining the point positions yields localized vectors pinpointing the charged particle beam position, such as entering 20 a patient and/or exiting the patient. The resulting charged particle state determination system using one or more coated layers is used in conjunction with a scintillation detector or a tomographic imaging system at time of tumor and surrounding tissue sample mapping and/or at time of tumor treatment where common synchrotron, beam transport, and/or nozzle elements are used for both 25 proton imaging and cancer treatment.

In combination, a method and apparatus for imaging a tumor of a patient using positively charged particles and X-rays, comprises the steps of: (1) transporting the positively charged particles from an accelerator to a patient position using a 30 beam transport line, where the beam transport line comprises a positively

2017208222 24 Jul 2017 charged particle beam path and an X-ray beam path; (2) detecting scintillation induced by the positively charged particles using a scintillation detector system; (3) detecting X-rays using an X-ray detector system; (4) positioning a mounting rail through linear extension/retraction to: at a first time and at a first extension 5 position of the mounting rail, position the scintillation detector system opposite the patient position from the exit nozzle and at a second time and at a second extension position of the mounting rail, position the X-ray detector system opposite the patient position from the exit nozzle; (5) generating an image of the tumor using output of the scintillation detector system and the X-ray detector 10 system; and (6) alternating between the step of detecting scintillation and treating the tumor via irradiation of the tumor using the positively charged particles.

In combination, a tomography system is optionally used in combination with a charged particle cancer therapy system. The tomography system uses 15 tomography or tomographic imaging, which refers to imaging by sections or sectioning through the use of a penetrating wave, such as a positively charge particle from an injector and/or accelerator. Optionally and preferably, a common injector, accelerator, and beam transport system is used for both charged particle based tomographic imaging and charged particle cancer therapy. In one case, 20 an output nozzle of the beam transport system is positioned with a gantry system while the gantry system and/or a patient support maintains a scintillation plate of the tomography system on the opposite side of the patient from the output nozzle.

In another example, a charged particle state determination system, of a cancer therapy system or tomographic imaging system, uses one or more coated layers in conjunction with a scintillation material, scintillation detector and/or a tomographic imaging system at time of tumor and surrounding tissue sample mapping and/or at time of tumor treatment, such as to determine an input vector

2017208222 24 Jul 2017 of the charged particle beam into a patient and/or an output vector of the charged particle beam from the patient.

In another example, the charged particle tomography apparatus is used in combination with a charged particle cancer therapy system. For example, tomographic imaging of a cancerous tumor is performed using charged particles generated with an injector, accelerated with an accelerator, and guided with a delivery system. The cancer therapy system uses the same injector, accelerator, and guided delivery system in delivering charged particles to the cancerous 10 tumor. For example, the tomography apparatus and cancer therapy system use a common raster beam method and apparatus for treatment of solid cancers. More particularly, the invention comprises a multi-axis and/or multi-field raster beam charged particle accelerator used in: (1) tomography and (2) cancer therapy. Optionally, the system independently controls patient translation 15 position, patient rotation position, two-dimensional beam trajectory, delivered radiation beam energy, delivered radiation beam intensity, beam velocity, timing of charged particle delivery, and/or distribution of radiation striking healthy tissue. The system operates in conjunction with a negative ion beam source, synchrotron, patient positioning, imaging, and/or targeting method and apparatus 20 to deliver an effective and uniform dose of radiation to a tumor while distributing radiation striking healthy tissue.

For clarity of presentation and without loss of generality, throughout this document, treatment systems and imaging systems are described relative to a 25 tumor of a patient. However, more generally any sample is imaged with any of the imaging systems described herein and/or any element of the sample is treated with the positively charged particle beam(s) described herein.

CHARGED PARTICLE BEAM THERAPY

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Throughout this document, a charged particle beam therapy system, such as a proton beam, hydrogen ion beam, or carbon ion beam, is described. Herein, the charged particle beam therapy system is described using a proton beam. However, the aspects taught and described in terms of a proton beam are not 5 intended to be limiting to that of a proton beam and are illustrative of a charged particle beam system, a positively charged beam system, and/or a multiply charged particle beam system, such as C⁴⁺ or C⁶⁺. Any of the techniques described herein are equally applicable to any charged particle beam system.

Referring now to Figure 1A, a charged particle beam system 100 is illustrated.

The charged particle beam preferably comprises a number of subsystems including any of: a main controller 110; an injection system 120; a synchrotron 130 that typically includes: (1) an accelerator system 131 and (2) an internal or connected extraction system 134; a radio-frequency cavity system 180; a beam 15 transport system 135; a scanning / targeting / delivery system 140; a nozzle system 146; a patient interface module 150; a display system 160; and/or an imaging system 170.

An exemplary method of use of the charged particle beam system 100 is 20 provided. The main controller 110 controls one or more of the subsystems to accurately and precisely deliver protons to a tumor of a patient. For example, the main controller 110 obtains an image, such as a portion of a body and/or of a tumor, from the imaging system 170. The main controller 110 also obtains position and/or timing information from the patient interface module 150. The 25 main controller 110 optionally controls the injection system 120 to inject a proton into a synchrotron 130. The synchrotron typically contains at least an accelerator system 131 and an extraction system 134. The main controller 110 preferably controls the proton beam within the accelerator system, such as by controlling speed, trajectory, and timing of the proton beam. The main controller then 30 controls extraction of a proton beam from the accelerator through the extraction

2017208222 24 Jul 2017 system 134. For example, the controller controls timing, energy, and/or intensity of the extracted beam. The controller 110 also preferably controls targeting of the proton beam through the scanning / targeting / delivery system 140 to the patient interface module 150 or a patient with a patient positioning system. One 5 or more components of the patient interface module 150, such as translational and rotational position of the patient, are preferably controlled by the main controller 110. Further, display elements of the display system 160 are preferably controlled via the main controller 110. Displays, such as display screens, are typically provided to one or more operators and/or to one or more 10 patients. In one embodiment, the main controller 110 times the delivery of the proton beam from all systems, such that protons are delivered in an optimal therapeutic manner to the tumor of the patient.

Herein, the main controller 110 refers to a single system controlling the charged 15 particle beam system 100, to a single controller controlling a plurality of subsystems controlling the charged particle beam system 100, or to a plurality of individual controllers controlling one or more sub-systems of the charged particle beam system 100.

Example I

CHARGED PARTICLE CANCER THERAPY SYSTEM CONTROL

Referring now to Figure 1B, an illustrative exemplary embodiment of one version of the charged particle beam system 100 is provided. The number, position, and described type of components is illustrative and non-limiting in nature. In the 25 illustrated embodiment, the injection system 120 or ion source or charged particle beam source generates protons. The injection system 120 optionally includes one or more of: a negative ion beam source, a positive ion beam soure, an ion beam focusing lens, and a tandem accelerator. The protons are delivered into a vacuum tube that runs into, through, and out of the synchrotron. The generated

2017208222 24 Jul 2017 protons are delivered along an initial path 262. Optionally, focusing magnets 127, such as quadrupole magnets or injection quadrupole magnets, are used to focus the proton beam path. A quadrupole magnet is a focusing magnet. An injector bending magnet 128 bends the proton beam toward a plane of the 5 synchrotron 130. The focused protons having an initial energy are introduced into an injector magnet 129, which is preferably an injection Lambertson magnet. Typically, the initial beam path 262 is along an axis off of, such as above, a circulating plane of the synchrotron 130. The injector bending magnet 128 and injector magnet 129 combine to move the protons into the synchrotron 130. Main 10 bending magnets, dipole magnets, turning magnets, or circulating magnets 132 are used to turn the protons along a circulating beam path 164. A dipole magnet is a bending magnet. The main bending magnets 132 bend the initial beam path 262 into a circulating beam path 164. In this example, the main bending magnets 132 or circulating magnets are represented as four sets of four magnets 15 to maintain the circulating beam path 164 into a stable circulating beam path.

However, any number of magnets or sets of magnets are optionally used to move the protons around a single orbit in the circulation process. The protons pass through an accelerator 133. The accelerator accelerates the protons in the circulating beam path 164. As the protons are accelerated, the fields applied by 20 the magnets are increased. Particularly, the speed of the protons achieved by the accelerator 133 are synchronized with magnetic fields of the main bending magnets 132 or circulating magnets to maintain stable circulation of the protons about a central point or region 136 of the synchrotron. At separate points in time the accelerator 133 / main bending magnet 132 combination is used to 25 accelerate and/or decelerate the circulating protons while maintaining the protons in the circulating path or orbit. An extraction element of an inflector/deflector system is used in combination with a Lambertson extraction magnet 137 to remove protons from their circulating beam path 164 within the synchrotron 130. One example of a deflector component is a Lambertson magnet. Typically the 30 deflector moves the protons from the circulating plane to an axis off of the circulating plane, such as above the circulating plane. Extracted protons are

2017208222 24 Jul 2017 preferably directed and/or focused using an extraction bending magnet 142 and optional extraction focusing magnets 141, such as quadrupole magnets, and optional bending magnets along a positively charged particle beam transport path 268 in a beam transport system 135, such as a beam path or proton beam 5 path, into the scanning / targeting / delivery system 140. Two components of a scanning system 140 or targeting system typically include a first axis control 143, such as a vertical control, and a second axis control 144, such as a horizontal control, in one embodiment, the first axis control 143 allows for about 100 mm of vertical or y-axis scanning of the proton beam 268 and the second axis control 10 144 allows for about 700 mm of horizontal or x-axis scanning of the proton beam

268. A nozzle system 146 is used for directing the proton beam, for imaging the proton beam, for defining shape of the proton beam, and/or as a vacuum barrier between the low pressure beam path of the synchrotron and the atmosphere.

Protons are delivered with control to the patient interface module 150 and to a 15 tumor of a patient. All of the above listed elements are optional and may be used in various permutations and combinations.

Ion Extraction from Ion Source

For clarity of presentation and without loss of generality, examples focus on 20 protons from the ion source. However, more generally cations of any charge are optionally extracted from a corresponding ion source with the techniques described herein. For instance, C⁴⁺ or C⁶⁺ are optionally extracted using the ion extraction methods and apparatus described herein. Further, by reversing polarity of the system, anions are optionally extracted from an anion source, 25 where the anion is of any charge.

Herein, for clarity of presentation and without loss of generality, ion extraction is coupled with tumor treatment and/or tumor imaging. However, the ion extraction is optional used in any method or apparatus using a stream or time discrete 30 bunches of ions.

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Beam Transport

The beam transport system 135 is used to move the charged particles from the accelerator to the patient, such as via a nozzle in a gantry, described infra.

Nozzle

After extraction from the synchrotron 130 and transport of the charged particle beam along the proton beam path 268 in the beam transport system 135, the charged particle beam exits through the nozzle system 146. In one example, the 10 nozzle system includes a nozzle foil covering an end of the nozzle system 146 or a cross-sectional area within the nozzle system forming a vacuum seal. The nozzle system includes a nozzle that expands in x/y-cross-sectional area along the z-axis of the proton beam path 268 to allow the proton beam 268 to be scanned along the x-axis and y-axis by the vertical control element and 15 horizontal control element, respectively. The nozzle foil is preferably mechanically supported by the outer edges of an exit port of the nozzle or nozzle system 146. An example of a nozzle foil is a sheet of about 0.1 inch thick aluminum foil. Generally, the nozzle foil separates atmosphere pressures on the patient side of the nozzle foil from the low pressure region, such as about 10^-5 to 20 10^-7 torr region, on the synchrotron 130 side of the nozzle foil. The low pressure region is maintained to reduce scattering of the circulating charged particle beam in the synchrotron. Herein, the exit foil of the nozzle is optionally the first sheet 760 of the charged particle beam state determination system 750, described infra.

TOMOGRAPHY / BEAM STATE

In one embodiment, the charged particle tomography apparatus is used to image a tumor in a patient. As current beam position determination / verification is used in both tomography and cancer therapy treatment, for clarity of presentation and

2017208222 24 Jul 2017 without limitation beam state determination is also addressed in this section. However, beam state determination is optionally used separately and without tomography.

In another example, the charged particle tomography apparatus is used in combination with a charged particle cancer therapy system using common elements. For example, tomographic imaging of a cancerous tumor is performed using charged particles generated with an injector, accelerator, and guided with a delivery system that are part of the cancer therapy system, described supra.

In various examples, the tomography imaging system is optionally simultaneously operational with a charged particle cancer therapy system using common elements, allows tomographic imaging with rotation of the patient, is operational on a patient in an upright, semi-upright, and/or horizontal position, is 15 simultaneously operational with X-ray imaging, and/or allows use of adaptive charged particle cancer therapy. Further, the common tomography and cancer therapy apparatus elements are optionally operational in a multi-axis and/or multi-field raster beam mode.

In conventional medical X-ray tomography, a sectional image through a body is made by moving one or both of an X-ray source and the X-ray film in relative to the patient during the exposure. By modifying the direction and extent of the movement, operators can select different focal planes, which contain the structures of interest. More modern variations of tomography involve gathering 25 projection data from multiple directions by moving the X-ray source and feeding the data into a tomographic reconstruction software algorithm processed by a computer. Herein, in stark contrast to known methods, the radiation source is a charged particle, such as a proton ion beam or a carbon ion beam. A proton beam is used herein to describe the tomography system, but the description

2017208222 24 Jul 2017 applies to a heavier ion beam, such as a carbon ion beam. Further, in stark contrast to known techniques, herein the radiation source is optionally stationary while the patient is rotated.

Referring now to Figure 2, an example of a tomography apparatus is described and an example of a beam state determination is described. In this example, the tomography system 200 uses elements in common with the charged particle beam system 100, including elements of one or more of the injection system 120, the accelerator 130, a positively charged particle beam transport path 268 within 10 a beam transport housing 261 in the beam transport system 135, the targeting/delivery system 140, the patient interface module 150, the display system 160, and/or the imaging system 170, such as the X-ray imaging system. The scintillation material is optionally one or more scintillation plates, such as a scintillating plastic, used to measure energy, intensity, and/or position of the 15 charged particle beam. For instance, a scintillation material 210 or scintillation plate is positioned behind the patient 230 relative to the targeting/delivery system 140 elements, which is optionally used to measure intensity and/or position of the charged particle beam after transmitting through the patient. Optionally, a second scintillation plate or a charged particle induced photon emitting sheet, 20 described infra, is positioned prior to the patient 230 relative to the targeting/delivery system 140 elements, which is optionally used to measure incident intensity and/or position of the charged particle beam prior to transmitting through the patient. The charged particle beam system 100 as described has proven operation at up to and including 330 MeV, which is 25 sufficient to send protons through the body and into contact with the scintillation material. Particularly, 250 MeV to 330 MeV are used to pass the beam through a standard sized patient with a standard sized pathlength, such as through the chest. The intensity or count of protons hitting the plate as a function of position is used to create an image. The velocity or energy of the proton hitting the 30 scintillation plate is also used in creation of an image of the tumor 220 and/or an image of the patient 230. The patient 230 is rotated about the y-axis and a new

2017208222 24 Jul 2017 image is collected. Preferably, a new image is collected with about every one degree of rotation of the patient resulting in about 360 images that are combined into a tomogram using tomographic reconstruction software. The tomographic reconstruction software uses overlapping rotationally varied images in the 5 reconstruction. Optionally, a new image is collected at about every 2, 3, 4, 5, 10,

15, 30, or 45 degrees of rotation of the patient.

Herein, the scintillation material 210 or scintillator is any material that emits a photon when struck by a positively charged particle or when a positively charged 10 particle transfers energy to the scintillation material sufficient to cause emission of light. Optionally, the scintillation material 210 emits the photon after a delay, such as in fluorescence or phosphorescence. However, preferably, the scintillator has a fast fifty percent quench time, such as less than 0.0001, 0.001,

0.01, 0.1, 1, 10, 100, or 1,000 milliseconds, so that the light emission goes dark, 15 falls off, or terminates quickly. Preferred scintillation materials include sodium iodide, potassium iodide, cesium iodide, an iodide salt, and/or a doped iodide salt. Additional examples of the scintillation materials include, but are not limited to: an organic crystal, a plastic, a glass, an organic liquid, a luminophor, and/or an inorganic material or inorganic crystal, such as barium fluoride, BaF2; calcium 20 fluoride, CaF2, doped calcium fluoride, sodium iodide, Nal; doped sodium iodide, sodium iodide doped with thallium, Nal(TI); cadmium tungstate, CdWC>4; bismuth germanate; cadmium tungstate, CdWCri; calcium tungstate, CaWCh; cesium iodide, Csi; doped cesium iodide; cesium iodide doped with thallium, Csl(TI);

cesium iodide doped with sodium Csl(Na); potassium iodide, KI; doped 25 potassium iodide, gadolinium oxysulfide, Gd2O2S; lanthanum bromide doped with cerium, LaBr3(Ce); lanthanum chloride, LaCb; cesium doped lanthanum chloride, LaCl3(Ce); lead tungstate, PbWCU; LSO or lutetium oxyorthosilicate (LwSiOs);

LYSO, Lui.8Yo.2Si05(Ce); yttrium aluminum garnet, YAG(Ce); zinc sulfide, ZnS(Ag); and zinc tungstate, ZnWO4.

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In one embodiment, a tomogram or an individual tomogram section image is collected at about the same time as cancer therapy occurs using the charged particle beam system 100. For example, a tomogram is collected and cancer 5 therapy is subsequently performed: without the patient moving from the positioning systems, such as in a semi-vertical partial immobilization system, a sitting partial immobilization system, or the a laying position. In a second example, an individual tomogram slice is collected using a first cycle of the accelerator 130 and using a following cycle of the accelerator 130, the tumor 220 10 is irradiated, such as within about 1, 2, 5, 10, 15 or 30 seconds. In a third case, about 2, 3, 4, or 5 tomogram slices are collected using 1, 2, 3, 4, or more rotation positions of the patient 230 within about 5, 10, 15, 30, or 60 seconds of subsequent tumor irradiation therapy.

In another embodiment, the independent control of the tomographic imaging process and X-ray collection process allows simultaneous single and/or multifield collection of X-ray images and tomographic images easing interpretation of multiple images. Indeed, the X-ray and tomographic images are optionally overlaid and/or integrated to from a hybrid X-ray / proton beam tomographic 20 image as the patient 230 is optionally in the same position for each image.

In still another embodiment, the tomogram is collected with the patient 230 in the about the same position as when the patient’s tumor is treated using subsequent irradiation therapy. For some tumors, the patient being positioned in the same 25 upright or semi-upright position allows the tumor 220 to be separated from surrounding organs or tissue of the patient 230 better than in a laying position. Positioning of the scintillation material 210 behind the patient 230 allows the tomographic imaging to occur while the patient is in the same upright or semiupright position.

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The use of common elements in the tomographic imaging and in the charged particle cancer therapy allows benefits of the cancer therapy, described supra, to optionally be used with the tomographic imaging, such as proton beam x-axis control, proton beam y-axis control, control of proton beam energy, control of 5 proton beam intensity, timing control of beam delivery to the patient, rotation control of the patient, and control of patient translation all in a raster beam mode of proton energy delivery. The use of a single proton or cation beamline for both imaging and treatment eases patient setup, reduces alignment uncertainties, reduces beam state uncertainties, and eases quality assurance.

In yet still another embodiment, initially a three-dimensional tomographic X-ray and/or proton based reference image is collected, such as with hundreds of individual rotation images of the tumor 220 and patient 230. Subsequently, just prior to proton treatment of the cancer, just a few 2-dimensional control 15 tomographic images of the patient are collected, such as with a stationary patient or at just a few rotation positions, such as an image straight on to the patient, with the patient rotated about 45 degrees each way, and/or the X-ray source and/or patient rotated about 90 degrees each way about the y-axis. The individual control images are compared with the 3-dimensional reference image.

An adaptive proton therapy is optionally subsequently performed where: (1) the proton cancer therapy is not used for a given position based on the differences between the 3-dimensional reference image and one or more of the 2dimensional control images and/or (2) the proton cancer therapy is modified in real time based on the differences between the 3-dimensional reference image 25 and one or more of the 2-dimensional control images.

Charged Particle State Determination / Verification / Photonic Monitoring

Still referring to Figure 2, the tomography system 200 is optionally used with a charged particle beam state determination system 250, optionally used as a 30 charged particle verification system. The charged particle state determination

2017208222 24 Jul 2017 system 250 optionally measures, determines, and/or verifies one of more of: (1) position of the charged particle beam, such as a treatment beam 269, (2) direction of the treatment beam 269, (3) intensity of the treatment beam 269, (4) energy of the treatment beam 269, (5) position, direction, intensity, and/or energy 5 of the charged particle beam, such as a residual charged particle beam 267 after passing through a sample or the patient 230, and/or (6) a history of the charged particle beam.

For clarity of presentation and without loss of generality, a description of the 10 charged particle beam state determination system 250 is described and illustrated separately in Figure 3 and Figure 4A; however, as described herein elements of the charged particle beam state determination system 250 are optionally and preferably integrated into the nozzle system 146 and/or the tomography system 200 of the charged particle treatment system 100. More 15 particularly, any element of the charged particle beam state determination system 250 is integrated into the nozzle system 146, a dynamic gantry nozzle, and/or tomography system 200, such as a surface of the scintillation material 210 or a surface of a scintillation detector, plate, or system. The nozzle system 146 or the dynamic gantry nozzle provides an outlet of the charged particle beam 20 from the vacuum tube initiating at the injection system 120 and passing through the synchrotron 130 and beam transport system 135. Any plate, sheet, fluorophore, or detector of the charged particle beam state determination system is optionally integrated into the nozzle system 146. For example, an exit foil of the nozzle is optionally a first sheet 252 of the charged particle beam state 25 determination system 250 and a first coating 254 is optionally coated onto the exit foil, as illustrated in Figure 2. Similarly, optionally a surface of the scintillation material 210 is a support surface for a fourth coating 292, as illustrated in Figure 2. The charged particle beam state determination system 250 is further described, infra.

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Referring now to Figure 2, Figure 3, and Figure 4A, four sheets, a first sheet 252, a second sheet 270, a third sheet 280, and a fourth sheet 290 are used to illustrate detection sheets and/or photon emitting sheets upon transmittance of a charged particle beam. Each sheet is optionally coated with a photon emitter, 5 such as a fluorophore, such as the first sheet 252 is optionally coated with a first coating 254. Without loss of generality and for clarity of presentation, the four sheets are each illustrated as units, where the light emitting layer is not illustrated. Thus, for example, the second sheet 270 optionally refers to a support sheet, a light emitting sheet, and/or a support sheet coated by a light 10 emitting element. The four sheets are representative of n sheets, where n is a positive integer.

Referring now to Figure 2 and Figure 3, the charged particle beam state verification system 250 is a system that allows for monitoring of the actual 15 charged particle beam position in real-time without destruction of the charged particle beam. The charged particle beam state verification system 250 preferably includes a first position element or first beam verification layer, which is also referred to herein as a coating, luminescent, fluorescent, phosphorescent, radiance, or viewing layer. The first position element optionally and preferably 20 includes a coating or thin layer substantially in contact with a sheet, such as an inside surface of the nozzle foil, where the inside surface is on the synchrotron side of the nozzle foil. Less preferably, the verification layer or coating layer is substantially in contact with an outer surface of the nozzle foil, where the outer surface is on the patient treatment side of the nozzle foil. Preferably, the nozzle 25 foil provides a substrate surface for coating by the coating layer. Optionally, a binding layer is located between the coating layer and the nozzle foil, substrate, or support sheet. Optionally, the position element is placed anywhere in the charged particle beam path. Optionally, more than one position element on more than one sheet, respectively, is used in the charged particle beam path and is 30 used to determine a state property of the charged particle beam, as described infra.

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Still referring to Figure 2 and Figure 3, the coating, referred to as a fluorophore, yields a measurable spectroscopic response, spatially viewable by a detector or camera, as a result of transmission by the proton beam. The coating is 5 preferably a phosphor, but is optionally any material that is viewable or imaged by a detector where the material changes, as viewed spectroscopically, as a result of the charged particle beam hitting or transmitting through the coating or coating layer. A detector or camera views secondary photons emitted from the coating layer and determines a position of a treatment beam 269, which is also 10 referred to as a current position of the charged particle beam or final treatment vector of the charged particle beam, by the spectroscopic differences resulting from protons and/or charged particle beam passing through the coating layer. For example, the camera views a surface of the coating surface as the proton beam or positively charged cation beam is being scanned by the first axis control 15 143, vertical control, and the second axis control 144, horizontal control, beam position control elements during treatment of the tumor 220. The camera views the current position of the charged particle beam or treatment beam 269 as measured by spectroscopic response. The coating layer is preferably a phosphor or luminescent material that glows and/or emits photons for a short 20 period of time, such as less than 5 seconds for a 50% intensity, as a result of excitation by the charged particle beam. The detector observes the temperature change and/or observe photons emitted from the charged particle beam traversed spot. Optionally, a plurality of cameras or detectors are used, where each detector views all or a portion of the coating layer. For example, two 25 detectors are used where a first detector views a first half of the coating layer and the second detector views a second half of the coating layer. Preferably, at least a portion of the detector is mounted into the nozzle system to view the proton beam position after passing through the first axis and second axis controllers 143, 144. Preferably, the coating layer is positioned in the proton beam path 268 30 in a position prior to the protons striking the patient 230.

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Referring now to Figure 1 and Figure 2, the main controller 110, connected to the camera or detector output, optionally and preferably compares the final proton beam position or position of the treatment beam 269 with the planned proton beam position and/or a calibration reference, such as a calibrated beamline, to 5 determine if the actual proton beam position or position of the treatment beam

269 is within tolerance. The charged particle beam state determination system

250 preferably is used in one or more phases, such as a calibration phase, a mapping phase, a beam position verification phase, a treatment phase, and a treatment plan modification phase. The calibration phase is used to correlate, as 10 a function of x-, y-position of the first axis control 143 and the second axis control

144 response the actual x-, y-position of the proton beam at the patient interface.

During the treatment phase, the charged particle beam position is monitored and compared to the calibration and/or treatment plan to verify accurate proton delivery to the tumor 220 and/or as a charged particle beam shutoff safety 15 indicator. Referring now to Figure 5, the position verification system 179 and/or a treatment delivery control system 112, upon determination of a tumor shift, an unpredicted tumor distortion upon treatment, and/or a treatment anomaly optionally generates and or provides a recommended treatment change 1070.

The treatment change 1070 is optionally sent out while the patient 230 is still in 20 the treatment position, such as to a proximate physician or over the internet to a remote physician, for physician approval 1072, receipt of which allows continuation of the now modified and approved treatment plan.

Example I

Referring now to Figure 2, a first example of the charged particle beam state determination system 250 is illustrated using two cation induced signal generation surfaces, referred to herein as the first sheet 252 and a third sheet 780. Each sheet is described below.

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Still referring to Figure 2, in the first example, the optional first sheet 252, located in the charged particle beam path prior to the patient 230, is coated with a first fluorophore coating 254, wherein a cation, such as in the charged particle beam, transmitting through the first sheet 252 excites localized fluorophores of the first 5 fluorophore coating 254 with resultant emission of one or more photons. In this example, a first detector 212 images the first fluorophore coating 254 and the main controller 110 determines a current position of the charged particle beam using the image of the fluorophore coating 254 and the detected photon(s). The intensity of the detected photons emitted from the first fluorophore coating 254 is 10 optionally used to determine the intensity of the charged particle beam used in treatment of the tumor 220 or detected by the tomography system 200 in generation of a tomogram and/or tomographic image of the tumor 220 of the patient 230. Thus, a first position and/or a first intensity of the charged particle beam is determined using the position and/or intensity of the emitted photons, 15 respectively.

Still referring to Figure 2, in the first example, the optional third sheet 280, positioned posterior to the patient 230, is optionally a cation induced photon emitting sheet as described in the previous paragraph. However, as illustrated, 20 the third sheet 280 is a solid state beam detection surface, such as a detector array. For instance, the detector array is optionally a charge coupled device, a charge induced device, CMOS, or camera detector where elements of the detector array are read directly, as does a commercial camera, without the secondary emission of photons. Similar to the detection described for the first 25 sheet, the third sheet 280 is used to determine a position of the charged particle beam and/or an intensity of the charged particle beam using signal position and/or signal intensity from the detector array, respectively.

Still referring to Figure 2, in the first example, signals from the first sheet 252 and 30 third sheet 280 yield a position before and after the patient 230 allowing a more

2017208222 24 Jul 2017 accurate determination of the charged particle beam through the patient 230 therebetween. Optionally, knowledge of the charged particle beam path in the targeting/delivery system 140, such as determined via a first magnetic field strength across the first axis control 143 or a second magnetic field strength 5 across the second axis control 144 is combined with signal derived from the first sheet 252 to yield a first vector of the charged particles prior to entering the patient 230 and/or an input point of the charged particle beam into the patient 230, which also aids in: (1) controlling, monitoring, and/or recording tumor treatment and/or (2) tomography development / interpretation. Optionally, signal 10 derived from use of the third sheet 280, posterior to the patient 230, is combined with signal derived from tomography system 200, such as the scintillation material 210, to yield a second vector of the charged particles posterior to the patient 230 and/or an output point of the charged particle beam from the patient 230, which also aids in: (1) controlling, monitoring, deciphering, and/or (2) 15 interpreting a tomogram or a tomographic image.

For clarity of presentation and without loss of generality, detection of photons emitted from sheets is used to further describe the charged particle beam state determination system 250. However, any of the cation induced photon emission 20 sheets described herein are alternatively detector arrays. Further, any number of cation induced photon emission sheets are used prior to the patient 730 and/or posterior to the patient 230, such a 1,2, 3, 4, 6, 8, 10, or more. Still further, any of the cation induced photon emission sheets are place anywhere in the charged particle beam, such as in the synchrotron 130, in the beam transport system 135, 25 in the targeting/delivery system 140, the nozzle system 146, in the treatment room, and/or in the tomography system 200. Any of the cation induced photon emission sheets are used in generation of a beam state signal as a function of time, which is optionally recorded, such as for an accurate history of treatment of the tumor 220 of the patient 230 and/or for aiding generation of a tomographic 30 image.

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Example II

Referring now to Figure 3, a second example of the charged particle beam state determination system 250 is illustrated using three cation induced signal generation surfaces, referred to herein as the second sheet 270, the third sheet 280, and the fourth sheet 290. Any of the second sheet 270, the third sheet 280, and the fourth sheet 290 contain any of the features of the sheets described supra.

Still referring to Figure 3, in the second example, the second sheet 270, positioned prior to the patient 230, is optionally integrated into the nozzle and/or the nozzle system 146, but is illustrated as a separate sheet. Signal derived from the second sheet 270, such as at point A, is optionally combined with signal from the first sheet 252 and/or state of the targeting/delivery system 140 to yield a first line or vector, v-i_a, from point A to point B of the charged particle beam prior to the sample or patient 230 at a first time, ti, and a second line or vector, V2a, from point F to point G of the charged particle beam prior to the sample at a second time, t2.

Still referring to Figure 3, in the second example, the third sheet 280 and the fourth sheet 290, positioned posterior to the patient 230, are optionally integrated into the tomography system 200, but are illustrated as a separate sheets. Signal derived from the third sheet 280, such as at point D, is optionally combined with signal from the fourth sheet 290 and/or signal from the tomography system 200 to yield a first line segment or vector, vib, from point C2 to point D and/or from point D to point E of the charged particle beam posterior to the patient 230 at the first time, ti, and a second line segment or vector, V2b, such as from point H to point I of the charged particle beam posterior to the sample at a second time, /2. Signal derived from the third sheet 280 and/or from the fourth sheet 290 and the

2017208222 24 Jul 2017 corresponding first vector at the second time, fr, is used to determine an output point, C2, which may and often does differ from an extension of the first vector, via, from point A to point B through the patient to a non-scattered beam path of point Ci. The difference between point Ci and point C2 and/or an angle, a, 5 between the first vector at the first time, via, and the first vector at the second time, vib, is used to determine / map / identify, such as via tomographic analysis, internal structure of the patient 230, sample, and/or the tumor 220, especially when combined with scanning the charged particle beam in the x/y-plane as a function of time, such as illustrated by the second vector at the first time, V2a, and 10 the second vector at the second time, V2b, forming angle β and/or with rotation of the patient 230, such as about the y-axis, as a function of time.

Still referring to Figure 3, multiple detectors / detector arrays are illustrated for detection of signals from multiple sheets, respectively. However, a single 15 detector / detector array is optionally used to detect signals from multiple sheets, as further described infra. As illustrated, a set of detectors 211 is illustrated, including a second detector 214 imaging the second sheet 270, a third detector 216 imaging the third sheet 280, and a fourth detector 218 imaging the fourth sheet 290. Any of the detectors described herein are optionally detector arrays, 20 are optionally coupled with any optical filter, and/or optionally use one or more intervening optics to image any of the four sheets 252, 270, 280, 290. Further, two or more detectors optionally image a single sheet, such as a region of the sheet, to aid optical coupling, such as F-number optical coupling.

Still referring to Figure 3, a vector or line segment of the charged particle beam is determined. Particularly, in the illustrated example, the third detector 216, determines, via detection of secondary emitted photons, that the charged particle beam transmitted through point D and the fourth detector 218 determines that the charged particle beam transmitted through point E, where points D and E are 30 used to determine the first vector or line segment at the second time, v-ib, as

2017208222 24 Jul 2017 described supra. To increase accuracy and precision of a determined vector of the charged particle beam, a first determined beam position and a second determined beam position are optionally and preferably separated by a distance, di, such as greater than 0.1, 0.5, 1, 2, 3, 5, 10, or more centimeters. A support 5 element 252 is illustrated that optionally connects any two or more elements of the charged particle beam state determination system 250 to each other and/or to any element of the charged particle beam system 100, such as a rotating platform 256 used to position and/or co-rotate the patient 230 and any element of the tomography system 200.

Example III

Still referring to Figure 4A, a third example of the charged particle beam state determination system 250 is illustrated in an integrated tomography-cancer therapy system 400.

Referring to Figure 4A, multiple sheets and multiple detectors are illustrated determining a charged particle beam state prior to the patient 230. As illustrated, a first camera 212 spatially images photons emitted from the first sheet 260 at point A, resultant from energy transfer from the passing charged particle beam, 20 to yield a first signal and a second camera 214 spatially images photons emitted from the second sheet 270 at point B, resultant from energy transfer from the passing charged particle beam, to yield a second signal. The first and second signals allow calculation of the first vector or line segment, vi_a, with a subsequent determination of an entry point 232 of the charged particle beam into the patient 25 230. Determination of the first vector, vi_a, is optionally supplemented with information derived from states of the magnetic fields about the first axis control 143, the vertical control, and the second axis control 144, the horizontal axis control, as described supra.

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Still referring to Figure 4A, the charged particle beam state determination system is illustrated with multiple resolvable wavelengths of light emitted as a result of the charged particle beam transmitting through more than one molecule type, light emission center, and/or fluorophore type. For clarity of presentation and 5 without loss of generality a first fluorophore in the third sheet 280 is illustrated as emitting blue light, b, and a second fluorophore in the fourth sheet 290 is illustrated as emitting red light, r, that are both detected by the third detector 216. The third detector is optionally coupled with any wavelength separation device, such as an optical filter, grating, or Fourier transform device. For clarity of 10 presentation, the system is described with the red light passing through a red transmission filter blocking blue light and the blue light passing through a blue transmission filter blocking red light. Wavelength separation, using any means, allows one detector to detect a position of the charged particle beam resultant in a first secondary emission at a first wavelength, such as at point C, and a second 15 secondary emission at a second wavelength, such as at point D. By extension, with appropriate optics, one camera is optionally used to image multiple sheets and/or sheets both prior to and posterior to the sample. Spatial determination of origin of the red light and the blue light allow calculation of the first vector at the second time, vib, and an actual exit point 236 from the patient 230 as compared 20 to a non-scattered exit point 234 from the patient 230 as determined from the first vector at the first time, via.

Still referring to Figure 4A and referring now to Figure 4B, the integrated tomography-cancer therapy system 900 is illustrated with an optional 25 configuration of elements of the charged particle beam state determination system 250 being co-rotatable with the nozzle system 146 of the cancer therapy system 100. More particularly, in one case sheets of the charged particle beam state determination system 250 positioned prior to, posterior to, or on both sides of the patient 230 co-rotate with the scintillation material 210 about any axis, 30 such as illustrated with rotation about the y-axis. Further, any element of the charged particle beam state determination system 250, such as a detector, two27

2017208222 24 Jul 2017 dimensional detector, multiple two-dimensional detectors, and/or light coupling optic move as the gantry moves, such as along a common arc of movement of the nozzle system 146 and/or at a fixed distance to the common arc. For instance, as the gantry moves, a monitoring camera positioned on the opposite 5 side of the tumor 220 or patient 230 from the nozzle system 146 maintains a position on the opposite side of the tumor 220 or patient 230. In various cases, co-rotation is achieved by co-rotation of the gantry of the charged particle beam system and a support of the patient, such as the rotatable platform 253, which is also referred to herein as a movable or dynamically positionable patient platform, 10 patient chair, or patient couch. Mechanical elements, such as the support element 251 affix the various elements of the charged particle beam state determination system 250 relative to each other, relative to the nozzle system 146, and/or relative to the patient 230. For example, the support elements 251 maintain a second distance, ch, between a position of the tumor 220 and the third 15 sheet 280 and/or maintain a third distance, ch, between a position of the third sheet 280 and the scintillation material 210. More generally, support elements 251 optionally dynamically position any element about the patient 230 relative to one another or in x,y,z-space in a patient diagnostic / treatment room, such as via computer control.

Referring now to Figure 4B, positioning the nozzle system 146 of a gantry 460 on an opposite side of the patient 230 from a detection surface, such as the scintillation material 210, in a gantry movement system 450 is described. Generally, in the gantry movement system 450, as the gantry 460 rotates about 25 an axis the nozzle / nozzle system 146 and/or one or more magnets of the beam transport system 135 are repositioned. As illustrated, the nozzle system 146 is positioned by the gantry 460 in a first position at a first time, ti, and in a second position at a second time, fr, where n positions are optionally possible. An electromechanical system, such as a patient table, patient couch, patient couch, 30 patient rotation device, and/or a scintillation plate holder maintains the patient

230 between the nozzle system 146 and the scintillation material 210 of the

2017208222 24 Jul 2017 tomography system 200. Similarly, not illustrated for clarity of presentation, the electromechanical system maintains a position of the third sheet 280 and/or a position of the fourth sheet 290 on a posterior or opposite side of the patient 230 from the nozzle 1 system 46 as the gantry 460 rotates or moves the nozzle 5 system 146. Similarly, the electromechanical system maintains a position of the first sheet 260 or first screen and/or a position of the second sheet 270 or second screen on a same or prior side of the patient 230 from the nozzle system 146 as the gantry 460 rotates or moves the nozzle system 146. As illustrated, the electromechanical system optionally positions the first sheet 260 in the positively 10 charged particle path at the first time, ti, and rotates, pivots, and/or slides the first sheet 260 out of the positively charged particle path at the second time, /2. The electromechanical system is optionally and preferably connected to the main controller 110 and/or the treatment delivery control system 112. The electromechanical system optionally maintains a fixed distance between: (1) the 15 patient and the nozzle system 146 or the nozzle end, (2) the patient 230 or tumor

220 and the scintillation material 210, and/or (3) the nozzle system 146 and the scintillation material 210 at a first treatment time with the gantry 460 in a first position and at a second treatment time with the gantry 460 in a second position. Use of a common charged particle beam path for both imaging and cancer 20 treatment and/or maintaining known or fixed distances between beam transport/guide elements and treatment and/or detection surface enhances precision and/or accuracy of a resultant image and/or tumor treatment, such as described supra. Optionally, the gantry comprises a counterweight on an opposite side of an axis of rotation of the gantry. Ideally, the counterweight 25 results in no net moment of the gantry-counterweight system about the axis of rotation of the gantry. In practice, the counterweight mass and distance forces, herein all elements on one side of the axis or rotation of the gantry, is within 10, 5, 2, 1, 0.1, or 0.01 percent of the mass and distance forces of the section of the gantry on the opposite side of the axis of rotation of the gantry.

SYSTEM INTEGRATION

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Any of the systems and/or elements described herein are optionally integrated together and/or are optionally integrated with known systems.

Treatment Delivery Control System

Referring now to Figure 5, a centralized charged particle treatment system 500 is illustrated. Generally, once a charged particle therapy plan is devised, a central control system or treatment delivery control system 112 is used to control subsystems while reducing and/or eliminating direct communication between major subsystems. Generally, the treatment delivery control system 112 is used to 10 directly control multiple subsystems of the cancer therapy system without direct communication between selected subsystems, which enhances safety, simplifies quality assurance and quality control, and facilitates programming. For example, the treatment delivery control system 112 directly controls one or more of: an imaging system, a positioning system, an injection system, a radio-frequency 15 quadrupole system, a linear accelerator, a ring accelerator or synchrotron, an extraction system, a beam line, an irradiation nozzle, a gantry, a display system, a targeting system, and a verification system. Generally, the control system integrates subsystems and/or integrates output of one or more of the above described cancer therapy system elements with inputs of one or more of the 20 above described cancer therapy system elements.

Still referring to Figure 5, an example of the centralized charged particle treatment system 1000 is provided. Initially, a doctor, such as an oncologist, prescribes 510 or recommends tumor therapy using charged particles.

Subsequently, treatment planning 520 is initiated and output of the treatment planning step 520 is sent to an oncology information system 530 and/or is directly sent to the treatment delivery system 112, which is an example of the main controller 110.

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Still referring to Figure 5, the treatment planning step 520 is further described. Generally, radiation treatment planning is a process where a team of oncologist, radiation therapists, medical physicists, and/or medical dosimetrists plan appropriate charged particle treatment of a cancer in a patient. Typically, one or 5 more imaging systems 170 are used to image the tumor and/or the patient, described infra. Planning is optionally: (1) forward planning and/or (2) inverse planning. Cancer therapy plans are optionally assessed with the aid of a dosevolume histogram, which allows the clinician to evaluate the uniformity of the dose to the tumor and surrounding healthy structures. Typically, treatment 10 planning is almost entirely computer based using patient computed tomography data sets using multimodality image matching, image co-registration, or fusion.

Forward planning

In forward planning, a treatment oncologist places beams into a radiotherapy treatment planning system including: how many radiation beams to use and 15 which angles to deliver each of the beams from. This type of planning is used for relatively simple cases where the tumor has a simple shape and is not near any critical organs.

Inverse planning

In inverse planning, a radiation oncologist defines a patient's critical organs and tumor and gives target doses and importance factors for each. Subsequently, an optimization program is run to find the treatment plan which best matches all of the input criteria.

Oncology Information System

Still referring to Figure 5, the oncology information system 530 is further described. Generally, the oncology information system 530 is one or more of:

2017208222 24 Jul 2017 (1) an oncology-specific electronic medical record, which manages clinical, financial, and administrative processes in medical, radiation, and surgical oncology departments; (2) a comprehensive information and image management system; and (3) a complete patient information management system that centralizes patient data; and (4) a treatment plan provided to the charged particle beam system 100, main controller 110, and/or the treatment delivery control system 112. Generally, the oncology information system 530 interfaces with commercial charged particle treatment systems.

Safety System / Treatment Delivery Control System

Still referring to Figure 5, the treatment delivery control system 112 is further described. Generally, the treatment delivery control system 112 receives treatment input, such as a charged particle cancer treatment plan from the treatment planning step 520 and/or from the oncology information system 530 15 and uses the treatment input and/or treatment plan to control one or more subsystems of the charged particle beam system 100. The treatment delivery control system 112 is an example of the main controller 110, where the treatment delivery control system receives subsystem input from a first subsystem of the charged particle beam system 100 and provides to a second subsystem of the 20 charged particle beam system 100: (1) the received subsystem input directly, (2) a processed version of the received subsystem input, and/or (3) a command, such as used to fulfill requisites of the treatment planning step 520 or direction of the oncology information system 530. Generally, most or all of the communication between subsystems of the charged particle beam system 100 25 go to and from the treatment delivery control system 112 and not directly to another subsystem of the charged particle beam system 100. Use of a logically centralized treatment delivery control system has many benefits, including: (1) a single centralized code to maintain, debug, secure, update, and to perform checks on, such as quality assurance and quality control checks; (2) a controlled 30 logical flow of information between subsystems; (3) an ability to replace a

2017208222 24 Jul 2017 subsystem with only one interfacing code revision; (4) room security; (5) software access control; (6) a single centralized control for safety monitoring; and (7) that the centralized code results in an integrated safety system 540 encompassing a majority or all of the subsystems of the charged particle beam system 100.

Examples of subsystems of the charged particle cancer therapy system 100 include: a radio frequency quadrupole 550, a radio frequency quadrupole linear accelerator, the injection system 120, the synchrotron 130, the accelerator system 131, the extraction system 134, any controllable or monitorable element of the beam line 268, the targeting/delivery system 140, the nozzle system 146, a 10 gantry 560 or an element of the gantry 560, the patient interface module 150, a patient positioner 152, the display system 160, the imaging system 170, a patient position verification system 179, any element described supra, and/or any subsystem element. A treatment change 570 at time of treatment is optionally computer generated with or without the aid of a technician or physician and 15 approved while the patient is still in the treatment room, in the treatment chair, and/or in a treatment position.

INTEGRATED CANCER TREATMENT - IMAGING SYSTEM

One or more imaging systems 170 are optionally used in a fixed position in a 20 cancer treatment room and/or are moved with a gantry system, such as a gantry system supporting: a portion of the beam transport system 135, the targeting / delivery control system 140, and/or moving or rotating around a patient positioning system, such as in the patient interface module. Without loss of generality and to facilitate description of the invention, examples follow of an 25 integrated cancer treatment - imaging system. In each system, the beam transport system 135 and/or the nozzle system 146 indicates a positively charged beam path, such as from the synchrotron, for tumor treatment and/or for tomography, as described supra.

Example I

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Referring now to Figure 6A, a first example of an integrated cancer treatment imaging system 600 is illustrated. In this example, the charged particle beam system 100 is illustrated with a treatment beam 269 directed to the tumor 220 of the patient 230 along the z-axis. Also illustrated is a set of imaging sources 610, imaging system elements, and/or paths therefrom and a set of detectors 620 corresponding to a respective element of the set of imaging sources 610. Herein, the set of imaging sources 610 are referred to as sources, but are optionally any point or element of the beam train prior to the tumor or a center point about which the gantry rotates. Hence, a given imaging source is optionally 10 a dispersion element used to form cone beam. As illustrated, a first imaging source 612 yields a first beam path 632 and a second imaging source 614 yields a second beam path 634, where each path passes at least into the tumor 220 and optionally and preferably to a first detector array 622 and a second detector array 624, respectively, of the set of detectors 620. Herein, the first beam path 15 632 and the second beam path 634 are illustrated as forming a ninety degree angle, which yields complementary images of the tumor 220 and/or the patient 230. However, the formed angle is optionally any angle from ten to three hundred fifty degrees. Herein, for clarity of presentation, the first beam path 632 and the second beam path 634 are illustrated as single lines, which optionally is 20 an expanding, uniform diameter, or focusing beam. Herein, the first beam path

632 and the second beam path 634 are illustrated in transmission mode with their respective sources and detectors on opposite sides of the patient 230. However, a beam path from a source to a detector is optionally a scattered path and/or a diffuse reflectance path. Optionally, one or more detectors of the set of 25 detectors 620 are a single detector element, a line of detector elements, or preferably a two-dimensional detector array. Use of two two-dimensional detector arrays is referred to herein as a two-dimensional - two-dimensional imaging system or a 2D-2D imaging system.

Still referring to Figure 6A, the first imaging source 612 and the second imaging source 614 are illustrated at a first position and a second position, respectively.

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Each of the first imaging source 612 and the second imaging source 622 optionally: (1) maintain a fixed position; (2) provide the first beam path(s) 632 and the second beam path(s) 634, respectively, such as to an imaging system detector 620 or through the gantry 460, such as through a set of one or more holes or slits; (3) provide the first beam path 632 and the second beam path 634, respectively, off axis to a plane of movement of the nozzle system 146; (4) move with the gantry 460 as the gantry 460 rotates about at least a first axis; (5) move with a secondary imaging system independent of movement of the gantry, as described supra', and/or (6) represent a narrow cross-diameter section of an 10 expanding cone beam path.

Still referring to Figure 6A, the set of detectors 620 are illustrated as coupling with respective elements of the set of sources 610. Each member of the set of detectors 620 optionally and preferably co-moves/and/or co-rotates with a 15 respective member of the set of sources 610. Thus, if the first imaging source

612 is statically positioned, then the first detector 622 is optionally and preferably statically positioned. Similarly, to facilitate imaging, if the first imaging source 612 moves along a first arc as the gantry 460 moves, then the first detector 622 optionally and preferably moves along the first arc or a second arc as the gantry 20 460 moves, where relative positions of the first imaging source 612 on the first arc, a point that the gantry 460 moves about, and relative positions of the first detector 622 along the second arc are constant. To facilitate the process, the detectors are optionally mechanically linked, such as with a mechanical support to the gantry 460 in a manner that when the gantry 460 moves, the gantry moves 25 both the source and the corresponding detector. Optionally, the source moves and a series of detectors, such as along the second arc, capture a set of images.

As illustrated in Figure 6A, the first imaging source 612, the first detector array 622, the second imaging source 614, and the second detector array 624 are coupled to a rotatable imaging system support 462, which optionally rotates 30 independently of the gantry 460 as further described infra. As illustrated in

Figure 6B, the first imaging source 612, the first detector array 622, the second

2017208222 24 Jul 2017 imaging source 614, and the second detector array 624 are coupled to the gantry 460, which in this case is a rotatable gantry.

Still referring to Figure 6A, optionally and preferably, elements of the set of sources 610 combined with elements of the set of detectors 620 are used to collect a series of responses, such as one source and one detector yielding a detected intensity and rotatable imaging system support 462 preferably a set of detected intensities to form an image. For instance, the first imaging source 612, such as a first X-ray source or first cone beam X-ray source, and the first 10 detector 622, such as an X-ray film, digital X-ray detector, or two-dimensional detector, yield a first X-ray image of the patient at a first time and a second X-ray image of the patient at a second time, such as to confirm a maintained location of a tumor or after movement of the gantry and/or nozzle system 146 or rotation of the patient 230. A set of n images using the first imaging source 612 and the first 15 detector 622 collected as a function of movement of the gantry and/or the nozzle system 146 supported by the gantry and/or as a function of movement and/or rotation of the patient 230 are optionally and preferably combined to yield a three-dimensional image of the patient 230, such as a three-dimensional X-ray image of the patient 230, where n is a positive integer, such as greater than 1, 2, 20 3, 4, 5, 10, 15, 25, 50, or 100. The set of n images is optionally gathered as described in combination with images gathered using the second imaging source 614, such as a second X-ray source or second cone beam X-ray source, and the second detector 624, such as a second X-ray detector, where the use of two, or multiple, source/detector combinations are combined to yield images where the 25 patient 230 has not moved between images as the two, or the multiple, images are optionally and preferably collected at the same time, such as with a difference in time of less than 0.01, 0.1, 1, or 5 seconds. Longer time differences are optionally used. Preferably the n two-dimensional images are collected as a function of rotation of the gantry 460 about the tumor and/or the patient and/or as 30 a function of rotation of the patient 230 and the two-dimensional images of the Xray cone beam are mathematically combined to form a three-dimensional image

2017208222 24 Jul 2017 of the tumor 220 and/or the patient 230. Optionally, the first X-ray source and/or the second X-ray source is the source of X-rays that are divergent forming a cone through the tumor. A set of images collected as a function of rotation of the divergent X-ray cone around the tumor with a two-dimensional detector that 5 detects the divergent X-rays transmitted through the tumor is used to form a three-dimensional X-ray of the tumor and of a portion of the patient, such as in Xray computed tomography.

Still referring to Figure 6A, use of two imaging sources and two detectors set at 10 ninety degrees to one another allows the gantry 460 or the patient 230 to rotate through half an angle required using only one imaging source and detector combination. A third imaging source / detector combination allows the three imaging source/detector combination to be set at sixty degree intervals allowing the imaging time to be cut to that of one-third that gantry 460 or patient 230 15 rotation required using a single imaging source-detector combination. Generally, n source-detector combinations reduces the time and/or the rotation requirements to 1/n. Further reduction is possible if the patient 230 and the gantry 460 rotate in opposite directions. Generally, the used of multiple sourcedetector combination of a given technology allow for a gantry that need not rotate 20 through as large of an angle, with dramatic engineering benefits.

Still referring to Figure 6A, the set of sources 610 and set of detectors 620 optionally use more than one imaging technology. For example, a first imaging technology uses X-rays, a second used fluoroscopy, a third detects fluorescence, 25 a fourth uses cone beam computed tomography or cone beam CT, and a fifth uses other electromagnetic waves. Optionally, the set of sources 610 and the set of detectors 620 use two or more sources and/or two or more detectors of a given imaging technology, such as described supra with two X-ray sources to n X-ray sources.

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Still referring to Figure 6A, use of one or more of the set of sources 610 and use of one or more of the set of detectors 620 is optionally coupled with use of the positively charged particle tomography system described supra. As illustrated in Figure 6A, the positively charged particle tomography system uses a second 5 mechanical support 643 to co-rotate the scintillation material 210 with the gantry 460, as well as to co-rotate an optional sheet, such as the first sheet 260 and/or the fourth sheet 290.

Example II

Referring now to Figure 6B, a second example of the integrated cancer treatment

- imaging system 600 is illustrated using greater than three imagers.

Still referring to Figure 6B, two pairs of imaging systems are illustrated.

Particularly, the first and second imaging source 612, 614 coupled to the first and 15 second detectors 622, 624 are as described supra. For clarity of presentation and without loss of generality, the first and second imaging systems are referred to as a first X-ray imaging system and a second X-ray imaging system. The second pair of imaging systems uses a third imaging source 616 coupled to a third detector 626 and a fourth imaging source 618 coupled to a fourth detector 20 628 in a manner similar to the first and second imaging systems described in the previous example. Here, the second pair of imaging systems optionally and preferably uses a second imaging technology, such as fluoroscopy. Optionally, the second pair of imaging systems is a single unit, such as the third imaging source 616 coupled to the third detector 626, and not a pair of units. Optionally, 25 one or more of the set of imaging sources 610 are statically positioned while one of more of the set of imaging sources 610 co-rotate with the gantry 460. Pairs of imaging sources/detector optionally have common and distinct distances, such as a first distance, ch, such as for a first source-detector pair and a second distance, ch, such as for a second source-detector or second source-detector 30 pair. As illustrated, the tomography detector or the scintillation material 210 is at

2017208222 24 Jul 2017 a third distance, cU The distinct differences allow the source-detector elements to rotate on a separate rotation system at a rate different from rotation of the gantry 460, which allows collection of a full three-dimensional image while tumor treatment is proceeding with the positively charged particles.

Example III

For clarity of presentation, referring now to Figure 6C, any of the beams or beam paths described herein is optionally a cone beam 690 as illustrated. The patient support 152 is an mechanical and/or electromechanical device used to position, 10 rotate, and/or constrain any portion of the tumor 220 and/or the patient 230 relative to any axis.

TOMOGRAPHY DETECTOR SYSTEM

A tomography system optically couples the scintillation material to a detector. As 15 described, supra, the tomography system optionally and preferably uses one or more detection sheets, beam tracking elements, and/or tracking detectors to determine/monitor the charged particle beam position, shape, and/or direction in the beam path prior to and/or posterior to the sample, imaged element, patient, or tumor. Herein, without loss of generality, the detector is described as a 20 detector array or two-dimensional detector array positioned next to the scintillation material; however, the detector array is optionally optically coupled to the scintillation material using one or more optics. Optionally and preferably, the detector array is a component of an imaging system that images the scintillation material 210, where the imaging system resolves an origin volume or origin 25 position on a viewing plane of the secondary photon emitted resultant from passage of the residual charged particle beam 267. As described, infra, more than one detector array is optionally used to image the scintillation material 210 from more than one direction, which aids in a three-dimensional reconstruction of

2017208222 24 Jul 2017 the photonic point(s) of origin, positively charged particle beam path, and/or tomographic image.

IMAGING

Generally, medical imaging is performed using an imaging apparatus to generate a visual and/or a symbolic representation of an interior constituent of the body for diagnosis, treatment, and/or as a record of state of the body. Typically, one or more imaging systems are used to image the tumor and/or the patient. For example, the X-ray imaging system and/or the positively charged particle imaging 10 system, described supra, are optionally used individually, together, and/or with any additional imaging system, such as use of X-ray radiography, magnetic resonance imaging, medical ultrasonography, thermography, medical photography, positron emission tomography (PET) system, single-photon emission computed tomography (SPECT), and/or another nuclear / charged 15 particle imaging technique.

FIDUCIAL MARKER

Fiducial markers and fiducial detectors are optionally used to locate, target, track, avoid, and/or adjust for objects in a treatment room that move relative to the 20 nozzle or nozzle system 146 of the charged particle beam system 100 and/or relative to each other. Herein, for clarity of presentation and without loss of generality, fiducial markers and fiducial detectors are illustrated in terms of a movable or statically positioned treatment nozzle and a movable or static patient position. However, generally, the fiducial markers and fiducial detectors are used 25 to mark and identify position, or relative position, of any object in a treatment room, such as a cancer therapy treatment room 922. Herein, a fiducial indicator refers to either a fiducial marker or a fiducial detector. Herein, photons travel from a fiducial marker to a fiducial detector.

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Herein, fiducial refers to a fixed basis of comparison, such as a point or a line. A fiducial marker or fiducial is an object placed in the field of view of an imaging system, which optionally appears in a generated image or digital representation of a scene, area, or volume produced for use as a point of reference or as a 5 measure. Herein, a fiducial marker is an object placed on, but not into, a treatment room object or patient. Particularly, herein, a fiducial marker is not an implanted device in a patient. In physics, fiducials are reference points: fixed points or lines within a scene to which other objects can be related or against which objects can be measured. Fiducial markers are observed using a sighting 10 device for determining directions or measuring angles, such as an alidade or in the modern era a digital detection system. Two examples of modern position determination systems are the Passive Polaris Spectra System and the Polaris Viera System (NDI, Ontario, Canada).

Referring now to Figure 7A, use of a fiducial marker system 700 is described. Generally, a fiducial marker is placed 710 on an object, light from the fiducial marker is detected 730, relative object positions are determined 740, and a subsequent task is performed, such as treating a tumor 770. For clarity of presentation and without loss of generality, non-limiting examples of uses of 20 fiducial markers in combination with X-ray and/or positively charged particle tomographic imaging and/or treatment using positively charged particles are provided, infra.

Example I

Referring now to Figure 8, a fiducial marker aided tomography system 800 is illustrated and described. Generally, a set of fiducial marker detectors 820 detects photons emitted from and/or reflected off of a set of fiducial markers 810 and resultant determined distances and calculated angles are used to determine relative positions of multiple objects or elements, such as in the treatment room 30 922.

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Still referring to Figure 8, initially, a set of fiducial markers 810 are placed on one or more elements. As illustrated, a first fiducial marker 811, a second fiducial marker 812, and a third fiducial marker 813 are positioned on a first, preferably rigid, support element 852. As illustrated, the first support element 852 supports a scintillation material 210. As each of the first, second, and third fiducial markers 811, 812, 813 and the scintillation material 210 are affixed or statically positioned onto the first support element 852, the relative position of the scintillation material 210 is known, based on degrees of freedom of movement of 10 the first support element, if the positions of the first fiducial marker 811, the second fiducial marker 812, and/or the third fiducial marker 813 is known. In this case, one or more distances between the first support element 852 and a third support element 856 are determined, as further described infra.

Still referring to Figure 8, a set of fiducial detectors 820 are used to detect light emitted from and/or reflected off one or more fiducial markers of the set of fiducial markers 810. As illustrated, ambient photons 821 and/or photons from an illumination source reflect off of the first fiducial marker 811, travel along a first fiducial path 831, and are detected by a first fiducial detector 821 of the set of fiducial detectors 820. In this case, a first signal from the first fiducial detector

821 is used to determine a first distance to the first fiducial marker 811. If the first support element 852 supporting the scintillation material 210 only translates, relative to the nozzle system 146, along the z-axis, the first distance is sufficient information to determine a location of the scintillation material 210, relative to the 25 nozzle system 146. Similarly, photons emitted, such as from a light emitting diode embedded into the second fiducial marker 812 travel along a second fiducial path 832 and generate a second signal when detected by a second fiducial detector 822, of the set of fiducial detectors 820. The second signal is optionally used to confirm position of the first support element 852, reduce error 30 of a determined position of the first support element 852, and/or is used to

2017208222 24 Jul 2017 determine extent of a second axis movement of the first support element 852, such as tilt of the first support element 852. Similarly, photons passing from the third fiducial marker 813 travel along a third fiducial path 833 and generate a third signal when detected by a third fiducial detector 823, of the set of fiducial detectors 820. The third signal is optionally used to confirm position of the first support element 852, reduce error of a determined position of the first support element 852, and/or is used to determine extent of a second or third axis movement of the first support element 852, such as rotation of the first support element 852.

If all of the movable elements within the treatment room 922 move together, then determination of a position of one, two, or three fiducial markers, dependent on degrees of freedom of the movable elements, is sufficient to determine a position of all of the co-movable movable elements. However, optionally two or more 15 objects in the treatment room 922 move independently or semi-independently from one another. For instance, a first movable object optionally translates, tilts, and/or rotates relative to a second movable object. One or more additional fiducial markers of the set of fiducial markers 810 placed on each movable object allows relative positions of each of the movable objects to be determined.

Still referring to Figure 8, a position of the patient 230 is determined relative to a position of the scintillation material 210. As illustrated, a second support element 854 positioning the patient 230 optionally translates, tilts, and/or rotates relative to the first support element 852 positioning the scintillation material 210. In this 25 case, a fourth fiducial marker 814, attached to the second support element 854 allows determination of a current position of the patient 230. As illustrated, a position of a single fiducial element, the fourth fiducial marker 814, is determined by the first fiducial detector 821 determining a first distance to the fourth fiducial marker 814 and the second fiducial detector 822 determining a second distance 30 to the fourth fiducial marker 814, where a first arc of the first distance from the

2017208222 24 Jul 2017 first fiducial detector 821 and a second arc of the second distance from the second fiducial detector 822 overlap at a point of the fourth fiducial marker 834 marking the position of the second support element 852 and the supported position of the patient 230. Combined with the above described system of 5 determining location of the scintillation material 210, the relative position of the scintillation material 210 to the patient 230, and thus the tumor 720, is determined.

Still referring to Figure 8, one fiducial marker and/or one fiducial detector is 10 optionally and preferably used to determine more than one distance or angle to one or more objects. In a first case, as illustrated, light from the fourth fiducial marker 814 is detected by both the first fiducial detector 821 and the second fiducial detector 822. In a second case, as illustrated, light detected by the first fiducial detector 821, passes from the first fiducial marker 811 and the fourth 15 fiducial marker 814. Thus, (1) one fiducial marker and two fiducial detectors are used to determine a position of an object, (2) two fiducial markers on two elements and one fiducial detector is used to determine relative distances of the two elements to the single detector, and/or as illustrated and described below in relation to Figure 10A, and/or (3) positions of two or more fiducial markers on a 20 single object are detected using a single fiducial detector, where the distance and orientation of the single object is determined from the resultant signals. Generally, use of multiple fiducial markers and multiple fiducial detectors are used to determine or overdetermine positions of multiple objects, especially when the objects are rigid, such as a support element, or semi-rigid, such as a person, 25 head, torso, or limb.

Still referring to Figure 8, the fiducial marker aided tomography system 800 is further described. As illustrated, the set of fiducial detectors 820 are mounted onto the third support element 856, which has a known position and orientation 30 relative to the nozzle system 146. Thus, position and orientation of the nozzle

2017208222 24 Jul 2017 system 146 is known relative to the tumor 720, the patient 230, and the scintillation material 210 through use of the set of fiducial markers 810, as described supra. Optionally, the main controller 110 uses inputs from the set of fiducial detectors 820 to: (1) dictate movement of the patient 230 or operator; (2) control, adjust, and/or dynamically adjust position of any element with a mounted fiducial marker and/or fiducial detector, and/or (3) control operation of the charged particle beam, such as for imaging and/or treating or performing a safety stop of the positively charged particle beam. Further, based on past movements, such as the operator moving across the treatment room 922 or relative 10 movement of two objects, the main controller is optionally and preferably used to prognosticate or predict a future conflict between the treatment beam 269 and the moving object, in this case the operator, and take appropriate action or to prevent collision of the two objects.

Example II

Referring now to Figure 9, a fiducial marker aided treatment system 3400 is described. To clarify the invention and without loss of generality, this example uses positively charged particles to treat a tumor. However, the methods and apparatus described herein apply to imaging a sample, such as described supra.

Still referring to Figure 9, four additional cases of fiducial marker - fiducial detector combinations are illustrated. In a first case, photons from the first fiducial marker 811 are detected using the first fiducial detector 821, as described in the previous example. However, photons from a fifth fiducial marker 815 are 25 blocked and prevented from reaching the first fiducial detector 821 as a sixth fiducial path 836 is blocked, in this case by the patient 230. The inventor notes that the absence of an expected signal, disappearance of a previously observed signal with the passage of time, and/or the emergence of a new signal each add information on existence and/or movement of an object. In a second case, 30 photons from the fifth fiducial marker 815 passing along a seventh fiducial path

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837 are detected by the second fiducial detector 822, which illustrates one fiducial marker yielding a blocked and unblocked signal usable for finding an edge of a flexible element or an element with many degrees of freedom, such as a patient’s hand, arm, or leg. In a third case, photons from the fifth fiducial marker 815 and a sixth fiducial marker 816, along the seventh fiducial path 837 and an eighth fiducial path 838 respectively, are detected by the second fiducial detector 822, which illustrates that one fiducial detector optionally detects signals from multiple fiducial markers. In this case, photons from the multiple fiducial sources are optionally of different wavelengths, occur at separate times, occur for 10 different overlapping periods of time, and/or are phase modulated. In a fourth case, a seventh fiducial marker 817 is affixed to the same element as a fiducial detector, in this case the front surface plane of the third support element 856. Also, in the fourth case, a fourth fiducial detector 824, observing photons along a ninth fiducial path 839, is mounted to a fourth support element 858, where the 15 fourth support element 858 positions the patient 230 and tumor 220 thereof and/or is attached to one or more fiducial source elements.

Still referring to Figure 9 the fiducial marker aided treatment system 900 is further described. As described, supra, the set of fiducial markers 810 and the set of 20 fiducial detectors 820 are used to determine relative locations of objects in the treatment room 922, which are the third support element 856, the fourth support element 858, the patient 230, and the tumor 220 as illustrated. Further, as illustrated, the third support element 856 comprises a known physical position and orientation relative to the nozzle system 146. Hence, using signals from the 25 set of fiducial detectors 820, representative of positions of the fiducial markers

810 and room elements, the main controller 110 controls the treatment beam 269 to target the tumor 220 as a function of time, movement of the nozzle system 146, and/or movement of the patient 230.

Example III

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Referring now to Figure 10A, a fiducial marker aided treatment room system 1000 is described. Without loss of generality and for clarity of presentation, a zero vector 1001 is a vector or line emerging from the nozzle system 146 when the first axis control 143, such as a vertical control, and the second axis control 5 144, such as a horizontal control, of the scanning system 140 is turned off.

Without loss of generality and for clarity of presentation, a zero point 1002 is a point on the zero vector 1001 at a plane of an exit face the nozzle system 146. Generally, a defined point and/or a defined line are used as a reference position and/or a reference direction and fiducial markers are defined in space relative to 10 the point and/or line.

Six additional cases of fiducial marker - fiducial detector combinations are illustrated to further describe the fiducial marker aided treatment room system 1000. In a first case, the patient 230 position is determined. Herein, a first 15 fiducial marker 811 marks a position of a patient positioning device 1020 and a second fiducial marker 812 marks a position of a portion of skin of the patient 230, such as a limb, joint, and/or a specific position relative to the tumor 220. In a second case, multiple fiducial markers of the set of fiducial markers 810 and multiple fiducial detectors of said set of fiducial detectors 820 are used to 20 determine a position/relative position of a single object, where the process is optionally and preferably repeated for each object in the treatment room 922. As illustrated, the patient 230 is marked with the second fiducial marker 812 and a third fiducial marker 813, which are monitored using a first fiducial detector 821 and a second fiducial detector 822. In a third case, a fourth fiducial marker 814 25 marks the scintillation material 210 and a sixth fiducial path 836 illustrates another example of a blocked fiducial path. In a fourth case, a fifth fiducial marker 815 marks an object not always present in the treatment room, such as a wheelchair 1040, walker, or cart. In a sixth case, a sixth fiducial marker 816 is used to mark an operator 1050, who is mobile and must be protected from an 30 unwanted irradiation from the nozzle system 146.

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Still referring to Figure 10A, clear field treatment vectors and obstructed field treatment vectors are described. A clear field treatment vector comprises a path of the treatment beam 269 that does not intersect a non-standard object, where a 5 standard object includes all elements in a path of the treatment beam 269 used to measure a property of the treatment beam 269, such as the first sheet 260, the second sheet 270, the third sheet 280, and the fourth sheet 290. Examples of non-standard objects or interfering objects include an arm of the patient couch, a back of the patient couch, and/or a supporting bar, such a robot arm. Use of 10 fiducial indicators, such as a fiducial marker, on any potential interfering object allows the main controller 110 to only treat the tumor 220 of the patient 230 in the case of a clear field treatment vector. For example, fiducial markers are optionally placed along the edges or corners of the patient couch or patient positioning system or indeed anywhere on the patient couch. Combined with a15 priori knowledge of geometry of the non-standard object, the main controller can deduce/calculate presence of the non-standard object in a current or future clear field treatment vector, forming a obstructed field treatment vector, and perform any of: increasing energy of the treatment beam 269 to compensate, moving the interfering non-standard object, and/or moving the patient 230 and/or the nozzle 20 system 146 to a new position to yield a clear field treatment vector. Similarly, for a given determined clear filed treatment vector, a total treatable area, using scanning of the proton beam, for a given nozzle-patient couch position is optionally and preferably determined. Further, the clear field vectors are optionally and preferably predetermined and used in development of a radiation 25 treatment plan.

Referring again to Figure 7A, Figure 8, Figure 9, and Figure 10A, generally, one or more fiducial markers and/or one or more fiducial detectors are attached to any movable and/or statically positioned object/element in the treatment room

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922, which allows determination of relative positions and orientation between any set of objects in the treatment room 922.

Sound emitters and detectors, radar systems, and/or any range and/or directional finding system is optionally used in place of the source-photon-detector systems described herein.

2D-2D X-RAY IMAGING

Still referring to Figure 10A, for clarity of presentation and without loss of generality, a two-dimensional-two-dimensional (2D-2D) X-ray imaging system 1060 is illustrated, which is representative of any source-sample-detector transmission based imaging system. As illustrated, the 2D-2D imaging system 1060 includes a 2D-2D source end 1062 on a first side of the patient 230 and a 2D-2D detector end 1064 on a second side, an opposite side, of the patient 230.

The 2D-2D source end 1062 holds, positions, and/or aligns source imaging elements, such as: (1) one or more imaging sources; (2) the first imaging source 612 and the second imaging source 622; and/or (3) a first cone beam X-ray source and a second cone beam X-ray source; while, the 2D-2D detector end 1064, respectively, holds, positions, and/or aligns: (1) one or more imaging detectors 1066; (2) a first imaging detector and a second imaging detector; and/or (3) a first cone beam X-ray detector and a second cone beam X-ray detector.

In practice, optionally and preferably, the 2D-2D imaging system 1060 as a unit rotates about a first axis around the patient, such as an axis of the treatment beam 269, as illustrated at the second time, t2. For instance, at the second time, t2, the 2D-2D source end 1062 moves up and out of the illustrated plane while the 2D-2D detector end 1064 moves down and out of the illustrated plane. Thus, the 2D-2D imaging system may operate at one or more positions through rotation

2017208222 24 Jul 2017 about the first axis while the treatment beam 269 is in operation without interfering with a path of the treatment beam 269.

Optionally and preferably, the 2D-2D imaging system 1060 does not physically obstruct the treatment beam 269 or associated residual energy imaging beam from the nozzle system 146. Through relative movement of the nozzle system

146 and the 2D-2D imaging system 1060, a mean path of the treatment beam

269 and a mean path of X-rays from an X-ray source of the 2D-2D imaging system 1060 form an angle from 0 to 90 degrees and more preferably an angle 10 of greater than 10, 20, 30, or 40 degrees and less than 80, 70, or 60 degrees.

Still referring to Figure 10A, as illustrated at the second time, fr, the angle between the mean treatment beam and the mean X-ray beam is 45 degrees.

The 2D-2D imaging system 1060 optionally rotates about a second axis, such as 15 an axis perpendicular to Figure 10A and passing through the patient and/or passing through the first axis. Thus, as illustrated, as the exit port of the output nozzle system 146 moves along an arc and the treatment beam 269 enters the patient 230 from another angle, rotation of the 2D-2D imaging system 1060 about the second axis perpendicular to Figure 10A, the first axis of the 2D-2D imaging 20 system 1060 continues to rotate about the first axis, where the first axis is the axis of the treatment beam 269 or the residual charged particle beam 267 in the case of imaging with protons.

Optionally and preferably, one or more elements of the 2D-2D X-ray imaging 25 system 1060 are marked with one or more fiducial elements, as described supra.

As illustrated, the 2D-2D detector end 1064 is configured with a seventh fiducial marker 817 and an eighth fiducial marker 818 while the 2D-2D source end 1062 is configured with a ninth fiducial marker 819, where any number of fiducial markers are used.

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In many cases, movement of one fiducial indicator necessitates movement of a second fiducial indicator as the two fiducial indicators are physically linked. Thus, the second fiducial indicator is not strictly needed, given complex code that 5 computes the relative positions of fiducial markers that are often being rotated around the patient 230, translated past the patient 230, and/or moved relative to one or more additional fiducial markers. The code is further complicated by movement of non-mechanically linked and/or independently moveable obstructions, such as a first obstruction object moving along a first concentric 10 path and a second obstruction object moving along a second concentric path.

The inventor notes that the complex position determination code is greatly simplified if the treatment beam path 269 to the patient 230 is determined to be clear of obstructions, through use of the fiducial indicators, prior to treatment of at least one of and preferably every voxel of the tumor 220. Thus, multiple fiducial 15 markers placed on potentially obstructing objects simplifies the code and reduces treatment related errors. Typically, treatment zones or treatment cones are determined where a treatment cone from the output nozzle system 146 to the patient 230 does not pass through any obstructions based on the current position of all potentially obstructing objects, such as a support element of the patient 20 couch. As treatment cones overlap, the path of the treatment beam 269 and/or a path of the residual charged particle beam 267 is optionally moved from treatment cone to treatment cone without use of the imaging/treatment beam continuously as moved along an arc about the patient 230. A transform of the standard tomography algorithm thus allows physical obstructions to the 25 imaging/treatment beam to be avoided.

ISOCENTERLESS SYSTEM

The inventor notes that a fiducial marker aided imaging system, the fiducial marker aided tomography system 800, and/or the fiducial marker aided treatment 30 system 900 are applicable in a treatment room 922 not having a treatment beam

2017208222 24 Jul 2017 isocenter, not having a tumor isocenter, and/or is not reliant upon calculations using and/or reliant upon an isocenter. Further, the inventor notes that all positively charged particle beam treatment centers in the public view are based upon mathematical systems using an isocenter for calculations of beam position 5 and/or treatment position and that the fiducial marker aided imaging and treatment systems described herein do not need an isocenter and are not necessarily based upon mathematics using an isocenter, as is further described infra. In stark contrast, a defined point and/or a defined line are used as a reference position and/or a reference direction and fiducial markers are defined 10 in space relative to the point and/or line.

Traditionally, the isocenter 263 of a gantry based charged particle cancer therapy system is a point in space about which an output nozzle rotates. In theory, the isocenter 263 is an infinitely small point in space. However, traditional gantry 15 and nozzle systems are large and extremely heavy devices with mechanical errors associated with each element. In real life, the gantry and nozzle rotate around a central volume, not a point, and at any given position of the gantrynozzle system, a mean or unaltered path of the treatment beam 269 passes through a portion of the central volume, but not necessarily the single point of the 20 isocenter 263. Thus, to distinguish theory and real-life, the central volume is referred to herein as a mechanically defined isocenter volume, where under best engineering practice the isocenter has a geometric center, the isocenter 263. Further, in theory, as the gantry-nozzle system rotates around the patient, the mean or unaltered lines of the treatment beam 269 at a first and second time, 25 preferably all times, intersect at a point, the point being the isocenter 263, which is an unknown position. However, in practice the lines pass through the mechanically identified isocenter volume 1012. The inventor notes that in all gantry supported movable nozzle systems, calculations of applied beam state, such as energy, intensity, and direction of the charged particle beam, are 30 calculated using a mathematical assumption of the point of the isocenter 263.

The inventor further notes, that as in practice the treatment beam 269 passes

2017208222 24 Jul 2017 through the mechanically defined isocenter volume but misses the isocenter 263, an error exists between the actual treatment volume and the calculated treatment volume of the tumor 220 of the patient 230 at each point in time. The inventor still further notes that the error results in the treatment beam 269: (1) not striking 5 a given volume of the tumor 220 with the prescribed energy and/or (2) striking tissue outside of the tumor. Mechanically, this error cannot be eliminated, only reduced. However, use of the fiducial markers and fiducial detectors, as described supra, removes the constraint of using an unknown position of the isocenter 263 to determine where the treatment beam 269 is striking to fulfill a 10 doctor provided treatment prescription as the actual position of the patient positioning system, tumor 220, and/or patient 230 is determined using the fiducial markers and output of the fiducial detectors with no use of the isocenter 263, no assumption of an isocenter 263, and/or no spatial treatment calculation based on the isocenter 263. Rather, a physically defined point and/or line, such as the 15 zero point 1002 and/or the zero vector 1001, in conjunction with the fiducials are used to: (1) determine position and/or orientation of objects relative to the point and/or line and/or (2) perform calculations, such as a radiation treatment plan.

Referring again to Figure 7A and referring again to Figure 10A, optionally and 20 preferably, the task of determining the relative object positions 740 uses a fiducial element, such as an optical tracker, mounted in the treatment room 922, such as on the gantry or nozzle system, and calibrated to a “zero” vector 1001 of the treatment beam 269, which is defined as the path of the treatment beam when electromagnetic and/or electrostatic steering of one or more final magnets 25 in the beam transport system 135 and/or an output nozzle system 146 attached to a terminus thereof is/are turned off. The zero vector 1001 is a path of the treatment beam 269 when the first axis control 143, such as a vertical control, and the second axis control 144, such as a horizontal control, of the scanning system 140 is turned off. A zero point 1002 is any point, such as a point on the 30 zero vector 1001. Herein, without loss of generality and for clarity of presentation, the zero point 1002 is a point on the zero vector 1001 crossing a

2017208222 24 Jul 2017 plane defined by a terminus of the nozzle of the nozzle system 146. Ultimately, the use of a zero vector 1001 and/or the zero point 1002 is a method of directly and optionally actively relating the coordinates of objects, such as moving objects and/or the patient 230 and tumor 220 thereof, in the treatment room 922 to one 5 another; not passively relating them to an imaginary point in space such as a theoretical isocenter than cannot mechanically be implemented in practice as a point in space, but rather always as an a isocenter volume, such as an isocenter volume including the isocenter point in a well-engineered system. Examples further distinguish the isocenter based and fiducial marker based targeting 10 system.

Example I

Referring now to Figure 10B, an isocenterless system 1005 of the fiducial marker aided treatment room system 1000 of Figure 10A is described. As illustrated, the 15 nozzle / nozzle system 146 is positioned relative to a reference element, such as the third support element 856. The reference element is optionally a reference fiducial marker and/or a reference fiducial detector affixed to any portion of the nozzle system 146 and/or a rigid, positionally known mechanical element affixed thereto. A position of the tumor 220 of the patient 230 is also determined using 20 fiducial markers and fiducial detectors, as described supra. As illustrated, at a first time, ti, a first mean path of the treatment beam 269 passes through the isocenter 263. At a second time, t2, resultant from inherent mechanical errors associated with moving the nozzle system 146, a second mean path of the treatment beam 269 does not pass through the isocenter 263. In a traditional 25 system, this would result in a treatment volume error. However, using the fiducial marker based system, the actual position of the nozzle system 146 and the patient 230 is known at the second time, /2, which allows the main controller to direct the treatment beam 269 to the targeted and prescription dictated tumor volume using the first axis control 143, such as a vertical control, and the second 30 axis control 144, such as a horizontal control, of the scanning system 140.

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Again, since the actual position at the time of treatment is known using the fiducial marker system, mechanical errors of moving the nozzle system 146 are removed and the x/y-axes adjustments of the treatment beam 269 are made using the actual and known position of the nozzle system 146 and the tumor 220, 5 in direct contrast to the x/y-axes adjustments made in traditional systems, which assume that the treatment beam 269 passes through the isocenter 263. In essence: (1) the x/y-axes adjustments of the traditional targeting systems are in error as the unmodified treatment beam 269 is not passing through the assumed isocenter and (2) the x/y-axes adjustments of the fiducial marker based system 10 know the actual position of the treatment beam 269 relative to the patient 230 and the tumor 220 thereof, which allows different x/y-axes adjustments that adjust the treatment beam 269 to treat the prescribed tumor volume with the prescribed dosage.

Example II

Referring now to Figure 10C an example is provided that illustrates errors in an isocenter 263 with a fixed beamline position and a moving patient positioning system. As illustrated, at a first time, ti, the mean/unaltered treatment beam path 269 passes through the tumor 220, but misses the isocenter 263. As described, 20 supra, traditional treatment systems assume that the mean/unaltered treatment beam path 269 passes through the isocenter 263 and adjust the treatment beam to a prescribed volume of the tumor 220 for treatment, where both the assumed path through the isocenter and the adjusted path based on the isocenter are in error. In stark contrast, the fiducial marker system: (1) determines that the 25 actual mean/unaltered treatment beam path 269 does not pass through the isocenter 263, (2) determines the actual path of the mean/unaltered treatment beam 269 relative to the tumor 220, and (3) adjusts, using a reference system such as the zero line 1001 and/or the zero point 1002, the actual mean/unaltered treatment beam 269 to strike the prescribed tissue volume using the first axis 30 control 143, such as a vertical control, and the second axis control 144, such as

2017208222 24 Jul 2017 a horizontal control, of the scanning system 140. As illustrated, at a second time, t2, the mean/unaltered treatment beam path 269 again misses the isocenter 263 resulting in treatment errors in the traditional isocenter based targeting systems, but as described, the steps of: (1) determining the relative position of: (a) the 5 mean/unaltered treatment beam 269 and (b) the patient 230 and tumor 220 thereof and (2) adjusting the determined and actual mean/unaltered treatment beam 269, relative to the tumor 220, to strike the prescribed tissue volume using the first axis control 143, the second axis control 144, and energy of the treatment beam 269 are repeated for the second time, fr, and again through the 10 n^th treatment time, where n is a positive integer of at least 5, 10, 50, 100, or 500.

Referring again to Figure 8 and Figure 9, generally at a first time, objects, such as the patient 230, the scintillation material 210, an X-ray system, and the nozzle system 146 are mapped and relative positions are determined. At a second time, 15 the position of the mapped objects is used in imaging, such as X-ray and/or proton beam imaging, and/or treatment, such as cancer treatment. Further, an isocenter is optionally used or is not used. Still further, the treatment room 922 is, due to removal of the beam isocenter knowledge constraint, optionally designed with a static or movable nozzle system 146 in conjunction with any 20 patient positioning system along any set of axes as long as the fiducial marking system is utilized.

Referring now to Figure 7B, optional uses of the fiducial marker system 700 are described. After the initial step of placing the fiducial markers 710, the fiducial 25 markers are optionally illuminated 720, such as with the ambient light or external light as described above. Light from the fiducial markers is detected 730 and used to determine relative positions of objects 740, as described above. Thereafter, the object positions are optionally adjusted 750, such as under control of the main controller 110 and the step of illuminating the fiducial markers 30 720 and/or the step of detecting light from the fiducial markers 730 along with the

2017208222 24 Jul 2017 step of determining relative object positions 740 is iteratively repeated until the objects are correctly positioned. Simultaneously or independently, fiducial detectors positions are adjusted 780 until the objects are correctly placed, such as for treatment of a particular tumor voxel. Using any of the above steps: (1) 5 one or more images are optionally aligned 760, such as a collected X-ray image and a collected proton tomography image using the determined positions; (2) the tumor 220 is treated 770; and/or (3) changes of the tumor 220 are tracked 790 for dynamic treatment changes and/or the treatment session is recorded for subsequent analysis.

REFERENCED CHARGED PARTICLE PATH

Referring now to Figure 11, a charged particle reference beam path system 1100 is described, which starkly contrasts to an isocenter reference point of a gantry system, as described supra. The charged particle reference beam path system 15 1100 defines voxels in the treatment room 922, the patient 230, and/or the tumor

220 relative to a reference path of the positively charged particles and/or a transform thereof. The reference path of the positively charged particles comprises one or more of: a zero vector, an unredirected beamline, an unsteered beamline, a nominal path of the beamline, and/or, such as, in the case 20 of a rotatable gantry and/or moveable nozzle, a translatable and/or a rotatable position of the zero vectors. For clarity of presentation and without loss of generality, the terminology of a reference beam path is used herein to refer to an axis system defined by the charged particle beam under a known set of controls, such as a known position of entry into the treatment room 922, a known vector 25 into the treatment room 922, a first known field applied in the first axis control

143, and/or a second known field applied in the second axis control 144. Further, as described, supra, a reference zero point or zero point 1002 is a point on the reference beam path. More generally, the reference beam path and the reference zero point optionally refer to a mathematical transform of a calibrated 30 reference beam path and a calibrated reference zero point of the beam path,

2017208222 24 Jul 2017 such as a charged particle beam path defined axis system. The calibrated reference zero point is any point; however, preferably the reference zero point is on the calibrated reference beam path and as used herein, for clarity of presentation and without loss of generality, is a point on the calibrated reference 5 beam path crossing a plane defined by a terminus of the nozzle of the nozzle system 146. Optionally and preferably, the reference beam path is calibrated, in a prior calibration step, against one or more system position markers as a function of one or more applied fields of the first known field and the second known field and optionally energy and/or flux/intensity of the charged particle 10 beam, such as along the treatment beam path 269. The reference beam path is optionally and preferably implemented with a fiducial marker system and is further described infra.

Example I

Ina first example, referring still to Figure 11, the charged particle reference beam path system 1100 is further described using a radiation treatment plan developed using a traditional isocenter axis system 1122. A medical doctor approved radiation treatment plan 1110, such as a radiation treatment plan developed using the traditional isocenter axis system 1122, is converted to a radiation 20 treatment plan using the reference beam path - reference zero point treatment plan. The conversion step, when coupled to a calibrated reference beam path, uses an ideal isocenter point; hence, subsequent treatment using the calibrated reference beam and fiducial indicators 1140 removes the isocenter volume error.

For instance, prior to tumor treatment 1170, fiducial indicators 1140 are used to 25 determine position of the patient 230 and/or to determine a clear treatment path to the patient 230. For instance, the reference beam path and/or treatment beam path 269 derived therefrom is projected in software to determine if the treatment beam path 269 is unobstructed by equipment in the treatment room using known geometries of treatment room objects and fiducial indicators 1140 indicating 30 position and/or orientation of one or more and preferably all movable treatment

2017208222 24 Jul 2017 room objects. The software is optionally implemented in a virtual treatment system. Preferably, the software system verifies a clear treatment path, relative to the actual physical obstacles marked with the fiducial indicators 1140, in the less than 5, 4, 3, 2, 1, and/or 0.1 seconds prior to each use of the treatment 5 beam path 269 and/or in the less than 5, 4, 3, 2, 1, and/or 0.1 seconds following movement of the patient positioning system, patient 230, and/or operator.

Example II

In a second example, referring again to Figure 11, the charged particle reference 10 beam path system 1100 is further described.

Generally, a radiation treatment plan is developed 1120. In a first case, an isocenter axis system 1122 is used to develop the radiation treatment plan 1120. In a second case, a system using the reference beam path of the charged 15 particles 1124 is used to develop the radiation treatment plan. In a third case, the radiation treatment plan developed using the reference beam path 1120 is converted to an isocenter axis system 1122, to conform with traditional formats presented to the medical doctor, prior to medical doctor approval of the radiation treatment plan 1110, where the transformation uses an actual isocenter point and 20 not a mechanically defined isocenter volume and errors associated with the size of the volume, as detailed supra. In any case, the radiation treatment plan is tested, in software and/or in a dry run absent tumor treatment, using the fiducial indicators 1140. The dry run allows a real-life error check to ensure that no mechanical element crosses the treatment beam in the proposed or developed 25 radiation treatment plan 1120. Optionally, a physical dummy placed in a patient treatment position is used in the dry run.

After medical doctor approval of the radiation treatment plan 1110, tumor treatment 1170 commences, optionally and preferably with an intervening step of

2017208222 24 Jul 2017 verifying a clear treatment path 1152 using the fiducial indicators 1140. In the event that the main controller 110 determines, using the reference beam path and the fiducial indicators 1140, that the treatment beam 269 would intersect an object or operator in the treatment room 922, multiple options exist. In a first 5 case, the main controller 110, upon determination of a blocked and/or obscured treatment path of the treatment beam 269, temporarily or permanently stops the radiation treatment protocol. In a second case, optionally after interrupting the radiation treatment protocol, a modified treatment plan is developed 1154 for subsequent medical doctor approval of the modified radiation treatment plan 10 1110. In a third case, optionally after interrupting the radiation treatment protocol, a physical transformation of a delivery axis system is performed 1130, such as by moving the nozzle system 146, rotating and/or translating the nozzle position 1134, and/or switching to another beamline 1136. Subsequently, tumor treatment 1170 is resumed and/or a modified treatment plan is presented to the 15 medical doctor for approval of the radiation treatment plan.

AUTOMATED CANCER THERAPY IMAGING/TREATMENT SYSTEM

Cancer treatment using positively charged particles involves multi-dimensional imaging, multi-axes tumor irradiation treatment planning, multi-axes beam 20 particle beam control, multi-axes patient movement during treatment, and intermittently intervening objects between the patient and/or the treatment nozzle system. Automation of subsets of the overall cancer therapy treatment system using robust code simplifies working with the intermixed variables, which aids oversight by medical professionals. Herein, an automated system is optionally 25 semi-automated, such as overseen by a medical professional.

Example I

In a first example, referring still to Figure 11 and referring now to Figure 12, a first example of a semi-automated cancer therapy treatment system 1200 is

2017208222 24 Jul 2017 described and the charged particle reference beam path system 1100 is further described. The charged particle reference beam path system 1100 is optionally and preferably used to automatically or semi-automatically: (1) identify an upcoming treatment beam path; (2) determine presence of an object in the upcoming treatment beam path; and/or (3) redirect a path of the charged particle beam to yield an alternative upcoming treatment beam path. Further, the main controller 110 optionally and preferably contains a prescribed tumor irradiation plan, such as provided by a prescribing doctor. In this example, the main controller 110 is used to determine an alternative treatment plan to achieve the 10 same objective as the prescribed treatment plan. For instance, the main controller 110, upon determination of the presence of an intervening object in an upcoming treatment beam path or imminent treatment path directs and/or controls: movement of the intervening object; movement of the patient positioning system; and/or position of the nozzle system 146 to achieve identical 15 or substantially identical treatment of the tumor 220 in terms of radiation dosage per voxel and/or tumor collapse direction, where substantially identical is a dosage and/or direction within 90, 95, 97, 98, 99, or 99.5 percent of the prescription. Herein, an imminent treatment path is the next treatment path of the charged particle beam to the tumor in a current version of a radiation 20 treatment plan and/or a treatment beam path/vector that is scheduled for use within the next 1, 5, 10, 30, or 60 seconds. In a first case, the revised tumor treatment protocol is sent to a doctor, such as a doctor in a neighboring control room and/or a doctor in a remote facility or outside building, for approval. In a second case, the doctor, present or remote, oversees an automated or semi25 automated revision of the tumor treatment protocol, such as generated using the main controller. Optionally, the doctor halts treatment, suspends treatment pending an analysis of the revised tumor treatment protocol, slows the treatment procedure, or allows the main controller to continue along the computer suggested revised tumor treatment plan. Optionally and preferably, imaging data 30 and/or imaging information, such as described supra, is input to the main

2017208222 24 Jul 2017 controller 110 and/or is provided to the overseeing doctor or the doctor authorizing a revised tumor treatment irradiation plan.

Example II

Referring now to Figure 12, a second example of the semi-automated cancer therapy treatment system 1200 is described. Initially, a medical doctor, such as an oncologist, provides an approved radiation treatment plan 1210, which is implemented in a treatment step of delivering charged particles 1228 to the tumor 220 of the patient 230. Concurrent with implementation of the treatment step, 10 additional data is gathered, such as via an updated/new image from an imaging system and/or via the fiducial indicators 1140. Subsequently, the main controller 110 optionally, in an automated process or semi-automated process, adjusts the provided doctor approved radiation treatment plan 1210 to form a current radiation treatment plan. In a first case, cancer treatments halts until the doctor 15 approves the proposed / adjusted treatment plan and continues using the now, doctor approved, current radiation treatment plan. In a second case, the computer generated radiation treatment plan continues in an automated fashion as the current treatment plan. In a third case, the computer generated treatment plan is sent for approval, but cancer treatment proceeds at a reduced rate to 20 allow the doctor time to monitor the changed plan. The reduced rate is optionally less than 100, 90, 80, 70, 60, or 50 percent of the original treatment rate and/or is greater than 0, 10, 20, 30, 40, or 50 percent of the original treatment rate. At any time, the overseeing doctor, medical professional, or staff may increase or decrease the rate of treatment.

Example III

Referring still to Figure 12, a third example of the semi-automated cancer therapy treatment system 1200 is described. In this example, a process of semiautonomous cancer treatment 1220 is implemented. In stark contrast with the

2017208222 24 Jul 2017 previous example where a doctor provides the original cancer treatment plan 1210, in this example the cancer therapy system 110 auto-generates a radiation treatment plan 1226. Subsequently, the auto-generated treatment plan, now the current radiation treatment plan, is implemented, such as via the treatment step 5 of delivering charged particles 1228 to the tumor 220 of the patient 230.

Optionally and preferably, the auto-generated radiation treatment plan 1226 is reviewed in an intervening and/or concurrent doctor oversight step 1230, where the auto-generated radiation treatment plan 1226 is approved as the current treatment plan 1232 or approved as an alternative treatment plan 1234; once 10 approved referred to as the current treatment plan.

Generally, the original doctor approved treatment plan 1210, the auto generated radiation treatment plan 1226, or the altered treatment plan 1234, when being implemented is referred to as the current radiation treatment plan.

Example IV

Referring still to Figure 12, a fourth example of the semi-automated cancer therapy treatment system 1200 is described. In this example, the current radiation treatment plan, prior to implementation of a particular set of voxels of 20 the tumor 220 of the patient 230, is analyzed in terms of clear path analysis, as described supra. More particularly, fiducial indicators 1140 are used in determination of a clear treatment path prior to treatment along an imminent beam treatment path to one or more voxels of the tumor 220 of the patient. Upon implementation, the imminent treatment vector is the treatment vector in the 25 deliver charged particles step 1228.

Example V

Referring still to Figure 12, a fifth example of the semi-automated cancer therapy treatment system 1200 is described. In this example, a cancer treatment plan is

2017208222 24 Jul 2017 generated semi-autonomously or autonomously using the main controller 110 and the process of semi-autonomous cancer treatment system. More particularly, the process of semi-autonomous cancer treatment 1220 uses input from: (1) a semi-autonomously patient positioning step 1222; (2) a semi5 autonomous tumor imaging step 1224, and/or for the fiducial indicators 1140;

and/or (3) a software coded set of radiation treatment directives with optional weighting parameters. For example, the treatment directives comprise a set of criteria to: (1) treat the tumor 220; (2) while reducing energy delivery of the charged particle beam outside of the tumor 220; minimizing or greatly reducing 10 passage of the charged particle beam into a high value element, such as an eye, nerve center, or organ, the process of semi-autonomous cancer treatment 1220 optionally auto-generates the original radiation treatment plan 1226. The autogenerated original radiation treatment plan 1226 is optionally auto-implemented, such as via the deliver charged particles step 1226, and/or is optionally reviewed 15 by a doctor, such as in the doctor oversight 1230 process, described supra.

Optionally and preferably, the semi-autonomous imaging step 1224 generates and/or uses data from: (1) one or more proton scans from an imaging system using protons to image the tumor 220; (2) one or more X-ray images using one or more X-ray imaging systems; (3) a positron emission system; (4) a computed 20 tomography system; and/or (5) any imaging technique or system described herein.

The inventor notes that traditionally days pass between imaging the tumor and treating the tumor while a team of oncologists develop a radiation plan. In stark 25 contrast, using the autonomous imaging and treatment steps described herein, such as implemented by the main controller 110, the patient optionally remains in the treatment room and/or in a treatment position in a patient positioning system from the time of imaging, through the time of developing a radiation plan, and through at least a first tumor treatment session.

2017208222 24 Jul 2017

Example VI

Referring still to Figure 12, a sixth example of the semi-automated cancer therapy treatment system 1200 is described. In this example, the deliver charged particle step 1228, using a current radiation treatment plan, is adjusted autonomously or semi-autonomously using concurrent and/or interspersed images from the semi-autonomously imaging system 1224 as interpreted, such as via the process of semi-automated cancer treatment 1220 and input from the fiducial indicators 1140 and/or the semi-automated patient position system 1222.

Referring now to Figure 13, a system for developing a radiation treatment plan 1310 using positively charged particles is described. More particularly, a semiautomated radiation treatment plan development system 1300 is described, where the semi-automated system is optionally fully automated or contains fully automated sub-processes.

The computer implemented algorithm, such as implemented using the main controller 110, in the automated radiation treatment plan development system 1300 generates a score, sub-score, and/or output to rank a set of auto-generated potential radiation treatment plans, where the score is used in determination of a 20 best radiation treatment plan, a proposed radiation treatment plan, and/or an auto-implemented radiation treatment plan.

Still referring to Figure 13, the semi-automated or automated radiation treatment plan development system 1300 optionally and preferably provides a set of inputs, 25 guidelines, and/or weights to a radiation treatment development code that processes the inputs to generate an optimal radiation treatment plan and/or a preferred radiation treatment plan based upon the inputs, guidelines, and/or weights. An input is a goal specification, but not an absolute fixed requirement. Input goals are optionally and preferably weighted and/or are associated with a

2017208222 24 Jul 2017 hard limit. Generally, the radiation treatment development code uses an algorithm, an optimization protocol, an intelligent system, computer learning, supervised, and/or unsupervised algorithmic approach to generating a proposed and/or immediately implemented radiation treatment plan, which are compared 5 via the score described above. Inputs to the semi-automated radiation treatment plan development system 1300 include images of the tumor 220 of the patient 230, treatment goals, treatment restrictions, associated weights to each input, and/or associated limits of each input. To facilitate description and understanding of the invention, without loss of generality, optional inputs are 10 illustrated in Figure 13 and further described herein by way of a set of examples.

Example I

Still referring to Figure 13, a first input to the semi-automated radiation treatment plan development system 1300, used to generate the radiation treatment plan 15 1310, is a requirement of dose distribution 1320. Herein, dose distribution comprises one or more parameters, such as a prescribed dosage 1321 to be delivered; an evenness or uniformity of radiation dosage distribution 1322; a goal of reduced overall dosage 1323 delivered to the patient 230; a specification related to minimization or reduction of dosage delivered to critical voxels 1324 of 20 the patient 230, such as to a portion of an eye, brain, nervous system, and/or heart of the patient 230; and/or an extent of, outside a perimeter of the tumor, dosage distribution 1325. The automated radiation treatment plan development system 1300 calculates and/or iterates a best radiation treatment plan using the inputs, such as via a computer implemented algorithm.

Each parameter provided to the automated radiation treatment plan development system 1300, optionally and preferably contains a weight or importance. For clarity of presentation and without loss of generality, two cases illustrate.

2017208222 24 Jul 2017

In a first case, a requirement/goal of reduction of dosage or even complete elimination of radiation dosage to the optic nerve of the eye, provided in the minimized dosage to critical voxels 1324 input is given a higher weight than a requirement/goal to minimize dosage to an outer area of the eye, such as the 5 rectus muscle, or an inner volume of the eye, such as the vitreous humor of the eye. This first case is exemplary of one input providing more than one sub-input where each sub-input optionally includes different weighting functions.

In a second case, a first weight and/or first sub-weight of a first input is compared 10 with a second weight and/or a second sub-weight of a second input. For instance, a distribution function, probability, or precision of the even radiation dosage distribution 1322 input optionally comprises a lower associated weight than a weight provided for the reduce overall dosage 1323 input to prevent the computer algorithm from increasing radiation dosage in an attempt to yield an 15 entirely uniform dose distribution.

Each parameter and/or sub-parameter provided to the automated radiation treatment plan development system 1300, optionally and preferably contains a limit, such as a hard limit, an upper limit, a lower limit, a probability limit, and/or a 20 distribution limit. The limit requirement is optionally used, by the computer algorithm generating the radiation treatment plan 1310, with or without the weighting parameters, described supra.

Example II

Still referring to Figure 13, a second input to the semi-automated radiation treatment plan development system 1300, is a patient motion 1330 input. The patient motion 1330 input comprises: a move the patient in one direction 1332 input, a move the patient at a uniform speed 1333 input, a total patient rotation 1334 input, a patient rotation rate 1335 input, and/or a patient tilt 1336 input. For

2017208222 24 Jul 2017 clarity of presentation and without loss of generality, the patient motion inputs are further described, supra, in several cases.

Still referring to Figure 13, in a first case the automated radiation treatment plan development system 1300, provides a guidance input, such as the move the patient in one direction 1332 input, but a further associated directive is if other goals require it or if a better overall score of the radiation treatment plan 1310 is achieved, the guidance input is optionally automatically relaxed. Similarly, the move the patient at a uniform rate 1333 input is also provided with a guidance 10 input, such as a low associated weight that is further relaxable to yield a high score, of the radiation treatment plan 1310, but is only relaxed or implemented an associated fixed or hard limit number of times.

Still referring to Figure 13, in a second case the computer implemented algorithm, in the automated radiation treatment plan development system 1300, optionally generates a sub-score. For instance, a patient comfort score optionally comprises a score combining a metric related to two or more of: the move the patient in one direction 1332 input, the move the patient at a uniform rate 1333 input, the total patient rotation 1334 input, the patient rotation rate 1335 20 input, and/or the reduce patient tilt 1336 input. The sub-score, which optionally has a preset limit, allows flexibility, in the computer implemented algorithm, to yield on patient movement parameters as a whole, again to result in patient comfort.

Still referring to Figure 13, in a third case the automated radiation treatment plan development system 1300 optionally contains an input used for more than one sub-function. For example, a reduce treatment time 1331 input is optionally used as a patient comfort parameter and also links into the dose distribution 1320 input.

2017208222 24 Jul 2017

Example III

Still referring to Figure 13, a third input to the automated radiation treatment plan development system 1300 comprises output of an imaging system, such as any 5 of the imaging systems described herein.

Example IV

Still referring to Figure 13, a fourth optional input to the automated radiation treatment plan development system 1300 is structural and/or physical elements 10 present in the treatment room 922. Again, for clarity of presentation and without loss of generality, two cases illustrate treatment room object information as an input to the automated development of the radiation treatment plan 1310.

Still referring to Figure 13, in a first case the automated radiation treatment plan 15 development system 1300 is optionally provided with a pre-scan of potentially intervening support structures 1382 input, such as a patient support device, a patient couch, and/or a patient support element, where the pre-scan is an image/density/redirection impact of the support structure on the positively charged particle treatment beam. Preferably, the pre-scan is an actual image or 20 tomogram of the support structure using the actual facility synchrotron, a remotely generated actual image, and/or a calculated impact of the intervening structure on the positively charge particle beam. Determination of impact of the support structure on the charged particle beam is further described, infra.

Still referring to Figure 13, in a second case the automated radiation treatment plan development system 1300 is optionally provided with a reduce treatment through a support structure 1344 input. As described supra, an associated weight, guidance, and/or limit is optionally provided with the reduce treatment through the support structure 1344 input and, also as described supra, the

2017208222 24 Jul 2017 support structure input is optionally compromised relative to a more critical parameter, such as the deliver prescribed dosage 1321 input or the minimize dosage to critical voxels 1324 of the patient 230 input.

Example V

Still referring to Figure 13, a fifth optional input to the automated radiation treatment plan development system 1300 is a doctor input 1236, such as provided only prior to the auto generation of the radiation treatment plan. Separately, doctor oversight 1230 is optionally provided to the automated 10 radiation treatment plan development system 1300 as plans are being developed, such as an intervention to restrict an action, an intervention to force an action, and/or an intervention to change one of the inputs to the automated radiation treatment plan development system 1300 for a radiation plan for a particular individual.

Example VI

Still referring to Figure 13, a sixth input to the automated radiation treatment plan development system 1300 comprises information related to collapse and/or shifting of the tumor 220 of the patient 230 during treatment. For instance, the 20 radiation treatment plan 1310 is automatically updated, using the automated radiation treatment plan development system 1300, during treatment using an input of images of the tumor 220 of the patient 230 collected concurrently with treatment using the positively charged particles. For instance, as the tumor 220 reduces in size with treatment, the tumor 220 collapses inward and/or shifts. The 25 auto-updated radiation treatment plan is optionally auto-implemented, such as without the patient moving from a treatment position. Optionally, the automated radiation treatment plan development system 1300 tracks dosage of untreated voxels of the tumor 220 and/or tracks partially irradiated, relative to the prescribed dosage 1321, voxels and dynamically and/or automatically adjusts the

2017208222 24 Jul 2017 radiation treatment plan 1310 to provide the full prescribed dosage to each voxel despite movement of the tumor 220. Similarly, the automated radiation treatment plan development system 1300 tracks dosage of treated voxels of the tumor 220 and adjusts the automatically updated tumor treatment plan to reduce and/or 5 minimize further radiation delivery to the fully treated and shifted tumor voxels while continuing treatment of the partially treated and/or untreated shifted voxels of the tumor 220.

Automated Adaptive Treatment

Referring now to Figure 14, a system for automatically updating the radiation treatment plan 1400 and preferably automatically updating and implementing the radiation treatment plan is illustrated. In a first task 1410, an initial radiation treatment plan is provided, such as the auto-generated radiation treatment plan 1226, described supra. The first task is a startup task of an iterative loop of tasks 15 and/or recurring set of tasks, described herein as comprising tasks two to four.

In a second task 1420, the tumor 220 is treated using the positively charged particles delivered from the synchrotron 130. In a third task 1430, changes in the tumor shape and/or changes in the tumor position relative to surrounding constituents of the patient 230 are observed, such as via any of the imaging 20 systems described herein. The imaging optionally occurs simultaneously, concurrently, periodically, and/or intermittently with the second task while the patient remains positioned by the patient positioning system. The main controller 110 uses images from the imaging system(s) and the provided and/or current radiation treatment plan to determine if the treatment plan is to be followed or 25 modified. Upon detected relative movement of the tumor 220 relative to the other elements of the patient 230 and/or change in a shape of the tumor 230, a fourth task 1440 of updating the treatment plan is optionally and preferably automatically implemented and/or use of the radiation treatment plan development system 1300, described supra, is implemented. The process of 30 tasks two to four is optionally and preferably repeated n times where n is a

2017208222 24 Jul 2017 positive integer of greater than 1, 2, 5, 10, 20, 50, or 100 and/or until a treatment session of the tumor 220 ends and the patient 230 departs the treatment room 922.

Automated Treatment

Referring now to Figure 15, an automated cancer therapy treatment system 1500 is illustrated. In the automated cancer therapy treatment system 1500, a majority of tasks are implemented according to a computer based algorithm and/or an intelligent system. Optionally and preferably, a medical professional oversees 10 the automated cancer therapy treatment system 1500 and stops or alters the treatment upon detection of an error but fundamentally observes the process of computer algorithm guided implementation of the system using electromechanical elements, such as any of the hardware and/or software described herein. Optionally and preferably, each sub-system and/or sub-task is 15 automated. Optionally, one or more of the sub-systems and/or sub-tasks are performed by a medical professional. For instance, the patient 230 is optionally initially positioned in the patient positioning system by the medical professional and/or the nozzle system 146 inserts are loaded by the medical professional. Optional and preferably automated, such as computer algorithm implemented, 20 sub-tasks include one or more and preferably all of:

• receiving the treatment plan input 1300, such as a prescription, guidelines, patient motion guidelines 1330, dose distribution guidelines 1320, intervening object 1310 information, and/or images of the tumor 220;

• using the treatment plan input 1300 to auto-generate a radiation treatment plan 1226;

• auto-positioning 1222 the patient 230;

• auto-imaging 1224 the tumor 220;

• implementing medical profession oversight 1238 instructions;

2017208222 24 Jul 2017 • auto-implementing the radiation treatment plan 1420 / delivering the positively charged particles to the tumor 220;

• auto-reposition the patient 1421 for subsequent radiation delivery;

• auto-rotate a nozzle position 1422 of the nozzle system 146 relative to the patient 230;

• auto-translate a nozzle position 1423 of the nozzle system 146 relative to the patient 230;

• auto-verify a clear treatment path using an imaging system, such as to observe presence of a metal object or unforeseen dense object via an

X-ray image;

• auto-verify a clear treatment path using fiducial indicators 1424;

• auto control a state of the positively charge particle beam 1425, such as energy, intensity, position (x,y,z), duration, and/or direction;

• auto-control a particle beam path 1426, such as to a selected beamline and/or to a selected nozzle;

• auto implement positioning a tray insert and/or tray assembly;

• auto-update a tumor image 1510;

• auto-observe tumor movement 1430; and/or • generate an auto-modified radiation treatment plan 1440 / new treatment plan.

Still yet another embodiment includes any combination and/or permutation of any of the elements described herein.

The main controller, a localized communication apparatus, and/or a system for communication of information optionally comprises one or more subsystems stored on a client. The client is a computing platform configured to act as a client device or other computing device, such as a computer, personal computer, a digital media device, and/or a personal digital assistant. The client comprises a processor that is optionally coupled to one or more internal or external input

2017208222 24 Jul 2017 device, such as a mouse, a keyboard, a display device, a voice recognition system, a motion recognition system, or the like. The processor is also communicatively coupled to an output device, such as a display screen or data link to display or send data and/or processed information, respectively. In one 5 embodiment, the communication apparatus is the processor. In another embodiment, the communication apparatus is a set of instructions stored in memory that is carried out by the processor.

The client includes a computer-readable storage medium, such as memory. The 10 memory includes, but is not limited to, an electronic, optical, magnetic, or another storage or transmission data storage medium capable of coupling to a processor, such as a processor in communication with a touch-sensitive input device linked to computer-readable instructions. Other examples of suitable media include, for example, a flash drive, a CD-ROM, read only memory (ROM), random access 15 memory (RAM), an application-specific integrated circuit (ASIC), a DVD, magnetic disk, an optical disk, and/or a memory chip. The processor executes a set of computer-executable program code instructions stored in the memory.

The instructions may comprise code from any computer-programming language, including, for example, C originally of Bell Laboratories, C++, C#, Visual Basic® 20 (Microsoft, Redmond, WA), Matlab® (MathWorks, Natick, MA), Java® (Oracle

Corporation, Redwood City, CA), and JavaScript® (Oracle Corporation, Redwood City, CA).

Herein, any number, such as 1, 2, 3, 4, 5, is optionally more than the number, 25 less than the number, or within 1,2,5, 10, 20, or 50 percent of the number.

Herein, an element and/or object is optionally manually and/or mechanically moved, such as along a guiding element, with a motor, and/or under control of the main controller.

2017208222 24 Jul 2017

The particular implementations shown and described are illustrative of the invention and its best mode and are not intended to otherwise limit the scope of the present invention in any way. Indeed, for the sake of brevity, conventional 5 manufacturing, connection, preparation, and other functional aspects of the system may not be described in detail. Furthermore, the connecting lines shown in the various figures are intended to represent exemplary functional relationships and/or physical couplings between the various elements. Many alternative or additional functional relationships or physical connections may be 10 present in a practical system.

In the foregoing description, the invention has been described with reference to specific exemplary embodiments; however, it will be appreciated that various modifications and changes may be made without departing from the scope of the 15 present invention as set forth herein. The description and figures are to be regarded in an illustrative manner, rather than a restrictive one and all such modifications are intended to be included within the scope of the present invention. Accordingly, the scope of the invention should be determined by the generic embodiments described herein and their legal equivalents rather than by 20 merely the specific examples described above. For example, the steps recited in any method or process embodiment may be executed in any order and are not limited to the explicit order presented in the specific examples. Additionally, the components and/or elements recited in any apparatus embodiment may be assembled or otherwise operationally configured in a variety of permutations to 25 produce substantially the same result as the present invention and are accordingly not limited to the specific configuration recited in the specific examples.

Benefits, other advantages and solutions to problems have been described 30 above with regard to particular embodiments; however, any benefit, advantage,

2017208222 24 Jul 2017 solution to problems or any element that may cause any particular benefit, advantage or solution to occur or to become more pronounced are not to be construed as critical, required or essential features or components.

As used herein, the terms “comprises”, “comprising”, or any variation thereof, are intended to reference a non-exclusive inclusion, such that a process, method, article, composition or apparatus that comprises a list of elements does not include only those elements recited, but may also include other elements not expressly listed or inherent to such process, method, article, composition or 10 apparatus. Other combinations and/or modifications of the above-described structures, arrangements, applications, proportions, elements, materials or components used in the practice of the present invention, in addition to those not specifically recited, may be varied or otherwise particularly adapted to specific environments, manufacturing specifications, design parameters or other 15 operating requirements without departing from the general principles of the same.

Although the invention has been described herein with reference to certain preferred embodiments, one skilled in the art will readily appreciate that other 20 applications may be substituted for those set forth herein without departing from the spirit and scope of the present invention. Accordingly, the invention should only be limited by the Claims included below.

Further, the reference to any prior art in this specification is not, and should not 25 be taken as, an acknowledgement or any form of suggestion that the referenced prior art forms part of the common general knowledge in Australia.

Claims (5)

1. An apparatus for treating a tumor of a patient, positioned at a patient position, with positively charged particles in a treatment room, comprising:

a synchrotron connected to an exit nozzle system, proximate the treatment

5 room, by a beam transport line, said exit nozzle system supported by a rotatable section of a gantry system, the positively charged particles passing through said rotatable section of said gantry system during use;

a main controller provided an initial radiation treatment plan, said main controller configured to implement the initial radiation treatment plan, as a current 10 radiation treatment plan, using the positively charged particles delivered from said synchrotron, along said beam transport line, through said exit nozzle system, and into the tumor;

an imaging system configured to, concurrent with implementation of the current radiation treatment plan by said main controller, image the tumor to 15 generate a current image, at least a portion of said imaging system mounted to said rotatable section of said gantry system;

said main controller configured to, upon detection of an inward collapse of a shape of the tumor of the patient using the current image, automatically generate an updated treatment plan, the updated treatment plan becoming the current 20 radiation treatment plan; and said main controller, during a single treatment session, configured to repeat the implementation of the current radiation treatment plan, use the current image, and generate the updated treatment plan at least n times, where n is a positive integer of at least one.

2. The apparatus of Claim 1, said imaging system further comprising:

a scintillation detector system, positioned on an opposite side of the patient from said exit nozzle system, configured to detect a proton, of the positively charged particles; and

2017208222 11 Feb 2019 a first sheet, positioned between the patient and said scintillation detector system, configured to emit first photons upon the proton traversing said first sheet.

3. The apparatus of Claim 2, said main controller further comprising:

5 computer implemented code configured to calculate a beam path of the proton between the patient position and the scintillation detector system using output of a first detector element optically coupled to said first sheet and output of said scintillation detector system.

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4. The apparatus of Claim 2, said computer implemented code further comprising:

an unsupervised computer implemented algorithm using a set of computer coded inputs to automatically generate the updated treatment plan.

15 5. The apparatus of Claim 4, said unsupervised computer implemented algorithm configured to automatically provide at least changes in the updated treatment plan relative to a prior version of the current radiation treatment plan, said main controller configured to implement and proceed with treatment of the tumor while using said updated treatment plan during a review of the changes.

6. The apparatus of Claim 4, said main controller configured to automatically implement said updated treatment plan provided by said unsupervised computer implemented algorithm without an explicit real-time approval to continue provided by a medical professional.

7. The apparatus of Claim 1, said main controller configured to move said exit nozzle system into an unplanned for position, in the original radiation treatment plan, according to the updated treatment plan.

2017208222 11 Feb 2019

8. The apparatus of Claim 7, said main controller, in said generation of said updated treatment plan, configured to use all of:

the current image;

5 input dose distribution parameters;

input patient motion parameters; and a dynamic state-space model of a movable treatment room object, said dynamic state space model comprising a geometry of the movable treatment room object.

9. The apparatus of Claim 8, further comprising at least one fiducial indicator mounted to at least one movable treatment room object comprising equipment in a beam path of the positively charged particles, said main controller configured to use output of said at least one fiducial 15 indicator in generation of the updated radiation treatment plan, computer implemented code, of said main controller, configured to automatically increase energy of particles extracted from said synchrotron to yield an energy requirement of the initial radiation treatment plan for a voxel of the tumor after loss of energy passing through the movable treatment room object as directed by the updated 20 treatment plan.

10. The apparatus of Claim 1, further comprising a fiducial indicator mounted to a movable treatment room object, said main controller further comprising computer implemented code configured to use output 25 of said at least one fiducial indicator in generation of the updated radiation treatment plan, said computer implemented code configured to automatically increase energy of particles extracted from said synchrotron to compensate for

2017208222 11 Feb 2019 passage through the movable treatment room object as directed by the updated treatment plan.

11. The apparatus of Claim 2, said main controller further comprising:

5 computer implemented code configured to calculate an exit point of the proton from the patient using output of a first detector element optically coupled to said first sheet and output of said scintillation detector system.

12. The apparatus of Claim 2, said imaging system further comprising:

10 a second sheet, positioned between said exit nozzle system and the patient, configured to emit second photons upon the proton traversing said second sheet; and a third sheet, positioned between said second sheet and the patient, configured to emit third photons upon the proton traversing said third sheet.

13. The apparatus of Claim 2, said computer imaging system further comprising:

a positron emission tomography system, rotatable about the patient, comprising a source and a detector continually out of a path of the positively 20 charged particles.

14. The apparatus of Claim 13, said computer implemented code configured to operate said positron emission tomography system while the positively charged particles are being delivered to the patient.

15. The apparatus of Claim 14, said imaging system further comprising:

2017208222 11 Feb 2019 an X-ray system configured to co-rotate and co-translate with said positron emission tomography system.

16. The apparatus of Claim 15, further comprising:

5 a gantry configured to rotate about an axis of rotation, said gantry comprising a counterweight counter balance, on a first side of the axis of rotation, comprising a first moment of force within ten percent of a second moment of force of elements of said gantry on an opposite side of the axis of rotation.

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17. The apparatus of Claim 1, further comprising:

a gantry configured to rotate about an axis of rotation passing within one meter of the patient during use, said gantry comprising:

all movable counterweight elements, on a first side of the axis of rotation, comprising a first combined moment of force; and

15 all movable gantry elements, on a second side of the axis of rotation opposite the first side of the axis of rotation, comprising a second moment of force within ten percent of the first moment of force.

2017208222 11 Feb 2019

18. A method for treating a tumor of a patient with positively charged particles in a treatment room, comprising the steps of:

providing an initial radiation treatment plan;

a main controller implementing the initial radiation treatment plan, as a

5 current radiation treatment plan, using the positively charged particles delivered from a synchrotron, along a beam transport line, through an exit nozzle system proximate the treatment room, and into the tumor, said exit nozzle system supported by a rotatable section of a gantry system;

the positively charged particles passing through said rotatable section of 10 said gantry system during use;

concurrent with said step of implementing, imaging the tumor to generate a current image;

upon detection of an inward collapse of a shape of the tumor of the patient using the current image, said main controller automatically generating an updated 15 treatment plan, the updated treatment plan becoming the current radiation treatment plan; and during a single treatment session, repeating said steps of implementing, imaging, and generating the updated treatment plan at least n times, where n is a positive integer of at least one.