Method and apparatus for facilitating optimizing a radiation treatment plan

Abstract

A control circuit (101) is configured to optimize a radiation treatment plan for a given patient (104) as a function, at least in part, of minimizing (402) collateral harm to immune system components for the given patient by, at least in part, identifying and protecting immunity-related organs and / or immunity-related organ substructures.

Description

METHOD AND APPARATUS FOR FACILITATING OPTIMIZING ARADIATION TREATMENT PLANTECHNICAL FIELD

[0001] These teachings relate generally to treating a patient's planning target volume with energy pursuant to an energy-based treatment plan and more particularly to optimizing an energy-based treatment plan.BACKGROUND

[0002] The use of energy to treat medical conditions comprises a known area of prior art endeavor. For example, radiation therapy comprises an important component of many treatment plans for reducing or eliminating unwanted tumors. Unfortunately, applied energy does not inherently discriminate between unwanted material and adjacent tissues, organs, or the like that are desired or even critical to continued survival of the patient. As a result, energy such as radiation is ordinarily applied in a carefully administered manner to at least attempt to restrict the energy to a given target volume. A so-called radiation treatment plan often serves in the foregoing regards.

[0003] A radiation treatment plan typically comprises specified values for each of a variety of treatment-platform parameters during each of a plurality of sequential fields. Treatment plans for radiation treatment sessions are often automatically generated through a so-called optimization process. As used herein, "optimization" will be understood to refer to improving a candidate treatment plan without necessarily ensuring that the optimized result is, in fact, the singular best solution. Such optimization often includes automatically adjusting one or more physical treatment parameters (often while observing one or more corresponding limits in these regards) and mathematically calculating a likely corresponding treatment result (such as a level of dosing) to identify a given set of treatment parameters that represent a good compromise between the desired therapeutic result and avoidance of undesired collateral effects.

[0004] Proper functioning of the immune system can help support tumor control. However, during radiotherapy, at least some healthy immune-related organs and substructures can be damaged by radiation exposure, depending on the treated area. These damages not only affect the function of immune related organs - for instance, the irradiation of bone marrow can reduce immune cell generation - but the applicant has determined that they also impact the overall immune cell composition. For example, radiation doses over 0.5Gy can trigger significant CD8 T cells apoptosis in the circulating system. Such damages can result in a compromised immune system, affecting both the efficacy of tumor control by radiotherapy alone and also the potential synergistic effects of radiotherapy and immunotherapy combined treatment.BRIEF DESCRIPTION OF DRAWINGS

[0005] The above needs are at least partially met through provision of the method and apparatus for facilitating optimizing a radiation treatment plan described in the following detailed description, particularly when studied in conjunction with the drawings, wherein:

[0006] FIG. 1 comprises a block diagram as configured in accordance with various embodiments of these teachings;

[0007] FIG. 2 comprises a block diagram as configured in accordance with various embodiments of these teachings;

[0008] FIG. 3 comprises a schematic representation as configured in accordance with various embodiments of these teachings;

[0009] FIG. 4 comprises a flow diagram as configured in accordance with various embodiments of these teachings;

[0010] FIG. 5 comprises a flow diagram as configured in accordance with various embodiments of these teachings;

[0011] FIG. 6 comprises a flow diagram as configured in accordance with various embodiments of these teachings;

[0012] FIG. 7 comprises a flow diagram as configured in accordance with various embodiments of the invention; and

[0013] FIG. 8 comprises a block diagram as configured in accordance with various embodiments of these teachings.

[0014] Elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions and / or relative positioning of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various embodiments of the present teachings. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are often not depicted in order to facilitate a less obstructed view of these various embodiments of the present teachings. Certain actions and / or steps may be described or depicted in a particular order of occurrence while those skilled in the art will understand that such specificity with respect to sequence is not actually required. The terms and expressions used herein have the ordinary technical meaning as is accorded to such terms and expressions by persons skilled in the technical field as set forth above except where different specific meanings have otherwise been set forth herein. The word "or" when used herein shall be interpreted as having a disjunctive construction rather than a conjunctive construction unless otherwise specifically indicated.DETAILED DESCRIPTION

[0015] The applicant has determined that an impaired immune system could be a key reason behind the failure of at least some clinical trials of combined radiotherapy and immunotherapy combined therapy. The applicant has therefore determined that it can be important to spare immune-related organs, substructures, and within immune cells during radiotherapy for better patient outcomes. Previous approaches to address such a concern tend to focus only on sparing circulating immune cells (i.e., lymphocytes in the bloodstream), and the applicant has determined that, at least in some application settings, a broader view can be more efficacious.

[0016] Generally speaking, pursuant to these various embodiments, a control circuit is configured to optimize a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for thegiven patient by, at least in part, identifying and protecting immunity-related organs and / or immunity-related organ substructures.

[0017] The foregoing immune system components may include, for example, at least one of, primary lymphoid organs (including bone marrow and thymus), secondary lymphoid organs (including lymph nodes and spleen), non-lymphoid organs (including but not limited to heart, liver, lung, kidney and digestive tract, these not being primarily associated with the lymphatic system but also being important for the immune system), organ substructures, tissue resident immune cells, and circulating immune cells. The term "tissue-resident immune cells" is herein loosely defined. They are the immune cells that long-term reside in all organs of the body including but not limited to the heart, liver, lung, kidney, and digestive tract. The specific expression profile and functional characteristics distinguish them from the circulating immune cells in the bloodstream.

[0018] The foregoing protection can comprise, for example, minimizing collateral harm to immune system physiological functionality that corresponds to the immune system components. Examples in the foregoing regards include, but are not limited to, immune cell generation, immune cell maturation, immune cell priming, immune cell circulating, immune cell residence, and immunological memory.

[0019] The foregoing optimization may comprise, for example, optimizing the radiation treatment plan as a function of at least one of a type of immune cell residents in at least one segmented volume (such as, but not limited to, a segmented organ substructure) and / or a number corresponding to immune cells that are resident in at least one segmented volume. In these regards, identifying and protecting immunity-related organs and / or immunity-related organ substructures may comprise at least one of identifying and quantifying resident immune cells based on clustering and marker gene annotation of single cell RNA-sequencing, identifying and quantifying resident immune cells based on a gene expression profile of bulk RNA-sequencing, and / or identifying and quantifying resident immune cells based on histological staining images including but not limited to immunohistochemistry and immunofluorescence.

[0020] By another approach, in lieu of the foregoing or in combination therewith, the foregoing optimization may comprise, at least in part, optimizing the radiationtreatment plan as a function of prioritizing amongst at least some of the immune system components based on immune system efficacy. Such prioritizing may be based, at least in part, on a volume of circulating blood passing through a particular patient volume, types and frequencies of resident immune cells in a particular patient volume, a relative radiation risk tissue weighting factor for a particular patient volume, and / or frequencies of hematopoietic stem cells in a particular patient volume. As a particular example in these regards, when the aforementioned immune system components comprise bone marrow, because red bone marrow contains a higher percentage of hematopoietic stem cells for immune cell generation while yellow bone marrow consists mostly of fat cells, these teachings will accommodate differentiating between yellow bone marrow and red bone marrow, such that red bone marrow can be prioritized to receive less radiation than yellow bone marrow for better protection of the immune system.

[0021] By yet another approach, again in lieu of any of the foregoing or in combination therewith, the foregoing optimization may comprise, at least in part, optimizing the radiation treatment plan as a function of characterizing different regions of a given one of the immune system components (such as, for example, a lymph node) based on a corresponding contribution of each region to immune system operability. This approach will allow, for example, for differentiating between an involved lymph node and an uninvolved lymph node, such that involved draining lymph nodes that contain metastatic tumor cells and exhausted T cells can be prioritized for elimination by irradiation while uninvolved lymph nodes that contain immune progenitor cells and dendritic cells that are key for initiation and maintenance of a strong immune response can be prioritized for protection.

[0022] These teachings are highly flexible in practice and will accommodate various modifications and / or supplemental features. As but one example in these regards, these teachings will accommodate automatically segmenting organ substructures to provide segmented organ substructures from medical images based on machine learning models. In this case, the above-mentioned immune system components can include at least some of those segmented organ substructures or even the whole segmented organ.

[0023] Generally speaking, these teachings provide a systematic methodology to identify and spare immune-related organs and substructures based on an understanding of the immune system itself. By better sparing the immune functions during radiotherapy, these teachings can improve tumor control and patient outcomes.

[0024] By one approach, the foregoing includes accounting for the importance of the various organs and substructures in the immune system. By one approach, the foregoing includes specifically accounting for one more of immune cell generation, maturation, immune priming, and immunological memory. This can include accounting for at least three major components that together can impact an antitumor immune response, these being primary and secondary lymphoid organs, the organ substructures, and circulating immune cells.

[0025] By one approach, these teachings can comprise auto-segmentation of the primary and secondary lymphoid organs, a method to segment organ substructures, a method to determine the types and frequencies of resident immune cells in each organ and organ substructure, a method to determine the priority of different organs in the context of immune sparing, and a method to distinguish the regions of lymph nodes and bone marrow based on their contributions to the immune system.

[0026] These and other benefits may become clearer upon making a thorough review and study of the following detailed description. Referring now to the drawings, and in particular to FIG. 1, an illustrative apparatus 100 that is compatible with many of these teachings will first be presented.

[0027] In this particular example, the enabling apparatus 100 includes a control circuit 101. Being a "circuit," the control circuit 101 therefore comprises structure that includes at least one (and typically many) electrically-conductive paths (such as paths comprised of a conductive metal such as copper or silver) that convey electricity in an ordered manner, which path(s) will also typically include corresponding electrical components (both passive (such as resistors and capacitors) and active (such as any of a variety of semiconductor-based devices) as appropriate) to permit the circuit to effect the control aspect of these teachings.

[0028] Such a control circuit 101 can comprise a fixed-purpose hard-wired hardware platform (including but not limited to an application-specific integrated circuit (ASIC)(which is an integrated circuit that is customized by design for a particular use, rather than intended for general-purpose use), a field-programmable gate array (FPGA), and the like) or can comprise a partially or wholly-programmable hardware platform (including but not limited to microcontrollers, microprocessors, and the like). These architectural options for such structures are well known and understood in the art and require no further description here. This control circuit 101 is configured (for example, by using corresponding programming as will be well understood by those skilled in the art) to carry out one or more of the steps, actions, and / or functions described herein.

[0029] It will be appreciated that the control circuit 101 may comprise a single integrated platform or may comprise a plurality of such circuits that work in cooperation with one another, either locally or remotely.

[0030] The control circuit 101 operably couples to a memory 102. This memory 102 may be integral to the control circuit 101 or can be physically discrete (in whole or in part) from the control circuit 101 as desired. This memory 102 can also be local with respect to the control circuit 101 (where, for example, both share a common circuit board, chassis, power supply, and / or housing) or can be partially or wholly remote with respect to the control circuit 101 (where, for example, the memory 102 is physically located in another facility, metropolitan area, or even country as compared to the control circuit 101). As with the control circuit 101, the memory 102 may comprise a singular structure or may comprise a plurality of memory platforms that collectively comprise the "memory" of this apparatus 100.

[0031] In addition to information such as optimization information for a particular patient and information regarding a particular radiation treatment platform as described herein, this memory 102 can serve, for example, to non-transitorily store the computer instructions that, when executed by the control circuit 101, cause the control circuit 101 to behave as described herein. (As used herein, this reference to "non-transitorily" will be understood to refer to a non-ephemeral state for the stored contents (and hence excludes when the stored contents merely constitute signals or waves) rather than volatility of the storage media itself and hence includes both non-volatile memory (such as read-only memory (ROM) as well as volatile memory (such as a dynamic random access memory (DRAM).)

[0032] By one optional approach the control circuit 101 also operably couples to a user interface 103. This user interface 103 can comprise any of a variety of userinput mechanisms (such as, but not limited to, keyboards and keypads, cursorcontrol devices, touch-sensitive displays, speech-recognition interfaces, gesturerecognition interfaces, and so forth) and / or user-output mechanisms (such as, but not limited to, visual displays, audio transducers, printers, and so forth) to facilitate receiving information and / or instructions from a user and / or providing information to a user.

[0033] If desired the control circuit 101 can also operably couple to a network interface (not shown). So configured the control circuit 101 can communicate with other elements (both within the apparatus 100 and external thereto) via the network interface. Network interfaces, including both wireless and non-wireless platforms, are well understood in the art and require no particular elaboration here.

[0034] By one approach, a computed tomography apparatus 106 and / or other imaging apparatus 107 as are known in the art can source some or all of any desired patient-related imaging information.

[0035] In this illustrative example the control circuit 101 is configured to ultimately output an optimized energy-based treatment plan (such as, for example, an optimized radiation treatment plan 113). This energy-based treatment plan typically comprises specified values for each of a variety of treatment-platform parameters during each of a plurality of sequential exposure fields. In this case the energy-based treatment plan is generated through an optimization process, examples of which are provided further herein.

[0036] By one approach the control circuit 101 can operably couple to an energybased treatment platform 114 that is configured to deliver therapeutic energy 112 to a corresponding patient 104 having at least one treatment volume 105 and also one or more organs-at-risk (represented in FIG. 1 by a first through an Nth organ-at-risk 108 and 109) in accordance with the optimized energy-based treatment plan 113. These teachings are generally applicable for use with any of a wide variety of energybased treatment platforms / appa ratuses. In a typical application setting the energybased treatment platform 114 will include an energy source such as a radiation source 115 of ionizing radiation 116.

[0037] By one approach this radiation source 115 can be selectively moved via a gantry along an arcuate pathway (where the pathway encompasses, at least to some extent, the patient themselves during administration of the treatment). The arcuate pathway may comprise a complete or nearly complete circle as desired. By one approach the control circuit 101 controls the movement of the radiation source 115 along that arcuate pathway, and may accordingly control when the radiation source 115 starts moving, stops moving, accelerates, de-accelerates, and / or a velocity at which the radiation source 115 travels along the arcuate pathway.

[0038] As one illustrative example, the radiation source 115 can comprise, for example, a radio-frequency (RF) linear particle accelerator-based (linac-based) x-ray source. A linac is a type of particle accelerator that greatly increases the kinetic energy of charged subatomic particles or ions by subjecting the charged particles to a series of oscillating electric potentials along a linear beamline, which can be used to generate ionizing radiation (e.g., X-rays) 116 and high energy electrons.

[0039] A typical energy-based treatment platform 114 may also include one or more support apparatuses 110 (such as a couch) to support the patient 104 during the treatment session, one or more patient fixation apparatuses 111, a gantry or other movable mechanism to permit selective movement of the radiation source 115, and one or more energy-shaping apparatuses (for example, beam-shaping apparatuses 117 such as jaws, multi-leaf collimators, and so forth) to provide selective energy shaping and / or energy modulation as desired.

[0040] In a typical application setting, it is presumed herein that the patient support apparatus 110 is selectively controllable to move in any direction (i.e., any X, Y, or Z direction) during an energy-based treatment session by the control circuit 101. As the foregoing elements and systems are well understood in the art, further elaboration in these regards is not provided here except where otherwise relevant to the description.

[0041] Generally speaking, these teachings serve to help better protect various immune system components. These components may comprise entire organs but can also comprise substructures of those organs. FIG. 2 presents four illustrative organs and anatomical substructures 200 that are involved in the generation and maturation of immune cells in the human body with clinical relevance toradiotherapy used commonly to treat cancer. In this illustrative example, these include the spleen 201, bone marrow 202, the thymus 203, and lymph nodes 204. Various substructures are shown for each of the latter. For example, the spleen 201 is shown as including the trabecula 205, white pulp 206, the vascular sinusoid 207, and red pulp 208.

[0042] FIG. 3 illustrates in a general way that therapeutic energy 112 as described above can impact (and harm) organs 301 (and in particular tissue resident immune cells 302), immune cells 303 circulating in a blood vessel 304 through the aforementioned organ 301, and various components of bone marrow 305 including hematopoietic stem cells 306 that can differentiate into various types of blood cells including red blood cells 307, white blood cells 308, and platelets 309.

[0043] Referring now to FIG. 4, a process 400 that can be carried out, for example, in conjunction with the above-described application setting (and more particularly via the aforementioned control circuit 101) will be described. Generally speaking, this process 400 serves to facilitate generating an optimized radiation treatment plan 113 to thereby facilitate treating a particular patient 104 with therapeutic radiation 112 using a particular radiation treatment platform 114 per that optimized radiation treatment plan 113.

[0044] At optional block 401, this process 400 provides for automatically segmenting organ substructures to provide segmented organ substructures from medical images based on, for example, machine learning models. By one approach, the foregoing immune system components include at least some of the segmented organ substructures and / or the whole segmented organ. The foregoing medical images may, by one approach, be images captured by the above-described CT apparatus 106 and / or imaging apparatus 107.

[0045] At block 402, this process 400 provides for optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient by, at least in part, identifying and protecting immunity-related organs and / or immunity-related organ substructures. These teachings are flexible in practice and will accommodate a wide variety of immune system components such as at least one of primary lymphoid organs (including bone marrow and thymus), secondary lymphoid organs (includinglymph nodes and spleen), non-lymphoid organs (including but not limited to heart, liver, lungs, kidneys, etc.), organ substructures, tissue resident immune cells, and circulating immune cells.

[0046] These teachings can serve to improve tumor control because these teachings can specifically optimize a radiation treatment plan to protect organs that facilitate immune cell priming, activation, and / or tumor infiltration (for example, draining lymph nodes). These teachings can also protect immune system components that may not directly impact the functions of immune cells, but which may nevertheless facilitate immune cells for migration and localization.

[0047] By one approach, the foregoing comprises, at least in part, minimizing collateral harm to immune system physiological functionality corresponding to the immune system components. Examples of immune system physiological functionality include one or more of immune cell generation, immune cell maturation, immune cell priming, immune cell circulation, immune cell residency, and immunological memory.

[0048] The foregoing optimization can include any one or more of such things as adjusting one or more physical treatment parameters including but not limited to beam energies, beam directions, the number of beams, delivery time(s), dose rate(s), margin area, and any of a variety of other therapy modalities.

[0049] That said, the foregoing optimization can serve to protect immune system functionality in a variety of ways. Block 403 illustrates some of these approaches.

[0050] As one illustrative approach in those regards, such optimizing of the radiation treatment plan can be undertaken as a function, at least in part, of at least one of a type of immune cell that is resident in at least one segmented volume (such as, for example, a segmented organ substructure) and / or a number that corresponds to immune cells that are resident in at least one segmented volume. Examples of resident immune cells include, but are not limited to, tissue resident immune cells such as CD4 T cells, CD8 T cell, regulatory T cells, NK cells, B cells, Neutrophils, Macrophages, and Monocytes. The foregoing number that corresponds to immune cells may comprise, for example, an absolute number (such as the number of immune cells in a particular given volume) or a relative number (such as a ratio that compares one biological entity to another) as desired.

[0051] As another illustrative approach in these regards, in lieu of the foregoing or in combination therewith, optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient can comprise, at least in part, identifying and protecting immunity-related organs and / or immunity-related organ substructures by at least one of identifying and quantifying resident immune cells based on clustering and marker gene annotation e of single cell RNA-sequencing, identifying and quantifying resident immune cells based on a gene expression profile of bulk RNA- sequencing, and / or identifying and quantifying resident immune cells based on histological staining images including but not limited to immunohistochemistry and immunofluorescence.

[0052] As yet another illustrative approach in these regards, and again in lieu of the foregoing or in combination therewith, the foregoing optimizing can comprise optimizing the radiation treatment plan as a function of prioritizing amongst at least some of the immune system components based on their corresponding immune system efficacy. These teachings will accommodate any of a variety of prioritization criteria or approaches. Some useful examples include, but are not limited to, prioritizing based on at least one of a volume of circulating blood passing through a particular patient volume, types and frequencies of resident immune cells in a particular patient volume, a relative radiation risk tissue weighting factor for a particular patient volume, and / or frequencies of hematopoietic stem cells in a particular patient volume.

[0053] As a more specific example in the foregoing regards, when the immune system components include bone marrow, these teachings can provide for differentiating between yellow bone marrow and red bone marrow such that red bone marrow is prioritized over yellow bone marrow to receive less radiation than the yellow bone marrow (because red bone marrow contains a higher percentage of hematopoietic stem cells for immune cell generation while yellow bone marrow consists mostly of fat cells).

[0054] As yet another illustrative approach in these regards, and again in lieu of the foregoing or in combination therewith, the foregoing optimizing can comprise optimizing the radiation treatment plan as a function of characterizing differentregions of a given one of the immune system components based on a corresponding contribution of each region to immune system operability. For example, when the given one of the immune system components comprises a lymph node, these teachings will provide for differentiating between an involved lymph node (i.e., a lymph node that contains cancerous cells and exhausted T cells) and an uninvolved lymph node (i.e., a lymph node that doesn't contain cancerous cells but contains immune progenitor cells and dendritic cells, which is important for initiating and maintaining strong immune response), such that involved draining lymph nodes that contain metastatic tumor cells are prioritized for elimination by irradiation while uninvolved lymph nodes can be prioritized for protection.

[0055] Further details that comport with these teachings will now be presented. It will be understood that the specific details of these examples are intended to serve an illustrative purpose and are not intended to suggest any particular limitations with respect to these teachings.

[0056] FIG. 5 presents a number of illustrative approaches 500 in these regards. In particular, this example presents approaches 500 to quantify the percentage and to identify cell types of tissue-resident immune cells within organs to be protected. As regards a selected healthy organ 501, a first analysis considers single-cell RNA- sequence data 502 and annotates 503 by marker genes. A second analysis considers bulk RNA-sequence data 504 and deconvolutes 505 corresponding expression profiles. And a third analysis considers histology staining images 506 that correspond to the healthy organ 501 and provides for immunohistochemical and / or immunofluorescence staining 507 thereof (histology staining being a known technique in pathology and research that involves the detection of specific antigens (proteins) within cells of a tissue section). At block 508 the above-described outputs serve to identify cell type(s) and a percentage of tissue-resident immune cells. A number of illustrative examples in these regards are depicted at reference numeral 509.

[0057] FIG. 6 presents a process 600 for scoring the relative priority of relevant major organs and substructures that are involved in the immune system. For a given major organ (or a major organ substructure) 601 this process 600 provides for determining a number of different characterizing features / aspects. The latterinclude, in this illustrative example, blood volume 602 in the organ / substructure 601, types and frequencies of resident immune cells 603 in the organ / substructure 601, a relative radiation risk tissue weighting factor 604 (for example, per the 2007 recommendations of the International Commission on Radiological Protection), and frequencies of hematopoietic stem cells 605 in the organ / substructure 601. Applying one or more computational biology methods 606 of choice, this approach 600 can output a priority score 607 for the corresponding organ / substructure 601. The computational biology methods described herein for priority calculation include but are not limited to weighted average scoring or rank product analysis.

[0058] FIG. 7 presents an approach 700 for auto-segmentation of organ substructures based on machine learning. In a first step 701, this approach 700 captures the whole structure of a given organ using deep learning. In a next step 702, the large regions of the organ are segmented based on, for example, multi-atlas mapping (multi-atlas mapping being a known technique used to segment anatomical structures that uses multiple pre-labeled so-called atlas images to guide the segmentation of structures in a new, unlabeled target image). In a last step 703, geometric models can be used to fine tune small anatomical substructures to yield a final resultant image that delineates organ substructures within the organ.

[0059] FIG. 8 presents an illustrative example of a medical system 800 configured to identify and protect immune-related organs / substructures per these teachings. This medical system 800 includes a medical image receiver 801 that provides received medical images to a segmentation processor 802 that segments the medical images. The latter segmented images are then provided to a number of processors. A first processor 803 generates priorities for organs / substructures regarding to what relative degree the latter are to be protected from radiation (or not). A second process 804 differentiates amongst lymph nodes (for example, to identify which lymph nodes contain targeted volumes and which do not). And a third process 805 differentiates amongst different types of bone marrow within the segmented medical image(s). An advisory unit 806 receives the foregoing as input and provides corresponding results to a results display interface 807 for subsequent use by a user to better inform the optimization process.

[0060] So configured, these teachings can go beyond a mere generic approach for sparing organs at risk during radiotherapy by focusing on organs and substructures that are responsible for immune cell generation and maturation. The applicant has determined that this can be beneficial at least because limiting radiation exposure of the specific organs where immune cells originate and develop allows for better preservation of immune cells which have the potential to improve the efficacy of radiotherapy and radiotherapy-immunotherapy combinations.

[0061] Unlike many prior art approaches that consider entire organs homogeneously as regards immune functions, these teachings can account for substructures within organs and / or different regions of lymph nodes and bone marrow, which can have distinct immune functions. Accordingly, these teachings can provide for more precise substructure level sparing rather than bulk sparing for entire organs.

[0062] These teachings can also go beyond merely sparing circulating immune cells by also considering tissue resident immune cells and hematopoietic stem cells in bone marrow. Though often ignored by typical prior art practices, these cell types can also be important for the immune system.

[0063] It will further be appreciated that these teachings will support use of machine learning-based segmentation for identifying and sparing immune-related organs and substructures with high accuracy, thereby facilitating precise and targeted protection of the immune system.

[0064] Further aspects of these teachings are provided by the subject matter of the following clauses:

[0065] Clause 1. A method comprising: by a control circuit: optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient by, at least in part, identifying and protecting immunity-related organs and / or immunity-related organ substructures.

[0066] Clause 2. In combination with any one or more of the clauses contained herein, wherein minimizing collateral harm to the immune system components comprises minimizing collateral harm to immune system physiological functionality corresponding to the immune system components.

[0067] Clause 3. In combination with any one or more of the clauses contained herein, wherein the immune system physiological functionality includes at least one of: immune cell generation; immune cell maturation; immune cell priming; immune cell circulating; immune cell residence; and immunological memory.

[0068] Clause 4. In combination with any one or more of the clauses contained herein, wherein the immune system components include at least one of: primary lymphoid organs; secondary lymphoid organs; non-lymphoid organs; organ substructures; tissue resident immune cells; and circulating immune cells.

[0069] Clause 5. In combination with any one or more of the clauses contained herein, further comprising: automatically segmenting organ substructures to provide segmented organ substructures from medical images based on machine learning models; and wherein the immune system components include at least some of the segmented organ substructures and / or a whole segmented organ.

[0070] Clause 6. In combination with any one or more of the clauses contained herein, wherein optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient comprises, at least in part, optimizing the radiation treatment plan as a function of at least one of: a type of immune cell resident in at least one segmented volume; and a number corresponding to immune cells that are resident in at least one segmented volume.

[0071] Clause 7. In combination with any one or more of the clauses contained herein, wherein the at least one segmented volume comprises a segmented organ substructure.

[0072] Clause 8. In combination with any one or more of the clauses contained herein, wherein optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient includes, at least in part, identifying and protecting immunity-related organs and / or immunity-related organ substructures by at least one of: identifying and quantifying resident immune cells based on clustering and marker gene annotation of single cell RNA-sequencing; identifying and quantifying resident immune cells based on a gene expression profile of bulk RNA-sequencing;identifying and quantifying resident immune cells based on histology staining images.

[0073] Clause 9. In combination with any one or more of the clauses contained herein, wherein optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient comprises, at least in part, optimizing the radiation treatment plan as a function of prioritizing amongst at least some of the immune system components based on immune system efficacy.

[0074] Clause 10. In combination with any one or more of the clauses contained herein, wherein the prioritizing is based, on at least one of: a volume of circulating blood passing through a particular patient volume; types and frequencies of resident immune cells in a particular patient volume; a relative radiation risk tissue weighting factor for a particular patient volume; and frequencies of hematopoietic stem cells in a particular patient volume.

[0075] Clause 11. In combination with any one or more of the clauses contained herein, wherein optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient comprises, at least in part, optimizing the radiation treatment plan as a function of characterizing different regions of a given one of the immune system components based on a corresponding contribution of each region to immune system operability.

[0076] Clause 12. In combination with any one or more of the clauses contained herein, wherein the given one of the immune system components comprises a lymph node.

[0077] Clause 13. In combination with any one or more of the clauses contained herein, further comprising: differentiating between an involved lymph node and an uninvolved lymph node, such that: involved draining lymph nodes that contain metastatic tumor cells are prioritized for elimination by irradiation; and uninvolved lymph nodes are prioritized for protection.

[0078] Clause 14. In combination with any one or more of the clauses contained herein, wherein the given one of the immune system components comprises bone marrow.

[0079] Clause 15. In combination with any one or more of the clauses contained herein, further comprising: differentiating between yellow bone marrow and red bone marrow, such that red bone marrow is prioritized to be less radiated than yellow bone marrow.

[0080] Clause 16. An apparatus comprising: a control circuit configured to: optimize a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient.

[0081] Clause 17. In combination with any one or more of the clauses contained herein, wherein the immune system components include at least one of: immune cell generation; immune cell maturation; immune cell priming; and immunological memory.

[0082] Clause 18. In combination with any one or more of the clauses contained herein, wherein the immune system components include at least one of: primary lymphoid organs; secondary lymphoid organs; non-lymphoid organs; organ substructures; and circulating immune cells.

[0083] Clause 19. In combination with any one or more of the clauses contained herein, wherein the control circuit is further configured to: segment organ substructures to provide segmented organ substructures; and wherein the immune system components include at least some of the segmented organ substructures.

[0084] Clause 20. In combination with any one or more of the clauses contained herein, wherein the control circuit is further configured to optimize the radiation treatment plan for the given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient by, at least in part, optimizing the radiation treatment plan as a function of at least one of: a type of immune cell resident in at least one segmented volume; and a number of immune cells resident in at least one segmented volume.

[0085] Clause 21. In combination with any one or more of the clauses contained herein, wherein the at least one segmented volume comprises a segmented organ substructure.

[0086] Clause 22. In combination with any one or more of the clauses contained herein, wherein the control circuit is further configured to optimize the radiation treatment plan for the given patient as a function, at least in part, of minimizingcollateral harm to immune system components for the given patient by, at least in part, optimizing the radiation treatment plan as a function of prioritizing amongst at least some of the immune system components based on immune system efficacy.

[0087] Clause 23. In combination with any one or more of the clauses contained herein, wherein the control circuit is further configured to optimize the radiation treatment plan for the given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient by, at least in part, optimizing the radiation treatment plan as a function of characterizing different regions of a given one of the immune system components based on a corresponding contribution of each region to immune system operability.

[0088] Clause 24. In combination with any one or more of the clauses contained herein, wherein the given one of the immune system components comprises a lymph node.

[0089] Clause 25. In combination with any one or more of the clauses contained herein, wherein the given one of the immune system components comprises bone marrow.

[0090] Those skilled in the art will recognize that a wide variety of modifications, alterations, and combinations can be made with respect to the above described embodiments without departing from the scope of the invention, and that such modifications, alterations, and combinations are to be viewed as being within the ambit of the inventive concept.

Claims

Claims1. A method comprising: by a control circuit: optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient by, at least in part, identifying and protecting immunity-related organs and / or immunity-related organ substructures.

2. An apparatus comprising: a control circuit configured to: optimize a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient.

3. The method or apparatus of claim 1 or claim 2 wherein minimizing collateral harm to the immune system components comprises minimizing collateral harm to immune system physiological functionality corresponding to the immune system components.

4. The method or apparatus of claim 3 wherein the immune system physiological functionality includes at least one of: immune cell generation; immune cell maturation; immune cell priming; immune cell circulating; immune cell residence; and immunological memory.

5. The method or apparatus of claim 1 or claim 2 wherein the immune system components include at least one of: primary lymphoid organs; secondary lymphoid organs; non-lymphoid organs;organ substructures; tissue resident immune cells; and circulating immune cells.

6. The method or apparatus of claim 1 or claim 2 further comprising: automatically segmenting organ substructures to provide segmented organ substructures from medical images based on machine learning models; and wherein the immune system components include at least some of the segmented organ substructures and / or a whole segmented organ.

7. The method or apparatus of claim 1 or claim 2 wherein optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient comprises, at least in part, optimizing the radiation treatment plan as a function of at least one of: a type of immune cell resident in at least one segmented volume; and a number corresponding to immune cells that are resident in at least one segmented volume.

8. The method of apparatus of claim 7 wherein the at least one segmented volume comprises a segmented organ substructure.

9. The method or apparatus of claim 7 wherein optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient includes, at least in part, identifying and protecting immunity-related organs and / or immunity-related organ substructures by at least one of: identifying and quantifying resident immune cells based on clustering and marker gene annotation of single cell RNA-sequencing; identifying and quantifying resident immune cells based on a gene expression profile of bulk RNA-sequencing; identifying and quantifying resident immune cells based on histology staining images.

10. The method or apparatus of claim 1 or claim 2 wherein optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient comprises, at least in part, optimizing the radiation treatment plan as a function of prioritizing amongst at least some of the immune system components based on immune system efficacy.

11. The method or apparatus of claim 10 wherein the prioritizing is based, on at least one of: a volume of circulating blood passing through a particular patient volume; types and frequencies of resident immune cells in a particular patient volume; a relative radiation risk tissue weighting factor for a particular patient volume; and frequencies of hematopoietic stem cells in a particular patient volume.

12. The method or apparatus of claim 1 or claim 2 wherein optimizing a radiation treatment plan for a given patient as a function, at least in part, of minimizing collateral harm to immune system components for the given patient comprises, at least in part, optimizing the radiation treatment plan as a function of characterizing different regions of a given one of the immune system components based on a corresponding contribution of each region to immune system operability.

13. The method or apparatus of claim 12 wherein the given one of the immune system components comprises a lymph node.

14. The method or apparatus of claim 13 further comprising: differentiating between an involved lymph node and an uninvolved lymph node, such that: involved draining lymph nodes that contain metastatic tumor cells and exhausted T cells are prioritized for elimination by irradiation; and uninvolved lymph nodes are prioritized for protection.

15. The method or apparatus of claim 12 wherein the given one of the immune system components comprises bone marrow.

16. The method or apparatus of claim 15 further comprising: differentiating between yellow bone marrow and red bone marrow, such that red bone marrow is prioritized to be less radiated than yellow bone marrow.

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