Systems and methods for biocompatible radiation therapy - Patents.com

Abstract

Providing a system and method for biocompatible radiation therapy. [Solution] Disclosed herein are systems and methods for adapting and / or updating a radiation therapy treatment plan based on biological and / or physiological and / or anatomical data extracted or calculated from imaging data acquired in real time (e.g., during a treatment session). Functional imaging data acquired during radiation treatment is used to modify the treatment plan and / or dose delivery instructions to provide a prescribed dose distribution to a patient target area. Also disclosed herein are methods for evaluating a treatment plan based on imaging data acquired in real time.

Description

[Technical field]

[0001] (Citation of Related Application) This application claims priority to U.S. Provisional Patent Application No. 62 / 523,691, filed June 22, 2017, the disclosure of which is incorporated herein by reference in its entirety.

[0002] (Technical field) Disclosed herein are systems and methods for adapting and / or updating radiation therapy treatment plans and / or radiation delivery during a treatment session based on biological and / or physiological and / or anatomical data extracted or calculated from imaging data acquired in real time (e.g., during treatment). Also disclosed herein are methods for evaluating treatment plans based on imaging data acquired in real time. [Background technology]

[0003] Radiation therapy treatment planning is typically performed (e.g., weeks, days, hours) in advance of a treatment session. Thus, various parameters may have changed in the time between the treatment planning session and the treatment session, and these changes may affect the dose delivered to the patient (i.e., insufficient radiation to the target area, increased radiation to non-target areas, etc.).

[0004] Typically, a patient imaging scan immediately prior to a treatment session provides information about any structural or geometric changes to the patient and / or target area. For example, anatomical images from a CT or MRI scan performed on the day of treatment and immediately prior to a treatment session can be used to shift the radiation fluence according to patient and / or tumor position shifts, expand or contract the size of the irradiated area to accommodate changes in the size of the patient and / or tumor, and / or adjust the contour of the irradiated area to accommodate changes in the shape of the patient and / or tumor. Modifying the treatment plan and / or radiation delivery based on the most recently obtained data can facilitate more efficient and targeted radiation therapy.

[0005] Therefore, it may be desirable to develop additional methods for updating radiation therapy treatment plans to reflect changes in the patient and / or target region. Summary of the Invention [Means for solving the problem]

[0006] Described herein are methods for adapting and / or updating a radiation therapy treatment plan based on biological and / or physiological data extracted or calculated from imaging data obtained during a treatment session. In some variations, the patient's biological activity and / or physiological data may include tracer uptake values ​​(e.g., standard uptake values ​​or SUVs), PET tracer kinetics, tissue metabolism data (e.g., spectroscopic imaging data, magnetic resonance spectroscopic imaging data), bone formation activity data, oxygenation data, gene expression data (e.g., human growth factor receptor type 2 (HER2) expression), free fatty acid uptake data, blood flow data, vascularity data, morphological shifts in tumor geometry (e.g., spiculation formation), and / or lymphatic activity data, etc. Updating or adapting the treatment plan based on these biological activity and / or physiological data may include updating or modifying dosimetry objectives of one or more target regions or other regions of interest (ROIs), geometry of one or more target regions or other regions of interest (ROIs), number of total treatment sessions, duration of treatment sessions, and / or fractionation patterns for multiple treatment sessions, etc. The biological activity and / or physiological data may be obtained using any imaging modality, for example, functional imaging modalities such as PET imaging, MRI imaging single photon emission computed tomography or SPECT imaging, magnetic particle imaging or MPI. Optionally, structural imaging modalities such as X-ray imaging, CT imaging, ultrasound imaging, etc. may also be used to update or adapt the treatment plan. Alternatively or in addition, the treatment plan may be updated or adapted based on dose delivery data from a previous treatment session or fraction.

[0007] Also disclosed herein are methods for evaluating treatment plans based on imaging data acquired in real time. These methods may be used to determine whether to proceed with a prescribed treatment plan based on patient and / or system parameters during a treatment session. In some variations, the decision as to whether to proceed with a treatment plan may depend on various clinical parameters, such as geometric changes (e.g., volume and / or shape changes) of one or more patient target regions, geometric changes of one or more radiation sensitive regions (e.g., organs at risk or OARs), changes in the relative distance between the target and OARs, changes in the patient's external contour such as size or shape, standard uptake values ​​(SUVs), changes in histoarchitectural characteristics of the patient target region (e.g., cluster shade, cluster prominence, cell uniformity), and whether such factors are within a prescribed range at the time of treatment (or immediately prior thereto). The prescribed range may be determined based on data acquired during a diagnostic imaging session, during a treatment planning session, and / or at the beginning of a treatment session (e.g., during a patient pre-scan), and / or may be a known or widely accepted range of normal activity. The decision as to whether to proceed with the treatment plan may also depend on the treatment plan quality (which may be quantified, for example, by a treatment plan index (PQI) value) and / or changes in the dose-volume histogram (DVH) curve. In some variations, the PQI value and / or the dose-volume histogram may be calculated based on biological activity and / or physiological data and / or anatomical data obtained at the time of (and / or immediately prior to) the treatment.

[0008] Biological activity data may include physiological data. Examples of biological activity data of the region of interest may include oxygenation and / or hypoxia levels, blood perfusion levels, expression of certain genes (e.g., by measuring cell protein binding), immune response activity, cell death and / or necrosis, fractal dimension shifts (e.g., changes in microvascular permeability), tumor growth vectors, or standard uptake values ​​of tracers associated with specific biological functions (e.g., metabolic activity or bone remodeling). Anatomical data may include structural information such as the shape, size, location (e.g., absolute and / or relative location to other anatomical regions, and / or markers or fiducials, and / or imaging system and / or radiation therapy system coordinates) of the region of interest and / or the patient.

[0009] A variation of the method of adapting a radiation therapy treatment plan may include measuring biological activity data of a patient region using one or more PET detectors during a radiation therapy session, comparing the measured biological activity data to an initial biological activity range, calculating a change in the biological activity data, and updating the radiation therapy treatment plan based on the calculated change in the biological activity data. The initial biological activity range may be measured during a radiation therapy session prior to measuring the biological activity data and / or may be measured during a previous radiation therapy session. Updating the radiation therapy treatment plan may include changing a dosimetry target of one or more patient target regions and / or changing a geometry of one or more patient target regions and / or a dose shaping structure. Updating the radiation therapy treatment plan may include changing a fractionation pattern for multiple treatment sessions. The radiation therapy treatment plan may include an initial number of treatment sessions, and updating the treatment plan may include changing the number of treatment sessions from an initial number of treatment sessions. The radiation therapy treatment plan may include an initial treatment session duration, and updating the treatment plan may include changing the treatment session duration from the initial treatment session duration. Measuring biological activity data can include measuring the standard uptake value (SUV) of the PET tracer in the patient area.

[0010] One or more PET tracers can be used in any of the methods described herein. Examples of PET tracers include, but are not limited to, 18F-FDG, 18F-NaF, 18FHX4, 18FFAZA, 18FFMISO, radiolabeled 5F7 anti-HER2 nanobody labeled with 18F, 11C-palmitic acid and 14-(R,S)-18F-fluoro-6-thiaheptadecanoic acid, 15O-water, 13N-ammonia, 82Rb-rubidium, 18F-fluorothymidine, 68Ga-gallium, 68Ge-germanium, F18-fluciclovine, Ga68-DOTATATE, C11-choline, Ga68-PSM A, F18-PyL (PSMA), PD-L1, 13N-nitrogen, 11C-methionine, 18F-fluoroerythronitroimidazole, 3'-aza-2'-[18F]fluorofolate, N-succinimidyl 3-((4-(4-(18)F-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate radiolabeled 5F7 antibody, 1-(2'-deoxy-2'-[18F]fluoroarabinofuranosyl)cytosine (18F-FAC), and F18-fluciclovine.

[0011] The biological activity data may include tissue metabolism data, and / or bone formation activity, and / or oxygenation levels, and / or human growth factor receptor type 2 (HER2) gene expression, and / or free fatty acid uptake, and / or physiological activity data. The physiological activity data may include blood flow data, and / or vascularity of the patient region, and / or morphological shifts in spine formation of tumor regions within the patient region, and / or lymphatic activity data. Measuring the biological activity data may include quantitatively measuring PET tracer kinetics in the patient target region. The radiation therapy treatment plan may include a target dose distribution, and updating the treatment plan may include changing the target dose distribution. In some variations, the updated treatment plan may be used for future radiation therapy sessions. Measuring the biological activity data of the patient target region may further include obtaining a functional image of the patient target region using magnetic resonance imaging, laser scanning fluorescence imaging, ultrasound imaging, magnetic particle imaging, or single photon emission computed tomography. Measuring biological activity data of the patient region may include providing a PET tracer to the patient and measuring positron emission data from the patient target region. In some variations, the PET tracer may be a hypoxic PET tracer such as [18F]HX4, [18F]FAZA, and [18F]FMISO, and measuring the positron emission data may include measuring a hypoxic PET tracer uptake value across the patient target region. Updating the radiation therapy treatment plan may include increasing a radiation dose of the radiation therapy treatment plan to patient target regions with hypoxic PET tracer uptake values ​​above a threshold.

[0012] In some variations, the PET tracer may include a HER2 PET tracer such as 18F-labeled 5F7 anti-HER2 nanobody (18F-RL-I-5F7) and 18F-SFB, and measuring the positron emission data may include measuring HER2 PET tracer uptake values ​​across the patient target region. Updating the radiation therapy treatment plan may include increasing the radiation dose of the radiation therapy treatment plan to the patient target region with a HER2 PET tracer uptake value that exceeds an upper threshold. The method may optionally include measuring HER2 PET tracer uptake values ​​of patient regions outside the target region and identifying patient regions outside the target region that have a HER2 PET tracer uptake value that exceeds an upper threshold. Updating the radiation therapy treatment plan may include changing the dose distribution to include the identified patient region for radiation dose delivery. Alternatively, or in addition, the PET tracer may include a HER2 PET tracer such as 18F-labeled 5F7 anti-HER2 nanobody (18F-RL-I-5F7) and 18F-SFB, and measuring the positron emission data may include measuring HER2 PET tracer uptake values ​​across the patient target area. Updating the radiation therapy treatment plan may include updating a HER2 PET tracer uptake value that exceeds an upper threshold. The method may include reducing the radiation dose of a radiation therapy treatment plan to an associated patient target area.

[0013] The method of adapting a radiation therapy treatment plan may additionally or alternatively include calculating a Plan Quality Index (PQI) value of the radiation therapy treatment plan based on the measured biological activity data, comparing the calculated PQI value to a predetermined range of PQI values, and updating the radiation therapy treatment plan if the calculated PQI value is not within the predetermined range of PQI values. The radiation therapy treatment plan may not be updated if the calculated PQI value is within the predetermined range of PQI values. In some variations, the method may include displaying a notification if the calculated PQI value is not within the predetermined range of PQI values. The predetermined range of PQI values ​​may be a range of clinician-approved PQI values.

[0014] In some variations, the radiation therapy treatment plan is updated if the measured biological activity data is not within the initial biological activity range. The method may include displaying a notification if the measured biological activity data is not within the initial biological activity range. The initial biological activity range may be a clinician-approved biological activity range, and / or the initial biological activity range may be calculated based on a range of clinician-approved PQI values ​​for the radiation therapy treatment plan. In some variations, the initial biological activity range may be calculated based on a clinician-approved bounded DVH for the radiation therapy treatment plan. Updating the radiation therapy treatment plan may include adjusting a range of acceptable plan quality index (PQI) values ​​and / or biological activity values ​​to create an updated treatment plan having a range of acceptable PQI values ​​and / or acceptable biological activity values ​​that includes the measured biological activity data. The predetermined bounded DVH may be calculated based on one or more of the following: a dose delivered to a patient target area in one or more previous treatment sessions, a clinician-approved dose delivery uncertainty, a maximum dose level, and / or a minimum dose level.

[0015] Some variations of the method for adapting the radiation therapy treatment plan may alternatively or additionally include calculating a dose-volume histogram (DVH) for the patient target area based on the radiation therapy treatment plan and the measured biological activity data, comparing the calculated DVH to a predetermined bounded DVH, and updating the radiation therapy treatment plan if the calculated DVH is not within the predetermined bounded DVH.

[0016] A method of generating an acceptable biological activity range for treatment is also disclosed herein. One variation of the method may include determining a range of acceptable plan quality index (PQI) values ​​for a treatment plan and calculating a range of biological activity values ​​corresponding to the range of PQI values. A method for radiation therapy may include determining a range of acceptable PQI values ​​for a treatment plan, measuring biological activity data of a patient region using one or more PET detectors during a radiation therapy session, comparing the measured biological activity data with a calculated range of biological activity values ​​to determine whether the measured biological activity data is within the calculated range, and applying radiation to the patient region if the measured biological activity data is within the calculated range of biological activity values. If the measured biological activity data is not within the calculated range of biological activity, the radiation therapy treatment plan may be updated based on the measured biological activity data.

[0017] Disclosed herein is a method for generating acceptable Plan Quality Index (PQI) ranges for a treatment. One variation of the method may include determining a range of acceptable biological activity values ​​for a treatment plan and calculating a range of PQI values ​​corresponding to the range of acceptable biological activity values. The calculated ranges of biological activity values ​​may be transmitted to a radiation therapy system and / or displayed to a clinician.

[0018] Described herein is a method for radiation therapy treatment. One variation of the method for radiation therapy may include measuring biological activity data of a patient region using one or more PET detectors, comparing the measured biological activity data of the patient region with a predetermined biological activity range, updating a treatment plan if the measured biological activity data is not within the predetermined biological activity range, and applying radiation to the patient region based on the updated treatment plan. The predetermined biological activity range may be a clinician-approved biological activity range. Measuring biological activity data of the patient region may include measuring a hypoxia PET tracer uptake value for the patient region, and applying radiation includes applying radiation such that a radiation dose to a region with a higher hypoxia PET tracer uptake value exceeds a radiation dose to a region with a lower hypoxia PET tracer uptake value.

[0019] A method for calculating a bounded dose-volume histogram (DVH) for evaluating a treatment plan is also described herein. An example of the method is to calculate a bounded dose-volume histogram (DVH) based on acquired patient images X, for a plurality of images X' 1,2,3,…,j a patient target volume (PTV) located at j different positions within a radiation firing zone (RFZ) of a patient; and a dose calculation matrix A is calculated based on radiation firing matrices P and X' j Image x' by multiplying with 1,2,3,…,j Dose for each of D j (D j =A·P·X' j ) and each dose D j Plotting dose-volume histogram (DVH) curves for each dose D to generate a set of j DVH curves, j The DVH curves for may represent a volume fraction for each dose value, and generating a minimum boundary curve (minimum DVH curve) and a maximum boundary curve (maximum DVH curve) of the family of DVH curves. The minimum DVH curve may include a first series of points representing a minimum volume fraction for each dose value of the family of DVH curves, and the maximum DVH curve may include a second series of points representing a maximum volume fraction for each dose value. jGenerating the image X' j Alternatively or in addition, multiple images X′ may be generated by simulating j three-dimensional rigid shifts of the PTV within the RFZ for each of the images X′. j Generating each image X' j In some variations, varying the intensity values ​​of the PTV in the range of 1000 to simulate a range of standard uptake values ​​(SUVs). In some variations, varying the intensity values ​​of the PTV may include increasing the intensity values ​​of the PTV to 25% above the nominal intensity value and / or decreasing the intensity values ​​of the PTV to 25% below the nominal intensity value. The acquired image X may be a PET image or a CT image. Generating the minimum DVH curve may include fitting a first series of points to the first curve, and generating the maximum DVH curve may include fitting a second series of points to the second curve. The dose calculation matrix A and the radiation firing matrix P may be derived based on the acquired patient image X prior to the treatment session. In one variation, the patient image X may be a first patient image, and the method may include obtaining a second patient image Y and multiplying the dose calculation matrix A by the radiation firing matrices P and Y to obtain the dose D. Y (D Y = A·P·Y) and plotting a DVH curve corresponding to the second patient image Y. The method may further include generating a notification if the DVH curve of the second patient image Y is not constrained between the minimum DVH curve and the maximum DVH curve. The notification may be a visual notification and / or an audible notification. The DVH curve corresponding to the second patient image Y may represent a volume fraction for each dose value relative to the PTV and / or the DVH curve corresponding to the second patient image Y may represent a volume fraction for each dose value relative to an organ at risk (OAR). The method may also include displaying the minimum DVH curve and the maximum DVH curve on a display or monitor / screen. In some variations, the display may be a display of the radiation therapy system. Each dose D jPlotting the DVH curves for each dose value may include plotting a volume fraction for each dose value relative to the PTV, generating a family of j DVH curves for the PTV. Alternatively, or in addition, some methods plot a volume fraction for each dose value relative to an organ at risk (OAR), generating a family of j DVH curves for the OARs. j where the minimum DVH curve may be an OAR minimum DVH curve and the maximum DVH curve may be an OAR maximum DVH curve. The DVH curve corresponding to the second image Y may be an OAR DVH curve, and the method may further include generating a notification if the DVH curve of the OAR in the second patient image Y exceeds the OAR maximum DVH curve.

[0020] A method for evaluating a radiation therapy treatment plan is also described herein. One variation of the method includes obtaining imaging data x of a patient and calculating a radiation dose D based on the obtained imaging data and a radiation firing matrix P. x (D x = A·P·x) and plotting a dose-volume histogram (DVH), and generating a notification to be displayed on a monitor if the DVH is not within a range defined by the minimum DVH curve and the maximum DVH curve. Optionally, some methods include calculating the radiation dose distribution D x may include generating a notification to be displayed on a monitor if x is not within a dose distribution range defined by a minimum dose threshold and a maximum dose threshold. The imaging data may be PET imaging data and / or CT imaging data. Some variations may include calculating a Plan Quality Index (PQI) based on the acquired imaging data x, and generating a notification to be displayed on a monitor if the PQI is not within a PQI range defined by a minimum PQI threshold and a maximum PQI threshold. The present invention provides, for example, the following: (Item 1) 1. A method for calculating a bounded dose-volume histogram (DVH) for evaluating a treatment plan, the method comprising: Based on the acquired patient image X, a plurality of images X' 1,2,3,…,jwherein a patient target volume (PTV) is located at j different locations within a radiation field of view (RFZ) of the patient; Dose calculation matrix A is the radiation projection matrix P and X' j by multiplying said image X' 1,2,3,…,j Dose for each of D j (D j =A·P·X' j ) and Each dose D j Plotting dose-volume histogram (DVH) curves for each dose D to generate a set of j DVH curves, j the DVH curve for represents a volume fraction for each dose value; generating a minimum boundary curve (minimum DVH curve) and a maximum boundary curve (maximum DVH curve) from said group of DVH curves; Including, The method of claim 1, wherein the minimum DVH curve includes a first series of points representing a minimum volume fraction for each dose value in the group of DVH curves, and the maximum DVH curve includes a second series of points representing a maximum volume fraction for each dose value. (Item 2) Multiple images X' j generating the image X' j 2. The method of claim 1, further comprising simulating j three-dimensional rigid shifts of the PTV within the RFZ for each of the j three-dimensional rigid shifts. (Item 3) Multiple images X' j Generating each image X' j 3. The method of any one of items 1 or 2, comprising varying intensity values ​​of the PTV in order to simulate a range of standard uptake values ​​(SUV). (Item 4) 4. The method of claim 3, wherein varying the intensity value of the PTV comprises increasing the intensity value of the PTV to 25% greater than the nominal intensity value. (Item 5) 4. The method of claim 3, wherein varying the intensity value of the PTV comprises decreasing the intensity value of the PTV to 25% less than the nominal intensity value. (Item 6) 6. The method according to any one of items 1-5, wherein the acquired image X is a PET image. (Item 7) 2. The method of claim 1, wherein generating a minimum DVH curve comprises fitting the first series of points to a first curve, and generating a maximum DVH curve comprises fitting the second series of points to a second curve. (Item 8) 2. The method of claim 1, wherein the dose calculation matrix A and the radiation firing matrix P are derived based on the acquired patient images X prior to a treatment session. (Item 9) The patient image X is a first patient image, and the method includes obtaining a second patient image Y and multiplying the dose calculation matrix A by the radiation firing matrices P and Y to obtain a dose D. Y (D Y 2. The method of claim 1, further comprising calculating a DVH curve corresponding to the second patient image Y (A=A·P·Y) and plotting a DVH curve corresponding to the second patient image Y. (Item 10) 10. The method of claim 9, further comprising generating a notification if the DVH curve of the second patient image Y is not constrained between the minimum DVH curve and the maximum DVH curve. (Item 11) Item 11. The method according to item 10, wherein the notification is a visual notification and / or an audible notification. (Item 12) 11. The method of claim 10, wherein the DVH curve corresponding to the second patient image Y represents a volume fraction for each dose value relative to the PTV. (Item 13) 11. The method of claim 10, wherein the DVH curve corresponding to the second patient image Y represents a volume fraction for each dose value for an organ at risk (OAR). (Item 14) 2. The method of claim 1, further comprising displaying the minimum DVH curve and the maximum DVH curve on a display. (Item 15) 15. The method of claim 14, wherein the display is a display of a radiation therapy system. (Item 16) Each dose D j 10. The method of claim 9, wherein plotting DVH curves for comprises plotting a volume fraction for each dose value relative to the PTV to generate a family of j DVH curves for the PTV. (Item 17) For each dose D, plot the volume fraction for each organ at risk (OAR) and generate a set of j DVH curves for the OAR. j 17. The method of claim 16, further comprising plotting a DVH curve for the OAR minimum DVH curve and the maximum DVH curve for the OAR maximum DVH curve. (Item 18) 18. The method of claim 17, wherein the DVH curve corresponding to the second image Y is an OAR DVH curve, the method further comprising generating a notification if the DVH curve of the OAR in the second patient image Y exceeds a maximum DVH curve of the OAR. (Item 19) 1. A method for evaluating a radiation therapy treatment plan, the method comprising: Obtaining imaging data x of a patient; Based on the acquired imaging data and the radiation firing matrix P, a radiation dose D x (D x = A P x) and plot the dose-volume histogram (DVH); generating a notification to be displayed on a monitor if the DVH is not within a range defined by a minimum DVH curve and a maximum DVH curve; A method comprising: (Item 20) The radiation dose distribution D x20. The method of claim 19, further comprising generating a notification to be displayed on the monitor if the dose distribution range defined by a minimum dose threshold and a maximum dose threshold is not within the dose distribution range defined by a minimum dose threshold and a maximum dose threshold. (Item 21) 20. The method of claim 19, wherein the imaging data is PET imaging data. (Item 22) Calculating a Planning Quality Index (PQI) based on the acquired imaging data x; generating a notification to be displayed on a monitor if the PQI is not within a PQI range defined by a minimum PQI threshold and a maximum PQI threshold; 20. The method of claim 19, further comprising: (Item 23) 1. A method of adapting a radiation therapy treatment plan, the method comprising: measuring biological activity data of a region of a patient using one or more PET detectors during a radiation therapy session; comparing said measured biological activity data with an initial biological activity range and calculating a change in said biological activity data; updating a radiation therapy treatment plan based on the calculated changes in the biological activity data; and A method comprising: (Item 24) 24. The method of claim 23, wherein the initial biological activity range is measured during the radiation therapy session prior to measuring the biological activity data. (Item 25) 24. The method of claim 23, wherein the initial biological activity range is measured during a previous radiation therapy session. (Item 26) 24. The method of claim 23, wherein updating the radiation therapy treatment plan comprises changing dosimetry targets of one or more patient target areas. (Item 27) 24. The method of claim 23, wherein updating the radiation therapy treatment plan comprises changing the geometry of one or more patient target areas and / or dose shaping structures. (Item 28) 24. The method of claim 23, wherein the radiation therapy treatment plan includes an initial number of treatment sessions, and updating the treatment plan includes changing a number of treatment sessions from the initial number of treatment sessions. (Item 29) 24. The method of claim 23, wherein the radiation therapy treatment plan includes an initial treatment session duration, and updating the treatment plan includes changing a treatment session duration from the initial treatment session duration. (Item 30) 24. The method of claim 23, wherein updating the radiation therapy treatment plan comprises changing a fractionation pattern for multiple treatment sessions. (Item 31) 25. The method of claim 24, wherein measuring biological activity data comprises measuring a standard uptake value (SUV) of the PET tracer in the patient area. (Item 32) The PET tracers include 18F-FDG, 18F-NaF, 18FHX4, 18FFAZA, 18FFMISO, radiolabeled 5F7 anti-HER2 nanobody labeled with 18F, 11C-palmitic acid and 14-(R,S)-18F-fluoro-6-thiaheptadecanoic acid, 15O-water, 13N-ammonia, 82Rb-rubidium, 18F-fluorothymidine, 68Ga-gallium, 68Ge-germanium, F18-fluciclovine, Ga68-DOTATATE, C11-choline, Ga68-PSMA, F18- 32. The method of claim 31, wherein the antibody is selected from the group consisting of PyL (PSMA), PD-L1, 13N-nitrogen, 11C-methionine, 18F-fluoroerythronitroimidazole, 3'-aza-2'-[18F]fluorofolate, N-succinimidyl 3-((4-(4-(18)F-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoic acid radiolabeled 5F7 antibody, 1-(2'-deoxy-2'-[18F]fluoroarabinofuranosyl)cytosine (18F-FAC). (Item 33) 24. The method of claim 23, wherein the biological activity data comprises tissue metabolism data. (Item 34) 24. The method according to item 23, wherein the biological activity data comprises osteogenic activity. (Item 35) 24. The method of claim 23, wherein the biological activity data comprises oxygenation levels. (Item 36) 24. The method of claim 23, wherein the biological activity data comprises human growth factor receptor type 2 (HER2) gene expression. (Item 37) 24. The method according to item 23, wherein the biological activity data comprises free fatty acid intake. (Item 38) 24. The method of claim 23, wherein the biological activity data comprises physiological activity data. (Item 39) 39. The method of claim 38, wherein the physiological activity data includes blood flow data. (Item 40) 39. The method of claim 38, wherein the physiological activity data includes vascularity of the patient region. (Item 41) 39. The method of claim 38, wherein the physiological activity data comprises a morphological shift in the spine formation of a tumor region within the patient region. (Item 42) 39. The method of claim 38, wherein the physiological activity data comprises lymphatic activity data. (Item 43) 24. The method of claim 23, wherein measuring biological activity data comprises quantitatively measuring PET tracer kinetics in the patient target area. (Item 44) 24. The method of claim 23, wherein the radiation therapy treatment plan includes a target dose distribution, and updating the treatment plan includes changing the target dose distribution. (Item 45) 24. The method of claim 23, wherein the updated treatment plan is used for future radiation therapy sessions. (Item 46) 24. The method of claim 23, wherein measuring biological activity data of a patient target area further comprises obtaining a functional image of the patient target area using magnetic resonance imaging, laser scanning fluorescence imaging, ultrasound imaging, magnetic particle imaging, or single photon emission computed tomography. (Item 47) Measuring biological activity data of a patient area providing a PET tracer to the patient; measuring positron emission data from the patient target region; 24. The method according to item 23, comprising: (Item 48) 48. The method of claim 47, wherein the PET tracer comprises a hypoxia PET tracer selected from the group consisting of [18F]HX4, [18F]FAZA, and [18F]FMISO, measuring positron emission data comprises measuring a hypoxia PET tracer uptake value across the patient target region, and updating the radiation therapy treatment plan comprises increasing a radiation dose of the radiation therapy treatment plan to patient target regions with hypoxia PET tracer uptake values ​​above a threshold. (Item 49) 48. The method of claim 47, wherein the PET tracer comprises a HER2 PET tracer selected from the group consisting of 18F-labeled 5F7 anti-HER2 nanobody (18F-RL-I-5F7) and 18F-SFB, measuring positron emission data comprises measuring HER2 PET tracer uptake values ​​across the patient target area, and updating the radiation therapy treatment plan comprises increasing a radiation dose of the radiation therapy treatment plan to patient target areas with HER2 PET tracer uptake values ​​above an upper threshold. (Item 50) measuring HER2 PET tracer uptake in areas of the patient outside the target area; identifying patient regions outside said target region having HER2 PET tracer uptake values ​​above said upper threshold; Further comprising: 50. The method of claim 49, wherein updating the radiation therapy treatment plan includes changing the dose distribution to include the identified patient region for radiation dose delivery. (Item 51) 48. The method of claim 47, wherein the PET tracer comprises a HER2 PET tracer selected from the group consisting of 18F-labeled 5F7 anti-HER2 nanobody (18F-RL-I-5F7) and 18F-SFB, measuring positron emission data comprises measuring a HER2 PET tracer uptake value across the patient target area, and updating the radiation therapy treatment plan comprises reducing a radiation dose of the radiation therapy treatment plan to patient target areas with HER2 PET tracer uptake values ​​above an upper threshold. (Item 52) calculating a Plan Quality Index (PQI) value for the radiation therapy treatment plan based on the measured biological activity data; comparing said calculated PQI value with a predetermined range of PQI values; Further comprising: 24. The method of claim 23, wherein updating the radiation therapy treatment plan comprises updating the radiation therapy treatment plan if the calculated PQI value is not within a predetermined range of PQI values. (Item 53) 53. The method of claim 52, wherein the radiation therapy treatment plan is not updated if the calculated PQI value is within a predetermined range of PQI values. (Item 54) 53. The method of claim 52, further comprising displaying a notification if the calculated PQI value is not within a predetermined range of the PQI value. (Item 55) 53. The method of claim 52, wherein the predetermined range of PQI values ​​is a range of clinician-approved PQI values. (Item 56) 24. The method of claim 23, wherein updating the radiation therapy treatment plan comprises updating the radiation therapy treatment plan if the measured biological activity data is not within the initial biological activity range. (Item 57) 57. The method of claim 56, wherein the radiation therapy treatment plan is not updated if the measured biological activity data is within the initial biological activity range. (Item 58) 57. The method of claim 56, further comprising displaying a notification if the measured biological activity data is not within the initial biological activity range. (Item 59) 57. The method of claim 56, wherein the initial biological activity range is a clinician-approved biological activity range. (Item 60) 57. The method of claim 56, wherein the initial biological activity range is calculated based on a range of clinician-approved PQI values ​​for the radiation therapy treatment plan. (Item 61) 57. The method of claim 56, wherein the initial biological activity range is calculated based on a clinician-approved bounded DVH for the radiation therapy treatment plan. (Item 62) 57. The method of claim 56, wherein updating the radiation therapy treatment plan comprises adjusting a range of acceptable Plan Quality Index (PQI) values ​​and / or biological activity values ​​to generate an updated treatment plan, the updated treatment plan having a range of acceptable PQI values ​​and / or a range of acceptable biological activity values ​​that includes the measured biological activity data. (Item 63) calculating a dose-volume histogram (DVH) for a patient target area based on the radiation therapy treatment plan and the measured biological activity data; comparing said calculated DVH with a predetermined bounded DVH; Further comprising: 24. The method of claim 23, wherein updating the radiation therapy treatment plan comprises updating the radiation therapy treatment plan if the calculated DVH is not within the predetermined bounded DVH. (Item 64) Item 64. The method of item 63, wherein the predetermined bounded DVH is calculated based on one or more of a dose delivered to the patient target area in one or more previous treatment sessions, a clinician-approved dose delivery uncertainty, a maximum dose level, and a minimum dose level. (Item 65) 1. A method for generating an acceptable biological activity range for treatment, the method comprising: determining a range of acceptable plan quality index (PQI) values ​​for the treatment plan; calculating said range of PQI values ​​and corresponding ranges of biological activity values; A method comprising: (Item 66) 1. A method for generating acceptable Planning Quality Index (PQI) ranges for a treatment, the method comprising: determining a range of acceptable biological activity values ​​for a treatment regimen; calculating said range of acceptable biological activity values ​​and corresponding ranges of PQI values; A method comprising: (Item 67) 67. The method of claim 66, further comprising transmitting the calculated range of biological activity values ​​to a radiation therapy system. (Item 68) 67. The method of claim 66, further comprising displaying the calculated range of biological activity values ​​to a clinician. (Item 69) 1. A method for radiation therapy, the method comprising: The method according to item 66, measuring biological activity data of a region of a patient using one or more PET detectors during a radiation therapy session; comparing the measured biological activity data to a calculated range of biological activity values ​​to determine whether the measured biological activity data is within the calculated range; applying radiation to the patient area if the measured biological activity data is within a calculated range of biological activity values; A method comprising: (Item 70) 70. The method of claim 69, further comprising updating the radiation therapy treatment plan based on the measured biological activity data if the measured biological activity data is not within the calculated range of biological activity. (Item 71) 1. A method for radiation therapy treatment, the method comprising: measuring biological activity data in a region of the patient using one or more PET detectors; comparing the measured biological activity data of the patient area with a predetermined biological activity range; updating a treatment plan if the measured biological activity data is not within the predetermined biological activity range; applying radiation to the patient region based on the updated treatment plan; A method comprising: (Item 72) 72. The method of claim 71, wherein the predetermined biological activity range is a clinician-approved biological activity range. (Item 73) 72. The method of claim 71, wherein measuring biological activity data of the patient region includes measuring hypoxia PET tracer uptake values ​​across the patient region, and applying radiation includes applying radiation such that a radiation dose to regions with higher hypoxia PET tracer uptake values ​​exceeds a radiation dose to regions with lower hypoxia PET tracer uptake values. [Brief description of the drawings]

[0021] [Figure 1A] FIG. 1A depicts one variation of a system for adaptive radiation therapy. [Figure 1B] FIG. 1B depicts another variation of a system for adaptive radiation therapy.

[0022] [Figure 1C] 1C-1D depict an example of a system for adaptive radiation therapy. [Figure 1D] 1C-1D depict an example of a system for adaptive radiation therapy.

[0023] [Figure 2A] FIG. 2A depicts a flow chart illustrating one variation of a method for adaptive radiation therapy.

[0024] [Figure 2B-1] FIG. 2B depicts a flowchart illustrating one variation of a method for online adaptive radiation therapy. [Figure 2B-2] FIG. 2B depicts a flowchart illustrating one variation of a method for online adaptive radiation therapy.

[0025] [Figure 2C-1] FIG. 2C depicts a flowchart illustrating one variation of a method for real-time adaptive radiation therapy. [Figure 2C-2] FIG. 2C depicts a flowchart illustrating one variation of a method for real-time adaptive radiation therapy.

[0026] [Figure 2D] FIG. 2D depicts a flowchart illustrating one variation of a method for offline adaptive radiation therapy.

[0027] [Figure 3A] FIG. 3A depicts a table of example prescribed radiation doses to various regions of interest.

[0028] [Figure 3B-1] FIG. 3B depicts an example table of Plan Quality Index (PQI). [Figure 3B-2] FIG. 3B depicts an example table of Plan Quality Index (PQI).

[0029] [Figure 4A] FIG. 4A depicts a table of example PQI values, prescribed PQI values, and ranges of acceptable PQI values.

[0030] [Figure 4B]FIG. 4B depicts a flow chart illustrating one variation of a method for evaluating a treatment plan using a PQI value calculated based on imaging data acquired in real time.

[0031] [Figure 5A] FIG. 5A depicts a table of exemplary clinical parameters and PQI values ​​calculated during a treatment planning session and at the time of treatment.

[0032] [Figure 5B] FIG. 5B depicts a flow chart illustrating one variation of a method for evaluating a treatment plan using clinical parameters derived from imaging data acquired in real time.

[0033] [Figure 5C] FIG. 5C depicts a flowchart illustrating one variation of a method for calculating the range of acceptable clinical parameters.

[0034] [Figure 5D] FIG. 5D depicts a flowchart illustrating one variation of a method for calculating the range of acceptable clinical parameters.

[0035] [Figure 6A] FIG. 6A depicts a flow chart illustrating one variation of a method for calculating a range of acceptable biological activity values ​​based on a selected range of PQI values.

[0036] [Figure 6B] FIG. 6B depicts a flowchart illustrating another variation of a method for calculating a range of acceptable biological activity values ​​based on a selected PQI threshold value.

[0037] [Figure 7A] FIG. 7A depicts an example of a dose-volume histogram (DVH) and a bounded DVH.

[0038] [Figure 7B]FIG. 7B depicts a flowchart illustrating another variation of a method for evaluating a treatment plan using DVHs derived from imaging data acquired in real time.

[0039] [Figure 8A] FIG. 8A depicts a flowchart representing one method of calculating bounded DVH curves that may be used to evaluate treatment plans based on biological and / or physiological data obtained during treatment.

[0040] [Figure 8B] FIG. 8B depicts a schematic diagram of shifting an image of a patient target volume (PTV) within a radiation firing zone (RFZ) to calculate a family of DVH curves as part of the method of FIG. 8A.

[0041] [Figure 8C] FIG. 8C illustrates an example of multiple DVH curves calculated for various shifted images of the PTV within the RFZ, including DVH curves for the PTV, the RFZ, and two OARs.

[0042] [Figure 8D] FIG. 8D illustrates an example of bounded DVH curves for a PTV, an RFZ, and one OAR. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0043] Disclosed herein are systems and methods for adapting and / or updating radiation therapy treatment plans based on biological and / or physiological and / or anatomical data extracted or calculated from imaging data acquired in real time (e.g., during a treatment session). Functional imaging data acquired during radiation treatment is used to modify the treatment plan and / or dose delivery instructions and provide a prescribed dose distribution to a patient target area. Also disclosed herein are methods for evaluating treatment plans based on imaging data acquired in real time.

[0044] ((system)) FIG. 1A diagrammatically depicts one variation of a system that may be used for adaptive radiation therapy. The system 100 may include an imaging system 102, a radiation therapy system 104, a controller 106 that communicates with the imaging system and the radiation therapy system, and a communication interface 108. The imaging system 102 and the radiation therapy system 104 may be arranged such that the patient may be easily positioned in the radiation therapy system immediately after the patient image data is acquired by the imaging system. For example, the imaging system 102 and the radiation therapy system 104 may be located in the same facility or building and / or in the same room or observation room and / or mounted on the same chassis or gantry. In some variations, the imaging system and the radiation therapy system may be arranged such that the patient area of ​​the imaging system is aligned with the patient area of ​​the treatment system. FIG. 1A depicts one example of an imaging system 130 with a patient area 132 and a treatment system 134 with a patient area 136, where the longitudinal axes L1, L2 of the patient areas 132, 136 are aligned or collinear. Alternatively, the imaging system and the radiation therapy system may be arranged such that the patient regions of each of the imaging system and the radiation therapy system are not aligned, but are adjacent to each other. FIG. 1B depicts an example of an imaging system 140 with a patient region 142 and a therapy system 144 with a patient region 146, where the longitudinal axes L3, L4 of the patient regions 142, 146 may not be in line, but may instead be parallel to each other or at an angle to each other. Imaging data acquired by the imaging system 102 during therapy (e.g., immediately prior to activation of the radiation therapy system and / or during application of therapeutic radiation to the patient) may be transmitted to the controller 106, and the controller processor may be configured to extract biological activity data (and / or physiological and / or anatomical data) of the patient from the acquired imaging data. The controller may also be configured to calculate a predicted quality and / or effectiveness of the treatment plan in light of the recently acquired biological activity data.Depending on the magnitude and / or characteristics of any changes in biological activity levels and / or physiological data, the controller may then evaluate whether the patient's radiation treatment should proceed or continue based on a given treatment plan and / or whether the treatment plan should be updated and / or adapted. Alternatively or additionally, these calculated qualities may be presented to a clinician via the communication interface 108 for evaluation and / or treatment plan approval. The radiation therapy system 104 may be configured to adapt the therapeutic radiation beam to the patient based on imaging data acquired during treatment as well as on the clinician's evaluation and / or approval.

[0045] The imaging system 102 may be configured to acquire imaging data using any one or more imaging modalities, including functional and / or anatomical imaging modalities, so long as the imaging system is capable of acquiring the data during a treatment session (i.e., in real time). The imaging system 102 may comprise one or more PET detectors, and / or X-ray detectors (e.g., kV or MV detectors), and / or MRI sensors, ultrasound detectors, etc. The imaging data from the imaging system 102 may provide biological activity and / or physiological and / or anatomical data associated with the patient's body and / or one or more regions of interest (ROIs) or target regions. Some imaging systems may acquire data related to the uptake of various types of tracers in the patient's body. For example, the patient may be injected with a tracer (e.g., a PET tracer, an X-ray contrast agent, etc.) and the imaging system may acquire data regarding the accumulation of the tracer (qualitatively and / or quantitatively). The tracer accumulation location, the size and shape of the tracer accumulation volume as well as the tracer kinetics may provide an indication of various biological activity levels and / or physiological phenomena in the patient. For example, the cellular metabolism level and the presence (or absence) of oxygen in the tissue region may be calculated from the amount and / or rate of tracer uptake as indicated by the intensity of the imaging data. Changes in the expression of genes tagged with the tracer may also be calculated by measuring changes in image intensity. The size and shape of the tumor region may be determined, at least in part, by the size and shape of the region of tracer uptake exceeding a predetermined threshold. Some imaging systems may be configured to obtain imaging data at any time regardless of the activation state of the radiotherapy system (e.g., whether the therapeutic radiation source is activated or not), while other imaging systems may be configured to obtain imaging data when the therapeutic radiation source of the radiotherapy system is not activated (e.g., not emitting a radiation beam). For example, an imaging system equipped with one or more x-ray detectors may obtain imaging data between therapeutic radiation beam pulses and / or when the therapeutic radiation source is not activated (due to the effect of x-rays scattering from a high-energy radiation source).An imaging system including one or more PET detectors may obtain PET data between therapeutic radiation beam pulses and / or at the beginning of a treatment session before the first therapeutic radiation pulse and / or at the end of a treatment session after the last therapeutic radiation pulse. In contrast, an imaging system including one or more MRI sensors may obtain imaging data whether or not a therapeutic radiation source is activated and / or applying a radiation beam pulse.

[0046] The radiation therapy system 104 may be configured to direct radiation to the patient according to a treatment plan that may be updated or adapted based on imaging data obtained by the imaging system (e.g., biological activity data and / or anatomical data calculated from the imaging data). The radiation therapy system may include a therapeutic radiation source (e.g., a MV X-ray radiation source such as a linear accelerator, a radioisotope source such as a cobalt-60 source, or a particle beam source such as a cyclotron), one or more beam-shaping structures that may be configured to direct or limit the therapeutic radiation beam, and a motion system configured to rapidly move the therapeutic radiation source and the beam-shaping structures to various firing positions around the patient area. In one variation, the radiation therapy system may include a MV X-ray radiation source and a dynamic multi-leaf collimator disposed in the beam path of the radiation source, both mounted on a motion system that includes a movable gantry. The gantry may be a circular gantry or a rotatable gantry, such as an L-arm or C-arm gantry, and / or an articulating robotic arm that is movable and / or rotatable around the patient area. The gantry may optionally be a continuously rotating gantry. The motion system may be configured to move the radiation source and the beam shaping structure from one firing position to another firing position within less than about 10 seconds, e.g., less than about 5 seconds, less than about 3 seconds, less than about 2 seconds, less than about 1 second, less than about 0.5 seconds, less than about 0.25 seconds, etc. The dynamic multi-leaf collimator may comprise multiple leaves, each attached to a leaf actuation mechanism that moves the leaf to a location designated by the controller. The dynamic multi-leaf collimator may be a binary multi-leaf collimator or a 2-D multi-leaf collimator. Other beam shaping devices or collimators may also be used, e.g., radial collimators that generate a circular field. The leaf actuation mechanism may be configured to rapidly move the leaves from one position to another before the radiation source fires the next beam pulse.For example, in a binary multi-leaf collimator, the leaf actuation mechanism may be configured to transition the leaves from a closed position to an open position (or vice versa) within less than about 5 seconds, e.g., less than about 3 seconds, less than about 2 seconds, less than about 1 second, less than about 0.5 seconds, less than about 0.75 seconds, less than about 0.5 seconds, less than about 0.3 seconds, less than about 0.25 seconds, less than about 0.2 seconds, less than about 0.1 seconds, etc. The combination of a rapid translation motion system and a rapid transition dynamic multi-leaf collimator may help reduce the latency between the acquisition of imaging data and the application of radiation beam pulses based on biological activity data extracted from the imaging data. The positions of the leaves at specific firing locations (e.g., locations around the patient area where the therapeutic radiation source may be located when firing the radiation beam) may be determined based on a treatment plan. The treatment plan may be calculated in a treatment planning session and updated immediately before or during a treatment session based on biological activity data and / or physiological data and / or anatomical data extracted from imaging data acquired (e.g., in real time) on the treatment day. In some variations, the controller processor may generate a set of multi-leaf collimator commands that drive the movement and positioning of each leaf at each firing location such that the radiation beam has an irradiation shape that conforms to the treatment plan. This calculation, also referred to as segmenting the treatment plan (and / or generating a fluence map of the treatment plan), may generate a sinogram or radiation firing matrix. A sinogram may represent a set of multi-leaf collimator commands that map the position of each leaf of the multi-leaf collimator to each firing position or angle. Some sinograms may map the multi-leaf collimator leaf pattern (e.g., the cumulative beam shape as a result of aggregating the individual leaf positions) to each firing position or angle. As the treatment plan is updated or adapted based on biological activity data and / or physiological data and / or anatomical data obtained by the imaging system, the leaf instructions may change or adapt to account for any changes in biological activity levels and / or physiological phenomena.In some variations, the dynamic multi-leaf collimator may be configured to change the position of one or more leaves while the therapeutic radiation source is being moved to the next firing location. Simultaneous leaf movement and radiation source movement may help reduce the latency between detection of biological activity data and application of radiation, which may help the radiation therapy system irradiate tumor regions before they substantially move. Additionally, the configuration of the multi-leaf collimator (e.g., the positions of the leaves at various firing locations) may be updated as the treatment plan is updated based on imaging data obtained during the treatment day (e.g., at the time of treatment, during treatment).

[0047] The controller 106 may communicate with the imaging system 102 and the radiation therapy system 104 so that the acquired imaging data may be processed (e.g., to extract or calculate biological activity data and / or physiological data and / or anatomical data) and so that the delivery of the therapeutic radiation beam may be adjusted based on the acquired imaging data. The controller 106 may comprise one or more processors (e.g., a central processing unit) and one or more memories. The controller memory may store data related to one or more treatment plans, treatment plan parameters (e.g., plan quality index, dose-volume histogram, etc.), previously collected imaging data (e.g., from diagnostic imaging sessions), real-time imaging data (e.g., acquired on the treatment session date, at the time of treatment), extracted biological activity and / or anatomical data, radiation therapy system commands and instructions, dynamic models and algorithms used for treatment plan adaptation, user-implemented programs, etc. The controller 106 may receive imaging data and imaging component feedback (e.g., image detector or sensor status, calibration data, etc.) from the imaging system 102 and may also transmit imaging commands (e.g., activation of any x-ray source and / or activation of image detectors or sensors, adjustment of detector gain and / or sensitivity levels, positioning of the imaging system relative to the patient and / or radiation therapy system, etc.) to the imaging system. The controller 106 may receive data from various components of the radiation therapy system and transmit commands to the radiation therapy system. For example, the radiation therapy system may include a motion system (e.g., a gantry), a therapeutic radiation source (e.g., a linear accelerator) and a beam shaping device (e.g., a dynamic MLC) mounted on the motion system, and a radiation detector (e.g., an MV detector) mounted on the motion system. The controller 106 may receive position and / or velocity data from the motion system, position and / or radiation beam generation data from the radiation source, leaf configuration data from the beam shaping device, and / or more generally, operation status, calibration data, error indicators, etc.The controller 106 may transmit MLC commands, gantry rotation / motion commands, linear accelerator pulse commands, etc., and these commands and instructions may be generated based on a combination of the treatment plan, previously acquired images, real-time acquired imaging data, patient biological activity and / or physiological data, and / or the state of the radiation therapy system.

[0048] The controller 106 may communicate with a display via a communication interface 108, which may project a graphical user interface (GUI) that provides a user with information regarding the treatment plan, imaging data, biological activity and / or physiological data, potential updates to the treatment plan based on the imaging data, patient identification, patient status, system status, treatment session progress, dose delivery status, etc. The GUI may also provide a menu of commands for user selection, and a programming interface so that the user may type in a predefined set of machine instructions and parameters. For example, the display may present one or more visual indicators representing real-time patient biological activity and / or physiological data, the effect of this data on the effectiveness of the current treatment plan (e.g., a plan quality index or PQI, a dose-volume histogram or DVH if radiation is delivered according to the current treatment plan with the current level of biological and / or physiological activity), allowing the clinician to determine whether to proceed with the current treatment plan, modify the treatment plan, or pause the treatment session. In some variations, the GUI on the display may include bounded DVH curves, PQI values, and / or any treatment plan evaluation metrics calculated during treatment planning (e.g., based on biological and / or physiological data derived from planning images such as planning CT and / or PET images). These DVH curves, PQI values, and / or any treatment plan evaluation metrics are pre-approved by the clinician. The DVH curves, PQI values, and / or any treatment plan evaluation metrics may be generated using patient biological activity and / or physiological data acquired in real time during treatment and displayed simultaneously with the same metrics calculated during treatment planning. For example, one or more DVH curves (e.g., for the PTV and / or OARs) calculated based on biological and / or physiological data extracted from imaging data acquired during treatment may be overlaid or superimposed on the bounded DVH curves generated by the treatment planning system.The display may also present additional and / or alternative treatment plans based on the patient's biological activity and / or physiological data according to one or more of the methods described herein. In some variations, the GUI on the display may include visual notifications regarding whether the treatment plan metrics calculated based on the real-time imaging data are within pre-approved ranges (e.g., pass) and / or outside pre-approved ranges (e.g., fail). Optionally, some variations may include additional notification tiers indicating, for example, various degrees of compliance with the treatment plan. For example, some variations may include notifications indicating that the variance of the calculated treatment plan metrics is within an acceptable tolerance range (e.g., pass within tolerance) and / or notifications indicating that the variance of the calculated treatment metrics is outside an acceptable tolerance range (e.g., pass with exceptions). Optionally, when the treatment plan metrics calculated based on the real-time imaging data are outside of a pre-approved range, a treatment plan adaptation recommendation may be provided in the GUI. The information presented on the display may help the clinician determine the best course of action given the patient's condition at the time of treatment. Alternatively, or in addition, the notification may include one or more audible signals or sounds produced by a speaker, and each type or tier of notification may have a different sound.

[0049] FIG. 1B depicts one variation of a system for adaptive radiation therapy. The system 120 may include an imaging system 122 with one or more PET detectors 124, a radiation therapy system 126 with a therapeutic radiation source 128 (e.g., an MV X-ray source such as a linear accelerator), a dynamic MLC or DMLC 130, and an MV detector 132. The system 120 may also include a controller 134 in communication with the imaging system and the radiation therapy system 126, and a communication interface 136. The radiation emission assembly may be mounted on a movable gantry, such as a rotatable gantry. In some variations, the rotatable gantry may be a circular gantry that is continuously rotatable. Optionally, the imaging system 122 may also be mounted on a movable gantry. The PET data (e.g., one or more individual positron annihilation emission paths) acquired by the one or more PET detectors 124 may be transmitted to the controller 134, where it may be stored in the controller memory and / or processed according to any of the methods described herein. The controller 134 may calculate and / or extract biological activity and / or physiological data from the PET data, which may optionally be presented to the clinician. The radiation therapy system 126 may move the therapeutic radiation source 128, vary the DMLC leaf configuration, and obtain data from the MV detector according to commands from the controller 134. In some variations, the gantry may be configured to rotate at about 40 RPM or more, e.g., about 60 RPM, about 70 RPM. The DMLC 130 may include a leaf actuation mechanism that changes the leaf position within the time interval that the gantry moves the radiation emission assembly from one firing position to another. For example, the DMLC 130 may include a leaf actuation mechanism configured to move the leaves from a fully closed position to a fully open position within less than about 10 ms. In some variations, a circular gantry having n firing positions and rotating at a frequency f may be configured to rotate at a frequency f of 0.7. *The DMLC may have a DMLC transition time of less than (f / n) seconds. For example, a circular gantry with n=100 firing positions and rotating at a frequency f of about 1 Hz may have a DMLC transition time of about 7 ms. The DMLC may include a leaf actuation mechanism comprising a pneumatic cylinder and one or more springs, which may provide sufficient motive force to change the leaf positions within the time interval between firing positions. Additional details and examples of multi-leaf collimator leaf actuation mechanisms and radiation therapy systems are provided in U.S. Patent Application No. 15 / 179,823, filed June 10, 2016, and U.S. Patent Application No. 62 / 422,404, filed November 15, 2016, which are incorporated herein by reference in their entireties.

[0050] ((method)) (Adaptive Radiation Therapy) A method for adapting radiation therapy based on biological activity and / or physiological data may include obtaining imaging data in real time (e.g., at the time of treatment and / or during treatment), extracting biological activity and / or physiological data from the imaging data, determining whether a previously generated treatment plan can be delivered based on the extracted biological activity and / or physiological data, and updating or adapting the treatment plan according to the biological activity and / or physiological data. The imaging data may not be limited to full resolution, high contrast, and / or high signal-to-noise ratio (SNR) images, but may include images that may have lower resolution, lower contrast, and / or lower SNR. In some variations, the imaging data may include partial PET images, partial MRI images, and / or partial CT images, etc. For example, a partial PET image may include one or more positron annihilation emission paths (e.g., a line of response defined by a pair of coincident photons emitted by a positron annihilation event), a partial MRI image may include one or more individual lines of k-space in the Fourier domain (e.g., subsamplings in k-space), and a partial CT image may include one or more 2-D projection X-ray images. Determining whether a previously generated treatment plan remains clinically appropriate in light of the biological activity and / or physiological data may include comparing those data values ​​to previously approved data values ​​(the comparison may be performed by a preprogrammed controller or processor) and / or calculating the effectiveness of the current treatment plan based on the current data values. In some variations, the system may display the extracted biological and / or physiological activity, the treatment plan quality parameters, and / or associated thresholds to the clinician.

[0051] In some variations, biological and / or physiological data extracted from imaging data acquired during treatment (such as data calculated from a PET pre-scan acquired before the therapeutic radiation source is activated) may be used to determine whether the treatment session can proceed with the current treatment plan (i.e., "OK to proceed" or "no proceed"). If it is determined that the current treatment plan is no longer suitable for delivery, the system may adapt and / or update the plan according to the biological and / or physiological data. In one example, a DVH curve and / or one or more PQIs may be calculated based on the current treatment plan and current (e.g., acquired in real time) biological and / or physiological data. That is, the system may calculate the radiation dose (e.g., DVH curve and / or one or more PQI metrics) to be delivered if the treatment should proceed with the current treatment plan in light of the acquired biological and / or physiological data. The calculated DVH curve and / or one or more PQI values ​​may be compared to DVH curve and / or PQI values ​​calculated based on the treatment plan and treatment plan images (e.g., planning CT and / or PET images). The radiation therapy system may be configured to provide the clinician or technician with multiple levels or hierarchies of notifications indicating the level of similarity between the calculated DVH and / or PQI values ​​and the treatment plan DVH and / or PQI values. For example, the clinician and / or radiation therapy system may specify that the target area coverage must be at least 95% coverage during the prescription of radiation, with a 1% tolerance, for radiation to be delivered according to the prescribed treatment plan (meaning that 94% coverage is acceptable but requires scrutiny and requires clinician evaluation and approval). Biological and / or physiological data from a PET pre-scan obtained at the beginning of a treatment session (i.e., before the therapeutic radiation source beam is turned on) may be used to calculate the target area coverage based on the prescribed treatment plan.Depending on the calculated target area coverage, the radiation therapy system may provide a notification (e.g., a visual notification via a GUI presented on a display and / or an auditory signal) that radiation should proceed to be delivered according to the prescribed treatment plan (i.e., "OK to proceed") or that the session should be terminated until the treatment plan is updated or (re)calculated based on the latest biological and / or physiological data (i.e., "DO NOT PROCEED"). Some variations may generate a notification indicating one or more of the statuses summarized in Table 1 below. [Table 1]

[0052] The DVH and / or PQI that are deemed acceptable for treatment plan delivery may vary by clinician and / or clinic. In one variation, the DVH and / or PQI are deemed pass / go if 95% of all DVH points above 10% of the prescribed dose in the nominal DVH of the OAR and BgROI are within (within ±1% tolerance) the minimum and maximum DVH points at the two boundaries of the bounded DVH. The test threshold, percent pass, and comparison tolerance may be configuration variables that may be adjusted during commissioning of the system. Other criteria for proceeding to go-go status may optionally include a check to ensure that the average activity within the target region (e.g., PET affinity region such as a tumor) is above a minimum level configured in the system. For example, a check that the average SUV within the target region is above a minimum level as defined by the system and / or clinician and / or treatment plan.

[0053] In some variations, if it is determined that the treatment plan is no longer deliverable because the delivered radiation would not be within a pre-approved range or boundary, the radiation therapy system may provide a recommendation or guidance to the clinician and / or technician regarding the type of treatment plan adaptation. Some variations may include a biological compatibility trigger, which includes one or more treatment plan quality and / or delivery criteria or metrics and a corresponding type (or types) of adaptation if the calculated dose delivered by the treatment plan (e.g., calculated based on real-time imaging data, biological and / or physiological data) does not meet those quality and / or delivery criteria. For example, a clinician or clinic may set a first treatment goal of at least 95% target area coverage level with a 1% tolerance during radiation delivery (meaning, e.g., that 94% coverage may be acceptable for delivery and may be optionally subject to clinician review and approval), and a second treatment goal of a maximum mean dose (MMD) value to the near-field OARs of less than 1,500 cGy maximum mean dose with a 200 cGy tolerance throughout the structure (meaning, e.g., that 1,500 cGy to 1,700 cGy maximum mean dose may be acceptable for delivery and may be optionally subject to clinician review and approval). If the treatment plan falls short of any of these goals or delivery metrics on the treatment day (i.e., based on imaging data from a pre-scan), the system may indicate that the delivery has "Failed / Do Not Proceed" with an optional indication of the type of fit recommended for the treatment plan, e.g., "Failed with recommendation."

[0054] For example, if the target coverage is below the 94% tolerance point but above 90% and the MMD value for the near-field OAR is within the target, the system may generate a notification indicating "Fail with recommendation." The recommendation may be to adapt the treatment plan to provide a dose escalation to increase the coverage as long as the near-field OAR does not violate its MMD constraint. For example, if the target coverage is 93% with an MMD value for an OAR of 1,300 cGy, the system may generate a notification indicating "Fail with recommendation." The recommendation may be to adapt the treatment plan to provide a uniform dose escalation to the target area to achieve an updated target coverage of 95% and 1,450 cGy.

[0055] In another example, if the MMD value for the near-field OAR is above the 1,700 cGy tolerance level and the target coverage is above the 95% target, the system may generate a notification indicating "Fail with recommendation". The recommendation may be to adapt the treatment plan to provide a dose reduction to reduce the MMD coverage as long as the target coverage remains above the 95% target. For example, if the target coverage is 99% with an MMD value for the OAR of 1,950 cGy, the system may generate a notification indicating "Fail with recommendation". The recommendation may be to adapt the treatment plan to provide a uniform dose reduction to the target structure and achieve an updated target coverage of 95% and 1,450 cGy. Alternatively or in addition, other objectives and / or radiation delivery metrics may also trigger updates or adaptations to the treatment plan. For example, the treatment plan may be updated in response to changes in dose shaping, structure modifications, changes in launch angle for a given location, or similar adjustments to the intended delivery.

[0056] FIG. 2A depicts a flow chart representation of a method for adapting radiation therapy based on biological activity and / or physiological data. This example is described in the context of using PET tracers, but it should be understood that any type of tracer and / or imaging modality may be used. The method 200 may include acquiring 202 imaging data of a patient at the beginning of a treatment session and / or during a treatment session, and extracting 204 biological activity and / or physiological data from the acquired imaging data. The imaging data may include, for example, positron annihilation emission pathways emitted from a PET tracer injected into the patient prior to a treatment session. The biological activity and / or physiological data may include tracer uptake values ​​(e.g., standard uptake values ​​or SUVs), PET tracer kinetics, tissue metabolism data, bone formation activity data, oxygenation data, gene expression data (e.g., human growth factor receptor type 2 (HER2) expression), free fatty acid uptake data, blood flow data, vascularity data, morphological shifts in tumor geometry (e.g., spiculation formation), and / or lymphatic activity data, etc. The SUV of a particular 2D or 3D region within an image can be calculated from the imaging data by multiplying the intensity of pixels or voxels within that region, calibrated to represent a known tissue tracer activity (typically in mCi / g), divided by the dose injected (typically in mCi) per patient weight (typically in kg) at a particular time since the initial injection (when the scan was obtained), as follows:

number

[0057] Various alternative derived values ​​are additionally available, such as mean SUV of 3D volume, minimum, maximum, standard deviation, multi-regional SUV ratio, and / or total body weight (sometimes referred to as SUV BW Instead of lean body mass (SUV LBM) or body surface area (SUV BSA ) may be calculated for a volume of interest. PET tracer kinetics may be calculated by monitoring changes in pixel intensity over time and calculating activity values ​​derived over time. That is, biological activity and / or physiological values ​​derived from PET tracer kinetics and SUV measurements (e.g., mean uptake values, change in SUV, etc.) may be calculated, optionally, as a function of time. Different types of PET tracers may target different types of cell markers (e.g., proteins, genes, etc.), and measuring PET tracer kinetics may provide an indication of changes in the tracer-tagged cell markers. For example, changes in tissue metabolism and / or aerobic and anaerobic glycolysis and / or glucose consumption or metabolism in a region of interest may be measured by injecting 18-F fluorodeoxyglucose (FDG) and measuring tracer activity levels (e.g., change in SUV) within a given defined target region over the course of a chronic treatment period (e.g., 30 minutes), and calculating a slope value K that represents the net uptake rate of entry into the tumor using the following formula:

number

[0058] Other types of tracers may also be used to measure different biological mechanisms and / or physiological and / or biological activity levels. For example, 13N-nitrogen tracers may be used in patients to monitor regional pulmonary function (RPF) and / or aeration of blood containing the tracer. This may provide an indication of whether blood aeration is within normal or expected ranges and whether blood is flowing through ventilated regions of the lung. Measuring 13N-nitrogen tracer kinetics may also provide information about blood flow to non-ventilated regions of the lung (i.e., blood diverted or redirected away from ventilated lung regions). The net flow rate of aerated blood may be calculated by calculating the tracer kinetics of the target region. For example, calculating net tracer kinetics (e.g., net tracer flow) may include using a multi-compartment model to calculate the difference between the flow rates of aerated tracers (e.g., tracers present in aerated blood that have been dispersed or diffused) and shunted or non-aerated tracers (e.g., tracers present in non-aerated blood or non-ventilated tissues such as alveoli that are perfused with fluid). The net tracer flow may be compared to expected tracer flow data (e.g., collected in a previous diagnostic or treatment session) to help determine whether treatment plan adaptation may be appropriate. For example, if the net tracer flow in a region is less than the expected tracer flow (e.g., as calculated during a previous treatment session), the treatment plan may be modified to allow a higher dose to be delivered to that region. A lower net tracer flow may indicate improved or robust lung function and / or blood flow, and thus that the target region may be able to tolerate increased levels of radiation. A higher net tracer flux may indicate reduced or ineffective lung function and / or blood flow and thus that the target region may be more sensitive or less tolerant to radiation (e.g., may be more susceptible to lung collapse and more likely to cause an increase in pulmonary perfusion).

[0059] In another example, changes in DNA synthesis and / or tumor cell proliferation rates during a treatment session can be measured by using 18F-fluorothymidine tracers. 11C-methionine tracers can also be used to measure changes in protein synthesis and / or tumor cell proliferation rates during a treatment session. The difference in SUV of the tumor area (e.g., SUV diff ) can be measured by subtracting the SUV of a voxel in the region of interest in the current treatment session from the SUV of the voxel in the previous treatment session. Changes in tumor region hypoxia can be measured using 18F-fluoromisonidazole (e.g., FMISO, FETNIM) and / or 18F-fluoroazomycin arabinoside tracers (e.g., FETNIM). SUV max For example, the gradient method is about 30-50% SUV max The gradient of SUV can be used to delineate between tumor and non-tumor tissue. A threshold can be set at a value along the gradient that can identify or delineate regions of elevated SUV levels and therefore regions of increased hypoxia. Changes in folate receptor density during a treatment session can be measured using 3'-aza-2'-[18F]fluorofolate tracer. Differences in SUV (e.g., SUV diff ) may be measured by subtracting the SUV of voxels in the region of interest in the current treatment session from the SUV of voxels in the previous treatment session. The level of HER2 gene expression (HER2GE) may be measured using N-succinimidyl 3-((4-(4-(18)F-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoic acid radiolabeled 5F7 antibody. The mean SUV (SUV mean_total ) was calculated by dividing the volume of the VOI by the mean SUV of the tumor volume (SUV meanAlternatively, or in addition, the change in HER2 expression level during a treatment session may be calculated by subtracting the SUV of a voxel within the VOI in the current treatment session from the SUV of the voxel in the previous treatment session or scan, i.e., the difference in the SUV of the VOI (e.g., SUV diff )

[0060] Optionally, biological activity and / or physiological data may be calculated based on the spectroscopic imaging data. For example, spectroscopic imaging may be used to calculate the spatial distribution of metabolite concentrations in one or more patient regions (e.g., any region of interest including OAR, PTV, etc.). In some variations, magnetic resonance (MR) spectroscopic image data may be obtained at each treatment session and compared to MR spectroscopic image data from previous treatment and / or diagnostic imaging sessions. Treatment planning and / or radiation delivery may be modified such that tumor regions with increased levels of metabolites may be irradiated with higher levels of radiation. Conversely, if metabolite levels in tumor regions decrease, treatment planning and / or radiation delivery may be modified such that the dose delivered to these tumor regions is reduced.

[0061] Some variations may also include calculating and / or extracting anatomical data, such as the size and location of any target regions, bone structure, radiation avoidance regions, patient weight, and the like.

[0062] The method 200 may further include determining 206 whether the current treatment plan is deliverable based on the extracted biological activity and / or physiological data. The treatment plan is generally formulated based on previously acquired patient data (e.g., anatomical, biological activity and / or physiological data), and if any patient parameters have changed since the initial data acquisition session and treatment session, the treatment plan may need to be updated or recalculated to achieve clinical treatment goals. At the time of treatment, determining whether the treatment plan may be considered deliverable may include evaluating the treatment plan based on the newly acquired imaging data and / or the extracted biological and / or physiological data, calculating an expected delivery dose to one or more target regions within the patient, and determining whether the expected delivery dose is within a predetermined dose range and / or conforms to a desired dose distribution. For example, the treatment plan may be considered deliverable if the expected delivery dose to the irradiation target region exceeds a lower threshold (e.g., a minimum boundary) and the expected delivery dose to the irradiation avoidance region does not exceed an upper threshold (e.g., a maximum boundary). In some variations, the controller may make a decision whether to proceed with a radiation therapy treatment plan based on data values ​​that have been pre-approved by a clinician. For example, one or more of the DVH curves and / or PQIs may be calculated during treatment planning, and these ranges (e.g., bounded DVH curves, ranges of PQI values) may be reviewed and approved by a clinician. Alternatively, or in addition, the decision whether to proceed with radiation therapy may be made by the clinician using information provided by the controller about biological and physiological activity levels, treatment plan efficiency, dose distribution, etc. As described above, in some variations, a GUI rendered on a display (e.g., monitor) may provide visual and / or audible notification of whether the current treatment plan is deliverable (i.e., whether the current treatment plan will deliver radiation within a previously approved range).For example, the GUI may provide one or more of the following notifications: pass / continue, and / or fail / don't continue, and / or pass with tolerance, and / or pass with exceptions, and / or fail with recommendation. Some systems may be configured to provide two tiers of notifications (e.g., pass / continue, and fail / don't continue), three tiers of notifications (e.g., pass / continue, pass with tolerance or pass with exceptions, and fail / don't continue), four tiers of notifications (e.g., pass / continue, pass with tolerance, pass with exceptions, and fail / don't continue), or five tiers of notifications as described above. The clinician and / or clinic may select the type or number of tiers of notifications desired and may decide whether to proceed or stop treatment according to or against the generated notifications.

[0063] If it is determined that the treatment session may proceed with the current treatment plan 208, the controller may generate a set of system instructions / commands and transmit them to the radiation emission assembly for radiation delivery to the patient. In some variations, this may include generating a fluence map based on the treatment plan and segmenting the fluence map into a DMLC leaf pattern or sinogram. Steps 202-206 may be repeated until the treatment session is completed (as defined by the treatment plan and / or clinician commands and / or patient commands). If it is determined that the treatment session should not proceed with the current treatment plan, the method 200 may include determining 210 whether the treatment session should be terminated. For example, the obtained biological activity and / or physiological data may indicate that the patient is unable to tolerate any radiation exposure, and / or that the region of interest has changed significantly since the treatment planning session, and / or that the patient has not adhered to the pre-treatment protocol (e.g., ingested a carbohydrate-rich food immediately prior to the treatment session, invalidating the patient's PET images when 18-F FDG was used), and / or that the planned radiation exposure may no longer provide adequate treatment (e.g., the tumor has become hypoxic, interfering with radiation therapy), adapting the plan is infeasible, and / or that the PET tracer uptake or SUV will not be able to ensure dose delivery of acceptable quality (e.g., poor uptake, non-specific uptake, high levels of background noise, etc.). Terminating 212 the treatment session may optionally include updating or recalculating the treatment plan to accommodate the changes in biological activity and / or physiological data. The updated or adapted treatment plan may then be used for future treatment sessions.

[0064] If it is determined that the treatment session should not be terminated 210, the method 200 may optionally include updating or recalculating the treatment plan (i.e., replanning, adapting the treatment plan) to account for any changes in the expected dose distribution due to differences in biological activity and / or physiological data obtained at the time of delivery compared to biological activity and / or physiological data obtained during treatment planning. The updated treatment plan may take into account the current condition of the patient and / or target region as indicated by the obtained biological activity and / or physiological data while meeting most (if not all) of the clinical goals set by the clinician. For example, the updated treatment plan may incorporate the obtained biological activity and / or physiological data and calculate updated radiation delivery parameters (e.g., RFM, fluence map, radiation emission assembly instructions, etc.) such that the dose delivered to one or more target regions is within a desired dose range.

[0065] The treatment plan may be updated in one or more aspects depending on the type and / or magnitude of changes in the physiological and / or biological activity data. The treatment plan may be updated to increase the dose delivered to the target area if the data indicates that the target area is more radiation resistant, and / or the irradiated area may be increased or decreased depending on the movement of the target area or the change in size of the target area. Alternatively or additionally, the treatment plan may be adjusted to decrease the irradiation of the OAR. Adaptations to the treatment plan due to changes in metabolic tumor volume (MTV) may include adjusting the target contour to fit the new size and shape of the MTV. Adaptations due to changes in metabolic rate may include decreasing the dose to areas of reduced metabolic rate and increasing the dose to areas of increased metabolic rate. Areas of reduced metabolic rate may correspond to non-tumor tissue, while areas of increased metabolic rate may correspond to tumor tissue. Changes in metabolic activity levels and / or concentrations of metabolites may be calculated based on changes in SUV and / or spectroscopy data (e.g., MR spectroscopy). Plan adaptations due to increased LG to NTG ratios (relative to surrounding OARs) may include increasing the dose gradient in those regions (e.g., steeper dose gradients). Plan adaptations may include increasing the dose to a region if an increase in LG levels in that region is detected. Plan adaptations due to detected changes in RPF, such as lower net flow, may include reducing irradiation of OARs near the target region (e.g., increasing OAR dose exclusion), which may optionally include reducing the dose delivered to the target region. Adaptations to the treatment plan due to increased DNA synthesis and / or protein synthesis rates may include increasing the dose gradient in those regions (e.g., steeper dose gradients). diff Increase the dose to voxels with negative SUV values. diff Adapting the treatment plan due to changes in hypoxia levels in the target region may include increasing the dose (e.g., increasing the minimum dose level) if the hypoxia level increases. Adapting the treatment plan due to changes in folate receptor density may include increasing the dose (e.g., increasing the minimum dose level) if the hypoxia level increases. diff Increase the dose to voxels with positive values ​​for the volume and SUVdiff Adaptation to the treatment plan due to changes in HER2 expression may include decreasing the dose to voxels with negative values ​​for volume. mean_total If SUV increases (e.g., indicating increased HER2 gene expression), the treatment plan may include extending the dose gradient between the tumor volume of interest and the normal tissue. If radiation therapy is pre-specified in conjunction with HER2-targeted immunotherapy, the treatment plan may include extending the dose gradient between the SUV diff Decrease dose to voxels with positive values ​​for volume and SUV diff The volume can be adjusted by increasing the dose to voxels with negative values.

[0066] Table 2 below summarizes examples of types of physiological and / or biological activity data that may be calculated based on the imaging data, methods for deriving this activity data from the imaging data, and corresponding treatment plan adaptations. [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4]

[0067] After generating an updated treatment plan (which may optionally be reviewed and approved by a clinician), method 200 may include delivering 216 radiation to the patient according to the updated treatment plan. In some variations, it may include generating a fluence map based on the updated treatment plan and segmenting the fluence map into a DMLC leaf pattern or sinogram. A therapeutic radiation source may be activated according to instructions from a controller based on the sinogram. Method 200 may be performed one or more times during a treatment session. For example, method 200 may be performed at the beginning of a treatment session to determine whether to proceed with the current treatment plan and / or to update or recalculate the current treatment plan, and not performed again until the next treatment session. This may be referred to as online adaptive radiation therapy. Alternatively, method 200 may be performed multiple times throughout a treatment session, such as at the beginning of a treatment session, periodically throughout a treatment session (e.g., at all firing positions, every other firing position, etc.), and / or at the end of a treatment session. This may continually update the treatment plan according to the patient's real-time condition throughout the treatment session. This may be referred to as real-time adaptive radiation therapy. Optionally, the method 200 may be performed as commanded by a clinician (e.g., via a GUI). Biological activity and / or physiological data obtained during a treatment session may be used after the treatment session to update or recalculate the treatment plan for the next treatment session. This may be referred to as offline adaptive radiation therapy.

[0068] (Online Adaptive Radiation Therapy) FIG. 2B depicts one variation of a method for online adaptive radiation therapy based on biological activity and / or physiological data. Prior to a treatment session (blocks 231a-231c), a treatment plan may be generated for the patient based on images or image data acquired using any desired imaging modality (e.g., PET, SPECT, MRI, CT, X-ray, etc.) and / or in conjunction with a clinician consultation. In some variations, a treatment plan simulation is performed to calculate and / or estimate the expected dose distribution profile of the treatment plan, and depending on the outcome of the simulation, there may be further changes to the treatment plan. Online adaptive radiation therapy may include updating or calculating a treatment plan based on biological and / or physiological data acquired at the beginning of a treatment session (e.g., before the therapeutic radiation source is turned on). The newly adapted or calculated treatment plan may be used to deliver radiation to the patient during the treatment session. For example, the online adaptive radiation therapy method 230 may include acquiring 232 imaging data, such as a functional imaging scan, during treatment delivery. This may include, for example, obtaining imaging data using any imaging modality (e.g., PET, SPECT, MRI, CT, X-ray, etc.) at the beginning of a treatment session, before the first radiation beam is applied to the patient. The controller may then evaluate whether biological activity and / or physiological data extracted from the imaging data indicates that a change to the current treatment plan is needed 234. Evaluating the biological activity and / or physiological data may include extracting various parameters of the patient and / or target region, including, but not limited to, target region contouring, target region isocenter, and / or OAR location. Dose delivery rate, treatment time, isodose gradients, dose non-uniformity, dose adaptation, beam characteristics, and motion management strategies may be adapted based on the biological activity and / or physiological data.This may include, for example, shortening treatment time by increasing dose delivery rate and couch speed when the motion envelope of a patient's target region is reduced in size due to a particular biological function (e.g., using PET tracer kinetics to detect reduced regional lung function, which may have the side effect of reducing the motion envelope of nearby region targets). Alternatively or in addition, it may include increasing the isodose gradient and dose non-uniformity of a given target region, for example, to provide a higher dose concentration to regions within the target region that were not present in the previous treatment planning reference image (e.g., hypoxic regions that were not present in the simulation image). This adaptation may also include, but is not required to include, an increased total delivered dose to the target region. Alternatively or additionally, it may include modifying the particular mechanism of the motion control mechanism to be used during treatment, for example, as a result of physiological indicators that the motion control mechanism may cause more harm than good (e.g., shifting or reducing the pressure applied by the abdominal compression unit upon detection of higher intra-abdominal pressure due to previously undetected perfusion, plus compensating the target area size of the treatment plan to match the now increased motion envelope). Optionally, the method may include determining 235 whether the radiation therapy system is capable of delivering the prescribed radiation dose and / or whether the prescribed radiation dose has been delivered according to the plan. Methods for evaluating the treatment plan based on the patient imaging data and determining whether the current treatment plan needs to be updated or adapted are further described below. If no changes are required, the radiation therapy system may proceed to deliver treatment according to the current treatment plan 236, and may optionally obtain imaging data (e.g., PET data) indicative of biological activity and / or physiological parameters.

[0069] If changes to the treatment plan are required, the extracted biological activity and / or physiological data may be used to recalculate or adapt the treatment plan 238. Optionally, the functional image data and / or the planning image data (from blocks 237a and 237b, respectively) may be used to adapt the treatment plan. Modifications to the treatment plan may include absolute dose values ​​for each target region, dose limits for each target region and / or cumulatively for the patient, biologically effective dose values, equivalent dose values, and treatment fractions. This may include adapting dose limits for target regions, for example, by increasing the maximum dose allowed over a percentage of the volume to account for hypoxic region formation between simulation and treatment. Additionally or alternatively, it may include increasing the allowed biologically effective dose constraints for a region to accommodate changes in treatment fractions resulting from, for example, substantially different metabolic activity detected within the target region that results in the current fraction being untreatable. Alternatively or additionally, depending on the type of tracer used, the treatment plan may be adapted as described above and summarized in Table 2. In some variations, recalculating or adapting the treatment plan to incorporate biological activity and / or physiological data obtained during treatment may include simulating one or more test treatment plans with the obtained biological activity and / or physiological data, and selecting an updated treatment plan from the one or more test treatment plans that meets the clinical goals and / or provides the desired dose distribution. In some variations, the updated or adapted treatment plan may conform to prescribed or approved PQI ranges and / or biological activity and / or physiological data ranges. The adaptive radiation therapy treatment planning process may generate the treatment plan and associated treatment plan artifacts following a similar methodology as normal treatment planning. In some variations, many of these artifacts are generated automatically or with the use of tools specifically designed to reduce the amount of time required to perform the operations.In some variations, the adapting and matching treatment plan process is performed on the same software as the initial treatment plan. The method 230 may then include delivering 236 radiation according to the updated or adapted treatment plan. In some variations, the updated or adapted treatment plan may be reviewed, evaluated, and / or approved by a clinician when created and / or before radiation is delivered according to the updated plan. The updated or adapted treatment plan may optionally be stored in a treatment plan database (e.g., in the controller's memory and / or a remote server memory). Future treatment sessions or fractions may reference the stored treatment plan as desired. Alternatively or additionally, the updated or adapted treatment plan may be stored in the patient treatment record for review and assessment by the patient and / or clinician. Future treatment sessions or fractions may reference the treatment plan stored in the patient record as desired.

[0070] Optionally, upon completion of a treatment session, additional imaging data may be obtained. For example, one or more final functional imaging scans may be obtained upon completion of a treatment session (e.g., after the last radiation beam is applied). Optionally, after a treatment session (i.e., after the patient exits the radiation therapy system), the controller may evaluate whether the treatment plan delivered within the treatment session should be updated for the next treatment session based on biological activity and / or physiological data extracted from the final imaging scan 240. If the biological activity and / or physiological data indicates that a change to the treatment plan is needed, the controller may then recalculate or adapt the treatment plan for a future treatment session 242 using any one or more of the adaptations described above. An offline adapted treatment plan may refer to the calculation and / or simulation of a treatment plan between treatment sessions using biological activity and / or physiological data obtained during a previous treatment session. Optionally, treatment plans generated during a treatment session and / or offline may be stored in a treatment plan database. The treatment plans in the database can be used in future treatment sessions, if desired.

[0071] (Real-time adaptive radiation therapy) FIG. 2C depicts one variation of a method for real-time adaptive radiation therapy based on biological activity and / or physiological data. In real-time adaptive radiation therapy, a treatment plan is updated or adapted multiple times during a treatment session based on biological activity and / or physiological data acquired during the same treatment session. For example, if the acquired biological activity and / or physiological data extracted from image data acquired at the beginning of a treatment session indicates that a treatment plan generated in a previous planning session is still applicable, the radiation therapy system may begin radiation dose delivery according to that treatment plan. As functional image data is acquired during a treatment session, the treatment plan may be updated or adapted according to any changes detected in the biological activity and / or physiological data. Real-time adaptive radiation therapy may include updating or calculating a treatment plan based on biological and / or physiological data acquired throughout a treatment session (e.g., during activation of a therapeutic radiation source). The newly adapted or calculated treatment plan may be delivered to the patient during the treatment session, and in some variations, in real time. At the end of a treatment session, the final iteration of the treatment plan may not be identical to the treatment plan from the beginning of the treatment session, depending on how patient biological activity and / or physiology may change over the course of treatment.

[0072] Turning now to FIG. 2C, prior to a treatment session (blocks 251a-251c), a treatment plan may be generated for the patient based on images or image data acquired using any desired imaging modality (e.g., PET, SPECT, MRI, CT, X-ray, etc.) and / or with the clinician's consultation. In some variations, a treatment plan simulation may be performed to calculate and / or estimate the expected dose distribution profile of the treatment plan, and further changes to the treatment plan may be made depending on the outcome of the simulation. The online adaptive radiation therapy method 250 may include acquiring 252 imaging data, such as a functional imaging scan, during treatment delivery. This may include, for example, acquiring imaging data using any imaging modality (e.g., PET, SPECT, MRI, CT, X-ray, etc.) at the beginning of a treatment session before the first radiation beam is applied to the patient. The controller may then evaluate 254 whether biological activity and / or physiological data extracted from the imaging data indicates that changes to the current treatment plan are required. Evaluating biological activity and / or physiological data may include extracting various parameters of the patient and / or target region, including, but not limited to, target region contouring, target region isocenter, and / or OAR location. The biological activity and / or physiological data may also provide information related to dose delivery rate, treatment time, isodose gradient, dose non-uniformity, dose conformance, beam characteristics, and motion management strategies. This may include, for example, shortening treatment time by increasing dose delivery rate and couch speed when the motion envelope of a patient's target region is reduced in size due to a particular biological function (e.g., using PET tracer kinetics to detect reduced regional lung function, which may have the side effect of reducing the motion envelope of nearby region targets). Alternatively or additionally, it may include increasing the isodose gradient and dose non-uniformity of a given target region, for example, to provide a higher dose concentration to regions within the target region that were not present in the previous treatment planning reference image (e.g., hypoxic regions that were not present in the simulation image). This adaptation may, but need not, include an increased total delivered dose to the target area.Alternatively or additionally, it may include modifying certain features of the motion control mechanism to be used during treatment, for example as a result of physiological indicators that the motion control mechanism may be causing more harm than benefit (e.g., shifting or reducing the pressure applied by the abdominal compression unit upon detection of higher intra-abdominal pressure due to previously undetected perfusion, plus compensating the target area size of the treatment plan to fit the now increased motion envelope). Methods for evaluating a treatment plan based on patient imaging data and determining whether a current treatment plan needs to be updated or adapted are further described below.

[0073] If no changes are required, the radiation therapy system may proceed to deliver treatment according to the current treatment plan 258. If changes to the treatment plan are required, the extracted biological activity and / or physiological data may be used to recalculate or adapt the treatment plan 260. Modifications to the treatment plan may include absolute dose values ​​for each target region, dose limits for each target region and / or cumulatively for the patient, biologically effective dose values, equivalent dose values, and treatment fractions, as described above with reference to FIG. 2B. Alternatively or additionally, depending on the type of tracer used, the treatment plan may be adapted, as described above and summarized in Table 2. In some variations, recalculating or adapting the treatment plan to incorporate the biological activity and / or physiological data obtained during treatment may include simulating one or more test treatment plans using the obtained biological activity and / or physiological data, as described above with reference to FIG. 2B, and selecting an updated treatment plan from the one or more test treatment plans that meets the clinical goals and / or provides the desired dose distribution. In some variations, the updated or adapted treatment plan may comply with defined or approved PQI ranges and / or biological activity and / or physiological data ranges. The method 250 may then include delivering 258 radiation according to the updated or adapted treatment plan. In some variations, the updated or adapted treatment plan may be reviewed, evaluated, and / or approved by a clinician at the time of creation and / or before radiation is delivered according to the updated plan.

[0074] During a treatment session, biological activity and / or physiological data may continue to be monitored (e.g., in real time) by acquiring imaging data while applying radiation according to a current version or iteration of the treatment plan. For example, imaging data may be acquired at predetermined time intervals (e.g., about 10 Hz, 5 Hz, 2 Hz, 1 Hz, 0.5 Hz, etc.) and / or at all or a subset of firing locations. Method 250 may then include determining 262 whether to modulate or adapt treatment delivery. Methods for evaluating the treatment plan in light of the updated biological activity and / or physiological data and determining whether the current treatment plan is suitable for treatment are further described below. Modulating or adapting treatment delivery 264 may include, for example, shifting or scaling a fluence map, and / or adjusting dose intensity for a target region, and / or increasing or decreasing dose for a target region, etc. Additionally or alternatively, treatment delivery may be modulated by varying the duty cycle of the treatment, increasing or decreasing the number of available firing locations to accommodate changes that would prevent or allow an area to receive a different amount of radiation than originally planned (e.g., detecting the severity of cardiac perfusion deteriorating midway through a treatment, which may allow the system to reduce the number of firing locations exposing that area to radiation, but increase the overall treatment time to reach the same prescribed dose of radiation). Alternatively or additionally, depending on the type of tracer used, the treatment plan may be adapted, as described above and summarized in Table 2. The radiation therapy system may then proceed to deliver radiation to the patient according to the modifications calculated above.

[0075] Optionally, upon completion of the treatment session, additional imaging data may be obtained. For example, one or more final functional imaging scans may be obtained upon completion of the treatment session (e.g., after the last radiation beam is applied). Optionally, after the treatment session (i.e., after the patient has exited the radiation therapy system), the controller may evaluate whether to update or adapt any of the treatment parameters or plans implemented during the treatment session based on biological activity and / or physiological data extracted from the final imaging scan 266. If the biological activity and / or physiological data indicates that a change to the treatment plan is needed, the controller may then recalculate or adapt the treatment plan for future treatment sessions using any one or more of the adaptations described above 268. Optionally, the treatment parameters and / or treatment plans generated during the treatment session and / or offline may be stored in a treatment plan database. The treatment plans in the database may be used in future treatment sessions, as desired.

[0076] (Offline Adaptive Radiotherapy) Imaging data (such as functional imaging data) acquired during a treatment session may be used to calculate or generate a treatment plan for the patient during the next treatment session. Offline adaptive radiation therapy may include calculating or generating a treatment plan between treatment sessions when the patient is not located in the treatment system. As previously described, imaging data may be acquired at the beginning of a treatment session, before the first radiation beam is applied to the patient. The imaging data may be acquired using any imaging modality, such as PET, SPECT, MRI, CT, X-ray, etc. The controller may then evaluate whether the previously calculated treatment plan is deliverable and / or meets clinical goals based on biological activity and / or physiological data extracted from the acquired imaging data. If not, the treatment session is terminated and the imaging data, extracted biological activity and / or physiological data are stored in the controller memory to update or adapt the treatment plan for the next treatment session. If the previously calculated treatment plan is deliverable and / or meets clinical goals, radiation therapy based on that treatment plan may proceed. Optionally, imaging data may be obtained during and / or at the end of a treatment session. All imaging data, extracted biological activity and / or physiological data, and any other calculated qualities may be stored in the controller memory. After the end of the treatment session, the controller may update or adapt the treatment plan (or generate a new treatment plan) based on the obtained imaging data using one or more of the adaptations described above. As previously mentioned, any treatment plan and / or treatment session parameters may be stored in a treatment plan database and / or a patient record database.

[0077] FIG. 2D depicts a method for offline adaptive radiation therapy. Prior to a treatment session (blocks 271a-271c), a treatment plan may be generated for the patient based on images or image data acquired using any desired imaging modality (e.g., PET, SPECT, MRI, CT, X-ray, etc.) and / or with a clinician's consultation, as described above. During a treatment session 273 in which radiation is delivered based on a previously generated treatment plan, the radiation therapy system acquires imaging data from which biological activity and / or physiological data may be extracted. This data may be stored in a controller memory and may be used to update or adapt the treatment plan (or generate a new treatment plan) after completion of the treatment session. The offline adaptive radiation therapy method 270 may include determining whether to update the treatment plan 272 based on biological activity and / or physiological data extracted from imaging data acquired during a previous treatment session. Evaluating biological activity and / or physiological data may include extracting various parameters of the patient and / or target region, including, but not limited to, target region contouring, target region isocenter, and / or OAR location. The biological activity and / or physiological data may also provide information related to dose delivery rate, treatment time, isodose gradient, dose non-uniformity, dose conformance, beam characteristics, and motion management strategies. This may include shortening treatment time by increasing dose delivery rate and couch speed, for example, when the motion envelope of the patient's target region is reduced in size due to a particular biological function (e.g., using PET tracer kinetics to detect reduced regional lung function, which may have the side effect of reducing the motion envelope of nearby region targets). Alternatively or in addition, it may include increasing the isodose gradient and dose non-uniformity of a given target region, for example, to provide a higher dose concentration to regions within the target region that were not present in the previous treatment planning reference image (e.g., hypoxic regions that were not present in the simulation image). This adaptation may, but need not, include an increased total delivered dose to the target area.Alternatively or additionally, it may include modifying certain features of the motion control mechanism to be used during treatment, for example as a result of physiological indicators that the motion control mechanism may cause more harm than good (e.g., shifting or reducing the pressure applied by the abdominal compression unit due to detection of higher intra-abdominal pressure due to previously undetected perfusion, plus compensating the target area size of the treatment plan to fit the now increased motion envelope). Alternatively or additionally, depending on the type of tracer used, the treatment plan may be adapted, as described above and summarized in Table 2. Methods for evaluating the treatment plan and determining whether the current treatment plan needs to be updated or adapted based on patient imaging data are further described below.

[0078] If no changes are required, the treatment plan may be used to deliver radiation for the next treatment session or fraction. If changes to the treatment plan are required and / or the biological activity data and / or physiological data meet the criteria for updating the treatment plan, the extracted biological activity and / or physiological data may be used to recalculate or adapt the treatment plan 274. Optionally, functional image data and / or planning image data (block 275a) may be used to adapt the treatment plan. Optionally, treatment simulations may be reacquired to adapt the treatment plan (block 275b). Modifications to the treatment plan may include absolute dose values ​​for each target region, dose limits for each target region and / or cumulatively for the patient, biologically effective dose values, equivalent dose values, and treatment fractions, as described above with reference to FIG. 2B. Alternatively or additionally, depending on the type of tracer used, the treatment plan may be adapted as described above and summarized in Table 2. In some variations, recalculating or adapting the treatment plan to incorporate biological activity and / or physiological data obtained during treatment may include simulating one or more test treatment plans using the obtained biological activity and / or physiological data, as described above with reference to FIG. 2B, and selecting an updated treatment plan from the one or more test treatment plans that meets the clinical goals and / or provides the desired dose distribution. In some variations, the updated or adapted treatment plan may conform to a prescribed or approved PQI range and / or biological activity and / or physiological data range. The updated treatment plan may be used for a subsequent treatment session or fraction. The method 270 may be repeated after each treatment session or a selected set of treatment sessions, as desired. In some variations, the treatment plan calculation may be performed by a radiation therapy system controller.Alternatively, or in addition, the radiation therapy system may transmit collected imaging data and / or biological activity and / or physiological data to a remote controller, such as a treatment planning system controller, which may perform treatment plan calculations and send a treatment plan (which may or may not be updated) back to the radiation therapy system.

[0079] (How to evaluate a treatment plan) One or more methods may be used to evaluate a treatment plan and determine whether the treatment plan will provide the desired dose of radiation to the ROI or target region. The desired radiation dose may, in some variations, be a prescription written by a radiation oncologist and may define dose-volume (DV) constraints for the target region (e.g., irradiation target region and / or irradiation avoidance region). These may include DV constraints for the tumor region and / or radiation sensitive regions (e.g., organs at risk). The irradiation target region containing the tumor may include the gross tumor volume and a margin surrounding the gross tumor volume to account for microscopic disease, tumor motion, and patient setup uncertainties. An example of a radiation dose prescription for lung stereotactic treatment is depicted in FIG. 3A. As illustrated in the table, the clinician may define different types of ROIs within the patient, such as one or more planning target volumes (PTVs; which may include a tumor mass and a margin surrounding the tumor mass) that include at least a portion of the arteriovenous system, spinal cord regions, the entire lung, skin regions, ribs, heart, esophagus, liver, and specific vascular regions (e.g., regions occupied by vessels such as the aorta, inferior vena cava, superior vena cava, pulmonary artery, or pulmonary veins). Some of these ROIs are irradiation target regions (e.g., PTVs), while others are irradiation avoidance regions (e.g., spinal cord, lung, skin, vasculature). For each of the ROIs, the clinician may define thresholds for the percentage of the ROI to be irradiated, the maximum cumulative amount of radiation that may be applied over the entire ROI, and the maximum amount of radiation that may be applied over a portion of the ROI. For example, for an irradiation target area such as the PTV region, the radiation dose prescription may specify that at least 95% of the PTV area is to be irradiated with a maximum cumulative radiation level of about 50 Gy, and no portion of the PTV should be exposed to radiation at more than 107% of the prescribed radiation level (e.g., 1.07 x 50 Gy = 53.5 Gy). In some variations, the clinician may specify that a small area of ​​the PTV should be irradiated. That is, the clinician may specify that only the tumor mass area of ​​the PTV should be irradiated, and / or that a percentage of the PTV volume (e.g., about 10%, about 20%, about 25%, about 35%, about 40%, about 50%, about 60%, about 65%, about 70%, about 75%, about 80%, about 90%, about 95%, etc.) should be irradiated.Examples of PTV sub-regions that a clinician may prescribe for irradiation may include a tumor mass region, a sub-region of a tumor mass region, a portion of multiple tumor mass regions, one or more hypoxic regions, one or more PET affinity regions, and / or any combination of the above. Without wishing to be bound by theory, irradiation of a portion of the PTV (instead of the entire PTV) may result in a sufficient level of tumor cell death to induce a patient immune response. Restoring the patient's immune system in conjunction with targeted radiation delivery may help reduce overall patient radiation exposure (compared to treatments in which the entire PTV is irradiated) while promoting tumor growth suppression. For irradiation avoidance regions such as the spinal cord region (and / or lungs, and / or skin, and / or vascular regions), the radiation dose prescription may prescribe that less than about 0.25 cc is irradiated, with a maximum cumulative radiation level of about 22.5 Gy, and no part of the spinal cord region should be exposed to more than about 30 Gy of radiation. Other radiation dose prescriptions may have different thresholds than the prescription in FIG. 3A because different types of tumors may require different levels of irradiation for eradication and different types of organs may have different sensitivities to radiation exposure. In some variations, the amount of radiation to be applied to the PTV may be determined, at least in part, based on patient parameters measured before or during the treatment planning session. For example, a tumor with areas of hypoxia may require a higher level of radiation for eradication compared to a tumor that does not have hypoxic areas. In a treatment planning session, if the measured patient parameters (e.g., PET tracer SUV uptake) indicate that the PTV has one or more hypoxic areas, the radiation dose prescription may specify that a greater proportion of the PTV is irradiated with a higher level of radiation than if the PTV did not have hypoxic regions.

[0080] The treatment planning system may generate a treatment plan that is aimed at delivering radiation dose levels to a patient ROI or target region as specified in a radiation dose prescription and according to patient parameters measured before or during a treatment planning session. Changes in patient parameters in the time between the treatment plan and the treatment session may affect the effectiveness of the treatment plan. Examples of patient parameter changes that may affect the effectiveness of the treatment plan may include, but are not limited to, any of the aforementioned biological activity and / or physiological parameters, such as the location and / or distance of the target region relative to the radiation avoidance region, the shape and size of the target region and / or radiation avoidance region, and the SUV and / or tracer activity of a tracer (e.g., a PET tracer, a tumor-specific tracer, etc.).

[0081] A method for evaluating whether a treatment plan delivers a prescribed dose distribution may include obtaining imaging data on a treatment day, but before treatment begins (e.g., before the first radiation beam is fired). This imaging data may be referred to as pre-scan data, and a controller may extract biological activity and / or physiological and / or anatomical data from the pre-scan data. The extracted biological activity and / or physiological and / or anatomical data may be used to calculate whether a current treatment plan will provide an adequate dose to a target area at the beginning of a treatment session. For example, a controller processor may simulate / calculate a dose distribution map or dose value histogram (DVH) based on the imaging data, the extracted biological activity and / or physiological and / or anatomical data, and the current treatment plan. Depending on whether the simulated dose distribution map or DVH meets certain criteria or thresholds, the controller and / or clinician may determine whether the treatment plan should be updated. For example, if the expected dose to be delivered to 95% of the simulated volume falls below the acceptable range of dose, either the volume definition or the dose to be delivered may be modified to bring the constraint back within the acceptable range. Alternatively or additionally, the method may also be used to evaluate the effectiveness of the treatment plan against imaging data acquired in real time during or after the treatment session. Some variations of the method may include calculating a range of acceptable clinical parameters during the treatment planning session (e.g., during treatment plan calculation), and biological activity and / or physiological and / or anatomical data extracted from the pre-scan imaging data and / or treatment session imaging data may be compared to the range of acceptable clinical parameters. The range of acceptable clinical parameters may be determined based on data acquired during the diagnostic imaging session, during the treatment planning session, and / or at the start of the treatment session (e.g., during the patient pre-scan), and / or may include a known or widely accepted range of normal activity.If the extracted data is within the range of acceptable clinical parameters, the controller and / or clinician may determine that it is appropriate to proceed with the current treatment plan without requiring the controller processor to simulate or calculate dose distribution maps or DVHs at the time of treatment. By reducing the time it takes to determine whether to proceed with the current treatment plan, the latency between obtaining imaging data and applying therapeutic radiation may be reduced. Examples of clinical parameters for which acceptability ranges may be calculated prior to a treatment session may include the location of the target region relative to the location of the OARs, the shape and volume of the target region, the SUV of the target region, PET tracer activity in the target region and / or OARs, etc.

[0082] Alternatively or additionally, during a treatment planning session, a range of acceptable treatment plan quality parameters may be calculated to calculate a range of acceptable clinical parameters. Treatment plan quality parameters may be any metric that assesses the degree to which a particular treatment plan provides a desired radiation dose to a target region while excluding non-target regions (e.g., radiation sensitive regions and / or normal tissue regions). Examples of plan quality scores or plan quality indices (PQIs) are depicted in the table in FIG. 3B and may include dose distribution indices or parameters that represent tumor dose coverage, DV relationship for a target region or ROI, conformity index, uniformity, and dose gradient index, etc. The target volume or TV may be the total volume of the ROI (e.g., planning target volume PTV or gross tumor volume GTV), and some PQIs may specify the percentage of the TV and / or the absolute volume of the TV (e.g., in cc) that should be irradiated at a specified radiation level. The Dvv index of a treatment plan may represent the predicted / calculated level of irradiation of a portion vv of the TV (e.g., percent of the total TV in cc or absolute volume) as a result of radiation delivery according to the treatment plan. For example, a treatment plan with a Dvv index of D95%=45Gy indicates that 95% of the TV will be irradiated with 45Gy if radiation delivery proceeds according to the treatment plan. The Vdd index of a treatment plan may represent the portion of the TV (e.g., percent of the total TV in cc or absolute volume) that is predicted / calculated to receive a dose dd (e.g., percent of the total target dose or absolute dose in Gy) as a result of radiation delivery according to the treatment plan. For example, a treatment plan with a Vdd index of V20Gy=40% indicates that 40% of the TV will be irradiated with 20Gy if radiation delivery proceeds according to the treatment plan. Another example of a PQI may include a compatibility index CI that represents the ratio of the volume of the PTV to the volume covered by the prescription isodose. The CI may define how tightly a particular target is covered by the prescription isodose. Numerically, the closer the ratio is to 1, the better the fit to the plan. In the ideal case, the PTV volume is very close to the prescription isodose volume, in which case CI=1. Clinicians may be willing to approve a plan if the CI is within some acceptable range, e.g., 1-1.2.If the CI>1.2, the clinician may request a replan (i.e., recalculation of the treatment plan) using different constraints. Another example of a PQI is the dose gradient index (DGI)=ratio of V50 to PTV, where V50 is the volume defined by the 50% isodose. An ideal plan would have a very high gradient around the target, which means that the V50 should be as close to the PTV as possible. Thus, the closer the DGI is to 1, the higher the gradient, with the result that the higher dose is concentrated around the target, and the dose drops off sharply away from the target. The clinician may set the range for the DGI to be <2. This would mean that the V50 volume should not be more than twice the PTV in order for the treatment plan to proceed. Other examples of plan quality indices may include mean dose metrics (e.g., the average radiation dose delivered over the PTV), uniformity index (e.g., the magnitude of dose variation with respect to the PTV), global maximum location (e.g., the location of the patient area receiving the highest radiation dose), etc. Another example of a PQI is a combined PQI that may be constructed as a function of different individual PQIs or the forms of the PQIs listed in Figure 3B. In this example, each PQI may be made unitless and may be represented by a formula that gives a value of 1 or less than 1. For example:

number

number

number

number

[0083] Another p i may use the following dose gradient index DGI:

number

number

[0084] (CI-1) is used as p1 because CI can be greater than or less than 1, but in an ideal scenario, CI=1, and therefore (CI-1) 2 Note that, measures the deviation from the ideal case. There may be other PQIs and different mathematical forms of PQI combinations used to define the combined PQI, for example, instead of the square root of the sum of weighted squares, a simple weighted sum of PQI forms may be used to represent the combined PQI. The goal of the combined PQI is to judge the overall quality of the treatment plan.

[0085] In some variations, the desired dose distribution may be imposed as a constraint on the treatment planning system and may be expressed by a constraint on the PQI. For example, a prescription for 98% of the PTV to receive a dose of at least 50 Gy may be referred to as the PQI constraint: PTV D98=50 Gy. A constraint on the maximum amount of radiation that can be delivered to the lung region may be expressed as D(1000cc)<13.5 Gy. These constraints may facilitate the generation of a treatment plan that is targeted to meet the desired dose distribution and / or clinical goal.

[0086] The effectiveness of a treatment plan may vary depending on the characteristics of the patient and / or the target region, which may change between and / or during a treatment planning session. That is, a treatment plan that may provide an acceptable radiation dose or distribution based on one set of patient or target region characteristics at a particular time may not provide an acceptable radiation dose or distribution if there is a change in any of those characteristics at a different time. Some variations may include calculating, at the time of treatment plan generation, a range of biological activity and / or physiological parameters where the treatment plan will provide an acceptable dose or distribution (i.e., the treatment plan will meet the PQI index threshold). Alternatively or additionally, the method may include calculating a PQI value based on real-time imaging data obtained during treatment. The imaging data, and / or biological activity and / or physiological data extracted from the imaging data, and / or the calculated PQI, and / or the range of acceptable clinical parameters and / or any recommendation on whether to proceed with the treatment plan may be presented to the clinician on the display. The clinician may then review these parameters and data and determine whether to begin or continue a treatment session with the current treatment plan, or to adapt or update the treatment plan to account for changes in the patient and / or target region. In some variations, the radiation therapy system may proceed to apply radiation according to the treatment plan if the treatment plan quality index, calculated based on biological activity and / or physiological data and / or real-time acquired data, is within a prescribed or predetermined range. The methods of evaluating a treatment plan described herein may be used before, during, and / or after a treatment session to determine whether to continue radiation therapy according to the current treatment plan, or to update / adapt the treatment plan to account for changes in the patient and / or target region that may render the current treatment plan undeliverable and / or ineffective.

[0087] (Evaluating treatment plans using the Plan Quality Index (PQI)) One variation for evaluating a treatment plan based on imaging data acquired in real time and / or biological activity and / or physiological data extracted from the imaging data is depicted in Fig. 4A-4B. The method may include calculating a PQI of a current treatment plan based on clinical parameters acquired during treatment (such as biological activity and / or physiological and / or anatomical data). The PQI calculated based on the real-time clinical parameters may be compared with a range of predetermined acceptable PQI values, and if the calculated PQI is within the range, the treatment system may recommend to the clinician and / or technician that the radiation treatment may proceed according to the current treatment plan. The range of acceptable PQI values ​​may be determined based on data acquired during a diagnostic imaging session, during a treatment planning session, and / or at the beginning of a treatment session (e.g., during a patient pre-scan), and / or may include a range of known or widely accepted PQI values. If the calculated PQI is not within the range of predetermined acceptable PQI values, the treatment system may recommend or alert the clinician and / or technician to update the treatment plan. FIG. 4A is a table providing examples of PQI: prescribed PQI values ​​that are met by dose calculations during a treatment planning session according to a physician's prescription (column "Prescribed PQI"), and PQI MAPO values ​​that would be acceptable for treatment at the time of treatment (column "PQI MAPO"). The ranges in FIG. 4A may vary for each patient and / or target region and / or treatment session, etc. For example, an initial prescription may specify that at least 99% of the PTV (planned treatment volume) is irradiated or "covered" with an isodose surface that corresponds to 90% of the prescribed dose (V90%=99%) (first row and second column of the table in FIG. 4A). However, at the time of treatment, based on imaging data acquired in real time, calculations based on patient clinical parameters may determine that the 90% isodose surface will encapsulate or cover only 96% of the target region (V90%=96%). Because this V90% value (96%) is within the MAPO range defined in the right-most column (i.e., greater than 95%), the treatment system may recommend that treatment proceed according to the treatment plan.As another example, the table of FIG. 4A may specify that a physician's prescription requires that less than 10% of the lung volume be irradiated with a radiation dose of 20 Gy or more (i.e., lung V20Gy<10%). However, at the time of treatment, a measured change in the patient clinical parameters may indicate that 23% of the lung volume will receive a radiation dose of 20 Gy or more (V20Gy=23%) if the treatment plan is delivered without any adaptation. This increase in lung volume irradiation to 23% may be the result of a changed tumor location within the lung, for example. However, because this 23% V20Gy value is not within the MAPO range (i.e., exceeds the MAPO value of 15%), the clinician may be alerted that the V20 PQI will be violated if the plan is delivered without any adaptation or modification. Additional PQI and / or treatment plan quality parameters may be included in a table similar to the table depicted in FIG. 4A and provided to the radiation therapy system controller. In some variations, a table similar to that of FIG. 4A may be generated for each target region and / or OAR. Optionally, a clinician and / or technician may be presented with the data in such a table or any other graphical representation. Clinicians may prefer to use PQI values ​​to evaluate treatment plans because they intuitively reflect changes in tumor coverage, conformance, dose-volume limitations, and may be expressed or presented in a format similar to a radiation therapy prescription.

[0088] FIG. 4B depicts a flow chart diagram of one method of evaluating a treatment plan using a PQI calculated based on real-time acquired imaging data and a current treatment plan. Method 400 may be performed by a controller of a radiation therapy system at the time of treatment (e.g., on a treatment day, before firing of the first radiation beam, and / or during application of the radiation beam) and / or after a treatment session (i.e., to determine whether to use the same treatment plan for the next treatment session). Method 400 may include measuring 402 biological activity and / or physiological and / or anatomical data (and / or any other patient or target area data) at the beginning and / or during a treatment session. As described herein, measuring biological activity and / or physiological and / or anatomical data may include acquiring imaging data such as PET data, SPECT data, X-ray or CT, data, MRI data, etc. In some variations, measuring biological activity data may include acquiring CT or PET-CT images. The biological activity and / or physiological and / or anatomical data may be extracted or calculated based on acquired imaging data. The method 400 may then include calculating 404 one or more PQIs based on the measured data, and comparing 406 the calculated one or more PQIs to their corresponding acceptable range values. In some variations, the updated PQI values ​​may be calculated by performing dose calculations for any altered geometry of the target region or changes in other non-geometric clinical parameters (e.g., biological activity and / or physiological data) that may be used in calculating the delivered dose distribution. Examples of non-geometric clinical parameters may include, but are not limited to, the PET SUV of the target region and / or the PET activity changes in those target regions. The acceptable ranges for each of the PQIs may be pre-determined by the clinician and transferred to the treatment system, for example, during a treatment planning session. The clinician and / or technician may decide whether to proceed with the treatment plan based on the comparison from step 406.

[0089] Optionally, if the calculated PQI is within the acceptable range, the method 400 may include delivering 408 radiation according to the treatment plan. If the calculated PQI is not within the acceptable range, the method 400 may optionally include updating 410 the treatment plan and delivering 412 radiation according to the updated treatment plan. Alternatively, the method 400 may include terminating the treatment session and updating the treatment plan for future sessions. In a situation where some of the one or more PQIs are within their corresponding desired ranges and one or more PQIs are not within their corresponding desired ranges, the decision of whether to proceed with the treatment plan may be at the discretion of the clinician. Alternatively or in addition, the method 400 may include provisions for prioritizing and / or ranking the different PQIs. For example, a recommendation as to whether to proceed with a treatment plan may be based on a weighted sum of the PQIs, where deviations from the highly weighted (e.g., relatively more important) PQIs may offset compliance in the lower weighted (e.g., relatively less important) PQIs. In some variations, as long as the highly weighted PQIs are within a desired or prescribed range, the controller may recommend that radiation delivery should proceed according to the treatment plan even if some of the lower weighted PQIs are outside the range.

[0090] (Evaluate treatment plans using clinical parameters) 5A-5B depict another variation of a method for evaluating a treatment plan based on imaging data acquired in real time and / or biological activity and / or physiological data extracted from the imaging data. The method may include calculating a range of acceptable clinical parameters (e.g., a range of acceptable biological activity, physiological, and / or anatomical data) before a treatment session (e.g., during a treatment planning session). During treatment, the biological activity and / or physiological data extracted from the imaging data acquired in real time may be compared to the range of acceptable clinical parameters. The range of acceptable clinical parameters may be calculated or derived by setting a range of desired PQI values ​​(e.g., a minimum PQI value) and iteratively calculating the corresponding range of acceptable clinical parameters (e.g., incrementing and / or decrementing one or more clinical values ​​and recalculating the treatment plan quality index until the calculated PQI is outside the range). Alternatively or additionally, a clinician may define a range of acceptable clinical parameters within which a patient is eligible to receive radiation therapy. In some variations, the ranges of acceptable clinical parameters may be determined based on data obtained during a diagnostic imaging session, during a treatment planning session, and / or at the start of a treatment session (e.g., during a patient pre-scan), and / or may include known or widely accepted ranges of normal activity.

[0091] FIG. 5A is a table providing examples of clinical parameters and their acceptable / desired value ranges ("Clinical Parameter Change" column), acceptable PQIs for that range of acceptable clinical parameters ("PQI" column), PQIs during the treatment planning session ("Simulation Day PQI" column), and PQIs at the time of the treatment session ("First Treatment Day PQI" column). The table maps the change in clinical parameters to a change in PQI value. The clinician and / or treatment system controller can determine whether the change in PQI value is acceptable to proceed with delivering radiation according to the current treatment plan. For example, it can be calculated that if the distance between the center of the PTV and the spinal cord at the time of treatment is 3 mm less than the distance as measured during the treatment planning session, the PQI may be increased from 29 Gy to 31 Gy (i.e., the spinal cord will be exposed to more radiation than expected). The clinician can determine at the time of treatment whether this is acceptable to proceed with the treatment. Alternatively, a clinician may determine a range of acceptable PQI values ​​prior to a treatment session such that a patient may proceed with treatment as long as the PQI value on the treatment day is within the range of acceptable PQI values.

[0092] FIG. 5B depicts a flow chart diagram of one method of evaluating a treatment plan using clinical parameters extracted from or calculated based on real-time acquired imaging data and a proposed / current treatment plan. The method 500 may include measuring 502 biological activity and / or physiological and / or anatomical data (and / or any other patient or target area data) at the beginning and / or during a treatment session. As described herein, measuring biological activity and / or physiological and / or anatomical data may include acquiring imaging data such as PET data, SPECT data, X-ray or CT, data, MRI data, etc. In some variations, measuring biological activity data may include acquiring CT or PET-CT images. The biological activity and / or physiological and / or anatomical data may be extracted or calculated based on the acquired imaging data. Examples of such data may include, but are not limited to, the size, shape, and location of the target areas, as well as any non-geometric clinical parameters such as the PET SUV of the target areas and / or the PET activity change of those target areas. The method 500 may then include comparing 504 the biological activity and / or physiological and / or anatomical data (which may be collectively referred to as clinical parameters) to a range of acceptable values. The acceptable range for each clinical parameter may be pre-determined by a clinician, for example, during a treatment planning session, and transferred to the treatment system. The clinician and / or technician may decide whether to proceed with the treatment plan based on the comparison from step 504. Optionally, if the biological activity and / or physiological and / or anatomical data is within the acceptable range, the method 500 may include delivering 506 radiation according to the treatment plan. If the biological activity and / or physiological and / or anatomical data is not within the acceptable range, the method 500 may optionally include updating 508 the treatment plan and delivering 510 radiation according to the updated treatment plan. Alternatively, the method 500 may include terminating the treatment session and updating the treatment plan for a future session.In a situation where some of the biological activities and / or physiological and / or anatomical data are within their corresponding desired ranges and others are not, the decision of whether to proceed with a treatment plan may be at the discretion of the clinician. Alternatively or additionally, the method 500 may include rules for prioritizing and / or ranking different biological activities and / or physiological and / or anatomical data. For example, a recommendation on whether to proceed with a treatment plan may be based on a weighted sum of the biological activities and / or physiological and / or anatomical data, and deviations from the highly weighted (e.g., relatively more important) biological activities and / or physiological and / or anatomical data may offset compliance within the less weighted (e.g., relatively less important) biological activities and / or physiological and / or anatomical data. In some variations, as long as the highly weighted biological activity and / or physiological and / or anatomical data are within a desired or prescribed range, the controller may recommend that radiation delivery proceed according to the treatment plan even if some of the lower weighted biological activity and / or physiological and / or anatomical data are outside the range. Evaluating the treatment plan based on clinical parameters may reduce the wait time between obtaining real-time imaging data and delivering radiation by not calculating the PQI value of the treatment plan, recontouring the target region, and / or calculating the dose distribution during the treatment session. This may help reduce the treatment session time for the patient.

[0093] One variation of a method for calculating a set or range of acceptable biological activity levels based on a set of acceptable PQI values ​​is depicted in FIG. 5C. FIG. 5D depicts an example of the method of FIG. 5C applied to a set of clinical parameters including tumor size (V) and tumor SUV (SUV), and a set of PQIs including lung V20 and PTV CI. A clinician may determine that a treatment plan is appropriate for delivery if a set of clinical parameters measured at the time of treatment are within ranges such that the corresponding set of PQI values ​​will also be within the corresponding acceptable ranges. A clinician may determine, for example, that the range of possible acceptable clinical parameter values ​​may be about ±20% from the planned tumor size (V_p) and about ±30% of the planned tumor SUV (SUV_p). A clinician may input clinical parameter values ​​within these ranges into a treatment planning system and determine a range of acceptable PQI values ​​for lung V20 and PTV CI that would correspond with the range of acceptable clinical parameter values. 5C depicts one method 520 for determining a range of acceptable clinical parameter values. The method 520 may include selecting 522 planned clinical parameter values ​​for each clinical parameter in the set of clinical parameters, selecting 524 a test set of values ​​for each clinical parameter, calculating 526 a treatment plan for each combination of test values ​​for each clinical parameter in the set of clinical parameters, calculating 528 a PQI value for each PQI in the set of PQIs for each of the calculated treatment plans, identifying 530 PQI values ​​within a predetermined range and corresponding sets of clinical parameter values ​​that result in those PQI values, and defining 532 a range of acceptable clinical parameter values ​​for each clinical parameter in the set of clinical parameters that correspond to the PQI values ​​identified as being within the predetermined range. Defining a range of acceptable clinical parameter values ​​for a particular PQI may include identifying a minimum clinical parameter value that results in a PQI value within the predetermined range, and identifying a maximum clinical parameter value that results in a PQI value within the predetermined range.The calculated ranges for each clinical parameter in the set of clinical parameters (e.g., ranges of V_p and SUV values ​​within (e.g., meeting) the range of PQI values) may be a set of acceptable clinical parameter values ​​at the time of treatment to be used to make a decision whether to proceed with treatment at the time of treatment, i.e., whether the measured clinical parameter is within the range (i.e., greater than or equal to the lowest clinical parameter value and less than or equal to the highest clinical parameter value). Since the ranges of acceptable clinical parameters are calculated prior to a treatment session, this may help reduce the latency between obtaining imaging data and the decision whether to proceed with a treatment plan. In some variations, the controller of the treatment system may decide whether to proceed with a treatment plan by comparing the extracted patient data (e.g., biological activity data, and / or physiological data, and / or anatomical data) to the ranges of acceptable clinical parameters. In some variations, the clinician is notified when one or more extracted patient data are outside the ranges of acceptable clinical parameters so that a final decision can be made whether to proceed with treatment and / or whether the treatment plan should be updated or adapted.

[0094] 5D depicts a method 540 of identifying ranges of acceptable values ​​for tumor volume V and tumor SUV such that a set of PQIs including lung V20 and tumor CI have values ​​within the acceptable range. The method 540 may include selecting 542 a set of clinical parameters and a set of PQIs for evaluation. The value of V based on the treatment plan is V_p and the value of SUV based on the treatment plan is SUV_p. The method 540 includes selecting 544 a test value for V and an SUV for the V_p parameter from the range of possible parameter values. For example, a test value for V may be 0.8 * The test values ​​for SUV include V_p, V_p, and 1.2V_p, which correspond to approximately ±20% increase or decrease in tumor volume from the planned volume. * SUV_p, 0.8 * SUV_p, SUV_p, 1.2 *SUV_p, and 1.3SUV_p. A plan may be calculated 546 for each combination of test V and test SUV values ​​(resulting in a set of calculated plans), and calculate 548 values ​​for the lung V20 and tumor CI for each of the calculated plans. The method may further include determining combinations of V_p and SUV values ​​that result in PTV CI and lung V20 values ​​within an acceptable range. For example, the method may include identifying 550 combinations of V_p and SUV values ​​that result in lung V20 and tumor CI values ​​that are within a predetermined range and combinations of V_p and SUV values ​​that result in PTV CI and lung V20 values ​​that are outside the acceptable range. The method may then include defining 552 a range of acceptable V and SUV values ​​that correspond to the lung V20 and tumor CI values ​​identified as being within the predetermined range (e.g., a range of V and SUV that meets a range of PQI values). Defining a range of acceptable values ​​for V and SUV may include identifying the lowest and highest V and SUV values ​​that result in lung V and tumor CI values ​​that still fall within the pre-determined / acceptable ranges.

[0095] 6A and 6B depict a method of calculating an acceptable PQI range for use in the methods described above. FIG. 6A depicts one method 600 for generating a biological activity level or value range that maps to a desired PQI value range. During treatment, acquired biological activity and / or physiological and / or anatomical data may be compared to this generated biological activity level or value range as described above. Alternatively or in addition, the acceptable biological activity or value range may be determined based on data acquired during a diagnostic imaging session, during a treatment planning session, and / or at the start of a treatment session (e.g., during a patient pre-scan) and / or may include a known or widely accepted normal activity range. The method 600 may include selecting 602 one or more PQI ranges having a first threshold PQI value and a second threshold PQI value, calculating 604 a first biological activity value corresponding to the first threshold PQI value, and calculating 606 a second biological activity value corresponding to the second threshold PQI value. Optionally, the method 600 may include transmitting the first and second biological activity value thresholds (biological activity ranges) to a treatment system controller 608. The method 600 may also be used to generate physiological and / or anatomical data ranges that map to a range of desired PQI values.

[0096] 6B depicts one variation of a method 610 for iteratively calculating a desired PQI value and a corresponding biological activity value. The method 610 may include selecting 612 an initial biological activity value, calculating 614 a PQI for a treatment plan based on the selected biological activity value, and comparing 616 the calculated PQI to a desired PQI value (such as a desired PQI threshold). If the calculated PQI does not match the desired PQI value, the method 600 includes selecting 618 a new biological activity value and repeating steps 614 and 616. Selecting a new biological activity value may include incrementing or decrementing the current biological activity value depending on whether the calculated PQI is above or below the desired PQI value. If the calculated PQI matches the desired PQI value (or is within a specified or acceptable tolerance or range of the desired PQI value), the controller may then store the biological activity value in a controller memory (e.g., a controller of a treatment planning system and / or a controller of a treatment system) 620. The method 610 may also be used to generate physiological and / or anatomical data values ​​that map to a desired PQI value.

[0097] (Evaluate treatment plans using bounded DVH) As an alternative or in addition to evaluating a treatment plan based on a PQI value calculated based on biological activity and / or physiological and / or anatomical data obtained in real time, a treatment plan may also be evaluated based on a dose-volume histogram or DVH. A DVH is a plot that depicts the dose levels delivered to an area or portion of a target volume. An example of a DVH plot is shown in FIG. 7A (solid line). In an ideal system, the dose D target However, if any "hot spot" (i.e., D target (area of ​​the target volume receiving a dose above target The dose is delivered to 100% of the target volume, with no areas of the target volume receiving less than 100% of the dose. However, in many cases, the dose D target is not delivered to 100% of the target volume (e.g., the actual delivered dose is Dtarget 7A ) but a range of delivered doses may be clinically acceptable. DVH plots may be calculated during a treatment planning session based on the patient parameters and treatment plan at that time. DVH plots may optionally be included as part of generating a treatment plan so that treatment plans that do not have the desired DVH profile for one or more of the irradiated target regions may be updated or refined. The range of desired DVH profiles may be represented by bounded DVHs, represented by the dotted lines in FIG. 7A . The bounded DVHs may be defined by minimum and maximum dose distributions. Treatment plans that result in a dose distribution between the minimum and maximum dose distributions may be deemed acceptable for delivery. During a treatment planning session, bounded DVH curves may be generated for each ROI (e.g., volume of interest) or target region based on biological activity and / or physiological and / or anatomical data obtained prior to or during the planning session. During treatment, imaging data acquired in real time may be used to calculate updated DVH curves for one or more of the target regions. That is, changes in biological activity and / or physiological and / or anatomical data may also modify the DVH curves for one or more target regions. The updated DVH curves may be compared to the bounded DVH curves. If within the range, the treatment system controller and / or clinician may determine that radiation delivery may proceed according to the treatment plan. If not within the range, the treatment system controller and / or clinician may determine to update the treatment plan before proceeding.

[0098] During treatment, DVH curves may be calculated for all of the target regions based on imaging data acquired in real time. In some variations, the imaging data acquired in real time may include PET imaging data (e.g., PET pre-scan). Nominal DVH curves for the PTV, and / or biological guideline region of interest (BgROI) or radiation firing zone (RFZ), and / or OAR may be calculated based on the PET imaging data. Other radiation delivery metrics such as PTV or target coverage, average activity within the BgROI / RFZ, average SUV of the PTV, etc. may also be calculated based on the PET imaging data, along with one or more normalization factors. The DVH curves for some target regions may be within the range defined by the bounded DVH for those regions, while the DVH curves for other target regions may not be within the bounded DVH range. The decision of whether to proceed with the treatment plan may be at the discretion of the clinician. Alternatively or additionally, rules for prioritizing and / or ranking different target regions may be generated during a treatment planning session and used to determine whether to proceed with a treatment plan. For example, a recommendation on whether to proceed with a treatment plan may be based on a weighted sum of target regions, with out-of-bounds DVH curves for highly weighted (e.g., relatively more important) target regions offsetting in-bounds DVH curves for less weighted (e.g., relatively less important) target regions. In some variations, the controller may recommend that radiation delivery proceed according to a treatment plan even if the DVH curves for some less weighted target regions are out-of-bounds, as long as the DVH curves for the highly weighted target regions are within desired or prescribed boundaries or ranges.

[0099] FIG. 7B depicts one variation of a method for evaluating a treatment plan using a bounded DVH. Although the method is depicted as evaluating a DVH for a single target region, it should be understood that the method may be used to evaluate DVHs for multiple target regions. The method may be performed at the beginning of a treatment session (e.g., before a first radiation beam is fired) and / or during a treatment session, as described above, as desired. The method 700 may include measuring 702 biological activity data during treatment. Measuring biological activity data may include measuring physiological and / or anatomical data and / or obtaining imaging data from which biological activity and / or physiological and / or anatomical data may be calculated. Such data obtaining may occur at the beginning of a treatment session (e.g., before a first radiation beam is fired, during a pre-scan) and / or during a treatment session (e.g., after a first radiation beam is fired). The method 700 may then include calculating 704 a DVH curve for the target region based on the radiation therapy treatment plan and the measured biological activity data, and comparing 706 the calculated DVH curve to a predefined bounded DVH for that region. If the calculated DVH curve is within the bounded DVH, the method 700 may optionally include delivering 708 radiation according to the treatment plan. If the calculated DVH curve is outside the bounded DVH, the method 700 may optionally include updating 710 the treatment plan, and optionally delivering 712 radiation according to the updated treatment plan. Alternatively, the method 700 may include terminating the treatment session and updating the treatment plan for future sessions. The method 700 may optionally include comparing deviations of all DVH curves for the target region, and weighting the deviations according to a rule or ranking of the target region. Calculating a weighted sum of all of the DVH curve deviations can assist the clinician in determining whether to proceed with radiation delivery in light of a certain DVH curve for a certain target area that is outside the boundaries of the bounded DVH.

[0100] (How to calculate bounded DVH curves) During treatment planning, a bounded DVH curve can be calculated for each region of interest in the patient, i.e., each irradiation target region and / or each irradiation avoidance region. For example, a bounded DVH curve can be calculated for the tumor region (i.e., gross tumor volume), and / or the PTV (i.e., gross tumor volume with margins), and / or the radiation firing zone or RFZ (i.e., the region that includes the potentially moving PTV and most or all of the possible locations of the PTV within the RFZ), and / or one or more OARs. In one variation, treatment planning can include, for example, calculating a radiation firing matrix P based on one or more PET images X and / or patient CT images (which can be referred to as planning images), and the RFZ (e.g., the target region and / or the PTV) and / or the OARs can be identified or contoured in the PET image X and / or the patient CT image (and / or other complementary patient images in the same coordinate system). Optionally, additional data for the RFZs and / or OARs, such as their size, shape, location, and degree of radiation sensitivity, maximum allowable radiation exposure, and / or prescribed radiation dose to be delivered to the irradiation target area, and / or other dose constraints, such as maximum and minimum dose delivered for each patient target area, may also be used in the calculation of the radiation firing matrix P. The planning patient CT images may also be used for dose calculations, e.g., to predict the distribution of dose delivered if radiation is applied to the patient according to the radiation firing matrix P. A family of bounded DVH curves may be calculated for each OAR, RFZ, and / or PTV based on the radiation firing matrix P by performing a fixed shift of the PET image X of the PTV within the RFZ and calculating the dose corresponding to the OAR, RFZ, and / or PTV for that particular shifted PTV position. For example, for a patient with a PTV within the RFZ and one OAR, a family of DVH curves for the PTV may be calculated for each shifted position of the PTV within the RFZ. Optionally, a second family of DVH curves for the RFZ and a third family of DVH curves for the OAR may be calculated for each shift position of the PTV within the RFZ.A minimum DVH curve may be derived from a group of DVH curves by extracting the leftmost point of the group of DVH curves (i.e., for each dose value, selecting the point with the lowest volume fraction or for each volume fraction, selecting the point with the lowest dose). A maximum DVH curve may be derived from a group of DVH curves by extracting the rightmost point of the group of DVH curves (i.e., for each dose value, selecting the point with the highest volume fraction or for each volume fraction, selecting the point with the highest dose). Bounded DVH curves for a particular region of interest (e.g., PTV, RFZ, OAR), including minimum DVH curves, maximum DVH curves, and nominal DVH curves (e.g., dose calculated based on planning images), may be transmitted from the treatment planning system to the radiation therapy system and used to evaluate the treatment plan based on updated imaging data and / or biological and / or physiological data.

[0101] 8A is a flow chart diagram of one variation of a method for calculating bounded DVH curves during treatment planning. The method 800 may include steps of acquiring 802 a patient CT image, defining 804 a dose constraint, prescription, PTV and / or RFZ and OAR contours and other data, acquiring 806 a patient PET image (X), calculating 808 a dose calculation matrix (A), and calculating 810 a radiation firing matrix (P) that specifies a transformation from the imaging data to a fluence map, which may include beamlet patterns and / or beamlet intensities to be applied to the patient during a treatment session. In some variations, acquiring the patient PET image 806 may occur before defining 804 the dose constraint, prescription, and / or contours. The dose constraints, prescription and / or contours may include prescribing minimum and / or maximum dose to certain patient regions (e.g., maximum dose to OARs or irradiation avoidance regions, minimum dose to PTV or irradiation target regions, fluence smoothness for different patient regions), prescribing the total dose to be delivered to the irradiation target regions (e.g., 10 Gy per PTV), and / or contouring the OARs and / or PTV. Additional dose constraints are described below. Method 800 may include retrieving image data (X' j) to simulate various positions and / or motions of the PTV within the RFZ and generate a family of DVH curves 812, which may include generating bounded DVH curves for each PTV and / or RFZ and / or OAR (i.e., each DVH curve represents the dose delivered to the PTV at a particular position within the RFZ). The bounded DVH curves include a minimum DVH curve, a nominal DVH curve, and a maximum DVH curve for a particular PTV and / or RFZ and / or OAR. The minimum DVH curve may be derived by extracting the leftmost point of the family of DVH curves 814 (i.e., for each dose value, selecting the point with the lowest volume fraction), and the maximum DVH curve may be derived by extracting the rightmost point of the family of DVH curves 814 (i.e., for each dose value, selecting the point with the highest volume fraction). Optionally, the method 800 may include calculating 816 a total dose to the patient if the radiation is delivered based on the radiation firing matrix P and the planning patient PET image X.

[0102] Dose calculation matrix A, as calculated in 808 of method 800, may map beamlet coefficients (e.g., fluence values) to dose values ​​at a set of preselected regions (i.e., sampling points or voxels) within the patient. The sampling points may include patient regions and / or patient regions of clinical interest where radiation delivery and dose may be monitored. For example, sampling points may be selected within one or more (e.g., all) of the PTV, OAR, and RFZ within the patient. Dose calculation matrix A may be an n by m matrix, where n corresponds to the number of sampling points within the patient and m corresponds to the number of candidate beamlets available to deliver a unit of radiation. That is, the m entries along a particular column of dose calculation matrix A may represent the dose contribution from a beamlet weighted by 1 to each of the m sampling points or voxels. In some variations, the unit of radiation delivered by a candidate beamlet may be the radiation level delivered through a single MLC leaf opening at a particular firing position (e.g., gantry angle relative to the radiation therapy system isocenter) at a particular patient platform position relative to the therapy beam plane (e.g., beam station). The dose calculation matrix A may be calculated column-by-column, for example, by ray tracing the aperture (or trajectory) of each beamlet along a path through the RFZ or patient volume and calculating the beamlet's contribution weighted by 1 to each of the n sampling points or voxels. The beamlet aperture may be an MLC aperture defined by a single MLC leaf opening (i.e., of a binary MLC or 2-D MLC). Examples of dose calculation algorithms may include Monte Carlo simulation, collapsed cone convolution superposition, pencil beam convolution, and others.

[0103] The radiation firing matrix P may be a matrix that specifies the transformation from imaging data to a fluence map, which may include the beamlet pattern and / or beamlet intensities to be applied to the patient during a treatment session. The radiation firing matrix P may represent the relationship between a fluence map F for radiation delivery to a patient region and an image X of that patient region. That is, the radiation firing matrix P may be any matrix such that y=P·X. The radiation firing matrix P may be calculated by iteratively solving for a fluence map that minimizes one or more cost functions (e.g., a cost function C(y) of the resulting dose distribution and fluence, which is formed based on the radiation dose constraints and objectives described above). C is a sum of penalty functions, C=ΣC i (y). Examples of penalty functions may include, without limitation, minimum dose for the target region, average or maximum dose for the OAR, and / or fluence smoothness, total radiation power, total tissue dose, treatment time, etc. Further examples of penalty functions include penalty functions (C i = |L(y)|1, i.e., the 1-norm of the Laplacian of the fluence map y), a penalty on the magnitude of the total fluence (i.e., the “total MU”; (C k =Σy k ), the penalty for dose values ​​D=A·y at sampling points in various volumes or regions of interest (e.g., C i = |Ay|1 may be a penalty function to encourage an overall minimum dose to the patient), and / or a penalty for the dose value D=A y corresponding to prescription goals and constraints (such as any of the constraints described above), such as a penalty for exceeding a maximum dose to an organ at risk.

number

number

[0104] In some variations, generating the radiation firing matrix P may include formulating an optimization problem to minimize a cost function C(y) and iterating through different sets of P such that the cost function C(y) is minimized while the following condition is satisfied:

number

[0105] The bounded DVH curves include a minimum DVH curve, a nominal DVH curve, and a maximum DVH curve, where the minimum and maximum DVH curves represent possible ranges of dose distributions or treatment outcomes due to various factors and / or uncertainties during treatment. Examples of factors and / or uncertainties that may affect the dose delivered on a treatment day may include setup errors, SUV variability, patient motion and / or shift, and / or tumor (e.g., PTV) motion and / or shift, and / or OAR motion and / or shift. The nominal DVH curve may represent a dose distribution that complies with a clinician's prescription. The minimum DVH curve may represent a lower boundary of the dose distribution, and the maximum DVH curve may represent an upper boundary of the dose distribution, where the range bounded by the minimum and maximum DVH curves represents the variation of the delivered dose due to various uncertainties during treatment. The dose distribution or range boundaries according to the minimum and maximum DVH curves may be reviewed and / or evaluated by a clinician to determine whether a dose delivered within those boundaries would be clinically relevant or therapeutic and / or desirable for the patient and / or safe. To derive the minimum and maximum DVH curves for a particular PTV within the RFZ (or any region of interest, e.g., OAR, RFZ, etc.), the treatment planning system may generate a number of images X' representing j positions of the PTV within the RFZ. j The j positions may simulate possible locations of the PTV within the RFZ on the treatment day due to, for example, patient motion and / or tumor motion. FIG. 8B is a schematic 2-D depiction of the RFZ 820 and PTV 822 at a location 824 within the RFZ, which is the location of the PTV 822 according to the planning patient CT image and / or the planning patient PET image X. To generate a family of DVH curves for the PTV 822 representing the j positions of the PTV 822 within the RFZ 820, the j images X' 1、2、3,…,jmay be generated by performing a rigid 3-D shift of the PTV 822 (and all anatomical structures of interest in image X, e.g., PET-affinity structures) to j positions. That is, a first image X'1 may have a PTV 822 at location 826 in the RFZ 820, a second image X'2 may have a PTV 822 at location 828 in the RFZ 820, a third image X'3 may have a PTV 822 at location 830 in the RFZ 820, a fourth image X'4 may have a PTV 822 at location 832 in the RFZ 820, etc. A family of j DVH curves may be generated by performing a rigid 3-D shift of the PTV 822 (and all anatomical structures of interest in image X, e.g., PET-affinity structures) to j positions. That is, a first image X'1 may have a PTV 822 at location 826 in the RFZ 820, a second image X'2 may have a PTV 822 at location 828 in the RFZ 820, a third image X'3 may have a PTV 822 at location 830 in the RFZ 820, a fourth image X'4 may have a PTV 822 at location 832 in the RFZ 820, etc. 1,2,3,···,j =A·P·X' 1,2,3,···,j Calculate the volume fraction at each dose level and plot the image X' 1、2、3,…,j Optionally, in addition to calculating the DVH curve as the location of the PTV varies within the RFZ, in some variations, X' j The intensity of the PTV in the X' image may also be varied, which may simulate the effect of different uptake values ​​(e.g., SUV) of the PET tracer on the treatment day. j The intensities of voxels in may vary ±25% from a nominal value (i.e., the intensity from planning PET image X). For example, three DVH curves for each PTV location in the RFZ may be calculated: a first DVH curve for the nominal SUV level, a second DVH curve for an SUV level of -25% from nominal, and a third DVH curve for an SUV level of +25% from nominal. In some variations, weighting factors are assigned to each image X' based on the probability / likelihood that the PTV will be at a particular location and / or the expected dwell time of the PTV at that location. 1、2、3,…,j8C depicts an example of groups of DVH curves for a PTV, an RFZ, and two OARs generated as described above. Each group of DVH curves may have from three DVH curves to 50 DVH curves or more (e.g., 10, 15, 25, 30, 45, 50, 70, 100, or more DVH curves). Group of DVH curves 840 may be for the PTV, group of DVH curves 842 may be for the RFZ (in which the PTV is located), group of DVH curves 844 may be for the first OAR, and group of DVH curves 846 may be for the second OAR. 8D depicts bounded DVH curves (850, 852, 854, respectively) for the PTV, RFZ, and OAR, each having a minimum DVH curve (850a, 852a, 854a, respectively), a maximum DVH curve (850b, 852b, 854b, respectively), and a nominal DVH curve (850c, 852c, 854c, respectively). To derive a minimum DVH curve for the PTV from a group of DVH curves 840, the leftmost point 841 of that group of DVH curves can be extracted (i.e., for each dose value, selecting the point with the lowest volume fraction, or for each volume fraction, selecting the point with the lowest dose) and curve-fitted. A maximum DVH curve may be derived from a family of DVH curves by extracting the rightmost points 843 of the family of DVH curves (i.e., for each dose value, selecting the point with the highest volume fraction or for each volume fraction, selecting the point with the highest dose) and fitting those points to a curve. Alternatively, or in addition, order statistics may be calculated from the DVH curves and used to evaluate the treatment plan on the treatment day. Examples of order statistics may include, but are not limited to, the maximum and minimum values ​​of the DVH curve, the 5% and 95% values ​​of the DVH curve, the 2% and 98% values ​​of the DVH curve, the absolute minimum and maximum dose values, and upper and lower thresholds for the uniformity index, upper and lower thresholds for the conformity index, etc.

[0106] On a treatment day, a DVH curve may be calculated based on the imaging data (and / or imaging data and / or biological and / or physiological data extracted from other sources). The DVH curve may be calculated at the beginning of a treatment session (e.g., before a therapeutic radiation source is activated), for example, by multiplying a radiation firing matrix P with the acquired imaging data (e.g., a PET pre-scan image X), i.e., D=P·X. If the calculated DVH curve is within a range defined by the minimum DVH curve and the maximum DVH curve, treatment may proceed according to the treatment plan. Optionally, one or more DVH curves may be calculated throughout a treatment session based on the acquired imaging data and / or biological and / or physiological data in real time, and the real-time generated DVH curves may be compared to the bounded DVH curve to determine whether radiation delivery should continue according to the treatment plan. Calculating the DVH curve based on the imaging data (which may be an incomplete or noisy low signal-to-noise ratio image x) may include multiplying the imaging data with a radiation firing matrix P, i.e., calculating the dose D by D=P·x. As mentioned above, some systems may include a GUI presented on a display or monitor that overlays the currently calculated DVH curve with a bounded DVH curve and / or provides one or more visual and / or audio notifications of whether the currently calculated DVH curve is within a range defined by the bounded DVH curve. Re-evaluating the radiation delivery and treatment at the start of and / or during a treatment session may help provide feedback to the clinician as to whether the treatment can be further adjusted for the patient's changing conditions.

[0107] It should be understood that the methods of evaluating a treatment plan described above (e.g., as depicted in Figures 4-7) may be employed separately in any of the adaptive radiation therapy methods described herein (e.g., as depicted in Figures 2A-2D), but one or more of these methods may be used in parallel (e.g., simultaneously) with one another. For example, the radiation therapy system and / or clinician may simultaneously review the updated PQI values ​​and the updated clinical parameters (e.g., biological activity and / or physiological and / or anatomical data) when determining whether the treatment plan is appropriate for the patient in the current treatment session (e.g., combining the methods depicted and described with reference to Figures 4-5). Alternatively, evaluating the treatment plan may include simultaneously reviewing the updated clinical parameters and the DVH curves (e.g., combining the methods depicted and described with reference to Figures 5-6). Alternatively, evaluating the treatment plan may include simultaneously reviewing the updated PQI values ​​and the DVH curves (e.g., combining the methods depicted and described with reference to Figures 4 and 6). In some variations, the clinical parameter data, PQI values, and / or DVH curves obtained in real time may be reviewed and considered when determining whether the treatment plan is appropriate for the patient in the treatment session. This may allow the suitability of the treatment plan for the patient at that particular time to be evaluated using multiple criteria. For example, if the patient's clinical parameters at the time of treatment are outside the range of pre-calculated acceptable clinical parameters, the treatment system may calculate updated PQI values ​​and evaluate whether those updated PQI values ​​are within the range of pre-calculated acceptable PQI values. That is, even if certain clinical parameters of the patient are not within the prescribed range, it is possible that changes in these parameters may have some synergistic effect, whereby the treatment plan calculated based on the initial set of clinical parameters will still provide the prescribed dose distribution.Calculating an updated PQI and / or updated DVH curve may reveal such synergy, and the clinician and / or radiation therapy system may decide to proceed with treatment if one or more of the updated clinical parameters, the updated DVH, and / or the updated PQI values ​​are within an acceptable range.

[0108] In some variations, the treatment plan may be generated based on one or more of the PQI values, clinical parameters, and / or DVH curves. For example, the treatment planning system may generate a treatment plan based on an acceptable range PQI value, calculate a range of clinical parameters for which the treatment plan would still be within the acceptable range PQI value, and then evaluate whether the calculated range of clinical parameters is appropriate for the patient (which may be determined by the controller using patient-specific data and / or a clinician). If the calculated range of clinical parameters is not appropriate for the patient, the treatment planning system may iterate over the range of clinical parameters selected by the controller and / or clinician appropriate for the patient, generate a new treatment plan, and calculate a PQI value for the new treatment plan.

[0109] ((Example Use Case)) Illustrative Use Case #1: Offline Adaptation for Regions of Tumor Hypoxia Although the patient may not exhibit hypoxic regions during the diagnostic and treatment planning session or simulation, prior to the radiation treatment session, the clinician may suspect that one or more regions of tumor hypoxia may be present. During the setup imaging scan (e.g., pre-scan) at the start of a treatment session or fraction and / or during imaging data acquisition during a treatment session, regions of the tumor may be identified based on acquired functional imaging data (e.g., 18 F]HX4 PET data, 18 F]FAZA PET data, 18 The patient is determined to be hypoxic based on CT scan data (e.g., F]FMISO PET data), and the patient's initial radiation therapy plan may be delivered for the current fraction or session to provide the patient with the initial planned dose.

[0110] The patient's treatment team (e.g., clinician) may update the treatment plan based on the hypoxic imaging data for the next radiation therapy fraction. For example, the treatment team may transfer the hypoxic imaging data from the treatment system to the treatment planning system. The treatment plan may be updated to modify the dose to the hypoxic region. For example, the updated treatment plan may provide a new target volumetric simultaneous boost intensity modulated radiation therapy (SIB-IMRT) fraction that increases the dose delivered to the tumor hypoxic radioresistant region. The dose to the hypoxic region is increased by a factor proportional to the maximum dose for the region based on the initial treatment plan. The updated treatment plan may be used for radiation delivery in the next fraction.

[0111] After each subsequent fraction of treatment, the patient's tumor hypoxia may be re-evaluated and the augmentation dose (both absolute dose values ​​and target augmentation area) delivered to the patient's tumor hypoxia may be adapted using the hypoxia data obtained from this subsequent fraction and previous fractions to further tailor the patient's course of treatment.

[0112] (Illustrative Use Case #2: Online and Offline Adaptation for Regions of Tumor Hypoxia) The patient exhibits hypoxic regions during diagnostic and treatment planning sessions and / or simulations. During a setup imaging scan (e.g., pre-scan) at the start of a radiation treatment session (or fraction) and / or during imaging data acquisition during a treatment session, the region of the tumor is identified as hypoxic in the acquired functional imaging data (e.g., 18 F]HX4 PET data, 18 F]FAZA PET data, 18 F]FMISO PET data) is used to determine hypoxia.

[0113] The current treatment plan may be updated to modify the dose to the hypoxic region during the current treatment session or fraction. For example, the updated treatment plan may provide a more precise intra-target volume simultaneous boost intensity modulated radiation therapy (SIB-IMRT) fraction than originally planned, increasing the dose delivered to the radioresistant region of tumor hypoxia. The dose to the hypoxic region is increased by a factor proportional to the maximum dose for the region based on the original treatment plan. In some variations, the treatment system may include an online treatment planning system that may be configured to receive and / or store hypoxic imaging data and calculate updates or modifications to the current treatment plan. The modified treatment plan may then be delivered to the patient during this current fraction, providing a more precise and effective treatment that provides the patient with more clinical benefits.

[0114] After each fraction of treatment, the patient's tumor hypoxia is re-evaluated and the augmentation dose (both absolute dose values ​​and target augmentation areas) delivered to the patient's tumor hypoxia is again adapted using the hypoxia data obtained from the previous fraction to help drive the online treatment planning process for the next fraction.

[0115] Illustrative Use Case #3: Real-time adaptation for regions of tumor hypoxia A patient exhibits hypoxic regions during diagnostic and treatment planning sessions and / or simulations, and may receive radiation therapy with a treatment plan created using functional imaging that defines expected regions of tumor hypoxia.

[0116] During the treatment session, precise areas of tumor hypoxia were identified based on real-time acquired functional imaging data (e.g., 18 F]HX4 PET data, 18 F]FAZA PET data, 18The dose to the detected hypoxic region may be determined based on the radioresistance data (e.g., F]FMISO PET data). In real time, the dose to the detected exact hypoxic region may be modified, which may help to deliver more dose to the radioresistant region of tumor hypoxia without requiring a replanning step. In some variations, the dose modification and / or any other modulation to the current treatment plan may be calculated by the treatment delivery software module of the treatment system. During the treatment session, the biological activity and / or physiological data feedback to the treatment plan and / or any dose modulation and / or any modulation may be displayed as active treatment parameters for patient monitoring. This may help to provide additional feedback to the patient's treatment team (e.g., clinician) during the treatment session.

[0117] Upon completion of the current treatment session or fraction, the patient's tumor hypoxia may be re-evaluated. For example, the expected boost delivered to the patient's tumor hypoxia (both absolute dose values ​​and target boost areas) may be further adapted using hypoxia data obtained from the previous fraction to help improve the ability of the treatment delivery software module to modulate the dose in the next fraction.

[0118] (Illustrative Use Case #4: Online Adaptation for Cardiac Perfusion) A patient presents with cardiac perfusion defects (e.g., from a previous course of radiation therapy) and is currently undergoing a second course of recurrent thoracic cancer. To provide improved dose savings for the patient's cardiac perfusion, the patient's treatment team decides to adapt the treatment plan (e.g., perform an online adaptation) based on physiological characteristics obtained at the time of treatment and immediately prior to radiation delivery. For example, at the beginning of a treatment session, cardiac perfusion PET imaging data may be obtained (e.g., 15 O]H2O, [ 13 [N]ammonia, and others have been shown to be effective for the extraction of physiological properties via functional imaging.

[0119] The patient may be treated with an initial (or current) treatment plan created using previously acquired imaging data (e.g., functional imaging data) that may define the patient's expected region of cardiac perfusion defect. The imaging data may be acquired during an initial setup pre-scan of the fraction, and the precise region of the cardiac perfusion defect may be determined based on the imaging data. If the cardiac perfusion defect is detected and noted to be substantially different from the simulation based on the blood flow characteristics extracted from the imaging data, the patient's treatment team may revise the current treatment plan and modify the dose delivery such that the cardiac perfusion defect region is exposed to lower levels of radiation and the target boundary near the cardiac perfusion defect region is refined. For example, updating or adapting the treatment plan may include modifying the absolute dose values ​​and target region delineation for the defect region and the area surrounding the defect region. In general, the update will reduce the number of available firing positions, increase the dose delivered at certain firing positions, and increase the avoidance of the defect region. These revisions to the treatment plan can help provide better dose gradients, isodose lines, and dose-volume histograms for regions of cardiac perfusion defects. In some variations, the cardiac perfusion imaging data can be transferred to an online treatment planning system of the treatment system to update the treatment plan.

[0120] A modified treatment plan can then be delivered to the patient during this current fraction, which may help provide a more effective treatment with fewer negative side effects and will provide the patient with a more overall clinical benefit. After each treatment fraction, the patient's cardiac perfusion defects can be re-evaluated and the specific dose delivered to the patient (both absolute dose values ​​and target / avoidance regions) can be adapted again using the physiological cardiac perfusion data obtained during the previous fraction. This can help facilitate the online treatment planning process for the next fraction.

[0121] (Illustrative Use Case #5: Online and Offline Adaptation for Immune Response) A patient presents with a HER2-positive primary tumor and an invasive HER2-positive metastasis during the diagnostic and treatment planning session and / or simulation. By the time radiation therapy begins, it is suspected that there may be additional metastases and / or changes in HER2 expression. Imaging data may be obtained during the initial pre-scan of the fraction and / or during the treatment session, and the precise area and amount of HER2 expression may be determined based on this imaging data. For example, PET imaging data may be obtained from: 18 via a residual label designated F-RL-I-5F7, and 18 Through a protein tag called F-SFB, 18 These labels have been shown to provide effective biological imaging of HER2 gene expression. The radiolabeled protein will then be detected on a PET scan and will concentrate in areas where the HER2 receptor is active, and the differences in concentration and relative intensity will be quantified, allowing precise identification of areas of HER2 gene expression.

[0122] The patient's treatment team may update the current treatment plan, for example, by modifying the dose to HER2 positive areas, providing a higher dose to areas of HER2 expression, and adding new target areas based on newly discovered metastatic tumors with HER2 expression. In some variations, the HER2 expression imaging data may be transferred to the treatment system's online treatment planning system for updating the treatment plan.

[0123] A modified treatment plan can then be delivered to the patient during this current fraction, which can help provide more precise and effective treatment with increased clinical benefit to the patient. After each treatment fraction, the patient's HER2 expression data can be reevaluated, and the dose delivered to the patient's HER2-positive tumor can be further adapted using the HER2 expression data obtained from the previous fraction. For cases seeking radiation priming of HER2-active regions for systemic therapy, the plan can be modified to increase the amount of radiation to HER2-expressing regions to amplify the effect of systemic therapy acting in those regions. Alternatively, for cases where additional radiation may interfere with systemic therapy from immunotherapy that interacts with HER2 gene expression, the plan can be modified to reduce the amount of radiation to HER2-expressing regions and instead focus on non-expressing nodes and take advantage of the long-range effect. This can help facilitate the online treatment planning process for the next fraction.

[0124] Any of the radiation therapy methods and / or systems described herein may be used alone or in conjunction with other tumor therapies. For example, adaptive radiation therapy may be combined with surgery and / or chemotherapy, and / or immunotherapy and / or gene therapy. In addition, the treatment methods and / or systems herein may use any type of tracer that may help identify an area of ​​interest or target (e.g., irradiation target area and / or irradiation avoidance area). For example, one or more of the following PET tracers may be used: 18F-FDG, 18F-NaF, 18FHX4, 18FFAZA, 18FFMISO, radiolabeled 5F7 anti-HER2 nanobody labeled with 18F, 11C-palmitic acid and 14-(R,S)-18F-fluoro-6-thiaheptadecanoic acid, 15O-water, 13N-ammonia, 82Rb-rubidium, fluorothymidine, 68Ga-gallium, and 68Ge-germanium. PET tracers may include agents that bind to specific proteins, cellular markers, metabolic products, etc. Alternatively, or in addition, any of the systems and methods described herein may use one or more fiducial markers, radiopaque markers, or any other identifiers that allow the ROI or target region to be tracked and identified during a treatment session.

[0125] (System Controller) Each of the radiation therapy treatment planning systems and radiation treatment systems described herein may include a controller having a processor and one or more memories. In some variations, the planning system and the treatment system may share a controller, if desired. The controller may include one or more processors and one or more machine-readable memories in communication with the one or more processors. The controller may be connected to the radiation therapy system and / or other systems by wired or wireless communication channels. In some variations, the controller of the treatment planning system may be located in the same or different room as the patient. For example, the controller may be coupled to the patient platform or located on a transport vehicle or medical cart adjacent to the patient and / or operator.

[0126] The controller may be implemented in accordance with numerous general-purpose or special-purpose computing systems or configurations. Various exemplary computing systems, environments, and / or configurations that may be suitable for use with the systems and devices disclosed herein may include, but are not limited to, software or other components embodied in or on personal computing devices, network equipment, servers or server computing devices such as routing / connectivity components, portable (e.g., handheld) or laptop devices, multiprocessor systems, microprocessor-based systems, and distributed computing networks.

[0127] Examples of portable computing devices include smartphones, personal digital assistants (PDAs), mobile phones, tablet PCs, phablets (personal computing devices larger than a smartphone but smaller than a tablet), wearable computers in the form of smart watches, portable music devices, and the like.

[0128] (Processor) In some embodiments, the processor may be any suitable processing device configured to run and / or execute a set of instructions or code, and may include one or more data processors, image processors, graphic processing units, physical processing units, digital signal processors, and / or central processing units. The processor may be, for example, a general-purpose processor, a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), etc. The processor may be configured to run and / or execute processes and / or functions associated with an application process and / or other modules, systems, and / or networks associated therewith. The underlying device technology may be provided in a variety of component types, for example, metal oxide semiconductor field effect transistor (MOSFET) technology such as complementary metal oxide semiconductor (CMOS), bipolar technology such as emitter coupled logic (ECL), polymer technology (e.g., silicon conjugated polymer and metal conjugated polymer metal structures), mixed analog and digital, etc.

[0129] (Memory) In some embodiments, the memory may include a database, which may be, for example, a random access memory (RAM), a memory buffer, a hard drive, an erasable programmable read only memory (EPROM), an electrically erasable read only memory (EEPROM), a read only memory (ROM), a flash memory, etc. The memory may store instructions for causing the processor to execute modules, processes, and / or functions associated with the system, such as one or more treatment plans, imaging data acquired during a previous treatment session and / or a current treatment session (e.g., real-time imaging data), biological activity, physiological and / or anatomical data extracted from the imaging data, updated or adapted treatment plans, updated or adapted dose delivery instructions, radiation therapy system instructions (which may, for example, direct the operation of the gantry, therapeutic radiation source, multi-leaf collimator, and / or radiation therapy system, and / or any other components of the diagnostic or treatment planning system), and images associated with processing treatment plans and / or delivery, and / or data processing.

[0130] Some embodiments described herein relate to computer storage products with non-transitory computer-readable media (which may also be referred to as non-transitory processor-readable media) having instructions or computer code thereon for performing various computer-implemented operations. The computer-readable media (or processor-readable media) is non-transitory in the sense that it does not itself include a transitory propagating signal (e.g., a propagating electromagnetic wave that carries information over a transmission medium such as space or a cable). The media and computer code (which may also be referred to as code or algorithms) may be designed and constructed for a specific purpose or purposes. Examples of non-transitory computer readable media include, but are not limited to, magnetic storage media such as hard disks, floppy disks, and magnetic tapes, optical storage media such as compact disks / digital video disks (CD / DVD), compact disks-read only memory (CD-ROM), and holographic devices, magneto-optical storage media such as optical disks, solid-state storage devices such as solid-state drives (SSD) and solid-state hybrid drives (SSHD), carrier signal processing modules, and hardware devices specially configured to store and execute program code such as application specific integrated circuits (ASICs), programmable logic devices (PLDs), read only memories (ROMs), and random access memory (RAM) devices. Other embodiments described herein relate to computer program products that may include, for example, the instructions and / or computer code disclosed herein.

[0131] The user interface may serve as a communication interface between an operator or clinician and the treatment planning system. The user interface may include an input device and an output device (e.g., a touch screen and a display) and may be configured to receive input and output data from one or more of the support arm, the external magnet, the sensor, the delivery device, the input device, the output device, the network, the database, and the server. Sensor data from one or more sensors may be received by the user interface and output by one or more output devices visually, audibly, and / or through tactile feedback. As another example, operator control of the input device (e.g., joystick, keyboard, touch screen) may be received by the user and then processed by a processor and memory for the user interface to output control signals to one or more of the support arm, the external magnet, the intracavity device, and the delivery device.

[0132] Some variations of treatment planning systems for generating fluence maps may include a display device that may enable an operator to view graphical and / or textual representations of the fluence map, and / or dose distribution, and / or regions and / or volumes of interest, and / or patient anatomical images, and / or patient data (e.g., physiological and / or biological), etc. In some variations, the output device may include a display device including at least one of a light emitting diode (LED), a liquid crystal display (LCD), an electroluminescent display (ELD), a plasma display panel (PDP), a thin film transistor (TFT), an organic light emitting diode (OLED), an e-paper / e-ink display, a laser display, and / or a holographic display.

[0133] (communication) In some embodiments, the treatment planning system and / or radiation therapy system may communicate with other computing devices via one or more networks, each of which may be any type of network (e.g., wired network, wireless network), for example. A wireless network may refer to any type of digital network that is not connected by any type of cable. Examples of wireless communication within a wireless network include, but are not limited to, cellular, radio, satellite, and microwave communications. However, a wireless network may connect to a wired network to interface with the Internet, other carrier voice and data networks, business networks, and personal networks. Wired networks are typically carried via copper twisted pair, coaxial cable, and / or fiber optic cable. There are many different types of wired networks, including wide area networks (WANs), metropolitan-wide networks (MANs), local area networks (LANs), Internet area networks (IANs), campus area networks (CANs), global area networks (GANs) such as the Internet, and virtual private networks (VPNs). Hereinafter, a network refers to any combination of wireless, wired, public, and private data networks that are typically interconnected through the Internet to provide a unified networking and information access system.

[0134] Cellular communications may encompass technologies such as GSM, PCS, CDMA or GPRS, W-CDMA, EDGE or CDMA2000, LTE, WiMAX, and 5G networking standards. Some wireless network deployments combine networks from multiple cellular networks or use a mix of cellular, Wi-Fi, and satellite communications. In some embodiments, the systems, apparatus, and methods described herein may include radio frequency receivers, transmitters, and / or optical (e.g., infrared) receivers and transmitters to communicate with one or more devices and / or networks.

Claims

1. 1. A method for calculating a bounded dose-volume histogram (DVH) for evaluating a treatment plan, the method comprising: Based on the acquired patient image X, J images X' １，２，３，…，ｊ and generating the J images X′ １，２，３，…，ｊ Each of the J images X′ has a patient target volume (PTV). １，２，３，…，ｊ each PTV is located at j different positions within a radiation field (RFZ) of the patient; The dose calculation matrix A is linearized into the radiation projection matrix P and the one-dimensional vector X' ｊ By multiplying by ｊ (D ｊ = A.P.X' ｊ ), wherein the radiation firing matrix P has rows and columns containing beamlet patterns and / or beamlet intensities to be applied to the patient, the dose calculation matrix A has columns representing a number of sampling voxels in the patient and rows representing a number of candidate beamlets available for delivering a unit of radiation, and the dose calculation matrix D ｊ is a total radiation dose distributed to the patient, and the sampling voxels include regions of the patient over which radiation delivery may be monitored; and Each dose D ｊ generating a set of j dose-volume histogram (DVH) curves by plotting DVH curves based on each dose D ｊ the DVH curve based on represents a volume fraction for each dose value; generating a minimum boundary curve (minimum DVH curve) and a maximum boundary curve (maximum DVH curve) from said group of DVH curves; Including, The method of claim 1, wherein the minimum DVH curve includes a first series of points representing a minimum volume fraction for each dose value in the group of DVH curves, and the maximum DVH curve includes a second series of points representing a maximum volume fraction for each dose value.

2. The J images X′ １，２，３，…，ｊ The generating of the J images X′ １，２，３，…，ｊ 2. The method of claim 1, further comprising simulating j three-dimensional rigid shifts of the PTV within the RFZ for each of

3. The J images X′ １，２，３，…，ｊ The generating of the J images X′ １，２，３，…，ｊ changing the intensity values ​​of image pixels representing the PTV in each of 3. The method of claim 1, further comprising simulating a range of standard uptake values ​​(SUVs) by:

4. The method of claim 3 , wherein varying the intensity values ​​of the image pixels representing the PTV comprises increasing the intensity values ​​of the image pixels representing the PTV to 25% greater than the nominal intensity values.

5. The method of claim 3 , wherein altering the intensity values ​​of the image pixels representing the PTV comprises decreasing the intensity values ​​of the image pixels representing the PTV to be 25% less than the nominal intensity values.

6. The method according to any one of claims 1 to 5, wherein the acquired image X is a PET image.

7. 2. The method of claim 1 , wherein generating a minimum DVH curve comprises fitting the first series of points to a first curve, and generating a maximum DVH curve comprises fitting the second series of points to a second curve.

8. The method of claim 1 , wherein the dose calculation matrix A and the radiation firing matrix P are derived based on the acquired patient images X prior to a treatment session.

9. The patient image X is a first patient image, and the method includes obtaining a second patient image Y and multiplying the dose calculation matrix A by the radiation firing matrices P and Y to obtain a dose D. Ｙ (D Ｙ 2. The method of claim 1 , further comprising: calculating A·P·Y) and plotting a DVH curve corresponding to the second patient image Y.

10. 10. The method of claim 9, further comprising generating a notification if the DVH curve of the second patient image Y is not constrained between the minimum DVH curve and the maximum DVH curve.

11. The method of claim 10 , wherein the notification is a visual and / or an audible notification.

12. The method of claim 10 , wherein the DVH curve corresponding to the second patient image Y represents a volume fraction for each dose value relative to the PTV.

13. 11. The method of claim 10, wherein the DVH curve corresponding to the second patient image Y represents a volume fraction for each dose value for an organ at risk (OAR).

14. The method of claim 1 , further comprising displaying the minimum DVH curve and the maximum DVH curve on a display.

15. The method of claim 14 , wherein the display is a display of a radiation therapy system.

16. Each dose D ｊ 10. The method of claim 9, wherein plotting DVH curves based on comprises generating a family of j DVH curves for the PTV by plotting a volume fraction for each dose value for the PTV.

17. The method generates a set of j DVH curves for an organ at risk (OAR) by plotting the volume fraction for each dose value for the OAR. ｊ 17. The method of claim 16, further comprising plotting a DVH curve based on: wherein the minimum DVH curve is an OAR minimum DVH curve and the maximum DVH curve is an OAR maximum DVH curve.

18. 20. The method of claim 17, wherein the DVH curve corresponding to the second image Y is an OAR DVH curve, the method further comprising generating a notification if the DVH curve of the OAR in the second patient image Y exceeds a maximum DVH curve of the OAR.

Images